Management of calcium and phosphate in biofluids is key to maintaining physiological mineral homeostasis (i.e., appropriate mineralization of hard tissues and an absence of mineral deposition in soft tissues). This review describes and contrasts the ways vertebrates manage calcium phosphate in two biological fluids (breast milk and serum) and illustrates the benefits of mineral sequestration by proteins. In milk, phosphoprotein-sequestered calcium magnesium phosphates provide nutritional support, whereas in serum, protein-sequestered calcium phosphates control transport and delivery of calcium and phosphate to tissues for biological function or excretion. In addition, subsets of sequestered phosphates in serum have been identified as culprits underlying ectopic deposition of calcium phosphates and toxicity.

Applying of blood biopolymers to regulate the phase composition is promising in designing the hydroxyapatite-based hybrid biomaterials with controllable resorbability. Hybrid materials based on hydroxyapatite and platelet-poor plasma (PPP) were formed in conditions of chemical precipi-tation at pH 11, [Ca2+] / [PO43–] ratio 1.67, PPP volume fraction of 6–24%, maturing time of 4–9 days. Mineral component of the materials was represented as 53% hydroxyapatite / 47% amor-phous calcium phosphate after 4 days of maturation, and 100% hydroxyapatite after 9 days of maturation. Varying PPP content from 6% to 24% provided forming of materials with rather de-fined content of amorphous calcium phosphate and biopolymer component, having desired mor-phology ranging from typical apatitic conglomerates to hybrid apatite-biopolymer fibers. Co-precipitated hybrid materials based on hydroxyapatite and PPP are promising for bone regen-eration in osteoplastic and maxillofacial applications.

A notable REE mineralization in Europe is associated with the Ditrău Alkaline Massif (DAM) in the Eastern Carpathians (Romania). It is an expression of the latest hydrothermal phase in the DAM and is found in the form of mineralized carbonate veins cross-cutting the complex in the NW (Jolotca region) and the SE (Belcina region) parts of the DAM. In the Belcina veins monazite-(Ce), xenotime-(Y), apatite, together with Fe-Mg-rich carbonate, thorite, thorogummite, gedrite and plagioclase are rock-forming. Three different textural and chemical types of the monazite-(Ce) and the xenotime-(Y) document a three-stage evolution. The relative phosphate age succession (from older to younger) thereby is xnt1 > xnt2 (>)+ mnz1 + Fe2O3 + Fe-gedrite > mnz2 + Fe-dolomite (+ plagioclase) > mnz3 + xnt3 + apatite. Phosphate chemistry shows that these crystallized from hydrothermal fluids, whereby each phosphate type follows a separate evolutionary path recommending growth from (at least) 3 independent and successive hydrothermal fluids. Chemistry and pathways within the DAM suggest that these hydrothermal fluids could be derived from a subsurface carbonatitic intrusion. Mnz1,2 and xnt1,2 ages are tightly cluster at 215.8 ± 0.7 Ma (Norian, Upper Triassic). The third-generation phosphate ages are younger, but associated with large analytical uncertainties and did not deliver geologically useful ages. The mean age of ca. 216 Ma is interpreted as timing the Belcina REE mineralization, what together with the fluid chemistry, supports a model of the presence of a late-stage, independent carbonatitic intrusion about 10 Ma after the main igneous activity (ca. 235 - 225 Ma) forming the DAM, synchronous with extension-related magmatism in the region.

The flow behavior of the administrated fluid matrices demands careful assessments for stability as consumed by individuals with dysphagia. In the present study, we incorporate tapioca starch (TS), hydroxypropyl distarch phosphate (HDP), and xanthan gum (XG) as thickeners into different nectars (300±20 mPa.s) undergoing thermal processing and evaluated their stability. The thickened nectars presented better water holding and oil binding capacities at 25 ℃ than 4 ℃, and the nectars with TS provided the best results for both capacities as well as the highest solubility index and swelling power (p<0.05). All prepared nectars appeared to be shear-thinning fluids with yield stress closely fitting the power law and Casson models. XG-contained nectars presented a higher yield stress and consistency index. Matrices thickened by HDP exhibited a higher viscoelastic property compared to those thickened by TS during thermal processing. TS nectars presented viscous behavior, whereas HDP and XG nectars presented elastic behavior at 80 ℃ processing. The 3-min thermal processing HDP-nectars remained stable and met dysphagia-friendly requirements under 4 ℃ storage for 28 days regardless of the types of fluid bases (distilled water, sport drink, or orange juice). The employed thickeners present adequate physicochemical properties to be potentially utilized for producing dysphagia-friendly formulations.

Different external stimuli are perceived by multiple sensor histidine kinases and transmitted by phosphorylation via the phosphotransfer protein Ypd1p in the multistep phosphorelay system of the high osmolarity glycerol signaling pathway of filamentous fungi. How the signal propagation takes place is still not known in detail, since multiple sensor histidine kinase genes in most filamentous fungi are coded in the genome, whereas only one gene for Ypd1 exists. That raises the hypothesis that various Ypd1 isoforms are produced from a single gene sequence, perhaps by alternative splicing, facilitating a higher variability in signal transduction. We found that the mRNA of MoYPD1 in the rice blast fungus Magnaporthe oryzae is subjected to an increased structural variation and amplified putative isoforms on a cDNA level. We then generated mutant strains overexpressing these isoforms, purified the products and present here one previously unknown MoYpd1 isoform on a proteome level. Alternative splicing was found to be a valid molecular mechanism to increase the signal diversity in eukaryotic multistep phosphorelay systems.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

To understand the biological relevance and mode of action of artificial protein ligands, crystal structures with their protein targets are essential. Here, we describe and investigate all known crystal structures that contain a so-called “molecular tweezer” or one of its derivatives with an attached natural ligand on the respective target protein. The aromatic ring system of these compounds is able to include lysine and arginine side chains, supported by one or two phosphate groups that are attached to the half-moon shaped molecule. We analyse the corresponding crystal structures with 14-3-3 proteins in complex with mono- and diphosphate tweezers. Furthermore, we solved crystal structures of two different tweezer variants in complex with the enzyme 1-Pyrroline-5-carboxyl-dehydrogenase (P5CDH), and found that the tweezers are bound to a lysine and methionine side chain, respectively. The different binding modes and their implications for affinity and specificity are discussed, as well as the general problems in crystallizing protein complexes with artificial ligands.

For Interferometry Synthetic Aperture Radar (InSAR), the normal baseline is one of the main factors that affect the accuracy of the ground elevation. For Gaofen-3 (GF-3) InSAR processing, the poor accuracy of the real-time orbit determination resulting in a large baseline error, leads to the modulation error in azimuth and the slope error in range for timely Digital Elevation Model (DEM) generation. In order to address this problem, a baseline estimation method based on external DEM is proposed in this paper. Firstly, according to the characteristic of the real-time orbit of GF-3 images, orbit fitting is executed to remove the non-linear error factor. Secondly, the height errors are obtained in slant-range plane between Shuttle Radar Topography Mission (SRTM) DEM and the GF-3 generated DEM after orbit fitting. At the same time, the height errors are used to estimate the baseline error which has a linear variation. In this way, the orbit error can be calibrated by the estimated baseline error. Finally, DEM generation is performed by using the modified baseline and orbit. This procedure is implemented iteratively to achieve a higher accuracy DEM. Based on the results of GF-3 interferometric SAR data for Hebei, the effectiveness of the proposed algorithm is verified and the accuracy of GF-3 real-time DEM products can be improved extensively.

The feasibility of using zeolites, synthesized from components found in municipal solid waste fly ash (MSW-FA), as sorbents for the recovery of nutrients (nitrate and phosphate) and heavy metals is critically assessed in this review. The inherent drawbacks of utilising a highly contaminated, variable, and relatively Al- and Si-dilute source such as MSW-FA to synthesize zeolites are discussed, and different methods to extract and decontaminate zeolite precursor materials from MSW-FA are considered. Ways to synthesize tailored zeolites and how their properties as well as the operational conditions impact the adsorption of cations such as ammonium and heavy metals are summarized. The use of surface-modified zeolites to adsorb nitrate and phosphate is also reviewed. And subsequently, approaches to utilise directly or recover for reuse the adsorbed compounds are considered, discussing potential challenges and mitigating measures related to leaching of unwanted compounds from the zeolites. Moreover, the possibility to regenerate the adsorption capacity of the zeolites for multiple adsorption cycles is considered. In the final chapter of the review a more general discussion of the main challenges and existing research gaps is provided, giving directions for recommended studies.

Oxidative stress is defined as an imbalance between the production of free radicals and reactive oxygen species (ROS) and the ability of the body to neutralize them by antioxidant defense systems. Cells produce ROS as a control of physiological processes, but increasing ROS becomes pathological leading to non-specific and irreversible damage to biological molecules, such as DNA, lipid, and protein. Endogenous ROS are mainly produced by mitochondria during both physiological and pathological conditions, and enzymes, such as nicotinamide adenine dinucleotide phosphate oxidase (NOX), xanthine oxidase (XO), lipoxygenase (LOX), myeloperoxidase (MPO) and monoamine oxidase (MAO). To neutralize ROS, the body employs enzymatic and non-enzymatic defense systems. The dietary intake of bioactive phenols, such as quercetin (Que), is a non-enzymatic system that can quench ROS and protect from pro-oxidative damage. In this review, we evaluate the ability of Que to target endogenous oxidant enzymes involved in ROS production and explore the mechanisms of action underlying its antioxidant properties. Que not only acts as a free radical scavenger by donating electrons through the negative charges in its phenolic and ketone groups, but it can effectively inhibit the activity of several endogenous oxidative enzymes, binding them with high affinity and specificity. Among all targets, Que showed the best results in molecular docking simulations with XO, followed by MAO-A, 5-LOX, NOX, and MPO. Taken together, these findings highlight the potential of Que as a natural antioxidant therapy for oxidative stress-related diseases.

Background: Initial phases of molecular and cellular maladaptive bone response at early CKD remain mostly unknown. Methods: We induced mild CKD in SHRs by either arterial hypertension lasting six months (sham-operated rats, SO6) or in its’ combination with 3/4 nephrectomy lasting two and six months (Nx2 and Nx6, correspondently). Sham operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. We measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact PTH and FGF23, Klotho, dickkopf-1, sclerostin. And assessed bone response by static histomorphometric indices and gene expression profiles. Results: Mild CKD groups had no increase in renal Pi excretion, FGF23 and PTH levels. Serum Pi, dickkopf-1, and sclerostin were higher in Nx6. Decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast number. The decline in eroded perimeter was only apparent in Nx6. Significant downregulation of genes related to Pi transport, MAPK, WNT, and BMP signaling accompanied histological alterations in Nx2 and Nx6. Conclusions: We found an association of mild CKD with histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.

Followed by the aspect of respect for rights 20, the social and environmental issue has a score of 19.9, the dialogue issue is 19. In short, the proximity plan indicates that the policies used regarding the issue of generating employment and economic growth (Empresa Mantaro Perú SAC), continue to be the strategic variables in the first instance, but they are far from the social actors (rural communities of Aco, Vico, Cruz Pampa and others) and environmental (Junín environmental dialogue table) and Ombudsman's Office (rights) that are currently closer together. The actor from the Archbishop of Huancayo referred to communication is one of the driving variables of power. The proximity plan shows us that the policies used regarding the issue of generating employment and economic growth (Empresa Mantaro Perú SAC), continue to be the strategic variables in the first instance, but that they are far from the social actors (Rural Communities of Aco , Vico, Cruz Pampa and others) and environmental (Junín Environmental Dialogue Table) and Ombudsman's Office (rights) that are currently closer together. The actor from the Archbishop of Huancayo referred to communication is one of the driving variables of power. The proximity plan shows us that the policies used regarding the issue of generating employment and economic growth (Empresa Mantaro Perú SAC), continue to be the strategic variables in the first instance, but that they are far from the social actors (Rural Communities of Aco , Vico, Cruz Pampa and others) and environmental (Junín Environmental Dialogue Table) and Ombudsman's Office (rights) that are currently closer together. The actor from the Archbishop of Huancayo referred to communication is one of the driving variables of power. but they are far from the social actors (rural communities of Aco, Vico, Cruz Pampa and others) and environmental (Junín Environmental Dialogue Table) and the Ombudsman's Office (rights) that are closer together today. The actor from the Archbishopric of Huancayo referred to communication, is within the driving variables of power. but they are far from the social actors (rural communities of Aco, Vico, Cruz Pampa and others) and environmental (Junín Environmental Dialogue Table) and the Ombudsman's Office (rights) that are currently closer together. The actor of the Archbishopric of Huancayo referred to communication, is within the driving variables of power.

A human organism depends on stable glucose blood levels in order to maintain the metabolic needs. Glucose is considered as the most important energy source and glycolysis is postulated as a backbone pathway. However, when glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. PPP generates and maintains levels of NADPH needed for reduction of oxidized glutathione and protein thiols, synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. Flux of glucose into a PPP, particularly under extreme oxidative and toxic challenges is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP⁺ that is required for activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload and provides new insights into positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.

The combination of calcium phosphates (CaP) with bioactive glasses (BG) has received an increased interest in the field of bone tissue engineering. In the present work, biphasic calcium phosphates (BCP) obtained by hydrothermal transformation (HT) of cuttlefish bone (CB) were coated with a Sr-, Mg- and Zn-doped sol-gel derived BG. The scaffolds were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The initial CB structure was maintained after HT and the scaffold functionalization did not jeopardize the internal structure. The results of in vitro bio-mineralization after immersing the BG coated scaffolds in simulated body fluid (SBF) showed extensive formation of bone-like apatite onto the surface of the scaffolds. Overall, the functionalized CB derived BCP scaffolds revealed promising properties for their use in bone tissue engineering field.

An interdigitated electrode sensor was designed and microfabricated for measuring the changes in the capacitance of three phosphate selective molecularly imprinted polymer (MIP) formulations, in order to provide hydroponics users with a portable nutrient sensing tool. The MIPs investigated were synthesised using different combinations of the functional monomers methacrylic acid (MAA) and N-allylthiourea, against the template molecules diphenyl phosphate, triethyl phosphate and trimethyl phosphate. A cross-interference study between phosphate, nitrate and sulfate was carried out for the MIP materials using an inductance, capacitance and resistance (LCR) meter. Capacitance measurements were taken applying an alternating current (AC) with a potential difference of 1 V root mean square (RMS) at a frequency of 1 kHz. The cross-interference study demonstrated a strong binding preference to phosphate over the other nutrient salts tested for each formulation. The size of template molecule and length of the functional monomer side groups also determined that a combination of a short chain functional monomer in combination with a template containing large R-groups produced the optimal binding site conditions when synthesising a phosphate selective MIP.

Biomass and biowaste valorisation is of major interest nowadays because of the spirit of circular economy and of the neutral environmental fingerprint global target. In the current project chondroitin sulphate (ChS) was incorporated with the crustaceous’ and shrimp’s byproduct chitosan (Chi) and the fish industry byproduct gelatine (FG) to obtain dense hydrogel membranes. Glycerol (Gly) was utilized to avoid brittleness. The formation of the hydrogel membranes is attributed to secondary interactions between the natural polymers and the plasticizer. The prepared hydrogel membranes were characterized by Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The surface morphology of the membranes was examined using scanning electron microscopy (SEM). Dynamic mechanical analysis (DMA) and tensile tests were also performed to evaluate the mechanical response of the membranes. The samples were also evaluated for membrane wettability, degradation rate and water vapor transmission rate (WVTR). Finally, in vitro endothelial cell attachment on the membrane were addressed. The overall results of the study indicate that the hydrogel membranes could be appropriate for external application in wound healing applications as dressings.

In the Quaternary paleosciences, the rationale behind analogical inference presupposes that former natural changes can be explained by causes operating now, although their intensity and rates can vary through time. In this paper we synthesise synthetize the results of different modern analog studies and discuss their value to obtain the best inferences from high resolution past records. This synthesis is based on the following: 1) The monthly monitoring of calcite precipitation reveals a strong connection with primary producers and between-years variability; this precipitation produces a seasonal signal with imprint on varve formation. 2) Clear pollen sedimentation peaks occur in spring/summer and fall/winter that coincide with temperature, precipitation, relative humidity and winds; this pattern converges with the two-layer coupled varves representing the same seasonality. 3) We assess the lake’s contemporary oxygenation dynamics over a three- year period; a combination of sedimentary REDOX proxies revealed different scenarios of oxic/anoxic shifts since 1500 CE. 4) We investigate presence of seasonality in the production/distribution of glycerol dialkyl glycerol tetraethers and derived temperature estimates in soils and particulate matter. Branched glycerol dialkyl glycerol tetraethers signatures and some derived temperature estimates proxies appear to mainly depend on the non-seasonal shifts in soil properties. 5) Currently we examine relationships and similarities between extant phytoplankton and derived pigments in water and traps, and their correspondence with subfossil pigments; some preliminary results are presented here.Keywords: high resolution, endogenic varves, calcite precipitation, pollen sedimentation, meromixis, freshwater glycerol dialkyl tetraether, subfossil pigments, long-term ecology.

Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single cell migration that KMT2D inactivation promoted in synergy with PI 3-kinase activation. Combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function, single cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase.

Among cross-sectional imaging modalities, computed tomography (CT) is more available and faster; however, magnetic resonance (MR) performs better in terms of sensitivity and specificity, due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR depends mainly on the primary tumour histology: in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights on the tumour origin. The time-point of tumour evolution, previous or ongoing treatments and the peritoneal spaces where they occur, also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is mandatory in detection and characterization of peritoneal deposits. Several benign and malignant conditions may show similar imaging features that overlap those of PC, making the differential diagnosis challenging. Clinical history, laboratory findings and previous imaging examinations must be considered to achieve the correct diagnosis.

Cellulose nanocrystals (CNCs) are a kind of nano-inclusions that have experienced tremendous expansion in the material industry due to their outstanding mechanical qualities, sizable surface area, and capacity for functional tuning. Due to their vast potential, however, present practises fall short of fully using them. For example, employing CNCs in various matrices with various surface chemistries can be challenging; this problem tends to get worse if the focus is furthered on bio-based applications. This paper reviews the use of CNCs as fillers in natural and man-made polymers; we have explored in depth the production, characterisation, and of CNCs from various sources and their inclusion into various matrices. Surface alterations and the introduction of CNCs in biodegradable polymer can have a significant impact on several industrial behemoths such as tissue engineering and biomedical applications; therefore, pursue of current manuscript is extremely warranted. Throughout the manuscript various assembly techniques that involves alteration and adjustment of polymer network in building up a hydrogel with higher fracture energy and mechanical properties are also included. From rheological perspective the hydrogel processing is also discussed with some models routinely used in the literature to describe these hydrogels. Finally, bio-based hydrogels mechanically reinforced with CNCs such as Xanthan Gum, Alginate, protein, and polysaccharides were discussed.

Background: Monoclonal antibodies against PD-1 or PD-L1 are established in clinical practice for the treatment of both early and advanced/metastatic triple-negative breast cancer. Beyond the established immune checkpoints (ICPs) (PD-1 and CTLA-4) additional ICPs such as lymphocyte activation gene-3 (LAG-3) are subject of current research. In the present retrospective gene ex-pression analysis, we evaluated the prognostic significance of LAG-3 in 461 patients with early breast cancer. In addition, we examined whether there was a correlation between the different ICPs and CD8 expression. Methods: Using microarray-based gene expression analysis, we examined the prognostic signif-icance for metastasis-free survival (MFS) of LAG-3 mRNA expression in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed us-ing Spearman-Rho correlation coefficient. Results: In the whole cohort, LAG-3 expression had no significant impact on MFS (p = 0.712, Log Rank). In the subgroup analyses, there was a trend, that higher LAG-3 expression was associated with favorable outcome in the luminal B (p = 0.217), basal-like (p = 0.370) and HER2 (p = 0.089) subtypes, although significance was not reached. In contrast, in multivariate Cox regression analysis adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and the proliferation marker Ki-67, LAG-3 showed a significant influence on MFS (HR 0.574; 95% CI 0.369–0.894; p = 0.014). High LAG-3 significantly correlated with CD8 ( = 0.571; p < 0.001). Conclusion: LAG-3 expression had an independent impact on MFS. In addition to PD-1 and PD-L1, further immune checkpoints such as LAG-3 could serve as therapeutic targets in breast cancer.

Salivarian trypanosomes are extracellular parasites causing anthroponotic and zoonotic infections. Anti-parasite vaccination in considered the only sustainable method for global trypanosomosis control. Unfortunately, not a single field applicable vaccine solution has been successful so far. Active destruction of the host’s adaptive immune system by trypanosomes is believed to contribute to this problem. Here we show Trypanosome brucei brucei infection results in the lasting obliteration of immunological memory, including vaccine-induced memory against non-related pathogens. Using the well-established DTPa vaccine model in combination with a T. b. brucei infection and diminazene diaceturate anti-parasite treatment scheme, our result demonstrate that while the latter ensured the full recovery from the T. b. brucei infection, it failed to restore an efficacious anti-pertussis vaccine recall response. DTPa vaccine failure coincided with a shift in the IgG1/IgG2a anti-pertussis antibody ratio in favor of the latter, and a striking impact on all spleen immune cell populations. Interestingly, an increased plasma IFNy level in DTPa vaccinated trypanosome infected mice did result in a temporary antibody-independent improvement of early-stage trypanosomosis control. In conclusion, our results are the first to show that trypanosome inflicted immune damage is permanent, and is not restored by successful anti-parasite treatment.

NS-3 is one of the most used Network Simulators because it includes different modules, applications and protocols to simulate a wide range of network. Since new proposals usually involve a large number of simulations, a procedure to automatize the simulation process and extract statistics is very useful. "Statistical Framework" (SF) is an important module of NS-3 because it fulfills this need. SF allows us to collect simulation data and obtain statistical reports for NS-3. In this report, we present a detailed description of statistical framework module and two useful examples of its configuration.

Network Simulators is typically used to study services and applications in complex scenarios due to the infeasibility of deploying real testbeds. Many problems can be solved by using network simulators such as NS-3. With this in mind, the aim of this article is to introduce new NS-3 users through detailed information. It is sometimes difficult to handle by new users the traditional manuals developed by NS-3 project official website. In this article, NS-3 for communication network and Eclipse Integrated Development Environment (IDE) for powerful programming language are integrated step-by-step, explaining the main features of these open source software packages and concluding with an example simulation. Our effort is to make it easy for a beginner to be part of the NS-3 research community and to maintain an open environment of knowledge.

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression's development. Given that obesity and depression mutually increase each other's risk of development by 50-60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines, and C-reactive protein (CRP). As pharmacotherapy fails in at least 30-40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further effort directed to implement these strategies in clinical practice could contribute to improved outcomes in patients with depression and comorbid obesity and/or metabolic dysregulation.

Rationale: The 14-3-3 protein family is known to interact with many proteins in non-cardiac cell types to regulate multiple signaling pathways, particularly those relating to energy and protein homeostasis; and the 14-3-3 network is a therapeutic target of critical metabolic and proteostatic signaling in cancer and neurological diseases. Although the heart is critically sensitive to nutrient and energy alterations, and multiple signaling pathways coordinate to maintain the cardiac cell homeostasis, neither the structure of cardiac 14-3-3 protein interactome, nor potential functional roles of 14-3-3 protein-protein interactions (PPIs) in heart has been explored. Objective: To establish the comprehensive landscape and characterize the functional role of cardiac 14-3-3 PPIs. Methods and Results: We evaluated both RNA expression and protein abundance of 14-3-3 isoforms in mouse heart, followed by co-immunoprecipitation of 14-3-3 proteins and mass spectrometry in left ventricle. We identified 52 proteins comprising the cardiac 14-3-3 interactome. Multiple bioinformatic analyses indicated that more than half of the proteins bound to 14-3-3 are related to mitochondria; and the deduced functions of the mitochondrial 14-3-3 network are to regulate cardiac ATP production via interactions with mitochondrial inner membrane proteins, especially those in mitochondrial complex I. Binding to ribosomal proteins, 14-3-3 proteins likely coordinate protein synthesis and protein quality control. Localizations of 14-3-3 proteins to mitochondria and ribosome were validated via immunofluorescence assays. The deduced function of cardiac 14-3-3 PPIs is to regulate cardiac metabolic homeostasis and proteostasis. Conclusions: Thus, the cardiac 14-3-3 interactome may be a potential therapeutic target in cardiovascular metabolic and proteostatic disease states, as it already is in cancer therapy.

The group III two-component hybrid histidine kinase MoHik1p in the filamentous fungus Magnaporthe oryzae is known to be a sensor for external osmotic stress and essential for the fungicidal activity of the phenylpyrrole fludioxonil. The mode of action of fludioxonil has not yet been completely clarified but rather assumed to hyperactivate the high osmolarity glycerol (HOG) signaling pathway. To date, not much is known about the detailed molecular mechanism of how osmotic stress is detected or fungicidal activity is initiated within the HOG pathway. The molecular mechanism of signaling was studied using a mutant strain in which the HisKA signaling domain was modified by an amino acid change of histidine H736 to alanine A736. We found that MoHik1pH736A is as resistant to fludioxonil but not as sensitive to osmotic stress as the null mutant ∆Mohik1. H736 is required for fludioxonil action but is not essential for sensing sorbitol stress. Consequently, this report provides evidence of the difference in the molecular mechanism of fludioxonil action and the perception of osmotic stress. This is an excellent basis to understand the successful phenylpyrrole-fungicides’ mode of action better and will give new ideas to decipher cellular signaling mechanisms.

Abstract: Composite sintered bodies comprising silicon dioxide (SiO2) nanoparticles dispersed in β-tricalcium phosphate (β-TCP) were prepared. The addition of nano-sized colloidal SiO2 to the β-TCP produced well-dispersed secondary phase nanoparticles that promoted densification by suppressing grain growth and increasing volume shrinkage of the sintered bodies. The SiO2 was found not to react with the β-TCP at 1120 °C and the substitution of silicon for phosphorous to produce a solid solution did not occur. This lack of a reaction is ascribed to the absence of avail-able calcium ions to compensate for the increase in charge associated with this substitution. The SiO2 nanoparticles were found to be present near the intersections of grain boundaries in the β-TCP. A β-TCP composite sintered body containing 4.0 wt% SiO2 exhibited a bending strength comparable to that of cortical bone and hence could potentially be used as a bone filling material.

RCH is known rapidly enhance cold tolerance of insects. Trehalose has been demonstrated to be one of the cryoprotectant in L. oryzophilus, an important invasive pest of rice in China. Trehalose synthesis mainly occurs through the TPS/TPP pathway in insects. In this study, LoTPS gene was cloned and characterized for the first time. Its expression and trehalose content changes elicited by RCH were investigated. Our results revealed that RCH not only increased the survival rate of adults but also upregulated the gene expression level of LoTPS and increased trehalose content under low temperature. We hypothesized upregulated LoTPS promoted trehalose synthesis and accumulation to protect adults from low-temperature damage. To further verify the function of LoTPS gene, we employed RNAi technology. Our findings showed that RCH efficiency disappeared and failed to increase the survival rate when the adults were fed dsRNA of LoTPS. Additionally, inhibiting LoTPS gene expression resulted in no significant difference in trehalose content between RCH and non-RCH treatments. Furthermore, the expression patterns of TRET and TRE were also affected. Collectively, these results indicate the critical role of LoTPS in L. oryzophilus cold resistance after RCH induction. LoTPS can enhance the survival ability by regulating trehalose metabolism. These findings contribute to further understanding of the role of TPS in insect cold resistance and invasiveness of L. oryzophilus. Moreover, RNAi of the LoTPS opens up possibilities for novel control strategies against L. oryzophilus in the future.

Phosphorus deficiency highly interferes with plant growth and development. Plants respond to the persistent P deficiency by coordinating the expression of genes involved in the alleviation of the stress. Promoters of phosphate transporter genes are of great choice for the development of genetically modified plants with enhanced phosphate uptake abilities, which improve crop yields in phosphate-deficient soils. In our previous study, the sugarcane phosphate transporter PHT1;2 gene, showed a significantly high expression under salinity stress. In this study, the Erianthus arundinaceus EaPHT1;2 gene was isolated and characterized using various in-silico tools. The deduced 542 amino acid residues have 10 transmembrane domains, with a molecular weight and isoelectric point of 58.9 kDa and 9.80, respectively. They displayed 71–96% similarity with Arabidopsis thaliana, Zea mays, and Saccharum hybrid. To elucidate the function of the 5’ regulatory region, the 1.1kb promoter was isolated and validated in tobacco transgenics under Pi stress. The EaPHT1;2 promoter activity was detected using the β-glucuronidase (GUS) assay. While the EaPHT1;2 promoter showed 3 to 4.2-fold higher expression than the most widely used CaMV35S promoter. The 5’ deletion analysis with and without 5’UTR regions, revealed that a small size 374 bp fragment with the highest promoter activity among 5′ truncated fragments, which was 2.7 and 4.2 times higher than the well-used CaMV35S promoter under normal and Pi-deprivation conditions, respectively. The strong and short promoter of EaPHT1;2 with 374 bp showed significant expression in low Pi-stress conditions and it could be a valuable source for the development of stress-tolerant transgenic crops

Bone growth plate abnormalities and skull shape defects are seen in hypophosphatasia, a heritable disorder in humans that occurs due to deficiency of Tissue Nonspecific Alkaline Phosphatase (TNAP, Alpl) enzyme activity. Abnormal development of the cranial base growth plates (synchondroses) and abnormal skull shapes have also been demonstrated in global TNAP-/- mice. To distinguish local vs. systemic effects of TNAP on skull development, we utilized P0-Cre to knockout TNAP only in cranial neural crest derived tissues using TNAP flox mice. Here we show that TNAP deficiency in cranial neural crest leads to leads to skull shape defects and deficient growth of the intersphenoid synchondrosis (ISS). ISS chondrocyte abnormalities included increased proliferation in resting and proliferative zones with decreased apoptosis in hypertrophic zones. ColX expression is increased, indicative of premature differentiation in the absence of TNAP. Sox9 expression is increased in both resting and prehypertrophic zones of mutant mice. Expression of PTHrP and IHH were also increased. Finally, cranial base organ culture revealed that inorganic phosphate (Pi) and pyrophosphate (PPi) have specific effects on cell signaling and phenotype changes in the ISS. Together, these results demonstrate that TNAP expression in growth plate chondrocytes is essential for normal development, and that the mechanism likely involves Sox9, PTHrP, IHH and PPi.

Cyanobacteria are photosynthetic microorganisms capable of using solar energy to convert CO2 and H2O into O2 and energy-rich organic compounds, thus enabling sustainable production of a wide range of bio-products. More and more strains of cyanobacteria are identified that show great promise as cell platforms for the generation of bioproducts. However, strain development is still required to optimize their biosynthesis and increase titers for industrial applications. This review describes the most well-known and newest most promising strains available to the community and gives an overview of current cyanobacterial biotechnology and the latest innovative strategies used for engineering cyanobacteria. We summarize advanced synthetic biology tools for modulating gene expression and their use in metabolic pathway engineering to increase the production of value-added compounds, such as terpenoids, fatty acids, and sugars, to provide a go-to source for scientists starting research in cyanobacterial metabolic engineering.

Disrupted nutrient recycling is a significant problem for Europe, while phosphorus and nitrogen are wasted instead of being used for plant nutrition. Mineral phosphate is critical raw material, which contains environmentally hazardous elements such as cadmium and uranium. Therefore, phosphorus recovery from agricultural by-product streams is critically important key priority. Phosphorus recovery from food grade animal bone by-products have been applied researched since 2002 with objective driven evolution progress towards specialized pyrolysis processing technology and animal bone char product (ABC) developments in economical industrial scale. Different animal bone by-products tested under different conditions at 400 kg/h throughput capacity in the continuously operated 3R zero emission autothermal carbonization system. The different material core treatment temperatures (between >300°C and <850°C) were combined with different residence times under industrial productive processing conditions. It has been industrial demonstrated that material core treatment temperature <850°C with 20 minutes residence time is necessary to achieve high quality ABC with useful agronomic value. The output ABC product having concentrated >30% phosphorus pentoxide (P2O5) and specific quality innovative fertilizer for agronomical efficient organic and low input farming applications as functional organic fertilizer, soil improver, growing medium and/or fertilizing product blend with high mineral phosphate fertiliser replacement value.

Although multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that results in many neurological disabilities, optic neuritis (ON) is developed in some MS patients. However, the molecular mechanism of ON remains unknown. Galectins, β-galactoside-binding lectins, are involved in various pathophysiology. We have previously shown that galectin-3 (gal-3) is associated with the pathogenesis of experimental autoimmune encephalomyelitis (EAE), its animal model for human MS. In the current study, the expression of gal-3 was explored in the visual pathway of the EAE mice to clarify the pathogenesis of ON. Immunohistochemical analysis demonstrated that expression of gal-3 was increased in the visual pathway of the EAE mice during the peak disease, compared with naïve and EAE mice during the chronic disease. Expression of gal-3 was observed in mainly microglia/macrophages and astrocytes in the visual pathway of the EAE mice. In addition, gal-3+Iba-1+ cells with the phagocytic activities reflected by immunostaining with cathepsin-D were accumulated at demyelinating lesions in the visual pathway during peak disease of EAE. Moreover, NLRP3 expression was also detected in most gal-3+Iba-1+ cells. These results indicate a considerable possibility that gal-3 regulates the NLRP3 signaling in microglia/macrophages, followed by neuroinflammatory demyelination in ON. By contrast, astrocytic expression of gal-3 was also observed from the peak to the chronic disease. Taken together, the current study suggests a critical role of gal-3 in the pathogenesis of ON and proposes gal-3 in glial cells as a potential therapeutic target for ON.

The patient was a 44-year-old woman with suspected Stevens-Johnson syndrome due to Baktar® (sulfamethoxazole trimethoprim) medication received at our outpatient dermatology clinic. Histopathological examination of the epidermis, dermis, and subcutaneous adipose tissue samples showed numerous necrotic keratinocytes in the epidermis. Apoptotic nuclei were visualized as diaminobenzidine brown deposits with immunoperoxidase staining for cleaved caspase-3. Cleaved-caspase3-positive findings were consistent with eosinophilic material that appeared to be necrotic cells within the epidermis. Therefore, these eosinophilic materials must be apoptotic bodies. Generally speaking, and especially in Japan, these materials are considered necrotic keratinocytes. To our best knowledge, no studies have used apoptotic immunohistochemical markers to examine whether these structures are apoptotic.

Crohn's disease is a non-specific inflammatory bowel disease, which is a chronic condition that affects the ileum and/or large intestine. At the same time, it can also involve any other part of the human body, that is, from the mouth to the anus. The symptoms are very bothersome and cause a significant reduction in quality of life and sometimes even crippling permanent damage to the gastrointestinal tract, which requires enteral or parenteral nutrition for life. The purpose of this study was to investigate tissue metalloproteinases as markers of recurrent Crohn's disease. The experimental groups included 31 patients and 10 patients with normal Crohn's disease, ranging in age from 23-70 years, with a mean age of 40.4. Collected tissues were frozen and then fragmented tissues were homogenized with Ripa Lysis buffer on ice. The supernatant was collared and four metalloproteinases - MMP 3, MMP 7, MMP 8 and MMP 9 - were an-alized by Enzyme-linked Immunosorbent Assay using SEA101HU, SEA102Hu, SEA103Hu and SEA553Hu kits (Cloud-Clone Corp., Kata, TX, USA). All chemical analyses were performed in triplicate. Metalloproteinase content was expressed as mean ± standard deviation. Metalloproteinase 3 and metalloproteinase 8) significantly influenced the possibility of Crohn recurrence

The antibodies targeting invasive proteins of Plasmodium falciparum (Pf) merozoites is a clever strategy against malaria parasite. The recent finding that Plasmodium merozoites surface enolase is a target for growth neutralizing antibodies has generated interest in identifying its re-ceptor (s) on erythrocytes. In the present study, several biochemical experiments were undertaken involving recombinant Pf enolase and antibody against it to search for its cognate receptor. The binding of rPfeno to erythrocytes was selectively sensitive to trypsin but resistant to neuramini-dase. Failure of yeast enolase binding to human red blood cells under similar conditions indicat-ed high specificity of parasite Pfeno. The mass spectrometric and immunological analyses of pro-teins obtained in pull downs and co-immunoprecipitation samples led to identification of band 3 as an interactor/receptor for Plasmodium enolase. Structural characterization of sequences of band 3 - rPfeno interacting regions revealed C-terminal exocytic regions of band 3 to be binding to Pfeno. Similarly, band 3 binding regions of rPfeno were also identified. Identification of receptor-ligand (band 3: Pfeno) pair paves the way for antimalarial anti-Pf enolase-based vaccine, anti-Pf enolase antibodies as drug and also for developing novel small molecule-based invasion inhibi-tory therapeutics including peptidomimetics that could disrupt the band 3: Pfeno protein-protein interactions.

Abstract: Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the antitumor response. Modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as the ecto-nucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemoresistance and poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that, while AraC induced immune response regulation by increasing CD39 expression and by reinforcing interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.

Let $\mathcal{N}$ be an arbitrary class of matroids, closed under isomorphism. For $k$ a positive integer, we say that $M \in \mathcal{N}$ is \emph{$k$-minor-irreducible} if $M$ has no minor $N \in \mathcal{N}$ such that $1\leq\left|E\left(M\right)\right|-\left|E\left(N\right)\right|\leq k $. Tutte's Wheels and Whirls Theorem establish that, up to isomorphism, there are only two families of 1-minor-irreducible matroids in the class of 3-connected matroids. More recently, Lemos classified the 3-minor-irreducibles with at least 14 elements in the class of triangle-free 3-connected matroids. Here we prove a local characterization for the 2-minor-irreducible matroids with at least 11 elements in the class of triangle-free 3-connected matroids. This local characterization is used to establish two new families of 2-minor-irreducible matroids in this class.

Thanks to the pioneering studies of Østerud and co-workers it is now increasingly understood that natural polyphenols present in marine oils play an essential role in protecting omega-3 lipids from oxidation and autooxidation ensuring that no proinflammatory products are formed after intake as it often happens with assumption of refined omega-3 concentrates. Strong antioxidants exerting multiple biological functions, olive biophenols are ideally suited to functionalize marine oils creating a synergy which has the potential to foster public health across the world. This study identifies suitable avenues to advance the sustainable production of health-beneficial formulations based on newly obtained natural marine oils and olive phenolic extracts. Important educational outcomes for bioeconomy educators conclude the study.

This document describes the theoretical basis of the algorithms used to determine properties of snow and ice from the measurements of the Ocean and Land Color Instrument (OLCI) onboard Sentinel-3 satellites within the Pre-operational Sentinel-3 snow and ice products (SICE) project: http://snow.geus.dk/. The code used for the SICE retrieval and its documentation can be found at https://github.com/GEUS-SICE/pySICE. The algorithms were developed after the work from Kokhanovsky et al. (2018, 2019, 2020).

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

A shrimp oil rich in omega-3 lipids and carotenoids is obtained in remarkably high 5 wt% yield extending to pink shrimp processing waste (head and carapace) the circular economy approach to extract fish oil from fish processing by-products using d-limonene. Biobased limonene, a powerful antimicrobial and antioxidant agent, is an excellent solvent for both lipids and astaxanthin-based carotenoids preventing oxidative degradation during the extraction cycle including solvent and oil separation at 85°C. A new low cost route is established to extract valued marine oil from biowaste annually made available in over 2.2 million tonnes.

Network Simulators (NS) is typically used to study services and applications in complex scenarios due to the infeasibility of deploying real testbeds. This is the case of Mobile Ad hoc Networks (MANETs) which can be extensively used in emergency situations or to gather information without infraestructure. An important factor to get realiable results in the MANETs’ simulations is the wireless channel module of NSs. In this report, we explain how thw wireless channel is implemented in NS-3 and it can be configured.

The efficacy of chemotherapy depends on sensitivity and intrinsic or acquired drug resistance of cancer cells. The n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic mechanisms. The specific mechanisms are not fully understood, but nowadays, it is widely accepted that there are a complex network of mechanisms, including alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species and lipid peroxidation. A crucial mechanism in the control of cell drug uptake and efflux is related to n-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, n-3 LCPUFAs often impact on the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting their adjuvant role in cancer treatment.

Hypercholesterolemia is a major risk for the development of cardiovascular diseases (CVDs), the main cause of mortality worldwide, and it is characterized by high levels of circulating cholesterol. The drugs currently available for hypercholesterolemia control have several side effects, so it is necessary to develop new effective and safer therapies. Seaweeds serve as sources of several bio-active compounds with claimed beneficial effects. Eisenia bicyclis (Aramé) and Porphyra tenera (Nori) are edible seaweeds which were previously recognized as rich in bioactive compounds. In the present study, we aim to evaluate the anti-hypercholesterolemia effect of these two seaweeds ex-tracts and their health potential. Both extracts, but more efficiently Aramé extract demonstrated to have liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitory activity and to reduce approximately 30 % cholesterol permeation through human Caco-2 cells simulating the intestinal lining, targets for hypercholesterolemia treatments. An untargeted metabolomic assay on human intestinal Caco-2 and liver Hep-G2 cells lines exposed to Aramé and Nori extracts revealed changes in the cell’s metabolism as indicators of the extract’s health beneficial effects. The metabolic pathways affected by exposure to both extracts were associated to lipid metabolism, such as phospholipids, and fatty acid metabolism, pathways of amino acid, cofactors and vitamins and cellular respiration metabolism. More profound for Aramé treated cells, but also seen for Nori ex-posed cells, the metabolites modifications were associated with the protection against CVDs and other diseases and, to the improvement of cells oxidative stress tolerance. The results obtained for the anti-hypercholesterolemia properties, in addition to the revelation of the positive impact on cells metabolism, are an important contribution for further evaluation of these seaweeds extracts as functional foods or for CVDs prevention.

Sphingosine 1-phosphate (S1P) is a signaling lipid molecule involved in various cellular processes. It is important to develop a quantitative method for S1P to determine endogenous levels and to investigate its functions. Especially since S1P is a tiny lipid component of most biological samples, highly sensitive analysis by LC-MS/MS is required. The main challenge in S1P analysis by chromatography is peak broadening due to the presence of a polar phosphate and zwitterion formation in S1P. In this study, we used hydrogen fluoride (HF) to efficiently remove a phosphate and then analyzed the surrogate, sphingosine, as a sharp peak by LC-ESI-MS/MS. We optimized the dephosphorylation reaction in terms of reaction time, temperature, and HF concentration. Multiple reaction monitoring (MRM) for dephosphorylated form of S1P and C17-S1P as internal standard at m/z transition 300.4&gt;282.4 (quantification ion), 300.4&gt;262.4 (qualification ion), 286.3&gt;268.2 (internal standard). This method was validated by essential parameters such as specificity, linearity, range, LOQ, LOD, accuracy, precision, and repeatability. To confirm this new method, we quantified S1P levels in various serum products (100.02 ~ 284.38 nM). To apply the method in vivo, we analyzed S1P in plasma and kidney tissues obtained from a chronic kidney disease (CKD) mouse model. S1P levels were increased only in CKD kidney tissue but not in plasma. In conclusion, by applying the dephosphorylation step with HF, we established a new sensitive LC-MS/MS quantitative method for S1P that can be applied to biological samples.

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.

Achievement of solid fusion of the lumbosacral junction (L5-S1 level) is an important factor in adult spinal deformity (ASD) surgery. The purpose of this study is to explore the effectiveness and feasibility of injectable rhBMP-2 (a combination of Eschericia coli-derived rhBMP-2 and hydrogel type β-TCP carrier; NOVOSIS Inject) as a bone substitute for the fusion of lumbosacral junction. 20 patients (average age 69.1 years) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including anterior lumbar interbody fusion (ALIF) in the L5-S1 level were evaluated. Injectable rhBMP-2 was applied in L5-S1 ALIF and followed-up for 1-year. Solid fusion rates and changes of clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] of back and leg) were measured and analyzed at 6 and 12 months after surgery. All postoperative adverse events were evaluated about the association with injectable rhBMP-2. Fusion rates were 68.4% and 100% at 6 and 12 months after surgery. Compared to baseline, ODI were improved to 45.8% and 63.7%, VAS(back) were improved to 69.2% and 72.8%, and VAS(leg) were improved to 49.2% and 64.8% at 6 and 12 months after surgery (p&lt;0.001, respectively). There were no adverse events associated with injectable rhBMP-2. Thus, injectable rhBMP-2 may be a suitable choice of a bone graft substitute when achieving solid interbody fusion in the lumbosacral junction.

Dentin bonding is a key in restorative dentistry. Herein, we developed self-etching two-bottle adhesive system containing 10-methacryloyloxidecyl dihydrogen phosphate monomer (MDP) and the physical, mechanical, and biocompatible properties were evaluated. The characteristics of MDP were analyzed using nuclear magnetic resonance (NMR). The water sorption and solubility, the shear-bond strengths to dentin and enamel, and cytotoxicity tests were performed. The newly blended experimental group showed the lowest thickness and water sorption and solubility values. The shear bond strength to enamel and dentin were comparable to control groups (the three other products) all test groups showed 60% of cell viability. In this study, the properties of the newly synthesized adhesive are comparable with the others. The fundamental goal of this study is to get the MDP patent released, as it is intended for domestic production. For this purpose, this dentin adhesive was developed and compared with the commercial product.

The problem of effective immobilization of liquid radioactive waste (LRW) is key to the successful development of nuclear energy. The possibility of using magnesium potassium phosphate (MKP) compound for LRW immobilization on the example of nitric acid solutions containing actinides and rare earth elements (REE), including high level waste (HLW) surrogate solution is considered in the research work. Under the study of phase composition and structure of the MKP compounds obtained by the XRD and SEM methods, it was established that the compounds are composed of crystalline phases - analogues of natural phosphate minerals (struvite, metaankoleite). The hydrolytic stability of the compounds was determined according to the semi-dynamic test GOST R 52126-2003. Low leaching rates of radionuclides from the compound are established, including a differential leaching rate of ²³⁹Pu and ²⁴¹Am - 3.5 × 10^-7 and 5.3 × 10^-7 g/(cm²∙day). As a result of the research work it was concluded that the MKP compound is promising for LRW immobilization and can become an alternative material combining the advantages of easy implementation of the technology like cementation and the high physical and chemical stability corresponding to a glass-like compound.

Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or cardiomyopathies. At the same time, oxidative stress is considered as one of the important mechanisms of cellular cytotoxicity and a target for the action of cytoprotectors. The aim of this study is to search for derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones. The probability of cytoprotective action was assessed by two tests by measuring cell viability (with neutral red dye and MTT test). It was found that some derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones under the conditions of our experiment have a pronounced cytoprotective activity, providing better cell survival in vitro, including the MTT test and conditions of blood hyperviscosity. To correlate the obtained results in vitro, molecular docking of the synthesized derivatives was also carried out. The standard drug omeprazole (co-crystallized with the enzyme) was used as a standard. It was shown that all synthesized derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones had higher affinity for the selected protein than the standard gastro-cytoprotector omeprazole. The studied derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones also fully satisfy Lipinski's rule of thumb of five (RO5), which increases their chances for possible use as orally active drugs with a good ability to absorption and moderate lipophilicity. Thus, the results obtained make it possible to evaluate derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones as having a relatively high cytoprotective potential.

The major auxin, indole-3-acetic acid (IAA), is associated with a plethora of growth and developmental processes including embryo development, expansion growth, cambial activity, and the induction of lateral root growth. Accumulation of the auxin precursor indole-3-acetamide (IAM) induces stress related processes by stimulating abscisic acid (ABA) biosynthesis. How IAM signaling is controlled is, at present, unclear. Here, we characterize an ami1/rooty double mutant, that we initially generated to study the metabolic and phenotypic consequences of a genetic blockade of the indole glucosinolate and IAM pathways in Arabidopsis thaliana. Our mass spectrometric analyses of the mutant revealed that the combination of the two mutations is not sufficient to fully prevent the conversion of IAM to IAA. The detected strong accumulation of IAM was, however, recognized to substantially impair seed development. We further show by genome-wide expression studies that the double mutant is broadly affected in its translational capacity, and that a small number of cell proliferation and plant growth regulating transcriptional circuits are repressed by the high IAM content in the seed. In accordance with the previously described growth reduction in response to elevated IAM levels, our data support the hypothesis that IAM is a growth repressing counterpart to IAA.

Abstract Introduction: Visual perceptual skills are essential for independent participation in self-care tasks, educational, work and leisure time activities. The effect of HIV on the visual perceptual skills is not well understood among children in low resource settings like Zimbabwe. Methods: A cross sectional comparative study was done with 30 children living with HIV and 30 children living without HIV residing in Harare urban area. The TVPS-3 was used to assess their visual perceptual skills. SPSS version 22, STATISTICA 13 and Microsoft 2016 were used for data analysis. Results: Both groups of children had mean percentile ranks below 50 on their TVPS-3 scores. Children without HIV generally performed better than those with HIV but the difference was not statistically significant in most cases. Through univariate analysis, only performance on Spatial Relations significantly differed between the two groups. Both groups had lowest scores in Basic visual perceptual skills. Age and school grade were the independent predictors of the children’s performances in the study. Conclusion: There is need for Occupational therapy services in public primary schools and in the pediatric Opportunistic Infections clinics in hospitals to be part of the health team which caters for children with visual perceptual challenges.

Predicting and evaluating the vitality level of public spaces of urban design is crucial before new construction and renewal, especially for developing countries, to avoid failures like "ghost neighborhood" and reduce resource waste. However, existing assessment methods for the urban vitality are either static and ignore changes in the time dimension, or rely on historical big data and are unable to predict unbuilt projects. This study combines previous methods and crowds’ characteristics observation in public space, puts forward the crowd-frequency hypothesis and constructs an algorithm, and establishes a time-dimensional urban vitality dynamic prediction model. Taking the Rundle Mall neighborhood in Adelaide, Australia, as an example, the effec-tiveness of the prediction model was proved through on-site observation sampling comparative verification method. In addition, the decision tree model was used to conduct machine learning on the case data, and a set of algorithm programs were obtained that can directly input some basic information to obtain the urban vitality level (high-medium-low) in a certain period. It can be used as a tool to support the design and decision-making processes of urban planners and government officials, providing a low-cost way to achieve sustainable urban vitality construction of late-developing cities directly.

Development of new techniques of multimodal treatment, diagnostics of various neoplasms and improvement of these techniques can significantly increase the life expectancy of patients with carcinomas of the colon and abdominal cavity organs, since prevention of various side effects of radiation therapy is one of the main problems of oncological care. Electron irradiation is one of the most promising types of radiation therapy. There are no data on proliferation and apoptosis of the colon epithelium after irradiation with electrons, especially in different modes (single and summary). Aim of the study: Morphological evaluation of apoptosis and proliferation of colonic epithelium after local irradiation with electrons at doses 2 Gy and 25 Gy. Materials and methods. Colon fragments from sexually mature Wistar rats (n=50, body weight 200 ± 10 g) were divided into three groups: I - control (n = 10); II - experimental group (n = 20; local single electron irradiation at a dose of 2 Gy), III - experimental group (n=30), local fractional irradiation with electrons at a total dose of 25 Gy. They were studied by light microscopy using hematoxylin and eosin staining and immunohistochemical reactions with antibodies to Ki-67 and Cas3. Morphological disorders were accompanied by increased expression of pro-apoptotic molecules (caspase-3), and the period of regeneration by proliferative marker (Ki-67). Conclusions: Local fractional irradiation of the colon with electrons at a dose of 2 Gy and 25 Gy resulted in minor changes in the epithelium, a decrease in the number of goblet cells, but with preservation of regenerative potential, mild degenerative-dystrophic lesions. Intestinal crypts were damaged, leading to a decrease in Ki-67 and an increase in the number of caspase-3-positive epitheliocytes.

Hip joint surgeries, including total hip replacement or resurfacing, have increased tremendously in the last decades. Number of patients of all ages, replace their hip, due to severe injuries or trauma problems, so as to have a better life. According to these factors, new material and processes in implants manufacturing are imported to medicine, through research programs, every year. In the scope of one of these programs, that has to do with ceramic coatings on metallic resurfacing implants, a new 3axis Hip simulator was designed and manufactured in the Laboratory of Manufacturing Technology of the National Technical University of Athens. The scope of this paper is to present the main parts, materials and process used to manufacture the simulator as well as the way the simulator is working and how its movement in 3axis is accomplished. Furthermore, the evaluation of the machine and its use to examine resurfacing implants is presented.

Background: Cell-free plasma DNA (cfDNA) is composed of circulating extracellular DNA originating from apoptosis or cell necrosis. It is generally present in healthy individuals, but its levels increase in different clinical conditions, such as kidney disease, sepsis, myocardial infarction, trauma and cancer. Caspase-3 plays a central role in apoptosis, a mechanism of programmed cell death involved in the pathogenesis of chronic kidney disease (CKD). Methods: We compared cfDNA and caspase-3 levels in 25 CKD patients and in 10 healthy subjects, evaluating the modification of their concentrations according to CKD stage. We also analyzed the correlation between cfDNA and caspase-3 levels in CKD patients and the correlation between cfDNA and caspase-3 levels and creatinine and urea. Results: CfDNA and caspase-3 levels were higher in CKD patients compared to healthy subjects, in particular in patients with advanced renal disease. A positive correlation between cfDNA and caspase-3 levels and between cfDNA and caspase-3 and creatinine and urea was also observed. Conclusion: Patients with chronic kidney disease present higher levels of cfDNA and caspase-3 levels compared with healthy subjects. The worsening of renal damage and the increase in uremic toxin concentration are associated to higher levels of cfDNA and caspase-3 levels, thus reflecting a central role of apoptosis in the pathogenesis of CKD.

The elderly present age-related morphological and histological changes of the oral cavity; Literature displays many studies regarding the specific pathologies of the oral cavity in elderly patients, but no etiologically based classification is available. The aim of this study was to analyze the series of patients over 65 who were treated by our Unit of Pathology between 2020 and 2022 for a suspicion of oral lesion or for preventive dental evaluation (in anticipation of cardiac surgery, anti-resorptive drugs intake, chemotherapy, radiotherapy of the head-neck district or transplantation). The analysis was conducted by dividing oral lesions into 5 groups depending on the etiology: reactive, immunological, traumatic, benign and malignant degenerative. The sixth group consisted of patients undergoing preventive dental evaluation. The study included 435 patients; 91 of them were diagnosed with a reactive origin pathology, 174 with immunological origin pathology, 48 with traumatic pathology and 86 with degenerative pathology (42 benign and 44 malignant). 36 patients went to our Unit for preventive specialist evaluation. Oral health has a major impact on the daily life of the elderly; The examination of oral mucosa in geriatric patients is a fundamental diagnostic moment to report lesions early, thus allowing easier prevention and treatment.

Aim: Evaluation of role of supplementation of omega-3 polyunsaturated fatty acids on endothelial function in patients with metabolic syndrome. Methods: Total of 80 patients with metabolic syndrome were enrolled to two groups. We evaluated endothelial function in subjects before and after three-month treatment with omega-3 polyunsaturated fatty acids in dose 2.4g daily (800mg 3 times a day) vs placebo. Using the Endo-PAT2000 device (Itamar Medical Ltd. Caesarea, Israel), reactive hyperemia index – a parameter of endothelial function and augmentation index– a parameter of arterial stiffness were measured. Plasmatic level of glutation peroxidase, homocysteine, apolipoprotein B and lipoprotein (a) were also evaluated. Results: The average values of reactive hyperemia index before the treatment with n-3PUFA was 1.62 ± 0.42 , whereas 1.96 ± 0.62 at the end of the study (p<0.005). Augmentation index changed from 14.66 ± 19.55 to 9.21 ± 15.64 after the treatment (p=0.003). We also observed statistically significant decrease of apolipopotein B (0.94 ± 0.36 vs 1.13 ± 0.35, p = 0.001) and homocysteine (19.31 ± 5.29 vs. 13.78 ± 3.05, p = 0.001) and increase of the glutathion perxidase plasma levels (41.65 ± 8.90 vs. 45.20 ± 8.01), p=0.001. Conclusion: We have observed significant improvement of the endothelial function in subjects with metabolic syndrome treated with omega-3 polyunsaturated fatty acids in dose 2.4g daily.

This article presents an experimental approach to fatigue testing of cableway gondolas, carried out in accordance with the EN 13796-3 standard. Due to the limitations of the aforementioned regulations and the lack of clarity in their content, when designing and conducting fatigue tests of gondolas, there is a need to find solutions that meet the normative requirements, while ensuring the cost-effectiveness of the tests. The work presents the method of loading, receiving the degrees of freedom, the methodology of gondola strength verification, and additional suggestions allowing for the satisfactory preparation of a plan of fatigue tests and their implementation. The paper shows problems and ways to solve it, what may occur during cableway gondolas fatigue test design. The research object is a 6-seater gondola designed by TRANSSYSTEM S.A. with its registered office in Wola Dalsza (Poland).

After a long limbo, RNA has gained its credibility as a druggable target, fully earning its de-served role in the next-generation area of pharmaceutical R&D. We have recently probed the Trans-Activation Response element (TAR), a RNA stem–bulge–loop domain of the HIV-1 genome with bis-3-chloropiperidines (B-CePs), and revealed the compounds unique behavior in stabiliz-ing TAR structure, thus impairing in vitro the chaperone activity of the HIV-1 nucleocapsid (NC) protein. Seeking to elucidate the determinants of B-CePs inhibition, we have further characterized here their effects on the target TAR and its NC recognition, while developing quantitative analyti-cal approaches for the study of multicomponent RNA-based interactions.

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ols (FL), a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FL possibly activates sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FL. In addition, we examined the impact of the repeated administration of 50 mg/kg FL for 14 days on adipose tissues in mice. In BAT, FL tended to increase the level of Ucp-1 along with thermogenic transcriptome factors, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Transcription of browning markers, such as CD137 and transmembrane protein (TMEM) 26 in addition to PGC-1α were increased in epididymal adipose (eWAT) by FL. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 following administration of FL. These results suggest that FL produces browning in adipose through activation of the SNS.

Bioactive glass (BG) represents a promising biomaterial for bone healing; here injectable BG pastes biological properties were improved by 25 wt% gelatin or chitosan, as well as mechanical resistance was enhanced by adding 10 or 20 wt% 3-Glycidyloxypropyl trimethoxysilane (GPTMS) cross-linker. Composites exhibited bioactivity as apatite formation was observed by SEM and XRD after 14 days immersion in SBF; moreover, polymers did not enhance degradability as weight loss was &gt;10% after 30 days in physiological conditions. BG-gelatin-20 wt% GPTMS composites demonstrated the highest compressive strength (4.8±0.5 MPa) in comparison with 100% BG control (1.9±0.1 MPa). Cytocompatibility was demonstrated towards human mesenchymal stem cells (hMSC), osteoblasts progenitors and endothelial cells. The presence of 20 wt% GPTMS conferred antibacterial properties thus inhibiting the joint pathogens Staphylococcus aureus and Staphylococcus epidermidis infection. Finally, hMSC osteogenesis was successfully supported in a 3D model as demonstrated by alkaline phosphatase release and osteogenic genes expression.

Image fusion is a useful tool for producing a high-resolution multispectral image to be used for land use and land cover mapping. In this study, we use nine pansharpening algorithms namely Color Normalized (CN), Gram-Schmidt (GS), Hyperspherical Color Space (HCS), High Pass Filter (HPF), Nearest-Neighbor Diffusion (NND), Principal Component Analysis (PCA), Resolution Merge (RM), Stationary Wavelet Transform (SWT), and Wavelet Resolution Merge (WRM) to fusion Worldview-3 multispectral Bands and panchromatic band. In spectral and spatial fidelity, several image quality metrics are used to evaluate the performance of pansharpening algorithms. The SWT and PCA algorithms showed better results compared to other pansharpening algorithms while GS and CN algorithms showed the worst results for the original image fusion. The effect of fusion on each band was separately investigated and according to the calculations, we found that the CoastalBlue band and the Blue band showed the best result and the NIR-1 band and NIR-2 band show the worst result for the original image fusion. In the end, we conclude that the choice of fusion method depends on the requirement of remote sensing application.

Preeclampsia (PE) is a common pregnancy complication. It is associated with high maternal morbidity and mortality rates and intrauterine foetal growth restriction. This condition is characterised by high blood pressure and urinary protein levels. Apelin and galectin-3 (Gal- 3) are peptides involved in the regulation of body fluid homeostasis, inflammation and cardiovascular functions. This study aimed to determine the correlations amongst serum apelin and Gal-3 levels and insulin resistance (IR) in women with PE. Sixty patients with PE and 30 healthy controls participated in this study. The PE group had significantly lower apelin levels (p < 0.01) and higher Gal-3 levels (p < 0.05) than the control group. The PE group had higher serum glucose levels and β-cell functions than the control group. Moreover, patients with PE exhibited dyslipidaemia. Correlation analysis indicated that apelin and Gal-3 levels were not significantly correlated. Moreover, no correlation existed between the apelin levels and any measured parameters of the PE group. In conclusion, the elevations in serum Gal-3 levels with increments in IR-related parameters and lipid profiles reflect the possible contribution of Gal-3 to the harmful effects of IR and dyslipidemia levels on women with PE.

Bacterial indole-3-acetic acid (IAA), an effector molecule in microbial physiology, plays an important role in plant growth-promotion. Here, we comprehensively analyzed about 7282 prokaryotic genomes representing diverse bacterial phyla, combined with root-associated metagenomic data to unravel the distribution of tryptophan-dependent IAA synthesis pathways and to quantify the IAA synthesis-related genes in the plant root environments. We found that 82.2% of the analyzed bacterial genomes were potentially capable of synthesizing IAA from tryptophan (Trp) or intermediates. Interestingly, several phylogenetically diverse bacteria showed a preferential tendency to utilize different pathways and tryptamine and indole-3-pyruvate pathways are most prevalent in bacteria. About 45.3% of the studied genomes displayed multiple coexisting pathways, constituting complex IAA synthesis systems. Furthermore, root-associated metagenomic analyses revealed that rhizobacteria mainly synthesize IAA via IAM and tryptamine (TMP) pathways and might possess stronger IAA synthesis abilities than bacteria colonizing other environments. The obtained results refurbished our understanding of bacterial IAA synthesis pathways and provided a faster and less labor-intensive alternative to physiological screening based on genome collections. The better understanding of IAA synthesis among bacterial communities could maximize the utilization of bacterial IAA to augment the crop growth and physiological function.

Nowadays, network simulators are very useful to model a communications system. In this technical note we will focus in the creation of a new error model in NS-3 network simulator. This note describes the main steps to create or modify an Wi-Fi error model in this network simulator. In our case, we have created a new error model to included the approach of [1] to compute PER (Packet Error Rate) for vehicular environments.

We show that given a Lie superalgebra and an element of its dual space one can construct the 3-Lie superalgebra. We apply this approach to Lie superalgebra of (m,n)-block matrices taking supertrace of a matrix as the element of dual space. Then we also apply this approach to commutative superalgebra and the Lie superalgebra of its derivations to construct 3-Lie superalgebra. The graded Lie brackets are constructed by means of a derivation and involution of commutative superalgebra, and we use them to construct 3-Lie superalgebras.

Satellite altimeters have been used to monitor river and reservoir water levels, from which water storage estimates can be derived. Inland water altimetry can therefore play an important role in continental water resource management. Traditionally, satellite altimeters were designed to monitor homogeneous surfaces such as oceans or ice sheets, resulting in a poor performance over small inland water bodies due to the contribution from land contamination in the returned waveforms. The advent of synthetic aperture radar (SAR) altimetry (with its improved along-track spatial resolution) has enabled the measurement of inland water levels with a better accuracy and an increased spatial resolution. This paper presents three specialized algorithms or retrackers to retrieve water levels from SAR altimeter data over inland water bodies dedicated to minimizing land contamination from the waveforms. The performances of the proposed waveform portion selection method with three retrackers, namely, the threshold retracker, Offset Centre of Gravity (OCOG) retracker and 2-step physical-based retracker, are compared. Time series of water levels are retrieved for water bodies in the Ebro River basin (Spain). The results show good agreement with in situ measurements from the Ebro Reservoir (width is approximately 1.8 km) and Ribarroja Reservoir (width is approximately 400 m) with un-biased root-mean-square errors (RMSEs) of approximately 0.28 m and 0.16 m, respectively. The performances of all three retrackers are also compared with the European Space Agency’s ocean retracker in the Sentinel-3 Level-2 product.

In the past decade, under the background of the carbon peaking and carbon neutrality era, the rapid development of new energy vehicles has put forward higher requirements for the performance of strike forces such as battery cycle life, energy density and cost. Lithium-ion batteries have gradually become the mainstream of electric vehicle power batteries due to their excellent energy density, rate performance and cycle life. At present, the most widely used cathode materials for power batteries are lithium iron phosphate (LFP) and ternary nickel-cobalt-manganese (NCM). However, these materials exhibit the bottlenecks that limit the improvement and promotion of power battery performance. In this review, the performance characteristics, cycle life attenuation mechanism (including structural damage, gas generation and active lithium loss, etc.) and improvement methods (including surface coating and element-doping modification) of LFP and NCM batteries are reviewed. Finally, the development prospects of this field are proposed.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

This article utilized electrodeposition technology to fabricate Zn and Zn-Y₂O₃-Al₂O₃ composite coatings on Q235 steel plates. The composite coatings were obtained by adding Y₂O₃/Al₂O₃ nanoparticles (0, 5, 10, and 15 g/L) to acidic chloride solutions. This study then examined the impact of these nanoparticles on the microstructure, morphology, microhardness, hydrophobicity, and corrosion resistance of the composite coatings. The results indicate that the addition of the nanoparticles increased the nucleation sites on the surface of the coating, thereby refining the grain size and reducing the roughness of the coating surface. When 10g/L of Y₂O₃ and 10g/L of Al₂O₃ nanoparticles were added, the hardness of the composite coating (369 Hv) was 2.49 times higher than that of the pure Zn coating (148 Hv), which was attributed to the dispersion strengthening and grain refinement effects of the nanoparticles. The corrosion resistance of the Zn and Zn-Y₂O₃-Al₂O₃ composite coatings was studied using linear sweep voltammetry and AC impedance spectroscopy. The addition of the nanoparticles improved the corrosion resistance of the composite coating, and the composite coating prepared in an electrolyte containing 10 g/L of Y₂O₃ and 10 g/L of Al₂O₃ nanoparticles exhibited the best corrosion resistance. Meanwhile, the composite coating exhibited good hydrophobicity, with a contact angle of 120.9°, 1.94 times that of the pure Zn coating (62.2°). The Zn-Y₂O₃-Al₂O₃ nanocomposite coating material has significant potential advantages in the field of steel corrosion.

The evolutionary success of land plants largely relies on their ability to cope with constant environmental fluctuations, which negatively impact their reproductive fitness and trigger adaptational responses to biotic and abiotic stresses. In this challenging scenario, comprehensive research efforts so far aimed at depicting the roles of well-known phytohormones, mainly auxins, along with brassinosteroids, jasmonates, and abscisic acid, although the signaling networks coordinating the crosstalk among them remains vaguely understood. Accordingly, this review focuses on the Arabidopsis Amidase Signature (AS) superfamily members, highlighting the hitherto relatively underappreciated functions of AMIDASE1 (AMI1) and FATTY ACID AMIDE HYDROLASE (FAAH), as crucial coordinators of the growth-defense response trade-off by modulating auxin and ABA homeostasis.

Endophytic fungi colonize the inner tissues of plants and provide direct and indirect benefits to the plant. Although Mongolia is rich in medicinal plants, due to climatic and anthropogenic reasons the resources are being depleted and many species are under the threat of gradual extinction, while the endophytic fungi of Mongolian plants are largely unknown. Understanding the diversity and metabolic potential of endophytic fungi is of great significance in terms of the utilization of beneficial fungal strains in plant propagation and the discovery of bioactive compounds. In this study, a total of 24 culturable endophytic fungal strains were isolated from Cynomorium songaricum (Rupr.), a medicinal and vulnerable plant species of Mongolia. Based on the morphological characteristics and the sequences of the rDNA internal transcribed spacer (ITS) region, the isolates were identified to 6 genera: Fusarium (8), Clonostachys (7), Penicillium (6), Alternaria (1), Aspergillus (1), and Madurella (1). The antimicrobial activity was assessed by agar-diffusion method, revealing that 15 strains were able to inhibit the growth of at least one of the test organisms. Among them, 1 strain showed inhibitory activity against Escherichia coli, 12 against Bacillus subtilis, 13 against Staphylococcus aureus, 8 against Aspergillus niger, respectively. All fungal strains were screened for their ability to solubilize complex phosphorus and zinc minerals and for their production of indole-3-acetic acid (IAA). The strains were preserved in the national culture collection for further sustainable exploitation of their biotechnological potential.

Endophytic microbes are a ubiquitous group of plant-associated communities that colonize the intercellular or intracellular host tissues while giving numerous beneficial effects to the plants. All the plant species are thought to be associated with endophytes, majorly constituted with bacteria and fungi. During the last two decades, there has been a considerable movement toward the study of endophytes associated with coffee plants. In this review, the main consideration is given to address the coffee-associated endophytic bacteria and fungi, particularly their action on plant growth promotion and the biocontrol of pests. In addition, we sought to identify and analyze the gaps in available research. Additionally, the potential of endophytes to improve the quality of coffee seeds is briefly discussed. Even though there are limited studies on the subject, it has been well recognized the potentiality of coffee endophytes in plant growth promotion through enhancing nitrogen fixation, availability of minerals, nutrient absorption, secretion of phytohormones, and other bioactive metabolites. Further, the antagonistic effect against various coffee pathogenic bacteria, fungi, nematodes, and also insect pests lead to the protection of the crop. Furthermore, it is recognized that endophytes enhance the sensory characteristics of coffee as a new field of study.

In Nitrate Vulnerable Zones (NVZ) site-specific techniques are needed to match N availability with durum wheat (Triticum turgidum subsp. durum Desf.) requirements. Enhanced-efficiency fertilizers (EEF) can improve efficient N supply and reduce leaching, thus contributing to sustainable agriculture. To study the effects of rates, sources and timings of nitrogen application, two-year field experiments were carried out at two Mediterranean NVZs of Central Italy (Pisa and Arezzo). The trial compared: i) two N rates: one based on the crop N requirements (NO), the other on the Action Programmes’ prescriptions of the two NVZ (NAP); ii) three N sources (urea, methylene urea (MU), and nitrification inhibitor (NI) 3,4-Dimethylpyrazole phosphate (DMPP); and two top-dressing timings (1st tiller visible and 1st node detectable). Grain yield and yield components were determined, together with N uptake. Results showed that: i) grain and biomass production were reduced with NAP at both locations; ii) urea performed better than slow-release fertilizers; iii) the best application time varied depending on N source and location: at Pisa enhanced-efficiency fertilizers achieved higher yields when applied earliest, while for urea the contrary was true; at Arezzo different N fertilizers showed similar performances between the two application timings. Different behaviors of top-dressing fertilizers at the two localities could be related to the diverse patterns of temperatures and rainfall. Therefore, optimal fertilization strategies vary according to environmental conditions.

Effects of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB), which removes the 4-sulfate group at the non-reducing end of chondroitin 4-sulfate, on the expression of PD-L1 were determined and the underlying mechanism of PD-L1 expression elucidated. Initial experiments in human melanoma cells (A375) showed PD-L1 expression increased from 357 ± 31 to 796 ± 50 pg/mg protein (p

The ubiquitous presence of microplastics (MPs) in the environment poses a threat to ecosystems and increases concerns about their exposure to the human body. However, despite being consumed for health improvement, limited research has been conducted on MPs in functional foods. This study aimed to investigate the occurrence of MPs and the relation of the source of raw material or the manufacture in various omega-3 oil in the Korean market. MPs in omega-3 capsule and raw oil, sourced from both plant-based (PB) and animal-based (AB) sources, were investigated. We developed the method by direct filtration with acetone washing and analyzed MPs greater than 5 μm using microscope-Raman spectroscopy. The average number of MPs was found to be 1.2 ± 1.7 MPs/g for PB raw oil, 2.2 ± 1.7 MPs/g for AB raw oil, 3.5 ± 3.9 MPs/g for PB capsule oil, and 10.6 ± 8.9 MPs/g for AB capsule oil. Polypropylene and polyethylene terephthalate were major specious (83-95 %) found in omega-3 oil. The ratio of size range remained consistent across all groups, with a trend of higher detection rates as the size diminished. The results reveal that the main reason of MPs contamination is not the source of raw material but the manufacturing and packaging process for omega-3 oil.

Ovarian cysts are linked to hormone imbalances and altered gene expressions, but the connection between cysts and ion channel expression is understudied. This study explored the role of TWIK-related acid-sensitive K+ (TASK) channels in bovine ovarian cyst formation. The ovarian follicles were split into small (5 to 10 mm in diameter) and large (> 25 mm in diameter) groups. Among the measured K+, Na+, and Cl- concentrations in follicular fluid (FF) obtained from small-sized follicles (SF) and large-sized follicles (LF), the K+ concentration was significantly lower in LFFF. Quantitative PCR, western blot, and immunocytochemistry data revealed that TASK-3 expression levels significantly decreased by approximately 50% in both LF and granulosa cells obtained from LF (LFGCs) compared to the corresponding controls. The TASK-3 protein was localized to the plasma membrane of GCs. The diameter of LFGCs was larger than that of SFGC. The cell swelling response to exposure to a hypotonic solution (200 mOsm/L) was highly reduced in TASK-3-overexpressing cells compared to vector-transfected cells. TASK-3-knockdown cells showed arrested growth. Senescence markers were detected in LFGCs and TASK-3-knockdown cells. These findings suggest that reduced TASK-3 expression in LF is associated with the inhibition of GC growth, leading to senescence and cyst formation.

The historical and cultural use of food as a remedy for diseases is evident in societies, such as using Hibiscus sabdariffa to address conditions like hypertension and high blood glucose. The natural biocompounds in this plant, including Delphinidin-3-Sambubioside (DS3), Quercetin (QRC), and Hibiscus Acid (HA), have been linked to various health benefits. Despite individual attention, molecular targets for these compounds remain unclear. In this study, in-silico analysis employed bioinformatic tools; including Swiss Target Prediction, ShinnyGo 0.77, KEGG, and Stringdb, to identify molecular targets, pathways, and hub genes. A PubMed literature search complemented the results. DS3 demonstrated potential modifications in genes related to nitrogen and glucose metabolism, inflammation, angiogenesis, and cell proliferation, particularly affecting the PI3K-AKT pathway. QRC displayed interconnected targets across multiple pathways, with overlap with DS3 and a focus on cancer-related pathways. HA showed distinct targets, particularly associated with nervous system-related pathways. These findings highlight the need for targeted research on the molecular effects of DS3, QRC, and HA, providing valuable insights into potential therapeutic pathways.

Although conventional chemotherapeutic drugs are the first line of treatment for cancer, they have numerous side effects. One of the emerging challenges in cancer treatment is drug resistance. Nat-ural compounds have proven effective against various hallmarks of cancer for their multi-target inhibition properties, but especially for their ability to synergistically bypass low bioavailability. Methods: The present study investigated the in vivo antitumor effects of a combination of two natural dietary agents, epigallocatechin-3-gallate (EGCG) from Camelia Sinensis and curcumin, a component of turmeric (Curcuma longa). We aimed to compare, for the first time in vivo, the antiangiogenic and antitumor effects of sunitinib with the combination of curcumin and EGCG in a mouse model of renal cell carcinoma (ccRCC). It was shown that they are able to inhibit cell survival, proliferation of several type of cancer, including renal cell carcinoma (ccRCC), by mod-ulating different signaling pathways and that their combination respect to single compound syn-ergistically decreased angiogenesis. Results: Herein, we highlighted that these compounds inhib-ited the growth of xenografted renal cancer in nude mice by significant inhibition of tumor vol-ume, tumor weight and CD31 expression with no signs of hepatic toxicity. Moreover, mice treated with these natural compounds showed a significant reduction in angiogenesis and an improve-ment in survival rate with p<0.05. Finally, pretreatment of mice with a diet containing 0.6% curcumin before injection of tumor cells showed a significant inhibition of tumor engraftment in 60% of mice with respect to controls and other groups. Conclusions: Taken together, our data in-dicate, for the first time, that the combination of curcumin and EGCG acts in a synergistic manner to inhibit the growth and angiogenesis of ccRCC and with less toxicity than sunitinib and provide an important rationale for future clinical development for chemoprevention and treatment of re-nal cancer.

Due to the growing interest in biopolymers, biosynthesizable and biodegradable polymers currently occupy a special place. Unfortunately, the properties of native biopolymers are not satisfactory, which explain that attempts are being made to modify them. The work attempts to improve the properties of poly(3-hydroxybutyrate) (P3HB) using linear aliphatic polyurethane (PU) based on 1,4-butanediol and hexamethylene 1,6-diisocyanate. The conducted studies on the effect of the amount of PU used (5, 10, 15 and 20 wt.%) showed an improvement in the thermal properties of the prepared polymer blends. There was an increase in the degradation temperature of the ob-tained blends in relation to the native P3HB by 12-57C, and the difference between the melting point and the degradation point was above 100°C for most of the obtained blends. As part of the tested mechanical properties of the new polymer blends, we noted the desired increase in the tensile strength, in the relative elongation at break and in the impact strength with a decrease in hardness, in particular with the presence of 5 wt.% PU. Therefore, for further improvement, hybrid nanobiocomposites with 5 wt.% PU and organically modified montmorillonite (MMT – Cloisite 30B) were produced. The nanoadditive was used in typical amount of 1-3 wt.%. The nanostructure of the biocomposites produced by extrusion was examined by small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM), the morphology by scanning electron microscopy (SEM), and compatibility by infrared spectroscopy (FT IR). In addition, selected mechanical properties were determined and thermal properties were tested by the thermogravimetric analysis (TGA) and the standard differential scanning calorimetry (DSC). The polyester and polyurethane chains penetrated into the interlayer spaces of organically modi-fied nanoclay – Cloisite30B and the complete delamination occurred during direct mixing in the extrusion process. FT IR spectral analysis showed the compatibility of the polymer biocomposite components by the coexistence of intermolecular interactions in the form of hydrogen bonds. The morphology studies of the produced hybrid nanobiocomposites showed an interaction of the bi-opolymer matrix with PU and Cloisite30B and the formation of easily migrating polyester-polyurethane-montmorillonite adducts, which resulted in improved mechanical properties com-pared to the properties of the native P3HB and P3HB-PU compositions. The influence of the presence of a nanofiller on the properties of the prepared nanobiocomposites was tested and it was found that, as expected, the smallest amount of nanofiller provides the best results.It was found that the obtained nanobiocomposites containing the smallest amount of nano-fillers, i.e. 1 wt.% Cloisite30B exhibited the best mechanical and thermal properties. The desired decrease in hardness by 15% and a higher value of impact strength by 15%, an increase in elonga-tion at break by 60% and an increase in thermal stability of the newly produced biocomposites compared to to the native P3HB were observed. The prepared nanobiocomposites combined the best features caused by the elasticizing effect of polyurethane and the formation of P3HB-PU-MMT adducts.

Background: Prostate cancer remains a significant global health concern, and understanding the molecular drivers of this disease is crucial for developing effective diagnostic and therapeutic strategies. Steroid Receptor Coactivator-3 (SRC-3), a member of the SRC family, has emerged as a key player in prostate cancer pathogenesis. This review comprehensively examine the role of SRC-3 in prostate cancer, encompassing molecular mechanisms, clinical implications, and therapeutic opportunities. Methods: A systematic literature search following PRISMA guidelines was conducted in PubMed, PMC, and other relevant databases to identify studies that investigate SRC-3 in prostate cancer. A total of 67 articles were selected based on predetermined inclusion criteria. Results: 785 articles were retrieved from databases using specific keywords and MeSH terms related to SRC-3 and Prostate Cancer. After removing 461 duplicates, 260 articles were excluded based on title and abstract review. Subsequently, a comprehensive screening by three researchers resulted in 47 relevant articles for this systematic review. We summarize its contributions to AR-mediated transcriptional regulation, tumor growth, and metastasis. Evidence suggests that SRC-3 expression correlates with prostate cancer aggressiveness, disease recurrence, and poor patient outcomes. Its potential as a diagnostic biomarker and therapeutic target is explored, offering insights into personalized medicine approaches. Conclusions: SRC-3 plays a pivotal role in prostate cancer, influencing disease progression and clinical outcomes. Understanding the molecular intricacies of SRC-3 in prostate cancer offers new opportunities for precision medicine and innovative therapeutic approaches. This review provides a comprehensive overview of SRC-3's involvement in prostate cancer, emphasizing its clinical relevance and potential as a therapeutic target, ultimately contributing to improved patient care in the era of personalized oncology.

Background: Galectin-3 (Gal-3) is a biomarker involved in a wide range of diseases including cardiac remodeling following acute myocardial infarction (AMI). Identification of prognostic markers in patients with AMI can guide strategies towards improved survival and the quality of life. Methods: Our study included 59 patients with AMI and preserved ejection fraction. We determined the Gal-3 plasma concentration within 24 hours of chest pain onset from aortic root, femoral/radial artery, coronary sinus and cubital vein. Major adverse cardiovascular events (MACE) were evaluated at six months follow-up. Results: MACE at six months post-AMI was recorded in 20 patients (34%). The Gal-3 plasma concentration from aortic root and the femoral/radial artery were independent predictors of MACE at six months follow-up after the first AMI (OR 1.228; 95%CI: 1.011-1.491; p=0.038; OR 3.438; 95%CI: 1.275-9.265; p=0.015). ROC analysis identifies the Gal-3 plasma concentration from aortic root as a better predictor of MACE or death (cut-off &gt;10.86 ng/ml; AUC 0.858; 95%CI: 0.744-0.973; p&lt;0.001) than Gal-3 plasma concentration from femoral/radial artery (cut-off &gt;10.18 ng/ml; AUC 0.742; 95%CI: 0.596-0.888; p=0.006). Conclusion: The Gal-3 plasma concentration in patients with AMI determined during coronary angiography, especially from the aortic root, within 24 hours after chest pain onset is a valuable biomarker of prognosis at six months follow-up.

Cluster of differentiation 44 (CD44) promotes tumor progression through the recruitment of growth factors, and the acquisition of stemness, invasiveness, and drug resistance. CD44 has multiple isoforms including CD44 standard (CD44s) and CD44 variants (CD44v), which have common and unique functions in tumor development. Therefore, the elucidation of each CD44 isoform’s function in tumor is essential for the establishment of CD44-targeting tumor therapy. We have established various anti-CD44s and anti-CD44v monoclonal antibodies (mAbs) through immunization of CD44v3–10-overexpressed cells. In this study, we established C44Mab-6 (IgG1, kappa), which recognized the CD44 variant 3-encoded region (CD44v3) determined by enzyme-linked immunosorbent assay. C44Mab-6 reacted with CD44v3–10-overexpressed Chinese hamster ovary (CHO)-K1 cells (CHO/CD44v3–10) or some cancer cell lines (COLO205 and HSC-3) by flow cytometry. The apparent KD of C44Mab-6 for CHO/CD44v3–10, COLO205, and HSC-3 was 1.5 × 10−9 M, 6.3 × 10−9 M, and 1.9 × 10−9 M, respectively. C44Mab-6 could detect the CD44v3–10 in western blotting, and stained the formalin-fixed paraffin-embedded tumor sections in immunohistochemistry. These results indicate that C44Mab-6 is useful for detecting CD44v3 in various experiments, and expected for the application of tumor diagnosis and therapy.

The traditional nomenclature system for classifying Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), based on clinical phenotype, described Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and every day clinical practice, yet, a substantial overlap in clinical presentation still exists, and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative), could be more accurate and also closer to the nature of the disease, instead of the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV, in terms of epidemiology, pathogenesis, histological and clinical manifestations, and response to therapeutic approaches.

The taxonomy of trilobites Abadiella Hupé, 1953 and Parabadiella Zhang, 1966 from the lower Cambrian of Gondwana has long been a controversy. Based on newly-collected and formerly-reported materials, 94 trilobite cranidia within 21 species are selected for morphometric analyses: principal components analysis (PCA) and canonical variates analysis (CVA). The integrated morphological characters are successfully accounted for by two principal components in PCA. The further validations for the presupposed qualitative groupings are indispensable to detect and calibrate the ultimate taxonomic results in CVA. By this way, all specimens distributed in a consistent morphospace in PCA and the short distances between them demonstrate their close morphological affinity, supporting their congeneric status within Abadiella. Additionally, three morphotypes were recognized from all selected specimens and they were eventually revised and incorporated into A. bourgini Hupé, 1953, A. huoi Zhang, 1966, and A. yunnanensis Luo, 1981, through stepwise test-calibration to get a high correct rate as far as possible in CVA. From this, it is certain that A. huoi is conspecific in South Australia and South China. Its occurrence allows to correlate the Australian A. huoi Range Zone to the identical zone in South China (in platform), having an approximately consistent stratigraphic range in the two regions. In comparison with A. huoi, A. bourgini was reported from fewer localities in South China. Nevertheless, its presence in the Daguinaspis Zone of Issendalenian Stage in Morocco permits a correlation with Chinese and Australian A. huoi Zone. As an auxiliary marker for A. huoi, the occurrence of A. bourgini in Morocco, South Australia and South China reinforce the correlation potential and resolution in species-level for the Cambrian Stage 3 in Gondwana region.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research pro-gresses in the effect of bacterial dysbiosis from a metabolic point of view, particularly on the bio-chemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with an-ti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyun-saturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.

The intake of omega-3 polyunsaturated fatty acids (PUFA) of the average consumer is generally low and products like fish oils high in omega-3 PUFA have become a popular dietary supplement. There is a need for more sources of omega-3 PUFA to cover the increasing demand. This study investigated whether livers from different lean fish species could be a potential new source of oils rich in omega-3 PUFA. The seasonal variation in lipid content, fatty acid composition, peroxide value and free fatty acid content of livers from cod, hake, ling, coalfish and monkfish was determined and the effect of storage conditions on the fishing vessel (ice vs frozen) was studied. Generally, the lipid content and composition of the livers from the five fish species varied similarly during the two years of sampling period with significantly lower values in spring (March, April) and higher values in fall (November, October). Storage conditions were found to have no significant effect on the quality and oil composition. Monkfish livers were less suitable for production of omega-3 oil due to their lower lipid and EPA content and higher FFA levels. Coalfish had higher fluctuations in oil composition during sampling period, which potentially makes a standardised quality difficult to obtain. Cod, hake and ling were the most suitable species for fish liver oil production.

Clonal evolution and cellular plasticity are the genetic and non-genetic driving forces of tumor heterogeneity that in turn determines the tumor cell response towards therapeutic drugs. Sever-al lines of evidence suggest that therapeutic interventions foster the selection of drug resistant neural crest stem-like cells (NCSCs) that establish minimal residual disease (MRD) in melano-ma. Here we established a dual reporter system enabling the tracking of NGFR expression and mRNA stability, providing insights into the maintenance of NCSC-states. We observed that the transcriptional reporter that contained a 1kb fragment of the human NGFR promoter was acti-vated only in a minor subset (0.72±0.49%, range 0.3-1.5) and ~2-4% of A375 melanoma cells re-vealed stable NGFR mRNA. The combination of both reporters provided insights into pheno-type switching and revealed that both cellular subsets gave rise to cellular heterogeneity. Moreover, whole transcriptome profiling and gene set enrichment analysis (GSEA) of the minor cellular subset revealed hypoxia-associated genes serving as potential drivers of a NGFR-associated phenotype switching in vitro and in relapsed, post-BRAF inhibitor treated tu-mors. Concordantly, we observed that the minor cellular subset increased in response to dabrafenib over time. In summary, our reporter-based approach provided insights into plastici-ty and identified a cellular subset that might be responsible for the establishment of MRD in melanoma.

Investigation of sea-level positions during the highly-dynamic Marine Isotope Stage 3 (MIS 3: 29-61 kyrs BP) proves difficult because: i) in stable and subsiding areas, coeval coastal sediments are currently submerged at depths of few to several tens of meters below present sea level; ii) in uplifting areas, the preservation of geomorphic features and sedimentary records is limited due to the erosion occurred during the Last Glacial Maximum (LGM) with sea level at depth of -130 m, followed by marine transgression that determined the development of ravinement surfaces. This study discusses previous research in the Mediterranean and elsewhere, and describes new fossiliferous marine deposits laying on metamorphic bedrock of Cannitello (Calabria, Italy). Radiocarbon ages of marine shells (about 43 kyrs cal BP) indicate that these deposits, presently between 28 and 30 meters above sea level, formed during MIS 3.1. Elevation correction of the Cannitello outcrops (considered in an intermediate-to-far-field position with respect to the ice sheet) with the local vertical tectonic rate and Glacial Isostatic Adjustment (GIA) rate allows to propose a revision of the eustatic depth for this highstand. Our results are consistent with recently proposed estimates based on a novel ice sheet modelling technique.

Atlantic salmon (Salmo Salar) is one of the fish species that rich in omega-3 fatty acids. Consumption of omega-3 fatty acids can lower down the risk of cardiovascular disease and coronary heart disease. The extraction of omega-3 fish oil from Atlantic salmon by using hexane and isopropanol was conducted in this research. Response Surface Methodology (RSM) was used to study the impact of parameters which were temperature (50-90°C), centrifuge speed (1000-3000rpm) and solvent ratio of hexane to isopropanol (0.5-1.5) to the percentage of oil yield. The results obtained shows that 15.23%± 0.61 of oil yield from Atlantic salmon under an optimum condition of 70°C, 3000 rpm and solvent ratio of hexane to isopropanol of 1.5. The acid value, peroxide value and p-anisidine value of the fish oil obtained were 7.48 mg KOH/g, 1.94 meq/kg and 5.56 respectively which were all within the acceptable limit which stipulated by Global Organization for EPA and DHA (GOED) and Food and Agricultural Organization of the United Nations (FAO). The FTIR analysis proved the presence of alkane and carboxylic acid in the fish oil. Furthermore, GC-MS analysis showed that the fish oil contains higher monounsaturated fatty acids (MUFA) contents followed by polyunsaturated fatty acids (PUFA) and 4.5525% of total omega-3 fatty acids.

In the last decades droughts, deforestation and wildfires have become recurring phenomena that have affected both human activities and natural ecosystems in Amazonia. The time an ecosystem requires to recover from carbon losses is a crucial metric to evaluate disturbance impacts on forests. However, the factors influencing and controlling the recovery time and its spatiotemporal patterns at the regional scale are still poorly understood. In this study, we combined forest growth model, remote sensing and field plots, to map Amazonia-wide (300-ha resolution) impact and recovery time of aboveground biomass (AGB) after drought, fire and a combination of logging and fire. Our simulated results indicate that AGB decreases by 4%, 19% and 46% in forests disturbed by drought, fire and logging + fire, respectively, with an average AGB recovery time of 27 years for drought, 44 years for burned and 63 years for logged + burned areas and with maximum values reaching 184 years in areas of high fire intensity. Our findings provide two major insights in the spatial and temporal patterns of drought and wildfire in the Amazon: 1) the recovery time of the forests takes longer in the southeastern part of the basin, and, 2) as droughts and wildfires become more frequent – since the intervals between the disturbances is getting shorter than forest regeneration – potentially causing a long-lasting damage in these fragile ecosystems and a permanent degradation.

In this manuscript we report new effects of resonance detuning on various dynamical parameters of a generic 3-wave system. Namely, for suitably chosen values of detuning the variation range of amplitudes can be significantly wider than for exact resonance. Moreover, the range of energy variation is not symmetric with respect to the sign of the detuning. Finally, the period of the energy oscillation exhibits non-monotonic dependency on the magnitude of detuning. These results have important theoretical implications where nonlinear resonance analysis is involved, such as geophysics, plasma physics, fluid dynamics. Numerous practical applications are envisageable e.g. in energy harvesting systems.

New corrosion inhibitor derived from coumarin-3-amine namely 3-((2-chlorobenzylidene)amino)coumarin was synthesized and characterized by CHN elemental analysis in addition to Fourier transform infrared and nuclear magnetic resonance techniques. The anti-corrosion ability of 3-((2-chlorobenzylidene)amino)coumarin to inhibit the impacts of corrosion has been demonstrated and damage reduction of the mild steel also. 3-((2-chlorobenzylidene)amino)coumarin, has been employed as a good corrosion inhibitor for mild steel in HCL solution. The efficiency of the inhibition was figured according to weight loss method and it was 74.6%.

Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine) as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation, acetylation, quaternization, and dehydrogenation, were adopted. Nineteen target derivatives were evaluated for their antiarrhythmic potential in the mouse model of ventricular fibrillation (VF), induced by CHCl₃, and five of the derivatives were investigated further in the rat model of arrhythmia, induced by BaCl₂. Meanwhile, preliminary structure-activity/toxicity relationship analyses were carried out. Significantly, N-acetamidesecocrebanine (1d), three bromo-substituted products of crebanine (2a, 2b, 2c), N-methylcrebanine (2d), and dehydrostephanine (4a) displayedantiarrhythmic effects in the CHCl₃-induced model. Among them, 7.5 mg/kg of 2b was able to significantly reduce the incidence of VF induced by CHCl₃ (p<0.05), increase the number of rats that resumed sinus rhythm from arrhythmia, induced by BaCl₂ (p<0.01), and the number of rats that maintained sinus rhythm for more than 20 minutes (p<0.01). Therefore, 2b showed remarkably higher antiarrhythmic activity and a lower toxicity (LD₅₀=59.62 mg/kg, mice), simultaneously, indicating that 2b could be considered as a promising candidate in the treatment of arrhythmia. Structural-activity analysis suggested that variationsin antiarrhythmic efficacy and toxicity of aporphines were related to the C-1,C-2-methylenedioxy group on ring A, restricted ring B structural conformation, N-quaternization of ring B, levoduction of 6a in ring C, and the 8-, 9-, 10-methoxy groups on ring D on the skeleton.

Porous β-tricalcium phosphate (Ca3(PO4)2; β-TCP) was prepared by freeze-drying and the effects of this process on pore shapes and sizes were investigated. Various samples were prepared by freezing β-TCP slurries above a liquid nitrogen surface at −180 °C with subsequent immersion in liquid nitrogen at −196 °C. These materials were then dried under reduced pressure in a freeze-dryer after which they were sintered by heating. Compared with conventional heat-based drying, the resulting pores were more spherical, which increased both the mechanical strength and porosity of the β-TCP. These materials had a wide range of pore sizes from 50 to 200 µm, with the mean and median values both approximately 100 µm regardless of the freeze-drying conditions. Mercury porosimetry data showed that the samples contained small, interconnected pores with sizes of up to 1.24 µm and macroscopic, interconnected pores up to 25.8 µm in size. The effects of non-ionic surfactants having different hydrophilic/lipophilic balance (HLB) values on foaming and pore size were also investigated. Materials made with surfactants having lower HLB values exhibited smaller pores and lower porosity whereas higher HLB surfactants gave higher porosity and slightly larger macropores. Even so, the pore diameter could not be readily controlled solely by adjusting the HLB value. The findings of this work indicated that high porosity (75%) and good compressive strength (&gt;2 MPa) can both be obtained in the same porous material and that foaming agents with HLB values between 12.0 and 13.5 were optimal.

In this report, we establish a straightforward method for estimating the equilibrium constant for the CK reaction over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq” is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells, and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism, and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we could estimate ΔGATP. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies but not when pH is altered, maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis for the role of submicromolar ADP in force generation.

Microbial production is a promising method that can overcome major limitations in conventional methods of lycopene production, such as low yields and variations in product quality. Significant efforts have been made to improve lycopene production by engineering either the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway or mevalonate (MVA) pathway in microorganisms. To further improve lycopene production, it is critical to utilize metabolic enzymes with high specific activities. Two enzymes, 1-deoxy-D-xylulose-5-phosphate synthase (Dxs) and farnesyl diphosphate synthase (IspA), are required in lycopene production using MEP pathway. Here, we evaluated the activities of Dxs and IspA of Vibrio sp. dhg, a newly isolated and fast-growing microorganism. Considering that the MEP pathway is closely related to the cell membrane and electron transport chain, the activities of the two enzymes of Vibrio sp. dhg were expected to be higher than the enzymes of E. coli. We found that Dxs and IspA in Vibrio sp. dhg exhibited 1.08-fold and 1.38-fold higher catalytic efficiencies, respectively. Consequently, the heterologous overexpression improved the specific lycopene production by 1.88-fold. Our findings could be widely utilized to enhance production of lycopene and other carotenoids.