From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl₂ or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.     

Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model

Tissue regeneration is often impaired in patients with metabolic disorders such as diabetes mellitus and obesity, exhibiting reduced wound repair and limited regeneration capacity. We and others have demonstrated that wound healing under normal metabolic conditions is potentiated by the secretome of human endothelial cell-differentiated mesenchymal stem cells (hMSC-EC). However, it is unknown whether this effect is sustained under hyperglycemic conditions. In this study, the wound healing effect of secretomes from undifferentiated human mesenchymal stem cells (hMSC) and hMSC-EC in a type-2 diabetes mouse model was analyzed. hMSC were isolated from human Wharton’s jelly and differentiated into hMSC-EC. hMSC and hMSC-EC secretomes were analyzed and their wound healing capacity in C57Bl/6J mice fed with control (CD) or high fat diet (HFD) was evaluated. Our results showed that hMSC-EC secretome enhanced endothelial cell proliferation and wound healing in vivo when compared with hMSC secretome. Five soluble proteins (angiopoietin-1, angiopoietin-2, Factor de crecimiento fibroblástico, Matrix metallopeptidase 9, and Vascular Endothelial Growth Factor) were enriched in hMSC-EC secretome in comparison to hMSC secretome. Thus, the five recombinant proteins were mixed, and their pro-healing property was evaluated in vitro and in vivo. Functional analysis demonstrated that a cocktail of these proteins enhanced the wound healing process similar to hMSC-EC secretome in HFD mice. Overall, our results show that hMSC-EC secretome or a combination of specific proteins enriched in the hMSC-EC secretome enhanced wound healing process under hyperglycemic conditions.     

COVID-19 and Lung Mast Cells: The Kallikrein–Kinin Activation Pathway

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein–kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE⁺ MCs, tryptase⁺ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.     

In situ compatibilization of a polyethylene,polypropylene, and polystyrene ternary blend through Friedel–Crafts alkylation

The Friedel–Crafts alkylation reaction has been applied to reactively compatibilize a ternary blend of high-density polyethylene (HDPE), polypropylene (PP), and polystyrene (PS). The reactions were carried out in an internal mixer using varying catalyst concentrations. The resulting compatibilizer was quantified after Soxhlet extraction. In addition, p-substitution due to the grafting of alkyl groups onto the PS benzene ring was identified via nuclear magnetic resonance spectroscopy. The size of the PS domain in the reactive compositions is decreased by 80%. Moreover, the phase in which PS droplets were dispersed varied, that is, in the nonreactive blends they were found in the PP phase and in the reactive blends they shifted toward the HDPE phase. The effect of the compatibilizing agent was to improve the mechanical properties of the blend. Even with the lowest catalyst content, the properties of elongation-at-break, tensile strength, toughness, and elastic modulus showed improvements. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48295.     

Fate of fertilizer 15N in intensive ridge cultivation with plastic mulching under a monsoon climate

Reducing nitrogen (N) leaching to groundwater requires an improved understanding of the effect of microtopography on N fate. Because of the heterogeneity between positions, ridge tilled fields, frequently used in intensive agriculture, should be treated as two distinct management units. In this study, we measured N dynamics in plastic-mulched ridges and bare furrows with the goal of developing more sustainable agricultural practices with optimal gains, namely crop production versus limited impacts on water quality. We investigated: (1) biomass production; (2) crop N uptake; (3) N retention in soil; and (4) N leaching using ¹⁵N fertilizer in a radish crop. Broadcast mineral N fertilizer application prior to planting resulted in high total leaching losses (of up to 390 N kg ha^?1). The application of plastic mulch in combination with local fertilizer management did not help to reduce N leaching. At all fertilizer N rates, the mean NO₃ ^? concentrations in seepage water were found to be above the WHO drinking water standard of 50 mg NO₃ ^? l^?1. To reduce NO₃ ^? leaching, we recommend: (1) decreasing the fertilizer N rates to a maximum of 150 kg N ha^?1; (2) applying fertilizer N in 3–4 split applications according to the plant’s N needs; (3) applying fertilizer N to the ridges (after their formation) to avoid losses from the furrows; and (4) increasing the soil organic matter content to enhance the water and nutrient retention by covering the furrows with plant residues.     

Advantages and limitations of in vitro and in vivo methods of iron and zinc bioavailability evaluation in the assessment of biofortification program effectiveness

ABSTRACT

Biofortification aims to improve the micronutrient concentration of staple food crops through the best practices of breeding and modern biotechnology. However, increased zinc and iron concentrations in food crops may not always translate into proportional increases in absorbed zinc (Zn) and iron (Fe). Therefore, assessing iron and zinc bioavailability in biofortified crops is imperative to evaluate the efficacy of breeding programs. This review aimed to investigate the advantages and limitations of in vitro and in vivo methods of iron and zinc bioavailability evaluation in the assessment of biofortification program effectiveness. In vitro, animal and isotopic human studies have shown high iron and zinc bioavailability in biofortified staple food crops. Human studies provide direct knowledge regarding the effectiveness of biofortification, however, human studies are time consuming and are more expensive than in vitro and animal studies. Moreover, in vitro studies may be a useful preliminary screening method to identify promising plant cultivars, however, these studies cannot provide data that are directly applicable to humans. None of these methods provides complete information regarding mineral bioavailability, thus, a combination of these methods should be the most appropriate strategy to investigate the effectiveness of zinc and iron biofortification programs.     

Acetone transformation into methyl isobutyl ketone over Pt/HMFI catalysts. IV. Effect of density and strength of the acidic sites

Acetone transformation into methyl isobutyl ketone (MIBK) was studied using a fixed-bed dynamic reactor at 160°C, 1 atm pressure and acetone/H₂ molar ratio=3. The reaction was carried out over Pt/HMFI bifunctional catalysts, with 0.30 wt% of platinum which was supported over three aluminosilicates (Si/Al ratio=40, 95 and 160) and a borosilicate (Si/B ratio=44) with similar dispersion. The results show that catalytic properties depend greatly on density and strength of the acidic sites of the catalysts. Moreover, the limiting step of the MIBK synthesis reaction (aldolization of two acetone molecules) is carried out over the acidic sites of the aluminosilicates, but not over those of the borosilicate, which considerably affects reaction selectivity. This revised version was published online in July 2006 with corrections to the Cover Date.     

Single phase 1-kVA amorphous core transformer: design, experimentaltests, and performance after annealing

The design and experimental implementation of a single-phase power transformer operating at 1 kVA, 110/220 V, and 60 Hz, with an amorphous alloy core are described. The prototype core material is annealed in an argon atmosphere, under a DC magnetic field applied along the ribbon length. The experimental results are presented to compare the amorphous core transformer performance with another transformer with the same rated power, but with a silicon steel core