In bone tissue engineering, ceramics have been the choice due to their excellent biological properties. But the paradigm changed with the discovery of bioactive glasses (BGs) in 1969 by Larry Hench and co-workers, due to their ability to bond to living tissues through the formation of an interfacial bone-like hydroxyapatite layer when the bioglass was put in contact with biological fluids in vivo. Among a number of tested compositions, the one exhibiting the highest bioactivity index is the well-known trademarked 45S5 Bioglass®. The topic received increasing attention particularly after 1985 when this material entered in the market of biomedical devices, inspiring many other investigations aiming at further exploring the in vitro and in vivo performances of this BG, or developing other related BG compositions. The research efforts gradually revealed a number of shortcomings of 45S5 Bioglass®, mostly derived from its high sodium content, initially intended to decrease the melting temperature and accelerating the degradation of the silicate network over time. But the extensive release of sodium from 45S5 Bioglass® in the biological fluids creates a high pH cytotoxic environment. Other serious drawbacks include a fast degradation rate, and a poor sintering ability, which hinders the reliable fabrication of porous scaffolds. Therefore, sol-gel was regarded as an attractive alternative to prepare alkali-free BG compositions. The process uses inorganic and/or organic precursors, which undergo hydrolysis and condensation at room-temperature, being less costly. When properly conducted, the sol-gel process might result in amorphous structures with all the components intimately mixed at the atomic scale. Moreover, developing new better performing materials for bone tissue engineering is a growing concern, as the ageing of the world’s population leads to lower bone density and osteoporosis. This work describes the sol-gel synthesis of a novel quaternary silicate-based BG with the composition 60 SiO2 – 34 CaO – 4 MgO – 2 P2O5 (mol%) was prepared using acidified distilled water as single solvent. By controlling the kinetics of the hydrolysis and condensation steps, an amorphous glass structure could be obtained. The results of XRD of samples calcined within the temperature range from 600-900 ºC demonstrated that amorphous nature was maintained until 800 ºC, followed by partial crystallization at 900 ºC. The specific surface area, an important factor in osteoconduction, was also evaluated over different temperatures, ranging from 160.6 ± 0.8 m2/g at 600 ºC down to 2.2 ± 0.1 m2/g at 900 ºC, being accompanied consistent changes in average pore size and agreeing pore size distribution. The immersion of the BG particles in simulated body fluid (SBF) led to the formation of an extensive apatite layer on its surface. These overall results indicate the proposed material is very promising for biomedical applications in bone regeneration and tissue engineering.

. This article presents, for the first time, the kinetics and the general conversion features of a 3-component system (A/B/N), based on proposed mechanism of Mau et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using various new copper complex (G2) as the initiator. Higher FRP and CP conversion can be achieved by co-additive of [B] and N, via the dual function of (i) regeneration [A], and (ii) generation of extra radicals. The FRP and CP conversion efficacy (CE) are proportional to the nonlinear power of bI[A][B], where b and I are the effective absorption coefficient and the light intensity, respectively. In the interpenetrated polymer network (IPN) capable of initiating both FRP and CP in a blend of TMPTA and EPOX, (as the monomer for FRP and CP, respectively), the synergic effects due to CP include:: (i) CP can increase viscosity limiting the diffusional oxygen replenishment, such that oxygen inhibition effects are reduced; (ii) the cationic monomer also acts as a diluting agent for the IPN network , and (iii) the exothermic property of the CP. Many new findings are explored via our analytical formuals include: (i) the CE of FRP is about twice of the CE of CP, due to the extra radicals involved in FRP; (ii) the catalytic cycle enhancing the efficacy is mainly due to the regenaration of the initiator, and (iii) the nonlinear dependence of light intensity of the CE (in both FRP and CP). For the first time, the catalytic cycle, synergic effects, and the oxygen inhibition are theoretically confirmed to support the experimental hypothesis. The measured results of Mau et al are well analyzed and matching the predicted features of our modeling. .

Studies have shown that in many practical applications, data interpolation by splines leads to better approximation and higher computational efficiency as compared to data interpolation by a single polynomial. Data interpolation by splines can be significantly improved if knots are allowed to be free rather than at a priori fixed locations such as data points. In practical applications, the smallest possible curvature is often desired. Therefore, optimal splines are determined by minimizing a derivative of continuously differentiable functions comprising the spline of the required order. The problem of obtaining an optimal spline is tantamount to minimizing derivatives of a nonlinear differentiable function over a Banach space on a compact set. While the problem of data interpolation by quadratic splines has been accomplished analytically, interpolation by splines of higher orders or in higher dimensions is challenging. In this paper, to overcome difficulties associated with the complexity of the interpolation problem, the interval over which data points are defined, is discretized and continuous derivatives are substituted by their discrete counterparts. It is shown that as the mesh of the discretization approaches zero, a resulting near-optimal spline approaches an optimal spline. Splines with the desired accuracy can be obtained by choosing an appropriate mesh of the discretization. By using cubic splines as an example, numerical results demonstrate that the linear programming (LP) formulation, resulting from the discretization of the interpolation problem, can be solved by linear solvers with high computational efficiency and resulting splines provide a good approximation to the optimal splines.

Complex systems can be described as the network of interactions between their components. In directed networks, information, energy and matter flow in dominant directions. Undirected networks, on the other hand, cannot easily capture these asymmetries. The local flow of information depends on the node spin, which is a function of the number of incoming and outgoing links attached to it. And yet, how the heterogeneous association between in-degree and out-degree constraints global dynamics remains poorly understood. Here, we develop a new theoretical model to study the relationship between node directionality and global flow dynamics. Our computational analysis of random and scale-free directed networks indicates that structural diversity constrains the dimensionality of reachable dynamical space. These results suggest how local directionality might be an universal driver of global dynamics in many systems, from social networks, to technological systems to the connectome.

The complex interplay among pathogens, host factors, and the integrity and composition of the endogenous microbiome determine the course and outcome of gastrointestinal infections. The model organism Yersinia entercolitica (Ye) is one of the five top frequent causes of bacterial gastroenteritis based on the Epidemiological Bulletin of the Robert Koch Institute (RKI) published on September 10, 2020. A fundamental challenge in predicting the course of an infection is to understand whether co-infection with two Yersinia strains differing only in their capacity to resist killing by the host immune system may decrease the overall virulence by competitive exclusion or increase it by acting cooperatively. Herein, we study the primary interactions among Ye, the host immune system and the microbiota, and their influence on Yersinia population dynamics. The employed model considers two host compartments, the intestinal mucosa and lumen, commensal bacteria, the co-existence of wild-type and mutant Yersinia strains, as well the host immune responses. We determine four possible equilibria: the disease-free, wild-type-free, mutant-free, and co-existence of wild-type and mutant equilibrium. We also calculate the reproduction number for each strain as a threshold parameter to determine if the population may either be eradicated or persist within the host. We conclude that the infection should disappear if the reproduction numbers for each strain fall below one, and the commensal bacteria’s growth rate exceeds the pathogens’ growth rates. These findings will help inform public health control strategies. The supplement includes MATLAB source script, Maple workbook, and figures.

This is a report on a dynamic autonomous magnetic interaction which does not depend on polarities resulting in short ranged repulsion involving one or more inertial bodies and a new class of bound state based on this interaction. Both effects are new to the literature, found so far. Experimental results are generalized and reported qualitatively. Working principles of these effects are provided within classical mechanics and found consistent with observations and simulations. The effects are based on the interaction of a rigid and finite inertial body (an object having mass and moment of inertia) endowed with a magnetic moment with a cyclic inhomogeneous magnetic field which does not require to have a local minimum. Such a body having some DoF involved in driven harmonic motion by this interaction can experience a net force in the direction of the weak field regardless of its position and orientation or can find stable equilibrium with the field itself autonomously. The former is called polarity free magnetic repulsion and the latter magnetic bound state. Experiments show that a bound state can be obtained between two free bodies having magnetic dipole moment. Various schemes of trapping bodies having magnetic moments by rotating fields are realized as well as rotating bodies trapped by a static dipole field in presence of gravity. Also, a special case of bound state called bipolar bound state between free dipole bodies is investigated.

Twenty-four extensively-reared Iberian pigs were used to study the influence of fattening period length (30, 60 or 90 days) on the fatty acid profiles of intramuscular and subcutaneous fat and the relationships between both profiles. Regarding fatty acid (FA) percentage, PUFA was greater in backfat and MUFA was greater in intramuscular fat (IMF), regardless fattening period length. The longer fattening period increased MUFA content in backfat (which had a more marked change in oleic acid) and decreased PUFA content in backfat and IMF, but it did not affect SFA content. Within the 3-layers subcutaneous backfat, SFA content was greater in the inner layer, MUFA was greater in the outer layer and PUFA was greater in both of these layers. The few differences in FA composition between both adipose tissues suggest that the changes due to the feeding regime are slow and, therefore, although the length of the fattening phase was increased, the fatty acid profile did not change substantially. The strong relationship between the FA profiles of IMF and backfat might be used to predict one profile from the other one when this latter was more readily available for sampling or analytical reasons.

The principles of causality and unitarity are studied within rational nonlinear electrodynamics proposed earlier. We investigate dyonic and magnetized black holes and show that in the self-dual case, when the electric charge equals the magnetic charge, corrections to Coulomb's law and Reissner-Nordstrom solutions are absent. In the case of the magnetic black hole, the Hawking temperature, the heat capacity and the Helmholtz free energy are calculated. It is shown that there are second-order phase transitions and it was demonstrated that at some range of parameters the black holes are stable.

Here we report highly efficient, indium tin oxide (ITO)-free polymer solar cells (PSCs) with an ultrathin copper (Cu) film(~10 nm) coated with a thin layer of poly[(9,9-bis(3‘-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] (PFN) as transparent electrode. Despite of its lower far-field transmittance of the electrode, the obtained ITO-free device based on the ultrathin Cu film can delivery higher absorption efficiency than that of the device based on ITO substrate in the long wavelength region, which can be attributed to the formation of metal resonant microcavity between the opaque back metal mirror (MoO3/Al electrode) and the transparent Cu film with high reflectance. As a result, polymer solar cells based on poly[[2,6'-4,8-di(5-ethylhexylthienyl)benzo[1,2-b;3,3-b]dithiophene][3-fluoro-2[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl]] (PTB7-Th) and [6,6]-phenyl C71-butyric acid methyl ester (PC71BM) blend show a high power conversion efficiency (PCE) of 8.21 %, comparable to that of the control device based on ITO electrode (with a PCE of 9.60% ). The results demonstrate that thermally evaporated Cu thin film electrode can be promising candidate to replace ITO for highly efficient PSCs, thus may open up the possibility for massive production of PSCs with low cost.

Here, we report the draft genome sequence of the type strain of Ideonella azotifigens DSMZ21438^T (formally 1a22^T = JCM15503^T). Ideonella azotifigens DSMZ21438T a novel betaproteobacterial non-symbiotic nitrogen-fixing grass rhizosphere dwelling microbe. The 891,561 paired-end shotgun reads were quality filtered and decontaminated with the ATLAS pipeline, then assembled with Unicycler. The genome size is 6,257,981 bp, an N50 size of 7,849 bp, with a G+C content of 66.71%, and with 5,882 predicted protein-coding genes. I. azotifigens DSMZ21438^T represents the first member of the genus isolated from rhizosphere soil, providing a framework for further study into non-alphaproteobacterial nitrogen fixation and synthetic biology applications.

The WTO is here to stay. Institutions are never perfect. The way the WTO, as an institution, runs its business may not be perfect either. Arab countries are attempting to broaden their engagement in the multilateral trading system in a manner that has many implications. This engagement includes accession to the WTO, participation in WTO dispute resolution mechanism, and representations at the WTO.

Background: Gluten neuropathy (GN) is defined as an otherwise idiopathic peripheral neuropathy in the presence of serological evidence of gluten sensitivity (positive antigliadin and/or transglutaminase or endomysium antibodies). We aimed to compare the quality of life (QoL) of GN patients with control subjects and to investigate the effect of a gluten free diet (GFD) on the QoL. Methods: All consecutive patients with GN attending a specialist neuropathy clinic were invited to participate. Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of neuropathy. The SF-36 questionnaire was used to measure participants’ QoL. A strict GFD was defined as effectively been able to eliminate all circulating gluten sensitivity-related antibodies whilst on the diet. Results: Fifty-three patients with GN and 53 age and gender matched controls were recruited. Compared to controls, GN showed significantly worse scores in physical functioning, role limitations due to physical health, energy/fatigue and general health subdomains of SF-36. After having adjusted for age, gender and disease severity, being on a strict GFD correlated with better SF-36 scores on the pain domain of the SF-36 (beta 0.317, p=0.019) and the overall health change domain of the SF-36 (beta 0.306, p=0.017). Conclusion: In GN physical dysfunctioning is the major determinant of poor QoL compared to controls. Routine checking for elimination of gluten sensitivity-related antibodies that results from a strict GFD should be encouraged as such elimination ameliorates the overall pain and health scores, indicating better QoL.

A series of novel sulfonylurea benzothiazoline were designed by splicing active groups and bioisosterism. A solvent-free synthetic route was developed for the sulfonylurea benzothiazoline derivatives via the cyclization and carbamylation. All the compounds were characterized by IR, 1H-NMR, 13C-NMR, HRMS. The biological activity tests indicated the compounds could protect maize against the injury caused by chlorsulfuron to some extent. The molecular docking result showed that the new compound competed with chlorosulfuron to bind with the herbicide target enzyme active site to attain detoxification.

Italian Directives recommends the good quality of natural mineral waters but literature data assert a potential risk from several microorganisms colonizing wellsprings and mineral water bottling plants. Aim of study is the identification of microorganisms from spring waters (SW) and bottled mineral waters (BMW) samples. Methods: Routine microbiological indicators, Legionella spp., Nontuberculous mycobacteria (NTM), protozoa (FLA) and physical-chemical parameters were assessed in 24 SW and 10 BMW samples performing culture methods and molecular tests as PCR and qPCR. Results: In 33 out of 34 samples no cultivable bacteria were isolated with the exception of 83 CFU/L of Mycobacterium gilvum, detected in one warm rich-mineralized SW. qPCR showed the presence of Legionella genomic units in 24% of samples (mean 2,9x10²±1,7x10² GU/L) and NTM genomic units in 18% of samples (mean 5,7x10^3±4,1x10³ GU/L). Vermamoeba vermiformis and Acanthamoeba polyphaga were recovered respectively in 70% of BMW samples (counts from 1,3x10³ to 1,2x10⁵) and 42% of SW samples (counts from 1,1x10³ to 1,3x10⁴). Vahlkampfia spp. was detected in 42% of SW and 70% of BMW samples (mean 1,3x10⁴ ±2,9x10³ GU/L). Conclusion: The study highlights a low rate of microbial risk and the importance of risk assessment in natural mineral waters.

Cell mechanics is a biophysical indicator of cell state, such as cancer metastasis, leukocyte activation, and cell cycle progression. Atomic force microscopy (AFM) is a widely used technique to measure cell mechanics, where the Young modulus of a cell is usually derived from the Hertz contact model. However, the Hertz model assumes that the cell is an elastic, isotropic, and homogeneous material and that the indentation is small compared to the cell size. These assumptions neglect the effects of the cytoskeleton, cell size and shape, and cell environment on cell deformation. In this study, we investigated the influence of cell size on the estimated Young’s modulus using liposomes as cell models. Liposomes were prepared with different sizes and filled with phosphate buffered saline (PBS) or hyaluronic acid (HA) to mimic the cytoplasm. AFM was used to obtain the force indentation curves and fit them to the Hertz model. We found that the larger the liposome, the lower the estimated Young’s modulus for both PBS-filled and HA-filled liposomes. This suggests that the Young modulus obtained from the Hertz model is not only a property of the cell material, but also depends on the cell dimensions. Therefore, when comparing or interpreting cell mechanics using the Hertz model, it is essential to account for cell size.

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.

Background: Biological processes are based on complex networks of cells and molecules. Single cell multi-OMICs is a new tool aiming to provide new incites in the complex network of events controlling the functionality of the cell.; Methods: Since single cell technologies provide many sample measurements, they are the ideal environment for the application of deep learning and machine learning approaches. An autoencoder (AE) is composed of an encoder and a decoder sub-model. AE are very powerful in data compression and noise removal. However, the decoder model remains a black box from which is impossible to depict the contribution of the single input elements. We have recently developed a new class of autoencoders, called Sparsely Connected Autoencoders (SCA), which have the advantage of providing a controlled association among the input layer and the decoder module. This new architecture has the benefit that the decoder model is no anymore a black box and it can be used to depict new biologically interesting features from single cell data; Results: In this paper, we show that SCA hidden layer can grab new information usually hidden in single cell data, like as providing clustering on meta-features difficult, i.e. transcription factors expression, or impossible, miRNA expression, to depict in single cell RNAseq data. Furthermore, a SCA representation of cell clusters has the advantage of simulating a conventional bulk RNAseq, which is a data transformation allowing the identification of similarity among independent experiments; Conclusions: In our opinion, SCA represent the bioinformatics version of a “Swiss Army knife” for the extraction of hidden knowledgeable features from single cell OMICs data.

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.

Cancer is the second leading cause of death worldwide. It is theorized that underlying genetic and epigenetic changes enable cells to proliferate out of control by escaping regulatory mechanisms. Although traditional molecular profiling techniques, i.e., bulk sequencing, can identify common mutations and gene expression patterns in cancer cells, they cannot detect tumour heterogeneity. However, single-cell technology has provided an ample opportunity to overcome this difficulty. Since this technology allows us to detect the heterogeneous properties of all cancer cells, this can further our knowledge of the signaling pathways in cancer cells. Indeed, single-cell transcriptomics technology has paved the road for identifying novel biomarkers and signaling pathways, which can serve as targets. This study aims to review the current knowledge about pathways involved in developing cancer cells and shed light on single-cell studies as promising therapeutic approaches.

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.

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.

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.

Hard tissue apposition along the root canal walls is a slow, normally occurring physiological aging process. In response to tooth wear, local deposition of hard tissue may also occur in the pulp at a slow pace. Sometimes, the rate of hard tissue deposition acceleration may seem to be uncontrolled after dental trauma, autotransplantation, and orthodontic therapy, leading to rapid partial or total obliteration of the root canal space. This situation is called calcific metamorphosis (CM) or pulp canal obliteration (PCO). Although the incidence of pulpal necrosis in these teeth is believed to be infrequent, conventional endodontic therapy in severely calcified canals poses extreme difficulties and a higher risk for procedural accidents. This article aims to review the available approaches for the predictable negotiation of calcified canals and to introduce the buckling resistance activation test (BRAT) technique.

Study design: Technical note. Objectives: To present a novel technique of treatment for patient with basilar invagination. Background : Basilar invagination (BI) is considered a congenital condition and can compress the cervicomedullary junction, causing neurologic deficit. Severe neurological deficit due to BI should be treated surgically. However, there is controversy regarding whether an anterior or posterior approach should be used. Anterior approach is optimal for decompression of cervicomedullary junction, but this approach has high complication rates. Posterior reduction has a high risk of occipital screws backout and/or instrument failure. Materials and Methods : A 15-year-old boy with severe myelopathy was referred to our hospital. He had neck pain, muscle weakness of bilateral upper limbs, gait disturbance appeared 3 months before he visited our hospital, he drops a cup several times recently. In the examination, he had hyperreflexia of upper and lower limbs and muscle weakness of bilateral arms (MMT 4), hypoesthesis was observed bilaterally below elbow and both legs. He also had clumsiness of bilateral hands, mild urinary and bowel incontinence, and spastic gait. His 10 second grip and release test was 16 in both hands. His grip power was 20 kg in right and 17 kg in left. Radiograms showed severe BI and spinal cord was severely compressed with odontoid process.. Results : The patinet underwent posterior surgery with C-arm free technique. All screws including occipital screws were inserted adequate position under navigation guidance. Reduction was achieved with skull rotation and distraction. A follow-up at one year we have these results : Manual muscle testing results and sensory function tests showed almost full recovery, bilateral arms (MMT 5) ,walking smoothly. Cervical Japanese orthopedic association score of the patient has improved from 9/17 to 16/17. Post-operative images showed an excellent spinal cord decompression, and no major or severe complications has occured . Conclusions/Level of Evidence : Basilar invagination with Klippel-Feil syndrome is relatively rare condition. Posterior approach and occipito-cervical fixation for BI treatment with navigation technique is a safe method to treat severe myelopaty with reducible odontoid. This novel navigation technique provides an excellent results for a patient with BI. Level V.

Cavitation bubbles are commonly existing in shipbuilding engineering, ocean engineering, mechanical engineering, chemical industry, and aerospace. Asymmetric deformation of bubble occurs near the boundary, and the non-spherical cavitation bubbles have strong destructive effects, inducing high amplitude loading at the nearby boundary. The purpose of this paper is to investigate the laser-induced of cavitation bubble, non-spherical collapse behavior near the boundary. In this study, experimental data such as bubble pulsation process and bubble surface velocity distribution were obtained by high-speed camera technique and full-field velocity calculation. The results show that the bubble appeared non-spherical collapse shapes, near different boundaries, with near-hemispherical, near-ellipsoidal, near-cone and near-pea shapes, and the bubble surface velocity distribution is not uniform. When bubble near the free surface or rigid boundary, the smaller the stand-off r is, the more obvious the repulsive effect of the free surface and the attractive effect of the rigid boundary are. As the stand-off r decreases, the larger the Bjerknes force and the bubble surface velocity difference, the more pronounced the non-spherical shape.

Band structure calculations using the spin-polarized relativistic Korringa-Kohn-Rostoker (SPRKKR) band structure method have been performed to determine the intrinsic magnetic properties (magnetic moments, magneto-crystalline anisotropy -MAE and Curie temperatures) of the Fe5-x-yCoxMySiB2 (M = Re, W) alloys. The general gradient approximation for ex-change-correlation potential and the atomic sphere approximation (GGA ASA) have been em-ployed. Previous studies showed that the Co doping is turning the in-plane into axial anisotropy for a certain doping range, whilst the 5d doping enables a strong spin-orbit coupling of Fe-3d and M-5d states which is needed to enhance the MAE. The theoretical calculations aim to find the dependence of the anisotropy constant K1 for combined Co and M doping, building a two-dimensional (2D) map of K1 for 0 ≤ x ≤ 2 and 0 ≤ y ≤ 1. Similar theoretical 2D maps for magnetization and Curie temperature vs. Co and M content (M = W and Re) have been built, allowing to select alloy compositions with enhanced values of uniaxial anisotropy, magnetization and Curie temperature. Magnetic properties of Fe4.1W0.9SiB2 alloy that meets the selection criteria for axial anisotropy K1 > 0.2 meV/f.u., Curie temperature Tc > 800 K determined by mean field approach and magnetization µ0Ms > 1 T are discussed.

This research investigates the utilization of human driving models in autonomous vehicles, particularly in scenarios with minimal or no interactions with other vehicles. Human driving models provide valuable insights into driver behavior and play a crucial role in shaping the behavior of autonomous vehicles, enhancing their performance and user experience. The primary focus of the study is the creation of a planning model for autonomous vehicles when navigating roundabouts in the absence of traffic. This model seeks to emulate human driving behavior, ensuring predictability, safety, optimization of traffic flow, and adaptation to various roundabout geometries. To achieve this, the research introduces a trajectory model that takes into account geometric attributes and speed variations within roundabouts. The model is calibrated using empirical data and generalizes parameters through statistical regression methodologies. This model is referred to as "MRoundabout" and is evaluated for its consistency in generating plans that closely mimic human driving behavior within roundabouts. While the study presents a promising approach, it acknowledges limitations related to the model's reliance on geometric attributes and its inability to account for external factors like weather conditions. This research underscores the importance of bridging the gap between theoretical research and practical application, with the aim of enhancing safety and the overall user experience in real-world driving scenarios.

This article presents the possibilities of using ferrite absorption material for shielding rooms with medical devices in order to additionally protect them against the limits of the electric component of the E field, which are up to 61 V/m. These values may appear in connection with the currently launched 5G system operating in the high-band frequency range, i.e. 28 GHz and 38 GHz, and may cause negative effects on the operation of medical devices. The possibilities of using ferrite absorption material for shielding rooms with medical devices were determined based on the results of measurements of the electrical properties of the ferrite material performed using two methods: the reflection method and the free space method. In the article, the complex electrical permittivity and complex magnetic permeability were determined for a ferrite plate based on measurements of the reflection coefficient and the transmission (attenuation) coefficient. The presented calculation and measurement results were used to show the properties of the ferrite material in the frequency range from 15 GHz to 45 GHz and to show the possibility of using it for shielding rooms as a material absorbing electromagnetic waves in this frequency range.

Rollover prevention of partially-filled tank trucks is an industry teaser, with the core challenge being real-time perception and observation of the liquid state inside the tank. In order realize re-liable observation of sloshing liquid, this article firstly proposes a sloshing modeling method based on multi-degree-of-freedom pendulum model, and derives the double mass trammel pendulum model (DMTP, 2DOF) accordingly, which accurately reflects the sloshing dynamics under more pervasive working conditions. Secondly, a free surface fluctuation sensor is designed based on magnetostriction, capable of measuring the inclination and height of the liquid level inside tanks filled with hazardous chemical. Finally, the unscented Kalman filter (UKF) is utilized to synthesize the information of the two, establishing a credible real-time observation of the sloshing liquid. Verified through vehicle-fluid coupled co-simulation, under condition of con-secutive double lane change, observation error of the proposed method is only 25.9% that of the open-loop calculation, providing a secure guarantee for the observation of the state variables of the single pendulum model (SP) used for most kinds of anti-rollover controller.

In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to the intermediate and elder patients. Therefore, it’s imperative to identify identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify prognostic factors. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients.

Roller milling of sorghum and quinoa seeds into flour fractions (course, middle, and fine) was investigated, chemically analysed and applied in the baking of gluten-free sourdough bread. Gap settings were adjusted to 0, 5, 8 and 10 for quinoa and 3, 5, and 7 for sorghum. The fine fractions reached values of up to about 41% (gap 8) for quinoa and around 20% for sorghum (gap 5). SEM pictographs illustrated clear separation of each fraction with chemical analysis showing high contents of protein, TDF (total dietary fibre) and IDF (insoluble dietary fibre) in the course fraction. Up to 77% starch content was obtained in the fine fraction with significant amounts of SDF (soluble dietary fibre) which has good health benefits. Increasing the dough moisture up to 90% helped in decreasing the bread crumb firmness, while low Avrami parameters and RVA pasting behaviour indicated slow bread staling rate for both sourdough breads.

Various vestibuloplasty techniques have been reported to increase the attached mucosa (AM) and vestibular depth around dental implants. However, these surgical methods have disadvantages, such as limitations in manipulation, necessity of suturing, postoperative discomfort, swelling, and pain. This study aimed to evaluate the efficacy of laser-assisted periosteal fenestration (LA-PF) in treating a patient with a shallow vestibule and insufficient AM around dental implants. The LA-PF technique was performed using an Er:YAG laser. First, a partial-thickness apically positioned flap (APF) was performed. Horizontal periosteal fenestration was performed using an Er:YAG laser to expose the bones. Periosteal suturing was not required. After 12 months, sufficient AM and deepened vestibule were obtained and maintained. Thus, the LA-PF technique may be a simple and predictable treatment modality for vestibuloplasty around dental implants.

Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. The data used in the analysis come from theoretical anc computational protocols, which have been proven to be very usefull in this context. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.

Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.

This work aimed to develop an easy-to-use smartphone-based electrochemical biosensor to quickly assess coffee blend's total polyphenol (Phs) content at industrial and individual level. The device is based on a commercial carbon-based screen-printed electrode (SPE) modified with multi-walled carbon nanotubes (CNTs) and gold nanoparticles (GNPs). At the same time, the biotransducer, Laccase from Trametes versicolor, TvLac, was immobilized on the sensor surface by using glutaraldehyde (GA) as cross-linking agent. The platform was electrochemically characterized to ascertain the influence of the SPE surface modification on its performance. The working electrode (WE) surface morphology characterization was obtained by scanning electron microscopy (SEM) and Fourier-transform infrared (FT-IR) imaging. All the measurements were carried out with a micro-potentiostat Sensit Smart by PalmSens connected to a smartphone. The developed biosensor provided a sensitivity of 0.12 μA/μM, a linear response ranging from 5 to 70 μM, and a lower detection limit (LOD) of 2.99 μM. Afterwards, the biosensor was tested for quantifying the total Phs content in coffee blends, evaluating the influence of both the variety and the roasting degree. The smartphone-based electrochemical biosensor performance has been validated though the Folin-Ciocâlteu standard method.

The free energy principle (FEP) is a mathematical and scientific principle that describes the relationship between the physical behavior of a dynamical system and the interpretation of such behavior as carrying out inference. It blurs the boundary between the ontological mode of the system of interest and the epistemological significance it acquires through its dynamic interaction with the environment. New materialism (or neo-materialism), despite lacking a single definition, refers to a range of emerging perspectives that attempt to dismantle the long-held divisions between ontology, epistemology, and even ethics, with the aim of achieving a comprehensive transformation of naturalized thinking. In this context, new materialism provides powerful tools to reframe some of the conceptual foundations of the FEP. This paper is the first in a series that aims to systematically construct a neo-materialistic perspective for the FEP, exploring its wide-ranging implications. It serves as an introduction to the series, arguing for the justification of deploying new materialism to reframe the FEP and introducing some essential concepts to be utilized in developing a neo-materialistic account of the FEP.

Diets that restrict the amount of carbohydrates positively affect markers related to metabolic syndrome (MS). However, completely carbohydrate-free diets have been studied in lesser extent, being their effect on biochemical and morphometric parameters in a rat model of MS the main objective of this study. MS was induced by a high-glucose diet for 20 weeks in male Wistar rats with a subsequent exposition to an essentially carbohydrate-free diet (CFD) for 20 weeks. Daily measurements of food consumption and monthly measurements of body weight were made. At week 40, glucose, insulin, lipid profile, ketone bodies, C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, liver and muscle glycogen, and serum, hepatic, renal and pancreatic malondialdehyde (MDA) were assessed. Exposition to CFD showed decrease in caloric intake and body weight. Likewise, the group showed normalization in liver and serum MDA parameters, insulin, lipid profile, ALT, liver glycogen, and creatinine. The CFD decreased glucose concentration and the inflammatory state, also, increased the concentration of ketone bodies and urea. The change towards CFD reverses the metabolic alterations generated with MS except for glycemia and uremia, probably due to the high rate of gluconeogenesis generated by the high protein content in the diet.

In this work we report recent theoretical calculations of a superconducting island in a strong vortex confinement regime. The obtained results reveal the evolution of superconducting condensate as a function of electron mean-free path (l) with the evolution of an applied magnetic field H0. The results of this study provide an insight about the emergent superconducting properties under such conditions, using the Ginzburg-Landau numerical simulations where spatial variation of thickness d on island, omnipresent in these kind of structures grown on Si (111), is taken into account. These results offer a new route to tailor superconducting circuits by using the controlled bombardment, in order to explore the impact on vortex distribution, phase of order parameter, number of vortices, free energy and the first H1 and second critical field H2.

In this work, we report the electric energy storage properties of (1-x)Bi0.5(Na0.8K0.2)0.5TiO3-xBi0.2Sr0.7TiO3 (BNKT-BST; x = 0.15-0.50) relaxor ferroelectric ceramics enhanced via a domain engineering method. A rhombohedral–tetragonal phase, the formation of highly dynamic PNRs, and a dense microstructure are confirmed from XRD, Raman vibrational spectra, and microscopic investigations. The relative dielectric permittivity (2664 at 1 kHz) and loss factor (0.058) were gradually improved with BST (x=0.45). The incorporation of BST into BNKT can disturb the long-range ferroelectric order, lowering the dielectric maximum temperature Tm and inducing the formation of highly dynamic polar nano-regions. In addition, the Tm shifts toward high temperature with frequency and a diffuse phase transition, indicating relaxor ferroelectric characteristics of BNKT-BST ceramics, which is confirmed by the modified Curie Weiss law (γ=1.83). The rhombohedral–tetragonal phase, fine grain size, and lowered Tm with relaxor properties synergistically contribute to a high recoverable energy density Wrec of 0.81 J/cm3 and a high energy efficiency η of 86.95% at 90 kV/cm for x = 0.45.

3D metal nanostructures are often the basis of several applications such as in catalysis, plasmonics, medical diagnosis, therapy, drug screening, ophthalmologic, and biomedical applications. Porous gold nanoparticles (PGNs) are intensively investigated due to their outstanding morphological as well as advantageous optical properties. Unfortunately, the thermal stability of these open-porous structures is poor, i.e. even as a result of low-temperature annealing (150$^\circ$C in air), their porosity disappears and they lose their favorable optical properties. In order to preserve their beneficial properties, a thin metal oxide coating can be applied. Changing the coating's thickness and/or composition, the optical response of the PGNs can also be tuned in a wide wavelength region. Moreover, these nanoparticles can be synthesized also in support-free form, which makes them more attractive from an application point of view. This review article summarizes some of the preparation modes of these complex nanostructures (fixed and support-free), as well as their thermal stability and optical responses.

A structural study of the 6√3 reconstruction conversion on 4H-SiC substrate surface in an Ar medium with a short sublimation annealing time into quasi-free epitaxial graphene by means of hydrogen intercalation between the upper layer of SiC and the adjacent reconstructed layer was carried out using the technique of reflection high-energy electron diffraction (RHEED) characterizing the surface of a crystalline material. A slight violation of the 6√3 reconstruction layer formation uniformity was found. The results of the study of the crystal structure of quasi-free graphene and single-layer graphene comprising a buffer layer formed on 4H-SiC in the traditional way in an Ar atmosphere without intercalation were compared.

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects and especially hydroxamic acid based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The models created show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.

Heterojunctions based on metal halide perovskites (MHPs) are promising systems for photocatalytic hydrogen evolution reaction (HER). In this work, we coupled Cs3Bi2Br9 nanocrystals (NCs), obtained by wet ball milling synthesis, with g-C3N4 nanosheets (NSs) produced by thermal oxidation of bulk g-C3N4 in air. These methods are reproducible, inexpensive, and easy to scale up. Heterojunctions with different loadings of Cs3Bi2Br9 NCs were fully characterized and tested for HER. A relevant improvement of H2 production with respect to pristine carbon nitride was achieved at low NCs levels reaching values up to about 4600 µmol g-1 h-1. This work aims to provide insights on the synthesis of inexpensive and high performing heterojunctions using MHP for photocatalytic applications.

Many countries have implemented free early childhood education to solve the affordability and accessibility problems without considering the sustainability of policy; thus, they have to discontinue the policy. The city of Nanjing, China, is no exception. This case study adopted a mixed-methods approach to understanding how and why the policy was formulated, implemented, and failed in the city, using the “policy cycle” framework. Altogether 232 kindergarten principals and teaching/research staff were randomly sampled and surveyed, and 5 kindergarten principals and 5 teaching/researcher staff were interviewed. The results indicated that there were many obstacles to the policy’s sustainability, including the conflict of interest, the inefficient policy implementation, the insufficient funding, and more social inequality issues. And the policymakers made mistakes in the five domains of the policy cycle: the context of influence, the context of policy text production, the context of practice, the context of outcomes, and the context of political strategy. Finally, the lessons for a more sustainable policy decision process are discussed.

Transcription factors (TFs) are proteins that recognize specific DNA fragments in order to decode the genome and ensure its optimal functioning. TFs work at the local and global scales by specifying cell type, cell growth and death, cell migration, organization and timely tasks. We investigate the structure of DNA-binding motifs with the theory of finitely generated groups. The DNA ‘word’ in the binding domain -the motif- may be seen as the generator of a finitely generated group Fdna on four letters, the bases A, T, G and C. It is shown that, most of the time, the DNA-binding motifs have subgroup structure close to free groups of rank three or less, a property that we call ‘syntactical freedom’. Such a property is associated to the aperiodicity of the motif when it is seen as a substitution sequence. Examples are provided for the major families of TFs such as leucine zipper factors, zinc finger factors, homeo-domain factors, etc. We also discuss the exceptions to the existence of such a DNA syntactical rule and their functional role. This includes the TATA box in the promoter region of some genes, the single nucleotide markers (SNP) and the motifs of some genes of ubiquitous role in transcription and regulation.

Gastric emptying rate (GER) may impact diabetes and obesity in humans and could provide a method to reduce canine weight gain. Starch, the most common source of carbohydrates (CHOs) in pet food, is classified as rapidly or slowly digestible, or resistant to digestion. This study investigated starch source effects in commercial extruded dog foods on the GER of 11 healthy adult Siberian Huskies (5.63±0.72 years; mean±SEM). Test diets were classified as traditional, grain-free, whole-grain, and vegan. Dogs received each diet once, a glucose control twice, and acetaminophen (Ac) as a marker for GER in a randomized, partially-replicated, 6x6 Latin square design. Pre- and post-prandial blood samples were collected at 16 timepoints from -15 to 480 minutes. Serum Ac concentrations were assessed via standard spectrophotometric assays and fitted with a mathematical model to estimate parameters of GER. Data was analyzed using a repeated measures ANOVA, followed by a Tukey-Kramer post-hoc test when significant (p<0.05). More total emptying (p= 0.0430) occurred at faster rate (p=0.0668) in dogs fed the grain-free diet, which contained the lowest total starch (34.03 ± 0.23%) and highest resistant starch (0.52 ± 0.007%). This research may benefit future diet formulations to reduce the prevalence of canine weight gain.

Background: Ultrasonography’s usefulness in endometrial cancer (EC) diagnosis consists of its staging and predictive roles. Ultrasound-measured tumor-free distance from the tumor to the uterine serosa (uTFD) is a promising marker for this variable. The aim of the study was to determine the usefulness of this biomarker in locoregional staging, and thus in the prediction of lymph node metastasis (LNM). Methods: We conducted a single-institutional, prospective study on 116 consecutive patients with EC who underwent 2D transvaginal ultrasound examination. The uTFD marker was compared with the depth of ultrasound-measured myometrial invasion (uMI). Univariate and multivariate logit models were evaluated to assess the predictive power of the uTFD and uMI in regard to LNM. The reference standard was a final histopathology result. Survival was assessed by the Kaplan-Meyer method. Results: LNM was found in 17% of the patients (20/116). In the univariate analysis, uMI and uTFD were significant predictors of LNM. Accuracy was 70.7%, and NPV was 92.68% (OR 4.746, 95% CI 1.710-13.174) for uMI (p = 0.002), and 63.8%, and 89.02% (OR 0.842, 95% CI 0.736 – 0.963), respectively, for uTFD (p = 0.01). The cut-off value for uTFD in the prediction of LNM was 5.2 mm. The absence of LNM was associated more with biomarker values uMI &lt;1/2 and uTFD &gt;=5.2 mm than with the presence of metastases with uMI &gt;1/2 and uTFD values &lt;5.2 mm. In the multivariate analysis, the accuracy of the uMI-uTFD model was 74%, and NPV was 90.24% (p = NS). Neither uMI nor uTFD are surrogates for overall and recurrence-free survivals in endometrial cancer. Conclusions: Both uMI and uTFD, either alone or in combination, are valuable tools for gaining additional preoperative information on expected lymph node status. Negative lymph nodes status is better described by ultrasound biomarkers than a positive status. It is easier to use uTFD measurement as a biomarker of EC invasion than uMI, and the former still maintains a similar predictive value for lymph node metastases to the latter at diagnosis.

This article presents, for the first time, the kinetics and the general conversion features of a 3-initiator system (A/B/N), based on proposed mechanism of Mokbel et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using copper complex as the initiator. Higher FRP and CP conversion can be achieved by co-initiators concentration [B] and [N], via the dual function of (i) regeneration [A], and (ii) generation of extra radicals S' and S. The FRP and CP conversion is proportional to, respectively, the nonlinear and linear power of bI[A][B], where b and I are the absorption coefficient and the light intensity, respectively. System in air has lower conversion than in laminate due to the oxygen inhibition effects. For thick samples (with thickness z), there is an optimal concentration [A*] which is inverse proportional (bzI), in contrast with very thin sample, in which the conversion is an increasing function of [A] and [B]. The unique feature of dark polymerization in CP conversion enables the polymerization to continue in living mode, in contrasts with that of the radical-mediated pathway in most conventional FRP. The measured results of Mokbel et al are well analyzed and matching the predicted features of our modeling.

In this article, a technology for producing wire and rod solder from 52In-48Sn alloy has been developed and investigated in the conditions of small-scale production. The use of direct extrusion of wire and rods instead of the traditional technology for producing solder, which includes pressing, rolling and drawing, can significantly reduce the fleet of required equipment. Using only a melting furnace and a hydraulic press, solder wires and rods can be produced in various sizes. Shortening the production cycle allows you to quickly fulfill small orders and be competitive in sales. The article developed a mathematical model of direct extrusion, which allows you to calculate: extrusion ratio, extrusion speed and pressing force. The results of modeling the process of extrusion of wire ∅2.00 mm and rods ∅8.0 mm made of 52In-48Sn alloy are presented. The temperature of the solder and the tool is simulation in software QForm based on the finite element method. Experimental results of manufacturing ∅2.0 mm solder wire and ∅8.0 mm rods are presented. The microstructure of the direct extruded solder is a eutectic of phases γ and β. Energy-dispersive X-ray spectroscopy (EDS) mapping of the 52In-48Sn alloy showed that the solder obtained by direct extrusion has a uniform distribution of structural phases. The developed technology can be used in the manufacture of wires and rods from other low-melting alloys.

The synthesis of additives for thinning mineral suspensions based on sodium polyacrylate was carried out. The effect of molecular weight regulators on the molecular weight characteristics of the polymer and the effect of such polymers on the rheological properties of suspensions was studied. Sodium acrylate polymers are synthesized by free radical polymerization in aqueous solution using molecular weight regulators. The molecular weight characteristics of the polymeric samples were estimated by viscometry using Mark-Houwink-Kuhn-Sakurada (MHKS) equation. Synthesized polymers were used as thinners ceramic slurries, prepared according to the recipe of the enterprises producing ceramic products. The thinning ability of polymer samples with different molecular weights was estimated using an Engler viscometer from the time of the ceramic slurry flow. The influence of the type and amount molecular weight regulator on polyacryates was revealed. It was found that molecular weight synthesized samples was in the range of 21000 - 91000. It was determined that samples with a molecular weight of 28000 - 35000 synthesized using mercaptoethanol (at a dosage of 0.5-1.5% by weight of the monomer) provide optimal fluidity to the ceramic slurry.

In this paper, we present and analyze a compact inner-wall grating slot microring resonator (IG-SMRR) with the footprint of less than 13 μm × 13 μm on the SOI platform for label-free sensing, which comprises a slot microring resonator (SMRR) and inner-wall grating (IG). Its detection range is significantly enhanced without the limitation of the free spectral region (FSR) owing to the combination of SMRR and IG. Structural parameters of IG and SMRR are investigated and optimized for favorable transmission properties. The simulation results shows that the IG-SMRR has an ultra-large quasi-FSR of 84.6 nm, and the concentration sensitivities of sodium chloride solutions and D-glucose solutions are up to 960.61 pm/% and 933.06 pm/%, respectively. The investigation on the combination of SMRR and IG is a valuable exploration of label-free sensing application for ultra-large detection range and ultra-high sensitivity in future.

High oxidative stress in cells due to inflammation process or excessive cell proliferation would produce oxidants or free radicals with biomarkers, one of which is malondialdehyde (MDA). Passion fruit seed’s contain high antioxidant and are expected to decrease the level of cholesterol and MDA. The objective is to identify the effect of passion fruit seed’s ethanol extract in Wistar rats that have been fed with atherogenic feed. The method was preclinical trial (post-test control group design) in rats, by administering passion fruit seed’s ethanol extract for 14 days. This study used 26 male rats aged two months, divided into 5 groups. The result showed significant difference in MDA level which was found in group that was given passion fruit seed extract 10mg/kg BW with positive control group that was given standard feed. Passion fruit seed’s extract showed significant difference in level of triglyceride, which was found in negative control group that was given atherogenic feed with group that was given passion fruit seed’s extract 5mg/kg BW (mean±standard deviation: 1.09±0.30 mg/dL vs 0.77±0.25mg/dL; p=0.048). This study showed that passion fruit seed’s ethanol extract had significant lowering effect in level of MDA, total cholesterol, and triglyceride for 14 days.

According to Copenhagen interpretation, a quantum particle can exist in a superposition of all possible states, out of which only one state is observed when it is measured. Interestingly, it has been observed that interaction with the quantum particle during measurement can also affect the outcome of the state. A scheme for interaction free measurement was proposed by Elitzur and Vaidman [Found. Phys. 23, 987 (1993)], where they used Mach Zehnder interferometer to detect whether a bomb is alive or dead. In 25 % of the cases they were able to detect that the bomb is alive without exploding it. Here, we demonstrate the above experiment using quantum computing, which can be realized in a quantum computer designing quantum circuits on it. We explicate all the cases, including whether the bomb is alive or dead by proposing new quantum circuits and executing those in QISKit as provided by IBM Quantum Experience platform and verify the obtained results.

Deep fat frying is not novel, but a classical antiquity culinary technique preferred chiefly for its swiftness, amenity, conferment of a crisp texture, attractive sensorial and organoleptic qualities and thus delectableness of the fries. Regrettably, repeated use of oils for deep frying impacts the storage life and nutritional suitability of fries. This concerted study investigated the effects of continuous deep fat frying on the physicochemical properties of ten brands of edible cooking oils: Fortune Butto, Roki, Tamu, Best Fry, Golden Fry, Mukwano, Sunny, Sunvita, Sunlite and Sunseed used in deep frying of potato chips in Kampala, Uganda. Three oil samples from local Irish chip fryers were also collected. The color value (CV) and the acidification of the oils as free fatty acid (FFA), peroxide value (POV), paraanisidine value (AnV) and iodine adsorption value (IV) before and between ten successive deep-fryings using potato chips were determined. The possible reuse of the oils was estimated from the frying round when a quality criterion surpassed national or CODEX specifications for the respective edible cooking oils. For fresh oils, the statistical parameter ranges were: CV (0.4R 3.4Y-7.7R 70Y), % FFA (0.0430-0.1508), POV (0.5951-6.6134 meqO₂/Kg), AnV (0.90-4.30) and IV (57.62-128.35gI₂/100g). By the tenth fry, the values were respectively 3.0R 23Y-20.4R 70Y, 0.2286-0.4817, 11.1138-15.7525 meqO₂/Kg, 10.31-22.16 and 53.66-126.03 gI₂/100g. Reuse of the oils for continuous frying of potatoes on the same day can be done only up to 7 times on average for hard oils and 6 times for soft oils.

As bakery products contribute considerably to the daily intake of the carcinogen acting substance acrylamide (AA), the aim of this study was to evaluate the impact of the cropping system (conventional vs. organic farming) on AA precursor levels of free asparagine (Asn) across different cultivars of the cereal species, namely winter wheat (Triticum aestivum), winter spelt (Triticum aestivum ssp. spelta) and winter rye (Secale cereale) with simultaneous consideration of gained grain yields and flour qualities. For this purpose, orthogonal field trials were established at two sites in Southwest Germany over two growing seasons (2006-2007 and 2007-2008). The results indicated a significant impact of the cropping system on free Asn contents. Across all species, free Asn contents in the flour were 26 % lower under organic compared to conventional farming. The impact of the cropping system on individual cultivars was obvious with a maximum reduction in free Asn contents of 50 % (e.g. for cultivars Ludwig, Privileg, Capo) if organically produced. For spelt, a significant impact of the cropping system was only found in 2008 with a reduction in free Asn of up to 25 % if organically produced. Across both cropping systems, cultivar Franckenkorn reached the lowest levels of free Asn. For rye, a significant impact of the cropping system was observed only in 2007 with 33 % higher Asn amounts in the conventional cropping system. Independent of the cropping system, rye reached the highest levels of free Asn followed by wheat and spelt. Across both cropping systems, species and cultivars, the amount of free Asn correlated with the AA content in heated flour with R2=0.63***. Furthermore, the results indicated that lower AA contents in bakery products can be achieved by proper selection of species (e.g. 66 % lower if rye is replaced by wheat) and cultivars. With an appropriate choice of the cultivar, a reduction of up to 65 % was possible within wheat, along with a reduction of 44 % within spelt and 12.5 % within rye. In summary, the results indicated that organically produced wheat especially offers the opportunity to significantly lower the AA potential of bread and bread rolls by the choice of raw materials low in free Asn.

Free vibration analysis of the porous functionally graded circular plates has been presented on the basis of classical plate theory. The three defined coupled equations of motion of the porous functionally graded circular/annular plate were decoupled to one differential equation of free transverse vibrations of plate. The one universal general solution was obtained as linear combination of the multiparametric special functions for the functionally graded circular and annular plates with even and uneven porosity distributions. The multiparametric frequency equations of functionally graded porous circular plate with diverse boundary conditions were obtained in the exact closed-form. The influences of the even and uneven distributions of porosity, power-law index, diverse boundary conditions and the negligibled effect of the coupling in-plane and transverse displacements on the dimensionless frequencies of the circular plate were comprehensively studied for the first time. The formulated boundary value problem, the exact method of solution and the numerical results for the perfect and imperfect functionally graded circular plates have not yet been reported.

Satellite remote sensing is a powerful tool to map flooded areas. In the last years, the availability of free satellite data sensibly increased in terms of type and frequency, allowing producing flood maps at low cost around the World. In this work, we propose a semi-automatic method for flood mapping, based only on free satellite images and open-source software. As case studies, we selected three flood events recently occurred in Spain and Italy. Multispectral satellite data acquired by MODIS, Proba-V, Landsat, Sentinel-2 and SAR data collected by Sentinel-1 were used to detect flooded areas using different methodologies (e.g., MNDWI; SAR backscattering variation; Supervised classification). Then, we improved and manually refined the automatic mapping using free ancillary data like DEM based water depth model and available ground truth data. For the areas affected by major floods, we also validated and compared the produced flood maps with official maps made by river authorities. We calculated flood detection performance (flood ratio) for the different datasets we used. The results show that it is necessary to take into account different factors for the choice of best satellite data, among these, the time of satellite pass with respect to the flood peak is the most important one. SAR data showed good results only for co-flood acquisitions, whereas multispectral images allowed detecting flooded areas also with the post-flood acquisition. With the support of ancillary data, it was possible to produce reliable geomorphological based flood maps in the study areas.

Clinical rehabilitation and sports performance analysis both require the objectification of movement. Kinovea^© is a free 2D motion analysis software that enables the establishment of kinematics parameters. This low-cost technology has been used in sports sciences, as well as clinical field and research work. Although it has been validated as a tool with which to assess time-related variables, this is not yet the case regarding angular and distance variables. The main objective of this study was to determine the validity and reliability of the Kinovea software in obtaining angular and distance data at different perspectives of 90°, 75°, 60° and 45°. For this purpose, a figure with 29 points was designed (in AutoCAD) and 24 frames analysed. Each frame was examined by three observers who each made two attempts. For each export data item, 20 angles and 20 distance variables were calculated, with intra- and inter-observer reliability also analysed. To evaluate Kinovea reliability and validity a multiple approach was applied involving the following analysis: -systematic error with a two-way ANOVA 2x4; -relative reliability with ICC and CV (95% confidence interval); -absolute reliability with Standard Error. The results thus obtained indicate that the Kinovea software is a valid and reliable tool that is able to measure accurately at distances up to 5 m from the object and at an angle range of 90°–45°. Nevertheless, for optimum results an angle of 90° is suggested.

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.

Plant cells are omnipotent and breeding of new varieties can be achieved by protoplast fusion. Such fusions can be achieved by treatment with poly(ethylene glycol) or by applying an electric field. Microfluidic devices allow for controlled conditions and targeted manipulation of small batches of cells down to single cell analysis. To provide controlled conditions for protoplast fusions and achieve high reproducibility, we developed and characterized a microfluidic device to reliably trap few of Arabidopsis thaliana protoplasts and induced a cell fusion by controlled addition of poly(ethylene glycol) (PEG, with a molecular weight of 6000). Experiments were conducted to determine the survival rate of isolated protoplasts in our microfluidic system. Afterwards, PEG induced fusion was studied. Our results indicate that the following fusion parameters had significant impact on the fusion efficiency and duration: PEG concentration, osmolarity of solution, and flow velocity. PEG concentration below 10% led to only partial fusion. Osmolarity of the PEG fusion solution was found to strongly impact the fusion process; complete fusion of two source cells sufficiently took part in slightly hyper osmotic solutions, whereas iso-osmotic solutions led to only partial fusion at 20% PEG concentration. We observed accelerated fusion for higher fluid velocities. Up to this study, it was common sense that fusion is one directional, i.e. once two cells were fused into one cell they stay fused. Here, we present for the first time reversible fusion of protoplasts. Our microfluidic device paves the way to a deeper understanding on the kinetics and processes of cell fusion.

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.