Active targeting can improve the retention of drugs and drug delivery systems in tumors, thereby enhancing their therapeutic efficacy. In this context, vitamin receptors that are overexpressed in many cancers are promising targets. In the last decade, attention and research were mainly centered on vitamin B9 (folate) targeting; however, the focus is slowly shifting towards vitamin B2 (riboflavin). Interestingly, while the riboflavin carrier protein was discovered in the 1960s, the three riboflavin transporters (RFVT 1-3) were only identified recently. It has been shown that riboflavin transporters and the riboflavin carrier protein are overexpressed in many tumor types, tumor stem cells, and the tumor neovasculature. Furthermore, a clinical study has demonstrated that tumor cells exhibit increased riboflavin metabolism as compared to normal cells. Moreover, riboflavin and its derivatives have been conjugated to ultrasmall iron oxide nanoparticles, polyethylene glycol polymers, dendrimers, and liposomes. These conjugates have shown a high affinity towards tumors in preclinical studies. This review article summarizes knowledge on RFVT expression in healthy and pathological tissues, discusses riboflavin internalization pathways, and provides an overview of RF-targeted diagnostics and therapeutics. Full article

Targeting and exploiting the immune system has become a valid alternative to conventional options for treating cancer and infectious disease. Dendritic cells (DCs) take a central place given their role as key orchestrators of immunity. Therapeutic vaccination with autologous DCs aims to stimulate the patient’s own immune system to specifically target his/her disease and has proven to be an effective form of immunotherapy with very little toxicity. A great amount of research in this field has concentrated on engineering these DCs through ribonucleic acid (RNA) to improve vaccine efficacy and thereby the historically low response rates. We reviewed in depth the 52 clinical trials that have been published on RNA-engineered DC vaccination, spanning from 2001 to date and reporting on 696 different vaccinated patients. While ambiguity prevents reliable quantification of effects, these trials do provide evidence that RNA-modified DC vaccination can induce objective clinical responses and survival benefit in cancer patients through stimulation of anti-cancer immunity, without significant toxicity. Succinct background knowledge of RNA engineering strategies and concise conclusions from available clinical and recent preclinical evidence will help guide future research in the larger domain of DC immunotherapy. Full article

Astrocytes are multi-functional cells, now recognized as critical participants in many brain functions. They play a critical physiological role in the clearance of neurotransmitters, such as glutamate and gamma-aminobutyric acid (GABA), and in the regulation of K⁺ from the space of synaptic clefts. Astrocytes also express the excitatory amino acid transporters (EAATs) and aquaporin-4 (AQP4) water channel, which are involved in both physiological functions and neurodegenerative diseases (ND). Some of the ND are the Alzheimer’s (AD), Huntington’s (HD), Parkinson’s diseases (PD), Cerebral edema, amyotrophic lateral sclerosis (ALS), and epilepsy pathological conditions in specific regions of the CNS. Parkinson’s disease is the second most common age-related neurodegenerative disorder, characterized by degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNpc). These project to the striatum, forming an important pathway within the basal ganglia. Mostly, PD has no clear etiology, and the mechanism of dopaminergic (DA) neuron loss is not well illustrated. The results of various studies suggest that astrocytes are involved in the pathophysiology of PD. Evidence has shown that the down-regulation of EAAT-2/GLT-1 and AQP4 expression is associated with PD pathogenesis. However, controversial results were reported in different experimental studies about the expression and function of EAAT-2/GLT-1 and AQP4, as well as their colocalization in different brain regions, and their involvement in PD development. Therefore, under neurological disorders, Parkinson’s disease is related to the genetic and phenotypic change of astrocytes’ biology. In this review, the authors summarized recent their research findings, which revealed the involvement of EAAT-2/GLT-1 and AQP4 expression, the physical interaction between EAAT-2/GLT-1 and AQP4 in astrocyte function, and their potential role in the development of PD in SNpc and Subthalamic nucleus (STN) of the basal ganglia nuclei. Full article

This article addresses the importance of oxidative processes in both the generation of functional gametes and the aetiology of defective sperm function. Functionally, sperm capacitation is recognized as a redox-regulated process, wherein a low level of reactive oxygen species (ROS) generation is intimately involved in driving such events as the stimulation of tyrosine phosphorylation, the facilitation of cholesterol efflux and the promotion of cAMP generation. However, the continuous generation of ROS ultimately creates problems for spermatozoa because their unique physical architecture and unusual biochemical composition means that they are vulnerable to oxidative stress. As a consequence, they are heavily dependent on the antioxidant protection afforded by the fluids in the male and female reproductive tracts and, during the precarious process of insemination, seminal plasma. If this antioxidant protection should be compromised for any reason, then the spermatozoa experience pathological oxidative damage. In addition, situations may prevail that cause the spermatozoa to become exposed to high levels of ROS emanating either from other cells in the immediate vicinity (particularly neutrophils) or from the spermatozoa themselves. The environmental and lifestyle factors that promote ROS generation by the spermatozoa are reviewed in this article, as are the techniques that might be used in a diagnostic context to identify patients whose reproductive capacity is under oxidative threat. Understanding the strengths and weaknesses of ROS-monitoring methodologies is critical if we are to effectively identify those patients for whom treatment with antioxidants might be considered a rational management strategy. Full article

Radioembolization with ⁹⁰Y-microspheres has been reported to induce contralateral liver hypertrophy with simultaneous ipsilateral control of tumor growth. The aim of the present systematic review was to summarize the evidence of contralateral liver hypertrophy and oncological outcome following unilateral treatment with radioembolization. A systematic literature search using the MEDLINE, EMBASE, and Cochrane libraries for studies published between 2008 and 2020 was performed. A total of 16 studies, comprising 602 patients, were included. The median kinetic growth rate per week of the contralateral liver lobe was 0.7% and declined slightly over time. The local tumor control was 84%. Surgical resection after radioembolization was carried out in 109 out of 362 patients (30%). Although the available data suggest that radioembolization prior to major hepatectomy is safe with a promising oncological outcome, the definitive role of radioembolization requires assessment within controlled clinical trials. Full article

New aluminum grain refiners, Al-TiO₂-C-XLa₂O₃ refiners, were manufactured by the in situ reaction of Al powder, TiO₂ powder, C powder, and La₂O₃ powder. The effects of La₂O₃ on the refiners’ microstructure and the grain refining effect of the Al-TiO₂-C-XLa₂O₃ refiners on industrial aluminum were studied. The effect of the sintering process was also studied. The results show that the refiners contain Al₃Ti, TiC, Al₂O₃, AlN, and Al₂₀Ti₂La. As the content of La₂O₃ increases, the amount of Al₂₀Ti₂La also increases. However, the amounts of Al₃Ti, Al₂O_3, and TiC decrease. Al₃Ti is a lath-like compound whose size becomes smaller. The distribution of Al₂O₃ and TiC, however, is more uniform. The Al-TiO₂-C-0.2La₂O₃ refiner has the best grain refining effect on industrial aluminum. The size of the industrial aluminum refined by the Al-TiO₂-C-0.2La₂O₃ refiner is 320 μm; the refiner’s grain size is 8.4% that of the industrial aluminum without refiners 0 μm (380). After adding the novel Al-TiO₂-C-0.2La₂O₃ refiner, the nucleation temperature T_N reached 679.21 °C, which is 17 °C above the nucleation temperature of the industrial aluminum without refiners. The primary transformation time is the longest at 25.5 s, which is 4.6 s higher than that of industrial aluminum (20.9 s). Furthermore, the ΔT of the aluminum is 0.5 °C, which is the lowest value. Full article

The increasing scarcity of water demands proper water management practices to ensure crop sustainability. In this study, the effect of drought stress and biostimulants application on the yield and chemical composition of green pods and seeds of common bean (Phaseolus vulgaris L.) was evaluated. For this purpose, four commercially available biostimulant products, namely Nomoren (G), EKOprop (EK), Veramin Ca (V), and Twin-Antistress (TW), were tested under two irrigation regimes: normal irrigation (W+) and water-holding (W-) conditions. The highest increase (20.8%) of pods total yield was observed in EKW+ treatment due to the formation of more pods of bigger size compared to control treatment (CW+). In addition, the highest yield under drought stress conditions was recorded for the GW- treatment (5691±139 kg/ha). Regarding the effects of biostimulants on the protein and ash content of pods, the application of VW+ treatment (first harvest of pods; 201±1 and 79±1 g/kg dw for proteins and ash content, respectively) and GW+ (second harvest of pods; 207.1±0.1 and 68.4±0.5 g/kg dw for proteins and ash content, respectively) showed the best results. For seeds, the application of GW+ treatment resulted in the highest content for fat, protein, and ash content (52.7±0.1, 337±1, 56±1 g/kg dw) and energetic value (5474±3 kcal/kg dw). γ-tocopherol was the main detected tocopherol in pods and seeds, and it was significantly increased by the application of TWW- (first harvest of pods; 6410±40 μg/kg dw), VW- (second harvest of pods; 3500±20 μg/kg dw), and VW+ (seeds; 39.8±0.1 g/kg dw) treatments. EKW- treatment resulted in the lowest oxalic acid content for both pod harvests (26.3±0.1 g/kg dw and 22.7±0.2 g/kg dw for the first and second harvest of pods, respectively) when compared with the rest of the treatments where biostimulants were applied, although in all the cases, the oxalic acid content was considerably low. Fructose and sucrose were the main sugars detected in pods and seeds, respectively, while the highest content was recorded for the TWW- (first harvest of pods) and GW- (second harvest of pods and seeds) treatments. The main detected fatty acids in pods and seeds were α-linolenic, linoleic, and palmitic acid, with a variable effect of the tested treatments being observed. In conclusion, the application of biostimulants could be considered as an eco-friendly and sustainable means to increase the pod yield and the quality of common bean green pods and seeds under normal irrigation conditions. Promising results were also recorded regarding the alleviation of negative effects of drought stress, especially for the application of arbuscular mycorrhizal fungi (AMF; G treatment), which increased the total yield of green pods. Moreover, the nutritional value and chemical composition of pods and seeds was positively affected by biostimulants application, although a product specific effect was recorded depending on the irrigation regime and harvesting time (pods and seeds). Full article

Lettuce is an economically important crop that can be grown either in the field or greenhouse. Different challenges are present in either environment; therefore, cultivar selection is important. For hydroponic greenhouse lettuce there is relatively little published information on cultivar selection under different lighting sources. The objective of phase 1 was to determine the influence of lighting using high pressure sodium (HPS) or light emitting diodes (LED) on plant fresh weight, height, tip burn index, bolting, and Brix. Phase 2 was similar to phase 1 but with fewer cultivars (1) to allow for greater number of replicates per treatment per crop cycle. Each experiment consisted of three crop cycles over time per phase. Light sources were controlled using an algorithm, Light and Shade System Implementation (LASSI), to achieve a constant average daily light integral under each treatment and crop cycle. Electrical consumption and efficacy (fresh weight per kWh) from each treatment was estimated using data collected on power consumption from representative lamps multiplied by the number of fixtures and the hours fixtures were on per crop cycle. In phase 1, the fresh weight of 2 to 3 cultivars was greater under HPS and 1 to 2 cultivars under LED, depending on production cycle. The HPS-grown lettuce tended to have more tip burn and bolting in crop cycles 1 and 2, with cycle 3 showing similar tip burn incidence. Bolting was only consistently observed in one cultivar, ‘Teodore’. The LED array used less than half as much electricity as the HPS array, while producing relatively similar size lettuce, therefore, leading to electrical efficacies two- to three-times higher in LED than in HPS treatments. In phase 2, significant differences in height were found in ‘Greenstar’ and ‘Xandra’, with HPS producing larger plants than LED. Significant differences were also found in diameter in ‘Greenstar’, ‘Xandra’, ‘Locarno’, and ‘Crunchita’, with HPS again being larger than LED. Full article

The fabrication and luminescent performance of novel phosphors Na₂YMg₂V₃O₁₂:Dy³⁺ were investigated by a conventional solid-state reaction method. Under near-UV light, the Na₂YMg₂V₃O₁₂ host self-activated and released a broad emission band (400–700 nm, with a peak at 524 nm) ascribable to charge transfer in the (VO₄)³⁻ groups. Meanwhile, the Na₂YMg₂V₃O₁₂:Dy³⁺ phosphors emitted bright yellow light within both the broad emission band of the (VO₄)^3- groups and the sharp peaks of the Dy³⁺ ions at 490, 582, and 663 nm at a quenching concentration of 0.03 mol. The emission of the as-prepared Na₂YMg₂V₃O₁₂:Dy³⁺ phosphors remained stable at high temperatures. The obtained phosphors, commercial Y₂O₃:Eu³⁺ red phosphors, and BaMgAl₁₀O₁₇:Eu²⁺ blue phosphors were packed into a white light-emitting diode (WLED) device with a near-UV chip. The designed WLED emitted bright white light with good chromaticity coordinates (0.331, 0.361), satisfactory color rendering index (80.2), and proper correlation to a color temperature (7364 K). These results indicate the potential utility of Na₂YMg₂V₃O₁₂:Dy³⁺ phosphor as a yellow-emitting phosphor in solid-state illumination. Full article

In this paper, laboratory batch adsorption tests were performed to study the adsorption behavior of coke powder in a quinoline aqueous solution with the absence and presence of inorganic ions (K⁺ and Ca²⁺). Adsorption isotherms, thermodynamic parameters, and kinetic models were used to understand the sorption mechanism, and zeta potential measurements were performed to elucidate the effect of the inorganic ions on the adsorption. The results showed that coke powder exhibited a reasonably good adsorption performance due to its pore structure and surface characteristics, and the presence of K⁺ and Ca²⁺ could further improve the adsorption. Without inorganic ions, the adsorption capacity of coke powder for quinoline and the removal efficiency of quinoline were 1.27 mg/g and 84.90%, respectively. At the ion concentration of 15 mmol, the adsorption capacity of coke powder and quinoline removal efficiency in the presence of K⁺ reached 1.38 mg/g and 92.02%, respectively, whereas those in the solutions with Ca²⁺ reached 1.40 mg/g and 93.31%, respectively. It was found that the adsorption of quinoline onto coke powder in the absence and presence of inorganic ions fit the Freundlich isotherm. Changes in the Gibbs free energy, the heat of adsorption, the entropy, and the activation energy of adsorption suggest that the adsorption was spontaneous and exothermic, which was dominated by physical adsorption, and that the added K⁺ and Ca²⁺ would favor the adsorption. In addition, the pseudo-second-order kinetic model was found to provide the best fit to the adsorption kinetic data, and K⁺ and Ca²⁺ increased the rate of quinoline adsorbed onto coke power. This improved adsorption due to inorganic ions was found to be a consequence of the decrease in the surface potential of coke powder particles, which resulted in a reduced thickness of water film around particles, as well as a decreased electrostatic repulsion between coke powder particles and quinoline molecules. Full article

Osteoporosis is a leading world health problem that results from an imbalance between bone formation and bone resorption. β-glucans has been extensively reported to exhibit a wide range of biological activities, including antiosteoporosis both in vitro and in vivo. However, the molecular mechanisms responsible for β-glucan-mediated bone formation in osteoblasts have not yet been investigated. The oyster mushroom Pleurotus sajor-caju produces abundant amounts of an insoluble β-glucan, which is rendered soluble by enzymatic degradation using Hevea glucanase to generate low-molecular-weight glucanoligosaccharide (Ps-GOS). This study aimed to investigate the osteogenic enhancing activity and underlining molecular mechanism of Ps-GOS on osteoblastogenesis of pre-osteoblastic MC3T3-E1 cells. In this study, it was demonstrated for the first time that low concentrations of Ps-GOS could promote cell proliferation and division after 48 h of treatment. In addition, Ps-GOS upregulated the mRNA and protein expression level of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor-2 (Runx2), which are both involved in BMP signaling pathway, accompanied by increased alkaline phosphatase (ALP) activity and mineralization. Ps-GOS also upregulated the expression of osteogenesis related genes including ALP, collagen type 1 (COL1), and osteocalcin (OCN). Moreover, our novel findings suggest that Ps-GOS may exert its effects through the mitogen-activated protein kinase (MAPK) and wingless-type MMTV integration site (Wnt)/β-catenin signaling pathways. Full article

Mitochondria are involved in many cellular processes and their main role is cellular energy production. They constantly undergo fission and fusion, and these counteracting processes are under strict balance. The cytosolic dynamin-related protein 1, Drp1, or dynamin-1-like protein (DNM1L) mediates mitochondrial and peroxisomal division. Defects in the DNM1L gene result in a complex neurodevelopmental disorder with heterogeneous symptoms affecting multiple organ systems. Currently there is no curative treatment available for this condition. We have previously described a patient with a de novo heterozygous c.1084G>A (p.G362S) DNM1L mutation and studied the effects of a small molecule, bezafibrate, on mitochondrial functions in this patient’s fibroblasts compared to controls. Bezafibrate normalized growth on glucose-free medium, as well as ATP production and oxygen consumption. It improved mitochondrial morphology in the patient’s fibroblasts, although causing a mild increase in ROS production at the same time. A human foreskin fibroblast cell line overexpressing the p.G362S mutation showed aberrant mitochondrial morphology, which normalized in the presence of bezafibrate. Further studies would be needed to show the consistency of the response to bezafibrate, possibly using fibroblasts from patients with different mutations in DNM1L, and this treatment should be confirmed in clinical trials. However, taking into account the favorable effects in our study, we suggest that bezafibrate could be offered as a treatment option for patients with certain DNM1L mutations. Full article

Human African Trypanosomiasis (HAT or sleeping sickness) is a life-threatening neglected tropical disease that is endemic in 36 sub-Saharan African countries. Until recently, treatment options were limited and hampered by unsatisfactory efficacy, toxicity, and long and cumbersome administration regimens, compounded by infrastructure inadequacies in the remote rural regions worst affected by the disease. Increased funding and awareness of HAT over the past two decades has led to a steady decline in reported cases (<1000 in 2018). Recent drug development strategies have resulted in development of the first all-oral treatment for HAT, fexinidazole. Fexinidazole received European Medicines Agency positive scientific opinion in 2018 and is now incorporated into the WHO interim guidelines as one of the first-line treatments for HAT, allowing lumbar puncture to become non-systematic. Here, we highlight the role of global collaborations in the effort to control HAT and develop new treatments. The long-standing collaboration between the WHO, Sanofi and the Drugs for Neglected Diseases initiative (Geneva, Switzerland) was instrumental for achieving the control and treatment development goals in HAT, whilst at the same time ensuring that efforts were led by national authorities and control programs to leave a legacy of highly trained healthcare workers and improved research and health infrastructure. Full article

LENS (Light Emitting Nano-pixel Structure), a new nano-metric device, was designed, simulated, and modeled for feasibility analysis, with the challenge of combining high resolution and high brightness for display, essentially adapted for Augmented Reality (AR) and Virtual Reality. The device is made of two parts: The first one is a reflective nano-cone Light Emitting Device (LED) structure to reduce the Total Internal Reflection effects (TIR), and to enable improved light extraction efficiency. The second part is a Compound Parabolic Concentrator (CPC) above the nano-LED to narrow the outgoing light angular distribution so most of the light would be "accepted" by an imaging system. Such a way is drastically limiting any unnecessary light loss. Our simulations show that the total light intensity gain generated by each part of the pixel is at least 3800% when compared to a typical flat LED. It means that, for the same electrical power consumption, the battery life duration is increased by 38. Furthermore, this improvement significantly decreases the display thermal radiation by at least 300%. Since pixel resolution is critical to offer advanced applications, an extensive feasibility study was performed, using the LightTools software package for ray tracing optimization. In addition to the simulation results, an analytical model was developed. This new device holds the potential to change the efficiency for military, professional and consumer applications, and can serve as a game changer. Full article

Synthetic amorphous silica is used in various applications such as cosmetics, food, or rubber reinforcement. These broad uses increase human exposure, and thus the potential risk related to their short- and long-term toxicity for both consumers and workers. These potential risks have to be investigated, in a global context of multi-exposure, as encountered in human populations. However, most of the in vitro research on the effects of amorphous silica has been carried out in an acute exposure mode, which is not the most relevant when trying to assess the effects of occupational exposure. As a first step, the effects of repeated exposure of macrophages to silica nanomaterials have been investigated. The experiments have been conducted on in vitro macrophage cell line RAW264.7 (cell line from an Abelson murine leukemia virus-induced tumor), as this cell type is an important target cell in toxicology of particulate materials. The bioaccumulation of nanomaterials and the persistence of their effects have been studied. The experiments carried out include the viability assay and functional tests (phagocytosis, NO and reactive oxygen species dosages, and production of pro- and anti-inflammatory cytokines) using flow cytometry, microscopy and spectrophotometry. Accumulation of silica nanoparticles (SiO₂ NP) was observed in both exposure scenarii. However, differences in the biological effects between the exposure scenarii have also been observed. For phagocytosis, NO production and Tumor Necrosis Factor (TNF) release, repeated exposure tended to induce fewer effects than acute exposure. Nevertheless, repeated exposure still induces alterations in the macrophage responses and thus represents a scenario to be tested in detail. Full article