Cell-culture meat is a novel concept to replace traditional meat produced from animals, and to satisfy rising food demands due to the world population growth. It is still a young field and requires to solve technical issues including cell sources and types, efficient culture for large scale production, taste and texture for customer satisfaction. The current review summarized traditional beef meat production and evaluation methods for customer satisfaction. In particular, serum biomarkers for beef meat evaluation are discussed, which can be applicated for cell-culture meat production.

The currently available anti-cancer therapies, such as gamma-radiation and chemotherapeutic agents, induce cell death and cellular senescence not only in cancer cells but also in the adjacent normal tissue. New anti-tumor approaches focus on limiting the side effects on normal cells. In this frame, the potential anti-tumor properties of Pulsed Electromagnetic Fields (PEMFs) through irradiation of breast cancer epithelial cells (MCF-7 and MDA-MB-231) and normal fibroblasts (FF95) were investigated. PEMFs had a frequency of 8 Hz, full-square wave type, magnetic flux density of 0.011 T and applied twice daily for 5 days. Data collected showcases that PEMF application decreases the proliferation rate and viability of breast cancer cells while having the opposite effect on normal fibroblasts. Moreover, PEMF irradiation induced cell death and cellular senescence only in breast cancer cells without any effect in the non-cancerous cells. These findings suggest PEMF irradiation as a novel, non-invasive anti-cancer strategy in combination with senolytic drugs, to eliminate both cancer and the remaining senescent cells while simultaneously avoiding the side effects of the current treatments.

Treating relapsed and refractory diffuse large B-cell lymphoma is still challenging for clinicians, but the available CAR-T and bispecific antibodies revolutionized therapy. Autologous stem cell transplantation was the most effective treatment modality previously. The authors report data from a single center over ten years. The retrospective study included 116 patients. There were 53 relapsed, 39 primary refractory cases, 19 had CNS involvement, and 5 received primary consolidation transplants. The median duration of follow-up was 46 months. The median event-free survival was 75 months, and the median overall survival was 105 months for all cases. Five-year overall survival was 59%, and event-free survival was 54%. Pretreatment prognostic factors at diagnosis had no effect on the outcome of transplantation. The authors found no difference between survival in relapsed or refractory cases, and the number of salvage lines or the germinal center / activated B-cell type also did not influence the results. Complete metabolic response before transplant confirmed by 18FDG PET/CT strongly affected survival. The pretransplant creatinine and CRP levels significantly influenced the long-term outcome. The number of stem cells infused did not affect survival, but engraftment within nine days did result in better survival. These data support the finding that the response to salvage therapy did select a better prognostic group who may still benefit from autologous transplantation.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

G‐quadruplexes (G4) are structures formed at the ends of the telomere, these are rich in guanines and were stabilized by molecules that bind to specific sites. TMPyP4 and Thymoquinone (TQ) are small molecules that bind to the G4, they have drawn attention because of their role as telomerase inhibitors. The aim of this study was to evaluate the effects of telomerase inhibitors on cellular proliferation, senescence, and death. Two cell lines LC‐HK2 (NSCLC) and RPE‐1 were treated with TMPyP4 (5μM) and TQ (10μM). Both inhibitors were effective in decreasing telomerase activity. TMPyP4 increased the percentage of cells with membrane damage associated with cell death and decreased the frequency of cells in the S‐phase. TMPyP4 changed the cell adhesion ability and modified the pattern of focal adhesion. TQ acted in a dose‐dependent manner, increasing the frequency of senescent cells, and inducing cell cycle arrest in the G1. In conclusion, the effects of both drugs on LC-HK2 and RPE-1 cell lines were different although both are telomerase inhibitors, because TMPyP4 decreased proteins of cell adhesion and TQ induces a decrease in cell viability.

Here, our data provide the first evidence for the existence of a previously unknown receptive system formed by novel DNA- and RNA-based receptors in eukaryotes. This system, named the TR-system, is capable of recognizing and generating a response to different environmental factors and has been shown to orchestrate major vital functions of fungi, mammalian cells, and plants.Recently, we discovered the existence of a similar regulatory system in prokaryotes. These DNA- and RNA-based receptors are localized outside of the membrane forming a type of a network around cells that respond to a variety of chemical, biological, and physical factors and enabled the TR-system to regulate major aspects of eukaryotic cell life as follows: growth, including reproduction and development of multicellular structures; sensitivity to temperature, geomagnetic field, UV, light, and hormones; interaction with viruses; gene expression, recognition and utilization of nutrients. The TR-system was also implicated in cell memory formation and was determined to be responsible for its maintenance and the forgetting of preceding events. This system is the most distant receptive and regulatory system of the cell that regulates interactions with the outer environment and governs the functions of other receptor-mediated signaling pathways.

Alzheimer’s disease is the most common neurodegenerative disease and affects persons of all races, ethnic groups, and sexes. The disease is characterized by neuronal loss leading to cognitive decline and memory loss. There is no cure and the effectiveness of existing treatments is limited and depends on the time of diagnosis. The long prodromal period, during which patients’ ability to live a normal life is not affected despite neuronal loss, often leads to a delayed diagnosis because it can be mistaken for normal aging of the brain. In order to make a substantial impact on AD patients, early diagnosis may provide a greater therapeutic window for future therapies to slow AD-associated neurodegeneration. Current gold standards for disease detection include magnetic resonance imaging and positron emission tomography scans, which visualize amyloid β and phosphorylated tau depositions and aggregates. Liquid biopsies, already an active field of research in precision oncology, are hypothesized to provide early disease detection through minimally or non-invasive sample collection techniques. Liquid biopsies in Alzheimer’s disease have been studied in cerebrospinal fluid, blood, ocular, oral, and olfactory fluids. However, most of the focus has been on blood and cerebrospinal fluid due to biomarker specificity and sensitivity attributed to the effects of the blood-brain barrier and inter-laboratory variation during sample collection. Many studies have identified amyloid β and phosphorylated tau levels as putative biomarkers, however, advances in next-generation sequencing-based liquid biopsy methods have led to significant interest in identifying nucleic acids species associated with Alzheimer’s disease from liquid tissues. Differences in cell-free RNAs and DNAs have been described as potential biomarkers for AD and hold the potential to affect disease diagnosis, treatment, and future research avenues.

Disruption of the in utero environment can have dire consequences on fetal growth and development. Intrauterine growth restriction (IUGR) is a pathological condition by which the fetus deviates from its expected growth trajectory, resulting in low birth weight and impaired organ function. The developmental origins of health and disease (DOHaD) postulates that IUGR has lifelong consequences on offspring well-being, as human studies have established an inverse relationship between birth weight and long-term metabolic health. While these trends are apparent in epidemiological data, animal studies have been essential in defining the molecular mechanisms that contribute to this relationship. One such mechanism is cellular stress, a prominent underlying cause of the metabolic syndrome. As such, this review considers the role of oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and inflammation in the pathogenesis of metabolic disease in IUGR offspring. In addition, we summarize how uncontrolled cellular stress can lead to programmed cell death within the metabolic organs of IUGR offspring.

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce retinal detachment to perform the subretinal placement of the transplanted cell; and (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

Submucosal invasion is a critical step in gastric cancer (GC) progression, which greatly enhances metastasis risk. Cancer stem cells are responsible for invasion, metastasis, and tumor growth. To identify stem cell-related markers associated with submucosal invasion in GCs, we investigated the expression of candidate cancer stem cell (CSC) markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs with submucosal invasion. Remarkably, expression of all ISC markers and CD133 was frequently confined to the basal area of the lamina propria (basal pattern) in mucosal cancer. The proportion of stem cell marker-positive cells substantially increased during submucosal invasion. Given that ISC markers are restricted to the crypt base of the normal intestinal mucosa, these findings suggest that many early GCs may retain hierarchical characteristics. CD44 expression showed a focal pattern, ALDH1A was predominantly expressed diffusely, and there was no expansion of CD44 or ALDH1A expression in the submucosal cancer cells. RSPO2 from muscularis mucosa seem to be partly responsible for the increased expression of ISC markers in GC cells at the basal areas. We also found that ISC markers were correlated with CDX2 expression in GCs, indicating that ISC markers are involved in the intestinal differentiation in GCs. Interestingly, ISC markers (EPHB2 and OLFM4) and CD133 showed a positive impact on clinical outcomes. In particular, the prognostic value of EPHB2 was significant for intestinal-type GCs in a multivariate analysis. In summary, ISC markers and CD133 showed a basal distribution pattern along with enhanced expression in submucosal invading cells in early GCs. EPHB2 was an independent prognostic marker in intestinal-type GCs.

Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that contributes to the progression of several cancers. MIF overexpression has been reported in head and neck squamous cell carcinoma (HNSCC) patients. However, the exact role of MIF in HNSCC is not fully understood. Our aim was to evaluate the amount of secreted MIF and the role of MIF in the proliferation, cell cycle, and apoptosis in HNSCC cell lines. The MIF levels in conditioned media from human primary (HN18 and HN30) and metastatic (HN17 and HN31) HNSCC cell lines were evaluated using ELISA. The HNSCC cell lines were treated with recombinant MIF and its effect on proliferation, cell cycle, and apoptotic status was determined by MTT and flow cytometry, respectively. The HNSCC-secreted MIF concentration ranged from 49.33‒860 pg/ml. Exogenous MIF (25 ng/ml) significantly increased HN18, HN30, and HN31 cell proliferation. Moreover, MIF induced cell cycle progression and inhibited apoptosis in these cells. However, MIF did not affect growth or apoptosis in HN17 cell. In conclusion, the HNSCC cell lines were evaluated secrete MIF. Exogenous MIF promotes various effects on proliferation, cell cycle, and apoptosis in HNSCC cells.

Buerger's disease or Thromboangiitis Obliterans (TAO) is a nonatherosclerotic segmental vascular disease which affects small and medium arteries and veins in the upper and lower extremities. Based on pathological findings, TAO can be considered as a distinct form of vasculitis that is most prevalent in young male smokers. There is no definitive cure for this disease as therapeutic modalities are limited in number and efficacy. Surgical bypass has limited utility and 24% of patients will ultimately require amputation. Recently, studies have shown that therapeutic angiogenesis and immunomodulatory approaches through the delivery of cells to target tissues are potential options for ischemic lesion treatment. In this review, we summarize the current knowledge of TAO treatment and provide an overview of stem cell-based treatment modalities.

The core components of regenerative medicine are stem cells with high self-renewal and tissue regeneration potentials. Adult stem cells can be obtained from many organs and tissues. NANOG, SOX2 and OCT4 represent the core regulatory network that suppresses differentiation-associated genes, maintaining the pluripotency of mesenchymal stem cells. The roles of NANOG in maintaining self-renewal and undifferentiated status of adult stem cells are still not perfectly established. In this study we define the effects of downregulation of NANOG in maintaining self-renewal and undifferentiated state in mesenchymal stem cells (MSCs) derived from subcutaneous adipose tissue (hASCs). hASCs were expanded and transfected in vitro with short hairpin Lentivirus targeting NANOG. Gene suppressions were achieved at both transcript and proteome levels. The effect of NANOG knockdown on proliferation after 10 passages and on the cell cycle was evaluated by proliferation assay, colony forming unit (CFU), qRT-PCR and cell cycle analysis by flow-cytometry. Moreover, NANOG involvement in differentiation ability was evaluated. We report that downregulation of NANOG revealed a decrease in the proliferation and differentiation rate, inducing cell cycle arrest by increasing p27/CDKN1B (Cyclin-dependent kinase inhibitor 1B) and p21/CDKN1A(Cyclin-dependent kinase inhibitor 1A) through p53 and regulate DLK1/PREF1. Furthermore, NANOG induced downregulation of DNMT1, a major DNA methyltransferase responsible for maintaining methylation status during DNA replication probably involved in cell cycle regulation. Our study confirms that NANOG regulates the complex transcription network of plasticity of the cells, inducing cell cycle arrest and reducing differentiation potential.

Caspase-3, onto which there is a convergence of the intrinsic and extrinsic apoptotic pathways, is the main executioner of apoptosis. We here review the current literature on the intervention of the protease in the execution of naturally occurring neuronal death (NOND) during cerebellar development. We will consider data on the most common altricial species (rat, mouse and rabbit), as well as humans. Among the different types of neurons and glia in cerebellum, there is ample evidence for an intervention of caspase-3 in the regulation of NOND of the post-mitotic cerebellar granule cells (CGCs) and Purkinje neurons as a consequence of failure to establish proper synaptic contacts with target (secondary cell death). It seems possible that also the GABAergic interneurons undergo a similar type of secondary cell death, but the intervention of caspase-3 in this case still remains to be clarified in full. Remarkably, CGCs also undergo primary cell death at the precursor/pre-migratory stage of differentiation, in this case without the intervention of caspase-3. Glial cells as well undergo a process of regulated cell death, but it seems possible that expression of caspase-3, at least in the Bergmann glia, is related to differentiation rather than death.

Although the migration of hepatic stellate cells (HSCs) is important for hepatic fibrosis, the regulation of HSC migration is poorly understood. Interestingly, transforming growth factor (TGF)-β1 induces monocyte migration to sites of injury or inflammation in the early phase but inhibits cell migration in the late phase. In this study, we investigated the role of RhoA signaling in TGF-β1-induced HSC migration. We found that TGF-β1 increased the protein and mRNA levels of α-SMA and collagen type I in HSC-T6 cells. The level of RhoA-GTP in TGF-β1-stimulated cells was significantly higher than that in control cells. Moreover, cofilin phosphorylation and F-actin formation was more strongly detected in TGF-β1-stimulated cells than in control cells. Additionally, TGF-β1 induced the activation of NF-κB and the expression of extracellular matrix proteins and several cytokines in HSC-T6 cells. The active form of Rap1 (Rap1 V12) suppressed RhoA-GTP levels, whereas the dominant negative form of Rap1 (Rap1 N17) augmented RhoA-GTP levels. Therefore, we confirmed that Rap1 regulates RhoA activation in TGF-β1-stimulated HSC-T6 cells. These findings suggest that TGF-β1 regulates Rap1, resulting in RhoA suppression, NF-κB activation and F-actin formation during the migration of HSCs.

Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with an array of acute and chronic diseases, in humans. However, their specific effects on the stem cells remain unclear. Here, we report the effects of PM collected from Jeddah city on bone marrow mesenchymal stem cells (BM-MSCs) on proliferation, cell death, related gene expression and systems biological analysis aiming to understand the underlying mechanisms. Two different sizes (PM_2.5-₁₀) were tested in vitro at various concentrations (15 to 300 µg/ml) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM_2.5 increased BM-MSCs proliferation, while higher concentrations decreased it. PM₁₀ decreased BM-MSCs proliferation in a concentration-dependant manner. The X-Ray Fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses showed that heavy metals were associated with signalling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential regulation of the apoptosis genes (BCL2, BAX); upregulation of inflammation associated genes (TNF-a and IL-6) and downregulation of cell cycle regulation gene (P53). We conclude that PM could affect different cellular functions and predispose to debilitating diseases.

The survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method to discover the gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). A cutoff point is usually used in survival analysis for the patients' dichotomization in the continuous gene expression. There is some optimization software for cutoff determination. However, the software's predetermined cutoffs are usually set at the median or quantiles of gene expression value to perform the analyses. There are also few clinicopathological features available on their pre-processed data sets. We applied an in-house workflow, including data retrieving and pre-processing, feature selection, sliding-window cutoff selection, Kaplan-Meier survival analysis, and Cox proportional hazard modeling for biomarker discovery. In our approach for the TCGA HNSCC cohort, we scanned human protein-coding genes to find optimal cutoff values. After adjustment with confounders, the clinical tumor stage and the surgical margin involvement are independent risk factors for patients' prognosis. According to the resulting tables with Bonferroni-adjusted P value under the optimal cutoff and the hazard ratio, three biomarker candidates, CAMK2N1, CALML5, and FCGBP, are significantly associated with the patients' overall survival. We validated this discovery by using the other independent HNSCC dataset (GSE65858). Thus, we suggest the transcriptomic analysis could help for biomarker discovery.

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single dose rifampicin post exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, a SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases both retrospectively (2010-2017) and prospectively (2018 onwards). We conducted a retrospective audit to determine comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,643 household contacts were identified (9,791 in the retrospective and 3,850 in the prospective cohort). In the retrospective cohort, 1,044 (11%) contacts were absent, 403 (4%) were ineligible for SDR and 42 new cases were detected (0.4%) Overall SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were a total of 23 SDR refusals. The median time to SDR ad-ministration was 220 days (IQR 162-468) and 120 days (IQR 36-283) for the retrospective and prospective cohorts respectively. SDR was readily accepted in both cohorts. The new case detec-tion rate (0.5%) is consistent with that seen in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

Sumatriptan is a serotonin receptor agonist approved by FDA in 1992 to treat migraines. Its’ solid form used in commercially available drugs Imitrex, Treximet, Onzetra Xsail and Zembrace symtouch is sumatriptan succinate. Herein we report on crystal structure of sumatriptane succinate hemi(ethanol solvate), HSum+·HSucc–·0.5EtOH, its comparison with previously reported solids containing derivatives of sumatriptan.

Along with the economic growth, the companies must contribute to social progress and promote environmental sustainability in equal harmony. Sustainable human resource management (SHRM) strategies make it possible to attain the economic, social and environmental goals of a firm. In this regard, a survey method is discussed using the literature review and online questionnaire to identify the main factors/indicators during the SHRM evaluation of manufacturing firms in India. Uncertainty is commonly occurred in the assessment of SHRM factors. As a generalized version of fuzzy sets, single-valued neutrosophic set (SVNS) has been demonstrated as a valuable tool to illustrate the indeterminate, inconsistent and uncertain data of realistic decision-making problems. Considering the idea of SVNSs, this study develops a hybrid multi-criteria group decision-making (MCGDM) approach for assessing the SHRM of manufacturing firms under uncertainty settings. For this purpose, an SVN-alternative ranking order method accounting for two-step normalization (AROMAN) is proposed based on VIFI-score function-based decision experts’ (DEs’) weighting tool and integrated criteria weight-determining model to solve the MCGDM problems with fully unknown DEs and criteria weights. In this regard, we develop new SVN-distance measure to compute the degree of difference between SVNSs. Some examples are presented to demonstrate the efficacy of developed measure over the existing ones. In addition, new criteria weight-determination model is presented with the integration of objective weights through IVIF-distance measure-based model and subjective weights through ranking comparison (RANCOM) tool on SVNSs. The proposed ranking method is applied to an empirical study of SHRM assessment for manufacturing firms in India, which shows its applicability and feasibility. In this study, the evaluation criteria are characterized into social, environmental and economic aspects with DE’s opinions. Comparative and sensitivity analyses are made to show the strength and steadiness of presented approach. This study provides an innovative MCGDM analysis framework, which makes a significant contribution to the SHRM assessment problem under indeterminate, inconsistent and uncertain setting.

Due to increasing concerns about global warming and energy crisis, intensive efforts have been made to explore renewable and clean energy sources. Single-atom metals and two-dimensional (2D) nanomaterials have attracted extensive attention in the fields of energy and environment because of their unique electronic structures and excellent properties. In this review, we sum-marize the state-of-art progress on the single-atom metal supported at 2D MoS2 (single-atom metal/2D MoS2) for electrochemical CO2 reduction and water splitting. First, we introduce the advantages of single-atom metal/2D MoS2 catalysts in the fields of electrocatalytic CO2 reduction and water splitting, followed by the strategies for improving electrocatalytic performances of single-atom metal/2D MoS2 hybrid nanomaterials and the typical preparation methods. Further, we discuss the important applications of the nanocomposites in electrocatalytic CO2 reduction and water splitting via some typical examples, particularly focusing on their synthesis routes, modification approaches, and physiochemical mechanisms for improving their electrocatalytic performances. Finally, our perspectives on the key challenges and future directions of exploring high-performance metal single-atom catalysts are presented based on recent achievements in the development of single-atom metal/2D MoS2 hybrid nanomaterials.

Genetic adaptation of Hermetia illucens (BSF) to suboptimal single sourced wastes can open new perspectives for insect production. Here, four replicate BSF lines were maintained on a single sourced, low-quality wheat bran diet (WB) or on a high-quality chicken feed diet (CF) for 13 generations. We continuously evaluated evolutionary responses in several performance traits to rearing at the two diets. Subsequently, we tested responses to interchanged diets, i.e. of larvae that had been adapted to low-quality feed and to high quality feed and vice versa to evaluate costs associated with diet adaptation. BSF were found to experience rapid adaptation to the diet composition. While performances on WB diet were always inferior to CF diet, the adaptive re-sponses were stronger to the former diet. This stronger response was likely due to stronger se-lection pressure experienced by BSF fed on the low-quality single sourced diet. The interchanged diet experiment found no costs associated with diet adaptation but confirmed diet adaptation for the larval biomass and insect frass traits for the WB diet treatment. Our results revealed that BSF can rapidly adapt to diet through evolutionary responses, which has potential to be utilized to produce lines tailored to specific diets.

Some studies show that patients with mutations in the SNCA gene, which codifies for the alpha-synuclein protein, show a particular phenotype. The effects of SNCA Single Nucleotide Polymorphism (SNPs) in recently diagnosed, drug-naïve patients with PD have been less explored. Therefore, we set out to explore the differences in the clinical characteristics of recently diagnosed drug-naïve sporadic PD patients with or without SNCA rs3910105 or rs356181 SNPs. 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, dementia, psychiatric conditions, a diagnosis change over the first five years from the initial PD diagnosis, or with a familial history of PD. Subjects were evaluated with the MDS-Unified PD Rating Scale (MDS-UPDRS), DAT imaging, the Geriatric Depression Scale (GDS), the State-Trait Anxiety Inventory (STAI), the Montreal Cognitive Assessment (MoCA), the SCOPA-AUT for autonomic function, the Epworth Sleepiness Scale (ESS), the RBD Questionnaire, and the University of Pennsylvania Smell Identification Test (UPSIT). We included 308 PD patients fulfilling all inclusion and exclusion criteria. A logistic regression analysis and Machine-Learning models did not disclose any difference between patients either with or without the SNCA rs3910105 SNP or with or without the SNCA rs3910105 polymorphism. Our results suggest that the SNCA polymorphisms rs3910105 and rs356181 have no impact on the phenotype of idiopathic, sporadic, recently diagnosed, drug naïve PD patients.

The 11 system in iron-based superconducting family has become one of the most extensively studied materials in the research of high-temperature superconductivity due to their simple structure and rich physical properties. However, the research on 11 iron-based superconductors faces numerous obstacles, mainly stemming from the challenges associated with producing high-quality single crystals. Since the discovery of FeSe superconductivity in 2008, researchers have made significant progress in crystal growth, overcoming the hurdles that initially impeded their studies. Consequently, they have successfully established the complete phase diagrams of 11 iron-based superconductors, including FeSe1-xTex, FeSe1-xSx and FeTe1-xSx. In this paper, we aim to provide a comprehensive summary of the preparation methods employed for 11 iron-based single crystals over the past decade. Specifically, we will focus on hydrothermal, chemical vapor transport (CVT), self-flux, and annealing methods. Additionally, we will discuss the quality, size, and superconductivity properties exhibited by single crystals obtained through different preparation methods. By exploring these aspects, we can gain a better understanding of the advantages and limitations associated with each technique.

Development of methods and algorithms to predict the effect of mutations on protein stability, protein-protein, and protein-DNA/RNA binding is necessitated by the needs of protein engineering and for understanding the molecular mechanism of disease-causing variants. The vast majority of the leading methods are either methods with adjustable parameters or machine learning algorithms, both requiring a database of experimentally measured folding and binding free energy changes. These databases are collections of experimental data taken from scientific investigations typically aimed at probing the role of particular residue on the above-mentioned thermodynamics characteristics, i.e., the mutations are not introduced at random and do not necessarily represent mutations originating from single nucleotide variant (SNV). Thus, the reported performance of the leading algorithms assessed on these databases or other limited cases, may not be applicable for predicting the effect of SNVs seen in the human population. Indeed, we demonstrate that the SNVs and non-SNVs are not equally presented in the corresponding databases and the distribution of the free energy changes are not the same. Furthermore, the Pearson correlation coefficients (PCCs) obtained on cases involving SNVs are less impressive than for non-SNVs, indicating that caution should be used in applying them to reveal the effect of human SNVs. All methods are found to underestimate the energy changes by roughly a factor of 2.

This study aimed to describe the injury profiles of young Korean baseball players according to position and age as the proportion and distribution of injuries based on playing position and age remains unclear. A total of 271 elite youth baseball players aged 8 to 16 years were divided into two groups: elementary school (ES) (n=135) and middle school (MS) (n=136). The participants' basic, baseball practice, and injury information were collected. Injuries in the MS group were not limited to the elbow and shoulder, and the injury prevalence varied by age group and baseball position. The most injured body region in the ES group was the elbow joint, regardless of the position. In contrast, the most injured body region in the MS group was the lower back, except for infielders whose elbows were the most injured. Additionally, the MS group was more likely to experience injuries of the lower back (OR=4.27, 95% CI=2.47–7.40), shoulder (OR=1.93, 95% CI=1.08–3.43; P=0.024), and knee (OR=2.15, 95% CI=1.17–3.94; P=0.012). Our findings indicate that excessive practice and lack of rest during MS (growth spurt period) can significantly increase the risk of lower back problems in young baseball players.

Deep learning has been introduced to single-image super-resolution (SISR) in the last decade. These techniques have taken over the benchmarks of SISR tasks. Nevertheless, most architectural designs necessitate substantial computational resources, leading to a prolonged inference time on embedded systems or rendering them infeasible for deployment. This paper presents a comprehensive survey of plausible solutions and optimization methods to address this problem. Then, we propose a pipeline that aggregates the latter in order to enhance the inference time without significantly compromising the perceptual quality. We investigate the effectiveness of the proposed method on a lightweight GAN-based perceptual-oriented model as a case study. The experimental results show that our proposed method leads to significant improvement in the inference time on both Desktop and Jetson Xavier NX, especially for higher resolution input sizes on the latter, thereby making it deployable in practice.

This paper proposes how to reduce the consumption of active electrical energy (kwh) by 90.3% while maintaining the same mechanical work speed (RPM) at variable torque loads (fans or air-fluid blowers, centrifugal pumps are not included). of water and similar fluids), by using the “Fan Law” in an innovative way in PMSM-type synchronous motors (a comparative study never before carried out on the Fan Law). The work is carried out comparatively between brushless a-synchronous motors with starting loop (or motor with a short-circuited loop) versus brushed a-synchronous motors and PMSM-type synchronous motors without the need to use VDF (variable frequency drives), simplifying technology (electronics) and saving costs in an innovative way (R+D+i). The case study was developed on a design applied to a centrifugal air extractor/blower with PMSM/IPM type synchronous motor. Applying one of the fan affinity laws –with the impeller diameter 10.5 (mm) constant- the electrical power absorbed by the blower motor is proportional to the cube of the shaft speed: . Being “P” power (Watts) and “N” speed (RPM). Carrying out a comparative study between power (watts), active energy consumption (kwh) and rotational speed (RPM). This has a direct impact on the costs of residential and commercial single-phase active electrical energy consumption, measured in kilowatt-hours (kwh). Carrying out a comparative study between three (3) types of alternating current (AC) electrical machines, according to the NEMA (National Electrical Manufacturers Association); AC motors fall into three (3) categories. One (1), synchronous motors (Syncrhonous Motor) of three types: (1a) excitation by DC (DC Excited Motor), (1b) permanent magnet (Permanent Magnet Motor) and (1c) reluctance motor (Reluctance Motor) or motor Step by Step. Two (2), asynchronous induction motors of two types: (2a) Squirrel-Cage Induction Motor and (2b) Wound-Rotor Induction Motor. Three (3) series-wound motor (Series-Wound Motor) also called universal motor (they have carbons).

Rural electrification rate (RER) in Africa is still low to date. Several countries in Sub-Saharan Africa have tried to address this problem using conventional single-phase two-wire or three-phase three-wire systems, however at large costs due to the nature of dispersed rural load centers, low load demand, and low population density. Another solution of off-grid generation creates associated health problems. Therefore, this paper undertakes a review of a single wire earth return (SWER) network as a RER improvement solution. The paper undertakes intensive literature review to elucidate challenges and solutions to the implementation of SWER technology. Advantages of SWER technology discussed make it the choice for RER improvement in Sub-Saharan African countries. After that, a case study is selected in rural Tanzania, and a preliminary SWER network design is undertaken.

Endometriosis is a chronic neuro-inflammatory disorder the defining feature of which is the growth of tissue (lesions) that resembles the endometrium in sites outside the uterus. Estimates of prevalence typically quote rates of ~10% of women of reproductive age, equating to ~190 million women world-wide. Three subtypes of endometriosis are usually considered when discussing the aetiology of the disorder - superficial peritoneal, ovarian (endometrioma cysts), and deep (infiltrating). Genetic, hormonal and immunological factors have all been proposed as contributing to risk factors associated with the development of lesions. Twin studies report the heritable component of endometriosis as ~50%. Genome wide association studies (GWAS) have been conducted allowing unbiased scanning of the genome for single nucleotide polymorphisms (SNPs) in many thousands of individuals. These studies have identified SNPs that appear over-represented in patients with endometriosis, particularly those with more extensive disease (stage III/IV). Amongst the larger scale GWAS there has been replication of SNPs near genes involved in oestrogen and other signalling pathways including ESR1 (oestrogen receptor alpha), GREB1, HOXA10, WNT4 and MAPK kinase signalling. The results from patients with endometriosis have also provided an opportunity to make comparisons with GWAS conducted on other patient cohorts including those with reproductive traits (age at menarche) and disorders (fibroids, endometrial and ovarian cancer) and conditions that are reported by women with endometriosis (migraine, depression). These comparative studies have highlighted some shared genetically-controlled biological mechanisms, including hormone-regulated pathways which might explain the co-occurrence of endometriosis with these disorders. In summary, unbiased genetic analysis has provided new insights into the genetic factors that may contribute to increased risk of developing endometriosis. New studies are needed to broaden the range of patients contributing to these datasets and to improve integration with non-genomic and tissue expression data before their full potential for diagnosis and improvements in patient care can be fully realised.

The response of a single tin oxide nanowire was collected at different temperatures to create a virtual array of sensors working as a nano-electronic nose. The single nanowire, acting as a chemiresistor, was first tested with pure ammonia and then used to determine the freshness status of trout fish (Oncorhynchus mykiss) in a rapid and non-invasive way. The gas sensor reacts to total volatile basic nitrogen, detecting the freshness status of the fish samples in less than 30 seconds. The sensor response at different temperatures correlates well with the total viable count (TVC), demonstrating that it is a good (albeit indirect) way of measuring the bacterial population in the sample. The nano-electronic nose is able to classify the samples according to their degree of freshness, but also to quantitatively estimate the concentration of microorganisms present. The system was tested with samples stored at different temperatures, managing to classify them perfectly (100%) and estimating their log(TVC) with an error lower than 5%.

Aims Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3- dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) has been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. Main methods SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. Key findings No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. Significance The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

The diagnosis of a rolling bearing for monitoring its status is critical for maintaining industrial equipment using rolling bearings. The traditional method of diagnosing faults of the rolling bearing has low identification accuracy, which needs artificial feature extraction to enhance the accuracy. 1D-CNN method not only can diagnose bearing faults accurately but also overcome shortcomings of the traditional methods. Different from machine learning and other deep learning models, the 1D-CNN method does not need pre-processing one-dimensional data of rolling bearing’s vibration. Thus, it enhances the processing speed and improves the network structure to have a reasonable design for small sample data sets. This study proposes and tests a 1D-CNN method for diagnosing rolling bearings. By introducing the dropout operation, the method obtains high accuracy and improves the generalizing ability. The experimental results show 99.52% of the average accuracy under a single load and 98.26% under different loads.

Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

This article reveals a best possible design for hybrid dispersion compensating fiber (HyDCF) with high birefringence established on modified broadband compensating structure through S, C and L telecommunication bands. The simulation outcome exhibits relatively higher birefringence of 3.76×10-2 at wavelength of 1550 nm. The suggested fiber also has dispersion compensation characteristics in an inclusive series of wavelengths which covers 1400-1625 nm. The reported design can achieve dispersion quantity of – 606 ps/ (nm.km) at 1550 nm effective wavelength. The reported fiber design matches the relative dispersion slope (RDS) 0.003694 nm-1 similar to single mode fiber at 1550 nm operating wavelength. This fiber demonstrates negatively flattened effective dispersion of – 2.703 ± 0.734 ps/ (nm.km) within 180 nm flat band ranging from 1460-1640 nm wavelength. It is also convenient to optical high bit rate communication systems. The low confinement loss is found 3.756×10-10 dB/m at the operating wavelength. This design also achieves highly nonlinear coefficient of 50.34 W-1km-1. In some cases, it can also be used in sensing applications.

Fostering fruitful collaboration between chemistry and physics scholars, the analysis of the differences in the practical approach to single atoms in chemistry and in physics affords a number of conceptual outcomes pointing to a more balanced relationship between chemistry and physics.

This paper proposes a novel single-stage buck-boost three-Level neutral-point-clamped (NPC) inverter with two independent dc sources coupled for the grid-tied photovoltaic (PV) application, which can effectively solve the unbalanced operational conditions generally appeared between two coupled independent PV sources induced by the unequal irradiation and temperature distribution. The proposed control scheme can simultaneously guarantee the maximum power point (MPP) operation of both PV sources and maintain the output waveform quality. Compared to the traditional two-stage PV inverter, the proposed NPC inverter could reduce the PV array voltage requirement and dc-link capacitors’ voltage rating, meanwhile show the advantage in operational efficiency. MATLAB simulations and the captured experimental results are presented to show the performance of the proposed three-level inverter.

Background: Strong indicators of inflammation, such as C-reactive protein (CRP), hypersensitive CRP (hs-CRP), and a series of hematological indices, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), hematocrit (HCT) and red blood cell distribution width (RDW), are regarded related with the incidence of contrast induced nephropathy (CIN) closely. Whereas, it remains unclear whether they can function as predictors of CIN onset. The objective of this meta-analysis was to determine the relationship between above indicators and CIN incidence among patients receiving coronary intervention. Methods: Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and science direct from their inception to June 3rd, 2020. Meta-analysis was performed on pool eligible studies. Two reviewers screened all titles and abstracts and independently assessed all articles. Results: A total of 26 studies involving 29,454 patients were included in the meta-analysis. Pooled analysis results revealed that patients with higher CRP (odds ratio [OR]=1.06, 95% confidence interval [CI]: 1.01–1.12, P=0.02), hs-CRP (OR=1.03, 95% CI: 1.01–1.06, P=0.004), NLR (OR=1.11, 95% CI: 1.01–1.20, P=0.02), RDW (OR=1.35, 95% CI: 1.19–1.53, P<0.00001), and lower HCT (OR=0.94, 95% CI: 0.92–0.97, P=0.0003) all exhibited significantly higher CIN rates, but there was no significant association between PLR and CIN risk (OR=1.12, 95% CI: 0.99–1.26, P=0.07). Conclusion: The meta-analysis reported here demonstrates that pre-angiography CRP/hs-CRP and some hematological indices are associated with CIN.

Conventional plaque assays rely on the use of overlays to restrict viral infection allowing the formation of distinct foci that grow in time as the replication cycle continues leading to counta-ble plaques that are visualized with standard techniques such as crystal violet, neutral red or immunolabeling. This classical approach takes several days until large enough plaques can be visualized and counted with some variation due to subjectivity in plaque recognition. Since plaques are clonal lesions produced by virus-induced cytopathic effect, we applied DNA fluores-cent dyes with differential cell permeability to visualize them by live cell imaging. We could observe different stages of that cytopathic effect corresponding to an early wave of cells with chromatin-condensation followed by a wave of dead cells with membrane permeabilization within plaques generated by different animal viruses. This approach enables an automated plaque identification using image analysis to increase single plaque resolution compared to crystal violet counterstaining and allows its application to plaque tracking and plaque reduction assays to test compounds for both antiviral and cytotoxic activities. This fluorescent real-time plaque assay sums to those next-generation technologies by combining this robust classical method with modern fluorescence microscopy and image analysis approaches for future applica-tions in virology.

Blood cancers, including leukemia, lymphoma, and myeloma, pose significant diagnostic challenges due to their diverse and complex nature. Detecting these cancers early and accurately is crucial for timely intervention and improved patient outcomes. This review explores current and emerging detection methods for human blood cancers, focusing on their principles, advantages, limitations, and potential clinical applications.

Cardiac development is a complex developmental process that results in the formation of the four-chambered organ from a single linear heart tube. In the early stages of development, the linear heart tube is composed of only two tissue layers, an external myocardium that is internally lined by the endocardium. Subsequently, the proepicardium emerges at the septum transversum and soon thereafter proepicardial cells will migrate into the naked myocardium, leading to the formation of the embryonic epicardium. As cardiac development proceeds, epicardial-derived cells migrate into the subepicardial space and subsequently invade the developing ventricular chambers leading to the contribution of distinct cardiovascular cell types such as the cardiac fibroskeleton and different components of coronary vasculature. At present, the molecular mechanisms that regulate the transitional process from the proepicardium to the embryonic myocardium are largely unexplored. In this study we have implemented an ex vivo proepicardium/septum transversum (PE/ST)-embryonic myocardium explant model and we demonstrated that miR-223, but not miR-195, is capable of modulating PE/ST migration, a process that seems to be mediated by Slug expression. Thus, our study demonstrates for the first time the implication of distinct microRNAs in the PE/ST to embryonic myocardium transition in chicken embryonic hearts.

The use of hydrogen fuel cells as a mobile source of electricity might prove to be a keystone in future decarbonization of heavy duty road and marine transport. Due to complex interplay of various physicochemical processes in the fuel cells, further development of these devices will rely on concerted effort of researchers from various fields, e.g. chemistry, physics, electric and mechanical engineering. This results in knowledge gaps which are filled by the information, dispersed in wide range of literature, but rarely covered in a short and condensed form. To address this issue and with the aim of providing a concise and simple explanation of fuel cell operation, we propose a simple educational model of the most relevant processes in the fuel cell, aimed at proper description of causal relations. The derivation of model equations provides an intuitive understanding of electric potentials acting on protons on the microscopic level and relates this knowledge to the common terminology in fuel cell research community, such as catalyst electric overpotential and internal membrane resistance. The results of the model fit well with experimental data, indicating that a simple description, provided in the paper, is sufficient for intuitive understanding of fuel cell operation.

Sublobar resection is a standard surgical procedure for small-sized non-small cell lung cancer (NSCLC). However, clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. Kaplan-Meier method with log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. Samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies using various types of stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity of unlimited proliferation and differentiation to cardiomyocytes, are a promising cell source for myocardial regeneration therapy. This review discusses the current status of cardiac regenerative therapy using iPSCs.

Abstract: The venom-containing barb attached to their ‘whip-like’ tail provides stingrays a defensive mechanism for evading predators such as sharks. From human encounters, dermal stingray envenomation is characterized by intense pain often followed by tissue necrosis occurring over several days to several weeks. The bioactive components in stingray venoms (SRV’s) and their molecular targets and mechanisms that mediate these complex responses are not well understood. Given the utility of venom-derived proteins from other venomous species for biomedical and pharmaceutical applications, we set out to characterize the bioactivity of SRV from three local species that belong to the Dasyatoidea ‘whiptail’ superfamily. Multiple cell-based assays were used to quantify and compare the in vitro effects of these SRV’s on different cell lines. All three SRV’s demonstrated concentration-dependent growth inhibitory effects on three different human cell lines tested. In contrast, a mouse fibrosarcoma cell line was markedly resistant to all three SRV’s, indicating the molecular target(s) for mediating the SRV effects are not expressed on these cells. The multifunctional SRV responses were characterized by an acute disruption of cell adhesion leading to apoptosis. These findings aim to guide future investigations of identified SRV proteins and their molecular targets for potential use in biomedical applications.

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells, and SeMNPV or Autographa californica mutiple nucleopolyhedrovirus (AcMNPV) infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in G2/M phase and or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, the BV production and the OB containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post infection (p < 0.05). Finally, arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression regulation.

(1) Background: P-cadherin (CDH3) is a transmembrane protein that plays a crucial role in maintaining the structural integrity of epithelial tissue and homeostasis. Its role in carcinogenesis remains a subject of debate, as its behavior can vary depending on the molecular context and the specific tumor cell model under study. In this study, we explored the role of P-cadherin in head and neck squamous cell carcinoma (HNSCC) and the mechanism underlying its function. (2) Methods: We analyzed P-cadherin expression in HNSCC patients using The Cancer Genome Atlas (TCGA) database. For in vitro functional analysis, we conducted proliferation, migration, invasion, and western blot assays after either suppressing or overexpressing P-cadherin. For in vivo functional analysis, we utilized mouse xenograft models. (3) Results: P-cadherin was significantly overex-pressed in tumor samples compared to normal samples in the TCGA-HNSCC cohort. P-cadherin knockdown resulted in decreased proliferation, migration, and invasion compared to control cells, while P-cadherin overexpression increased cell proliferation and migration in HNSCC cells. We discovered that c-Met functioned as an upstream regulator of P-cadherin. Surprisingly, we found that P-cadherin knockdown increased the phosphorylation of c-Met and STAT3. Combining P-cadherin siRNA with the c-Met inhibitor SU11274 resulted in a more effective reduction in HNSCC cell growth, both in vitro and in vivo, compared to either treatment alone. (4) Conclusions: Our study uncovered a previously unknown aspect of P-cadherin-mediated c-Met regulation. The enhanced activation of c-Met/STAT3 following P-cadherin inhibition could be responsible for the survival of resistant tumor cells. Therefore, dual inhibition of P-cadherin and c-Met may be a potentially effective approach for treating HNSCC.

Z-ligustilide is a main active ingredient in the volatile oil of Angelica sinensis, a traditional Chinese medicine. Cisplatin is a commonly used chemotherapy drug for the treatment of lung cancer. Efficacy is often limited by the development of drug resistance after long-term treatment. Here, we investigated the effect of the combination of Z-ligustilide and cisplatin (Z-ligustilide+cisplatin) on resistance of cisplatin-resistant lung cancer cells and its action mechanism. Cell viability was analyzed by cell counting kit-8 (CCK-8) assay. Cell cycle and cell apoptosis were examined by flow cytometry assay. mRNA and protein levels of factors related to cell cycle and apoptosis were analyzed by real-time PCR and western blot. Liquid chromatography-mass spectrometry (LC-MS) analysis and RNA sequencing in A549, A549/DDP and A549/DDP cells treated with the Z-ligustilide+cisplatin were performed. The expression of PLPP1 was analyzed by the Cancer Genome Atlas (TCGA). The correlation between PLPP1 and prognosis was evaluated by immunohistochemistry and Kaplan-Meier (KM) plotter analysis. We found that Z-ligustilide+cisplatin could decrease the cell viability of cisplatin-resistant lung cancer cells. Z-ligustilide+cisplatin induced cell cycle arrest, and promoted cell apoptosis of cisplatin-resistant lung cancer cells. Metabolomics combined with transcriptomics revealed that Z-ligustilide+cisplatin inhibited phospholipid synthesis by upregulating the expression of PLPP1. Furthermore, PLPP1 expression was positively correlated with good prognosis. Knockdown of PLPP1 abolished the effects of Z-ligustilide+cisplatin on cell cycle and apoptosis. Z-ligustilide+cisplatin inhibited the activation of AKT by reducing the levels of PIP3 levels. Z-ligustilide+cisplatin induced cell cycle arrest and promoted cell apoptosis of cisplatin-resistant lung cancer cells by inhibiting PLPP1-mediated phospholipid synthesis.

The precise differentiation of renal cell tumours (RCTs) is sometimes hard to achieve using standard imaging and histopathological methods. This study investigated 43 cell renal cell car-cinomas (ccRCC), 15 papillary renal cell carcinomas (pRCC), 20 chromophobe renal cell carcino-mas (chRCC), and 18 renal oncocytomas (RO), stained with anti-mitochondria antibody (Thermo Scientific) by immunohistochemistry and immunofluorescence, and assessed by electron micros-copy, in order to define mitochondria distribution pattern (coarse scanty, moderate granular and diffuse granular). Thus, the majority of males had coarse granular staining in the tumours, while females were almost equally distributed among groups (p=0.005). An average patient age, tumour side and dimension, and tumour stage were similar in all staining pattern groups. However, pathohistological tumour types had significantly different expression patterns, with the lower amount of staining detected in majority of ccRCC, moderate expression in all chRCC, and diffuse expression in all RO, pRCC and two cases of ccRCC (p<0.001) presented with higher nuclear grade (p=0.005). Moreover, with increased distribution of mitochondria, the intensity of staining was higher (p<0.001). Here we present a strategy that utilizes mitochondria detection to differentiate RO from chRCC, as well as to distinguish other frequent RCTs, such as ccRCC and pRCC.

The neural-crest derived enteric nervous system (ENS) is the intrinsic nervous system of the gastrointestinal (GI) tract and controls all gut functions, including motility. Lack of ENS neurons causes various ENS disorders such as Hirschsprung Disease. One treatment option for ENS dis-orders includes the activation of resident stem cells to regenerate ENS neurons. Regeneration in the ENS has mainly been studied in mammalian species using surgical or chemically-induced injury methods. These mammalian studies showed a variety of regenerative responses with generally limited regeneration of ENS neurons, but (partial) regrowth and functional recovery of nerve fibers. Several aspects might contribute to the variety in regenerative responses, including observation time after injury, species, and gut region targeted. Zebrafish have recently emerged as a promising model system to study ENS regeneration as larvae possess the ability to generate new neurons after ablation. As the next steps in ENS regeneration research, we need a detailed under-standing of how regeneration is regulated on a cellular and molecular level both in animal models with high and low regenerative capacity. Understanding the regulatory programs necessary for robust ENS regeneration will pave the way for using neural regeneration as a therapeutic approach to treating ENS disorders.

The modern paradigm of studying the processes of carcinogenesis and vital activity of tumor tissues implies increased attention to constituents of tumor microenvironment (TME) and their interactions. These interactions between the cells in TME can be mediated via protein junctions of different types. Connexins (Cnxs) are one of the major contributors to intercellular communication. They form gap junctions responsible for the transfer of ions, metabolites, peptides, miRNA, etc. between neighboring tumor cells as well as between tumor and stromal cells. Cnx hemichannels mediate purinergic signaling and bidirectional molecular transport with the extracellular environment. Additionally, Cnxs were reported to localize in tumor-derived exosomes and facilitate the release of their cargo. A large body of evidence implies that the role of connexins in cancer is multifaceted. Pro- or anti-tumorigenic properties of connexins are determined by their abundance, localization and functionality as well as channel assembly and non-channel functions. In this review we have summarized the data on the Cnxs contribution in TME and to the cancer initiation and progression.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

Human Cytomegalovirus (HCMV) infection is a serious complication in hematopoietic stem cell transplant (HSCT) recipients due to virus-induced myelosuppression and impairment of stem cell engraftment. Despite the clear clinical link between myelosuppression and HCMV infection, little is known about the mechanism(s) by which the virus inhibits normal hematopoiesis because of the strict species specificity and the lack of surrogate animal models. In this study, we developed a novel humanized mouse model system that recapitulates the HCMV-mediated engraftment failure after hematopoietic cell transplantation. We observed significant alterations in the hematopoietic populations in peripheral lymphoid tissues following engraftment of a subset of HCMV+ CD34+ HPCs within the transplant suggesting that a small proportion of HCMV-infected CD34+ HPCs can profoundly affect HPC differentiation in the bone marrow microenvironment. This model will be instrumental to gain insight into the fundamental mechanisms of HCMV myelosuppression after HSCT and provides a platform to assess novel treatment strategies.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

Small-cell lung cancer (SCLC) is a cancer with poor prognosis. For relapsed extensive-stage (ES) SCLC, second-line treatment options are scarce. Topotecan was the only approved treatment in this setting until 2020. Since topotecan induces significant toxicities, alternative off-label regimens are being used. This study evaluated real-world efficacy and safety of Paclitaxel Gemcitabine chemotherapy in patients with relapsed ES-SCLC. We retrospectively reviewed data from all consecutive patients with relapsed ES-SCLC who received Paclitaxel Gemcitabine chemotherapy from september 2008 to january 2022 in two centers. Patient characteristics (n=188) were: PS≥2: 24.5%; brain metastasis: 42%; platinum-sensitive disease: 41%. Patients received Paclitaxel Gemcitabine as second- (77%) third (18%) or fourth (6%) line of therapy. Median progression-free and overall survival were 2.1 (95CI 1.8–2.4) and 3.8 (95CI 3.3–4.8) months in the overall population, respectively, with 17% response rate (RR) and 28% disease-control rate. PS, history of brain radiation, platinum-sensitive disease, liver, and adrenal gland metastasis were associated with longer survival in univariate analysis. PS was the only prognostic factor in multivariate analysis, with 21% RR and 4.1 months median DOR in PS 0-1 patients. Paclitaxel Gemcitabine chemotherapy may represent a treatment option in PS0-1 relapsed SCLC.

Though early-stage colorectal cancer has a high 5-year survival rate of 65-92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells. Preclinical and clinical investigations of immunotherapy for treatment of colorectal cancer including immune checkpoint blockade, adoptive cell therapy, monoclonal antibodies, oncolytic viruses, anti-cancer vaccines, and immune system modulators have been promising, but demonstrate limitations for patients with proficient mismatch repair enzymes. In this review, we discuss preclinical and clinical studies investigating immunotherapy for treatment of colorectal cancer and predictive biomarkers for response to these treatments. We also consider open questions including optimal combination treatments to maximize efficacy, minimize toxicity, and prevent acquired resistance and approaches to sensitize mismatch repair proficient patients to immunotherapy.

Background: Developing an efficient and standardized method to isolate and characterize adipose-derived stem cells (ASCs) from the stromal vascular fraction (SVF) of the adipose tissue for clinical application represents one of the major challenges in cell therapy and tissue engineering. Methods: In this study, we proposed an innovative, non-enzymatic protocol to collect clinically useful ASCs within freshly isolated SVF from adipose tissue by centrifugation of the infranatant portion of lipoaspirate and to determine the characteristic cytofluorimetric pattern, prior to in vitro culture. Results: The SVF yielded a mean of 73,32 \pm\ 10,89% cell viability evaluated with CALCEINA-FITC, i.e. cell-permeant dye. The ASCs were positive for PC7-labeled mAb anti-CD34 and negative for both PE-labeled mAb anti-CD31 and APC-labeled mAb anti-CD45. The frequency of ASCs estimated according to the panel of cell surface markers used was 51,06%\ \pm 5,26% versus the unstained ASCs subpopulation that was 0,74%\pm0,84% (P<0.0001). The ASCs events/\muL were 1602,13/\muL \pm 731,87/\muL. Conclusion: Our findings suggested that ASCs found in freshly isolated adipose SVF obtained by centrifugation of lipoaspirate can be immunophenotypically identified with a basic panel of cell surface markers. These findings aimed to provide standardization and contribute to reducing the inconsistency on reported cell surface antigens of ASC derived from the existing literature.

It has been proposed that tumourigenicity was an intrinsic feature of embryonic/germ cell developmental axis as well as embryonic/germ cell-related genes play a crucial role in tumourigenicity. Our previous studies indicated that primordial germ cell (PGC)-like potential could be reactivated in tumourigenesis. In this study, 4T1, 168FARN and 67NR cells which originated from the same mouse breast cancer were studied and the results indicated that the acquisition of embryonic/germ cell-like state is essential for tumourigenicity. We further demonstrated that somatic to PGC-like transformation (SPLT) was activated in 4T1 cells and that inhibition of PGC-like cell formation by depleting pluripotency and/or PGC specification-related genes markedly repressed SPLT and the tumourigenicity. Collectively, our findings reveal that tumourigenicity is linked to the acquisition of PGC-like state through SPLT in 4T1 cells, provide new insight into deeper understanding the biological nature of tumours and novel therapeutical strategies for cancer targeting.

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.