Antarctic krill protein-iron complex and peptide-iron complex were obtained to investigate their iron bioavailability, expression of iron-regulated genes, and in vivo antioxidant capacity. Results indicated that Antarctic krill peptide-iron complex increased significantly the hemoglobin (Hb), serum iron (SI) and iron content in the liver and spleen in iron-deficiency anemia (IDA) mice (P < 0.05) compared with those of Antarctic krill protein-iron complex. Despite the gene expressions of divalent metal transporter 1(DMT1), transferrin (Tf) and transferrin receptor (TfR) could be better regulated by both Antarctic krill peptide-iron complex and protein-iron complex, the relative iron bioavailability of the Antarctic krill peptide-iron complex group (152.53±21.05%) was significantly higher than that of the protein-iron complex group (112.75±9.60%) (P<0.05). Moreover, Antarctic krill peptide-iron complex could enhance the antioxidant enzyme activities of superoxidase dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce the malondialdehyde (MDA) level in IDA mice compared with the protein-iron complex, reducing the cell damage caused by IDA. Therefore, these results demonstrated that Antarctic krill peptide-iron complex could be used as a highly efficient and multifunctional iron supplement.

Pygoscelis penguin populations in the Antarctic Peninsula have dropped dramatically in the last 50 years. The main probable cause is the reduction in Krill (Euphausia superba), the most important feeding item for Pygoscelis penguins during breeding. The scientific community has expressed concerns on the potential that competition with the fishery during periods of low krill availability might be exacerbating the effects of climate change. By bringing together data on breeding success of penguin colonies throughout the Antarctic Peninsula with information of krill availability from acoustic survey and krill fishery monitoring data, we were able to show that fishery has had in the past an effect over breeding success. That is a consequence of a management strategy based on a constant catch level enabling the fishery to maintain the same levels of production even when krill availability is low. The total catch limit may have represented a substantial amount of the available krill biomass in some years, and we detected that when the catch goes over 5% of the available biomass during summer, breeding success of penguins decreased by one third. We discuss the implications of our findings to the revised ecosystem-based management strategy of the krill fishery in Antarctica.

It is important to realize the transformation behavior of wüstite because it greatly affects the final structure of the oxide layer and the surface quality of the steel products. In the present study, the transformation behaviors of the wüstite layer are examined under nearly-oxygen-free conditions, to simulate the cooling processes after the hot rolled strip is coiled. As the single phase wüstite was prepared at 950˚C, the 460˚C transformed oxide layer was composed of a mixture of iron and magnetite formed through eutectoid reactions. For the 750˚C-fabricated wüstite, only magnetite was observed after transformation, without iron precipitates and residual wüstite. It is speculated that the unusual transformation behavior of the low-temperature-made wüstite results from the pseudo-structural intermediate phase transformation between wüstite and magnetite. This pseudo-structure is a pre-transformed wüstite and of various concentration of ferrous ion, which is determined by the fabrication conditions. During the hot strip mill process, the so-called wet scale, wüstite, is produced continuously from finish mill to laminar flow sections and ended at 570˚C. Consequently, the final eutectoid transformation below 570˚C is dominantly controlled by the surface temperature ranged from 750˚C to 950˚C for low carbon steel.

Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties putting them on a new path in medicine. Their conformational rigidity that improves proteolytic stability, leads to rapid penetration into tissues via any possible route of administration and elimination, occurring by renal metabolism, is of great importance for people with a history of liver diseases. In addition, each ring can function independently, making them extremely versatile molecules for further optimization. In this paper we compared the potentiometric and spectroscopic properties studied by UV-Vis, MCD, and EPR, of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH). In particular we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL (Ac-PKKHPc(CFWKTC)PKKH-NH2) that contains the unbinding cycle and N- and C-terminal linear parts, with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH2) and in the C-terminal position i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH2), respectively, and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH2).

Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a MHC class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and ehsp70.

Pretreatment of cells with proteolysis inhibitors diminished intensity and changed shape of DNICs specific EPR signal in a treatment time-dependent manner. The level of DNIC formation was significantly influenced by the presence of protein degradation products. Interestingly, formation of HMWDNICs depended on the availability of LMWDNICs. The extent of glutathione involvement in the in vivo formation of DNICs is minor yet noticeable, aligning with our prior research findings.

Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have an elevated resistance to exogenous antimicrobial peptides (AMPs) – both, with regard to peptide bulk concentration in the medium, and the numbers of peptide molecules per cell. By monitoring integration of the AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy-coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings.

A recent report in PNAS that Candidatus Nanohaloarchaeum antarcticus requires haloarchaeon Halorubrum lacusprofundi for growth expands the list of known symbiotic or parasitic associations between the members of DPANN archaea, which are relatively small cells with reduced genomes and limited metabolic capacity, and free-living archaea. In line with previous studies addressing the enigmatic mechanism(s) for the transfer of metabolites from Ignicoccus hospitalis to Nanoarchaeum equitans, this new study presents additional evidence supporting a direct cytoplasmic connection facilitated by the fusion of parasite’s membrane with that of its host. Here I show that this novel mechanism for accessing the host resources by a membrane fusing mechanism, which eliminates the need for sophisticated multivalent transport systems, is fundamentally similar to that employed by several viral lineages. These new findings support an evolutionary model on the origin of incipient viral lineages from parasitic cellular lineages that started their parasitic life cycle by fusing with their host cells.

Bacteria can colonize and develop biofilm on a large variety of biotic and abiotic materials, it is accountable for nosocomial infections and chronic illness and consequently, it is a serious economic and public health problem. Staphylococcus epidermidis, thanks to its ability to form biofilm and colonize biomaterials, represents the most frequent causative agent involved in bio-film-associated infections of medical devices. Due to the biofilm presence, S. epidermidis infections are extremely difficult to treat and the research of new molecules able to interfere with its biofilm formation has a remarkable interest. In the present work, the attention was focused on Pseudomonas sp. TAE6080, an Antarctic marine bacterium able to produce and secrete an effective antibiofilm compound. The molecule responsible for this activity was purified by an activity-guided approach and it resulted to be a periplasmic protein, named Cold-Azurin. The Cold-Azurin was recombinantly produced in E. coli and purified. The recombinant protein was able to impair S. epidermidis attachment to the polystyrene surface and effectively prevent biofilm formation.

For the last two decades, an increasing demand for low-cost adsorbents for drinking water treatment has been challenged in the rural areas of developing countries that have problems with arsenic (As) contamination. In this work, spent bleaching earth (SBE), a residual material that is formed during the process of refining vegetable oil, has been utilized to prepare the new magnetic adsorbent Fe-SBE/C by modifying its surface area through calcination and co-precipitation with iron. The experimental results demonstrate that Fe-SBE/C exhibits a substantial adsorption capacity towards both arsenite (As(III)) and arsenate (As(V)). Optimal pH conditions were found to be pH 10 for As(III) and pH 3 for As(V), resulting in adsorption percentages of 76.7% and 94.1%, respectively. Other experimental parameters such as calcination conditions, adsorbent dosage, iron-loading ratio, and the presence of co-existing ions were thoroughly investigated. The kinetic study revealed that the adsorption processes follow the Elovich and intraparticle diffusion models, suggesting a combined adsorption mechanism of boundary layer control and chemisorption. Furthermore, the isotherm followed the Langmuir model with a maximum adsorption capacity of 202.61 μg g-1 for As(III) and 187.61 μg g-1 for As(V). Through thermodynamic analysis and reinforcement by activation energy data, this research validates that the observed adsorption process is indicative through chemisorption. The regeneration study revealed the potential for multiple cycles of arsenic removal, highlighting the practical applicability of Fe-SBE/C in environmental contexts. In conclusion, the findings of this study underscore the efficacy of Fe-SBE/C in arsenic removal and present it as a promising and environmentally friendly solution for mitigating arsenic pollution.

In the cold deserts of the McMurdo Dry Valleys (MDV) the suitability of soil for microbial life is determined by both contemporary processes and legacy effects. Climatic changes and accompanying glacial activity have caused local extinctions and geochemical changes to soil ecosystems over several million years, while high elevation refugia may have escaped these disturbances and existed under relatively stable conditions. This study describes the impact of historical glacial and lacustrine disturbance events on microbial communities across the MDV. Soil bacterial communities from 17 sites representing either putative refugia or sites disturbed during the Last Glacial Maximum (LGM) (22-17kya) were characterized using 16S metabarcoding. Regardless of geographic distance, several putative refugia sites at elevations above 600 meter displayed highly similar microbial communities. At a regional scale, community composition was found to be influenced by elevation and geographic proximity more so than soil geochemical properties. These results suggest that despite the extreme conditions, diverse microbial communities exist in these putative refugia that have presumably remained undisturbed at least through the last glacial maximum. We suggest that similarities in microbial communities can be interpreted as evidence for historical climate legacies on an ecosystem-wide scale.

Iron is an essential nutrient and necessary for biological functions from DNA replication and repair to transcriptional regulation, mitochondrial respiration, electron transfer, oxygen transport, photosynthesis, enzymatic catalysis, and nitrogen fixation. However, due to iron’s propensity to generate toxic radicals which can cause damage to DNA, proteins, and lipids, multiple processes regulate uptake and distribution of iron in living systems. Understanding how intracellular iron metabolism is optimized and how iron is utilized to regulate other intracellular processes is important to our overall understanding of a multitude of biological processes. One of the tools that the cell utilizes to regulate a multitude of functions is ligation of the iron-sulfur (Fe-S) cluster cofactor. Fe-S clusters comprised of iron and inorganic sulfur are ancient components of living matter on earth that are integral for physiological function in all domains of life. Here we will explore the ways in which the cell utilizes Fe-S clusters to sense the intracellular environment and respond to maintain equilibrium.

The carbonyl iron particles were dispersed in a polychloroprene rubber (CR) matrix under an external magnetic field for practical application as microwave absorption composites film. The film prepared under external magnetic field with a thickness of only 0.54 mm showed least reflection loss of -15.98 dB and the reflection loss value less than -10.0 dB over the frequency range of 11.4~14.8 GHz. In comparison with the microwave absorption properties of calculation by transmission line theory based on the tested relative complex permittivity and permeability and film prepared by general route without external magnetic field, the film made with external magnetic field exhibited more excellent microwave absorption properties, strongly depending on the increment of anisotropy and rearrangement of magnetic particles. The results indicated the composite film made under external magnetic field have excellent microwave absorption properties, which suggest that the composites thin film could be used as a thinner and lighter microwave absorber.

Krill oil (KO) shows promise as a natural marine-derived ingredient for improving skin health. This study investigated its antioxidant, anti-inflammatory, anti-wrinkle, and moisturizing effects on skin cells and UVB-induced skin photoaging in hairless mice. In vitro assays on HDF, HaCaT, and B16/F10 cells, and in vivo experiments on 66 hairless mice, were conducted. Mice received oral KO administration (100, 200, or 400 mg/kg) once a day for 15 weeks and UVB radiation three times a week. In vitro, KO significantly countered UVB-induced oxidative stress, reduced wrinkles, and prevented skin water loss by enhancing collagen and hyaluronic synthesis. In vivo, all KO dosages showed dose-dependent inhibition of oxidative stress-induced inflammatory photoaging-related skin changes. Skin mRNA expressions for hyaluronan synthesis and collagen synthesis genes also increased dose-dependently after KO treatment. Histopathological analysis confirmed that Krill Oil (KO) ameliorated the damage caused by UVB-irradiated skin tissues. These findings suggest that KO may be a valuable intervention to mitigate UVB-induced skin photoaging and address various skin concerns.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly to most parts of the world, causing high numbers of deaths and significant social and economic impacts. SARS-CoV-2 is a novel coronavirus with a suggested zoonotic origin and with the potential for cross-species transmission among animals. Antarctica can be considered the only continent free of SARS-CoV-2 although at the end of the 2019-2020 tourist season, at least one SARS-CoV-2 positive tourist visited the Antarctic Peninsula. Therefore, concerns have been expressed regarding the potential human introduction of this virus to the continent through the activities of research or tourism with potential effects including those related to human health, but also the potential for virus transmission to Antarctic wildlife. This reverse-zoonotic transmission risk to Antarctic wildlife is assessed considering the available information on host susceptibility, dynamics of the infection in humans, and contact interactions between humans and Antarctic wildlife. Measures to reduce the risk are proposed as well as the identification of knowledge gaps related to this issue.

The paper provides a discussion on the results of studies of the effect exerted by combined degradation factors typical of four types of wear: abrasion, impact-abrasion, tribocorrosion, and impact-abrasion-corrosion, conducted for chain wheels made of Ni-Cu alloyed Austempered Ductile Iron. The studies consisted in determining the content of retained austenite in the structure of the cast irons in question, establishing the measures of wear following wear testing, and identifying basic surface degradation mechanisms observed in the chain wheels tested following multifactorial wear processes. The chain wheels made of ADI were found to have sustained the greatest damage under the impact-abrasion-corrosion (three-factor) wear scenario, while the wear was least advanced in the abrasion (one-factor) wear case. Another observation derived from the studies is that the combined effect of dynamic forces, corrosion, and quartz sand-based abrasives causes increased surface degradation in the cast iron grades taken into consideration compared to processes characterised by a reduced number of degradation factors (i.e. one- or two-factor wear processes). Additional hardness tests and XRD analyses have revealed a distinctive effect attributable to combined degradation factors on the surface hardness increase value and implied that bench testing was followed by phase transition.

CoCrFeNiMn high-entropy alloy coatings were prepared on compacted graphite iron（CGI） through plasma cladding to strength the CGI substrate. The effects of heat treatment temperatures and times on the microstructure and mechanical properties of the CoCrFeNiMn coatings were investigated. After heat treatment, a single FCC phase was remained in the coating as compared to the deposited one, with smaller dendrites, larger dendritic spacing and more Cr-rich compounds precipitated between dendrites. The coatings’ microhardness was increased after heat treatment. After heat treated at 660°C for 90 minutes, the coating had the highest microhardness of 563±6.9 HV0.2, the lowest frictional coefficient of 0.71 and the smallest wear mass loss of 1.12 mg, and it had the best wear resistance.

Several observations have shown that patients with polycythemia have iron deficiency. Our objectives were to report the prevalence of iron deficiency, to evaluate the diagnostic performance of serum ferritin in polycythemia vera and to describe the mechanisms of this association. This is a retrospective descriptive and analytical study carried out in the internal medicine department of the Henri Mondor Hospital, Aurillac, France. The study involved 114 patients with polycythemia, followed in the department from January 1, 2010 to December 31, 2021. To evaluate the diagnostic performance, the JAK2 mutation was considered as the gold standard of diagnosis. Thirty-three patients had polycythemia vera and 76 patients had secondary polycythemia. The mean age of the patients was 61.79 years (±15.44) with a sex ratio of 4.43. The overall prevalence of iron deficiency was 21.05%. The prevalence was 53% in polycythemia vera group and 1.32% in secondary polycythemia group. The risk of iron deficiency was high in polycythemia vera (OR=115; 95% CI [14.4-918.2], p<0.000). The sensitivity and specificity of serum ferritin were 52.63% and 100% respectively. Assessment of iron deficiency should be part of the initial evaluation of polycythemia. The presence of iron deficiency is specific for polycythemia vera.

One consequence of the global technological advancement in conventional metallurgy is the fast depletion rate of valuable minerals, which are also becoming increasingly difficult to find in pure and economically viable forms. This has spurred more interest in technologies that investigate ability of different microorganisms to mobilize valuable metals from their ores via diverse metabolic processes. This study was carried out therefore to isolate, identify and characterize iron solubilizing bacteria from Iron stones of Agbaja iron ore mining site of Kogi State, Nigeria. Crushed samples in the range of 0.25µm and 0.75µm particle sizes were cultured in a modified 9k media to facilitate bacterial growth and pure cultures were then isolated and sub-cultured for further bioleaching studies. Morphological and biochemical analysis suggests that some of the bacteria identified are members of Acidithiobacillus spp, Pseudomonas spp, and Leptospirillum spp. Studies conducted on pure cultures and mixed consortium of the identified organisms shows that a mixture of the three organisms leached iron ore to about 96.16%. Also results of growth pattern due to bacteria countafter 24-72hours of incubation ranged between 0.1×10³ cfu/ml and 12.3 ×10³ cfu/ml for Acidithiobacillus spp. The need to explore the molecular characteristics of these organisms with a view to generating more information on the quality/quantity of their DNA for future cloning activities was also investigated in this work. DNA was extracted using zymo fungal/bacterial extraction mini prep kit ^TM (cat #6001) and subsequently subjected to 1% agarose gel electrophoresis. Visible bands were obtained with Alpha Innotech Gel Documentation Machine. DNA amplification was carried out using a pettier based thermo cycler PCR machine and electrophoresed on 1.5% agarose gel. Results of the PCR shows a visible band corresponding to 1.5kbp using this primer 27F (5¹-GAGTTTGATCCTGGCTCAG-3¹) and 1492R (5^1-GGTTACCTTGTTACGACT-3¹). DNA purity check shows two of the bacteria possess very good qualities for sequencing for further molecular analysis.

The study aimed to compare the cardiovascular benefits of Omega-3 Polyunsaturated Fatty Acids from fish oil versus krill oil in different forms and dosages. Following PRISMA 2015, data analysis with R software, and databases were searched from 1993 to 2023, (ID PROSPERO: CRD42024502338). Sixty high-quality studies were analyzed, covering various forms of fish oil and krill oil at different dosages (fish oil (ethyl ester-EE, triglyceride-TG, re-esterified triglycerides-rTG, capsules, emulsion-EM); krill oil (phospholipid/free fatty acid-PL/FFA, high concentration phospholipid-HPL, low concentration phospholipid-LPL)). Meta-analysis revealed that krill oil with phospholipid/free fatty acid at doses 2000-2900 mg effectively lowered triglycerides, while fish oil in ethyl ester form at doses above 3000 mg significantly reduced total cholesterol. Fish oil in triglyceride form at doses 2000-2900 mg and other variations positively impacted HDL-C levels. Fish oil in EE form above 3000 mg and triglyceride form below 2000 mg notably reduced LDL-C. However, there was limited effectiveness observed for other interventions. Analysis for LDL-C exhibited publication bias, while other parameters demonstrated reliability (Egger's test). In conclusion, krill oil - PL/FFA, Fish oil - EE above 3000 mg, Fish oil - TG 2000-3000 mg, and fish oil - rTAG 300-1900 mg effectively in reducing heart risk patients.

Combining modern thermodynamics theory branches, including finite time thermodynamics or entropy generation minimization, constructal theory and entransy theory, with metallurgical process engineering, this paper provides a new exploration on generalized thermodynamic optimization theory for iron and steel production processes. The theoretical core is to thermodynamically optimize performances of elemental packages, working procedure modules, functional subsystems, and whole process of iron and steel production processes with real finite-resource and/or finite-size constraints with various irreversibilities toward saving energy, decreasing consumption, reducing emission and increasing yield, and to achieve the comprehensive coordination among the material flow, energy flow and environment of the hierarchical process systems. A series of application cases of the theory are reviewed. It can provide a new angle of view for the iron and steel production processes from thermodynamics, and can also provide some guidelines for other process industries.

Copper toxicity has been a selective pressure on the sea-ice bacteria due to its widespread occur-rence in Antarctica. Here, with a combined biochemical and metabolomic approach, the Cu2+ ad-aptation mechanisms of Antarctic bacteria were analyzed. Heavy metal resistance pattern of Pb2+ > Cu2+ > Cd2+ > Hg2+ > Zn2+ was observed. Copper treatment did increase the activity of antioxidants and enzymes, maintaining cellular redox state balance and normal cell division and growth. Metabolomics analysis demonstrated that fatty acids, amino acids, and carbohydrates played dominant roles in copper stress adaptation. The results indicated that the adaptation mechanisms of strain O5 to copper stress included protein synthesis and repair, accumulation of organic per-meable substances, up-regulation of energy metabolism, and formation of fatty acids. This study increases the resistance mechanism understanding of Antarctic strains to heavy metals in extreme environments.

2017 was an excellent year in terms of new drugs (chemical entities and biologics) approved by the FDA, with a total of forty-six. In turn, one of the highlights was the number of peptides (six) included in this list. Here, the six peptides are analysed in terms of chemical structure, synthetic strategy used for their production, source, biological target, and mode of action.

Antarctica is one of the most inhospitable continents on the planet, with lichens and mosses being the most common terrestrial organisms in ice-free areas. Antarctica is represented by only two species of Angiosperms, Deschampsia antarctica Desv. (Poaceae) and Colobanthus quitensis (Kunth) Bartl. (Caryophyllaceae). In this study, we characterized fungi isolated from the leaves of this grass species. The fungi were isolated from 4 individual plants from Half Moon Island (246 leave fragments investigated), and 7 from King George Island - Keller Peninsula (with 111 leave fragments investigated) Antarctica. Neoascochyta paspali, Phaeosphaeria elongata, Pyrenophora cf. chaetomioides and Alternaria sp. were associated with the plant and identified through analysis of the sequences of the internal transcribed spacer region (ITS) of the rDNA and nuclear ribosomal large subunit rRNA gene (LSU) as well as macro and micro-morphological characteristics. The isolates showed a better growth rate ranging from 10–20°C. An interesting result was that the fungi are already recognize as both plant pathogens and endophytic fungi. The results demonstrate that D. antarctica is an interesting fungal source. Those species might provide important information about the relationship on the endemic Antarctic biota.

The consequences of climate change and anthropogenic stressors, such as habitat loss and overexploitation, are threatening the subsistence of species and communities across the planet. Therefore, it is crucial to analyze the impact of environmental perturbations on the diversity, structure and function of ecosystems. In this work, in silico simulations of biodiversity loss were carried out on the marine food web of Caleta Potter (25 de Mayo Island, Antarctica) where global warming has caused critical changes in the abundance and distribution of benthic and pelagic communities during the last 30 years. We performed species removal considering their degree and trophic level and including four different thresholds on the occurrence of secondary extinctions. We examined the impact of extinctions on connectance, modularity and stability of the food web. We found different responses of these properties depending on the extinction criteria used, e.g., large increase in modularity and rapid decrease in stability when most-connected and relatively high-trophic level species were removed. Additionally, we studied the complexity-stability relationship of the food web founding two regimes: 1) high sensitivity to small perturbations suggesting that Potter Cove would be locally unstable, and 2) high persistence to long-range perturbations suggesting global stability of this ecosystem.

The paper presents the observational, remote sensing and model simulation to analyze Southern Brazil Antarctic Ozone Hole influence (SBAOHI) events occurred between 2005 and 2014. To an-alyze it we use Total Ozone Column (TOC) data provide by Brewer Spectrophotometer (BS) and OMI (Ozone Monitoring Instrument) instrument satellite, besides the AURA/MLS (Microwave Limb Sounder) instrument satellite ozone profiles was utilized with DYBAL (Dynamical Barrier Localization) code in MIMOSA (Modélisation Isentrope du transport Mésoéchelle de l’Ozone Stratosphérique par Advection) model Potential Vorticity (PV) fields. TOC has 7.0 ± 2.9 DU re-ductions average in 62 events. October have more events (30.7%). Polar Tongue events are 19.3% of total, being in October more frequently observed (50% of cases), with medium intensity (58.2%) and in stratosphere medium levels (55.0%). Already Polar Filament events (80.7%) are more frequent in September (32.0%), medium intensity (42.0%) and in stratosphere medium lev-els (40.7%). ENSO index positive phase influenced 61.3% of events, having dominance in all in-tensity categories (minor 57.9%, medium 51.6%, major 58.3%), while the equilibrium dominate the QBO influence with 50% of total cases in positive phase and 50 % in negative phase.

Within an amplicon-based metagenomic study of Archaea, Fungi, and Bacteria in Livingston Island, Maritime Antarctica, in many of the samples antagonisms between these three super kingdoms were observed under the form of an inversely proportional dependence of the richnesses of the three types of microorganisms. This was quantified - based on the observed numbers of the total tags and the numbers of the operational taxonomic units (OTUs), as well as based on four alpha diversity parameters – the Shannon, the Simpson, the Chao1, and the ACE indices. We found that the most discriminative results in the antagonism measuring were observed in the comparison of the numbers of the OTUs and the ACE community richness estimator. The antagonism between Archaea and Fungi was strongest, followed by that of Archaea and Bacteria. The Fungi-Bacteria antagonism was slightly detectable. Pearson and Spearman correlation analysis also showed a statistically significant negative correlation between the fungal and archaeal effective tags, while the correlation between archaeal and bacterial diversity was positive. Indications of the order of primary microbial succession in barren ecological niches were also observed, demonstrating that Archaea and Bacteria are the pioneers, followed by Fungi which in time would displace Archaea.

Minigastrin (MG) analogs for therapy of CCK2R-expressing malignancies are limited by low stability in vivo or excessive accumulation in non-target organs. By modifying the C-terminal receptor-binding sequence, metabolization could be prevented and tumor targeting significantly improved. In this work, N-terminal changes of the peptide length were evaluated. Based on the amino acid sequence of DOTA-MGS5 (DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1Nal-NH₂), two new MG analogs were synthesized, by either introduction of a penta-DGlu moiety or depletion of the four N-terminal amino acids and introduction of a non-charged hydrophilic linker. Two CCK2R-expressing cell lines were used to demonstrate receptor interaction. Stability of the ¹⁷⁷Lu-labeled peptide analogs was evaluated in human serum up to 24 h after incubation and in BALB/c mice up to 30 min after injection. The biodistribution profile and tumor targeting potential was evaluated in xenografted BALB/c nude mice. For both new MG analogs, the combination of strong receptor-specific cell interaction, high stability and enhanced tumor targeting could be demonstrated. Shortening of the peptide sequence lowered the absorption in the dose-limiting organs, whereas elongation increased uptake in renal tissue.

Iron and zinc are essential micronutrients required for growth and health. Deficiencies of these nutrients are highly prevalent among populations, but can be alleviated by supplementation. Cross-sectional studies in humans showed positive association of serum zinc levels with hemoglobin and markers of iron status. Dietary restriction of zinc or intestinal specific conditional knock out of ZIP4 (SLC39A4), an intestinal zinc transporter, in experimental animals demonstrated iron deficiency anemia and tissue iron accumulation. Similarly increased iron accumulation has been observed in cultured cells exposed to zinc deficient media. These results together suggest a potential role of zinc in modulating whole body iron metabolism. Studies in intestinal cell culture models demonstrate that zinc induces iron uptake and transcellular transport via induction of divalent metal iron transporter-1 (DMT1) and ferroportin (FPN) expression, respectively. It is interesting to note that intestinal cells are exposed to very high levels of zinc through pancreatic secretions, which is a major route of zinc excretion from the body. Therefore, zinc appears to be modulating the iron metabolism possibly via regulating the DMT1 and FPN1 levels. Herein we critically reviewed the available evidence to hypothesize novel mechanism of Zinc-DMT1/FPN axis in regulating intestinal iron absorption and tissue iron accumulation to facilitate future research aimed at understanding the yet elusive mechanisms of iron and zinc interactions.

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.

Sideroflexins (SLC56 family) are highly conserved multi-spanning transmembrane proteins inserted in the inner mitochondrial membrane in eukaryotes. Few data are available on their molecular function but, since their first description, they were thought to be metabolite transporters probably required for iron utilization inside the mitochondrion. Such as numerous mitochondrial transporters, sideroflexins remain poorly characterized. The prototypic member SFXN1 has been recently identified as the previously unknown mitochondrial transporter of serine. Nevertheless, pending questions on the molecular function of sideroflexins remain unsolved, especially their link with iron metabolism. Here, we review the current knowledge on sideroflexins, their presumed mitochondrial functions and the sparse - but growing - evidence linking sideroflexins to iron homeostasis and iron-sulfur cluster biogenesis. Since an imbalance in iron homeostasis can be detrimental at the cellular and organismal levels, we also investigate the relationship between sideroflexins, iron and physiological disorders. Investigating Sideroflexins’ functions constitutes an emerging research field of great interest and will certainly lead to main discoveries on mitochondrial physiopathology.

Polymeric based nanoparticles are garnering significant interest for their potential in drug delivery. Specially, nanopolymers that have been functionalized with molecules, such as proteins or peptides, are a versatile vehicle for drug delivery. Curcumin (Cur) is one of the most commonly studied anticancer compounds and is widely acknowledged as having positive effects on human health. However, its insolubility and low bio-distribution greatly hinder the exploitation of its beneficial traits. In this study, our team created a nano delivery system which utilized a nanopolymer called PCL-PEG (poly(ε-caprolactone)-poly (ethylene glycol)). This system was functionalized with A6 peptide to enable targeted delivery of Cur. The system was designed with advantageous nanoparticles (NPs), including a stable zeta potential (–32.7), small size (54.3), uniform surface morphology, and high hydrophilicity (13.72°). In addition, targeted delivery systems exhibited high encapsulation efficacy (93 ± 0.89 %), and drug loading (16.7 ± 0.9 %), and were characterized by a slow and gradual release profile with a release of approximately 83.13 ± 0.12%. The MTT assay results showed that the formulation known as Cur-NPs-A6 caused a significant increase in cell death in MDA-MB-231 cancer cells (IC50 = 23.31 ± 0.85 µM). The designed delivery system did not cause any harm to the noncancerous MCF-10A cells (normal group). Furthermore, the results of both the RT-qPCR and invasion assays demonstrated that the designed system was able to effectively activate the apoptosis pathway and inhibit cell invasion. Our findings suggest that the use of the designed smart delivery system, which is functionalized with A6 peptide that has a high affinity for CD44 receptor - known to be upregulated in numerous malignant conditions, could be a highly efficient approach to treating cancer.

Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions but in case of copper(II) and nickel(II) the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ion but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relative low thermodynamic stability with these peptides. Copper(II) catalyzed oxidation of the peptides was also studied. In the presence of H2O2 the fragmentation of peptides can be detected in all cases. In the simultaneous presence of of H2O2 and ascorbic acid the extent of the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.

Iron is the most abundant micronutrient in plant mitochondria and it has a crucial role in biochemical reactions involving electron transfer. It has been described in Oryza sativa that Mitochondrial Iron Transporter (MIT) is an essential gene and that knockdown mutant rice plants have a decreased amount of iron in mitochondria, strongly suggesting that OsMIT is involved in mitochondrial iron uptake. In Arabidopsis thaliana, two genes encode MIT homologues. In this study, we analyzed different AtMIT1 and AtMIT2 mutant alleles, confirming that individually AtMIT1 nor AtMIT2 genes are essential. When we generated crosses between Atmit1 and Atmit2 alleles we were able to isolate homozygous double mutant plants. Interestingly, homozygous double mutant plants were obtained only when mutant alleles of Atmit2 with the T-DNA insertion in the intron region were used for crossings, and in these cases a correctly spliced AtMIT2 mRNA was generated, although at a low level. Atmit1 Atmit2 double homozygous mutant plants, which were knockout for AtMIT1 and knockdown for AtMIT2, were grown and chacterised in iron sufficient conditions. Pleiotropic developmental defects were observed including abnormal seeds, increased number of cotyledons, slow growth rate, pinoid stems, defects in flower structures and reduced seed set. We observed a possible phenomenon of T-DNA suppression in the next generation of Atmit1 Atmit2 double homozygous mutant plants, correlating with an increased splicing of the AtMIT2 intron containing the T-DNA. Molecular analysis of gene expression markers for mitochondrial and oxidative stress showed that Atmit1 Atmit2 double homozygous mutant plants express a degree of mitochondrial perturbation. A RNA-Seq study was performed and we could identify more than 760 genes differentially expressed in Atmit1 Atmit2, including genes involved in iron transport, coumarin metabolism, and hormones metabolism, transport and signaling. Our data suggest that some of the phenotypes observed in Atmit1 Atmit2 double homozygous mutant plants are mediated by defects in auxin homeostasis.

The dynamic equilibrium of iron homeostasis has an important role in sustaining metabolic and neurological functions during human life. Iron excretion is modest and unregulated hence this overall equilibrium is tightly regulated in normal conditions by increasing deficient or limiting excessive iron assimilation. Here we focus on neural tissue overload, dyshomeostasis that is preceded by excessive assimilation, disturbances in internal homeostasis or both. Normal steps in iron homeostasis include its uptake across the apical membrane of the enterocytes in a mildly acidic duodenal milieu by the major importer of ferrous iron, Divalent Metal Transporter 1 (DMT1) (Nramp2/DCT1/SLC11A2, solute carrier family 11 member 2) [1, 2], responsible for the uptake of Non-Transferrin Bound Iron (NTBI) and divalent metals [3], passage through enterocytes bound to a chaperone and crossing the basal membrane via the only known cellular ferrous iron exporter, ferroportin [4] with the iron bound to transferrin (Tf) as it exits. Cells in peripheral tissues largely utilize circulating iron after uptake by receptor-mediated endocytosis of Tf-bound Iron [5]. Derangement of duodenal NTBI absorption of iron and heavy metals is influenced by systemic iron metabolism associated with inflammation that leads to iron accumulation into peripheral tissues and potential development of neurodegenerative diseases, involving distribution and fine regulation of DMT1 also in the central nervous system, where inflammatory-related acidosis influences DMT1 uptake, via its action as a proton cotransporter. Pharmacological strategies to inhibit NTBI transport selectively will be illustrated in relationship to protection, particularly neuroprotection, against iron overload associated with acidosis, inflammation, neuroinflammation and subsequent neurodegeneration.

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on gram-negative bacteria and can eliminate 99.99% of E. coli within 100 minutes at the minimal MIC concentration. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be disruption of Gram-negative cell membrane.

2023 was the hottest year ever recorded, global warming accelerates its rising, we witness a series of extreme weather events, more frequent and more intense, climate refugees, infrastructure harmed, forests burning, “meteorological tsunamis”. We failed to meet the main goals of the Kyoto protocol; we are very close to fail in meeting the Paris agreement’s slowing global warming goal. Greenhouse gases emissions are at rise and, even if completely halt, temperatures would keep rising, enhancing the global average. Carbon capture and storage technologies are being developed to counterbalance these emissions by removing such gases from the atmosphere and physically storing or transforming them into useful molecules for the society. In this work we prospect microorganisms that can serve as a platform for developing carbon capture technologies. We process samples from the seabed of Brainsfield Strait region, Antarctica, prospecting for an organism capable of fixing carbon dioxide without light (chemoautotrophic bacterias) and capable of enduring extreme conditions of pressure (100 bar) under 100% supercritical state carbon dioxide atmosphere (scCO2), conditions like those found in oil deposits, where the technology can be of particular use.

Cryonotothenioidea is the main group of fishes that thrive in the extremely cold Antarctic environment, thanks to the acquisition of peculiar morphological, physiological and molecular adaptations. We have previously disclosed that IgM, the main immunoglobulin isotype in teleosts, display typical cold-adapted features. Recently, we have analyzed the gene encoding the heavy chain constant region (CH) of the IgT isotype from the Antarctic teleost Trematomus bernacchii (family Nototheniidae), characterized by the near-complete deletion of the CH2 domain. Here, we aimed to track the loss of the CH2 domain along notothenioid phylogeny and to identify its ancestral origins. To this end, we obtained the IgT gene sequences from several species belonging to the Antarctic families Nototheniidae, Bathydraconidae and Artedidraconidae. All species display a CH2 remnant of variable size, encoded by a short Cτ2 exon, which retains functional splicing sites and therefore is included in the mature transcript. We also considered representative species from the three non-Antarctic families: Eleginopsioidea (Eleginops maclovinus), Pseudaphritioidea (Pseudaphritis urvillii) and Bovichtidae (Bovichtus diacanthus and Cottoperca gobio). Even though only E. maclovinus, the sister taxa of Cryonotothenioidea, shared the partial loss of Cτ2, the other non-Antarctic notothenioid species displayed early molecular signatures of this event. These results shed light on the evolutionary path that underlies the origins of this remarkable gene structural modification.

Abstract: Peptide pools composed of short amino acid sequences have proven to be versatile tools in various research areas and clinical applications. They are powerful tools for epitope mapping, immunotherapy, and vaccine development. Their importance lies in their ability to map complex protein structures, enabling a comprehensive understanding of immune responses and facilitating the identification of potential therapeutic agents. The application of peptide pools also extends to the field of personalized medicine, offering tailored solutions for diseases such as cancer and infectious diseases. Peptide pools are complex mixtures of immunostimulatory antigens primarily intended for T-cell stimulation. They are commercially available in many different compositions and variants. However, unlike other reagents that consist of only one or a few compounds, peptide pools are highly complex products with limited stability. This makes their quality control a major challenge. Quantitative peptide analysis usually requires sophisticated methods, in most cases isotope-labeled standards and reference materials. None of these are routinely available for these products. Synthesis and purification of all labeled peptides might be required. Usually, this approach would be prohibitively laborious and expensive. Therefore, an approach is needed to provide a practical and feasible method for quality control of peptide pools. With insufficient quality control, the use of such products could lead to incorrect experimental results, which would worsen the well-known reproducibility crisis in the biomedical sciences. Here we propose the use of ultra-high performance liquid chromatography (UHPLC) with two detectors, a standard UV detector (at 214 nm) for quantitative analysis and a high-resolution mass spectrometer (HRMS) for identity confirmation. To be cost-efficient and fast, quantification and identification are performed in one chromatographic run. An optimized protocol is shown, and different peak integration methods are compared and discussed. This work was performed using a peptide pool known as CEF, which consists of 32 peptides derived from cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza virus, ranging from 8 to 12 amino acids in length.

After screening nearly 1000 synthetic peptides, a synthetic peptide termed JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI) derived from the BoxA domain in Tob1 protein was found to activate both unfolded and folded proMMP-7. In addition, JAL-AK22 showed auto-proteolytic activity. Interestingly, the smaller derivative of JAL-AK22 termed JAL-TA9 (YKGSGFRMI) also possessed auto-proteolytic activity and cleaved 2 fragment peptides (MMP18-33 and MMP18-40) derived from the prodomain of proMMP-7 under physiological conditions. These proteolytic activities were inhibited by AEBSF, a serine protease inhibitor. Our results demonstrate that a small synthetic peptide consisting of only 9 amino acids has serine protease-like activity and activates proMMP-7 by cleaving the prodomain region. We thus propose calling small peptides possessing with protease-like activity Catalytides (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications.

Mn-promoted bulk iron catalysts with high specific surface area (82-211 m2.g-1) were synthesized by coprecipitation followed by drying under supercritical conditions. The catalysts were tested in the CO2 hydrogenation reaction. The Mn-promoted iron catalysts showed better textural properties than the bare Fe2O3 catalyst, allowing better dispersion of the active phase, easier reduction of iron oxide, better carburization of iron oxides and higher catalytic activity than the bare Fe2O3 catalyst. The best activity results were obtained by catalyst promotion with a very low amount of Mn (Mn/Fe ratio of 0.05). Upon steady-state conditions (T=340 ºC, total pressure of 20 bar and H2/CO2=3), this catalyst showed high CO2 conversion (44.2%) and selectivity to C2-C4 hydrocarbons (68%, olefin to paraffin ratio of 0.54), while the selectivity to C5+ hydrocarbons, CH4 and CO was about 3.2, 38.5 and 5%, respectively. A close correlation was found between catalyst textural properties and CO2 conversion. The most active MnFe-0.05 catalyst shows high stability during 72 h of reaction related to low amount of soft coke formation and catalyst activation through the formation of χ-Fe5C2 phase during the on-stream reaction.

In pigs, iron deficiency anemia (IDA) is the most prevalent deficiency disorder during the early postnatal period frequently developing into a critical illness. Meanwhile, in humans, only low-birth-weight infants, including premature infants are especially susceptible to developing IDA. In both human and pig neonates, the initial cause of IDA is low birth iron stores. In piglets this shortage of stored iron results mainly from genetic selection over the past few decades for large litter size and high birth weight. In consequence, pregnant sows cannot provide sufficient amount of iron to the increasing number of developing fetuses. Supplementation with iron is a common practice for the treatment of IDA in piglets. For decades, the preferred procedure for delivering iron supplements during early life stages has been through the intramuscular injection of large amount of iron dextran. However, this relatively simple therapy, which in general, efficiently corrects IDA, may generate toxic effects, and by inducing hepcidin expression, may decrease bioavailability of supplemental iron. New iron supplements are considered now with the aim to combine improvement of hematological status, blunting hepcidin expression, and minimizing toxicity of the administered iron. We propose that iron-deficient piglets constitute a convenient animal model for performing pre-clinical studies with iron supplements.

Dietary iron assimilation is critical for health and essential to prevent iron deficient states and related comorbidities, such as anemia. The bioavailability of iron is limited, while its absorption and metabolism are tightly controlled to keep body iron stores within a relatively narrow range. Genetic inactivation of the iron hormone hepcidin causes hereditary hemochromatosis, an endocrine disorder of iron overload characterized by chronic hyperabsorption of dietary iron, with deleterious clinical complications if untreated. The impact of high dietary iron intake and elevated body iron stores in the general population is not well understood. Herein, we summarize epidemiological data suggesting that high intake of heme iron, which is abundant in meat products, poses a risk factor for metabolic syndrome pathologies, cardiovascular diseases, and some cancers. We discuss clinical relevance and potential limitations of data from cohort studies, as well as the need to establish causality and elucidate molecular mechanisms.

Hereditary hemochromatosis (HH) is the main genetic cause of iron overload and is regarded as metal-related human toxicosis. HH may result from HFE and non-HFE gene mutations causing hepcidin deficiency or hepcidin resistance. The disorder has a high biochemical penetrance, but a low clinical prevalence. Unfortunately, the majority of patients with HH remain undiagnosed at their disease-curable stage. The main aim of HH therapy is to prevent iron overload in the early-phase disease and elimination of excess iron from the body by phlebotomy in its late stage. Raising global awareness of HH among health professionals, their training to pay attention to early HH signs and symptoms, and strict patient monitoring are critical management strategies for preventing treatment delays, upgrading its efficacy, and improving patient prognosis.

In eutrophic waters, such as Mikawa Bay, Japan, anoxic bottom water develops in summer. This causes sulfide release into seawater by sulfate reduction in the sediment, leading to environmental problems. The addition of iron to sediments is a method used to improve the sediment environment, which was devised from a natural phenomenon. However, this method has not yet been quantitatively evaluated. In this study, we aim to quantitatively evaluate the suppressive effect of iron on sulfide release. First, we develop a sediment model that focuses on S and Fe. We then attempted to reproduce the observations and experiments on sulfide dynamics using the model. Consequently, the proposed model was able to reproduce field sulfur and Fe dynamics in sediments. Additionally, the model described the characteristics of sulfide release considering the effects of additive iron materials. Finally, we conducted predictive calculations and quantitatively evaluated the effects of adding iron materials to the sediments in terms of sulfur and iron cycles.

The healing of osteochondral defects (OCD) resulting from injury, osteochondritis, or osteoarthritis in middle- and old-age individuals, bearing lesions in the cartilage and bone, pain, and loss of joint function, presents challenges to the clinical practitioners because of non-regenerative cartilage and the limitations of current therapies. Bioactive peptide-based osteochondral (OC) tissue regeneration is becoming more popular because it does not have the immunogenicity, misfolding, or denaturation problems associated with original proteins. Periodically, reviews are published on the regeneration of bone and cartilage; however, none of them address the simultaneous healing of these tissues in the complicated heterogeneous environment of the OC interface. As regulators of cell adhesion, proliferation, differentiation, angiogenesis, immunomodulation, and antibacterial activity, potential therapeutic strategies for OC defects utilizing bone and cartilage-specific peptides should be examined and investigated. Therefore, the main goal of this review is to study how they contribute to the healing of OC defects, either alone or in conjunction with other peptides and biomaterials.

Despite significant strides in prevention, diagnosis, and treatment, cardiovascular diseases remain the number one cause of mortality in the United States, with rates climbing at an alarming rate in the developing world. Targeted delivery of therapeutics to the heart has been a lofty goal to achieve with strategies ranging from direct intra-cardiac or intra-pericardial delivery, intra-coronary infusion, to adeno-associated viral vectors which have preference, if not complete cardio-selectivity, for cardiac tissue. Cell penetrating peptides (CPP) are 5-30 amino acid long peptides that are able to breach cell membrane barriers while carrying cargoes up to several times their size, in an intact functional form. Identified nearly three decades ago, the first of these CPPs came from the HIV coat protein transactivator of transcription. Although a highly efficient CPP, its clinical utility is limited by its robust ability to cross any cell membrane barrier, including crossing the blood-brain barrier and transducing neuronal tissue non-specifically. Several strategies have been utilized to identify cell or tissue specific CPPs, one of which is phage display. Using this latter technique, we identified a cardiomyocyte targeting peptide (CTP) more than a decade ago, a finding that has been corroborated by several independent labs across the world that have utilized CTP for myriad different purposes in pre-clinical animal models. The goal of this publication is to provide a comprehensive review of the identification, validation, and application of CTP, and outlining its potential in diagnostic and therapeutic applications especially in the field of targeted RNA interference.

Based on a new model of a possible origin of life, we establish an efficient and stable system undergoing structural reproduction, self-optimization and molecular evolution. This system is being formed under realistic conditions by the interaction of two cyclic processes, one of which offering vesicles as the structural environment, the other supplying peptides from a variety of amino acids as versatile building blocks. We demonstrate that structures growing in a combination of both cycles have the potential to support their own existence, to undergo chemical and structural evolution and to develop unpredicted functional properties. The key mechanism is the mutual stabilization of the peptides by the vesicles and of the vesicles by the peptides together with a constant production and selection of both. The development of the proposed system over time not only would represent one of the principles of life, but could also be a model for the formation of self-evolving structures ultimately leading to the first living cell. The experiment yields clear evidence on a vesicle-induced accumulation of membrane-interacting peptide which could be identified by liquid chromatography combined with high-resolution mass spectroscopy. We found that the selected peptide has an immediate effect on the vesicles, leading to i) reduced vesicle size, ii) increased vesicle membrane permeability, and iii) improved thermal vesicle stability.

Two Iron Age settlements, Tuzusai and Taldy Bulak 2 (ca. 500 BCE to 1 CE), located in Southeastern Kazakhstan on the Talgar alluvial fan north of the Tian Shan range, have yielded a small collection of bone, antler/horn, bronze, and stone artifacts with affinity to nomadic art of the first millennium BCE. Both settlements date within the period of late Saka culture. Two pieces have decorative ornamentations with zoomorphic imagery: a small carved fragment of a with carved images of a wing and an ear and a perforated bone disk with the carving of three birds’ heads. The other artifacts include objects associated with Saka weaponry or nomadic economy such as the two antler/horn psalia (cheek pieces) and a bronze amulet. A carnelian bead will also be described as an imported object. These special finds are found on the occupation floors of mud brick houses and pit houses of settlements, not in grave or burial contexts. The objects are placed in stratigraphic sequence in the settlement sites. Then the method for placing these objects within the chronological framework of “animal-style art” is through comparisons with similar objects found throughout Eurasia—a method used in Soviet and Post-Soviet archaeology. The results show that functional and stylistic elements of the six objects indicate that the Talgar settlements were part of a larger world-system of trade and communication along the early Silk Route(s).

The study of ecological connectivity is a global priority due to the important role it plays in the conservation of diversity. However, few studies in this context have focused on marine benthic ecosystems. To address this issue, the present work determines the ecological connectivity between two sub-Antarctic macrobenthic assemblages through assessment of the α-, β-, and functional diversity indices. Samples were collected using a van Veen grab at stations located in Bahia Inútil and Seno Almirantazgo. The ecological analysis was based on a total of 113 invertebrate taxa. The mean abundance values were lower in Bahia Inútil (888.9 ± 26.8 ind m-2) than in Seno Almirantazgo (1358.6 ± 43.4 ind m-2). While the mean α-diversity values showed significant differences between assemblages, β- and functional diversity indices presented no significant differences. These results indicate that, despite the distance (56 km) separating the two basins from each other, there is a high degree of connectivity at the functional level between the assemblages, due to the high number of shared species and their functional traits. The species most responsible for this observation were the polychaetes Capitela capitata and Aricidia (Acmira) finitima, as well as the bivalves Nucula pisum and Yoldiella sp. 1. In terms of functional biodiversity, species characterized as omnivorous and with lecithotrophic larval development were mostly responsible for connectivity between assemblages. These results suggest the importance of including β- and functional diversity indices as criteria in the future planning of marine protected areas for the maintenance of marine ecosystem integrity.

Pathogenic microorganisms can cause a range of infectious diseases and are often treated with antimicrobial agents. The rise of antimicrobial resistance caused by inappropriate use of these agents in various settings has become a global health threat. There is, therefore, a need to find new and effective agents to combat infections caused by resistant pathogens. Nanotechnology has seen significant growth and development in recent years and has a wide range of applications in various fields, including health, agriculture, and industry. This novel area offers the potential for the synthesis of nanoparticles (NPs) with antimicrobial activity, such as iron oxide nanoparticles (IONPs). The use of IONPs is a promising way to overcome antimicrobial resistance or pathogenicity because of their ability to interact with several biological molecules and to inhibit microbial growth. This review focuses on the most common green synthesis methods for producing IONPs using bacteria, fungi, plants, and organic waste, as well as the most common methods for the characterization of these IONPs. Finally, it summarizes their application as promising antibacterial, antifungal, antiparasitic, and antiviral agents.

Advances in nanomedicine bring the attention of researchers to the molecular targets which can play a major role in the development of novel therapeutic and diagnostic modalities for cancer management. The choice of a proper molecular target can decide on the efficacy of the treatment and endorse the personalized medicine approach. Gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled membrane receptor, well known to be overexpressed in numerous malignancies including pancreatic, prostate, breast, lung, colon, cervical and gastrointestinal cancers. Therefore, many research groups express a deep interest in targeting GRPR with their nanoformulations. A broad spectrum of the GRPR ligands has been described in the literature, which allows tuning of the properties of the final formulation, particularly in the field of the ligand affinity to the receptor and internalization possibilities. Hereby the recent advances in the field of applications of various nanoplatforms which are able to reach the GRPR expressing cells are reviewed.

AIUS (Atmospheric Infrared Ultraspectral Sounder) is an infrared occultation spectrometer onboard the Chinese GaoFen-5 satellite, which covers a spectral range of 2.4--13.3 μm (750--4100 cm-1) with a spectral resolution of about 0.02 cm-1. AIUS was designed to measure and to study chemical processes of ozone (O3) and other trace gases in the upper troposphere and stratosphere over Antarctic. In this study, the corresponding retrieval methodology is described. The comparison between AIUS measurements and simulated spectra illustrates that AIUS measurements agree well to the simulated spectra. To first evaluate the reliability of our retrieval algorithm, three retrieval O3 experiments are performed based on ACE-FTS observation spectra. A comparison between our retrieved profiles and the ACE-FTS official products shows that the relative difference of these three retrieval experiments is mostly within 10% between 20 km and 70 km. These retrieval experiments demonstrate that the retrieval algorithm described in this study work fine and reliable. Furthermore, O3, H2O and HCl profiles are retrieved from eight orbits of AIUS measurements and compared with the official AURA/MLS level-2 v4.2 profiles. Comparison experiments show that the relative difference is mostly within 10% (about 0.02 - 0.4 ppm) between 18 and 58 km for O3 retrieval, within 10% (0-0.5 ppm) between 15 and 80 km for H2O retrieval, and within 10% (about 0.1 ppb) between 30 and 60 km for HCl retrieval. There is a good agreement in the retrieved trace gas profiles obtained from AIUS and from coincident profiles from MLS.

Iron deficiency (ID) is by far the most common nutritional disorder in developing and developed countries. When left untreated, ID leads to anemia. Although the usual recommended treatment for iron deficiency anemia (IDA) is oral iron therapy with countless products, such therapy necessitates administration for &gt;3-6 months with questionable patient compliance since most oral iron products have an unpleasant metallic aftertaste and cause intestinal side effects. In addition, in certain gastrointestinal conditions, such as inflammatory bowel diseases or untreated gluten-sensitive enteropathy, oral iron therapy is contraindicated or unsuccessful. Intravenous iron is considered safe in adults, where adverse events are mild and easily managed. The experience with parenteral iron in children is much more limited and many pediatricians appear reluctant to use it because of uncorroborated fears of serious anaphylactic reactions. In the current article, we thoroughly review the available pediatric literature on the use of all commercially available parenteral iron products except ferumoxytol, which was recently removed from the market. We conclude that parenteral iron appears to be safe in children, it works faster than oral iron and the newer third-generation products allow replacement of the total iron deficit at a single setting.

Antibody-Drug Conjugates (ADCs) are a powerful therapeutic modality for cancer treatment. ADCs are multi-functional biologics in which a disease-targeting antibody is conjugated to an effector payload molecule through a linker. The success of currently used ADCs has been largely attributed to the development of linker systems which allow targeted release of cytocidal payload drugs inside cancer cells. Many lysosomal proteases are over-expressed in human cancers. They can effectively cleave a variety of peptide sequences, which can be exploited in the design of ADC linker systems. As a well-established linker, valine-citrulline-p-aminobenzyl carbamate (ValCitPABC) is used in many ADCs that are already approved or under preclinical and clinical development. Although ValCitPABC and related linkers are readily cleaved by cathepsins in the lysosome while remaining reasonably stable in human plasma, many studies have shown that they are susceptible to carboxylesterase 1C (Ces1C) in mouse and rat plasma, which hinders preclinical evaluation of the ADCs. Furthermore, neutropenia and thrombocytopenia, two of the most commonly observed dose-limiting adverse effects of ADCs, are believed to result from the premature hydrolysis of ValCitPABC by human neutrophil elastase. In addition to cathepsin-cleavable linkers, there is also growing interest in legumain-sensitive linkers for ADC development. Increasing plasma stability while maintaining lysosomal cleavability of ADC linkers is an objective of intensive current research. This review reports recent advances in the design and structure-activity relationship studies of various peptide/peptidomimetic linkers in this field.

The determination of the three-dimensional structure is a key step for the identification of new targets as well as the rational design of bioactive compounds. Herein, we report the synthesis and the structural elucidation of novel tetrameric macrocycles. Measurements were taken in solid and solution states with the help of X-ray scattering and NMR spectroscopy. The investigations made will help to find diverse applications for this new, promising compound class.

Oral ferric citrate hydrate (FCH) is effective for iron deficiency in hemodialysis patients.; however, it remains unclear how iron balance in the body affects iron absorption from the intestinal tract. This prospective, observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406), conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables on ΔFe2h and the secondary outcome was the description of the predictors of body iron balance. Generalized estimating equations (GEE) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and MCH decreased (-0.155, -0.242 to -0.068, p = 0.001; -2.574, -4.421 to -0.726, p = 0.006, respectively) in GEE. Hepcidin-25 increased when erythropoiesis-stimulating agent (ESA) decreased (-0.002, -0.002 to -0.001, p=0.000). FTN increased when RBC and ESA decreased (-0.466, -0.605 to -0.327, p=0.000; -0.002, -0.004 to -0.000, p=0.05, respectively. Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC-iron to FTN-iron, inhibiting iron absorption even with continued FCH intake.

Ghrelin and obestatin, two antagonist peptide hormones, are purportedly involved in stimulating appetite and controlling energy balance in humans. Serum ghrelin level is also associated with iron deficiency anemia (IDA), but no study has yet been made of the obestatin level in patients with IDA, even though both hormones are a single gene product. Therefore, the purpose of this investigation is to see whether there is a link between IDA and these two hormones among other hematological parameters in patients with IDA. To measure ghrelin and obestatin, human saliva and serum were collected from 30 women with IDA, aged 31.7 ± 10.7 years, and 30 control women, aged 30.2 ± 8.0 years, with repeated collection of samples over a period of 1 week and 1 month. Saliva and serum ghrelin levels were measured by ELISA. Serum hemoglobin, ferritin, hematocrit and total iron-binding capacity (TIBC) values were determined with an Olympus AU2700. Saliva and serum ghrelin and obestatin levels were significantly lower in the IDA group compared with controls; these levels increased slightly above baseline with iron treatment, but remained below the control values. Furthermore, and as expected, serum hemoglobin, ferritin, and hematocrit levels were significantly increased with iron treatment, while total iron-binding capacity decreased compared to baseline concentrations. The findings suggest that IDA might be linked to imbalance of circulating (serum) and non-circulating (saliva) ghrelin and obestatin levels. Decreased ghrelin and obestatin might destroy iron homeostasis through its effect on intestinal absorption. Measuring these hormone levels might be useful for monitoring the response to iron treatment. Also, serum and saliva levels for both hormones were well correlated. Thus, using saliva in place of serum for monitoring the two hormones should minimize inconvenience and patient discomfort.

Abstract: The aim of this study was to find out the incidence of anemia in pregnant women of Swat District; to analyze the iron variations and its dietary effects.Data were collected during the periods of January – September 2016. The study of samples comprised of 250 pregnant women in the different trimester. Blood sample from each woman was collected and full blood count (FBC) was conducted through Mindray BC-3000 plus hem analyzer for all pregnant individuals. Confirmed anemic cases were then examined for IDA with serum ferritin, serum iron, total iron binding capacity (TIBC) through Randox kit and serum transferrin saturation was estimated by formula (serum ferritin saturation =serum iron ×100/TIBC). The total number of participants in the first trimester were 50, among them 26 women were suffer from iron deficiency anemia (IDA) with 52% weightage of prevalence rate, (mean Hb concentration 9.602 ± 0.87 g/dl). The rates of IDA were 63.3%; ( mean Hb concentration 8.48 ± 1.24 g/dl) and 54%; ( mean Hb concentration 9.18 ± 1.28 g/dl), among 150 and 50 participants in the second and third trimester, respectively. A significant correlation was found between serum ferritin and Hb, serum ferritin against MCV and serum ferritin against MCH. The high prevalence of anemia was found 78.2% in the age group from 26-30 followed by 78.2% in the age group 36-40 years compared to those of other age groups in the second trimester. In this study the prevalence of IDA in third trimester is lower compared to first and second trimester.

Inflammation is an underlying problem for many disease states and has been implicated in iron deficiency (ID). This study aimed to determine whether iron status is improved by epigallocate-chin-3-gallate (EGCG) through reducing inflammation. Thirty-two male Sprague-Dawley rats were randomly divided into four groups (n = 8 each): positive controls, negative controls, lipo-polysaccharide (LPS, 0.5 mg/kg body weight), and LPS + EGCG (LPS plus 600 mg EGCG/kg diet). Iron status, hepcidin, C - reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were measured. There were no differences in treatment groups compared with control in CRP, hepcidin, and liver iron concentrations. Serum iron concentrations were significantly lower in the LPS (p=0.02) and the LPS+EGCG (p=0.01) than in the positive control group. Compared to the positive control group, spleen iron concentrations were significantly lower in the negative con-trol (p<0.001) but not with both LPS groups. SAA concentrations were significantly lower in LPS + EGCG group compared to LPS alone group. IL-6 concentrations were significantly higher in LPS+EGCG (p= 0.004) than in any of the three groups. EGCG reduced SAA concentrations but did not affect hepcidin or improve serum iron concentration or other iron markers.

We present a simple strategy to generate a family of carbon dot/iron oxide nanoparticles (C/Fe-NPs) that relies on the thermal decomposition of iron (III) acetylacetonate in the presence of a highly fluorescent carbon-rich precursor, while polyethylene glycol serves as the passivation agent. By varying the molar ratio of the reactants, a series of C/Fe-NPs have been synthesized with tuneable elemental composition in terms of C, H, O, N, Fe. The quantum yield is enhanced from 6% to 9% as the carbon content increases from 27% to 36%, while the room temperature saturation magnetization is improved from 4.1 emu/g to 17.7 emu/g as the iron content is enriched from 17 to 31%. In addition, the C/Fe-NPs show excellent antimicrobial properties, minimal cytotoxicity and demonstrate promising bioimaging capabilities, thus showing great potential for the development of advanced diagnostic tools.

Two billion people worldwide suffer from anemia with reproductive-age women being disproportionately affected. Iron plays a crucial role in cellular function and impacts cognition, physical function, and quality of life. Iron deficiency (ID) and iron deficiency anemia (IDA) are associated with adverse effects on pregnancy and fetal development. Oral iron supplementation has been the standard treatment for IDA for decades often producing sub-optimal outcomes. Many babies are still being born with ID and suffer adverse sequelae due to inadequate iron levels in the mothers. Is it time to consider broad scale-up of parenteral iron as a new standard of care?

The study of biologically active substances from natural sources shows the prospect of obtaining a new type of antimicrobial agents, highly effective against pathogenic microorganisms and non-toxic to humans. Our study reveals for the first time that Cornu aspersum mucus has the potential to act as a source of antibacterial agents against bacterial pathogens such as Bacillus cereus 1085, Propionibacterium acnes 1897, Salmonella enterica 8691, Enterococcus faecalis 3915, and Enterococcus faecium 8754. Both mucus fractions with MW<20 kDa and MW>20 kDa showed antimicrobial activity and antioxidant properties that’s why they can be turned into an alternative agent to expensive synthetic antibacterial compounds. Using de novo sequencing 16 novel peptides with potential antibacterial activity were identified by in a fraction with MW<20 kDa. The results of electrophoretic and proteomic analysis of mucus fraction with MW >20 kDa presented proteins with potential antibacterial activity highly homologous to hemocyanins, mucus protein Aspernin, lectins, L-amino acid oxidase-like protein, and mucins (mucin-5AC, mucin-5B, mucin-2 and mucin-17). Thanks to the synergistic action of the bioactive components, the mucus fraction with MW > 20 kDa in low concentrations per 8–2 µg/mL showed promising antimicrobial activity against the tested bacteria, comparable to Vancomycin and without unwanted cytotoxic effects against non-target cells. Additionally, C. aspersum mucus fractions were found to have a positive effect on eukaryotic organisms by reducing the levels of intracellular oxidative damage and increasing the antioxidant capacity of the cell. These findings could serve as a basis for the development of a potent non-cytotoxic antibacterial agent to replace conventional antibiotics and avoid the development of antibiotic resistance.

The cytosolic PNGase (peptide:N-glycanase; Png1 in yeast; NGLY1/Ngly1 in human/mice), also known as peptide-N4-(N-acetyl-beta-glucosaminyl)-asparagine ami-dase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-D-glucosaminyl) asparagine residue into N-acetyl-β-D-glucosaminylamine and a peptide containing an aspartate residue. This enzyme (NGLY1) plays essential roles in clearance of misfolded or unassembled gly-coproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive hu-man genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP path-way, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review indeed uncovers the detailed NGLY1’s structure and its im-portant roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.

Description of a novel bovine antimicrobial peptide and its antimicrobial spectrum. RNA isolation and RT-PCR were done from various tissues. DCD peptide was synthesized, and antimicrobial activity was analyzed. Bovine dermcidin gene contains five exons intermittent by 4 introns. Bovine DCD-mRNA was 398 bp with ORF 336 bp. Bovine DCD was expressed in skin and blood. Analysis of the amino acid compositions revealed that cysteine was repeated 6 times indicating the presence of 3 disulfide bonds that play role in the peptide stability. Staphylococcus epidermidis, Streptococcus bovis, and Enterococcus faecalis were affected by Bovine DCD peptide. Highest antimicrobial effect was at 50 and 100 µg/ml. The effect on Escherichia coli and Candida albicans was slightly low. In all bacteria, Bovine DCD peptide activity did not affect by varying pH values, but in Staphylococcus aureus, the activity was affected greatly at pH 4.5 and 5.5. The optimum salt concentrations were 100 and 50 mM NaCl with all bacterial strains and E. coli, respectively. In case of C. albicans, the antimicrobial activity of Bovine DCD peptide decreased with increasing the pH value regardless the NaCl concentration. The pH 6.5 of the sweat buffer was the optimum for the Bovine DCD peptide activity.

Thalassemia treatment still relies on supportive care, including mainly blood transfusion and iron chelation therapy. Iron chelation therapy is considered the main responsible factor for the marked improvement in survival of thalassemic patients. Hemosiderosis should be prevented with appropriate chelation therapy from early childhood, timely dose adjustment according to changing body weight, as well as close monitoring of organ iron overload. Three iron chelators are currently available and the choice of appropriate chelator or their combination in pediatric population is individualized, depending on iron overload in target organs, patient age, adverse events and compliance issues, due to the limitations in their administration.

Iron (Fe) deficiency specifically is the most common nutritional disorder due to insufficient absorbable Fe. Biofortification is a process of enriching the nutrient content of staple crops and is considered as a sustainable and cost-effective strategy to address micronutrient deficiency problems especially in the less developed countries. Chickpea (Cicer arietinum L.) is a staple food in many developing countries worldwide and is an excellent source of micronutrients. Biofortification of chickpea is a possible solution to address Fe deficiency problem. Chickpea biofortification experiment was conducted under field conditions to evaluate the effects of different doses of Fe fertilizer (0 kg ha-1,10 kg ha-1 and 30 kg ha-1 of Fe-EDDHA) on Fe content in seeds of 18 chickpea cultivars. The experiment was designed as a factorial combination of 18 chickpea cultivars and 3 different doses in a randomized complete block design with 4 replications at two locations in Saskatchewan in 2015 and 2016. Fe concentration in seeds across 18 different chickpea cultivars increased with Fe fertilization. Fe concentration in X05TH20-2 and CDC Frontier cultivars increased from 57 ppm to 59 ppm and 56 ppm to 58 ppm, respectively, after adding Fe fertilizer in both location in 2015 and 2016.

Summary: PURPOSE. Development of a drainless energy-saving technology for the processing of high-moisture iron-containing sludge from metallurgical production. RESEARCH METHOD. The regularities of the combined process of chemical dehydration of high-moisture iron-containing sludge by powdered waste of lime and dolomite, hardening and agglomeration by pressing in a single technological cycle on the developed experimental plant were studied. In the course of laboratory studies, the temperature of the mass, the rate of dehydration, the chemical composition of the mixtures, the appearance of the resulting briquettes, the weight loss during agglomeration-humidity of the mixtures, and mechanical strength of the briquettes were measured. RESULTS. New patterns have been established that have made it possible to develop a nonfiring method for producing iron-containing materials and self-healing briquettes. The essence of his method, which is one of the main provisions of scientific novel provisions, is to combine dehydration and self-hardening of the mixture with the process of shaping by applying external pressure to the hardening mixture in molds to obtain agglomerated material in the form of briquettes in a single technological cycle. The proposed technology does not require drying or firing, and a set of strength properties occurs as the material is cooled in air during the day. A new energy-efficient and drainless method for the production of iron-containing briquettes has been developed, which combines the processes of chemical dehydration and agglomeration in one technological cycle. CONCLUSION. The proposed project and technology will allow organization of production for the processing of high-moisture iron-containing sludge and the production a complex iron-containing material as a secondary metal-containing raw material for metallurgical plants for the production of steel and rolled metal. and dolomite dust from dry gas cleaning as dehydrating and binding materials, as well as screening of coke and coal as a reducing agents. The proposed technology also solves the problems of environmental pollution and land acquisition for the storage of production waste.

Iron powders having average particle sizes of ~40µm are mechanically mixed thoroughly with aluminum powders ranging from 1 to 10 in wt.% with an average particle size of ~10µm. Two different powder metallurgical techniques cold and hot pressing are used to study the effect of the additive element powder on the mechanical properties, wear properties and the microstructure of the iron based alloys. The hot pressing technique was performed at a temperature up to 500°C at 445.6 MPa. The cold pressing technique was performed at 909 MPa in room temperature. By increasing the Al content to 10 wt. % in the base Fe-based matrix, the hardness was decreased from 780 to 690 MPa and the radial strength was decreased from 380 to 202 MPa with reductions of 11.5% and 40%, respectively. Improvement of the wear resistance with the increase addition of the Al powder to the Fe matrix up to 5 times was achieved compared to the alloy without Al addition for different wear parameters namely; wear time and sliding speed.

As belonging to one of the most isolated continents on our planet, the microbial composition of different environments in Antarctica could hold a plethora of undiscovered species with potential for biotechnological applications. This manuscript delineates our discoveries after an expedition to the Bulgarian Antarctic Base "St. Kliment Ohridski" situated on Livingston Island, Antarctica. Amplicon-based metagenomics targeting the 16S rRNA genes and ITS2 region were employed to assess the metagenomes of the bacterial, fungal and archaeal communities across diverse sites within and proximal to the research station. The predominant bacterial assemblages identified included Oxyphotobacteria, Bacteroidia, Gammaprotobacteria and Alphaprotobacteria. A substantial proportion of cyanobacteria reads were attributed to a singular uncultured taxon within the family Leptolyngbyaceae. The bacterial profile of a lagoon near the base exhibited indications of penguin activity, characterized by a higher abundance of Clostridia, similar to lithotelm samples from Hannah Pt. Although most fungal reads in the samples could not be identified at the species level, noteworthy genera, namely Betamyces and Tetracladium, were identified. Archaeal abundance was negligible, with prevalent groups including Woesearchaeales, Nitrosarchaeum, Candidatus Nitrosopumilus and Marine Group II.

OBJECTIVES: To assess the predictive value of serum trypsin and Trypsinogen Activation Peptide (TAP) for the severity of AP by means of a single center cohort study as well as a systematic review of the current literature. METHODS: The literature search was conducted using Medline (PubMed), EMBASE and the Cochrane Central Register. A total of 142 patients with acute pancreatitis (AP) were included in the cohort study and parameters of the revised Atlanta criteria of 2012 and the APACHE II were assessed. RESULTS: The review showed promising results for the predictive value of serum trypsinogen-2, but conflicting results for serum TAP and trypsin. In the cohort study, patients were observed for 4 days after diagnosis of AP: 9 patients had severe AP, 35 patients had moderate AP and 81 patients had mild AP. The ratio of the geometric mean of severe vs mild AP for trypsin was 0.72 (95% CI: 0.51-1.00), p=0.053 and for TAP 0.74 (95% CI: 0.54-1.01), p=0.055 respectively. CONCLUSION: The cohort study showed an inverse correlation of serum levels of TAP and trypsin with severity of AP. Serum TAP and trypsin have an inferior predictive value of severity of AP compared to the clinical APACHE II score.

We introduced a novel biotin-binding peptide for sensing biotin, biotinylated proteins, and nu-cleotides. From a 15-mer library displayed on the RNA coliphage Qβ, a 15-amino acid long peptide (HGHGWQIPVWPWGQG) hereby referred to as nanotag was identified to selectively bind biotin. The targets selection was achieved through panning with elution by infection. The selected peptide was tested as a transducer for an immunogenic epitope of the foot-and-mouth disease virus (FMDV) on Qβ phage platform separated by a linker. The biotin-tag showed no significant in-fluence on the affinity of the epitope to its cognate antibody (SD6). The nanotag bound biotin selectively when fused either to the C- or N-terminus of the epitope. The epitope would not bind or recognize SD6 while positioned at the N-terminus of the nanotag. Additionally, the biotin com-peted linearly with the SD6 antibody in a competitive ELISA. Competition assays using the se-lected recombinant phage itself as a probe, or transducer, enable the operationalization of this technology as a biosensor toolkit to sense and quantify SD6 analyte. Herein, the published Strep II nanotag (DVEWLDERVPLVET) was used as a control and has similar functionalities to our pro-posed novel biotin-tag thereby providing a new platform for developing devices for diagnostic purposes.

Hepcidin-25 was identified as the main iron regulator in the human body by binding to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II)-binding site known as ATCUN (amino terminal Cu(II)- and Ni(II)- binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the formed complex of hepcidin-25 with copper could reveal insights into its biological role. The present work is mainly focused on the study of the metal-bound form of hepcidin-25, which could be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25, which was achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandem mass spectrometry MS/MS, high resolution mass spectrometry HRMS) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a 3D model of hepcidin-25 with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or reference material comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.

Byers Peninsula is considered one of the largest ice-free areas in Maritime Antarctica. Since 2006, the Spanish Polar Program has taken part in a large number of environmental studies involving effects of climate changes in lives cycles, limnology and microbiology. Soils from maritime Antarctica are generally weakly developed and have chemical, physical and morphological characteristics strongly influenced by the parent material. However, biological activity during the short Antarctic summer promotes intense transference of nutrients and organic matter in areas occupied by different species of birds and marine mammals. To mapping and monitoring those areas with high biological occupation, could be very useful to have models of edaphic properties prepared from satellite images. In this approach, Deep Learning and Linear Regression models of soil properties and spectral indexes as explicative variables were performed. We training models of soil properties closely related to biological activity such as Dissolved Organic Carbon (DOC) and the iron fraction associated with organic matter (Fe). We tested the best approach to model the spatial distribution of DOC, Fe and pH by training models of Linear Regression and Deep Learning over Sentinel2 and WorldView2 images. The most robust models were used to track possible areas with ornithogenic soils as well as areas of the Byers Peninsula that could support the highest biological development.

The IgM and IgT classes were previously identified and characterized in the Antarctic teleost Trematomus bernacchii, a species belonging to the Perciform suborder Notothenoidei. Herein we characterized the gene encoding the polymeric immunoglobulin receptor (pIgR) in the same species and compared it to pIgR of multiple teleost species belonging to five perciform sub-orders, including 11 Antarctic and one non-Antarctic (Cottoperca gobio) notothenioid species, the latter living in less cold periantarctic sea. Antarctic pIgR genes displayed particularly long in-trons marked by sites of transposable elements and transcription factors. Furthermore, analysis of T. bernacchii pIgR cDNA unveiled multiple amino acid substitutions unique to Antarctic species, all introducing adaptive features, including N-glycosylation sequons. Interestingly, C. gobio shared most features with the other perciforms rather than with the cold adapted relatives. T. bernacchii pIgR transcripts were predominantly expressed in mucosal tissues, as indicated by q-PCR and in situ hybridization analysis. These results suggest that in cold adapted species pIgR preserved its fundamental role in mucosal immune defense, although remarkable gene structure modifications occurred.

The nucleation of voids in alpha iron and the influence of carbon were investigated through a combination of rate theory and nucleation theory calculations. The steady rates of void nucleation exhibit high sensitivity to carbon. Even a seemingly negligible carbon concentration, as low as a few atomic parts per million (appm), can dramatically reduce the nucleation rates and narrow the temperature window for nucleation. This study highlights the challenges in certifying and qualifying nuclear materials for use in reactor environments. It emphasizes the necessity for precise control of impurity levels during materials processing and stringent requirements for irradiation testing, which are susceptible to contamination. Furthermore, the study provides an explanation for the significant data scattering observed in void swelling behaviors as reported in the literature.

Iron deficiency in the fetal and neonatal period (perinatal iron deficiency) bodes poorly to neuro-development. Given its common occurrence and the negative impact on brain development, a screening and treatment strategy that is focused on optimizing brain development in perinatal iron deficiency is necessary. Pediatric societies currently recommend a universal iron supple-mentation strategy for full-term and preterm infants that does not consider individual variation in the body iron status and could lead to under-treatment or over-treatment. Moreover, the focus is on hematological normalcy and not optimal brain development. Several serum iron indices and hematological parameters in the perinatal period are associated with risk of abnormal neurodevelopment, suggesting their potential use as biomarkers for screening and monitoring treatment in infants at risk for perinatal iron deficiency. A biomarker-based screening and treatment strategy that is focused on optimizing brain development will likely improve outcome in perinatal iron deficiency.

Additive Manufacturing and nanotechnology have been used as basic tools for the manufacture of nanostructured parts with magnetic properties to expand the variety of applications in additive processes by tank photopolymerization. Magnetic cobalt ferrite (CoFe2O4) and barium ferrite (BaFe12O19) nanoparticles with the size distribution of average value DTEM of 12 ± 2.95 nm and 37 ± 12.78 nm, respectively were generat-ed by hydroxide precipitation method. The dispersion of the nanoparticles on commercial resins (Anycubic Green and IRIX White resin) was obtained by mechanochemical reactions carried out in an agate mortar for 20 minutes, at room temperature and with limited exposure to light. The product of each reaction was placed in amber vials, also being kept in a box, to avoid contact with light. The photopolymerization process was carried out only at low concentrations (w/w % nanoparticles/resin) since, at high concentrations, there is no for-mation of pieces due to the high refractive index of ferrites. Raman shift spectroscopy of the final pieces showed that they contain the magnetic nanoparticles, with no apparent chemical changes. The EPR results of the pieces maintain the magnetic properties and apparently, they are not modified during the photopolymer-ization. Although significant differences were found in the dispersion process of the nanoparticles in each piece, we determined that the photopolymerization did not influence the structure and superparamagnetic behavior of ferrite nanoparticles during processing, and the magnetic properties were successfully transferred to the final 3D-printed magnetic obtained piece.

Background: Iron chelation medications (desferoxamine, desferasirox, desferiprone) are used to manage iron overload. These medications are partially excreted via the kidneys, desferoxamine and desferiprone excretes primarily in the urine, and desferasirox had about 8% excreted in the urine. Their use in severe kidney disease and dialysis patients is caution as “avoided” concerning adverse effects; however, there are reports safe use. This manuscript reviews the literature in this population. Data Sources: Pubmed: desferasirox, deferiprone, deferoxamine, kidney disease, ESKD, Dialysis. Case reports and case series that described experiences with using iron chelation medications in ESKD patients are included. Data also gathered from reading-related sources. Results: This is a review of desferoxamine, desferasirox, and deferiprone use in kidney disease from 1976 to the present time. Table 1 provides a summary of findings. These are mostly reports and brief descriptions of the experiences used in severe kidney disease and dialysis, but lack of randomized control trials and small number of participants. Conclusions: Iron chelation medications are important for treating iron overload but concerns with adverse effects. Due to limited medications available to treat iron overload in patients with severe kidney disease, their safe use has been reporting in the literature. This is an area that warrants further research.

Introduction: In the recent years alternate day dosing has been recommended in iron deficieny treatment. The aim of this study is to compare the efficacy and side effects of oral iron treatments given daily 1x1, alternate day 1x1 and 2x1 alternate day dosing in iron deficieny anemia patients. Methods: A total of 52 patients with a diagnosis of iron deficiency anemia with serum ferritin level of 25 µg/L or less were included in this retrospective study. Statistical analyzes were done with SPSS V.25. Results: The patients included in our study were between the ages of 18-51. All of the patients included in the study were female. A statistically significant increase was found between 0-14 days(p<0.001), 14-28 days(p<0.001) and 0-28 days(p<0.001) hemoglobin values in all patients. There was no statistically significant difference between 0-14 days (p=0.397) and 0-28 days(p=0.310) ferritin values in all patients. A statistically significant difference was found between 14-28 days(p<0.001) ferritin values. When the rate of change of hemoglobin and ferritin values between the groups was compared and no statistically significant difference was observed between the groups. The rate of change of ferritin values for 14-28 days was significant (p=0.012). There was no significant difference in the frequency of symptoms in the 14th day and 28th day controls for each group (p>0.05). The incidence of metallic taste and bloating symptoms was found to be statistically significant in the third control in the group with 2x1 drug use alternate day (p=0.094). Discussion: The only difference in efficacy was observed in ferritin values between 14th and 28th days. The increase in ferritin values was higher in the group that used 1x1 oral iron every day. However, since no difference was observed between the groups in terms of ferritin and hemoglobin values on days 0 and 28, all three groups were considered equally efficient. Side effects were mainly gastrointestinal side effects. Since the group that received 2x1 oral treatment alternate day had a statistically significantly higher rate of side effects, the patients’ treatment tolerance will be lower compared to the other groups. In conlusion, there is no difference in efficacy and side effects between the patient groups receiving 1x1 daily and 1x1 alternate day oral iron therapy, so 1x1 use alternate day is the most appropriate treatment method for oral iron therapy in terms of patient tolerance, adherence to treatment and pharmacoeconomics.

Legumes are important sources of nitrogen and, therefore, the nitrogen fixing ability of the legume-rhizobia symbiosis has great potential to improve crop yields or reduce nitrogen fertilizer use. Unfortunately, legumes face serious and increasing threats of both biotic and abiotic stresses among which Fe-deficiency has been increased from past years. Fe nutrient deficiency limits pulse production and nitrogen fixation by specifically affecting any one of the four phases of legume-rhizobium symbiosis. Although Fe in soil is often present in adequate quantities, it is mainly present in insoluble Fe-(III) precipitates, limiting its uptake and utilization. The present review has focused on the iron nutrition and deficiency and probable uptake, transport and metabolism in legumes.

Aβ peptides are known to bind neural plasma membranes in a process leading to the deposit of Aβ-enriched plaques. These extracellular structures are characteristic of Alzheimer’s disease, the major cause of late-age dementia. The mechanisms of Aβ plaque formation and deposition are far from being understood. A vast amount of literature describes the efforts to analyze those mechanisms, using a variety of tools. The present review focuses on biophysical studies, mostly carried out with model membranes, or with computational tools. The review starts by describing basic physical aspects of lipid phases, and commonly used model membranes (monolayers and bilayers). This is followed by a discussion of biophysical techniques applied to these systems, mainly but not exclusively Langmuir monolayers, isothermal calorimetry, density-gradient ultracentrifugation, and molecular dynamics. The methodological section is followed by the core of the review, a summary of important results obtained with each technique. The last section is devoted to an overall reflection and an effort in understanding Aβ-bilayer binding. Concepts such as Aβ peptide membrane binding, adsorption, and insertion are defined and differentiated. The roles of membrane lipid order, nanodomain formation, and electrostatic forces in Aβ-membrane interaction are separately identified and discussed.

Myocardial infarction (MI) remains the leading cause of death in the western world. Although medical advancements have been made in interventional revascularization technologies, a large percentage of patients are not candidates for them due to co-morbidities or lack of local resources. Thus, there remains a need for the development of novel non-invasive strategies to treat MI. Approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been shown to be effective in animal models but not in humans likely due to its short half-life and systemic toxicity. We previously showed that a small peptide (PR1P) we developed stabilizes VEGF in its active dimer state, increases VEGF binding to its receptors and potentiates VEGF activity. Here we show that systemic PR1P treatment targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium following left coronary artery surgery in mice and rats. Targeted VEGF upregulation led to augmentation of heart function at two weeks following surgery. We conclude that PR1P is a potential candidate therapeutic for MI.

Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsis. Methods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery. Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients. Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.

Keywords: iron deficiency anemia; IDA; anemia; knowledge; awareness.

Neuronal lesions in Parkinson’s disease (PD) are commonly associated with α-synuclein (α-Syn)-induced cell damage that are present both in the central and peripheral nervous systems of patients, with the enteric nervous system also being especially vulnerable. Here we bring together evidence that the development and presence of PD depends on specific sets of interlinking factors that include neuro-inflammation, systemic inflammation, α-Syn-induced cell damage, vascular dysfunction, iron dysregulation, gut and periodontal dysbiosis. We argue that there is significant evidence that bacterial inflammagens fuel this systemic inflammation, and might be central to the development of PD. We also discuss the processes whereby lipopolysaccharides may be involved in causing nucleation of proteins, including of α-Syn. Lastly, we review evidence that pre-and probiotics, as well as antibiotics and faecal transplant treatment might be valuable treatments in PD. A most important consideration, however, is that these therapeutic options need to be validated and tested in randomized controlled clinical trials. However, targeting underlying mechanisms of PD, including gut dysbiosis and iron toxicity, have potentially opened up possibilities of a wide variety of novel treatments which may relieve the characteristic non-motor deficits of PD, and may even slow the progression and/or accompanying gut-related conditions of the disease.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library containing a total of 24,624 pentapeptides and screened the mixture-based library samples using a 55 °C warm-water tail-withdrawal assay. Using this phenotypic screening approach, we deconvoluted the mixture-based samples to identify a novel cyclic peptide Tyr-[D-Lys-Dap(Ant)-Thr-Gly] (CycloAnt), which produced dose- and time-dependent antinociception with an ED50 (and 95% confidence interval) of 0.70 (0.52-0.97) mg/kg i.p. mediated by the mu-opioid receptor (MOR). Additionally, higher doses (≥ 3 mg/kg, i.p.) of CycloAnt antagonized delta-opioid receptors (DOR) at least 3 hours. Pharmacological characterization of CycloAnt showed the cyclic peptide did not reduce breathing rate in mice at doses up to 15 times the analgesic ED50 value, and dramatically less hyperlocomotion than the MOR agonist, morphine. While chronic administration of CycloAnt resulted in antinociceptive tolerance, it was without opioid-induced hyperalgesia and significantly reduced signs of naloxone-precipitated withdrawal suggestive of reduced physical dependence as compared to morphine. Collectively, the results suggest this dual MOR/DOR multifunctional ligand is an excellent lead for the development of peptide-based safer analgesics.

For more than twenty years chemists use peptidic organocatalysts to transfer acyl groups onto alcohols. The goal was and still is the increase of selectivity towards the substrate of choice. One carefully designed example is a highly enantioselective tetrapeptide organocatalyst for the kinetic resolution of trans-cycloalkane-1,2-diols. Until now, the intermediate responsible for the acyl transfer of this tetrapeptide has never been directly observed. It was proposed computationally that a π-methylhistidine moiety is acylated as an intermediate step in the catalytic cycle. In this study we set out to investigate whether we can detect and characterize this key intermediate using NMR-spectroscopy and mass spectrometry. Different mass spectrometric experiments using a nano-ElectroSpray Ionization (ESI) source and tandem MS-techniques allowed the identification of tetrapeptide acylium ions using different acylation reagents. The complexes of trans-cyclohexane-1,2-diols with the tetrapeptide were also detected. Additionally, we were able to detect acylated tetrapeptides in solution using NMR-spectroscopy and monitor the acetylation reaction of a trans-cyclohexane-1,2-diol. These findings are important steps towards the understanding of this organocatalyst and its high enantioselectivity.

Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide specific ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon resonance (SPR) analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide and a complement activating peptide were used to induce selective depletion of ACPA producing B cells. Results: KD values of affinity purified ACPA IgGs varies between 10-6-10-8 M and inversely correlate with disease activity. Based on their cross-reaction with citrulline-peptides we designed a novel multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two-two copies, separated with a short, neutral spacer. This peptide detects antibodies in RA sera with 66 % sensitivity and 98 % specificity in ELISA and is recognized by 90% of RA sera, while none of the healthy samples in SPR. When coupled to nanoparticles, the multi-epitope peptide specifically targets and depletes ACPA producing B cells ex vivo. Conclusions: The unique multi-epitope peptide designed on the basis of ACPA cross-reactivity might be suitable to develop better diagnostics and novel therapies for RA.

BMAP-27 peptide known to exert cytotoxic effects against cancer cells by membrane integrity disruption. In the current investigation, we aimed to study the role of the BMAP-27 peptide in reducing colon cancer cell proliferation and inducing apoptosis. This study utilized both primary and metastatic colon cancer cell lines (SW480 and SW620). Proliferation was measured using CCK-8, and cellular damage was analyzed by lactate dehydrogenase assay. The study assessed apoptosis, cell cycle, and proliferation by measuring the expression of CASPASE3, BAX, BCL-2, TP53, CDK-6, PCNA, Wnt11, AXIN1, and CTNNB1. Additionally, in-silico studies were conducted to determine the binding affinities of BMAP-27 with APC and β-catenin proteins. BMAP-27 peptide reduced colon cancer cell proliferation, upregulated CASPASE3, BAX, TP53, AXIN1 expression, and downregulated BCL-2, CDK-6, PCNA, WNT11, CTNNB1 in both colon cancer cell lines, however, demonstrated higher activity in primary than metastatic colon cancer cells. The molecular dynamic simulation revealed substantial binding affinity of the peptide to adenomatous polyposis coli and β-catenin proteins.BMAP-27 peptide effectively inhibited the proliferation and enhanced apoptosis in the primary than in metastatic colon cancer cells. In-silico findings suggest that BMAP-27 exhibits a strong binding affinity with APC and β-catenin, highlighting its potential role as an anti-colon cancer agent.

The development of dosimetry and studies in peptide receptor radionuclide therapy (PRRT) over these two last decades are reviewed. Differences in kidney and bone marrow toxicity reported between ⁹⁰Y, ¹⁷⁷Lu and external beam radiotherapy (EBRT) are discussed with regards to the physical properties of these beta emitter radionuclides. The impact of these properties on the response to small and large tumors is also considered. Capacities of the imaging modalities to assess the dosimetry to target tissues are evaluated. Studies published in the last two years that confirm a red marrow uptake in ¹⁷⁷Lu-DOTATATE therapy, as already observed 20 years ago in ⁸⁶Y-DOTATOC PET studies, are commented and analyzed in the light of the recent knowledges in transferrin transport mechanism. The review enlightens the importance i) of using state of the art imaging modalities, ii) of individualizing the activity to be injected with regards to the huge tissue uptake variability observed between patients, iii) of challenging the currently used but inappropriate blood based red marrow dosimetry and iv) of considering individually tandem therapy. Last, a smart individually optimized tandem therapy taking benefit of the bi-orthogonal toxicity-response pattern of ¹⁷⁷Lu-DOTATATE and of ⁹⁰Y-DOTATOC is proposed.

Mineral extraction is one of the most important for the economies of different countries, and Brazil is one of the world's primary iron ore producers. Unfortunately, the dams are still the main problem, mainly in Minas Gerais, especially after the Fundão Dam rupture happened in 2015. Additionally, there is still a massive presence of buildings produced on earth throughout the Minas Gerais mining region, built from the 18th century to today. Investigating the potential of IOT to be incorporated into traditional earthen construction techniques in regions affected by dam ruptures presents a relevant and innovative research approach. In addition, the local reuse of these sediments should be the priority. Thus, the main objective of this work was to collect, characterize, and analyze the possibilities of application of these tailings to produce RE. XRD, XRF, granulometry, porosity, specific density, toxicity, and MEV/EDS were performed on the samples collected at three points. To analyze the soil-IOT compatibility, representative mixtures of RE were produced, and the specific mass, compaction, and compressive strength were performed. It was observed that the IoT samples have a high silica content and that the mixtures of IOT-soil, even without cement, reached compressive strength values above the current international standards.

Our investigations show that electrochemical corrosion of copper is faster than electrochemical corrosion of aluminium at temperatures below 100oC. Literature data analysis shows that the Al atoms diffuse faster than the Cu atoms at temperatures higher than 475oC, Al rich intermetallic compounds (IMCs) are formed faster in the Cu-Al system, and the Kirkendall plane shifts toward Al side. Electrochemical corrosion occurs due to electric current and due to diffusion. An electronic devise working time, for example, depends on initial copper cover thickness on aluminium wire, connected to the electronic devise, temperature, and volume and dislocation pipe diffusion coefficients, so copper, iron, and aluminium electrochemical corrosion rates are investigated experimentally at room temperature and at temperature 100oC. Intrinsic diffusivities ratios of copper and aluminium at different temperatures and diffusion activation energies in the Cu-Al system are calculated by proposed here methods using literature experimental data. Dislocation pipe and volume diffusion activation energies of pure iron are calculated separately by earlier proposed method using literature experimental data. Aluminium dissolved into NaCl solution as the Al3+ ions at room temperature and at temperature 100oC, iron dissolved into NaCl solution as the Fe2+ (not Fe3+) ions at room temperature and at temperature 100oC, copper dissolved into NaCl solution as the Cu+ ions at room temperature and as the Cu+ and the Cu2+ ions at temperature 100oC. It is founded experimentally that copper corrosion is higher than aluminium corrosion, and ratio of electrochemical corrosion rates, kCu/kAl>1, decreases with temperature increasing, although iron electrochemical corrosion rate doesn’t depend on temperature below 100oC. It is obvious, because melting point of iron is more higher then melting point of copper or aluminium. It is calculated that copper electrochemical corrosion rate is approximately equal to aluminium electrochemical corrosion at temperature about 300oC, so copper can dissolve into NaCl solution mostly as the Cu2+ ions at temperature about 300oC. Ratio of intrinsic diffusivities, DCu/DAl <1, increases with temperature increasing, and intrinsic diffusivity of aluminium could be approximately equal to intrinsic diffusivity of copper at temperature about 460oC.

Despite great strides in diagnosis and treatment, cardiac diseases remain the number one cause of mortality in the developed world, with rates catching up at an alarming rate in the developing world. Targeted delivery of therapeutics, specifically to cardiomyocytes, would open up new frontiers. Our prior work using a combinatorial in vitro and in vivo phage display methodology identified a 12-amino acid long peptide that targets cardiomyocytes selectively after an intravenous injection in as little as 5 mins, and hence was termed cardiac targeting peptide (CTP: APHLSSQYSRT). CTP has been used to deliver imaging agents, small drug molecules, photosensitizing nanoparticles, exosomes, and even miRNA to cardiomyocytes. As a natural extension for development of CTP as a clinically viable cardiac vector, we now present toxicity studies performed on the peptide. In vitro viability studies were performed in a human left ventricular myocyte cell line with 10µM of Cyanine-5.5 labeled CTP (CTP-Cy5.5). In vitro ion channel profiles were completed for CTP followed by more extensive studies performed by Eurofins in stably transfected cell lines for an extensive list of GPCR-coupled receptors. Positive data for GPCR-coupled receptors was interrogated further with RT-qPCRs performed on mouse heart tissue. In vivo studies consisted of pre- and post-blood pressure monitoring acutely after a single CTP (10 mg/Kg) injection. Further in vivo toxicity studies consisted of injecting 60, 6-week-old, wild-type CD1, male/female mice (1:1) injected with CTP (150 µg/Kg) intravenously. Mice were weighed immediately before injections and daily thereafter. Cohorts of mice were euthanized on day 0, 1, 2, 7 and 14 with inhalational CO2, followed by opening of the chest cavity, collection of blood via cardiac puncture, complete blood count analysis, metabolic profiling, and finally, liver, renal and thyroid studies. Lastly, mouse cardiac MRI was performed immediately before and after injections of CTP (150 µg/Kg) to assess changes in cardiac size or function. Human left ventricular cardiomyocytes showed no decrease in viability after a 30 min incubation with CTP-Cy5.5. In the Eurofins Cardiac Profiler Qube, no significant activation or inhibition of any of seventy-eight protein channels was observed other than OPRM1 and COX2 at the highest tested concentration, neither of which were expressed in mouse heart tissue as assessed by RT-qPCR. There was no change in blood pressures before and after injections with CTP at 10 mg/Kg. Blood counts and chemistries showed no evidence of significant hematological, hepatic or renal toxicities. Lastly, there was no significant difference in cardiac function, size or mass before and after CTP injections. Our studies with CTP showed no activation or inhibition of GPCR-associated receptors in vitro. We found no signals indicative of toxicity in vivo. Most importantly, cardiac functions remained unchanged acutely in response to CTP uptake. Further studies, in good laboratory practices fashion, are needed with more prolonged, chronic administration of CTP conjugated to a specific cargo of choice before human studies can be contemplated.

The threat of antimicrobial resistance to society is compounded by a relative lack of new clinically effective licensed therapies reaching patients over the past three decades. This has been particularly problematic within antifungal drug development leading to a rise in fungal infection rates and associated mortality. This paper highlights the potential of an ultrashort peptide, (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFKK-OH), encompassing hydrogel-forming and antifungal properties within a single peptide motif, thus overcoming formulation (e.g. solubility, drug loading) issues associated with many current employed highly hydrophobic antifungals. A range of fungal susceptibility (colony counts) and cell cytotoxicity (MTS cell viability, LIVE/DEAD staining® with fluorescent microscopy, haemolysis) assays were employed. Scanning electron microscopy confirmed the nanofibrous architecture of our self-assembling peptide, existing as a hydrogel at concentrations of 1% w/v and above. Broad-spectrum activity was demonstrated against a range of fungi clinically relevant to infection (Aspergillus niger, Candida glabrata, Candida albicans, Candida parapsilosis and Candida dubliniensis) with greater than 4 log10 CFU/mL reduction at concentrations of 0.5% w/v and above. We hypothesise antifungal activity is due to targeting of anionic components present within fungal cell membranes resulting in membrane disruption and cell lysis. NapFFKK-OH demonstrated reduced toxicity against mammalian cells (NCTC 929, ARPE-19) suggesting increased selectivity for fungal cells. However, further studies relating to safety for systemic administration is required, given the challenges toxicity has presented in the wider context of antimicrobial peptide drug development. Overall this study highlights the promise of NapFFKK-OH hydrogels, particularly as a topical formulation for the treatment of fungal infections relating to the skin and eyes, or as a hydrogel coating for the prevention of biomaterial related infection.

Iron is an essential nutrient for humans and microbes, such as bacteria. Iron deficiency occurs commonly in critically ill patients, but iron replacement therapy is not considered during the acute phase of critical illness, since it increases iron availability for invading microbes and oxidative stress. However, persistent iron deficiency in the recovery phase is harmful with potential adverse outcomes such as cognitive dysfunction, fatigue and cardiopulmonary dysfunction. Therefore, it is important to treat iron deficiency timely and efficiently. This article reviews current knowledge about iron-related biomarkers in critically ill patients and provides possible criteria to guide decision-making for iron supplementation in the recovery phase of critical illness.

Many drastic actions are taken by cocaine users for the sake of experiencing high dopamine levels, which depends on iron for its synthesis. Dopamine depletion and iron deficiency are also involved in the symptoms of restless leg syndrome (RLS). The intersecting biochemical pathways of cocaine use, iron deficiency, and RLS have not been adequately investigated. This case report reveals the successful treatment of a patient with these conditions. A 63-year-old male with a history of cocaine use disorder, insomnia, and RLS sought emergency care for suicidality. Upon admission, he was also found to be iron-deficient. He revealed that his RLS worsened when he attempted to abstain from cocaine. He also used alcohol to sustain the effects of cocaine when the cost of cocaine was too high. During hospitalization, his mood, cravings, and RLS were resolved with adjunctive iron supplementation as well as 300 mg of Wellbutrin. If iron-deficient, replenishment of adequate dopaminergic receptor density and function via supplementation may play an essential role in the prevention of cocaine use and cessation of cocaine withdrawal. Further research is warranted to validate these findings and understand the implications of iron supplementation in addiction medicine.

Organometallic drug development is still in its early stage, but recent studies show that organometallics having iron as the central atom have the possibility of becoming good drug candidates because iron is an important micro-nutrient, and it is compatible with many biological systems, including the human body. Being an eco-friendly Lewis acid, iron can accept the lone pair of electrons from imino(sp2)-nitrogen, and the resultant iron-imine complexes with iron as a central atom have the possibility of interacting with several proteins and enzymes in humans. Iron-imine complexes have demonstrated significant potential as anticancer, bactericidal, fungicidal, and other medicinal activities in recent years. This article systematically discusses major synthetic methods and pharmacological potentials of iron-imine complexes having in vitro activity to significantly affect clinical performance from 2016 to date. In a nutshell, this manuscript offers a simplistic view of iron complexes in medicinal inorganic chemistry: for instance, iron is presented as an "eco-friendly non-toxic" metal (as opposed to platinum) that will lead to non-toxic pharmaceuticals. The abundant literature on iron chelators shows that many iron complexes, particularly if redox-active in cells, can be quite cytotoxic, which can be beneficial for future targeted therapies. While we made every effort to include all the related papers, any omission is purely unintentional.

Nuclear receptor coactivator 4 (NCOA4) is a selective cargo receptor that mediates the autophagic degradation of ferritin (“ferritinophagy”), the cytosolic iron storage complex. NCOA4-mediated ferritinophagy maintains intracellular iron homeostasis by facilitating ferritin iron storage or release according to demand. Ferritinophagy is involved in iron-dependent physiological processes such as erythropoiesis, where NCOA4 mediates ferritin iron release for mitochondrial heme synthesis. Recently, ferritinophagy has been shown to regulate ferroptosis, a newly described form of iron-dependent cell death mediated by excess lipid peroxidation. Dysregulation of iron metabolism and ferroptosis have been described in neurodegeneration, cancer, and infection, but little is known about the role of ferritinophagy in the pathogenesis of these diseases. Here, we will review the biochemical regulation of NCOA4, its contribution to physiological processes and its role in disease. Finally, we will discuss the potential of activating or inhibiting ferritinophagy and ferroptosis for therapeutic purposes.