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Lipid mediators (LM) play crucial roles in the complex inflammation process with respect to initiation, maintenance, and resolution. Proinflammatory leukotrienes (LTs), generated by 5-lipoxygenase (LOX) and the 5-LOX-activating protein (FLAP), initiate and maintain inflammation while specialized pro-resolving mediators (SPMs) formed by various LOXs as key enzymes promote inflammation resolution and the return to homeostasis. Since 5-LOX also contributes to SPM biosynthesis, smart pharmacological manipulation of the 5-LOX pathway and accompanied activation of 12-/15-LOXs may accomplish suppression of LT formation but maintain or even elevate SPM formation. Here, we demonstrated that the FLAP antagonist BRP-201 possesses such pharmacological profile and causes a switch from LT toward SPM formation. Comprehensive LM metabololipidomics with activated human monocyte-derived macrophages (MDM) of M1 or M2 phenotype showed that BRP-201 strongly inhibits LT formation induced by bacterial exotoxins. In parallel, SPM levels and 12/15-LOX-derived products were markedly elevated, in particular in M2-MDM. Intriguingly, in unstimulated MDM, BRP-201 induced formation of 12/15-LOX products including SPM and caused 15-LOX-1 subcellular redistribution without affecting 5-LOX. Experiments with HEK293 cells stably expressing either 5-LOX with or without FLAP, 15-LOX-1 or 15-LOX-2 confirmed suppression of 5-LOX product formation due to FLAP antagonism by BRP-201 but activated 15-LOX-1 in the absence of FLAP. Finally, in zymosan-induced murine peritonitis, BRP-201 (2 mg/kg, ip) lowered LT levels but elevated 12/15-LOX products including SPMs. BRP-201 acts as FLAP antagonist but also as 12/15-LOX activator switching formation of pro-inflammatory LTs toward inflammation-resolving SPM, which reflects a beneficial pharmacological profile for intervention in inflammation.

A novel flow-based approach for the preparation of benzimidazol-2-one (1) scaffold by the 1,1′-carbonyldiimidazole (CDI)-promoted cyclocarbonylation of o-phenylenediamine (2) is reported. Starting from a preliminary batch screening, the model reaction was successfully translated under flow conditions and optimised by means of design of experiment (DoE). The method allowed the efficient preparation of this privileged scaffold and to set up a general protocol for the multigram-scale preparation in high yield, purity, and productivity, and was successfully applied for the multigram flow synthesis of N-(2-chlorobenzyl)-5-cyano-benzimidazol-2-one, which is a key synthon for hit-to-lead explorations in our anti-inflammatory drug discovery program.

Background: The last decade has seen a dramatic shift toward the study of fitness surveillance, thanks in part to the emergence of mobile health (mHealth) apps that allow users to track their health through a variety of data-driven insights. This study examines the adoption trends and community mediation of the mobile fitness application ‘FanFit’, a platform aimed at promoting physical activity among sports fans by creating a fitness app branded to their favourite team for health promotion. Objective: Our study looked at the impact of a specially designed mobile app (FanFit) as a digital health intervention for initiating and maintaining physical activity as part of football club membership. Our analysis indicates that app users will adopt healthier behaviours as a result of the app’s sense of fan community and behaviour change. Methods: The findings reported here are based on an implementation of the FanFit app and, in particular, on those who participated in a more in-depth study (n = 30). These participants were Rangers FC supporters with a mix of genders (n = 19 males and n = 11 females). Focus groups and interviews were conducted with participants to ascertain users’ perspectives on the most effective methods for nudging users toward adopting and maintaining a pattern of fitness behaviours. Results: The findings show that the user community was interested in fitness and wanted to live a ‘healthy lifestyle,’ which was augmented and fuelled by the app’s competitive architecture design. Furthermore, the data reveal a new fan-health discourse about a person’s developing wants, talents, and identities as embodied beings. Conclusions: We have developed and presented valid links between the use of sports club apps and health programmes. The app could be useful for sports programmes and club providers looking for mHealth applications that provide community support through fan discourse with opportunities for both male and female fans.

The outbreaks of the COVID-19 pandemic at the beginning of 2020 have led to considerable economic pressure worldwide, including in Malaysia. The Malaysian government has issued a series of Movement Control Orders (MCOs) requiring companies in most sectors to be closed to the public, with the exception of essential services and certain sectors. The objective of this study is to analyse whether there is a difference in the financial distress of Malaysian companies before and during the COVID-19 pandemic by using the Altman Z-score method. In this study, the annual reports of 83 different companies from 2017 to 2019 and the post-pandemic period (2020 to 2021) were analysed. This study shows that the global COVID-19 pandemic scenario has a significant impact on the logistics and transport sectors, the consumer goods market, and the manufacturing sector. A significant number of companies have been shaken and are now struggling with difficult circumstances as a direct result of the COVID-19 outbreak. This study also shows that almost half of the companies face the possibility of going bankrupt within this period. Surprisingly, there are companies that seem to have improved their performance despite the widespread COVID-19 epidemic. The findings of this study can provide valuable insights for regulators looking to develop strategies to help listed companies cope with future pandemic-related problems.

We study the structural, magnetic, and magneto-thermal properties of the GdRhIn compound. The room-temperature X-ray diffraction measurements show a hexagonal crystal structure. Temperature and field dependence of magnetization suggest two magnetic transitions—antiferromagnetic to ferromagnetic at 16 K and ferromagnetic to paramagnetic at 34 K. The heat capacity measurements confirm both the magnetic transitions in GdRhIn. The magnetization data were used to calculate isothermal magnetic entropy change and refrigerant capacity in GdRhIn, which was found to be 10.3 J/Kg-K for the field change of 70 kOe and 282 J/Kg for the field change of 50 kOe, respectively. The large magnetocaloric effect in GdRhIn suggests that the material could be used for magnetic refrigeration at low temperatures.

Conceptions of human–wildlife coexistence that acknowledge nonhuman wild animals as fellow urban dwellers with legitimate claims on shared urban spaces are starting to influence urban wildlife management practices. Insofar as at least some wild animals have successfully achieved membership in urban society, how has this revaluation affected how urban wildlife is governed? Our interpretive policy analysis explores this question in two areas of urban wildlife management where practices are becoming less lethal: predator management and rodent control. A directed qualitative content analysis of U.S. urban wildlife management plans and rodent control strategies reveals a shift from conflict to coexistence as the basis for understanding human–wildlife relations in urban settings. Indiscriminate killing of urban wildlife is condemned as unethical as well as impractical, and lethal control figures as a measure of last resort that must be rationally justified. Commensal rodents, however, do not benefit from this shift toward coexistence between humans and nonhuman species. Campaigns to restrict the use of rodenticides are intended to protect carnivores, not the rodents themselves. Though urban wildlife management is consistent with some elements of the vision of multispecies flourishing developed by human–animal studies scholars, not all species benefit equally from this transition, and the legitimacy of wild animals’ claims on shared urban spaces often remains contingent on their good behavior.

Despite advances in biomedical research, gastric cancer remains the leading cause of morbidity and mortality worldwide due to the limited efficacy of conventional therapies. In recent decades, oncolytic viruses have emerged as a biological therapeutic alternative to cancer due to their selectivity, effectiveness, and low toxicity. However, clinical trials have shown that developing a virus with selectivity for multiple tumor receptors and the ability to penetrate and diffuse through the tumor microenvironment to reactivate the immune system remains challenging. This study aimed to examine the oncolytic potential of tumor cell-adapted rotavirus Wt1-5 in gastric adenocarcinoma samples. This study focused on determining the propagation capacity of the RV Wt1-5 through the tumor and the importance of the expression of cell surface co-receptors, including integrin β3, protein disulfide isomerase (PDI), and heat shock proteins (Hsp-90, -70, -60, -40, and Hsc 70), during infection of tumor cells. These proteins were found to be differentially expressed in tumor cells compared to adjacent non-tumor cells. Preincubation of gastric tumor cells with antibodies against these proteins decreased rotavirus infections, validating their importance in the binding and entry of RV Wt1-5 into tumor cells, as previously reported. Upon RV infection, apoptosis was one of the types of death that was observed. This was evidenced by evaluating the expression of CASP-3, -9, PARP, cytochrome C, Bax, Bid, p53, and Bcl-2, as well as observing morphological changes such as chromatin margination, nuclear condensation, and fragmentation. Finally, at 60 h.p.i, histological analysis revealed that oncolysis compromised the entire thickness of the tumor. Therefore, the results suggest that RV Wt1-5 could be a novel therapeutic agent co-adjuvant agent for conventional and targeted therapies in managing GC. Ex vivo infection of the tumor tissue model showed characteristics of an immune response that could be explored in future studies.

The study of metapelitic sillimanite- and garnet-bearing granulite xenoliths brought to the surface by the basanite of the 650 ka Tafraoute maar shed new light on the lower crust of the Tabular Middle Atlas (Morocco). Two main types of granulites are distinguished: (1) layered quartzo-feldspathic and (2) unlayered restitic. Mineralogy, petrology, P–T estimates, and electron backscatter diffraction (EBSD) data support that these granulites underwent two successive tectono-metamorphic events before their entrapment in lava. During the first event, probably the Hercynian orogeny, the Tafraoute lower crust acquired its foliation and primary paragenesis, likely including kyanite; it yields P and T conditions of 1.1 ± 0.1 GPa and 850–880 °C. The second event corresponds to a reheating up to ultrahigh temperatures (1050 ± 50 °C) under slightly lower-pressure conditions (0.9 ± 0.1 GPa). This led first to the transformation of kyanite into large prismatic sillimanite. The latter displays uncommon evidence of the dislocation creep deformation of a moderate intensity that points to a tectonic episode occurring after their formation. After deformation has stopped, a reaction between sillimanite and garnet resulted in the crystallization of orthopyroxene and spinel-deformation-free coronas around garnets. Approaching the peak of temperature, anhydrous partial melting of quartzo-feldspathic layers likely occurred, and the resulting felsic melt spread into the rocks. This reheating event might be the consequence of the Late Permian to Mid Jurassic rifting that preceded the formation of the Middle Atlas range, possibly associated with underplating of hot gabbroic magma. This event was followed by gradual cooling down to ∼ 800 °C, leading to static crystallization of the felsic melt in the quartzo-feldspathic granulites. The last event susceptible to have affected the lower crust is the alkali magmatism active in the Middle Atlas during the Mio-Plio-Quaternary. In this context, the origin of restitic granulites is questionable. It may result either from the thermal event associated with the pre-alpine rifting or from the emplacement of basaltic dikes in the lower crust before the Quaternary eruption of the Tafraoute volcano. During this eruption, the studied granulites were entrapped in the ascending lava and very quickly transferred up to the surface, triggering the formation of small vesicular glass pockets. This study highlights the contrasted post-Hercynian evolution of the lower crust in the northern coastal alpine orogen (Rif) and the Tabular Middle Atlas; the first one underwent a tectonic exhumation without reheating during the Alpine orogeny, while the second one is characterized by a reheating to ultrahigh temperature, probably during the pre-alpine rifting, but was probably not or only slightly affected by the alpine events.

In the research on mathematics education, numerous Likert-type instruments estimating attitudes toward mathematics are sometimes composed of factors with a high correlation, which can make it difficult to assign the statements from the scale to each estimated factor. Further, the measurement of attitudes is usually done by adding the scores but ignoring the existence of possible differences in the importance that each item can have in its factor estimation. A revision of the methodology for the study of attitudes toward mathematics for the correct validation of the instrument is carried out in this research, and an estimation of the factors of attitude is proposed using the calculation of the weighted average of scores based on the importance that each item has in the explanation of its factor, which is given by a structural equation model. This methodology has been applied to Auzmendi's scale of attitudes toward mathematics measurement in a sample of 1293 university students. The factors were estimated using simple and weighted averages; significant differences have been obtained in the measurements, as well on those shown with the organization proposed by Auzmendi.