The civil construction industry is one of the sectors that most consume natural resources in the world and, consequently, one of that generate more waste. Thinking about constructive techniques that generate less impact on the environment is vital to ensure sustainable development. In this scenario, the Life Cycle Assessment (LCA) has been presented as an internationally recognized approach, that assesses the potential impact of products and services on human health and the environment, throughout its entire life cycle. Aimed to identify construction techniques and vertical closing systems that generate less impact and consumption of natural resources, the impacts generated by the life cycle of the three vertical closing systems most applied in construction sites in Brazil were compared: ceramic brick masonry system (CBr); concrete block masonry system (CBk); and structural blocks masonry system (SBk). The SBk proved to be the least impacting to the “Resource Scarcity”, “Damage to Human Health”, and “Damage to the diversity of Ecosystems” interesting areas. This performance is directly related to the use of cement CPIII type and also by the fact that the SBk consumes less concrete and mortar than the others. Already the "Water Consumption" area, the CBk was the least impacting due to the lower consumption of electricity during its life cycle. The reliability of the results was proven through a sensitivity analysis of the normalization and characterization factors, which consisted of comparing the results obtained by applying two different methodologies. It is believed that the LCA study carried out can assist in the decision-making process regarding the choice of the most sustainable construction method.

Proprotein convertases activate various envelope glycoproteins and participate in cellular entry of many viruses. We recently showed that the convertase furin is critical for the infectivity of SARS-CoV-2. This study investigated the implication of the two cholesterol-regulating convertases SKI-1 and PCSK9 in SARS-CoV-2 entry. We used cell-to-cell fusion assays in HeLa cells and pseudoparticle entry into Calu-3 cells. SKI-1 increases cell-to-cell fusion by enhancing the activation of SREBP-2, whereas PCSK9 reduces cell-to-cell fusion by promoting the cellular degradation of ACE2. Metalloprotease activation is sensitive to enhanced cholesterol levels resulting from SKI-1-activated SREBP-2 that leads to enhanced S2’ formation. However, high metalloprotease activity results in S2’ shedding into a new C-terminal fragment (S2”), leading to reduced cell-to-cell fusion. Indeed, S-mutants that increase S2’’ formation, abolish S2’ and cell-to-cell fusion, as well as pseudoparticles entry, indicating that the formation of S2’’ prevents SARS-CoV-2 cell-to-cell fusion and entry. We next demonstrated that PCSK9 enhanced the cellular degradation of ACE2, thereby reducing cell-to-cell fusion. However, different from the LDLR, a canonical target of PCSK9, the C-terminal CHRD domain of PCSK9 is dispensable for the PCSK9-induced degradation of ACE2. Molecular modeling suggested binding of ACE2 to the Pro/Catalytic domains of mature PCSK9. Thus, both cholesterol-regulating convertases SKI-1 and PCSK9 can modulate SARS-CoV-2 entry via two independent mechanisms.

PCSK9 is implicated in familial hypercholesterolemia via targeting the cell surface PCSK9-LDLR complex toward lysosomal degradation. The M2 repeat in the PCSK9's C-terminal domain is essential for its extracellular function, potentially through its interaction with an unidentified “protein X”. The M2 repeat was recently shown to bind an R-x-E motif in MHC-class-I proteins (implicated in the immune system), like HLA-C, and causing their lysosomal degradation. These findings suggested a new role of PCSK9 in the immune system and that HLA-like proteins could be “protein X” candidates. However, the participation of each member of the MHC-I protein family in this process and their regulation of PCSK9's function have yet to be determined. Herein, we compared the implication of MHC-I-like proteins such as HFE (involved in iron homeostasis) and HLA-C on the extracellular function of PCSK9. Our data revealed that the M2 domain regulates the intracellular sorting of the PCSK9-LDLR complex to lysosomes, and that HFE is a new target of PCSK9 that inhibits its activity on the LDLR, whereas HLA-C enhances its function. This work suggests the potential modulation of the PCSK9 functions through interactions of HFE and HLA-C.

This paper investigates the effect of Fe contamination on the microstructure and mechanical properties of Al-7Si-0.7Mg-Fe2.5 alloy processed by Laser Powder Bed Fusion (LPBF) and heat treated in two different conditions: (1) Solution Heat Treatment (SHT) at 520 °C, followed by artificial ageing at 160 °C (T6), and (2) Direct Artificial Ageing of the as-printed material at 160 °C (DAA). Microstructural characterization was carried out by Optical Microscopy (OM), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Transmission Electron Microscope (TEM). Mechanical characterization was carried out by tensile tests at room temperature. The formation of fine AlSiFe phases such as α-AlFeSi, β-AlFeSi, and π-Al8Si6Mg3Fe had no deleterious effect on the mechanical properties compared to previous studies for AlSIMg alloys without Fe. However, compared to the as-printed condition, the T6 heat treatment decreased the ultimate tensile strain significantly, while the elongation to the fracture presented a slight improvement.

Characterized by severe and fatal arrhythmias induced by cardiac ischemia/reperfusion (CIR), acute myocardial infarction (AMI) is the main cause of morbidity and mortality worldwide. To investigate the cardioprotective role of cardiac Ca2+/cAMP/adenosine signaling in AMI, the effects of L-type Ca2+ channels (LTCC) blocker Nifedipine (NIF) and Verapamil (VER), in the absence and presence of A1-adenosine receptors (A1R) blocker (DPCPX), on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) induced by CIR in rats were evaluated. CIR was induced in adult male Wistar rats (290-320 g) by occlusion of the left anterior descendent coronary artery (10 min) followed by reperfusion (75 min). VA, AVB and LET incidences were evaluated by ECG analysis and compared between control (CIR group) and intravenously treated 5 min before CIR with NIF 1, 10, and 30 mg/kg (NIF+CIR groups) or DPCPX 100 µg/kg plus NIF 10 mg/kg (DPCPX+NIF+CIR group) and VER 1 mg/kg (VER+CIR group) or DPCPX 100 µg/kg plus VER 1 mg/kg (DPCPX+VER+CIR group). Serum levels of cardiac injury biomarkers (TCK and CK-MB) were quantified. In CIR group, VA, AVB and LET incidences were 90, 80 and 70%, respectively. In NIF+CIR group, incidence of VA was reduced to 50, 30 and 30%, AVB to 25, 10 and 20%, and LET to 25, 20 and 20%, and respectively. In DPCPX+NIF+CIR group, these incidences were not different from CIR group. TCK and CK-MB levels were similar in all groups. These results indicate that pharmacological modulation of the Ca2+/cAMP/adenosine signaling in cardiac cells by LTCC blockade and A1R stimulation could be a new strategy cardioprotective for human AMI therapy.