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An association of ABO blood group and COVID-19 remains controversial. Following STROBE guidance for observational research, we explored the distribution of ABO blood group in patients hospitalized for acute COVID-19 and in those with Long COVID. Contingency tables were made and risk factors were explored using crude and adjusted Mantle-Haentzel odds ratios (OR and 95% CI). Up to September 2022, there were a total of 5,832 acute COVID-19 hospitalizations in our hospital, corresponding to 5,503 individual patients, of whom blood group determination was available for 1,513 (27.5%). Their distribution by ABO was: 653 (43.2%) group 0, 690 (45.6%) A, 113 (7.5%) B, and 57 (3.8%) AB, which corresponds to the expected frequencies in the general population. In parallel, of 676 patients with Long COVID, blood group determination was available for 135 (20.0%). Their distribution was: 60 (44.4%) from group 0, 61 (45.2%) A, 9 (6.7%) B, and 5 (3.7%) AB. The distribution of the ABO system of Long COVID patients did not show significant differences with respect to that of the total group (p ≥ 0.843). In a multivariate analysis adjusting for age, sex, ethnicity, and severity of acute COVID-19 infection, subgroups A, AB, and B were not significantly associated with developing Long COVID with an OR of 1.015 [0.669-1.541], 1.327 [0.490-3.594] and 0.965 [0.453-2.058], respectively. The effect of the Rh+ factor was also not significant 1,423 [0.772-2,622] regarding Long COVID. No association of any ABO blood subgroup with COVID-19 or developing Long COVID was identified.

How a history of influenza virus infections contributes to protection is not fully understood, but such protection might explain the contrasting age distributions of cases of the two lineages of influenza B, B/Victoria and B/Yamagata. Fitting a statistical model to those distributions using surveillance data from New Zealand, we found they could be explained by historical changes in lineage frequencies combined with cross-protection between strains of the same lineage. We found additional protection against B/Yamagata in people for whom it was their first influenza B infection, similar to the immune imprinting observed in influenza A. While the data were not informative about B/Victoria imprinting, B/Yamagata imprinting could explain the fewer B/Yamagata than B/Victoria cases in cohorts born in the 1990s and the bimodal age distribution of B/Yamagata cases. Longitudinal studies can test if these forms of protection inferred from historical data extend to more recent strains and other populations. The earliest infections with influenza A shape the immune responses to future infections, but it is not known if this phenomenon applies to influenza B. Here, the authors use influenza B case data from New Zealand and find evidence for both lineage-specific and imprinting protection.

Diaphorina citri Kuwayama (Hemiptera: Liviidae) stands out as the most critical pest in citriculture. With chemical pesticides facing reduced efficacy and increased resistance in populations, biological control has emerged as a promising strategy. The performance of entomopathogenic fungi is influenced by abiotic factors such as RH and ultraviolet radiation (UV-B). Understanding how these factors interact with entomopathogens enables us to optimize their efficiency against the pest, guiding the ideal timing for application and identifying the most favorable seasons. Our study aimed to assess the impact of different RH levels and UV-B exposure on the efficacy of the entomopathogenic fungus Cordyceps javanica (Frieder. and Bally) Kepler, B. Shrestha, and Spatafora (Hypocreales: Cordycipitaceae) strain ESALQ1296 in controlling D. citri . C. javanica with 0.075% KBRAdj® exhibited superior performance in D. citri control across all moisture levels, particularly during periods of low RH (≤ 50%) and extended UV-B exposure (> 4 h), when compared to Tween 80. However, it is expected to perform better when spraying during periods with lower UV-B radiation incidence and higher RH. Considering the high efficacy required to control this vector, implementing the fungus is contingent on the formulation utilized and the prevailing environmental conditions.

The Asian citrus psyllid, Diaphorina citri , is the most serious threat to citrus crops worldwide, and its management relies exclusively on frequent applications of chemical insecticides. Entomopathogenic fungi may play an important role for regulating this citrus pest. Two virulent fungal strains, Isaria fumosorosea ESALQ-1296 and Beauveria bassiana ESALQ-PL63, were selected among 17 fungal isolates under laboratory conditions and caused 77.8 and 78.4% adult mortality, respectively, while in semifield trials the adult mortality reached up to 83.5% with B. bassiana and 80.6% with I. fumosorosea . The bioefficacy of these two fungi on D. citri adults was assessed through monthly applications during 1 year in a commercial citrus grove located in Itapetininga, São Paulo, Brazil. The application of I. fumosorosea ESALQ-1296 and B. bassiana ESALQ-PL63 was as effective as the chemical insecticides in most trials. The fungal-induced mortality of D. citri adults ranged from 96.1% in December 2011 to 57.8% in October 2012. This mortality level tended to build up with the increase in the maximum relative humidity; the percentage of sporulated cadavers was positively correlated with both higher relative humidity and rainfall but negatively associated with maximum temperatures. These results support the use of I. fumosorosea or B. bassiana as an eco-friendly biopesticide for the integrated management of D. citri .

In the mouse embryo, the transition from the preimplantation to the postimplantation epiblast is governed by changes in the gene regulatory network (GRN) that lead to transcriptional, epigenetic, and functional changes. This transition can be faithfully recapitulated in vitro by the differentiation of mouse embryonic stem cells (mESCs) to epiblast-like cells (EpiLCs), that reside in naïve and formative states of pluripotency, respectively. However, the GRN that drives this conversion is not fully elucidated. Here we demonstrate that the transcription factor OCT6 is a key driver of this process. Firstly, we show that Oct6 is not expressed in mESCs but is rapidly induced as cells exit the naïve pluripotent state. By deleting Oct6 in mESCs, we find that knockout cells fail to acquire the typical morphological changes associated with the formative state when induced to differentiate. Additionally, the key naïve pluripotency TFs Nanog, Klf2, Nr5a2, Prdm14, and Esrrb were expressed at higher levels than in wild-type cells, indicating an incomplete dismantling of the naïve pluripotency GRN. Conversely, premature expression of Oct 6 in naïve cells triggered a rapid morphological transformation mirroring differentiation, that was accompanied by the upregulation of the endogenous Oct6 as well as the formative genes Sox3 , Zic2/3, Foxp1, Dnmt3A and FGF5. Strikingly, we found that OCT6 represses Nanog in a bistable manner and that this regulation is at the transcriptional level. Moreover, our findings also reveal that Oct6 is repressed by NANOG. Collectively, our results establish OCT6 as a key TF in the dissolution of the naïve pluripotent state and support a model where Oct6 and Nanog form a double negative feedback loop which could act as an important toggle mediating the transition to the formative state.

Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB). By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM), characterized by a highly heterogeneous cell population (including tumor stem cells), extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the BBB and the concerns that arise when this barrier is affected.

In planta RNAi or host-induced gene silencing (HIGS) has undergone significant advancements that have rendered it efficient and stable at the transgenerational level in plants for regulating host genes and targeting genes of insect pests and plant pathogens. Similarly, topical RNAi or spray-induced gene silencing (SIGS) has garnered considerable attention as an environmentally sustainable, selective, and alternative approach to chemical control of insect pests and plant pathogens. Several biotechnology companies and startups have focused their efforts on RNAi-based solutions for topical application in agriculture. Nevertheless, further technological advancements are required to enhance the efficacy of topical RNAi in agriculture, including improved dsRNA delivery systems, better target gene selection, and addressing biosafety regulatory issues. Herein, this review discusses key advances and bottlenecks in RNAi, and summarizes successful applications of these RNAi-based technologies in agriculture focusing on in planta and topical RNAi to control insect pests and plant pathogens. Furthermore, this review delves into the patenting landscape, biosafety considerations, risk evaluations, and the current regulatory status of RNAi in Latin America. Finally, it explores the contributions of RNAi to plant science, food production, and fostering a more sustainable form of agriculture.

Intrahost genetic diversity is thought to facilitate arbovirus adaptation to changing environments and hosts, and it might also be linked to viral pathogenesis. Dengue virus serotype 2 (DENV-2) has circulated in Brazil since 1990 and is associated with severe disease and explosive outbreaks. Intending to shed light on the viral determinants for severe dengue pathogenesis, we sought to analyze the DENV-2 intrahost genetic diversity in 68 patient cases clinically classified as dengue fever (n = 31), dengue with warning signs (n = 19), and severe dengue (n = 18). Unlike previous DENV intrahost diversity studies whose approaches employed PCR, here we performed viral whole-genome deep sequencing from clinical samples with an amplicon-free approach, representing the real intrahost diversity scenario. Striking differences were detected in the viral population structure between the three clinical categories, which appear to be driven mainly by different infection times and selection pressures, rather than being linked with the clinical outcome itself. Diversity in the NS2B gene, however, showed to be constrained, irrespective of clinical outcome and infection time. Finally, 385 non-synonymous intrahost single-nucleotide variants located along the viral polyprotein, plus variants located in the untranslated regions, were consistently identified among the samples. Of them, 124 were exclusively or highly detected among cases with warning signs and among severe cases. However, there was no variant that by itself appeared to characterize the cases of greater severity, either due to its low intrahost frequency or the conservative effect on amino acid substitution. Although further studies are necessary to determine their real effect on viral proteins, this heightens the possibility of epistatic interactions. The present analysis represents an initial effort to correlate DENV-2 genetic diversity to its pathogenic potential and thus contribute to understanding the virus’s dynamics within its human host.

The SARS-CoV-2 virus has created an unprecedented impact on healthcare globally. Being a novel virus, several treatments have been explored against COVID-19. During the early stages of the disease, treatment is mainly supportive. While several studies have suggested different treatment modalities, there is still no definitive treatment against COVID-19. Re-purposing already established medications, with excellent safety profiles, is a possible approach for treating the disease in its early stage. Having a mode of transmission as a droplet mode, several studies have supported how the nose can contain the primary route of entry of SARS-CoV-2. Hence, we postulated that re-purposing a commercially available nasal spray containing xylitol and grapefruit seed extract (GSE), namely Xlear Nasal Spray® (Xlear, Inc., American Fork, USA) could be used as an adjunct treatment of COVID-19. With a well-established safety profile, the components of this nasal spray have been studied and have been shown to have potential efficacy against viral pathogens, including coronavirus, and may potentially regulate pathways important in the initial entry of infection, replication, and systemic response to SARS-CoV-2. We present a series of three mild-moderate risks, symptomatic, COVID-19 patients, treated with the intranasal combination, as an adjuvant to their ongoing treatment, with rapid clinical improvement and shorten time to negativization on repeat intranasal swab test via PCR. No safety issues were noted during the course of treatment. Xlear nasal spray, containing xylitol plus GSE, given its established safety profile and compelling clinical results described here, could be a potential adjunct treatment option in mild-moderate COVID-19 cases.The SARS-CoV-2 virus has created an unprecedented impact on healthcare globally. Being a novel virus, several treatments have been explored against COVID-19. During the early stages of the disease, treatment is mainly supportive. While several studies have suggested different treatment modalities, there is still no definitive treatment against COVID-19. Re-purposing already established medications, with excellent safety profiles, is a possible approach for treating the disease in its early stage. Having a mode of transmission as a droplet mode, several studies have supported how the nose can contain the primary route of entry of SARS-CoV-2. Hence, we postulated that re-purposing a commercially available nasal spray containing xylitol and grapefruit seed extract (GSE), namely Xlear Nasal Spray® (Xlear, Inc., American Fork, USA) could be used as an adjunct treatment of COVID-19. With a well-established safety profile, the components of this nasal spray have been studied and have been shown to have potential efficacy against viral pathogens, including coronavirus, and may potentially regulate pathways important in the initial entry of infection, replication, and systemic response to SARS-CoV-2. We present a series of three mild-moderate risks, symptomatic, COVID-19 patients, treated with the intranasal combination, as an adjuvant to their ongoing treatment, with rapid clinical improvement and shorten time to negativization on repeat intranasal swab test via PCR. No safety issues were noted during the course of treatment. Xlear nasal spray, containing xylitol plus GSE, given its established safety profile and compelling clinical results described here, could be a potential adjunct treatment option in mild-moderate COVID-19 cases.

This study aimed to create an equation to predict dry matter intake (DMI) and milk production and N-ureic in the milk of dairy cows managed in tropical conditions in Brazil. We used 113 observations from three experiments using lactating Jersey, Girolando, and Holstein cows. The goodness of fit of the developed equations was evaluated using the coefficients of determination (r2) and root mean square error (RMSE). There was a positive correlation between body weight and milk yield (MY) of r = 0.73. The equation considered DMI to be the most important variable to estimate the MY (r2 = 0.65). Four equations were adjusted to estimate the DMI, where, by a stepwise procedure, the first variable included in the equation was the neutral detergent fibre intake, which explained 92% of the DMI of the cows. However, when the variables BW, MY, and milk fat were included in the equation, there was a reduction of 0.06 in RMSE and an increase in precision (r2 = 0.94). The nutrient intake, milk production, and characteristics prediction equations present satisfactory precision and accuracy for dairy cows managed in tropical conditions in Brazil.