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Nancy E Lozoya-Pérez,1 Sergio Casas-Flores,2 José Roberto Fogaça de Almeida,3 José A Martínez-Álvarez,1 Luz A López-Ramírez,1 Grasielle Pereira Jannuzzi,3 Elías Trujillo-Esquivel,1 Eine Estrada-Mata,1 Sandro R Almeida,3 Bernardo Franco,1 Leila M Lopes-Bezerra,3,4 Héctor M Mora-Montes1 1Department of Biology, Division of Exact and Natural Sciences, Universidad de Guanajuato, Guanajuato, Mexico; 2Division of Molecular Biology, IPICYT, San Luis Potosí, Mexico; 3Laboratory of Clinical Mycology, Faculty of Pharmacy, Universidade de São Paulo, São Paulo, Brazil; 4Laboratory of Cellular Mycology and Proteomics, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil Background: Sporothrix schenckii is a neglected fungal pathogen for the human being and other mammals. In several fungal systems, Och1 is a Golgi α1,6-mannosyltransferase with a key function in the synthesis of N-linked glycans; which are important elements during the host-fungus interplay. The role of OCH1 in fungal virulence seems to be species-specific, being an essential component for Candida albicans virulence and dispensable during the interaction of Aspergillus fumigatus with the host. Methods: Here, we silenced S. schenckii OCH1 and characterized the phenotype of the mutant strains. Results: The mutant strains did not show defects in the cell or colony morphology, the growth rate or the ability to undergo dimorphism; but the cell wall changed in both composition and exposure of inner components at the surface. When interacting with human monocytes, the silenced strains had a reduced ability to stimulate TNFα and IL-6 but stimulated higher levels of IL-10. The interaction with human macrophages was also altered, with reduced numbers of silenced cells phagocytosed. These strains showed virulence attenuation in both Galleria mellonella and in the mouse model of sporotrichosis. Nonetheless, the cytokine levels in infected organs did not vary significantly when compared with the wild-type strain. Conclusion: Our data demonstrate that OCH1 silencing affects different aspects of the S. schenckii-host interaction. Keywords: cell wall, protein glycosylation, sporotrichosis, gene silencing, host–fungus interplay, mannosyltransferase

Proteins found within the fungal cell wall usually contain both N - and O -oligosaccharides. N -glycosylation is the process where these oligosaccharides (hereinafter: glycans) are attached to asparagine residues, while in O -glycosylation the glycans are covalently bound to serine or threonine residues. The PMT family is grouped into PMT1 , PMT2 , and PMT4 subfamilies. Using bioinformatics analysis within the Botrytis cinerea genome database, an ortholog to Saccharomyces cerevisiae Pmt4 and other fungal species was identified. The aim of this study was to assess the relevance of the bcpmt4 gene in B. cinerea glycosylation. For this purpose, the bcpmt4 gene was disrupted by homologous recombination in the B05.10 strain using a hygromycin B resistance cassette. Expression of bcpmt4 in S. cerevisiae Δ Scpmt4 or Δ Scpmt3 null mutants restored glycan levels like those observed in the parental strain. The phenotypic analysis showed that Δ bcpmt4 null mutants exhibited significant changes in hyphal cell wall composition, including reduced mannan levels and increased amounts of chitin and glucan. Furthermore, the loss of bcpmt4 led to decreased glycosylation of glycoproteins in the B. cinerea cell wall. The null mutant lacking PMT4 was hypersensitive to a range of cell wall perturbing agents, antifungal drugs, and high hydrostatic pressure. Thus, in addition to their role in glycosylation, the PMT4 is required to virulence, biofilm formation, and membrane integrity. This study adds to our knowledge of the role of the B. cinerea bcpmt4 gene, which is involved in glycosylation and cell biology, cell wall formation, and antifungal response.

Sporothrix brasiliensis is one of the leading etiological agents of sporotrichosis, a cutaneous and subcutaneous mycosis worldwide distributed. This organism has been recently associated with epidemic outbreaks in Brazil. Despite the medical relevance of this species, little is known about its virulence factors, and most of the information on this subject is extrapolated from Sporothrix schenckii . Here, we generated S. brasiliensis mutants, where GP70 was silenced. In S. schenckii , this gene encodes a glycoprotein with adhesive properties required for virulence. The S. brasiliensis GP70 silencing led to an abnormal cellular phenotype, with smaller, round yeast-like cells that aggregate. Cell aggregation was disrupted with glucanase, suggesting this phenotype is linked to changes in the cell wall. The cell wall characterization confirmed changes in the structural polysaccharide β-1,3-glucan, which increased in quantity and exposure at the cell surface. This was accompanied by a reduction in protein content and N -linked glycans. Mutant strains with high GP70 -silencing levels showed minimal levels of 3-carboxy-cis,cis-muconate cyclase activity, this glycoprotein's predicted enzyme function, and decreased ability to bind laminin and fibronectin. These phenotypical changes coincided with abnormal interaction with human peripheral blood mononuclear cells, where production of IL-1β, IL-17, and IL-22 was reduced and the strong dependence on cytokine stimulation via mannose receptor was lost. Phagocytosis by monocyte-derived macrophages was increased and virulence attenuated in a Galleria mellonella larvae. In conclusion, Gp70 is an abundant cell wall glycoprotein in S. brasiliensis that contributes to virulence and proper interaction with innate immnune cells., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

The hypothalamic-pituitary-adrenal (HPA) axis in mammals and the hypothalamic-pituitary-interrenal (HPI) axis in fish are open systems that adapt to the environment during development. Little is known about how this adaptation begins and regulates early stress responses. We used larval zebrafish to examine the impact of prolonged forced swimming at 5 days post-fertilization (dpf), termed early-life challenge (ELC), on cortisol responses, neuropeptide expression in the nucleus preopticus (NPO), and gene transcript levels. At 6 dpf, ELC-exposed larvae showed normal baseline cortisol but reduced reactivity to an initial stressor. Conversely, they showed increased reactivity to a second stressor within the 30-min refractory period, when cortisol responses are typically suppressed. ELC larvae had fewer corticotropin-releasing hormone (crh), arginine vasopressin (avp), and oxytocin (oxt)-positive cells in the NPO, with reduced crh and avp co-expression. Gene expression analysis revealed upregulation of genes related to cortisol metabolism (hsd11b2, cyp11c1), steroidogenesis (star), and stress modulation (crh, avp, oxt). These results suggest that early environmental challenge initiates adaptive plasticity in the HPI axis, tuning cortisol regulation to balance responsiveness and protection during repeated stress. Future studies should explore the broader physiological effects of prolonged forced swimming and its long-term impact on cortisol regulation and stress-related circuits., Competing Interests: Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. Published by The Company of Biologists Ltd.)

Vitamin D status has been involved with coronavirus disease 19 (COVID-19) severity. This may be mediated by vitamin D metabolism regulatory genes. Of interest is the vitamin D receptor (VDR) gene, which has been previously associated with other inflammatory and respiratory diseases. In order to investigate the role of VDR gene polymorphisms in COVID-19 severity and outcome, a total of 292 COVID-19 patients were classified according to severity in moderate (n = 56), severe (n = 89) and critical (n = 147) and, according to outcome in survivor (n = 163) and deceased (n = 129), and analysed for FokI and TaqI VDR gene polymorphisms by polymerase chain reaction-based restriction enzyme digestion. The FokI and TaqI single nucleotide polymorphisms (SNPs) were not associated with COVID-19 severity or mortality individually but when analysed by haplotype, TC was associated with an increased risk of presenting critical COVID-19. Additionally, FokI CT genotype was more frequent in COVID-19 patients with hypertension, and T allele carriers presented higher aspartate aminotransferase levels. Our results suggest a relationship between VDR FokI and TaqI SNPs and COVID-19 severity in Mexican population. Although there are some previous reports of VDR polymorphisms in COVID-19, this represents the first report in Latin American population. Further studies on other populations are encouraged., (© 2024 John Wiley & Sons Ltd.)

Zebrafish larvae show a rapid increase in cortisol in response to acute stressors, followed by a decline. While these responses are documented, both the duration of the refractory period to repeated stressors and the role of glucocorticoid receptors (GR) in specific phases of the glucocorticoid negative feedback are still being clarified. We explored these questions using water vortices as stressors, combined with GR blockage and measurements of whole-body cortisol in zebrafish larvae subjected to single and repeated stress protocols. Cortisol levels were elevated 10 min after stress onset and returned to baseline within 30-40 min, depending on the stressor strength. In response to homotypic stress, cortisol levels rose above baseline if the second stressor occurred 60 or 120 min after the first, but not with a 30-min interval. This suggests a rapid cortisol-mediated feedback loop with a refractory period of at least 30 min. Treatment with a GR blocker delayed the return to baseline and suppressed the refractory period, indicating GR-dependent early-phase feedback regulation. These findings are consistent with mammalian models and provide a framework for further analyses of early-life cortisol responses and feedback in zebrafish larvae, ideal for non-invasive imaging and high-throughput screening., Competing Interests: Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. Published by The Company of Biologists Ltd.)

High-density lipoprotein cholesterol (HDL-c) removes cholesterol, an essential component in lipid rafts, and this cholesterol removal can regulate protein attachment to lipid rafts, modulating their functionality in the immune cell response. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can alter the lipid profile, there is little information on the role of HDL-c and other lipids in prognostic of the coronavirus disease 2019 (COVID-19) in Mexican population. This study aims to evaluate the predictive value of HDL-c and lipid profile on severity and survival of 102 patients infected with SARS-CoV-2 during the COVID-19 first wave. Our findings, derived from univariate and multivariate Cox proportional hazards regression models, highlighted age and hypertension as significant predictors of survival (HR = 1.04, p = 0.012; HR = 2.78, p = 0.027), while gender, diabetes, and obesity showed no significant impact. Triglycerides and HDL-c levels notably influenced mortality, with elevated triglycerides and lower HDL-c associated with higher mortality risk (p = 0.032). This study underscores the importance of lipid profiles alongside traditional risk factors in assessing COVID-19 risk and outcomes. It contributes to the understanding of COVID-19 patient management and emphasizes the need for further investigation into the role of dyslipidemia in influencing COVID-19 prognosis, potentially aiding in refined risk stratification and therapeutic strategies., (© 2024. The Author(s).)

Sporothrix schenckii is one of the etiological agents of sporotrichosis, a cutaneous and subcutaneous infection distributed worldwide. Like other medically relevant fungi, its cell wall is a molecular scaffold to display virulence factors, such as protective pigments, hydrolytic enzymes, and adhesins. Cell wall proteins with adhesive properties have been previously reported, but only a handful of them have been identified and characterized. One of them is Gp70, an abundant cell wall protein mainly found on the surface of yeast-like cells. Since the protein also has a role in the activity of 3-carboxy- cis , cis -muconate cyclase and its abundance is low in highly virulent strains, its role in the Sporothrix -host interaction remains unclear. Here, a set of GP70 -silenced strains was generated, and the molecular and phenotypical characterization was performed. The results showed that mutants with high silencing levels showed a significant reduction in the adhesion to laminin and fibrinogen, enzyme activity, and defects in the cell wall composition, which included reduced mannose, rhamnose, and protein content, accompanied by an increment in β-1,3-glucans levels. The cell wall N -linked glycan content was significantly reduced. These strains induced poor TNFα and IL-6 levels when interacting with human peripheral blood mononuclear cells in a dectin-1-, TLR2-, and TLR4-dependent stimulation. The IL-1β and IL-10 levels were significantly higher and were stimulated via dectin-1. Phagocytosis and stimulation of neutrophil extracellular traps by human granulocytes were increased in highly GP70 -silenced strains. Furthermore, these mutants showed virulence attenuation in the invertebrate model Galleria mellonella . Our results demonstrate that Gp70 is a versatile protein with adhesin properties, is responsible for the activity of 3-carboxy- cis , cis -muconate cyclase, and is relevant for the S. schenckii -host interaction.

Citral is a monoterpene constituted by two isomers known as neral and geranial. It is present in different plant sources and recognized as safe (GRAS) by the Food and Drug Administration (FDA). In recent years, investigations have demonstrated that this compound exhibited several biological activities, such as antibacterial, antifungal, antibiofilm, antiparasitic, antiproliferative, anti-inflammatory, and antioxidant properties, by in vitro and in vivo assays. Additionally, when incorporated into different food matrices, citral can reduce the microbial load of pathogenic microorganisms and extend the shelf life. This compound has acceptable drug-likeness properties and does not present any violations of Lipinski's rules, which could be used for drug development. The above shows that citral could be a compound of interest for developing food additives to extend the shelf life of animal and vegetable origin foods and develop pharmaceutical products.

HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3'UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of endogen cell factors; nevertheless, the reports are discrepant and controversial. Herein, the relationship of the 14-bp Ins/Del variant (rs66554220) with breast cancer (BC) and its clinical characteristics were analyzed in 182 women with non-familial BC and 221 disease-free women as a reference group. Both groups from western Mexico and sex-age-matched (sm-RG). The rs66554220 variant was amplified by SSP-PCR and the fragments were visualized in polyacrylamide gel electrophoresis. The variant rs66554220 was not associated with BC in our population. However, we suggest the Ins allele as a possible risk factor for developing BC at clinical stage IV (OR = 3.05, 95% CI = 1.16-7.96, p = 0.01); nevertheless, given the small stratified sample size (n = 11, statistical power = 41%), this is inconclusive. In conclusion, the 14-bp Ins/Del (rs66554220) variant of HLA-G is not associated with BC in the Mexican population, but might be related to advanced breast tumors. Further studies are required.

One of the effects of climate change in warm areas is the asynchrony between the dates of the technological and the phenolic maturity of grapes. This is important because the quality and color stability of red wines are directly related to the content and distribution of phenolic compounds. A novel alternative that has been proposed to delay grape ripening and make it coincide with a seasonal period more favorable for the formation of phenolic compounds is crop forcing. This consists of severe green pruning after flowering, when the buds of the following year have already differentiated. In this way, the buds formed during the same season are forced to sprout, initiating a new delayed cycle. The aim of the present work is to study the effect on the phenolic composition and color of wines elaborated from vines fully irrigated (C), grown using conventional non-forcing (NF) and forcing (F) techniques (C-NF and C-F), and wines from vines subjected to regulated irrigation (RI), grown using NF and F techniques (RI-NF and RI-F). The trial was carried out in an experimental vineyard of the Tempranillo variety located in a semi-arid area (Badajoz, Spain) in the 2017-2019 seasons. The wines (four by treatment) were elaborated and stabilized according to the classic methodologies for red wine. All wines had the same alcohol content, and malolactic fermentation was not carried out in any of them. Anthocyanin profiles were analyzed by HPLC, and total polyphenolic content, anthocyanin content, catechin content, the contribution to color due to co-pigmented anthocyanins, and various chromatic parameters were also determined. Although a significant effect of year was found for almost all the parameters analyzed, a general increasing trend in F wines was found for most of them. The anthocyanin profile of F wines was found to differ from that of C wines, especially in delphinidin, cyanidin, petunidin, and peonidin content. These results indicate that by using the forcing technique it was possible to increase the polyphenolic content by ensuring that the synthesis and accumulation of these substances occurred at more suitable temperatures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lavado Rodas, Uriarte Hernández, Moreno Cardona, Mancha Ramírez, Prieto Losada and Valdés Sánchez.)

Introduction: The HLA-G molecule functions as a critical immunomodulatory checkpoint, its expression is significantly associated with pathological processes that may be responsible in part for autoimmune conditions such as non-segmental vitiligo (NS-V), characterized by chronic skin depigmentation. In this sense, the rs66554220 (14 bp ID) variant located in the 3'UTR, implicated in the regulation of HLA-G production, is associated with autoimmune diseases., Aim: To evaluate the role of the HLA-G rs66554220 variant in NS-V and its clinical features in Northwestern Mexicans., Material and Methods: We genotyped the rs66554220 variant by SSP-PCR in 197 NS-V patients and 198 age-sex matched non-related healthy individuals (HI)., Results: Del allele and genotype Del/Ins were the most prevalent in both study groups (NS-V/HI = 56%/55% and 46.70%/46.46%, respectively). Despite lacking association between the variant and NS-V, we found an association of the Ins allele in different inheritance models with familial clustering, onset of the illness, universal clinical subtype and Koebner's phenomenon., Conclusions: The rs66554220 (14 bp ID) variant is not a risk factor for NS-V in the Mexican population studied. To our knowledge, this is the first report about the topic in the Mexican population and worldwide that includes clinical features related with this HLA-G genetic variant., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

Background: Vitiligo is an autoimmune disease that courses with skin depigmentation because of the destruction of melanocytes. Vitiliginous melanocyte is prone to damage because of oxidative stress which activates cellular stress response and the release of heat shock proteins such as HSP70 promoting immune activation against the melanocyte. Variants in HSP70 genes (HSPA) might alter their expression and thus modulate vitiligo susceptibility. Therefore, we sought to evaluate the role of the 5' untranslated region HSPA1A G/C (rs1043618) and the exonic HSPA1B A/G (rs1061581) and HSPA1L T/C (rs2227956) gene variants in nonsegmental vitiligo., Methods: A total of 200 nonsegmental vitiligo patients and 208 age/gender-matched healthy subjects were genotyped for rs1043618, rs1061581, and rs2227956 variants by PCR-RFLP., Results: Variants rs1043618 and rs1061581 were not associated with vitiligo susceptibility. On the other hand, the rs2227956 C allele and TC genotype were associated with protection against vitiligo. A similar effect was observed for the GAC haplotype. Any of the aforementioned HSP70 gene variants were associated with the clinical characteristics of vitiligo., Conclusion: Our findings suggest that the HSPA1L rs2227956 gene variant might influence the susceptibility to vitiligo. Being the first study of HSP70 gene variants in vitiligo, further research is encouraged to corroborate these results., (© 2022 the International Society of Dermatology.)

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic study in which the duodenum is observed laterally, and the bile duct is instrumented. There are several indications and complications in the procedure., Objective: To determine the incidence of duodenal perforations, using the Stapfer classification in the Hospital Juárez de Mexico over a period of 5 years, as well as the management implemented in such cases., Method: The study was carried out at the Hospital Juárez de Mexico of the Ministry of Health. All patients who underwent ERCP between January 1, 2017, to May 30, 2022 were included., Results: 485 ERCP were performed in the study period. Incidence of 1.6% post-ERCP duodenal perforation. The average age of the subjects 56.37 years. In-hospital stay of post-ERCP perforations averaged 9.37 days. The time of the endoscopic study at the time of the surgical procedure is 10 h on average., Conclusions: Post-ERCP duodenal perforation is a complication that occurs with a low incidence, it tends to increase the number of days of in-hospital stay and increases morbimortality of patients; therefore, it is important to be always alert., (Copyright: © 2023 Permanyer.)

The mineral reaction pathways that yield organic compounds of increasing complexity would have required a means of protective screening against strong ultraviolet radiation for macromolecular assembly on early Earth. In this study, a bacterial chromosomal plasmid DNA was used as a model biomolecule that represents a complex polymeric nucleic acid containing genetic information. The plasmid DNA was exposed to UV radiation through a medium containing air, water, iron (Fe 3+ ), or silica-iron rich aqueous solutions. Our results demonstrate that the plasmid DNA underwent covalent breakage in an aqueous solution when exposed to UV radiation but was shielded against damage due to the presence of iron and silica. It is demonstrated that a suspension of ca. 40 nm colloidal particles of silica gel embedded with Fe 3+ ions adsorbed on silanol groups that formed nanoclusters of noncrystalline iron hydroxide is an extremely efficient shelter against intense UV radiation. The implications for our understanding of primitive Earth and Earth-like planets, moons, and asteroids are discussed. The stability of a chromosomal DNA molecule against UV radiation in the presence of iron and silica may provide support on how macromolecules endured early Earth environments and brought forth important implications on early molecular survival against UV radiation.

Background: Febrile neutropenia (FN) is an early indicator of infection in oncology patients post-chemotherapy. We aimed to determine clinical predictors of septic shock and/or bacteremia in pediatric cancer patients experiencing FN and to create a model that classifies patients as low-risk for these outcomes., Methods: This is a retrospective analysis with clinical data of a cohort of pediatric oncology patients admitted during July 2015 to September 2017 with FN. One FN episode per patient was randomly selected. Statistical analyses include distribution analysis, hypothesis testing, and multivariate logistic regression to determine clinical feature association with outcomes., Results: A total of 865 episodes of FN occurred in 429 subjects. In the 404 sampled episodes that were analyzed, 20.8% experienced outcomes of septic shock and/or bacteremia. Gram-negative bacteria count for 70% of bacteremias. Features with statistically significant influence in predicting these outcomes were hematological malignancy (P < .001), cancer relapse (P = .011), platelet count (P = .004), and age (P = .023). The multivariate logistic regression model achieves AUROC = 0.66 (95% CI 0.56-0.76). The optimal classification threshold achieves sensitivity = 0.96, specificity = 0.33, PPV = 0.40, and NPV = 0.95., Conclusions: This model, based on simple clinical variables, can be used to identify patients at low-risk of septic shock and/or bacteremia. The model's NPV of 95% satisfies the priority to avoid discharging patients at high-risk for adverse infection outcomes. The model will require further validation on a prospective population., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Sporothrix schenckii is a member of the Sporothrix pathogenic clade and one of the most common etiological agents of sporotrichosis, a subcutaneous fungal infection that affects both animal and human beings. Like other fungal pathogens, the Sporothrix cell wall is composed of structural polysaccharides and glycoproteins that are covalently modified with both N -linked and O -linked glycans. Thus far, little is known about the N -linked glycosylation pathway in this organism or its contribution to cell wall composition and interaction with the host. Here, we silenced ROT2 , which encodes the catalytic subunit of the endoplasmic reticulum α-glucosidase II, a processing enzyme key for the N -linked glycan core processing. Silencing of ROT2 led to the accumulation of the Glc 2 Man 9 GlcNAC 2 glycan core at the cell wall and a reduction in the total content of N -linked glycans found in the wall. However, the highly silenced mutants showed a compensatory mechanism with increased content of cell wall O -linked glycans. The phenotype of mutants with intermediate levels of ROT2 silencing was more informative, as they showed changes in the cell wall composition and exposure of β-1.3-glucans and chitin at the cell surface. Furthermore, the ability to stimulate cytokine production by human mononuclear cells was affected, along with the phagocytosis by human monocyte-derived macrophages, in a mannose receptor-, complement receptor 3-, and TLR4-dependent stimulation. In an insect model of experimental sporotrichosis, these mutant cells showed virulence attenuation. In conclusion, S. schenckii ROT2 is required for proper N -linked glycosylation, cell wall organization and composition, and interaction with the host.

Soil mechanical impedance precludes root penetration, confining root system development to shallow soil horizons where mobile nutrients are scarce. Using a two-phase-agar system, we characterized Arabidopsis responses to low and high mechanical impedance at three root penetration stages. We found that seedlings whose roots fail to penetrate agar barriers show a significant reduction in leaf area, root length, and elongation zone and an increment in root diameter, while those capable of penetrating show only minor morphological effects. Analyses using different auxin-responsive reporter lines, exogenous auxins, and inhibitor treatments suggest that auxin responsiveness and PIN-mediated auxin distribution play an important role in regulating root responses to mechanical impedance. The assessment of 21 Arabidopsis accessions revealed that primary root penetrability varies widely among accessions. To search for quantitative trait loci (QTLs) associated to root system penetrability, we evaluated a recombinant inbred population derived from Landsberg erecta (Ler-0, with a high primary root penetrability) and Shahdara (Sha, with a low primary root penetrability) accessions. QTL analysis revealed a major-effect QTL localized in chromosome 3, ROOT PENETRATION INDEX 3 (q-RPI3), which accounted for 29.98% (logarithm of odds=8.82) of the total phenotypic variation. Employing an introgression line (IL-321) with a homozygous q-RPI3 region from Sha in the Ler-0 genetic background, we demonstrated that q-RPI3 plays a crucial role in root penetrability. This multiscale study reveals new insights into root plasticity during the penetration process in hard agar layers, natural variation, and genetic architecture behind primary root penetrability in Arabidopsis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

One of the biggest drawbacks in endodontic filling is the problem of insufficient root sealing, due to the microleakage of bacteria into the canal. The objective of the research was to carry out a narrative review of the characteristics of the use of methylene blue as an evaluator of microleakage in studies that compared the quality of root sealing with different endodontic filling techniques. The research method used was literature review. Methylene blue was used in experimental in vitro studies, which compared filling techniques such as lateral condensation, cold injectable gutta-percha, thermomechanics, among others, the sealed dental pieces were immersed in a 1% methylene blue dye at 5% concentration. This procedure allowed reevaluating the samples in different periods of time. In conclusion, for endodontic filling penetration testing, methylene blue is an easy-to-use and reliable option., Competing Interests: Declaración de conflictos de interés: Los autores declaran no tener ningún conflito de interés

Polylactic acid (PLA) is a leading bioplastic of which the market share is predicted to increase in the future; its growing production capacity means its end-of-life treatment is becoming increasingly important. One beneficial disposal route for PLA is its chemical recycling via alcoholysis. The alcoholysis of PLA leads to the generation of value-added products alkyl lactates; this route also has potential for a circular economy. In this work, PLA was chemically recycled via methanolysis to generate methyl lactate (MeLa). Four commercially available catalysts were investigated: zinc acetate dihydrate (Zn(OAc) 2 ), magnesium acetate tetrahydrate (Mg(OAc) 2 ), 4-(dimethylamino)pyridine (DMAP), and triazabicyclodecene (TBD). Dual catalyst experiments displayed an increase in reactivity when Zn(OAc) 2 was paired with TBD or DMAP, or when Mg(OAc) 2 was paired with TBD. Zn(OAc) 2 coupled with TBD displayed the greatest reactivity. Out of the single catalyst reactions, Zn(OAc) 2 exhibited the highest activity: a higher mol% was found to increase reaction rate but plateaued at 4 mol%, and a higher equivalent of methanol was found to increase the reaction rate, but plateaued at 17 equivalents. PLA methanolysis was modelled as a two-step reversible reaction; the activation energies were estimated at: Ea 1 = 25.23 kJ∙mol -1 , Ea 2 = 34.16 kJ∙mol -1 and Ea -2 = 47.93 kJ∙mol -1 .

This dataset was compiled to estimate the levels of thermal comfort and mental health in a sample group of university students confined due to the COVID-19 pandemic. By the time research was carried out, these students of a hot and humid region of Mexico, had already spent 200 days on distance learning using online platforms. A total of 324 records were documented with a final sample of 316 valid participants. The total records were collected directly from the students through a web platform (Microsoft forms). This data set can be used to generate correlations between mental health, thermal comfort, and individual characteristics in the study population that will allow to identify the influence of the built environment and local climate on the levels of stress and anxiety that university students experienced under confinement. It can also be used to issue recommendations to improve the quality of built spaces and for the construction of adaptive models of thermal comfort considering mental health as a study variable ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

COVID-19 and dengue disease are challenging to tell apart because they have similarities in clinical and laboratory features during the acute phase of infection, leading to misdiagnosis and delayed treatment. The present study evaluated peripheral blood cell count accuracy to distinguish COVID-19 non-critical patients from non-severe dengue cases between the second and eleventh day after symptom onset. A total of 288 patients infected with SARS-CoV-2 (n = 105) or dengue virus (n = 183) were included in this study. Neutrophil, platelet, and lymphocyte counts were used to calculate the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the neutrophil-lymphocyte*platelet ratio (NLPR). The logistic regression and ROC curves analysis revealed that neutrophil and platelet counts, NLR, LPR, and NLPR were higher in COVID-19 than dengue. The multivariate predictive model showed that the neutrophils, platelets, and NLPR were independently associated with COVID-19 with a good fit predictive value ( p = 0.1041). The neutrophil (AUC = 0.95, 95% CI = 0.84-0.91), platelet (AUC = 0.89, 95% CI = 0.85-0.93) counts, and NLR (AUC = 0.88, 95% CI = 0.84-0.91) were able to discriminate COVID-19 from dengue with high sensitivity and specificity values (above 80%). Finally, based on predicted probabilities on combining neutrophils and platelets with NLR or NLPR, the adjusted AUC was 0.97 (95% CI = 0.94-0.98) to differentiate COVID-19 from dengue during the acute phase of infection with outstanding accuracy. These findings might suggest that the neutrophil, platelet counts, and NLR or NLPR provide a quick and cost-effective way to distinguish between dengue and COVID-19 in the context of co-epidemics in low-income tropical regions.

Megtec Systems pilot-plant scale continuous convective coater. The data was generated as part of an experimental design involving the following coating-drying process variables and ranges: comma bar gap, 80-140 µm; web speed, 0.5-1.5 m/min; coating ratio, 110-150%; drying temperature, 85-110 °C and drying air speed, 5-15 m/s. The manufacturing data include pre-calendered coating thickness, mass loading dry and wet, pre-calendered porosity, spatial autocorrelation and join counting (SAJC) Z -score for carbon and for fluorine, cell thickness, coating weight and porosity of 15 different electrode coatings and 45 half-coin cells. The electrochemical data was obtained at 25 °C in a Maccor 4000 series battery cycler and consists of charge and discharge capacities at C/20, C/5, C/2, 1C, 2C, 5C and 10C C-rates. Discharge gravimetric and volumetric capacities, rate performance (at 5C:0.2C) and first cycle loss data is also reported. Details of the experimental design and a comprehensive analysis of the data can be found in the co-submitted manuscript (Román-Ramírez et al., 2021). Additional collected data not used in Román-Ramírez et al. (2021) is reported in the present manuscript and include visual observations of coating defects, rheological properties of the electrode slurries (solid content, viscosity, coating shear rate and viscosity at coating shear rate), room temperature and room humidity during the coatings and first cycle loss of the coin cells. Raw and analyzed data is made available. The reported data can be used to extend the analysis reported in Román-Ramírez et al. (2021), and for the comparison of relevant data obtained at different manufacturing scales., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2021 The Author(s). Published by Elsevier Inc.)

Background: According to the World Health Organization, Mexico presents one of the highest mortality rates due to coronavirus disease 2019 (COVID-19). The "cytokine storm" phenomenon has been proposed as a pathological hallmark of severe COVID-19., Objective: To determine the association of serum cytokine levels with COVID-19 severity., Methods: We studied the cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and the IFN-γ serum levels through flow cytometry in 56 COVID-19 patients (24 critical and 32 non-critical) from Northwest Mexico., Results: We observed a significant increase in the IL-6 and the IL-10 levels in the sera of critical patients. These cytokines were also associated with mechanical ventilation necessity and death, IL-6 showing AUC values above 0.7 for both variables; and correlated with Na+, creatinine, and platelet levels. On the other hand, no association was found between IL-2, IL-4, TNF-α, and IFN-γ with tested variables., Conclusion: Our results corroborate previous observations regarding IL-6 and IL-10 involvement in the severity of COVID-19.

Interleukin-10 ( IL-10 ) gene polymorphisms have been associated with severity and outcomes in patients with respiratory and nonrespiratory viral infections. The aim of this study was to assess whether rs1800871 and rs1800872 polymorphisms of IL-10 gene are associated with the clinical outcomes of COVID-19 in a Mexican population. Study subjects were 193 COVID-19 patients. The genotyping was carried out with real-time PCR and serum IL-10 levels were measured with enzyme-linked immunosorbent assay. Logistic regression analysis was used for analysis association with clinical outcomes. There was no evidence of an association between alleles, genotypes, or haplotypes frequencies between patient groups according to severity and outcomes. The rs1800871 and rs1800872 polymorphisms might not be genetic risk factors for severity and mortality for COVID-19 in Mexican mestizos patients from northwest Mexico.

Sporotrichosis is a fungal disease caused by the members of the Sporothrix pathogenic clade, and one of the etiological agents is Sporothrix schenckii. The cell wall of this organism has been previously analyzed and thus far is known to contain an inner layer composed of chitin and β -glucans, and an outer layer of glycoproteins, which are decorated with mannose and rhamnose-containing oligosaccharides. The L-rhamnose biosynthesis pathway is common in bacteria but rare in members of the Fungi kingdom. Therefore, in this study, we aimed to disrupt this metabolic route to assess the contribution of rhamnose during the S. schenckii -host interaction. We identified and silenced in S. schenckii a functional ortholog of the bacterial rmlD gene, which encodes for an essential reductase for the synthesis of nucleotide-activated L-rhamnose. RmlD silencing did not affect fungal growth or morphology but decreased cell wall rhamnose content. Compensatory, the β-1,3-glucan levels increased and were more exposed at the cell surface. Moreover, when incubated with human peripheral blood mononuclear cells, the RmlD silenced mutants differentially stimulated cytokine production when compared with the wild-type strain, reducing TNFα and IL-6 levels and increasing IL-1 β and IL-10 production. Upon incubation with human monocyte-derived macrophages, the silenced strains were more efficiently phagocytosed than the wild-type strain. In both cases, our data suggest that rhamnose-based oligosaccharides are ligands that interact with TLR4. Finally, our findings showed that cell wall rhamnose is required for the S. schenckii virulence in the G. mellonella model of infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Coccidioidomycosis is a systemic fungal disease caused by Coccidioides immitis and Coccidioides posadasii. The lungs are the most common and often the initial site of involvement, and the non-pulmonary presentation is infrequent. We describe an unusual case of primary craniocutaneous coccidioidomycosis in a pregnant woman with infected bilateral periorbital nodules, intense pain at paranasal sinuses, and several osteolytic skull lesions. The analysis of 54 cases available in the literature makes us suggest that the area between the United States and Mexico is a risk zone for primary cutaneous coccidioidomycosis.

Objectives: To summarize the procedure for reporting adverse drug reactions (ADRs) in a Mexican hospital, with the purpose of promoting and facilitating the report of ADRs by the heath team. We outline the relevance of pharmacists in performing these activities in Mexican hospitals., Methods: A pharmacovigilance study was carried out following the establishment of the Pharmacovigilance Unit of a Mexican hospital on January 2014 through March 2019., Key Findings: There is an undernotification rate of ADRs, since only 137 ADRs were notified in a five-year period, mostly by biopharmaceutical chemists holding bachelor's degrees that were acting as pharmacists., Conclusions: To improve the safety of medications, it is necessary to improve ADR notifications in Mexico's health system. One important step in this direction is to establish a Pharmacy degree with training for promoting and performing ADR notifications., (© 2020 Royal Pharmaceutical Society.)

Sporothrix schenckii , Sporothrix brasiliensis , and Sporothrix globosa are etiological agents of sporotrichosis, a human subcutaneous mycosis. Although the protocols to evaluate Sporothrix virulence in animal models are well described, the cell preparation before inoculation is not standardized, and several culturing media are used to grow yeast-like cells. Here, we found that carbon or nitrogen limitation during fungal cell preparation negatively impacted the ability of S. schenckii and S. brasiliensis to kill Galleria mellonella larvae, but not S. globosa . The fungal growth conditions associated with the short median survival of animals were accompanied by increased hemocyte countings, phenoloxidase activity, and cytotoxicity. The fungal growth under carbon or nitrogen limitation also affected the cell wall composition of both S. schenckii and S. brasiliensis and showed increased exposure of β-1,3-glucan at the cell surface, while those growing conditions had a minimal impact on the S. globosa wall, which had higher levels of this polysaccharide exposed on the wall regardless of the culture condition. This polysaccharide exposure was linked to the increased ability of insect hemocytes to uptake fungal cells, suggesting that this is one of the mechanisms behind the lower virulence of S. globosa or cells from the other species grown in carbon or nitrogen limitation.

Fungal infections are a serious and increasing threat for human health, and one of the most frequent etiological agents for systemic mycoses is Candida spp. The gold standard to assess Candida virulence is the mouse model of systemic candidiasis, a restrictive, expensive, and time-consuming approach; therefore, invertebrate models have been proposed as alternatives. Galleria mellonella larvae have several traits that make them good candidates to study the fungal virulence. Here, we showed that a reduction in circulating hemocytes, increased melanin production, phenoloxidase, and lactate dehydrogenase activities were observed at 12 and 24 h postinoculation of highly virulent Candida tropicalis strains, while minimal changes in these parameters were observed in low-virulent strains. Similarly, the most virulent species Candida albicans , Candida tropicalis , Candida auris , Candida parapsilosis , and Candida orthopsilosis have led to significant changes in those parameters; while the low virulent species Candida guilliermondii , Candida krusei , and Candida metapsilosis induced modest variations in these immunological and cytotoxicity parameters. Since changes in circulating hemocytes, melanin production, phenoloxidase and lactate dehydrogenase activities showed a correlation with the larval median survival rates at 12 and 24 h postinoculation, we proposed them as candidates for early virulence predictors in G. mellonella .

The catalyzed methanolysis of end-of-life poly(lactic acid) (PLA) products by an ethylenediamine Zn(II) complex to form biodegradable methyl lactate was studied experimentally at 70, 90, and 110 °C. The PLA samples consisted of typical consumer waste materials, including a cup, a toy, and a three-dimensional (3D) printing material. High selectivities and yields (>94%) were possible depending on temperature and reaction time. Additionally, and to develop a predictive kinetic model, kinetic parameters (pre-exponential factor and activation energies) of the PLA transesterification reaction were first obtained from virgin PLA. These parameters were subsequently used to estimate the conversion of PLA, selectivity, and yield of methyl lactate after 1 and 4 h of the reaction, and the results were compared with the experimental values of the end-of-life PLA. Despite the presence of unknown additives in the PLA waste material and uncontrolled particle size, the model was able to predict the overall conversion, selectivity, and yield to an average deviation of 5, 7, and 12%, respectively. A greater agreement between the model and experimental values is observed for the higher temperatures and the longer reaction time. Larger deviations were observed for the PLA toy, which we attribute to the presence of additives, since despite its lower molecular weight, it possessed a higher structural strength., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Introduction: Bidens odorata Cav (Asteraceae) is a medicinal plant employed for the treatment of pain, anxiety, and depression. This study aimed to evaluate some neuropharmacological effects of an ethanol extract of B. odorata (BOE) and assess its antinociceptive interaction with naproxen and paracetamol., Materials and Methods: The following neuropharmacological effects were evaluated with the ethanolic extract of B. odorata leaves (BOE) (10-200 mg/kg p.o.): the strychnine-induced-convulsion assay (anticonvulsant effect), rotarod test (locomotor activity), tail suspension test (anti-depressant-like activity), cylinder exploratory test (anxiolytic-like actions), and pentobarbital-induced sleep test (sedative effect). The interaction of the BOE-paracetamol and BOE-naproxen combinations were evaluated with the acetic acid-induced writhing test. The ED 50 value of each drug was estimated and the combinations of paracetamol and naproxen with BOE were calculated., Results: BOE (100-200 mg/kg) showed anti-convulsant activity by increasing the latency to occurrence of strychnine-induced convulsions, antidepressant-like effects by 28% and 33%, respectively, exerted anxiolytic actions (ED 50  = 125 mg/kg), but did not affect motor locomotion. The pre-treatment with 2 mg/kg flumazenil or 20 mg/kg pentylenetetrazol partially reverted the anxiolytic activity shown by BOE alone. BOE (200 mg/kg) prolonged the duration of sleep with similar effect in comparison to clonazepam (1.5 mg/kg). The combinations of BOE-paracetamol (1:1) and BOE-naproxen (1:1) showed antinociceptive synergism., Conclusion: BOE induces sedative and anticonvulsant effects. The anxiolytic actions shown by BOE are probably induced by the participation of the GABAergic system. BOE exerts antinociceptive synergistic interaction with paracetamol and naproxen probably by the participation of nitric oxide and ATP-sensitive K + channels, respectively.

The kinetics of the transesterification of polylactic acid (PLA) with methanol to form methyl lactate catalyzed by Zn(II) complexes was studied experimentally and numerically. The complexes, Zn( 1 Et ) 2 and Zn( 2 Pr ) 2 , were synthesized from ethylenediamine and propylenediamine Schiff bases, respectively. The temperature range covered was 313.2-383.2 K. An increase in the reaction rate with the increase in temperature was observed for the Zn( 1 Et ) 2 -catalyzed reaction. The temperature relationship of the rate coefficients can be explained by a linear Arrhenius dependency with constant activation energy. The kinetics of Zn( 2 Pr ) 2 , on the other hand, is only explained by non-Arrhenius kinetics with convex variable activation energy, resulting in faster methyl lactate production rates at 323.2 and 343.2 K. The formation of a new catalyst species, likely through reaction with protic reagents, appears to promote the formation of intermediate complexes, resulting in the nonlinear behavior. Stirring speed induced the stability of the intermediate complexes. Contrary to Zn( 1 Et ) 2 , Zn( 2 Pr ) 2 was susceptible to the presence of air/moisture in solution. The kinetic parameters were obtained by fitting the experimental data to the mass and energy balance of a consecutive second step reversible reaction taking place in a jacketed stirred batch reactor. For the case of Zn( 2 Pr ) 2 , the activation energy was fitted to a four-parameter equation. The kinetic parameters presented in this work are valuable for the design of processes involving the chemical recycling of PLA into green solvents., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Recurrent glenohumeral dislocation is usually associated with bone loss of the glenoid portion, with the anteroinferior location being the most affected. The understanding of the related structures, as well as the use of current imaging studies such as computed axial tomography and magnetic resonance imaging, have made progress in understanding the pathology, as well as the development of surgical materials and minimally invasive tools, they allow us to continue innovating with respect to the previously described treatments, being possible to intervene in technical details with the intention of improving the results. That is why we have done what described by Eden-Hybinette, using tricortical cadaveric graft and as fixation method, limiting the comorbidities associated with the autograft taking, resulting a wide benefit for the patient, during the surgical procedure and in the recovery period.

Background: Pulmonary aspergillosis is a severe invasive infection that mainly affects immunocompromised patients, causing a great mortality., Clinical Case: We present a male patient with chronic ethilism, diabetes mellitus, and work exposure of inhalated harmful chemicals, who had a fatal outcome, that even when not presenting typical risk factors, developed a clinical presentation compatible, and mycological evaluation that support the diagnosis of a probably invasive pulmonary aspergillosis., Conclusion: The effect of the combination of the described non-typical situations as predisposing factors for pulmonary aspergillosis requires further research, given that they are non-typical factors.