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Sidney Julio Faria-e-Sousa,1 Monike de Paula Gomes Vieira,1 Jailton Vieira Silva21University of São Paulo, São Paulo, Brazil; 2Federal University of Ceará, Ceará, BrazilPurpose: Intermittent entropion may go unnoticed by both patient and physician, in some instances resulting in ocular surface disorders. Unfortunately, the current work-up used to diagnose entropion is not always sufficient to uncover the problem. We present an alternative diagnostic test.Cases: Two case reports are presented showing different situations where the current methods for detection of entropion failed and the diagnosis was only made with an alternative diagnostic test.Results: The common denominator of both cases is an intermittent entropion which could not be detected by the conventional clinical work-up. Diagnosis was easy however using the “TIE test” described in the text.Conclusion: The important clues for suspicion of intermittent entropion are an intermittent foreign-body sensation in the eye accompanied with central punctate keratopathy. The TIE test is a simple and useful test for the diagnosis of intermittent entropion.Keywords: eyelids, lid abnormality, TIE test

Introduction: Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established.Purpose: Elucidate the mechanisms of induction of delayed diarrhea and determine the effects of the cytokine production inhibitor pentoxifylline (PTX) and thalidomide (TLD) in the experimental model of intestinal mucositis, induced by CPT-11.Materials and Methods: Intestinal mucositis was induced in male Swiss mice by intraperitoneal administration of CPT-11 (75 mg/kg) daily for 4 days. Animals received subcutaneous PTX (1.7, 5 and 15 mg/kg) or TLD (15, 30, 60 mg/kg) or 0.5 ml of saline daily for 5 and 7 days, starting 1 day before the first CPT-11 injection. The incidence of delayed diarrhea was monitored by scores and the animals were sacrificed on the 5th and 7th experimental day for histological analysis, immunohistochemistry for TNF-alpha and assay of myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and KC ELISA.Results: CPT-11 caused significant diarrhea, histopathological alterations (inflammatory cell infiltration, loss of crypt architecture and villus shortening) and increased intestinal tissue MPO activity, TNF-alpha, IL-1beta and KC level and TNF-alpha immuno-staining. PTX inhibited delayed diarrhea of mice submitted to intestinal mucositis and reduced histopathological damage, intestinal MPO activity, tissue level of TNF-alpha, IL-1beta and KC and TNF-alpha immuno-staining. TLD significantly reduced the lesions induced by CPT-11 in intestinal mucosa, decreased MPO activity, TNF-alpha tissue level and TNF-alpha immuno-staining, but did not reduce the severity of diarrhea.Conclusion: These results suggest an important role of TNF-alpha, IL-1beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11. [ABSTRACT FROM AUTHOR]

In order to benefit from antiretroviral therapy, pregnant women infected with HIV must be tested and diagnosed. Not infrequently, however, women present in labor without prior prenatal care and are thus unable to benefit fully from HIV testing and, if infected, antiretroviral therapy. In this study we evaluated the need for rapid perinatal HIV testing for untested mothers presenting in labor in a public maternal-child hospital that provides care for metropolitan Porto Alegre, Brazil, and potentially modifiable risk factors for noncompliance with national recommendations. We surveyed a consecutive sample of women who gave birth at Hospital Materno-Infantil Presidente Vargas (Presidente Vargas Mother-and-child Hospital) in August-October 2001and administered a structured questionnaire to consenting participants. The questionnaire consisted of demographic data, information on health-seeking behavior, knowledge of HIV infection, and testing during pregnancy. We confirmed information on HIV testing, syphilis, and hepatitis B by examination of the patient's prenatal records. We also obtained data regarding laboratory testing and treatment during labor and delivery (e.g., HIV testing, antiretroviral treatment, and suppression of lactation) from hospital inpatient charts. Of 214 eligible participants, 209 (98%) agreed to participate in the study. Overall 173 (83%) of the 209 participants had had a previous HIV test and 36 (17%) had not. Women with fewer pregnancies were more likely to have been tested (p = .017), as were women with lower family incomes (p = .007). No women had received rapid tests in the delivery room. Of the 209 participants, 201 (96%) had had at least one prenatal visit and 169 (81%) had had three or more visits; 12 (6%) of these reported that they had not been offered an HIV test, 5 (2%) did not know if testing had been offered or not, and 191 (95%) reported that they had been offered a test. We were able to obtain prenatal records for 190 (95%) of the 201participants who had received prenatal care. HIV testing was not mentioned in 9% of charts. Results of syphilis tests were recorded on prenatal records or hospital charts for 167 (80%)participants, and results of hepatitis B surface antigen were found for 93 (45%). Women who to 30pchad had three or more prenatal visits were significantly more likely to have been tested for to 30pcHIV (OR 46.96, 95% CI, 15.92-144.85, .0001), syphilis (OR 31.64, 95% CI, 11.81-87.42, p < .0001) or HBsAg (OR, 4.88, 95% CI, 1.91-12.99, p < .0001) than women who had had two prenatal visits or fewer. Our study showed shown that in 12% of the pregnancies included in our sample national recommendations for prenatal or perinatal testing were not followed, and in an additional 5%, HIV testing, though offered, was not obtained. These women could potentially have benefited from rapid HIV testing. As knowledge of HIV and risk factors for transmission were almost universal in our sample, we believe that the passive health-seeking behavior we observed may offer an opportunity for targeting new efforts to promote the importance of prenatal care and prenatal diagnosis of HIV. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a global challenge to the clinical field and food industry. Therefore, the development of antimicrobial photodynamic therapy (aPDT) has become one of the valuable methods to control this pathogen. The antibacterial activity of photoinactivation by erythrosine (Ery) against S. aureus has been reported, but its modes of action are unclear. This study aimed to employ a proteomic approach to analyze modes of action of Ery-aPDT against S. aureus. We determined the antibacterial effect by Ery-aPDT assays, quantified reactive oxygen species (ROS) and injury to the cell membrane, and determined protein expression using a proteomic approach combined with bioinformatic tools. Ery-aPDT was effective in reducing S. aureus to undetectable levels. In addition, the increment of ROS accompanied the increase in the reduction of cell viability, and damage to cellular membranes was shown by sublethal injury. In proteomic analysis, we found 17 differentially expressed proteins. These proteins revealed changes mainly associated with defense to oxidative stress, energy metabolism, translation, and protein biosynthesis. Thus, these results suggest that the effectiveness of Ery-aPDT is due to multi-targets in the bacterial cell that cause the death of S. aureus., (© 2024 American Society for Photobiology.)

Globally, illegal sport hunting can threaten prey populations when unregulated. Due to its covert nature, illegal sport hunting poses challenges for data collection, hindering efforts to understand the full extent of its impacts. We gathered social media data to analyze patterns of illegal sport hunting and wildlife depletion across Brazil. We collected data for 2 years (2018-2020) across 5 Facebook groups containing posts depicting pictures of illegal sport hunting events of native fauna. We described and mapped these hunting events by detailing the number of hunters involved, the number of species, the mean body mass of individuals, and the number and biomass of individuals hunted per unit area, stratified by Brazilian biome. We also examined the effects of defaunation on hunting yield and composition via regression models, rank-abundance curves, and spatial interpolation. We detected 2046 illegal sport hunting posts portraying the hunting of 4658 animals (∼29 t of undressed meat) across all 27 states and 6 natural biomes of Brazil. Of 157 native species targeted by hunters, 19 are currently threatened with extinction. We estimated that 1414 hunters extracted 3251 kg/million km 2 . Some areas exhibited more pronounced wildlife depletion, in particular the Atlantic Forest and Caatinga biomes. In these areas, there was a shift from large mammals and reptiles to small birds as the main targeted taxa, and biomass extracted per hunting event and mean body mass across all taxonomic groups were lower than in other areas. Our results highlight that illegal sport hunting adds to the pressures of subsistence hunting and the wild meat trade on Brazil's wildlife populations. Enhanced surveillance efforts are needed to reduce illegal sport hunting levels and to develop well-managed sustainable sport hunting programs. These can support wildlife conservation and offer incentives for local communities to oversee designated sport hunting areas., (© 2024 The Author(s). Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Yield gap analysis is used to characterize the untapped production potential of cropping systems. With emerging large-n agronomic datasets and data science methods, pathways for narrowing yield gaps can be identified that provide actionable insights into where and how cropping systems can be sustainably intensified. Here we characterize the contributing factors to rice yield gaps across seven Indian states, with a case study region used to assess the power of intervention targeting. Primary yield constraints in the case study region were nitrogen and irrigation, but scenario analysis suggests modest average yield gains with universal adoption of higher nitrogen rates. When nitrogen limited fields are targeted for practice change (47% of the sample), yield gains are predicted to double. When nitrogen and irrigation co-limitations are targeted (20% of the sample), yield gains more than tripled. Results suggest that analytics-led strategies for crop intensification can generate transformative advances in productivity, profitability, and environmental outcomes., (© 2024. The Author(s).)

Lisdexamfetamine dimesylate (LDX) is a prodrug of dextroamphetamine, which has been widely recommended for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). There are still no data in the literature relating the possible toxic effects of LDX in the kidney. Therefore, the present study aims to evaluate the effects of LDX exposure on morphological, oxidative stress, cell death and inflammation parameters in the kidneys of male pubertal Wistar rats, since the kidneys are organs related to the excretion of most drugs. For this, twenty male Wistar rats were distributed randomly into two experimental groups: LDX group-received 11,3 mg/kg/day of LDX; and Control group-received tap water. Animals were treated by gavage from postnatal day (PND) 25 to 65. At PND 66, plasma was collected to the biochemical dosage, and the kidneys were collected for determinations of the inflammatory profile, oxidative status, cell death, and for histochemical, and morphometric analyses. Our results show that there was an increase in the number of cells marked for cell death, and a reduction of proximal and distal convoluted tubules mean diameter in the group that received LDX. In addition, our results also showed an increase in MPO and NAG activity, indicating an inflammatory response. The oxidative status showed that the antioxidant system is working undisrupted and avoiding oxidative stress. Therefore, LDX-exposition in male rats during the peripubertal period causes renal changes in pubertal age involving inflammatory mechanisms, antioxidant activity and apoptosis process., (© 2024 Wiley Periodicals LLC.)

Attalea phalerata Martius ex Spreng is a palm tree that is widely distributed in the Central-West region of Brazil. In this study, we investigated whether the oil-loaded nanocapsules of A. phalerata (APON) have acute and long-lasting antihypertensive effects in male spontaneously hypertensive rats (SHR), as well as explored the underlying molecular mechanisms. APON was prepared using the interfacial polymer deposition method. The particle size, polydispersity index, and zeta potential were investigated using dynamic and electrophoretic light scattering. The antihypertensive effects of APON (administered at doses of 1, 3, and 10 mg/kg) were evaluated after acute intraduodenal administration and after 7 days of oral treatment. To investigate the molecular pathways involved, we used pharmacological antagonists and inhibitors that target prostaglandin/cyclic adenosine monophosphate, nitric oxide/cyclic guanosine monophosphate, and potassium channels. Both acute and prolonged administration of APON (at doses of 3 and 10 mg/kg) resulted in a significant reduction in systolic, diastolic, and mean arterial pressure. Prior treatment with a non-selective nitric oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester), guanylyl cyclase inhibitor (methylene blue), or non-selective calcium-sensitive K + channel blocker (tetraethylammonium) abolished the antihypertensive effects of APON. Our study showed that A. phalerata oil-loaded nanocapsules have a significant antihypertensive effect in SHR after both short-term and long-term (7-day) use. This effect seems to rely on the vascular endothelium function and involves the NO-cGMP-K + channel pathway. This research suggests a new direction for future studies to definitively prove the therapeutic benefits of APON in treating cardiovascular disease.

Background: Fungal keratitis is a severe eye infection that can result in blindness and visual impairment, particularly in developing countries. Fusarium spp. are the primary causative agents of this condition. Diagnosis of Fusarium keratitis (FK) is challenging, and delayed treatment can lead to serious complications. However, there is limited epidemiological data on FK, especially in tropical areas., Objectives: This study aimed to describe the clinical, laboratorial and epidemiological characteristics of FK in a tropical semi-arid region of Brazil., Patients/methods: Adult patients with laboratory-confirmed FK diagnosed between October 2019 and March 2022 were evaluated. Fusarium isolates were characterized at molecular level and evaluated regarding antifungal susceptibility., Results: A total of 226 clinical samples from patients suspected of keratitis were evaluated; fungal growth was detected in 50 samples (22.12%); out of which 42 were suggestive of Fusarium spp. (84%). Molecular analysis of a randomly selected set of 27 isolates identified F. solani species complex (n = 14); F. fujikuroi sensu lato (n = 6) and F. dimerum sensu lato (n = 7); a total of 10 haplotypes were identified among the strains. All but one Fusarium strains were inhibited by amphotericin B, natamycin and fluconazole. Most patients were male (71.42%; 30 out of 42), aged from 27 to 73 years old. Trauma was the most important risk factor for FK (40.47%; 17 out of 42). Patients were treated with antifungals, corticoids and antibiotics; keratoplasty and eye enucleation were also performed., Conclusions: The study provided insights into the characteristics of FK in tropical regions and emphasized the importance of enhanced surveillance and management strategies., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

The expansion of globalized industrial societies is causing global warming, ecosystem degradation, and species and language extinctions worldwide. Mainstream conservation efforts still focus on nature protection strategies to revert this crisis, often overlooking the essential roles of Indigenous Peoples and Local Communities (IP&LC) in protecting biodiversity and ecosystems globally. Here we assess the scientific literature to identify relationships between biodiversity (including ecosystem diversity) and cultural diversity, and investigate how these connections may affect conservation outcomes in tropical lowland South America. Our assessment reveals a network of interactions and feedbacks between biodiversity and diverse IP&LC, suggesting interconnectedness and interdependencies from which multiple benefits to nature and societies emerge. We illustrate our findings with five case studies of successful conservation models, described as consolidated or promising 'social-ecological hope spots', that show how engagement with IP&LC of various cultures may be the best hope for biodiversity and ecosystem conservation, particularly when aligned with science and technology. In light of these five inspiring cases, we argue that conservation science and policies need to recognize that protecting and promoting both biological and cultural diversities can provide additional co-benefits and solutions to maintain ecosystems resilient in the face of global changes., (© 2024. Springer Nature Limited.)

Heavy metal exposure leads to multiple system dysfunctions. The mechanisms are likely multifactorial and involve inflammation and oxidative stress. The aim of this study was to evaluate markers and risk factors for atherosclerosis in the LDL receptor knockout mouse model chronically exposed to inorganic mercury (Hg) in the drinking water. Results revealed that Hg exposed mice present increased plasma levels of cholesterol, without alterations in glucose. As a major source and target of oxidants, we evaluated mitochondrial function. We found that liver mitochondria from Hg treated mice show worse respiratory control, lower oxidative phosphorylation efficiency and increased H 2 O 2 release. In addition, Hg induced mitochondrial membrane permeability transition. Erythrocytes from Hg treated mice showed a 50% reduction in their ability to take up oxygen, lower levels of reduced glutathione (GSH) and of antioxidant enzymes (SOD, catalase and GPx). The Hg treatment disturbed immune system cells counting and function. While lymphocytes were reduced, monocytes, eosinophils and neutrophils were increased. Peritoneal macrophages from Hg treated mice showed increased phagocytic activity. Hg exposed mice tissues present metal impregnation and parenchymal architecture alterations. In agreement, increased systemic markers of liver and kidney dysfunction were observed. Plasma, liver and kidney oxidative damage indicators (MDA and carbonyl) were increased while GSH and thiol groups were diminished by Hg exposure. Importantly, atherosclerotic lesion size in the aorta root of Hg exposed mice were larger than in controls. In conclusion, in vivo chronic exposure to Hg worsens the hypercholesterolemia, impairs mitochondrial bioenergetics and redox function, alters immune cells profile and function, causes several tissues oxidative damage and accelerates atherosclerosis development., Competing Interests: Declaration of Competing Interest All authors have no financial and personal relationships with other people or organizations that could inappropriately influence this work. The data that support the findings of this study are available from the corresponding author upon reasonable request., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic was initiated by the rapid spread of a SARS-CoV-2 strain. Though mainly classified as a respiratory disease, SARS-CoV-2 infects multiple tissues throughout the human body, leading to a wide range of symptoms in patients. To better understand how SARS-CoV-2 affects the proteome from cells with different ontologies, this work generated an infectome atlas of 9 cell models, including cells from brain, blood, digestive system, and adipocyte tissue. Our data shows that SARS-CoV-2 infection mainly trigger dysregulations on proteins related to cellular structure and energy metabolism. Despite these pivotal processes, heterogeneity of infection was also observed, highlighting many proteins and pathways uniquely dysregulated in one cell type or ontological group. These data have been made searchable online via a tool that will permit future submissions of proteomic data ( https://reisdeoliveira.shinyapps.io/Infectome&#95;App/ ) to enrich and expand this knowledgebase., (© 2024. The Author(s).)

In Brief: Pyruvate metabolism is one of the main metabolic pathways during oocyte maturation. This study demonstrates that pyruvate metabolism also regulates the epigenetic and molecular maturation in bovine oocytes., Abstract: Pyruvate, the final product of glycolysis, undergoes conversion into acetyl-CoA within the mitochondria of oocytes, serving as a primary fuel source for the tricarboxylic acid (TCA) cycle. The citrate generated in the TCA cycle can be transported to the cytoplasm and converted back into acetyl-CoA. This acetyl-CoA can either fuel lipid synthesis or act as a substrate for histone acetylation. This study aimed to investigate how pyruvate metabolism influences lysine 9 histone 3 acetylation (H3K9ac) dynamics and RNA transcription in bovine oocytes during in vitro maturation (IVM). Bovine cumulus-oocyte complexes were cultured in vitro for 24 h, considering three experimental groups: Control (IVM medium only), DCA (IVM supplemented with sodium dichloroacetate, a stimulant of pyruvate oxidation into acetyl-CoA), or IA (IVM supplemented with sodium iodoacetate, a glycolysis inhibitor). The results revealed significant alterations in oocyte metabolism in both treatments, promoting the utilization of lipids as an energy source. These changes during IVM affected the dynamics of H3K9ac, subsequently influencing the oocyte's transcriptional activity. In the DCA and IA groups, a total of 148 and 356 differentially expressed genes were identified, respectively, compared to the control group. These findings suggest that modifications in pyruvate metabolism trigger the activation of metabolic pathways, particularly lipid metabolism, changing acetyl-CoA availability and H3K9ac levels, ultimately impacting the mRNA content of in vitro matured bovine oocytes.

Sustainable agricultural practices such as conservation agriculture have been promoted in southern Africa for nearly three decades, but their adoption remains low. It is of policy interest to unpack behavioural drivers of adoption to understand why adoption remains lower than anticipated. This paper assesses the effects of risk aversion and impatience on the extent and intensity of the adoption of conservation agriculture using panel data collected from 646 households in 2021 and 2022 in Zambia. We find that 12% and 18% of the smallholders were impatient and risk averse, respectively. There are two main empirical findings based on panel data Probit and Tobit models. First, on the extensive margin, being impatient is correlated with a decreased likelihood of adopting combined minimum-tillage (MT) and rotation by 2.9 percentage points and being risk averse is associated with a decreased propensity of adopting combined minimum tillage (MT) and mulching by 3.2 percentage points. Being risk averse is correlated with a decreased chance of adopting basins by 2.8 percentage points. Second, on the intensive margin, impatience and risk aversion are significantly correlated with reduced adoption intensity of basins, ripping, minimum tillage (MT), and combined MT and rotation by 0.02-0.22 ha. These findings imply a need to embed risk management (e.g., through crop yield insurance) in the scaling of sustainable agricultural practices to incentivise adoption. This can help to nudge initial adoption and to protect farmers from yield penalties that are common in experimentation stages., 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., (© 2024 The Authors.)

The use of carbon nanotubes (CNTs), which are nanometric materials, in pathogen detection, protection of environments, food safety, and in the diagnosis and treatment of diseases, as efficient drug delivery systems, is relevant for the improvement and advancement of pharmacological profiles of many molecules employed in therapeutics and in tissue bioengineering. It has contributed to the advancement of science due to the development of new tools and devices in the field of medicine. CNTs have versatile mechanical, physical, and chemical properties, in addition to their great potential for association with other materials to contribute to applications in different fields of medicine. As, for example, photothermal therapy, due to the ability to convert infrared light into heat, in tissue engineering, due to the mechanical resistance, flexibility, elasticity, and low density, in addition to many other possible applications, and as biomarkers, where the electronic and optics properties enable the transduction of their signals. This review aims to describe the state of the art and the perspectives and challenges of applying CNTs in the medical field. A systematic search was carried out in the indexes Medline, Lilacs, SciELO, and Web of Science using the descriptors "carbon nanotubes", "tissue regeneration", "electrical interface (biosensors and chemical sensors)", "photosensitizers", "photothermal", "drug delivery", "biocompatibility" and "nanotechnology", and "Prodrug design" and appropriately grouped. The literature reviewed showed great applicability, but more studies are needed regarding the biocompatibility of CNTs. The data obtained point to the need for standardized studies on the applications and interactions of these nanostructures with biological systems., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Context and Results: Flavivirus diseases' cycles, especially Dengue and Yellow Fever, can be observed all over Brazilian territory, representing a great health concern. Additionally, there are no drugs available in therapy. In this scenario, in silico methodologies were applied to obtain physicochemical properties, as well as to better understand the ligand-biological target interaction mode of 20 previously reported NS2B/NS3 protease inhibitors of Dengue virus. Since catalytic site of flavivirus hold similarities, such as the same catalytic triad (His51, Asp75 e Ser135), the ability of this series of molecules to fit in Zika NS3 domains can be achieved. We performed an exploratory data analysis, using statistical methodologies, such as PCA (Principal Component Analysis) and HCA (Hierarchical Component Analysis), to assist the comprehension of how physicochemical properties impact the interaction observed by the docking studies, as well as to build a correlation between the respective ranked characteristics. Based on these previous studies, peptides were selected for the dynamics simulations, which were useful to better understand the ligand-protein interactions. Information relating to, for instance, energy, ΔG, average number of hydrogen bonds and distance from Ser135 (one of the main amino acids in the catalytic pocket) were discussed. In this sense, peptides 15 (considering ΔG value and Hbond number), 7 (ΔG and energy) and 1, 6, 7 and 15 (the proximity to Ser135 throughout the dynamics simulation) were highlighted as promising. Those interesting results could contribute to future studies regarding Zika virus drug design, since this infection represents a great concern in neglected populations., Methods: The models were constructed in the ChemDraw software. The ligand parametrization was performed in the CHEM3D 17.0, UCSF Chimera. Docking simulations were carried out in the GOLD software, after the redocking validation. We used ASP as the function score. Additionally, for dynamics simulations we applied GROMACS software, exploring, mainly, free binding energy calculations. Exploratory analysis was carried out in Minitab 17.3.1 statistical software. Prior to the exploratory analysis, data of quantum chemical properties of the peptides were collected in Microsoft Excel spreadsheet and organized to obtain Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The advent of proteomics provides new opportunities to investigate the molecular mechanisms underlying male infertility. The selection of relevant targets based on a single analysis is not always feasible, due to the growing number of proteomic studies with conflicting results. Thus, this study aimed to systematically review investigations comparing the sperm proteome of normozoospermic and infertile men to define a panel of proteins with the potential to be used to evaluate sperm quality., Materials and Methods: A literature search was conducted on PubMed, Web of Science, and Scopus databases following the PRISMA guidelines. To identify proteins systematically reported, first the studies were divided by condition into four groups (asthenozoospermia, low motility, unexplained infertility, and infertility related to risk factors) and then, all studies were analysed simultaneously (poor sperm quality). To gain molecular insights regarding identified proteins, additional searches were performed within the Human Protein Atlas, Mouse Genome Informatics, UniProt, and PubMed databases., Results: Thirty-two studies were included and divided into 4 sub-analysis groups. A total of 2752 proteins were collected, of which 38, 1, 3 and 2 were indicated as potential markers for asthenozoospermia, low motility, unexplained infertility and infertility related to risk factors, respectively, and 58 for poor sperm quality. Among the identified proteins, ACR, ACRBP, ACRV1, ACTL9, AKAP4, ATG3, CCT2, CFAP276, CFAP52, FAM209A, GGH, HPRT1, LYZL4, PRDX6, PRSS37, REEP6, ROPN1B, SPACA3, SOD1, SPEM1, SPESP1, SPINK2, TEKT5, and ZPBP were highlighted due to their roles in male reproductive tissues, association with infertility phenotypes or participation in specific biological functions in spermatozoa., Conclusions: Sperm proteomics allows the identification of protein markers with the potential to overcome limitations in male infertility diagnosis and to understand changes in sperm function at the molecular level. This study provides a reliable list of systematically reported proteins that could be potential targets for further basic and clinical studies., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Background: Ruminants harbor a complex microbial community within their gastrointestinal tract, which plays major roles in their health and physiology. Brazil is one of the largest producers of beef in the world and more than 90% of the beef cattle herds are composed of pure and crossbred Nelore ( Bos indicus ). Despite its importance to the Brazilian economy and human feeding, few studies have characterized the Nelore microbiome. Therefore, using shotgun metagenomics, we investigated the impact of diet on the composition and functionality of the Nelore microbiome, and explored the associations between specific microbial taxa and their functionality with feed efficiency and methane emission., Results: The ruminal microbiome exhibited significantly higher microbial diversity, distinctive taxonomic profile and variations in microbial functionality compared to the fecal microbiome, highlighting the distinct contributions of the microbiomes of these environments. Animals subjected to different dietary treatments exhibited significant differences in their microbiomes' archaeal diversity and in the abundance of 89 genera, as well as in the functions associated with the metabolism of components of each diet. Moreover, depending on the diet, feed-efficient animals and low methane emitters displayed higher microbial diversity in their fecal microbiome. Multiple genera were associated with an increase or decrease of the phenotypes. Upon analyzing the functions attributed to these taxa, we observed significant differences on the ruminal taxa associated with feed efficient and inefficient cattle. The ruminal taxa that characterized feed efficient cattle stood out for having significantly more functions related to carbohydrate metabolism, such as monosaccharides, di-/oligosaccharides and amino acids. The taxa associated with methane emission had functions associated with methanogenesis and the production of substrates that may influence methane production, such as hydrogen and formate., Conclusion: Our findings highlight the significant role of diet in shaping Nelore microbiomes and how its composition and functionality may affect production traits such as feed efficiency and methane emission. These insights provide valuable support for the implementation of novel feeding and biotechnological strategies., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Conteville, da Silva, Andrade, Cardoso, Bruscadin, de Oliveira, Mourão, Coutinho, Palhares, Berndt, de Medeiros and Regitano.)

The precise mechanisms underlying the cardiovascular complications due to acute kidney injury (AKI) and the retention of uremic toxins like p-cresyl sulfate (PCS) remain incompletely understood. The objective of this study was to evaluate the renocardiac effects of PCS administration in animals subjected to AKI induced by ischemia and reperfusion (IR) injury. C57BL6 mice were subjected to distinct protocols: (i) administration with PCS (20, 40, or 60 mg/L/day) for 15 days and (ii) AKI due to unilateral IR injury associated with PCS administration for 15 days. The 20 mg/L dose of PCS led to a decrease in renal mass, an increase in the gene expression of Cystatin C and kidney injury molecule 1 (KIM-1), and a decrease in the α-actin in the heart. During AKI, PCS increased the renal injury biomarkers compared to control; however, it did not exacerbate these markers. Furthermore, PCS did not enhance the cardiac hypertrophy observed after 15 days of IR. An increase, but not potentialized, in the cardiac levels of interleukin (IL)-1β and IL-6 in the IR group treated with PCS, as well as in the injured kidney, was also noticed. In short, PCS administration did not intensify kidney injury, inflammation, and cardiac outcomes after AKI.

The trend to delay parenthood is increasing, impacting fertility and reproductive outcomes. Advanced paternal age (APA), defined as men's age above 40 years at conception, has been linked with testicular impairment, abnormal semen parameters, and poor reproductive and birth outcomes. Recently, the significance of sperm microRNA for fertilization and embryonic development has emerged. This work aimed to investigate the effects of men's age on semen parameters and sperm microRNA profiles. The ejaculates of 333 Portuguese men were collected between 2018 and 2022, analyzed according to WHO guidelines, and a density gradient sperm selection was performed. For microRNA expression analysis, 16 normozoospermic human sperm samples were selected and divided into four age groups: ≤30, 31-35, 36-40, and >40 years. microRNA target genes were retrieved from the miRDB and TargetScan databases and Gene Ontology analysis was performed using the DAVID tool. No significant correlation was found between male age and conventional semen parameters, except for volume. Fifteen differentially expressed microRNAs (DEMs) between groups were identified. Enrichment analysis suggested the involvement of DEMs in the sperm of men with advanced age in critical biological processes like embryonic development, morphogenesis, and male gonad development. Targets of DEMs were involved in signaling pathways previously associated with the ageing process, including cellular senescence, autophagy, insulin, and mTOR pathways. These results suggest that although conventional semen parameters were not affected by men's age, alterations in microRNA regulation may occur and be responsible for poor fertility and reproductive outcomes associated with APA.

Agricultural commodity production is one the main drivers of deforestation in Legal Brazilian Amazonia resulting in a deforested and/or fragmented landscape formed by forest remnants of different sizes and shape embedded within the agricultural matrix. As an ecosystem engineer and a crucial seed predator, white-lipped peccaries ( Tayassu pecari ) play a pivotal role in forest structure, biodiversity, and nutrient cycling. However, they are highly sensitive to habitat fragmentation and hunting pressure. White-lipped peccaries are, therefore, a wide-ranging "landscape species," the spatial and ecological requirements of which can be used to guide conservation planning in human-modified landscapes. Using data from GPS-tracked individuals in large-scale mechanized agriculture landscapes in the state of Mato Grosso, Brazil's largest soybean and maize producer, we investiated the home range size and resource selection during both the crop and non-crop season. We observed a seasonal variation in home range size and an increased selection for croplands during the crop season. White-lipped peccaries favored native vegetation patches and also exhibited avoidance of locations distant from perennial water bodies and distant cropland locations far from forest remmants. This study can contribute to inform effective conservation strategies and land management practices aimed at preserving suitable habitats and promoting wildlife coexistence with working agricultural landscapes., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Context: Collection and analysis of large volumes of on-farm production data are widely seen as key to understanding yield variability among farmers and improving resource-use efficiency., Objective: The aim of this study was to assess the performance of statistical and machine learning methods to explain and predict crop yield across thousands of farmers' fields in contrasting farming systems worldwide., Methods: A large database of 10,940 field-year combinations from three countries in different stages of agricultural intensification was analyzed. Random effects models were used to partition crop yield variability and random forest models were used to explain and predict crop yield within a cross-validation scheme with data re-sampling over space and time., Results: Yield variability in relative terms was smallest for wheat and barley in the Netherlands and for wheat in Ethiopia, intermediate for rice in the Philippines, and greatest for maize in Ethiopia. Random forest models comprising a total of 87 variables explained a maximum of 65 % of cereal yield variability in the Netherlands and less than 45 % of cereal yield variability in Ethiopia and in the Philippines. Crop management related variables were important to explain and predict cereal yields in Ethiopia, while predictive (i.e., known before the growing season) climatic variables and explanatory (i.e., known during or after the growing season) climatic variables were most important to explain and predict cereal yield variability in the Philippines and in the Netherlands, respectively. Finally, model cross-validation for regions or years not seen during model training reduced the R 2 considerably for most crop x country combinations, while for wheat in the Netherlands this was model dependent., Conclusion: Big data from farmers' fields is useful to explain on-farm yield variability to some extent, but not to predict it across time and space., Significance: The results call for moderate expectations towards big data and machine learning in agronomic studies, particularly for smallholder farms in the tropics where model performance was poorest independently of the variables considered and the cross-validation scheme used., 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., (© 2023 The Authors.)

Leishmaniasis is a complex disease caused by infection with different Leishmania parasites. The number of medications used for its treatment is still limited and the discovery of new drugs is a valuable approach. In this context, here we describe the in vitro leishmanicidal activity and the in silico interaction between trypanothione reductase (TryR) and (-)-5-demethoxygrandisin B from the leaves of Virola surinamensis (Rol.) Warb. The compound (-)-5-demethoxygrandisin B was isolated from V. surinamensis leaves, a plant found in the Brazilian Amazon, and it was characterized as (7R,8S,7'R,8'S)-3,4,5,3',4'-pentamethoxy-7,7'-epoxylignan. In vitro antileishmanial activity was examined against Leishmania amazonensis , covering both promastigote and intracellular amastigote phases. Cytotoxicity and nitrite production were gauged using BALB/c peritoneal macrophages. Moreover, transmission electron microscopy was applied to probe ultrastructural alterations, and flow cytometry assessed the shifts in the mitochondrial membrane potential. In silico methods such as molecular docking and molecular dynamics assessed the interaction between the most stable configuration of (-)-5-demethoxygrandisin B and TryR from L. infantum (PDB ID 2JK6). As a result, the (-)-5-demethoxygrandisin B was active against promastigote (IC 50 7.0 µM) and intracellular amastigote (IC 50 26.04 µM) forms of L. amazonensis , with acceptable selectivity indexes. (-)-5-demethoxygrandisin B caused ultrastructural changes in promastigotes, including mitochondrial swelling, altered kDNA patterns, vacuoles, vesicular structures, autophagosomes, and enlarged flagellar pockets. It reduced the mitochondria membrane potential and formed bonds with important residues in the TryR enzyme. The molecular dynamics simulations showed stability and favorable interaction with TryR. The compound targets L. amazonensis mitochondria via TryR enzyme inhibition.

Background: The high rates of unintended pregnancy and the ever-growing world population impose health, economic, social, and environmental threats to countries. Expanding contraceptive options, including male methods, are urgently needed to tackle these global challenges. Male contraception is limited to condoms and vasectomy, which are unsuitable for many couples. Thus, novel male contraceptive methods may reduce unintended pregnancies, meet the contraceptive needs of couples, and foster gender equality in carrying the contraceptive burden. In this regard, the spermatozoon emerges as a source of druggable targets for on-demand, non-hormonal male contraception based on disrupting sperm motility or fertilization., Objective and Rationale: A better understanding of the molecules governing sperm motility can lead to innovative approaches toward safe and effective male contraceptives. This review discusses cutting-edge knowledge on sperm-specific targets for male contraception, focusing on those with crucial roles in sperm motility. We also highlight challenges and opportunities in male contraceptive drug development targeting spermatozoa., Search Methods: We conducted a literature search in the PubMed database using the following keywords: 'spermatozoa', 'sperm motility', 'male contraception', and 'drug targets' in combination with other related terms to the field. Publications until January 2023 written in English were considered., Outcomes: Efforts for developing non-hormonal strategies for male contraception resulted in the identification of candidates specifically expressed or enriched in spermatozoa, including enzymes (PP1γ2, GAPDHS, and sAC), ion channels (CatSper and KSper), transmembrane transporters (sNHE, SLC26A8, and ATP1A4), and surface proteins (EPPIN). These targets are usually located in the sperm flagellum. Their indispensable roles in sperm motility and male fertility were confirmed by genetic or immunological approaches using animal models and gene mutations associated with male infertility due to sperm defects in humans. Their druggability was demonstrated by the identification of drug-like small organic ligands displaying spermiostatic activity in preclinical trials., Wider Implications: A wide range of sperm-associated proteins has arisen as key regulators of sperm motility, providing compelling druggable candidates for male contraception. Nevertheless, no pharmacological agent has reached clinical developmental stages. One reason is the slow progress in translating the preclinical and drug discovery findings into a drug-like candidate adequate for clinical development. Thus, intense collaboration among academia, private sectors, governments, and regulatory agencies will be crucial to combine expertise for the development of male contraceptives targeting sperm function by (i) improving target structural characterization and the design of highly selective ligands, (ii) conducting long-term preclinical safety, efficacy, and reversibility evaluation, and (iii) establishing rigorous guidelines and endpoints for clinical trials and regulatory evaluation, thus allowing their testing in humans., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hyperprolactinemia is a pathological condition resulting from increased prolactin that directly affects reproduction, as this condition inhibits the release of LH, FSH and gonadal steroidogenesis, bringing several negative clinical associations in reproduction. In contrast, melatonin (MEL) plays an important role in the regulation of steroidogenesis and modulates damages to the process of spermatogenesis. The objective was to analyze the protective effects of exogenous melatonin on the testis of hyperprolactinemic adult rats. Forty-eight male rats were used, divided into two treatment periods: 30 and 60 days, each treatment was subdivided into three groups: Control, Hyper (hyperprolactinemia), and Hyper+MEL (hyperprolactinemia and melatonin). Treatment with melatonin was 200 μg/100 g, subcutaneously. Induction of hyperprolactinemia was obtained with a dose of 4 mg/kg of domperidone, subcutaneously. The results of the histopathology demonstrated that the animals in the Hyper group presented degeneration of germ cells when compared to the control. In addition, the degenerations were presented in smaller quantities in the Hyper+MEL, in both treatment periods, evidencing the benefits of the melatonin in gonadal regeneration. The Hyper group of both treatment periods showed a decrease in tubular diameter, epithelium height, and tubular area, in addition to a decrease in Sertoli cells, when compared to the control and the Hyper+MEL group. In conclusion, the hyperprolactinemia can affect the germinal epithelium and testicular microstructure; the exogenous melatonin has a protective effect against hyperprolactinemia, reducing testicular damage., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2023 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Biotransformations are reactions mediated by microorganisms, such as fungi. These bioreactions have high chemo- and stereoselectivity on organic substrates and can be applied in the search for new bioactive compounds. In this study, acanthoic acid (AA) was biotransformed using the fungus Xylaria sp., giving the novel compound 3β,7β-dihydroxyacanthoic acid ( S1 ). Both the AA and the product S1 were tested against Gram-positive and Gram-negative bacteria. To identify and validate possible biological targets as enzymes or proteins involved in the activity observed in vitro, we used the molecular docking method. Hydroxylation at the C-3 and C-7 positions of the biotransformation product enhanced its activity against Escherichia coli as well as its binding affinity and interactions with superoxide dismutase 1 (SOD1; PDB ID 4A7G). Based on our results, the SOD1 enzyme was suggested to be a possible target for the antioxidant activity of product S1 .

Polycystic Echinococcosis (PE), a neglected life-threatening zoonotic disease caused by the cestode Echinococcus vogeli, is endemic in the Amazon. Despite being treatable, PE reaches a case fatality rate of around 29% due to late or missed diagnosis. PE is sustained in Pan-Amazonia by a complex sylvatic cycle. The hunting of its infected intermediate hosts (especially the lowland paca Cuniculus paca ) enables the disease to further transmit to humans, when their viscera are improperly handled. In this study, we compiled a unique dataset of host occurrences (~86000 records) and disease infections (~400 cases) covering the entire Pan-Amazonia and employed different modeling and statistical tools to unveil the spatial distribution of PE's key animal hosts. Subsequently, we derived a set of ecological, environmental, climatic, and hunting covariates that potentially act as transmission risk factors and used them as predictors of two independent Maximum Entropy models, one for animal infections and one for human infections. Our findings indicate that temperature stability promotes the sylvatic circulation of the disease. Additionally, we show how El Niño-Southern Oscillation (ENSO) extreme events disrupt hunting patterns throughout Pan-Amazonia, ultimately affecting the probability of spillover. In a scenario where climate extremes are projected to intensify, climate change at regional level appears to be indirectly driving the spillover of E. vogeli . These results hold substantial implications for a wide range of zoonoses acquired at the wildlife-human interface for which transmission is related to the manipulation and consumption of wild meat, underscoring the pressing need for enhanced awareness and intervention strategies.

Drought is projected to occur more frequently and intensely in the coming decades, and the extent to which it will affect forest functioning will depend on species-specific responses to water stress. Aiming to understand the hydraulic traits and water dynamics behind water-saver and water-spender strategies in response to drought and recovery, we conducted a pot experiment with two species with contrasting physiological strategies, Scots pine (Pinus sylvestris L.) and Portuguese oak (Quercus faginea L.). We applied two cycles of soil drying and recovery and irrigated with isotopically different water to track fast changes in soil and stem water pools, while continuously measuring physiological status and xylem water content from twigs. Our results provide evidence for a tight link between the leaf-level response and the water uptake and storage patterns in the stem. The water-saver strategy of pines prevented stem dehydration by rapidly closing stomata which limited their water uptake during the early stages of drought and recovery. Conversely, oaks showed a less conservative strategy, maintaining transpiration and physiological activity under dry soil conditions, and consequently becoming more dehydrated at the stem level. We interpreted this dehydration as the release of water from elastic storage tissues as no major loss of hydraulic conductance occurred for this species. After soil rewetting, pines recovered pre-drought leaf water potential rapidly, but it took longer to replace the water from conductive tissues (slower labeling speed). In contrast, water-spender oaks were able to quickly replace xylem water during recovery (fast labeling speed), but it took longer to refill stem storage tissues, and hence to recover pre-drought leaf water potential. These different patterns in sap flow rates, speed and duration of the labeling reflected a combination of water-use and storage traits, linked to the leaf-level strategies in response to drought and recovery., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4 + T helper cells, but not CD8 + T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients., Competing Interests: NB, GD, Dd, AF, GS, SM, TK, VB, LM, JV, GP, NW, LN, VC, AD, FV, LT, JF, IC, LS, AP, EM, RU, AB, TN, LR, MA, MM, LB, FC, RL, JG, NM, AM, RS, MA, DT, PP, MM, KB, CS, FG, VS, Ed, VF, MC, BC, AP, LC, MD, PR, AG, FP, LS, LB, SS, MP, SW, AS, RC, AV, MV, AD, LV, AF, Ld, TC, HN, HM, RM, DM, MS, JP, PM, MM, AF No competing interests declared, (© 2023, Brunetti, Davanzo, de Moraes et al.)

Leishmaniasis is a public health concern, especially in Brazil and India. The drugs available for therapy are old, cause toxicity and have reports of resistance. Therefore, this paper aimed to carry out initial structure-activity relationships (applying molecular docking and dynamic simulations) of arylindole scaffolds against the pteridine reductase (PTR1), which is essential target for the survival of the parasite. Thus, we used a series of 43 arylindole derivatives as a privileged skeleton, which have been evaluated previously for different biological actions. Compound 7 stood out among its analogues presenting the best results of average number of interactions with binding site (2.00) and catalytic triad (1.00). Additionally, the same compound presented the best binding free energy (-32.33 kcal/mol) in dynamic simulations. Furthermore, with computational studies, it was possible to comprehend and discuss the influences of the substituent sizes, positions of substitutions in the aromatic ring and electronic influences. Therefore, this study can be a starting point for the structural improvements needed to obtain a good leishmanicidal drug.

This two-arm, parallel-group, double-blind, randomized clinical trial design evaluated the risk of postoperative bleeding in anticoagulated patients undergoing dental extraction treated with topical TXA in comparison to collagen-gelatin sponge. Forty patients were randomly included in one of the study groups: (1) topical use of 4.8% TXA solution; and (2) resorbable hydrolyzed collagen-gelatin sponge applied to the surgical alveolus. Primary outcomes were postoperative bleeding episodes and secondary outcomes were thromboembolic events and postoperative INR values. The relative risk (RR), the absolute risk reduction (RAR) and the number needed to treat (NNT) were used as effect estimates and calculated from the counting of bleeding episodes observed during the first postoperative week. The bleeding rate under the TXA treatment was 22.2%, while in the collagen-gelatin sponge group it was 45.7%, resulting in a RR of 0.49 (95% CI 0.24-099; p = 0.046), RAR 23.5% and NNT 4.3. TXA was more effective in reducing bleeding in surgical sites located in the mandible (RR = 0.10; 95% CI 0.01-0.71; p = 0.021) and the posterior region (RR = 0.39; 95% CI 0.18-0.84; p = 0.016). Within the limitations of the study it seems that topical TXA is more effective in controlling bleeding after tooth extractions in anticoagulated patients than collagen-gelatin sponge. CLINICAL TRIAL REGISTRATION: RBR-83qw93., Competing Interests: Declaration of competing interest None., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

A growing urban population and dietary changes increased wheat import bills in Africa to 9% per year. Though wheat production in the continent has been increasing over the past decades, to varying degrees depending on regions, this has not been commensurate with the rapidly increasing demand for wheat. Analyses of wheat yield gaps show that there is ample opportunity to increase wheat production in Africa through improved genetics and agronomic practices. Doing so would reduce import dependency and increase wheat self-sufficiency at national level in many African countries. In view of the uncertainties revealed by the global COVID-19 pandemic, extreme weather events, and world security issues, national policies in Africa should re-consider the value of self-sufficiency in production of staple food crops, specifically wheat. This is particularly so for areas where water-limited wheat yield gaps can be narrowed through intensification on existing cropland and judicious expansion of rainfed and irrigated wheat areas. Increasing the production of other sources of calories (and proteins) should also be considered to reduce dependency on wheat imports., 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., (© 2023 The Authors.)

Gastric cancer is among the major causes of death from neoplasia leading causes of death worldwide, with high incidence rates and problems related to its treatment. Here, we outline how Geissospermum sericeum exerts antitumor activity on the ACP02 cell line (human gastric adenocarcinoma) and the mechanism of cell death. The ethanol extract and fractions, neutral fraction and alkaloid fraction, were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid (geissoschizoline N4-methylchlorine) identified by NMR. The cytotoxicity activity of the samples (ethanol extract, neutral fraction, alkaloid fraction, and geissoschizoline N4-methylchlorine) in HepG2 and VERO cells was determined by MTT. The ACP02 cell line was used to assess the anticancer potential. Cell death was quantified with the fluorescent dyes Hoechst 33342, propidium iodide, and fluorescein diacetate. The geissoschizoline N4-methylchlorine was evaluated in silico against caspase 3 and 8. In the antitumor evaluation, there was observed a more significant inhibitory effect of the alkaloid fraction (IC50 18.29 µg/mL) and the geissoschizoline N4-methylchlorine (IC 50 12.06 µg/mL). However, geissoschizoline N4-methylchlorine showed lower cytotoxicity in the VERO (CC 50 476.0 µg/mL) and HepG2 (CC 50 503.5 µg/mL) cell lines, with high selectivity against ACP02 cells (SI 39.47 and 41.75, respectively). The alkaloid fraction showed more significant apoptosis and necrosis in 24 h and 48 h, with increased necrosis in higher concentrations and increased exposure time. For the alkaloid, apoptosis and necrosis were concentration- and time-dependent, with a lower necrosis rate. Molecular modeling studies demonstrated that geissoschizoline N4-methylchlorine could occupy the active site of caspases 3 and 8 energetically favorably. The results showed that fractionation contributed to the activity with pronounced selectivity for ACP02 cells, and geissoschizoline N4-methylchlor is a promising candidate for caspase inhibitors of apoptosis in gastric cancer. Thus, this study provides a scientific basis for the biological functions of Geissospermum sericeum , as well as demonstrates the potential of the geissoschizoline N4-methylchlorine in the treatment of gastric cancer.

In order, understanding the antimicrobial action of photodynamic therapy and how this technique can contribute to its application in the control of pathogens. The objective of the study was to employ a proteomic approach to investigate the protein profile of Staphylococcus aureus after antimicrobial photodynamic therapy mediated by rose bengal (RB-aPDT). S. aureus was treated with RB (10 nmoL L -1 ) and illuminated with green LED (0.17 J cm -2 ) for cell viability evaluation. Afterward, proteomic analysis was employed for protein identification and bioinformatic tools to classify the differentially expressed proteins. The reduction in S. aureus after photoinactivation was ~2.5 log CFU mL -1 . A total of 12 proteins (four up-regulated and eight down-regulated) correspond exclusively to alteration by RB-aPDT. Functionally, these proteins are distributed in protein binding, structural constituent of ribosome, proton transmembrane transporter activity and ATPase activity. The effects of photodamage include alterations of levels of several proteins resulting in an activated stress response, altered membrane potential and effects on energy metabolism. These 12 proteins required the presence of both light and RB suggesting a unique response to photodynamic effects. The information about this technique contributes valuable insights into bacterial mechanisms and the mode of action of photodynamic therapy., (© 2022 American Society for Photobiology.)

Peach palm ( Bactris gasipaes Kunth) is an amazonian fruit in which its peel has been appointed as a carotenoid-rich byproduct with biological properties. For analytical purposes, carotenoids are frequently extracted by non-green (use of toxic organic solvents) and time-consuming methods, which can affect the quality (carotenoid profile) and safety of extracts for direct food applications. We investigated herein the effect of different extraction methods on the individual carotenoid profile of extracts of peach palm peels by HPLC-DAD. Carotenoid extractions were carried out by maceration in mortar with pestle (with acetone or ethanol), magnetic stirring, shaker and ultrasound-assisted extraction (UAE) using ethanol. UAE provided the highest carotenoid contents (67 mg/100 g), followed by maceration with acetone and ethanol (63 and 52 mg/100 g, respectively), while the lowest contents were observed for the magnetic stirring and shaker extractions (44 mg/100 g), being (all- E )-β-carotene and a Z- isomer of γ-carotene accounted 54-73% of the carotenoid composition. HPLC-DAD data showed the same carotenoid profile regardless the extraction method, yet the percentage of Z -isomers of β-carotene was higher for the shaking (18%), UAE (17%) and magnetic stirring (15%) than for both maceration methods (7 and 8%, with acetone and ethanol, respectively). Thus, the tested extraction methods affected the total carotenoid contents, whereas the chromatographic profile did not change. Furthermore, a carotenoid-rich extract was effectively obtained by using ethanol associated with ultrasound technique (less time-consuming) instead of toxic and non-safe solvents., Competing Interests: The authors declare no conflicts of interest. Renan Campos Chisté is part of the Editorial Advisory Board of Heliyon journal (Food Science and Nutrition section)., (©2023PublishedbyElsevierLtd.)

Acid tropical soils may become more productive when treated with agricultural lime, but optimal lime rates have yet to be determined in many tropical regions. In these regions, lime rates can be estimated with lime requirement models based on widely available soil data. We reviewed seven of these models and introduced a new model (LiTAS). We evaluated the models' ability to predict the amount of lime needed to reach a target change in soil chemical properties with data from four soil incubation studies covering 31 soil types. Two foundational models, one targeting acidity saturation and the other targeting base saturation, were more accurate than the five models that were derived from them, while the LiTAS model was the most accurate. The models were used to estimate lime requirements for 303 African soil samples. We found large differences in the estimated lime rates depending on the target soil chemical property of the model. Therefore, an important first step in formulating liming recommendations is to clearly identify the soil property of interest and the target value that needs to be reached. While the LiTAS model can be useful for strategic research, more information on acidity-related problems other than aluminum toxicity is needed to comprehensively assess the benefits of liming., 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., (© 2023 The Author(s).)

Invariant natural killer T (iNKT) cells are a distinct population of lymphocytes characterized by their reactivity to glycolipids presented by CD1d. iNKT cells are found throughout the body, and little is known about their tissue-specific metabolic regulation. Here, we show that splenic and hepatic iNKT cells are metabolically comparable and rely on glycolytic metabolism to support their activation. Deletion of the pyruvate kinase M2 (Pkm2) gene in splenic and hepatic iNKT cells impairs their response to specific stimulation and their ability to mitigate acute liver injury. In contrast, adipose tissue (AT) iNKT cells exhibit a distinctive immunometabolic profile, with AMP-activated protein kinase (AMPK) being necessary for their function. AMPK deficiency impairs AT-iNKT physiology, blocking their capacity to maintain AT homeostasis and their ability to regulate AT inflammation during obesity. Our work deepens our understanding on the tissue-specific immunometabolic regulation of iNKT cells, which directly impacts the course of liver injury and obesity-induced inflammation., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The pathologies of the kidney and heart have instigated a large number of researchers around the world to try to better understand what the exact connectors responsible for the emergence and establishment of these diseases are. The classification of these pathologies into different types of cardiorenal syndromes (CRSs) over the last 15 years has greatly contributed to understanding pathophysiological and diagnostic aspects, as well as treatment strategies. However, with the advent of new technologies classified as "Omics", a new range of knowledge and new possibilities have opened up in order to effectively understand the intermediaries between the kidney-heart axis. The universe of micro-RNAs (miRNAs), epigenetic factors, and components present in extracellular vesicles (EVs) have been protagonists in studying different types of CRSs. Thus, the new challenge that is imposed is to select and link the large amount of information generated from the use of large-scale analysis techniques. The present review seeks to present some of the future perspectives related to understanding CRSs, with an emphasis on CRS type 3., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

This study evaluated the growth and immune function of beef calves born to cows supplemented with bakery waste containing two concentrations of crude fat. On day 0 (~90 d before calving), 108 multiparous Brangus crossbred cows were stratified by body weight (BW; 551 ± 65 kg) and body condition score (BCS, 5.5 ± 0.9) and randomly allocated into 1 of 18 bahiagrass (Paspalum notatum) pastures (6 cows and 4.3 ha per pasture). Treatments were randomly assigned to pastures (6 pastures per treatment) and consisted of no prepartum supplementation (NOSUP) and isocaloric and isonitrogenous supplementation of low-fat (LFAT; 6.4% crude fat) or high-fat (HFAT; 10.7% crude fat) bakery waste from days 0 to 70 (1 kg DM per cow per day). Calves were weaned on day 292 (201 ± 17 d of age). Then, 15 heifers per treatment were randomly selected and assigned to drylot pens from days 300 to 345 and vaccinated against respiratory pathogens on days 300 and 315. Cow BCS near calving (day 70) was the least (P ≤ 0.05) for NOSUP cows and did not differ (P = 0.12) between LFAT and HFAT cows. Cow BCS at the start of the breeding season (day 140) was greater (P = 0.05) for HFAT vs. NOSUP cows and intermediate (P ≥ 0.35) for LFAT cows. Plasma concentrations of total polyunsaturated fatty acids in HFAT cows did not differ (P ≥ 0.76) compared with LFAT cows but were greater (P ≤ 0.05) compared to NOSUP cows on day 70. Final pregnancy percentage did not differ (P ≥ 0.26) among treatments, but a greater percentage of HFAT cows calved (P ≤ 0.05) their second offspring during the first 21 d of the calving season compared to NOSUP and LFAT cows (bred by natural service). Weaning BW was the greatest (P ≤ 0.05) for LFAT and least for NOSUP calves. Maternal treatments did not impact (P ≥ 0.11) postweaning growth and total DM intake of calves. Average plasma cortisol concentrations were greater (P = 0.03) for NOSUP vs. HFAT calves and intermediate for LFAT calves (P ≥ 0.26). Serum titers against infectious bovine rhinotracheitis and bovine respiratory syncytial virus were greater or tended to be greater (P ≤ 0.08) for HFAT vs. LFAT calves and intermediate (P ≥ 0.27) for NOSUP calves at the end of preconditioning. Thus, supplemental fat concentration fed to late-gestating beef cows had variable effects on calf performance. Low-fat bakery waste led to the greatest calf preweaning growth, whereas high-fat bakery waste enhanced maternal reproduction and had minor benefits to calf humoral immune function., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Arylindole derivatives are promising scaffolds in the design of new drugs. These scaffolds exhibit a wide biological activity, including inhibition of COX-2, antitumor activity, receptor GABA agonism, and estrogen receptor modulation., Objectives: Taking this into account, this paper presents a study to understand the inhibitory action of certain 2-arylindole derivatives, specifically a series of 2,3-diarylindoles with IC 50 values from 0.006 nM to 100 nM, on the COX-2 enzyme and supports its structural-activity relationship (SAR) through molecular docking simulations., Methods: Applying molecular modelling, especially molecular docking, we assessed the SAR of a series of 2,3-arylindoles derivatives in the COX-2 enzyme., Results: The results indicated that Gly 526 and Phe 381 residues are relevant for improving inhibitory activity on para-substituted 3-phenyl- compounds. Arg 120 was also demonstrated to be an important residue for COX-2 inhibition since it enables a π-cation interaction with the best compound in series A5 (experimental IC 50 = 0.006 nM determined in advance). Furthermore, COX-2 presents flexibility in some regions of the active site to adequately accommodate 5-substituted compounds containing an indole ring., Conclusion: Therefore, such structural features can be used as support for further Structural-Based Drug Design (SBDD) and/or Ligand-Based Drug Design (LBDD) studies on new selective COX-2 inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The trematode Schistosoma mansoni causes schistosomiasis, and this parasite's life cycle depends on the mollusk Biomphalaria glabrata. The most effective treatment for infected people is administering a single dose of Praziquantel. However, there are naturally resistant to treatment. This work has developed, considering this parasite's complex life cycle., Methods: The synthetics compound were evaluated: i) during the infection of B. glabrata , ii) during the infection of BALB /c mice, and iii) during the treatment of mice infected with S. mansoni., Results and Discussion: For the first objective, snails infected with miracidia treated with compounds C1 and C3 at concentrations of 25% IC50 and 50% IC50, after 80 days of infection, released fewer cercariae than the infected group without treatment. For the second objective, compounds C1 and C3 did not show significant results in the infected group without treatment. For the third objective, the mice treated with C3 and C1 reduced the global and differential cell count. The results suggest that although the evaluated compounds do not present schistosomicidal properties when placed in cercariae suspension, they can stimulate an immune reaction in snails and decrease mice's inflammatory response. In general, we can conclude that compound C1 and C3 has an anti-schistosomicidal effect both in the larval phase (miracidia) and in the adult form of the parasite., Competing Interests: Author AA was employed by company Quantoom’s Bioscience. The remaining 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. The handling editor DZ declared a shared affiliation with the authors, EGS and AA, at the time of review., (Copyright © 2022 da Silva, Moreira, Montija, Feitosa, Correia, Domingues, Soares, Allegretti, Afonso and Anibal.)

Male fertility relies on the ability of spermatozoa to fertilize the egg in the female reproductive tract (FRT). Spermatozoa acquire activated motility during epididymal maturation; however, to be capable of fertilization, they must achieve hyperactivated motility in the FRT. Extensive research found that three protein phosphatases (PPs) are crucial to sperm motility regulation, the sperm-specific protein phosphatase type 1 (PP1) isoform gamma 2 (PP1γ2), protein phosphatase type 2A (PP2A) and protein phosphatase type 2B (PP2B). Studies have reported that PP activity decreases during epididymal maturation, whereas protein kinase activity increases, which appears to be a requirement for motility acquisition. An interplay between these PPs has been extensively investigated; however, many specific interactions and some inconsistencies remain to be elucidated. The study of PPs significantly advanced following the identification of naturally occurring toxins, including calyculin A, okadaic acid, cyclosporin, endothall and deltamethrin, which are powerful and specific PP inhibitors. This review aims to overview the protein phosphorylation-dependent biochemical pathways underlying sperm motility acquisition and hyperactivation, followed by a discussion of the PP inhibitors that allowed advances in the current knowledge of these pathways. Since male infertility cases still attain alarming numbers, additional research on the topic is required, particularly using other PP inhibitors.