Oleuropein (OLE), a main constituent of olive, displays a pleiotropic beneficial dynamic in health and disease, based mainly on its antioxidant and hypolipidemic properties, and its capacity to protect myocardium during ischemia. Furthermore, OLE activates peroxisome proliferator-activated receptor (PPARα) in neurons and astrocytes, providing neuroprotection against noxious biological reactions that are induced following cerebral ischemia. Current study investigated the effect of OLE in the regulation of various neural plasticity indices, emphasizing the role of PPARα. For this purpose, 129/Sv wild-type (WT) and Pparα-null mice were treated with OLE for three weeks. The present findings revealed that chronic treatment with OLE up-regulated the brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the prefrontal cortex (PFC) of mice via activation of ERK1/2, AKT and PKA/CREB signaling pathways. No similar effects were observed in the hippocampus. The OLE-induced effects on BDNF and TrkB appear to be mediated by PPARα, because no similar alterations were observed in the PFC of Pparα-null mice. Notably, OLE did not affect the neurotrophic factors NT3 and NT4/5 in both brain tissues. Fenofibrate though, a selective PPARα agonist, up-regulated BDNF and NT3 in the PFC of mice, whereas the drug induced NT4/5 in both brain sites tested. Interestingly, OLE provided neuroprotection in differentiated human SH-SY5Y cells against β-amyloid and H2O2 toxicity independently from PPARα activation. In conclusion, OLE and similar drugs acting either as PPARα agonists or via PPARα independent mechanisms could improve synaptic function/plasticity mainly in the PFC and to a lesser extent in the hippocampus, thus beneficially affecting cognitive functions.

Methicillin-resistant Staphylococcus aureus (MRSA) constitutes a serious public health concern with a considerable impact on patients' health and substantial healthcare costs. In this study, patients, and healthcare workers (HCWs)from six public hospitals in Benin were screened for MRSA. Strains were identified as MRSA using conventional microbiological methods in Benin and confirmed using Matrix-Assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF) mass spectrometry in Belgium. Whole genome sequencing (WGS) was used on confirmed MRSA isolates to characterize their genomic content and study their relatedness. In total,304 and 61 samples were collected from patients and HCWs, respectively. The mecA gene was detected in all isolates. The isolates were assigned to five sequence types (STs), with ST8 (55.6%, n=15), ST152 (18.52%, n=5), and ST121 (18.52%, n=5) being the most common. All isolates carried multiple virulence genes, including genes encoding the Panton-Valentine leukocidin toxin (48.15%, n=13) and the test gene (29.63%, n=8) associated with toxic shock syndrome. The presence of strains carrying numerous genomic features associated with antibiotic resistance and virulence in HCWs is a major public health concern. This study highlights the need to implement a multimodal strategy for reducing the risk of cross-transmission of MRSA in hospitals.

Because most of the recognized causes of superior gluteal nerve (SGN) injury are iatrogenic, detailed knowledge of the anatomy of the SGN is crucial to prevent its injury associated with surgical procedures. This study aims to describe the precise location of SGN or its branches at the greater sciatic foramen, measure the distances of these nervous structures to palpable bony landmarks, and evaluate the possible correlation between these parameters and pelvis size. Twenty human cadaveric hemipelvises were studied. After dissection to expose the SGN or its branches at the greater sciatic foramen, the distances from these nervous structures to the greater trochanter (GT), to the anterior superior iliac spine (ASIS), to the posterior superior iliac spine (PSIS), to the ischial tuberosity (IT), and to the greater sciatic notch were measured. We found that at the greater sciatic foramen the SGN emerges as a common trunk in 75% of hemipelvises, and already divided in its superior and inferior branches in 25% of hemipelvises. When the SGN exits the pelvis as a common trunk, it does so, in most cases, in contact with the bone at the apex of the greater sciatic notch or superior to it. The median distance from the SGN at the greater sciatic notch to the PSIS, ASIS, GT and IT is 7.6 cm, 10.9 cm, 7.5 cm and 10.8 cm, respectively. We found a positive correlation between some of the analyzed parameters and the size of the pelvis. The anatomical data of this study may serve as pivotal guides during orthopedic pelvic surgery, contributing to minimize SNG iatrogenic lesions with significant implications in the patient's quality of life.

As the use of microbial inoculants in agriculture rises, it becomes important to understand how the environment may influence microbial ability to promote plant growth. This work examines whether there are light dependencies in the biological functions of Azospirillum brasilense, a commercialized prolific grass-root colonizer. Though classically defined as non-phototrophic, A. brasilense possesses photoreceptors that could perceive light conducted through its host’s roots. Evidence for light dependency of four microbial processes were examined and noted: biological nitrogen fixation (BNF), auxin biosynthesis, ATP biosynthesis, and iron and manganese uptake. Functional mutants of A. brasilense were leveraged and studied in light and dark environments: HM053 (high BNF and auxin production), ipdC (capable of BNF, deficient in auxin production), and FP10 (capable of auxin production, deficient in BNF). HM053 exhibited the highest rate of nitrogenase activity with the greatest light dependency comparing iterations in light and dark environments. The ipdC mutant showed similar behavior with relatively lower nitrogenase activity observed, while FP10 did not show a light dependency. Auxin biosynthesis showed strong light dependencies in HM053 and FP10 strains, but not for ipdC. Iron is involved in the BNF biological process, and light dependency was observed for microbial 59Fe2+ uptake in HM053 and ipdC, but not FP10. Surprisingly, a light dependency for 52Mn2+ uptake was only observed in ipdC. Finally, ATP biosynthesis was sensitive to light across all three mutants favoring blue light over red light compared to darkness with observed ATP levels in descending order for HM053 > ipdC > FP10.

The use of allometric tools allows estimating the biomass of a plant species with greater precision. Tree roots are the least studied part of the vegetation due to the difficulty in obtaining complete root systems. For this reason, the objective was to generate an allometric model to estimate the amount of biomass accumulated in the root system of Abies religiosa trees in El Chico National Park, Hidalgo. For this purpose, 61 trees of A. religiosa were extracted from 0.06 to 3.56 m in height, using a backpack sprayer of pressurized water that detached the soil from the root. The response variable was root fresh weight and the independent variables were height, diameter and age+1, according to the fit of the models tested. Diameter was the variable with the best fit (r2 = 0.95 ± 0.04), obtaining the following equation PFR = (20.918 + D (2.4475)). The allometric model accurately estimates the below-ground biomass contained in the roots, which will allow us to obtain the complete biomass of an A. religiosa forest by having access to data on both the aerial and root components.

The aim of this research was to evaluate the essential oil of Cymbopogon schoenanthus (L.) Spreng. (C. schoenanthus) from Burkina Faso in cytotoxic activity against LNCaP cells, derived from prostate cancer, and HeLa cells, derived from cervical cancer. Antioxidant activities were evaluated in vitro. Essential oil (EO) was extracted by hydrodistillation and analyzed by GC / FID and GC / MS. Thirty-seven compounds were identified, the major compounds being piperitone (49.9%), alpha terpinene isomer (24.02%), elemol (5.79%) and limonene (4.31%). EO exhibited a poor antioxidant activity, as shown by the inhibition of DPPH radicals (IC50 =1730 ± 80 µg/mL) and ABTS+. (IC50 = 2890 ± 26.9 µg/mL). Conversely, EO decreased the proliferation of LNCaP and HeLa cells with respective IC50s of 135.53 ± 5.27 µg/mL and 146.17 ± 11 µg/mL. EO also prevented LNCaP cell migration and led to the arrest of their cell cycle in the G2/M phase. Altogether, this work points out for the first time that EO of C. schoenanthus from Burkina Faso could be an effective natural anticancer agent.

Objective. Whether a minimum quantity of saliva is needed to inhibit the caries process is unclear. Here, we evaluated the effect of saliva dilutions on an in vitro caries model with Streptococcus mutans (S. mutans) biofilms. Methods. S. mutans biofilms were grown on enamel and root dentin slabs, in culture media containing different proportions of saliva (v/v): 0%, 5%, 10%, 25%, 50%, 75% and 100% saliva, and exposed to a 10% sucrose solution (5 min, 3x/day), with appropriate controls. After 5 (enamel) and 4 (dentin) days, demineralization, biomass, viable bacteria and polysaccharide formation were analyzed. The acidogenicity of the spent media was monitored overtime. Assays were carried out in triplicate in 2 independent experiments (n=6). Results. An inverse relationship was observed between acidogenicity, demineralization, and saliva proportion, both in enamel and dentin. A marked reduction in enamel and dentin demineralization was observed when small amounts of saliva were incorporated in the medium. For both tissues, a significant reduction in biomass, viable S. mutans cells and polysaccharides were observed when saliva was present, in a concentration-dependent manner. Conclusions. High quantities of saliva can almost completely inhibit sucrose-induced cariogenicity, but small amounts can also exert a dose-dependent caries-protective effect.

Remanufacturing is a way for product recovery initiative and maintaining sufficient production flow to satisfy customer demand through circular economy. Recently, manufacturers have been progressively incorporating remanufacturing processes, making their supply chain vulnerable to disruptions. Among the disruptions that usually occur is the shortage in spare parts supply, which causes unexpected delay in production and possible loss of sales. In the face of potential disruption, it is essential for remanufacturing facilities to manage their supply chains in an optimum manner as to decrease the adverse impact of disruptions to their business. In this study, a two-stage production-inventory system is analysed by developing a cost-minimisation model focusing on the recovery schedule after a disruption occurrence in sourcing spare parts for a remanufacturer’s production cycle. The developed model was solved using the branch and bound algorithm. Through numerical experiments, the results indicate that the optimal recovery schedule and the number of recovery cycles are significantly dependant on disruption time, lost sales and backorder costs. Moreover, a sensitivity analysis shows that the lost sales option seems to be more effective than the backorder option in optimising the system’s overall cost. The proposed model could assist managers in deciding the optimal production strategy while providing interesting managerial insights into vital spare parts recovery issues when disruption strikes.

In the mammalian isocortex CD44, a cell surface receptor for extracellular matrix molecules, is present in pial-based and fibrous astrocytes of white matter, but not the protoplasmic astrocytes. In the hominid isocortex, CD44+ astrocytes comprise the subpial “interlaminar” astrocytes, sending long processes into the cortex. The hippocampus also contains similar astrocytes. We have examined all levels of the human CNS and found CD44+ astrocytes in every region. Astrocytes in white matter and astrocytes that interact with large blood vessels, but not capillaries in gray matter, are CD44+, the latter extending long processes into the parenchyma. Motor neurons in the brainstem and spinal cord, such as oculomotor, facial, hypoglossal, and in the anterior horn of the spinal cord, are surrounded by CD44+ processes, contrasting with neurons in the cortex, basal ganglia and thalamus. We found CD44+ processes that intercalate between ependymal cells to reach the ventricle and that show a location-specific presence. We also found a CD44+ astrocyte in the molecular layer of the cerebellar cortex. Protoplasmic astrocytes, which do not normally contain CD44, acquire it in pathologies like hypoxia and seizures.

As a result of the spread of SARS-CoV-2, a global pandemic was declared. Indiscriminate COVID-19 vaccination has been extended to include age groups and naturally immune people with minimal danger of suffering serious complications due to COVID-19. Solid immuno-histopathological evidence demonstrates that the COVID-19 genetic vaccines can display an off-target distribution in tissues that are terminally differentiated, triggering autoimmune reactions. These include the heart and brain, which may incur in situ production of spike protein eliciting a strong autoimmunological inflammatory response. Due to the fact that every human cell which synthesizes non-self antigens becomes inevitably the target of the immune system, and since the human body is not a strictly compartmentalized system, accurate pharmacokinetic and pharmacodynamic studies are needed in order to determine precisely which tissues can be harmed. Therefore, our article aims to draw the attention of the scientific and regulatory communities on the critical need of bio-distribution studies for the genetic vaccines against COVID-19, as well as of rational harm-benefit assessments by age group.

Background: Combinatorial therapy- “nano antibiotics” is an emerging field in nanoscience. In this present investigation, we attempted to combine the green synthesized noble metal nanoparticle and the antibiotic Streptomycin to form bio-conjugated nanoparticles. The newly synthesized Nano antibiotics acted as the antibiotic carrier, functioned as cargo, and delivered the antibiotic. Methods: Comparative studies between the noble metal nanoparticles were attempted for the first time on the grounds of their antibacterial activity. The antibacterial activity of the three noble metal nanoparticles was assessed against Streptomycin-resistant Bacillus sp.; the results obtained proved that silver nanoparticles were a potent antibacterial agent. Still, no antibacterial activity was exerted by gold, and platinum nanoparticles were for the Streptomycin-resistant strain Bacillus sp. To our surprise, the gold and platinum fabricated/bio-conjugated nanoparticle with the antibiotic showed 100% antibacterial activity, whose antibacterial activity was zero when functioning as a nanoparticle alone. Results: The combinatorial therapy of two different clauses of drugs majorly increased antibacterial activity. It enhanced the antibiotic to overcome the resistance exhibited by the bacterial pathogen, and the possible mechanism is elucidated in the present study. Also, an attempt has been made to assess the nanotoxicity of the nano-bioconjugates on RBC and compare their hemocompatibility. The results obtained in the current investigation demonstrate the enhanced antibacterial activity of the green synthesized nanoparticles conjugated with the streptomycin; their efficacy for combinational therapy against resistance in pathogenic organisms highlights the novelty of the work and the comparative study of three different noble metals nanoparticles (Ag, Au, Pt) from single agro-waste for the first time.

Alloys based on TiNi are widely used in various fields of technology and medicine. In the present work, we report on preparation of TiNi-alloy based wire with the shape memory effect, which was used for compression clips for surgery. Composition and structure of the wire, and its martensitic and physical-chemical properties were studied using SEM, TEM, optic microscopy, profilometry, mechanical tests, etc. The TiNi alloy was found to consist of B2 and B19' and secondary-phase particles of Ti2Ni, TiNi3 and Ti3Ni4. Its matrix was slightly enriched in Ni (50.3 at. % of Ni). Homogeneous grain structure was revealed (an average grain size of 19±0.3 μm) with equal quantities of grain boundaries of special and general types. Surface oxide layer provide improved biocompatibility and promote adhesion of protein molecules. Overall, the obtained TiNi wire was concluded to exhibit martensitic, physical and mechanical properties suitable for its use as an implant material. The wire was then used for manufacturing compression clips with the shape memory effect and applied in surgery. The medical experiment that involved 46 children demonstrated that the use of such clips in children with double-barreled enterostomies permitted to improve the results of surgical treatment.

Chagas disease (CD) is one of the most devasting parasitic diseases in the Americas affecting 7 to 8 million people worldwide. In vitro and in vivo experiments have demonstrated that decreased growth hormone (GH) serum levels occur as CD progresses. Interestingly, inactivating mutations in the GH receptor in humans induce Laron syndrome (LS), a clinical entity characterized by increased GH and decreased insulin growth factor-1 (IGF-1) serum levels. The largest cohort of LS subjects lives in the southern provinces of Ecuador. Remarkably, CD prevalence in these individuals is diminished despite living in highly endemic areas. In the current ex vivo study, we employed serum from GHR -/- mice, also known as LS mice (a model of GH resistance with high GH and low IGF-1 levels), and serum from bovine GH (bGH) transgenic mice (high GH and IGF-1), to test the effect on T. cruzi infection. We infected mouse fibroblast L-cells treated with serum from each type of mouse with metacyclic trypomastigotes from Trypanosoma cruzi (etiological CD infectious agent). Treatment with GHR-/- serum (LS mice) significantly decreased infection by 28% compared to 48% seen in control wild-type mouse serum (WT). Treatment with bGH mouse serum significantly decreased infection by only 41% compared to 54% from WT controls. Our results suggest that high GH and low IGF-1 in blood circulation, as typically seen in LS individuals, confers partial protection against T. cruzi infection.

Magnesium and Aluminum alloys continue to be important in the context of modern and lightweight technologies. With the advancement of additive manufacturing (AM), components can be produced directly in a net shape, widen up the usage of magnesium and aluminum alloys as well as holding new ideas for the application of unique physical structures made feasible by 3D printing. Laser-based approach, one of the metal additive manufacturing (AM) methods, enables the formation of arbitrary 3D structures. With promising findings, research in this area is advancing quickly, bringing up a variety of potential applications in both the scientific and industrial sectors. Complex structures can now be manufactured easily utilizing AM technologies to meet the pre-requisite objectives like reduced part numbers, greater functionality, and lightweight, among others. AM has the ability to meet demands by lowering costs and speeding up the manufacturing process. Due to their popularity in numerous high-value applications, aluminum, and magnesium alloys are one of the key material systems being researched in the laser-based additive manufacturing approaches. The review here aims to comprehensively examine the additive manufacturing of magnesium and aluminum alloys, highlighting the influence of the laser-based additive manufacturing approach on the mechanical characteristics, microstructure, and tribological performance of magnesium and aluminum alloys.

The eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate 1, with promising insecticidal capability was encapsulated in liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and of 100% dioleoylphosphatidylglycerol (DOPG). Compound-loaded Egg-PC:Ch liposomes exhibit small hydrodynamic diameters (below 100 nm), high encapsulation efficiency (88.8% ± 2.7%), higher stability and a more efficient compound release, being chosen for assays in Sf9 insect cells. Compound 1 elicited a loss of cell viability up to 80% after 72h of incubation. Relevantly, encapsulation maintained the toxicity of compound 1 towards insect cells, while it lowered toxicity towards human cells, thus showing the selectivity of the system. Structure based inverted virtual screening was used to predict the most likely targets and molecular dynamics simulations and free energy calculations were used to demonstrate that this molecule can form a stable complex with insect odorant binding proteins and/or acetylcholinesterase.

Human pluripotent stem cells (hPSCs) have widespread potential biomedical applications. There is a need for large-scale in vitro production of hPSCs, and optimal culture methods are vital in achieving this. Physiological oxygen (2% O2) improves key hPSCs attributes, including genomic integrity, viability, and clonogenicity, however, its impact on hPSC metabolism remains un-clear. Here, Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) was used to detect and quantify metabolic Volatile Organic Compounds (VOCs) in the headspace of hPSCs and their differentiated progeny. hPSCs were cultured in either 2% O2 or 21% O2. Media was collected from cell cultures and transferred into glass bottles for SIFT-MS measurement. The VOCs acetaldehyde and dimethyl sulfide (DMS)/ethanethiol were significantly increased in undifferentiated hPSCs compared to their differentiating counterparts, and these observations were more apparent in 2% O2. Pluripotent marker expression was consistent across both O2 concentrations tested. Transcript levels of ADH4, ADH5, and CYP2E1, encoding enzymes involved in converting ethanol to acetaldehyde, were upregulated in 2% O2, and chemical inhibition of ADH and CYP2E1 decreased acetaldehyde levels in hPSCs. Acetaldehyde and DMS/ethanethiol may be indicators of altered metabolism pathways in physiological oxygen culture conditions. The identification of non-destructive biomarkers for hPSC characterization has the potential to facilitate large-scale in vitro manufacture for future biomedical application.

The aim of the present study was to evaluate the association between television viewing/physical activity (TVV/PA) interactions and cardiometabolic risk in an adult European population. A total of 2,155 subjects (25-64 years) (45.2% males), a random population-based sample were evaluated in Brno, Czechia. TVV was classified as low (<2hours/day), moderate (2-4), and high (≥4). PA was classified as insufficient, moderate, and high. To assess the independent association of TVV/PA categories with cardiometabolic variables, multiple linear regression was used. After adjustments, significant associations were: high TVV/insufficient PA with body mass index (BMI) (β=2.61,SE=0.63), waist circumference (WC) (β=7.52,SE=1.58), body fat percent (%BF) (β=6.24,SE=1.02), glucose (β=0.25,SE=0.12), triglycerides (β=0.18,SE=0.05), and HDL-C (β=-0.10,SE=0.04); high TVV/moderate PA with BMI (β=1.98,SE=0.45), WC (β=5.43,SE=1.12), %BF (β =5.15,SE=0.72), triglycerides (β =0.08,SE=0.04), total cholesterol (β=0.21,SE=0.10), LDL-c (β=0.19,SE=0.08), and HDL-c (β=-0.07,SE=0.03); and moderate TVV/insufficient PA with WC (β=2.68,SE=1.25), %BF (β=3.80,SE=0.81), LDL-c (β=0.18,SE=0.09), and HDL-c (β=-0.07,SE=0.03). Independent of PA levels, higher TVV was associated with higher amounts of adipose tissue. Higher blood glucose and triglycerides were present in subjects with high TVV and insufficient PA, but not in those with high PA alone. These results affirm the independent cardiometabolic risk of sedentary routines even in subjects with high-levels of PA.

Uveal melanoma is the most common primary intraocular malignancy in adults characterized by insidious onset and poor prognosis strongly associated with tumor size and the presence of distant metastases, most commonly in the liver. Contrary to most tumor identification, biopsy followed by pathological exam is not recommended in ophthalmic oncology. Therefore, early and non-invasive diagnosis is essential to enhance patients’ chances for early treatment possibilities. We reviewed imaging modalities currently used in the diagnosis of uveal melanoma, i.e., fundus imaging, ultrasonography (US), optical coherence tomography (OCT), single-photon emission computed tomography (SPECT), positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF). The principle of imaging techniques was briefly explained, along with their role in the diagnostic process and a summary of their advantages and limitations. Further, the experimental data and the advancements in imaging modalities were searched. We described their innovations, showed current usage and research, and explained the possibilities of utilizing them to diagnose uveal melanoma and their potential application in personalized medicine such as theranostics.

RNA interference (RNAi) molecules have tremendous potential for cancer therapy but are limited by insufficient potency after i.v. administration. We previously found that polymer complexes (polyplexes) formed between 3’-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase RNAi potency against stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily i.v. dosing. Chol-DsiRNA Polyplexes, however, maintain LUC mRNA suppression ~48 h longer after the final dose than Chol-siRNA Polyplexes, suggesting they are a better candidate formulation. Here, we directly compared the activities of Chol-siRNA and Chol-DsiRNA Polyplexes in primary murine 4T1 breast tumors against STAT3, a therapeutically relevant target gene overexpressed in many solid tumors including breast cancer. We found that Chol-siSTAT3 Polyplexes suppressed STAT3 mRNA in 4T1 tumors with similar potency (half-maximal ED₅₀ 0.3 mg/kg) and kinetics over 96 hours as Chol-DsiSTAT3 Polyplexes but with slightly lower activity against total Stat3 protein (29% vs. 42% suppression) and tumor growth (11.5% vs. 8.6% rate-based T/C ratio) after repeated i.v. administration of tumor-saturating doses every other day. Thus, both Chol-siRNA Polyplexes and Chol-DsiRNA Polyplexes may be suitable clinical candidates for RNAi therapy of breast cancer and other solid tumors.

The aim of the study was to gain deeper insights in the potential for polyclonal stimulation of PBMC from cows and pigs with banana lectin (BanLec) from Musa paradisiaca. BanLec induced a marked proliferative response in cow and pig PBMC. The response in pigs was even higher than to Concanavalin A. Molecular processes associated with respective responses were examined with differential proteome analyses. Discovery proteomic experiments was applied to BanLec stimulated PBMC and cellular and secretome responses were analyzed with label free LC-MS/MS. In PBMC, 3955 proteins were identified. After polyclonal stimulation with BanLec, 459 proteins showed significantly changed abundance in PBMC. In respective PBMC secretomes, 2867 proteins were identified with 231 differentially expressed candidates as reaction to BanLec stimulation. The transcription factor `E74 like ETS transcription factor 1 (ELF1)` was solely enriched in BanLec stimulated PBMC. BanLec induced secretion of several immune regulators, amongst them positive regulators of activated T cell proliferation and Jak-STAT signaling pathway. Top changed immune proteins were CD226, CD27, IFNG, IL18, IL2, CXCL10, LAT, ICOS, IL2RA, LAG3 and CD300C. BanLec stimulates PBMC of cows and pigs polyclonally and induces IL2 pathway and further proinflammatory cytokines. Proteomics data are available via ProteomeXchange with identifier PXD027505.

During type 1 diabetes mellitus (T1DM) development, beta-cells undergo intense endoplasmic reticulum (ER) stress that could result in apoptosis through the failure of adaptation to the unfolded protein response (UPR). Islet transplantation is considered an attractive alternative among beta-cell replacement therapies for T1DM. To avoid the loss of beta-cells that will jeopardize the transplant´s outcome, several strategies are being studied. We have previously shown that prolactin induces protection against pro-inflammatory cytokines and redox imbalance-induced beta-cell death by increasing heat shock protein B1 (HSPB1) levels. Since the role of HSPB1 in beta cells has not been deeply studied, we investigated the mechanisms involved in unbalanced protein homeostasis caused by intense ER stress and overload of the proteasomal protein degradation pathway. We tested whether HSPB1-mediated cytoprotective effects involved UPR modulation and improvement of protein degradation via the ubiquitin-proteasome system. We demonstrated that increased levels of HSPB1: attenuated levels of pro-apoptotic proteins like CHOP and BIM, increased protein ubiquitination and the speed of proteasomal protein degradation. Our data showed that HSPB1 induced resistance to proteotoxic stress and thus enhanced cell survival via an increase in beta-cell proteolytic capacity. These results could contribute to generate strategies aiming at optimization of beta-cell replacement therapies.

Phylogenetic and phylogeographic assessments of species should ideally include individuals of all known populations. However, this is difficult for species with large distribution areas. Previous molecular studies of the wide-ranging Eurasian lynx Lynx lynx focused mainly on its northern Palearctic populations, with the consequence that the reconstruction of this species’ evolutionary history did not include genetic variation present in its southern Palearctic distribution. We sampled a previously not considered Asian subspecies (L. l. dinniki), added published data from another Asian subspecies (L. l. isabellinus), and reassessed the Eurasian lynx mtDNA phylogeny along with previously published data from northern Palearctic populations. Our mitogenome-based analyses revealed that the subspecies L. l. isabellinus harbours the most basal matriline, consistent with the origin of Lynx lynx in this subspecies’ current range. L. l. dinniki harbours the second-most basal matriline, which is related to, and may be the source of, the mtDNA diversity of the critically endangered Balkan lynx L. l. balcanicus. Our results suggest that the Anatolian peninsula was a glacial refugium for Eurasian lynx, with previously unconsidered implications for the colonization of Europe by this species. Genetic variation present in southern Palearctic populations of Lynx lynx is clearly important for elucidating the evolutionary history of this species.

Disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause epilepsy. Our study aims at revealing therapeutic potential of vitamins B1 and B6 in epilepsy by estimating effects of their combined administration on a seizure and its consequences in rats subjected to pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to Racine’s scale along with delayed physiological and biochemical consequences next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than male rats. Next day after a seizure, gender differences in behavior and brain biochemistry arise. The induced gender differences in anxiety, exploratory and locomotor activity correspond to disappearance of gender differences in the brain GABA, aspartate, alanine and serine, with appearance of those in glutamate, glutamine and tyrosine. PTZ decreases the brain malate dehydrogenase activity, glutamine and urea in the males, and phenylalanine in the females. Administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5-2 h) between the vitamins and PTZ administration. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. Delayed effects of vitamins and/or PTZ are mostly gender-specific and interacting. Our findings on the gender differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

To characterize the mechanisms by which the highly-conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on exoc5 (aka sec10), a central exocyst component. We analyzed both exoc5 zebrafish mutants and retinal pigmented epithelium (RPE)-specific Exoc5 knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. Exoc5-/- zebrafish showed smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post fertilization, loss of rod and cone opsins were observed in zebrafish Tg:exoc5 mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function, and loss of visual photoreceptor pigments. This retinal phenotype in Exoc5-/- mice was present at 20-weeks, and the phenotype was more severe at 27-weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that exoc5 mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. As RPE cells are “downstream” of photoreceptor cells in the visual process, these data suggest exocyst-mediated retrograde communication and dependence between the RPE and photoreceptors.

Proper treatment of infectious air could potentially mitigate the spread of airborne viruses such as porcine reproductive and respiratory syndrome virus (PRRSV). The objective of this research is to test the effectiveness of ultraviolet (UV) in inactivating aerosolized PRRSV, specifically, four UV lamps, UV-A (365 nm, both fluorescent and LED-based), "excimer" UV-C (222 nm), and germicidal UV-C (254 nm), were tested. The two UV-C lamps effectively irradiated fast-moving PRRSV aerosols with short treatment times (<2 s). One-stage and two-stage UV inactivation models estimated the UV doses needed for target percentage (%) reductions on PRRSV titer. UV-C (254 nm) dose needed for 3-log (99.9%) reduction was 0.521 and 0.0943 mJ/cm2, respectively, based on one-stage and two-stage models. An order of magnitude lower UV-C (222 nm) doses were needed for a 3-log reduction, i.e., 0.0882 and 0.048 mJ/cm2, based on one-stage and two-stage models, respectively. However, the cost of 222-nm excimer lamps is still economically prohibitive for scaling-up trials. The UV-A (365 nm) lamps could not reduce PRRSV titers for tested doses up to 4.11 mJ/cm2. Pilot-scale or farm-scale testing of UV-C on PRRSV aerosols simulating barn ventilation rates are recommended based on its effectiveness and reasonable costs comparable to HEPA filtration.

Over two years (2012-2014), 719 nasopharyngeal samples were collected from 6 weeks to 12 months old infants presenting at emergency department with moderate to severe acute bronchiolitis. Viral testing was performed and we found 98% positive samples including 90% Respiratory Syncytial Virus, 34% Human Rhino Virus, and 55% viral co-detections with predominance of RSV/HRV co-infections (30%). Interestingly, we found that the risk of being infected by HRV is higher in the absence of RSV, suggesting interferences or exclusion mechanisms between these two viruses. Conversely, Coronavirus infection had no impact on the likelihood of co-infection involving HRV and RSV. Bronchiolitis is the leading cause of hospitalizations in infants before 12 months of age, and many questions about its role in the later chronic respiratory diseases (asthma and chronic obstructive pulmonary disease) do exist. Role of virus detection and burden of viral codetections need to be further explored, in order to understand the physiopathology of chronic respiratory diseases, a major public health issue.

Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance due to an increased knowledge of its underlying molecular mechanisms and its modulation by the tumor microenvironment and immune cell repertoire. In this study the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 pathologically classified human papilloma virus (HPV)-negative OSCC lesions and correlated to the intra-tumoral immune cell response, IFN- signaling and to the patients outcome. A heterogeneous, but predominantly lower constitutive protein expression of HLA-I APM components was found in OSCC sections when compared to non-neoplastic cells. Tumoral HLA-I APM component expression was further categorized into the three major phenotypes HLA-Ihigh/APMhigh, HLA-Ilow/APMlow and HLA-Idiscordant high/low/APMhigh. In the HLA-Ihigh/APMhigh group, the highest frequency of intra-tumoral CD8+ T cells and lowest number of CD8+ T cells close to FoxP3+ cells was found. Patients within this group presented the most unfavorable survival, which was significantly evident in stage T2 tumors. Despite a correlation with the number of intra-tumoral CD8+ T cells, tumoral JAK1 expression as a surrogate marker for IFN- signaling was not associated with HLA-I/APM expression. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

The rural communities are affected by gaseous emissions from intensive livestock production. Practical mitigation technologies are needed to minimize emissions from stored manure and improve air quality inside barns. In our previous research, the one-time surficial application of biochar to swine manure significantly reduced emissions of NH3 and phenol. We observed that the mitigation effect decreased with time during the 30-day trials. In this research, we hypothe-sized that bi-weekly reapplication of biochar could improve the mitigation effect on a wider range of odorous compounds using larger scale and longer trials. The objective was to evaluate the effectiveness of biochar dose and reapplication on mitigation of targeted gases (NH3, odor-ous VOCs, odor, GHGs) from stored swine manure on a pilot-scale setup over 8-weeks. The bi-weekly reapplication of the lower biochar dose (2 kg/m2) showed much higher significant percent reductions of emissions for NH3 (33% without & 53% with reapplication) and skatole (42% without & 80% with reapplication), respectively. In addition, the reapplication resulted in the emergence of statistical significance to the mitigation effect for all other targeted VOCs. Spe-cifically, for indole, the % reduction improved from 38% (p=0.47, without reapplication) to 78% (p=0.018, with reapplication). For phenol, the % reduction improved from 28% (p=0.71, without reapplication) to 89% (p=0.005, with reapplication). For p-cresol, the % reduction improved from 31% (p=0.86, without reapplication) to 74% (p=0.028, with reapplication). For 4-ethyl phenol, the percent emissions reduction improved from 66% (p=0.44, without reapplication) to 87% (p=0.007, with reapplication). The one-time 2 kg/m2 and 4 kg/m2 treatments showed similar effectiveness in mitigating all targeted gases, and no statistical difference was found between the dosages. The one-time treatments showed significant % reductions of 33% & 42% and 25% & 48% for NH3 and skatole, respectively. The practical significance is that the higher (one-time) biochar dose may not necessarily result in improved performance over the 8-week manure storage, but the bi-weekly reapplication showed significant improvement in mitigating NH3 and odorous VOCs. The lower dosages and the frequency of reapplication on the larger-scale should be explored to optimize biochar treatment and bring it closer to on-farm trials.

Livestock production systems generate nuisance odor and gaseous emissions affecting local communities and regional air quality. Also, there are concerns about the occupational health and safety of farm workers. Proven mitigation technologies that are consistent with the socio-economic challenges of animal farming are needed. We have been scaling up the photocatalytic treatment of emissions from lab-scale, aiming at farm-scale readiness. In this paper, we present the design, testing, and commissioning of a mobile laboratory for on-farm research and demonstration of performance in real farm conditions. The mobile lab is capable of treating up to 1.2 m3·s-1 of air with TiO2-based photocatalysis and adjustable UV-A dose based on LED lamps. We summarize the main technical requirements, constraints, approach, and performance metrics for the mobile laboratory, such as the effectiveness (measured as the percent reduction) and cost of photocatalytic treatment of air. The commissioning of all systems with standard gases resulted in ~9% and 34% reduction of NH3 and butan-1-ol, respectively. We demonstrated that as the percent reduction of standard gases increased with increased light intensity and treatment time. These results show that the mobile laboratory was ready for on-farm deployment and evaluating the effectiveness of UV treatment.

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction, and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in a BP-induced mutagenesis in mice. The tested products significantly (p<0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16±9.09 μg/mL, 5.96±1.55 μg/mL and 3.05±0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1±63.40 μg/mL and 203.10±17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p<0.05) benzo[a]pyrene (BP)-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p<0.05) the BP-induced micronuclei and oxidative damage, together with an increase of glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for adjuvant therapy of cancer.

In 2015, the World Health Organization substantially revised its guidance for vaccination coverage cluster surveys (revisions were finalized in 2018) and has since developed a set of accompanying resources, including definitions for standardized coverage indicators and software (named the Vaccination Coverage Quality Indicators - VCQI) to calculate them. The current WHO vaccination coverage survey manual was used to design and conduct two nationally representative vaccination coverage surveys in Nigeria – one to assess routine immunization and one to measure post-measles campaign coverage. The primary analysis for both surveys was conducted using VCQI. In this paper, we describe those surveys and highlight some of the analyses that are facilitated by the new resources. In addition to calculating coverage of each vaccine-dose by age group, VCQI analyses provide insight into several indicators of program quality such as crude coverage versus valid doses, vaccination timeliness, missed opportunities for simultaneous vaccination, and, where relevant, vaccination campaign coverage stratified by several parameters, including the number of previous doses received. The VCQI software furnishes several helpful ways to visualize survey results. We show that routine coverage of all vaccines is far below targets in Nigeria and especially low in northeast and northwest zones, which also have highest rates of dropout and missed opportunities for vaccination. Coverage in the 2017 measles campaign was higher and showed less geospatial variation than routine coverage. Nonetheless, substantial improvement in both routine program performance and campaign implementation will be needed to achieve disease control goals.

In Brazil, malaria transmission is mostly confined to the Amazon, where substantial progress has been achieved towards disease control in the past decade. Vector control has been historically considered a fundamental part of the main malaria control programs implemented in Brazil. However, the conventional vector-control tools have been insufficient to eliminate local vector populations due to the complexity of the Amazonian rainforest environment and ecological features of malaria vector species in the Amazon, especially Anopheles darlingi. Malaria elimination in Brazil and worldwide eradication will require a combination of conventional and new approaches that takes into account the regional specificities of vector populations and malaria transmission dynamics. Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, these new vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put on research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the development of such innovative tools.

In late 2018, an epidemic myxomatosis outbreak emerged on the Iberian Peninsula leading to high mortality in Iberian hare populations. Soon, a recombinant virus (MYXV-Tol or ha-MYXV) was identified, harboring a 2.8 kb insertion containing evolved duplicates of M060L, M061L, M064L, and M065L from MYXV. Since 2017, 1616 rabbits and 82 hares were tested by a qPCR directed to M000.5L/R gene, conserved in MYXV and MYXV-Tol/ ha-MYXV strains. A subset (20%) of the positive samples was tested for the insert with MYXV being detected in rabbits and recombinant MYXV in hares. Recently, two wild rabbits found dead in South Portugal, showing skin oedema and pulmonary lesions tested positive for the 2.8 Kb insert. Sequencing showed 100% similarity with the insert sequences described in Iberian hares from Spain. Viral particles were observed in the lungs of both rabbits by electron microscopy, and isolation in RK13 cells showed virus infectivity. Despite the analysis of recombinant MYXV genomes may predict its ability to infect rabbit, routine analyses showed species segregation for the circulation of MYXV and recombinant MYXV in wild rabbit and in Iberian hares, respectively. This study demonstrates, however, that recombinant MYXV can effectively infect and cause myxomatosis in wild rabbits and domestic rabbits, which raises serious concerns for the future of the Iberian wild leporids and emphasizes the need to continue monitoring MYXV and recombinant MYXV in both species.

Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance with growing evidence of its underlying molecular mechanisms and its interaction with the immune cell control. In this study the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 consecutive human papilloma virus (HPV)-negative OSCC lesions and correlated to tumor specific parameters, the intratumoral immune cell response and to the patients outcome. A heterogeneous, but predominantly lower constitutive protein expression of HLA-I APM components was seen in OSCC sections when compared to non-neoplastic cells. Based on the expression levels of HLA-I APM components three main OSCC subgroups were detected and categorized into HLA-Ihigh/APMhigh, HLA-Ilow/APMlow and HLA-Idiscordant high/low/APMhigh phenotypes. In the HLA-Ihigh/APMhigh group, the highest frequency of intratumoral CD8+ T cells and lowest number of CD8+ T cells close to FoxP3 cells was found. Despite being associated with the highest T cell infiltration, patients within this group presented the most unfavorable survival, which was most evident in stage T2 tumors. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

Oleylamine capped WS2 nanostructures were successfully formed at 320 °C via a relatively simple colloidal route. SEM and TEM analyses showed that the 3D nanoflowers that were initially formed disintegrated into 2D nanosheets after prolonged incubation. XPS and XRD analyses confirmed oxidation of WS2 into WO3. Sensors based on these oleylamine capped WS2 nanoflowers and nanosheets still showed a change in electrical response towards various concentrations of NH3 vapour at room temperature in a 25% relative humidity background despite the oxidation. The nanoflowers exhibited n-type response while the nanosheets displayed a p-type response towards NH3 exposure. The nanoflower based sensors showed better response to NH3 vapour exposure than the nanosheets. The sensors showed a good selectivity towards NH3 relative to acetone, ethanol, chloroform and toluene. Meanwhile, a strong interference of humidity to the NH3 response was displayed at high relative humidity levels. The results demonstrated that oleylamine limited the extent of oxidation of WS2 nanostructures. The superior sensing performance of the nanoflowers can be attributed to their hierarchical morphology which enhances the surface area and diffusion of the analyte.

Diet influences, and is influenced by, a wide range of socioeconomic, cultural, geographic, and genetic variables. Here we survey a matrix of such interactions as well as their connection to a variety of health outcomes, in a cohort of 689 diverse adults employed at Emory University and enrolled in the Center for Health Discovery and Well-Being (CHDWB) study. Principal component analysis (PCA) of the Block Food Frequency Questionnaire revealed seven PC cumulatively explaining 25.8% and each individually at least 2% of the proportional consumption of 110 food items. PC1 is strongly correlated with the Healthy Eating Index-2015 measure, and accordingly healthier scores associate with multiple measures of physical and mental health. It, as well as PC2 (likely a measure of food expense) and PC3 (carbohydrate versus protein consumption) show significant geographic structure across the Atlanta metropolitan area, correlating with race and ethnicity, income level, age and sex. Notably, a polygenic score for body mass index (BMI) consisting of 281 SNPs explains 2.8% of the variance in PC5, which is as strong as its association with BMI itself. PC5 appears to differentiate participants with respect to conscious eating behavior related to the choice of diet or comfort foods. Our analysis adds to the growing literature on factor analysis of socio-demographic influences on nutrition and health.

Structure-based design and synthesis of two biphenyl-N-acyl-β-D-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

The Ti-6Al-4V alloy is widely used in the manufacture of components that should have low density, high corrosion resistance, and fatigue strength. The fatigue strength can be improved by surface modification. The aim of this study was to determine the influence of plasma nitriding on the fatigue behavior of Ti-6Al-4V alloy with a lamellar microstructure (Widmanstätten type). Nitriding was executed at 720 °C for 4 hours in an atmosphere with N₂, Ar and H₂. Samples microstructure characterization was carried out by X-ray diffraction analysis, optical microscopy and scanning electron microscopy. The average roughness of the specimens was determined, and fatigue tests were executed in a bending-rotating machine with reverse tension cycles (R= -1). X-ray diffraction analysis revealed the matrix phases α and β, and the phases Ɛ-Ti₂N and δ-TiN in the nitrided alloy. A nitrogen diffusion layer was formed between the substrate and the titanium nitrides. Plasma nitriding resulted in an increase in low cycle fatigue strength, whereas at high cycles, both conditions exhibit similar behavior. The fracture surface of the fatigue tested specimens clearly revealed the lamellar microstructure. The fracture mechanism appears to be due to cracking at the interface of α and β phases of the lamellar microstructure.

Purpose: To create a highly balanced comparison of ab interno trabeculectomy (Trabectome, AIT) and trabecular bypass stenting (iStent, TBS).Setting: Eye and Ear Institute, Pittsburgh, Ross Eye Institute, Buffalo, and Glaucoma Associates of Texas, Dallas, USA.Design: Retrospective Exact Matching analysis.Methods: AIT and TBS patients were included from three large glaucoma practices. The primary outcome measure was the unmedicated IOP ≤ 21 mmHg at 2-year follow-up visit. A secondary measure was unmedicated IOP reduction ≥ 20% at 2 years. Patients were matched by baseline IOP, the number of glaucoma medications and glaucoma type using Exact Matching and by age using Nearest Neighbor matching. Patients without a close match were excluded. All surgeries were combined with phacoemulsification. Results: 154 AIT and 110 TBS eyes were analyzed. 48 AIT patients were exactly matched to 48 TBS patients. Both groups had a baseline IOP of 15.3±3.1 mmHg. At 24 months, the mean IOP was 13.9±3.3 for AIT versus 16.8±2.8 mmHg for TBS (p=0.04), while the number of medications was 0.7±1.0 for AIT versus 1.7±1.2 for TBS (p=0.04). The proportion of subjects achieving IOP ≤ 21 mmHg without medications at 24 months was 53% in AIT versus 16.6% in TBS (P < 0.05). At 24-month follow up 17.6% of patients in AIT had ≥ 20% IOP reduction without medication versus no patient in TBS. Conclusions: An Exact Matching comparison of AIT and TBS demonstrated greater IOP reduction with fewer medications in AIT.

N-glycosylation has been shown to affect the pharmacokinetic properties of several classes of biologics including monoclonal antibodies, blood factors, and lysosomal enzymes. In the last two decades, N-glycan engineering has been employed to achieve a N-glycosylation profile that is either more consistent or aligned with a specific improved activity (i.e. effector function or serum half-life). In particular, attention has focused on engineering processes in vivo or in vitro to alter the structure of the N-glycosylation of the Fc region of anti-cancer monoclonal antibodies in order to increase antibody-dependent cell-mediated cytotoxicity (ADCC). Here we applied the mannosidase I inhibitor kifunensine to the Nicotiana benthamiana transient expression platform to produce an afucosylated anti-CD20 antibody (rituximab). We determined the optimal concentration of kifunensine used in the infiltration solution, 0.375 µM, which was sufficient to produce exclusively oligomannose glycoforms, at a concentration 14 times lower than previously published levels. The resulting afucosylated rituximab revealed a 14-fold increase in ADCC activity targeting the lymphoma cell line Wil2-S when compared with rituximab produced in the absence of kifunensine. When applied to the cost-effective and scalable N. benthamiana transient expression platform, the use of kifunensine allows simple in-process glycan engineering without the need for transgenic hosts.

There is evidence that spaceflight poses acute and late risks on the central nervous system. To explore possible mechanisms, the proteomic changes following spaceflight in mouse brain were characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Within 3–5 hours after landing, brain tissue was collected to evaluate protein expression profiles using quantitative proteomic analysis. Our results showed that there were 26 proteins that were significantly altered after spaceflight in the grey and/or white matter. While there was no overlap between the white and grey matter in terms of individual proteins, there was overlap in terms of function, synaptic plasticity, vesical activity, protein/organelle transport, and metabolism. Our data demonstrate that exposure to the spaceflight environment induces significant changes in protein expression related to neuronal structure and metabolic function. This might lead to a significant impact on brain structural and functional integrity that could affect the outcome of space missions.

Tantalum doped ZnO structures (ZnO:Ta) were synthesized and some of their characteristics were studied. ZnO material was deposited on silicon substrates by using a hot filament chemical vapor deposition (HFCVD) reactor. The raw materials were a pill made of a mixture of ZnO and Ta₂O₅ powders, and molecular hydrogen was used as a reactant gas. Percentage of tantalum was varied from 0 to 500 mg by varying the percentage of tantalum oxide in the mixture of the pill source, by holding a fixed amount of 500 mg of ZnO in all experiments. X-ray diffractograms confirmed the presence of zinc oxide in the wurtzite phase and metallic zinc with a hexagonal structure, and no other phase was detected. Displacements to lower angles of reflection peaks, compared with those from samples without contamination, were interpreted as the inclusion of the Ta atoms in the matrix of the ZnO. This fact was confirmed by EDS and XRD measurements. From SEM images from undoped samples exhibited mostly micro sized semi-spherical structures while doped samples displayed a trend to grown as nanocrystalline rods. The presence of tantalum during the synthesis affects the way of the growth. Green photoluminescence at naked eye was observed when Ta doped samples were illuminated by ultraviolet radiation and confirmed by PL spectra. PL intensity on Ta doped ZnO varied from those undoped samples up to 8 times.

Mesenchymal stem cells (MSCs) have emerged as a promising treatment for inflammatory diseases. It is described that the immunomodulatory effect of MSCs takes place both by direct cell-to-cell contact and by means of soluble factors that leads to an increased accumulation of regulatory immune cells at the sites of inflammation. Similar efficacy of MSCs has been described regardless the route of administration used, the inflammation conditions and the MHC context. These observations arise the question as to whether the migration of the MSCs to the inflamed tissues is a pre-requisite to achieve their beneficial effect. To address this, we examined the biodistribution and the efficacy of intraperitoneal luciferase-expressing human expanded adipose derived stem cells (Luci-eASCs) in a mouse model of colitis. Luci-eASC-infused mice were stratified according to their response to the Luci-eASC treatment. According to the stratification criteria, there was a tendency to increase the bioluminescence signal in the intestine at the expense of a decrease in the bioluminescence signal in the liver in the `responder´ mice. These data thus suggest that the accumulation of the eASCs to the inflamed tissues is beneficial to achieve an optimal modulation of inflammation.

1-[(4-ethyl-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl)methyl]-4-phenyl-1H-1,2,3-triazole (Ph4) and1-[(4-ethyl-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl)methyl]-5-phenyl-1H-1,2,3-triazole (Ph5) are new isomers of the triazole derivative family, were synthesized and tested on the corrosion of mild steel in molar hydrochloric acid molar media using weight loss, electrochemical polarization and impedance spectroscopy. Then the experimental results were confirmed by quantum chemical calculations using DFT at B3LYP /6-31G (d,p). The compound Ph4 is the best inhibitor and its inhibitory efficiency increased with increasing concentration and reaching 95% at 10⁻³ M. Polarization curves studies show that both compounds tested are mixed-type inhibitors. Nyquist curves presented a single capacitive loop, their diameter increases progressively with both inhibitors concentration. The change of the substitution phenyl from position 5 to position 4 in the triazole ring increases the inhibitory effect of the triazole compounds. The effect of temperature on the corrosion behavior of iron indicates that the inhibitory efficiency of the two inhibitors decreases with increasing temperature in the range of 308 to 338K. DFT study is in good correlationwith the experimental results.

The Atoyac River crosses the metropolitan area of Puebla, Mexico, and presents a condition of severe degradation that has been poorly studied. The research was conducted in the year 2016 and analyzed the space-time dynamics of the water quality of the river, the increase in pollution in the period 2011–2016, and the water quality of the Atoyac River used for agricultural irrigation and human consumption in the population of Emilio Portes Gil, Ocoyucan, based on official Mexican standards (NOMs). The anoxic state of the river was demonstrated (~1.47 mgO₂/L) and the high organic pollution, particularly in drought, as well as the presence of large populations of coliform bacteria, and 11 enterobacteries of pathogenic importance. The pollution recorded an average increase of 49% in the period 2011-2016, and the values of Fe, Al, Pb, and Cd in variable percentages. It was evidenced that water for irrigation and wells is contaminated with fecal bacteria (104–549 NMP/100 mL), including pathogenic. In wells, the concentration of heavy metals was 5 times higher in drought. These results represent a serious threat for the population of Emilio Portes Gil and the environment in the metropolitan area of Puebla.

This work investigated the isothermal holding time dependence of the densification, microstructure, weight loss and tensile properties of Fe-Mn-Si powder compacts. Elemental Fe, Mn and Si powder mixtures with a nominal composition of Fe-28Mn-3Si (in weight percent) were ball milled for 5h and subsequently pressed under a uniaxial pressure of 400 MPa. The compacted Fe-Mn-Si powder mixtures were sintered at 1200 ℃ for 0, 1, 2 and 3 h, respectively. In general, the density, weight loss and tensile properties increased with the increase of isothermal holding time. A significant increase in density, weight loss and tensile properties occurred in the compacts isothermally holding for 1 h, as compared to those with no isothermal holding. However, further extension of isothermal holding time (2 and 3 h) only played a limited role in promoting the density and tensile properties. The weight loss of the sintered compacts was mianly caused by the sublimation of Mn in Mn depletion region on the surface layer of the sintered Fe-Mn-Si compacts. The length of the Mn depletion region increased as isothermal holding time increased. A single α-Fe phase was detected on the surface of all the sintered compacts, and the locations beyond the Mn depletion region were comprised of a dual dominant γ-austenite and minor ε-martensite.

Background: Excessive sun exposure is a significant risk factor for various skin conditions, including sunburn, premature aging, and skin cancer. This study aims to assess the awareness, attitudes, and practices regarding sun exposure and sunscreen use among college students in Saudi Arabia. Methodology: A cross-sectional study was conducted with 388 college students from various disciplines. Data were collected using a structured questionnaire covering demographic information, knowledge, and practices related to sun exposure and sunscreen use. Descriptive statistics, chi-square tests, and multivariate logistic regression analysis were employed to analyze the data. Results: The study comprised 53.9% females, with the majority aged 18-23 years. Formal education on sun exposure dangers was lacking for 43.0% of participants. The most recognized consequences of excessive sun exposure were sunburn (80.6%) and skin cancer (74.4%). Intermediate knowledge of sun exposure effects was most common (40.7%). Sunscreen use was inconsistent, with 27.3% never using it during peak sunlight hours. Factors influencing sunscreen use included weather conditions and healthcare provider recommendations. Males were significantly less likely to use sunscreen. First-year students and participants without formal education on sun exposure were less likely to use sunscreen regularly. Conclusion: Despite awareness of the risks associated with excessive sun exposure, sunscreen use among college students in Saudi Arabia is inconsistent and influenced by various factors, including gender and education level. These findings highlight the need for enhanced educational initiatives to promote regular sunscreen use and other sun protection behaviors to mitigate the risk of skin conditions associated with sun exposure.

The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently limited as rotaviruses are highly species-specific and replication of human rotaviruses is minimal in mice. To enable characterisation of immune responses to human rotavirus in mice, we have generated chimeric viruses that combat the issue of rotavirus host range restriction. Using reverse genetics, the rotavirus outer capsid proteins (VP4 and VP7) from either human or murine rotavirus strains were encoded in a murine rotavirus backbone. Neonatal mice were infected with chimeric viruses and monitored daily for development of diarrhoea. Stool samples were collected to quantify viral shedding, and antibody responses were comprehensively evaluated. We demonstrated that chimeric rotaviruses were able to efficiently replicate in mice. Moreover, the chimeric rotavirus containing human rotavirus outer capsid proteins elicited a robust antibody response to human rotavirus antigens, whilst the control chimeric murine rotavirus did not. This chimeric human rotavirus therefore provides a new strategy for studying human rotavirus-specific immunity, and could be used to investigate factors causing variability in rotavirus vaccine efficacy. This small animal platform therefore has the potential to test the efficacy of new vaccines and antibody-based therapeutics.

Rising organic charge in northern freshwaters is attributed to increasing levels of Dissolved Natural Organic Matter (DNOM) and shifts in water chemistry. Organic charge concentration may be determined by charge balance calculations (Org.-) or modelled (OAN-) using the conceptual Oliver and Hruška models based on the density of weak acid functional sites (SD) present in DNOM. The charge density (CD) is governed by the SD and protonation and complexation reactions on the functional groups. The models use this SD as a key parameter in empirically fitting the model to Org.-. Utilizing extensive datasets of water chemistry, this study shows that spatial and temporal differences in SD and CD are influenced by variations in the humic-to-fulvic ratio of DNOM and the organic aluminum (Al) complexation, as well as the mole fraction of CD to SD governed by the acidity. Site median SD obtained for 44 long-term monitored acid-sensitive lakes was 11.1 and 13.9 µEq/mg C for the Oliver and the Hruška model, respectively. During the 34 years of monitoring the CD increased by 70%, likely due to rising pH and declining Al complexation with DNOM. Present-day median SD values for the Oliver and Hruška models in 16 low-order streams are 13.8 and 15.8 µEq/mg C, respectively, and 10.8 and 12.5 µEq/mg C, respectively, in 10 high order rivers.

Forests across the world stand at the crossroad with climate and land use changes shaping their future. Despite the demonstration of political will and global efforts, forest loss, fragmentation and land degradation continue unabated. No clear evidence exists that these initiatives are working. Why are policies designed to halt deforestation and increase restoration of forest landscapes failing? A key reason for this apparent ineffectiveness lies in the failure to recognize the agency of the stakeholders involved and the adaptive capacities of the systems we seek to steer. Landscapes do not happen. We make them. They are the result of the sum of individual actions and decisions made by all stakeholders, and the interactions between these and biophysical processes. Likewise, forest transitions are not ecological, but social and behavioral. They are a product of the way humans manage ecosystems. Decision-makers need to integrate better representations of people’s agency in their mental models. We suggest possible solution pathways to overcome this key current barrier. These involve eliciting mental models behind policy decision, changing perspectives to better understand divergent points of view and refining strategies through explicit theories of change. Games designed to represent the constraints and opportunities that exist in the landscapes can help decision makers in these task.

An imbalance between production and excretion of amyloid β peptide (Aβ) in the brain tissues of Alzheimer’s disease (AD) patients leads to Aβ accumulation and formation of noxious Aβ oligomers/plaques. A promising approach to AD prevention is reduction of free Aβ level by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). We previously demonstrated the ability of specific low-molecular-weight ligands (LMWLs) of HSA to improve its affinity for Aβ. Here we develop this approach by bioinformatic search for the clinically approved AD-related LMWLs of HSA, followed by classification of the candidates according to the predicted location of their binding sites on HSA surface, ranking of the candidates, and selective experimental validation of their impact on HSA affinity for Aβ. The top 100 candidate LMWLs were classified into the five clusters. The specific representatives of the different clusters exhibit dramatically different behavior, with 3- to 13-fold changes in equilibrium dissociation constants for the HSA-Aβ40 interaction: prednisone favors HSA-Aβ interaction, mefenamic acid shows the opposite effect, while levothyroxine exhibits the bidirectional effects. Overall, the LMWLs of HSA chosen here provide a basis for drug repurposing for AD prevention, and for search for the medications promoting AD progression.

Recently, flares have been considered as a major source of air pollution from the petroleum refining industry. The United Nations have instigated an international effort related to the management of flare emissions to reduce the global warming impact related to flaring. Eliminating or removing the need for gas flares is difficult because these devices are generally used as safety devices to allow combustion of flammable gases in a controlled fashion which supports safe operation. However, reducing flaring is generally possible using well designed efficiently operated flare equipment. In general, flare performance can be enhanced following the API-521 methodology and using assist- media including air and steam to achieve smokeless operation. This present work will discuss flare emissions in petroleum refining industry, and a method to manage flare emissions. Moreover, this work will discuss flare Combustion Efficiency (CE) and Distraction and Removal Efficiency (DRE) in terms of efficient flare operation. This work uses actual operating flare data, published previously, will be used in this work together with the CFD Code C3d. This code, developed at the USDOE Sandia National Laboratory is based on a standard LES methodology to conduct transient flare analysis is used to simulate flare operation to estimate flame shape and emissions produced. In this work, a new air-assisted flare tip design which uses the Coanda effect to improve flare operation was analysed. This new flare design reduces the emission rate that demonstrates the design effectiveness. The analysis considers a flare 1m high and (6") diameter in the centre of a 4m*4m*4m domain. Boundary conditions considering no cross wind and an ambient temperature of 300K. The initial condition is a hydrostatic pressure profile across the computational domain. In the air assist simulation, stoichiometric ratio will be a variable and therefore more than one case was considered.

To evaluate analgesic practices in perioperative treatment during SARS-CoV-2 pandemic; recording parameters collected in the PAIN OUT database, and to compare COVID and no-Covid data. Data were analyzed for 277 patients (87 with COVID-19 confirmed diagnosis): 67.55 +/- 15.714 years aged; predominance of male gender (54.02%), 200.67+/118.582 minutes of surgery, Likert Scale punctuation 1.55+/-1.461; 4.63+/-3.233 hours in severe pain; minimum pain intensity of 1.11+/-1.582 and maximum of 5.68+/-2.166; interference with sleep quality 4.45 +/-2.867; 0-10); anxiety of 4.83 +/-3.175; need for help 3.83 +/-3.100; nausea 1.75 +/- 2.469; drowsiness of 3.70+/-2.694; itching of 2.80+/-2.102; dizziness of 3.78+/-2.347; perception of care of 51.75+/-28.315; pain relief of 6.65+/-2.477, participation of 7.27+/-2.892; satisfaction of 79.84 +/-17.459, and information received of 81.75 +/-17.647. Postoperative mortality one month after surgery was recorded at 25.3% in COVID-19. Significant differences were found in postoperative pain intensity (p=0.019), time with severe pain (p&lt;0.01), lower sleep quality (p&lt;0.01); and better outcomes in functional ítems (p&gt;0.01), more side effects and satisfaction with pain relief (p&lt;0.01) in Covid-patients than no COVID-19 patients. In conclusion, COVID-19 patients presented. greater intensity and duration of severe postoperative pain, greater somnolence, pruritus, and dizziness, lower physical activity limitation, and higher quality index.

In strawberry cultivation, precise disease management is crucial for maximizing yields and reducing unnecessary fungicide use. Traditional methods for measuring Leaf Wetness Duration (LWD), a critical factor in assessing the risk of fungal diseases such as botrytis fruit rot and anthracnose, have been reliant on sensors with known limitations in accuracy and reliability and difficulties with calibrating. To overcome these limitations, this study introduced an innovative algorithm for leaf wetness detection systems employing high-resolution imaging and deep learning technologies, including convolutional neural networks (CNNs). Implemented at the University of Florida's Plant Science Research and Education Unit (PSREU) in Citra, Florida, USA and expanded to three additional locations across Florida, USA, the system captured and analyzed images of a reference plate to accurately determine the wetness and, consequently, the LWD. The comparison of system outputs with manual observations across diverse environmental conditions demonstrated the enhanced accuracy and reliability of the artificial intelligence-driven approach. By integrating this system into the Strawberry Advisory System (SAS), this study provided an efficient solution to improve disease risk assessment and fungicide application strategies, promising significant economic benefits and sustainability advances in strawberry production.

Quantum thermal engines are receiving much attention in recent years, due to their potential applications.~For a candidate group, harmonically trapped gases under Bose-Einstein condensation (BEC), we see little investigation on the energy transference around that transition.~Therefore, we present an empirical study with rubidium-87 gas samples in a magnetic harmonic trap.~We developed an empirical Equation of State model to fit to our experimental dataset, expressing the pressure parameter ($\mathcal{P}$) in terms of temperature ($T$) and six technical coeffcients ($\{a_i\}_{0,\dots,4}$, $T_\mathrm{th}$), functions of volume parameter ($\mathcal{V}$) and number of atoms ($N$).~For weakly interacting gases, the internal energy is $U\cong3\mathcal{P}\mathcal{V}$, thus we determine the entropy with $U = TS - \mathcal{P}\mathcal{V}$ for fixed $N$.~As expected, we show that the entropy at the BEC transition ($S_c$) is constant for varying $\mathcal{V}$.~Being isentropic makes BEC transition an energy source for non-mechanical work.~Hence, we observed that the enthalpy at the BEC transition $H_c = E_c + \mathcal{P}_c\mathcal{V} = T_cS_c$, at fixed values of $\mathcal{V}$ and varying $N$, grows fairly linearly with $N$.~We fitted $H_c=\eta{N}-H_c^0$ to that data, being $\eta$ the specific enthalpy of BEC transformation and $H_c^0$ an intrinsic enthalpic loss.~We deem this study to be a step closer to practical quantum-based engines.

Pulmonary sarcoidosis is a multisystem granulomatous interstitial lung disease (ILD) with a variable presentation and prognosis. Early accurate detection of pulmonary sarcoidosis may prevent progression to pulmonary fibrosis, a serious and potentially life-threatening form of the disease. However, the lack of a gold-standard diagnostic test and specific radiographic findings pose challenges in diagnosing pulmonary sarcoidosis. Chest computed tomography (CT) imaging is commonly used but requires expert, chest-trained radiologists to differentiate pulmonary sarcoidosis from lung malignancies, infections, and other ILDs. In this work, we developed a multichannel, CT and radiomics-guided ensemble network (RadCT-CNNViT) with visual explainability for pulmonary sarcoidosis vs. lung cancer (LCa) classification using chest CT images. We leverage CT and hand-crafted radiomics features as input channels, and a 3D convolutional neural network (CNN) and vision transformer (ViT) ensemble network for feature extraction and fusion before a classification head. The 3D CNN sub-network captures localized spatial information of lesions, while the ViT sub-network captures long-range, global dependencies between features. Through multichannel input and feature fusion, our model achieved the highest performance with accuracy, sensitivity, specificity, and combined AUC of 0.93±0.04, 0.94±0.04, 0.93±0.08 and 0.97 respectively in a 5-fold cross-validation study with pulmonary sarcoidosis (n=126) and LCa (n=93) cases. The model offers promising potential for improving the diagnosis of pulmonary sarcoidosis. A detailed ablation study showing the impact of CNN+ViT compared to CNN or ViT alone, and CT+radiomics input, compared to CT or radiomics alone, is also presented in this work.

Advancements in computer vision are rapidly revolutionizing the way traffic agencies gather roadway geometry data, leading to significant savings in both time and money. Utilizing aerial and satellite imagery for data collection proves to be more cost-effective, more accurate, and safer compared to traditional field observations, considering factors such as equipment cost, crew safety, and data collection efficiency. Consequently, there is a pressing need to develop more efficient methodologies for promptly, safely, and economically acquiring roadway geometry data. While image processing has previously been regarded as a time-consuming and error-prone approach for capturing these data, recent developments in computing power and image recognition techniques have opened up new avenues for accurately detecting and mapping various roadway features from a wide range of imagery data sources. This research introduces a novel approach combining image processing with a YOLO-based methodology to detect turning lane pavement markings from high-resolution aerial images, specifically focusing on Florida's public roadways. Upon comparison with ground truth data from Leon County, Florida, the developed model achieved an average accuracy of 87% at a 25% confidence threshold for detected features. Implementation of the model in Leon County identified approximately 3,026 left turn, 1,210 right turn, and 200 center lane features automatically. This methodology holds paramount significance for transportation agencies in facilitating tasks such as identifying deteriorated markings, comparing turning lane positions with other roadway features like crosswalks, and analyzing intersection-related accidents. The extracted roadway geometry data can also be seamlessly integrated with crash and traffic data, providing crucial insights for policymakers and road users.

Goat milk's medicinal properties and potential cosmetic and health benefits have prompted extensive scientific investigation into its therapeutic applications, particularly for human skin conditions like eczema and psoriasis. Genetic factors, including genes such as lactoferrin (LTF), lysozyme (LYZ), and β-casein (CSN2), play a crucial role in shaping milk composition and its effects on skin health. This review explores the utilization of genomic tools to elucidate the genomic profiles of dairy goat breeds and the medicinal properties of goat milk, particularly in addressing key skin diseases. Genetic determinants of milk composition, quality, nutritional quality, and functional properties such as the growth hormone receptor (GHR), butyrophilin (BTN1A1) and lactoglobulin (LGB) genes, facilitating targeted breeding strategies to enhance the production of bioactive compounds with dermatological relevance have been identified. Future genomic approaches should aim at exploring goat milk's immunomodulatory, antimicrobial, and antioxidant activities, offering potential applications in skin care formulations for managing inflammatory skin conditions. Furthermore, the integration of genomic data with functional studies can provide valuable insights into the therapeutic effects of goat’s milk and its derivatives in addressing skin diseases.

Most existing coal-fired power plants were designed for sustained operation at full load to maximize efficiency, reliability, and revenue, as well as to operate air pollution control devices at design conditions. Depending on plant type and design, these plants can adjust output within a fixed range in response to the plant operating or market conditions. The need for flexibility driven by increased penetration of variable and non-dispatchable power generation such as wind and solar is shifting the traditional mission profile of thermoelectric power plants in three ways: more frequent shutdowns when market or grid conditions warrant, more aggressive load ramp rates (rate of output change), and lower minimum sustainable load, which provides a wider operating range and helps avoid costly plant shutdowns. Recent studies have shown that flexibility of a coal-fired power plant can be improved by energy storage. The objective of this work was to analyze a set of energy storage options and determine their impact on flexibility and economics of a representative coal-fired power plant. The effect of three energy storage systems integrated with a coal power plant on plant flexibility and economics was investigated. The results obtained in this project show that Energy Storage Systems integrated with a thermal power plant improves plant flexibility and participation in the Energy and Ancillary Services markets which improves plant financial performance. The study was funded by the U.S. Department Office of Fossil Energy FE-1 under Award Number DE-FE0031903.

Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

The superconductivity of CaC6 as a function of pressure and of abundant Ca isotopes is revisited using DFT calculations on a 2c – double hexagonal superlattice. The introduction of superlattices is motivated by previous synchrotron absorption and Raman spectroscopy results on other superconductors that show evidence of superlattice vibrations at low (THz) frequencies. A 2c superlattice for CaC6 is illustrative of atomic orbital symmetry and periodicity, including bonding and antibonding s-orbital character implied by cosine modulated electronic bands. Inspection of the cosine band reveals that the cosine function has a small (meV) energy difference between bonding and antibonding regions relative to a midpoint non-bonding energy. Fermi surface nesting is apparent in an appropriately folded Fermi surface using a superlattice construct. Nesting relationships identify phonon vectors for conservation of energy and for phase coherency between coupled electrons at opposite sides of the Fermi surface. Detailed analysis of this Fermi surface nesting provides accurate estimates of the superconducting gaps for CaC6 with change in applied pressure. Recognition of superlattices within a rhombohedral or hexagonal representation provides consistent mechanistic insight on superconductivity and electron−phonon coupling in CaC6.

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

The delivery of therapeutical molecules through the skin, particularly to its deeper layers is impaired due to the stratum corneum layer, which acts as barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consists on an array of microscale needles. This particular biomedical device had been drawing attention due to their ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size and composition. The design process of a microneedle device must take in account several factors, like the location delivery, the material and manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application, cosmetics, therapy, diagnosis, tissue engineering, sample extraction, cancer research, wound healing, among others.

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying non-invasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small non-coding RNA such as microRNA and transfer RNA-derived fragments (tRF). Here we performed small-RNA next-generation sequencing for urine EVs, serum EVs and serum supernatant from 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. Serum and urine samples were collected before transurethral resection of bladder tumors (TUR-b) and at routine postsurgery check-ups. Expression levels of tRFs in presurgery samples were compared to those at postsurgery check-ups and to NCPs. To strengthen the reliability of our results, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between BC patients with stage T1 disease and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing presurgery to postsurgery samples, and four DEtRFs were found when comparing presurgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.

Hepatitis C virus (HCV) is a major medical health burden and leading cause of chronic liver disease and cancer worldwide. More than 58 million people are chronically infected with HCV, with 1.5 million new infections occurring each year. An effective HCV vaccine is a major public health and medical need as recognized by the World Health Organization. However, due to the high variability of the virus and its ability to escape the immune response, HCV rapidly accumulates mutations making a vaccine a formidable challenge. An effective vaccine must elicit broadly neutralizing antibodies (bnAbs) in a consistent fashion. After decades of studies from basic research through clinical development, the antigen of choice is considered to be the E1E2 envelope glycoprotein due to conserved, broadly neutralizing antigenic domains located in the constituent subunits of E1, E2, and the E1E2 heterodimeric complex itself. The challenge has been elicitation of robust humoral and cellular responses leading to broad virus neutralization due to the relatively low immunogenicity of this antigen. In view of this challenge, structure-based vaccine design approaches to stabilize key antigenic domains have been hampered due to the lack of E1E2 atomic-level resolution structures to guide them. Another challenge has been development of a delivery platform in which a multivalent form of the antigen can be presented in order to elicit a more robust anti-HCV immune response. Recent nanoparticle vaccines are gaining prominence in the field due to their ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both the cellular and humoral components of the immune system. This review focuses on recent advances in understanding the E1E2 heterodimeric structure to facilitate a rational design approach and the potential for development of a multivalent nanoparticle-based HCV E1E2 vaccine. Both aspects are considered important in the development of an effective HCV vaccine that can effectively address viral diversity and escape.

We study epidemic spreading in complex networks by a multiple random walker approach. Each walker performs an independent simple Markovian random walk on a complex undirected (ergodic) random graph where we focus on Barabási-Albert (BA), Erdös-Rényi (ER) and Watts-Strogatz (WS) types. Both, walkers and nodes can be either susceptible (S) or infected and infectious (I) representing their states of health. Susceptible nodes may be infected by visits of infected walkers, and susceptible walkers may be infected by visiting infected nodes. No direct transmission of the disease among walkers (or among nodes) is possible. This model mimics a large class of diseases such as Dengue and Malaria with transmission of the disease via vectors (mosquitos). Infected walkers may die during the time span of their infection introducing an additional compartment D of dead walkers. Infected nodes never die and always recover from their infection after a random finite time. This assumption is based on the observation that infectious vectors (mosquitos) are not ill and do not die from the infection. The infectious time spans of nodes and walkers, and the survival times of infected walkers, are represented by independent random variables. We derive stochastic evolution equations for the mean-field compartmental populations with mortality of walkers and delayed transitions among the compartments. From linear stability analysis, we derive the basic reproduction numbers R M , R 0 with and without mortality, respectively, and prove that R M < R 0 . For R M , R 0 > 1 the healthy state is unstable whereas for zero mortality a stable endemic equilibrium exists (independent of the initial conditions) which we obtained explicitly. We observe that the solutions of the random walk simulations in the considered networks agree well with the mean-field solutions for strongly connected graph topologies, whereas less well for weakly connected structures and for diseases with high mortality. Our model has applications beyond epidemic dynamics, for instance in the kinetics of chemical reactions, the propagation of contaminants, wood fires, among many others.

A very detailed water budget was conducted on Lake Trafford in southern Florida. The inflow was dominated by surface-water influx via five canals (61%) with groundwater influx constituting 12% and direct rainfall 27%. Lake discharge was dominated by sheet-flow (69%) and evapotranspiration (30.5%) with groundwater recharge of the hydraulically connected unconfined aquifer accounting for only 0.5%. Removal of 30 M tons (4.4 x 106 m3) of organic sediment impacted groundwater influx, causing enhanced groundwater flows into the deeper parts of the lake and mixed flows along the banks creating a rather unusual pattern. The large number of groundwater seepage meters used during the investigation led to a very reliable set of measurements with occasional failure of only a few meters. A distinctive relationship was found between the wet season lake stage, heavy rainfall events and pulses of exiting sheet-flow from the lake. Estimation of the evapotranspiration loss using data collected from a weather station on the lake allowed the use of three different models which, when averaged, produced results comparable to Lake Okeechobee (southern Florida). A limitation of the investigation was the inability to directly measure sheet-flow discharges, which had to be estimated as a residual within the calculated water budget.

Neutrophil elastase (NE) is taken up by macrophages, retains intracellular protease activity and induces a pro-inflammatory phenotype. However, the mechanism of NE-induced pro-inflammatory polarization of macrophages is not well understood. We hypothesized that intracellular NE degrades histone deacetylases (HDAC) and Sirtuins, disrupting the balance of lysine acetylation and deacetylation, and resulting in nuclear to cytoplasmic translocation of a major alarmin, High Mobility Group Box 1 (HMGB1), a pro-inflammatory response in macrophages. Human blood monocytes were obtained from healthy donors, or from subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Monocytes were differentiated into blood monocyte derived macrophages (BMDM) in vitro. Human BMDM were exposed to NE or control vehicle and the abundance of HDACs and Sirtuins was determined by western blotting of total cell lysates or nuclear extracts, or determined by ELISA. HDAC, Sirtuin, and Histone acetyltransferase (HAT) activities were measured. NE degraded most HDACs and Sirtuin (Sirt)1, resulting in decreased HDAC and sirtuin activities, with minimal change in HAT activity. We then evaluated whether the NE-induced loss of Sirt activity or loss of HDAC activities would alter the cellular localization of HMGB1. NE-treatment or treatment with Trichostatin A (TSA), a global HDAC inhibitor, both increased HMGB1 translocation from the nucleus to the cytoplasm, consistent with HMGB1 activation. NE significantly degraded Class I and II HDAC family members and Sirt 1 which shifted BMDM to a pro-inflammatory phenotype.

Background: Monocyte-derived dendritic cells (mo-DCs) play a vital role in the innate immune response by activating Th17 cells, which in turn release the pro-inflammatory cytokine IL-17. We hypothesised that following repetitive mechanical strain, tenocytes activate monocyte-derived dendritic cells, which in turn, drive the pathogenesis of tendinopathy. Aim: The aim of the study was to determine if monocyte-derived dendritic cells are upregulated in a human tendinopathy model. Method: Torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from 7 patients undergoing arthroscopic shoulder surgery. Healthy control samples of subscapularis tendon were collected from 5 patients undergoing arthroscopic stabilization surgery. Tendon biopsy samples were evaluated immunohistochemically by quantifying the presence of monocyte-derived dendritic cells (CD11C and CD206). Results: Tendinopathic tendon samples exhibited significantly greater (2-3-fold) monocyte-derived dendritic cell expression when compared with healthy control tissue (P &lt; .05). Conclusion: This study provides evidence for a monocyte-derived dendritic cell upregulation in early-stage human tendinopathy.

Monomeric Ubiquitin (Ub) is a 76-amino acid highly conserved protein found in eukaryotes. The first described biological activity of Ub in the 1970s was extracellular, but it quickly gained relevance due to its intracellular role, i.e., post-translational modification of intracellular proteins (ubiquitination) that regulate numerous eukaryotic cellular processes. In the following years, the extracellular role of Ub was relegated to the background, until a correlation between higher survival rate and increased serum Ub concentrations in patients with sepsis and burns was observed. Although the mechanism of action (MoA) of extracellular ubiquitin (eUb) is not yet well understood, further studies have shown that it may ameliorate the inflammatory response in tissue injury and multiple sclerosis diseases. These observations compounded with the high stability and low immunogenicity of eUb due to its high conservation in eukaryotes have made this small protein a relevant candidate for biotherapeutic development. Here, we review the in vitro and in vivo effects of eUb on immunologic, cardiovascular, and nervous systems, and discuss the potential MoAs of eUb as an anti-inflammatory, antimicrobial, cardio- and brain-protective agent.

Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

Curcumin attracts a huge attention because of its biological properties: antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the suspension method and were characterized by dynamic and electrophoretic light scattering, transmission electron microscopy and atomic force microscopy. The average particle size was 200 nm, and ζ-potential was -4 mV. Curcumin release studies showed that nanoparticles are stable in water solution. In vitro release study showed prolonged action in gastric, intestinal and colonic fluids, consistently and in PBS. In vitro studies on epidermoid carcinoma and human embryonic kidney cells showed that the cells absorbed more curcumin in nanoparticles compared to pure curcumin. Nanoparticles are safe for healthy cells and show high cytotoxicity for glioblastoma cells in cytotoxicity studies in vitro. Median lethal dose was determined in acute toxicity assay on Zebrafish and was 23 μM. Overall, the curcumin-loaded nanoparticles seem promising for cancer treatment.

The genus Colias Fabricius, 1807 includes numerous taxa and forms with uncertain status and taxonomic position. Among such taxa are Colias mongola Alphéraky, 1897 and Colias tamerlana Staudinger, 1897, interpreted in the literature either as conspecific forms, as subspecies of different but morphologically somewhat similar Colias species, or as distinct species-level taxa. Based on mitochondrial and nuclear DNA markers, we reconstruct a phylogeographic pattern of the taxa in question. We recover and include in our analysis DNA barcodes of the century-old type specimens, the lectotype of C. tamerlana deposited in the Natural History Museum (Museum für Naturkunde), Berlin, Germany (ZMHU), the paralectotype of C. tamerlana and the lectoptype of C. mongola deposited in the Zoological Institute, Russian Academy of Sciences, Saint-Petersburg, Russia (ZISP). Our analysis grouped all specimens within four (HP_I-HP-IV) deeply divergent but geographically poorly structured clades which did not support nonconspecifity of C. mongola–C. tamerlana. We also show that all studied females of the widely distributed haplogroup HP_II were infected with a single Wolbachia strain belonging to the supergroup B, while the males of this haplogroup, as well as all other investigated specimens, were not infected. Our data underline the relevance of large-scale sampling dataset analysis and the need of testing for Wolbachia infection to avoid erroneous phylogenetic reconstructions and species misidentification.

This study reports the synthesis and characterization of novel per-fluorinated organic polymers with azo- and azomethine-based linkers using nucleophilic aromatic substitution. The polymers reveal variations in the fluorine content via the incorporation of decafluorobiphenyl and hexafluorobenzene linkers, which enhanced their hydrophobic nature. The rich fluorine polymers were slightly soluble in THF and have shown molecular weights between 4886 to 11948 g/mol. All polymers exhibit thermal stability in the range of 350-500°C, with varying thermal stability depending on the fluorine and nitrogen content. Conjugation of the polymers was confirmed through changes in the UV-Vis spectra, with a hypsochromic shift observed in all cases, more pronounced in azo-based fluorinated chains due to H-bonding on the nitrogen sites, chain conformations, and planarity. The optical band gap (Eg) of the polymers was determined from the UV-Vis data, with the Eg values of the azo-based fluorinated polymers being 1 eV higher than those of their corresponding linkers. The cross-linking formation was characterized by porosity measurements, with the azo-based polymer exhibiting the highest surface area of 770 m²/g with a pore volume of 0.35 cm³/g, while the open-chain azomethine-based polymer exhibited the lowest surface area of 285 m²/g with a pore volume of 0.0872 cm³/g. Porous structures with varied hydrophobicities were investigated as adsorbents for separating water-benzene and water-phenol mixtures and selectively binding methane/carbon dioxide gases from the air. The most hydrophobic polymers containing the decafluorbiphenyl linker were suitable for benzene separation, while the best methane uptake values were 6.14 and 3.46 mg/g for DAB-Z-1O and DAB-A-1O, respectively. DAB-Z-1h, with the highest surface area and rich in nitrogen sites, exhibited the highest CO₂ uptake at 298 K (17.25).

The practice of voluntary depigmentation is still prevalent in Africa, with a wide range of lightening cosmetics used. Our objective was to research and quantify three regulated and/or prohibited depigmenting ingredients present in lightening cosmetics sold in Ouagadougou. Twenty-nine lightening cosmetic samples were collected from vendors and HPLC analysis was subsequently conducted to identify and measure the concentrations of hydroquinone, clobetasol propionate, and kojic acid. The presence of hydroquinone was indicated on the label of 13.79% of the products, while 51.72% contained it after analysis. Furthermore, none of the products mentioned a concentration of hydroquinone exceeding 2.00%, even though 27.58% of them contained high concentrations. For clobetasol propionate, its presence was stated on the labels of 13.79% of the products, while 31.03% contained it. One sample had a clobetasol content exceeding 0.05%, although none mentioned a concentration higher than this value. Finally, while 24.13% of the samples claimed to contain kojic acid, only 17.24% did. We also observed that 41.38% of the samples contained combinations of two depigmenting ingredients investigated, with a predominance of the hydroquinone + clobetasol propionate (27.38%). These results demonstrate that manufacturers' declarations regarding the compositions of active ingredients in lightening cosmetics can sometimes be deceptive.

One of the main constraints of agriculture in sub-Saharan Africa is the steady decline in the level of soil fertility resulting in a continuous decline in crop yields. This study assessed the impact of grass mulch on: the productivity, the income, the soil carbon, and the phytodiversity within three pineapple-based systems of the ecovillage of Donomade in Togo. They are: a model farm with mulch, adopters’ farms, and non-adopters. Production-related data (e.g., number of plants, the number of productive individuals, the mass of products harvested) was obtained by a sampling an area of 100 m². These measurements were coupled with a semi-structured individual’s interviews of producers on the history of the plots and production costs in order to assess their profitability. The fruit production was three times higher within the adopters’ plots (21240 ± 11890 kg/ha) than the non-adopters (7840 ± 7890 kg/ha) and the two thirds of the model farm (33838 ± 9460 kg/ha). Consequently, the net income was 8 to 11 times higher than the conventional pineapple cropping system. According to the cropping systems, the total soil carbon was higher within mulching plots including the model farm and the adopters’ plots and lower within the non-adopters’ plots.

Complex interactions between gene variants and environmental risk factors underlie the pathophysiological pathways in major psychiatric disorders. Autism Spectrum Disorder is a psychiatric condition in which susceptible alleles along with epigenetic memories contribute to the mutational landscape of the ailing brain. The present work reviews recent evolutionary, molecular, and epigenetic mechanisms potentially linked to the etiology of autism. First, we present a clinical vignette to describe clusters of maladaptive behaviors frequently diagnosed in autistic patients. Next, we microdissect brain regions pertinent to the nosology of autism as well as cell networks from the bilateral body plan. Lastly, we catalog a number of pathogenic environments associated with disease risk factors. This set of perspectives provides emerging insights into the dynamic interplay between epigenetic and environmental variation in the development of Autism Spectrum Disorders.

Recent studies have demonstrated an important role for vitamin C in the epigenetic regulation of cancer-related genes via DNA demethylation by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. DNA methyltransferase (DNMT) reverses this, increasing DNA methylation and decreasing gene expression. Dual oxidase (DUOX) enzymes produce hydrogen peroxide (H2O2) in normal pancreatic tissue but are silenced in pancreatic cancer (PDAC). Treatment of PDAC with pharmacologic ascorbate (P-AscH-, intravenous, high dose vitamin C) increases DUOX expression. We hypothesized that inhibiting DNMT may act synergistically with P-AscH- to further increase DUOX expression and cytotoxicity of PDAC. PDAC cells demonstrated dose-dependent increases in DUOX mRNA and protein expression when treated with DNMT inhibitors. PDAC cells treated with P-AscH- + DNMT inhibitors demonstrated increased DUOX expression, increased intracellular oxidation, and increased cytotoxicity in vitro and in vivo compared to either treatment alone. These findings suggest a potential therapeutic, epigenetic mechanism to treat PDAC.

Progesterone receptor (PGR) expression level determines biological characteristics of the serous ovarian carcinoma, and low PGR expression appears to be associated with chemoresistance and worse outcome. In this study, we aimed to find relationships between tumor progesterone receptor level and RNA-profile (miRNAs, piwiRNAs, and mRNAs), determining its biological characteristics and behavior. For this purpose, we applied next generation sequencing of small noncoding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze FFPE and frozen tumor samples as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumour (SBT), low-grade and high-grade serous ovarian carcinoma (LGSOC and HGSOC, respectively). We found significant upregulation of MMP7 and MUC16 and downregulation of PGR in LGSOC and HGSOC in comparison with BSC. The tissue content of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, miR-125b-5p significantly inversely correlated with the expression level of MUC16 and blood serum CA125 concentration, and significantly directly correlated with the PGR expression level in tumor tissue. On the contrary, the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, miR-93-5p, responsible for epithelial-mesenchymal transition (EMT) of the cell, significantly directly correlated with the blood serum CA125 concentration and significantly inversely correlated with the PGR expression level in the tumor tissue. Levels of the EMT-associated miRNAs significantly directly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, hsa_piR_019914 in tumor tissues. Among them, expression level of hsa_piR_004307 significantly inversly correlated with the PGR expression level in the tumor. Two optimal logistic regression models were developed based on the quantitation of hsa_piR_020813, miR-16-5p, hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, miR-93-5p in the tumor tissue, both of which significantly diagnose PGR-negative tumor phenotype with 93% sensitivity. According to FunRich3.1.3 functional enrichment analysis tool, 72 gene-targets of miRNA and piRNA identified here as markers of PGR-negative ovarian tumor phenotype were proven to be mutated in different cancers such as ovarian, breast, colorectal, liver, stomach, lung, endometrial, thyroid cancer. Among them, the blood plasma levels of miR-16-5p and hsa_piR_022437 can be used to diagnose PGR-negative tumor phenotype with 86% sensitivity before surgery and chemotherapy to choose the treatment strategy for this most aggressive type of ovarian cancer (for instance, neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy) to increase the effectiveness of treatment and longevity of the patient.

In Brazil, sucrose-rich broths (cane juice and/or molasses) are used to produce billions of liters of both fuel ethanol and cachaça per year using selected Saccharomyces cerevisiae industrial strains. Aiming to improve this disaccharide fermentation, we have first determined the genetic characteristics, by array comparative genomic hybridization, of a group of 8 fuel ethanol and 5 cachaça industrial yeasts that tend to dominate the fermentors during the production season. The widespread presence of SUC genes encoding invertase at multiple telomeres has been shown to be a common feature of both baker’s and distillers’ yeast strains and is postulated to be an adaptation to sucrose-rich broths. Our results show that only two strains (one fuel ethanol and one cachaça yeast) have amplification of the SUC genes, with high invertase activity. The other industrial yeast strains had a single SUC locus (SUC2) in their genome, with different patterns of invertase activity. These results indicate that invertase activity probably does not limit sucrose fermentation during fuel ethanol and cachaça production by these industrial strains. Using this knowledge, we changed the mode of sucrose metabolism of an industrial strain by avoiding extracellular invertase activity, overexpressing the intracellular invertase, and increasing its transport through the AGT1 permease. This approach allowed higher ethanol production from sucrose by the modified industrial yeast when compared to its parental strain.

Syringomyelia can be associated with multiple etiologies. The treatment of the underlying causes is the first-line therapy, however, a direct approach to the syrinx is accepted as rescue treatment. Any direct intervention on the syrinx requires a myelotomy, posing a significant risk of iatrogenic spinal cord (SC) injury. Intraoperative neurophysiological monitoring (IONM) is crucial to detect and prevent surgically induced damage in neural SC pathways. We retrospectively reviewed the perioperative and intraoperative neurophysiological data and perioperative neurological examinations in ten cases of syringomyelia surgery. All monitored modalities remained stable throughout the surgery in six cases, correlating with no new postoperative neurological deficits. In two patients, significant transitory attenuation, or loss of motor evoked potentials (MEPs), were observed and recovered after a corrective surgical maneuver, with no new postoperative deficit. In two cases, a significant MEP decrement was noted, which lasted until the end of the surgery and was associated with postoperative weakness. A transitory train of neurotonic electromyography (EMG) discharges was reported in one case, the surgical plan was adjusted and the patient showed no postoperative deficit. The dorsal nerve roots were stimulated and identified in the seven cases where the myelotomy was performed via the dorsal root entry zone. Dorsal column mapping guided the myelotomy entry zone in four cases. In conclusion, multimodal IONM is feasible and reliable and may help prevent iatrogenic SC injury during syringomyelia surgery.

The prolonged exposure to nicotine and the development of nicotine dependence have significant implications for cancer risk. Tobacco use, driven by nicotine addiction, is a major contributing factor to the development of various types of cancer. Smoking tobacco, in particular, has been strongly associated with an increased risk of lung cancer, as well as other malignancies. The harmful chemicals present in tobacco products, including carcinogens, can cause DNA damage and promote the initiation and progression of cancerous cells. This article presents a comprehensive literature review on the neurobiology of nicotine dependence and its implications for tobacco use treatment. Nicotine dependence is a complex phenomenon involving various neurobiological mechanisms. When nicotine enters the body, it binds to nicotinic acetylcholine receptors in the brain's reward circuitry, triggering the release of neurotransmitters like dopamine, serotonin, and norepinephrine. Over time, repeated nicotine exposure leads to neuroadaptive changes in the brain, resulting in increased motivation to seek and use the drug. Understanding the neurobiology of nicotine dependence is crucial for developing effective treatment strategies. Pharmacological interventions, such as nicotine replacement therapy and medications like bupropion and varenicline, can help individuals manage cravings and withdrawal symptoms. Additionally, behavioral therapies and counseling play a vital role in enhancing self-efficacy and providing support for smoking cessation efforts. By reviewing the existing literature, this article sheds light on the intricate neural pathways and processes involved in nicotine addiction. It emphasizes the importance of a multidimensional approach that combines pharmacological treatments and behavioral interventions to address the physiological and psychological aspects of nicotine dependence. This knowledge can inform the development of more targeted and personalized treatment approaches to help individuals overcome tobacco addiction and improve their chances of successful smoking cessation.

Deep brain stimulation (DBS) is an effective and safe medical treatment that improves the lives of patients with a wide range of neurological and psychiatric diseases, and has been consolidated as a first-line tool in the last two decades. Closed loop deep brain stimulation (CLDBS) pushes this tool further by automatically adjusting the stimulation parameters to the brain response in real-time. This paper presents a CLDBS with 2 stimulation channels and 2 acquisition channels. Each channel has a low-noise amplifier (LNA) buffer in differential configuration to eliminate the DC signal component of the input. Energy management is efficiently done by the control and communication unit. The battery supports almost 9 hours with both the acquisition and stimulation circuits active. If only the stimulation circuit is used as an Open Loop DBS (OLDBS), the battery can hold sufficient voltage for 24 hours of operation. The whole system is low-cost and portable and therefore it could be used as a wearable.

Background: Studying anxiety, stress and the selection of coping strategies in the COVID-19 pandemic is necessary to minimize the adverse changes associated with the risk of infection and the consequences of the disease. Objective: To investigate the level of anxiety, stress perception and coping strategies in relation to the presence of illness. Material and Methods: The anonymous cross-sectional online survey was conducted among 3950 university students of northeastern Poland (1822), Lithuania (232) and the Russian exclave of Kaliningrad (1896). Due to the almost identically applied anti-epidemic measures, the respondents were treated as a unified group. The State-Trait Anxiety Inventory, Perceived Stress Scale-10 and Coping Orientations to Problems Experienced questionnaires were used. Results: Among 1212 men and 2738 women, COVID-19 was diagnosed in 348 (28.7%) and 1020 (37.3%) individuals, respectively, according to the clinical protocol. The prolonged nature of the process and the longer consequences of the disease were indicated by an increase in anxiety levels. Conclusions: The risk of possible infection and coping with illness required the adoption of active anti-stress strategies, which was observed regardless of going through the disease. Convalescents differed from non-diseased individuals in having higher levels of concern about their own emotions and their more frequent turn to religion, notably among the females. The repertoire of strategies among women was broader, with elevated levels of helplessness and avoidance seen as integral strategies.

The appearance of brain metastasis is the most serious complication of breast cancer with mostly fatal outcomes. To reach the brain, tumor cells need to pass the blood-brain barrier (BBB). The molecular mechanisms underlying penetration of the BBB are largely unknown. Previously we found that tumor-infiltrating T lymphocytes enhance the development of brain metastasis of estrogen receptor-negative (ER-) breast cancer. In the current study, we investigate the contribution of T lymphocytes and the IFN- pathway in enabling breast cancer cells to pass the in vitro BBB. CD8+ cells display the strongest stimulatory effect on breast cancer cell passage. We show that inhibition of the IFN- receptor in MDA-MB-231 breast cancer cells, or neutralization of soluble IFN-, impairs the in vitro trespassing of breast cancer cells. Importantly, we validated our findings using gene expression data of breast cancer patients. CXCL-9,-10,-11/CXCR3 axis, dependent on IFN- signaling activity, was overexpressed in primary breast cancer samples of patients who developed brain metastasis. The data support a role for T-lymphocytes and the IFN- pathway in the formation of brain metastasis of ER- breast cancer, and offer targets to design future therapies for preventing breast cancer cells to cross the BBB.

To evaluate the anti-obesity effects of Smilax sieboldii (Smilacaceae), we screened methylene chlo-ride (CH2Cl2), ethyl acetate (EtOAc), aqueous-saturated n-butanol, and ethanol (EtOH) extracts of the whole plant at various concentrations to inhibit adipogenesis in adipocytes. The 3T3-L1 cell line with Oil red O staining with the help of fluorometry was used as an indicator of anti-obesity ac-tivity. Bioactivity-guided fractionation of the EtOH extract and subsequent phytochemical inves-tigation of the active CH2Cl2- and EtOAc-soluble fractions resulted in the isolation of 19 secondary metabolites (1–19), including a new α-hydroxy acid derivative (16) and two new lanostane-type triterpenoids (17 and 18). The structures of these compounds were characterized using various spectroscopic methods. All the isolated compounds were screened for adipogenesis inhibition at concentration of 100 μM. Of these, compounds 1, 2, 4-9, 15, and 19 significantly reduced fat ac-cumulation in 3T3-L1 adipocytes, especially compounds 4, 7, 9, and 19 showing 37.05 ± 0.95, 8.60 ± 0.41 15.82 ± 1.23, and 17.73 ± 1.28% lipid content, respectively, at a concentration of 100 μM. These findings provide experimental evidence that isolates from S. sieboldii extracts exert beneficial ef-fects regarding the regulation of adipocyte differentiation.

Two different silica conformations (Xerogels and Nanoparticles) both formed by the mediation of dendritic poly (ethylene imine) were tested at low pHs on the problematic uranyl cation sorption. The effect of crucial factors i.e., temperature, electrostatic forces, adsorbent composition, accessibility of the pollutant to the dendritic cavities and MW of the organic matrix was investigated to conclude the optimum formulation for water purification under these conditions. This was attained with the aid of UV-Visible and FTIR spectroscopy, dynamic light scattering (DLS), ζ-potential; Brunauer–Emmett–Teller (BET) porosimetry, Thermo Gravimetric Analysis (TG) and Scanning Electron Microscopy (SEM) Results highlighted that both adsorbents have extraordinary sorp-tion capacity. Xerogels are cost-effective since they approximate the performance of na-noparticles with much lesser organic content. Furthermore, they are more practicable materials since they may penetrate the pores of a metal or ceramic solid substrate in the form of a precursor, gel-forming solution.

Ants of the genus Solenopsis are important invasive pests in the world. Due to their high dispersion capacity, aggressive behavior and because they feed on various sources of vegetable and animal protein, these insects have caused serious damage to public health and agriculture. The control has usually been carried out through the use of organosynthetic insecticides. However, due to the ecological and environmental impacts caused by the use these products, more sustainable alternatives have been sought for their control. Faced with these problems and due to the scarcity of registered products for the control of these insects, we aimed with this study to synthesize and evaluate the anticidal potential of carvacrol derivatives. The lethal and sublethal effects caused by these derivatives were compared with the essential oil of Lippia gracilis (50.7% carvacrol) and with the base molecule — carvacrol. Carvacryl benzoate was the most toxic derivative to Solenopsis sp. with an LD50 of 3.20 g/ mg. This compound was about 2 and 7.6 times, more toxic than carvacrol at the doses needed to kill 50 and 90% of populations, respectively. The workers of Solenopsis sp. showed a rapid reduction in survival when exposed to carvacrol (LT50 = 8.43h) and carvacryl benzoate (LT50 = 8.87h). Insects treated with sublethal doses of the compounds did not show significant effects on self-cleaning, allogrooming and aggregation, with the exception of those treated with L. gracilis essential oil. The oil increased self-cleaning and reduced allogrooming and aggregation. Ants treated with carvacrol and carvacryl benzoate showed greater distance and speed when compared to the control. These compounds decreased meanders and angular velocity. When live workers were exposed to dead individuals at the LD90 of the compounds, carvacryl benzoate was the derivative that most reduced insects survival, due to horizontal transfer. These results show the potential of the carvacrol derivative — carvacryl benzoate — for the alternative management of ants of the genus Solenopsis sp.

Terminalia arjuna possesses significant cardio protective, antidiabetic and antioxidant properties as these properties are described in Ayurveda. In the present study, three flavonoids were isolated through the separation and chromatographic purification of the whole plant material of T. arjuna. Spectroscopic characterization identified one of them as a new flavonoid “Terminalone A (1)” and two known flavonoids i.e. 6-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one (2) and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one (3). The bioactivity studies showed considerable antibacterial and antioxidant (DPPH was used as a scavenger) potential for all the three compounds 1-3 where the compound 1 showed strong antibacterial and antioxidant activity.

Cryptococcus neoformans threaten the health, causing cryptococcal meningitis and pneumonia, especially in immunosuppressed patients, which can be fatal. Recently, our research group evaluated and studied the mechanisms of action of four synthetic peptides (SP) against C. neoformans. Here, in silico and in vitro analyses help deepen understanding of peptides' mechanisms of action. The interaction of the peptides with a membrane receptor was analyzed by docking analysis, in addition to ROS overproduction and the modulation of redox metabolism, inhibition of ergosterol biosynthesis, and release of cytochrome c. Out of four, three peptides interacted with membrane receptor PHO36 altering its structure and function and leading to a higher accumulation of O₂- and H2O2. C. neoformans cells treated with SP presented a reduction in the activity of antioxidant enzymes, corroborating ROS accumulation. However, in the presence of the antioxidant ascorbic acid, some peptides could not induce this oxidative stress and have the activity against C. neoformans affected. Curiously, two of these SPs still maintained the activity against C. neoformans and even induced the membrane pore formation as revealed by propidium iodide uptake assay, revealing their mechanism of action is ROS-independent. Additionally, SPs inhibited the biosynthesis of ergosterol, which corroborates the pore formation on the membrane of C. neoformans cells, inhibited the lactate dehydrogenase activity affecting the cell metabolism, and induced the release of Cyt c from the mitochondria inducing death by apoptosis in the cryptococcal cells. Our findings strongly suggest that SPs act by multiple mechanisms, making it difficult for C. neoformans to acquire resistance highlighting the potential of SPs as alternative molecules in treating infections caused by C. neoformans.

Glyphosate　(GLYP)　is a broad-spectrum, non-selective, organic phosphine post emergence herbicide registered for use on many food and non-food field. Herein, we developed a biosensor (Mbs@dsDNA) based on carboxylated modified magnetic beads incubated with NH2-polyA and then hybridized with polyT-glyphosate aptamer and complementary DNA. Afterward, a quantitative detection method based on qPCR was established.　When the glyphosate aptamer on Mbs@dsDNA specifically recognized glyphosate, a complementary DNA is released and then enters the qPCR signal amplification process. The linear range of the method was 0.1-5 μg/mL, and the detection limit was set at 0.1 μg/mL. The recoveries in tap water were ranged from 103.4 ~ 104.9%, and the relative standard deviations (RSDs) were < 1%. The aptamer proposed in this study has a good potential for recognizing glyphosate. The detection method combined with qPCR might have a good application prospect in detecting and supervising other pesticide residues.

Plant diseases are among the major factors affecting plant productivity. Biological control of plant diseases is preferred over chemical control as it is environment-friendly, cost-effective, and sustainable. Among many microbes capable of providing biological control of plant diseases, probiotic Bacillus species are most promising as they can survive in adverse conditions, provide plants with a wide range of benefits including protection from phytopathogens. Wheat blast caused by Magnaporthe oryzae Triticum pathotype (MoT) has emerged as a potential threat to global wheat production. Due to unreliability of fungicides and limited cultivar resistance, we aimed to screen and identify potential antagonist bacteria collected from internal tissues of rice and wheat seeds to determine their in vitro and in vivo inhibitory effects against MoT. Dual culture and seedling assays were performed to evaluate the efficacy of probiotic bacteria. Out of 170 bacterial isolates, three bacteria (BTS-3, BTS-4, and BTLK6A) were screened as potential antagonists against MoT in vitro. Artificial inoculation at the seedling stage showed that the isolates BTS-4, BTS–3, and BTLK6A reduced 89, 88, and 85% of wheat blast disease severity, respectively, compared to mock-inoculated control. The bacterial isolates were identified as Bacillus subtilis (BTS-3) and B. velezensis (BTS-4 and BTLK6A) through genome phylogeny. The whole genome sequence of these three bacterial strains decoded a number of orthologs to intrinsic genes of antimicrobial peptides, antioxidant defense enzymes, cell wall degrading enzymes, compounds involved in the induction of systemic resistance (ISR) in host plants, and volatile compounds to make them promising biologicals to control MoT in wheat. Combined data of in vitro and in vivo along with genome analysis suggest that Bacillus spp. suppress the destructive wheat blast disease likely through antibiosis and ISR in the host plants. Further field evaluation and characterization of antimicrobial compounds are needed for a better understanding of the mode of action and practical recommendation of these bacteria for wheat blast control in the farmers’ fields.

Management of urinary tract infection is challenged by increasing antimicrobial re-sistance (AMR) worldwide. In this study we describe the trends in antimicrobial re-sistance of uropathogens isolated from the largest private sector laboratory in Ghana over a five-year period. We reviewed positive urine cultures at the MDS Lancet Laboratories from 2017 to 2021. Proportions of uropathogens with antimicrobial resistance to oral and parenteral antimicrobials recommended by the Ghana standard treatment guidelines were determined. The proportion of multi-drug resistant isolates, ESBL and car-bapenemase-producing phenotypes were determined. Of 94,134 urine specimens submitted for culture, 20,010 (22.1%) were culture positive. Enterobacterales were the commonest group of organisms, E. coli (70.6) being the commonest isolate and Enterococcus spp. the commonest gram positive (1.3%) organisms. Among oral antimicrobials the highest resistance was observed to ciprofloxacin (62.3%) and cefuroxime (60.2) %) and the least resistance to Fosfomycin (1.9%). The least resistance among parenteral antimicrobials was to meropenem ( 0.3%). Highest multi-drug resistance levels were observed among Klebsiella spp. (68.6%) and E. coli (64.0%). ESBL positivity was highest in Klebsiella spp. (58.6%) and E. coli (50.0%). There may be a need to review the Ghana standard treatment guidelines to reflect increased resistance among uropathogens to recom-mended antimicrobials

Anion exchange of the halides, Br and I, is demonstrated through the direct mixing of two pure perovskite quantum dot solutions, CsPbBr3 and CsPbI3, and is shown to be both facile and result in a completely alloyed single phase mixed halide perovskite. Anion exchange is also observed in an interlayer printing method utilizing the pure, unalloyed perovskite solutions and a commercial inkjet printer. The halide exchange was confirmed by optical absorption spectroscopy, photoluminescent spectroscopy, X-ray diffraction, and X-ray photoemission spectroscopy characterization, and indicates that alloying is thermodynamically favorable, while the formation of a clustered alloy is not favored. Additionally, a surface-to-bulk photoemission core level transition is observed for the Cs 4d photoemission feature which indicates the electronic structure of the surface is different from the bulk. Time resolved photoluminescence spectroscopy indicates the presence of multiple excitonic decay features which is argued to originate from states residing at surface and bulk environments.

Background: Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is highly prevalent in women of Indian ethnicity. Clinical practice guidelines do not adequately consider ethnic-cultural differences in the care of women with PCOS. This study aimed to explore ethnic Indian women’s experiences with PCOS diagnosis and management, their concerns and it’s impact on their quality of life (QoL). Methods: Global online survey of ethnic Indian women of reproductive age living with PCOS. Results: Respondents (n=4409) had a mean age of 26.8 (SD 5.5) years and the majority were diagnosed with one or more co-morbidities (anxiety/depression being the most common). Women waited one year on average before seeking treatment following symptom onset. Irregular periods, cysts on the ovaries and excess unwanted facial hair growth were their three major concerns. Weight and emotional concerns had the greatest impact on QoL. One-third did not receive information on long-term complications, appropriate behavioral advice to improve diet or exercise, or emotional support following diagnosis. Among those who received information at diagnosis, the majority were dissatisfied. Conclusions: Ethnic Indian women wait for a considerable time before seeking medical help for PCOS, have poor QoL relating to weight and mental health and are dissatisfied with the information and support provided at diagnosis. These gaps in care should be addressed in clinical practice and future research.

This work presents the first evidence that dissolved globular proteins change the arrangement of hydrogen bonds in water, with different proteins showing quantitatively different effects. Using ATR-FTIR (Attenuated Total Reflection – Fourier Transform Infrared) spectroscopic analysis of OH-stretch bands, we obtain quantitative estimates of the relative amounts of the previously reported four subpopulations of water structures coexisting in a variety of aqueous solutions. Where solvatochromic dyes can measure the properties of solutions of non-ionic polymers, the results correlate well with ATR-FTIR measurements. In protein solutions to which solvatochromic dye probes cannot be applied, NMR (Nuclear Magnetic Resonance) spectroscopy was used for the first time to estimate the hydrogen bond donor acidity of water. We found strong correlations between the solvent acidity and arrangement of hydrogen bonds in aqueous solutions for several globular proteins. Even quite similar proteins are found to change water properties in dramatically different ways.

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin releasing factor (CRF)-CRF1 receptor and GABAergic signaling dysregulation occurring in alcohol dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch clamp electrophysiology to examine the effects of alcohol dependence on the CRF-modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had less CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

An updated, binary-coded message has been developed for transmission to extraterrestrial intelligences in the Milky Way galaxy. The proposed message includes basic mathematical and physical concepts to establish a universal means of communication followed by information on the biochemical composition of life on Earth, the Solar System’s time-stamped position in the Milky Way relative to known globular clusters, as well as digitized depictions of the Solar System, and Earth’s surface. The message concludes with digitized images of the human form, along with an invitation for any receiving intelligences to respond. Calculation of the optimal timing during a given calendar year is specified for potential future transmission from both the Five-hundred-meter Aperture Spherical radio Telescope in China and the SETI Institute’s Allen Telescope Array in northern California to a selected region of the Milky Way which has been proposed as the most likely for life to have developed. These powerful new beacons, the successors to the Arecibo radio telescope which transmitted the 1974 message upon which this expanded communication is in part based, can carry forward Arecibo’s legacy into the 21st century with this equally well-constructed communication from Earth’s technological civilization.

Ceramic samples based on b-calcium pyrophosphate b-Ca2P2O7 were prepared using firing at 900, 1000, and 1100 oC from powders of g-calcium pyrophosphate g-Ca2P2O7 with preset molar ratios Ca/P=1; 0,975 and 0,95. To prepare powders of g-calcium pyrophosphate g-Ca2P2O7 with preset molar ratio Ca/P=1; 0,975 and 0,95 powder mixtures based on calcium lactate pentahydrate Ca(C3H5O3)2⋅5H2O and, monocalcium phosphate monohydrate Ca(H2PO4)2⋅H2O were treated in an aqua medium in mechanical activation conditions, dried, disaggregated in acetone, and heat-treated at 600 oC. The phase composition of powder mixtures after treatment if planetary mill in aqua medium included both brushite CaHPO4⋅2H2O or monetite CaHPO4, and starting salts. The phase composition of all powder mixtures after disaggregation in acetone in planetary mill included monetite CaHPO4 and starting salts. After heat treatment at 600 oC according to the XRD data phase composition of all powder mixtures was presented by g-calcium pyrophosphate g-Ca2P2O7. The grain size of ceramics increased both with the growth of firing temperature and with decreasing of molar ratio Ca/P of powder mixtures. Calcium polyphosphate (t melt =960–968 oC) formed from monocalcium phosphate monohydrate Ca(H2PO4)2⋅H2O acted like a liquid phase sintering additive. It was confirmed by tests in vitro, that prepared ceramic materials with preset molar ratio Ca/P=1; 0,975 and 0,95 and phase composition presented by b-calcium pyrophosphate b-Ca2P2O7 according to XRD data were biocompatible and could maintain bone cells proliferation.

The incidence and prevalence of food allergy (FA) are increasing. While several studies have established the safety and efficacy of early introduction of single allergens in infants for the prevention of FA, the exact dose, frequency, and number of allergens that can be safely introduced to infants particularly in those at high or low risk of atopy are still unclear. This 1-year study evaluated the safety of early introduction of single foods (milk, egg, or peanut), vs. two foods (milk/egg, egg/peanut, milk/peanut), vs. multiple foods (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/fish/soy at low, medium, or high doses) vs no early introduction in infants between 4-6 months of age. At the end of the study, they were evaluated for plasma biomarkers associated with food reactivity with standardized blood tests. Two to four years after the start of the study, participants were evaluated by standardized food challenges. The serving sizes for the single, double, and low dose mixtures were 300 mg total protein per day. The serving sizes for the medium and high dose mixture was 900 mg and 3000 mg total protein, respectively. Equal parts of each protein were used for double or mixture foods. All infants were breastfed until at least 6 months of age. Results demonstrate that infants at either high or low risk for atopy were able to tolerate early introduction of multiple allergenic foods with no increases in any safety issues, including eczema, FA, or food protein induced enterocolitis. The mixtures of foods at either low, medium, or high doses demonstrated trends for improvement in food challenge reactivity and plasma biomarkers compared to single and double food introductions. The results of this study suggest that early introduction of foods, particularly simultaneous mixtures of many allergenic foods is efficacious for preventing FA and can occur safely.