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The transition from fossil fuels dependency to embracing renewable alternatives is pivotal for mitigating greenhouse gas emissions, with biorefineries playing a central role at the forefront of this transition. As a sustainable alternative, lignocellulosic feedstocks hold great promise for biofuels and biochemicals production. However, the effective utilization of complex sugars, such as xylose, remains a significant hurdle. To address this challenge, yeasts can be engineered as microbial platforms to convert the complex sugars derived from biomass. The efficient use of xylose by XR-XDH strains still poses a significant challenge due to redox imbalance limitations, leading to the accumulation of undesirable by-products. In this study, we focused on engineering the industrial S. cerevisiae strain PE-2, known for its robustness, and compared different strategies to balance cellular redox homeostasis, guided by a genome-scale metabolic model. Flux balance analysis guided the selection of four approaches: i. decoupling NADPH regeneration from CO 2 production; ii. altering XDH cofactor affinity; iii. shifting XR cofactor preference; iv. incorporating alternate phosphoketolase and acetic acid conversion pathways. A comparative time-course targeted metabolic profile was conducted to assess the redox status of xylose-fermenting cells under anaerobic conditions. The main limitations of xylose-fermenting strains were tested and the replacement of xylose reductase with a NADH-preferred XR in the LVY142 strain proved to be the most effective strategy, resulting in an increase in ethanol yield and productivity, coupled with a reduction in by-products. Comparative analysis of various genetic approaches provided valuable insights into the complexities of redox engineering, highlighting the need for tailored strategies in yeast metabolic engineering for efficient biofuels and biochemicals production from lignocellulosic feedstocks., Competing Interests: Declararion of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The use of antibiotics by dentist surgeons faces a lack of consensus among professionals and researchers, whether in relation to prophylaxis, or at least regarding the real need for their use. Recent studies increasingly question the use of prophylactic antibiotic therapy in healthy patients. This study aimed to evaluate the knowledge of dentist surgeons working in offices across Brazil regarding antibiotic use protocols and antibiotic resistance. A questionnaire was made via Google Forms and sent by email. The results showed that most dentists prescribe antibiotics for all surgical procedures performed in their office, regardless of the complexity and the patient. Furthermore, low scientific basis was observed among some of the professionals interviewed regarding the best therapeutic choice and the role of antibiotics in the surgical procedure. The present study highlights the urgent need to improve the knowledge of these professionals in Brazil, to reduce the impact on antibiotic resistance., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study was approved by the Ethical Committee from Universidade São Francisco (Process Number: 58541322.5.0000.5514). This study is in accordance with Brazilian General Data Protection Law (LGPD) available in Portuguese language in https://www.gov.br/defesa/pt-br/acesso-a-informacao/lei-geral-de-protecao-de-dados-pessoais-lgpd/arquivos/PortariaGMMDn5.814DiretrizparaaProteodeDadosPessoais.pdf . All subjects consent to participate in this study before being included and consent with data publication in a scientific media. Consent for publication: All authors consent to publication of this study. The participants were not identified in this study. All participants consent to publish these results in a scientific journal., (© 2024. The Author(s).)

This study investigated the effects of a single dose of desvenlafaxine via oral administration on the pharmacokinetic parameters and clinical and laboratory characteristics in healthy volunteers using a pharmacometabolomics approach. In order to optimize desvenlafaxine's therapeutic use and minimize potential adverse effects, this knowledge is essential. Methods: Thirty-five healthy volunteers were enrolled after a health trial and received a single dose of desvenlafaxine (Pristiq ® , 100 mg). First, liquid chromatography coupled to tandem mass spectrometry was used to determine the main pharmacokinetic parameters. Next, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to identify plasma metabolites with different relative abundances in the metabolome at pre-dose and when the desvenlafaxine peak plasma concentration was reached (pre-dose vs. post-dose). Results: Correlations were observed between metabolomic profiles, such as tyrosine, sphingosine 1-phosphate, and pharmacokinetic parameters, as well as acetoacetic acid and uridine diphosphate glucose associated with clinical characteristics. Our findings suggest that desvenlafaxine may have a broader effect than previously thought by acting on the proteins responsible for the transport of various molecules at the cellular level, such as the solute carrier SLC and adenosine triphosphate synthase binding cassette ABC transporters. Both of these molecules have been associated with PK parameters and adverse events in our study. Conclusions: This altered transporter activity may be related to the reported side effects of desvenlafaxine, such as changes in blood pressure and liver function. This finding may be part of the explanation as to why people respond differently to the drug.

With the advent of high-throughput technologies, the field of omics has made significant strides in characterizing biological systems at various levels of complexity. Transcriptomics, proteomics, and metabolomics are the three most widely used omics technologies, each providing unique insights into different layers of a biological system. However, analyzing each omics data set separately may not provide a comprehensive understanding of the subject under study. Therefore, integrating multi-omics data has become increasingly important in bioinformatics research. In this article, we review strategies for integrating transcriptomics, proteomics, and metabolomics data, including co-expression analysis, metabolite-gene networks, constraint-based models, pathway enrichment analysis, and interactome analysis. We discuss combined omics integration approaches, correlation-based strategies, and machine learning techniques that utilize one or more types of omics data. By presenting these methods, we aim to provide researchers with a better understanding of how to integrate omics data to gain a more comprehensive view of a biological system, facilitating the identification of complex patterns and interactions that might be missed by single-omics analyses.

The high consumption of dietary supplements was a fundamental driver for the creation of the regulatory framework by the Brazilian governmental authorities. However, the regulatory agencies lack official low-cost methodologies to evaluate the quality of food supplements. A preliminary screening method by HPLC-DAD was proposed and validated for screening and quantification of adulterants in dietary supplements. The limits of detection and quantification were <0.11 and 0.37 µg.g -1 , respectively. The method was applied for the investigation of ten unauthorized substances (spironolactone, hydrochlorothiazide, furosemide, clenbuterol, testosterone, testosterone propionate, yohimbine, vardenafil, tadalafil, and sildenafil) with a time of analysis of <5 min. Sixteen percent of the 44 samples analyzed had at least one adulterant at or above therapeutic concentrations. Subsequently, in vitro evaluations were performed of the potential cytotoxicity to evaluate the cell viability, DNA damage, determination of nitric oxide levels, and quantification of reactive oxygen species. Despite the necessity of further studies, the results indicate a relationship between the presence of adulterants in food supplements and a potential cytotoxic effect.

Satellite-based land use monitoring and farm-level traceability offer opportunities for targeted zero-deforestation interventions on private lands. Brazil's Rural Environmental Registry (Cadastro Ambiental Rural, or "CAR"), a land cadaster based on self-declaration of property boundaries, was created to monitor compliance with national forest laws. It has become an important enabling measure for sustainable supply chain initiatives like the Amazon Soy Moratorium. However, CAR enrollment is increasingly used to bolster illegal land claims, putting it at the heart of land grabbing dynamics. Self-declaration of properties in the CAR offers a unique situation to study land conflicts and their impact on land use decisions on a large scale. We quantified competing land claims among 846,420 registrations in the Brazilian Legal Amazon and applied a series of generalized linear mixed-effects models. We determined that CAR overlaps are more prevalent on larger registrations, in more densely settled areas, and in areas with less secure land tenure. We tested how landholders respond to land conflicts, finding significantly more deforestation and declared legal forest reserve on lands with multiple claims. CAR overlap results in an overestimation of forest reserves by up to 9.7 million hectares when considering double-counted and deforested areas of reserves, highlighting an overlooked form of Forest Code noncompliance. While the CAR continues to be used as evidence of land tenure, we conclude that the formalization of land claims through self-declarations is inadequate to decrease conflicts. CAR overlap information provides objective evidence of land conflict that authorities can leverage with field inspection to ensure peaceful occupation before issuing land titles., Competing Interests: Competing interests statement:The authors declare no competing interest.

Aluminum and silicon are contaminants found in formulations used to prepare parenteral nutrition. Both elements are leached from glass containers, mainly during the heating cycle for sterilization. Insoluble and biologically inactive species of hydroxyaluminosilicates have been shown to form in solutions containing Al and Si. Therefore, this interaction may play an important role in protecting the body against Al toxicity. In this study, the bioavailability of Al in the presence of Si, calcium gluconate (Gluc.), and potassium phosphate (Phosf.) was investigated in rats. The rats were divided into 10 groups of 5 animals each: control, Al, Si, Al + Si, Gluc, Gluc + Al, Gluc + Al + Si, Phosf, Phosf + Al, and Phosf + Al + Si. The doses, consisting of 0.5 mg/kg/day Al and 2 mg/kg/day Si in the presence or absence of Gluc. or Phosf., were intraperitoneally administered for 3 months. Tissues were analyzed for Al and Si content. Al accumulated in the liver, kidneys, and bones, and the simultaneous administration of Si decreased Al accumulation in these tissues. The presence of Si reduced the amount of Al present by 72% in the liver, by 45% in the kidneys, and by 16% in bone. This effect was lees pronounced in the presence of parenteral nutrition compounds though. Si tissue accumulation was also observed, mainly when administered together with phosphate. These results suggest that Si may act as a protector against Al toxicity, by either reducing Al absorption or increasing its excretion, probably through hydroxyaluminosilicates formation. The presence of calcium gluconate and potassium phosphate decreases or inhibits this effect., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Parasitic diseases can affect animal health and welfare, and they may also constitute a danger to public health, particularly in island ecosystems. Fecal samples were collected from 205 dogs and 115 cats on the islands of São Miguel and Terceira, Azores archipelago (Portugal), using the Willis flotation technique and modified Baermann method, for further analysis. The overall prevalence of gastrointestinal parasitism in dogs was 53%, with the following results: Ancylostomatidae (hookworms) (42.44%), Trichuris vulpis (17.56%), Toxocara canis (12.68%) and Cystoisospora spp. (4.39%). In cats, the overall prevalence was also 53%, with the following results: Toxocara cati (31.3%), Ancylostomatidae (30.43%), Cystoisospora spp. (14.78%) and Trichuris sp. (0.87%). The prevalence of lungworms was 0.49% in canines and 20.87% in felines, with Angiostrongylus vasorum and Aelurostrongylus abstrusus species being detected in dogs and cats, respectively. The present survey detected a high prevalence of gastrointestinal infection, in both dogs and cats, probably because the samples came mainly from kennels and catteries and due to the peculiar climatic conditions in this insular territory, with mild temperature and high relative humidity. A considerable prevalence of aelurostrongylosis was also detected (20.87%), so it should be included in the list of differential diagnoses of diseases concerning the respiratory tract in cats of the archipelago.

Eimeria spp. are the pathogen that causes coccidiosis, a significant disease that affects intensively reared livestock, especially poultry. Anticoccidial feed additives, chemicals, and ionophores have routinely been employed to reduce Eimeria infections in broiler production. Therefore, the shift to antibiotic-free and organic farming necessitates novel coccidiosis preventive strategies. The present study evaluated the effects of potential feed additives, liver free and chitosan, against Eimeria tenella infection in White Leghorn broiler female chickens. One hundred sixty-five 1-day-old White Leghorn broiler female chicks were divided into 11 groups (15 female chicks per group), including the positive control group (G1), the negative control group (G2), a chitosan-treated group (G3), a chitosan-treated-infected group (G4), the liver free-treated group (G5), the liver free-treated-infected group (G6), the liver free-and-chitosan-treated group (G7), the liver free-and-chitosan-infected group (G8), the therapeutic liver free-and-chitosan-treated-infected group (G9), the sulfaquinoxaline-treated group (G10), and the sulfaquinoxaline-treated-infected group (G11). Chitosan was fed to the chicks in G3 and G4 as a preventative measure at a dose of 250 mg/kg. The G5 and G6 groups received 1.5 mg/kg of Liverfree. The G7 and G8 groups received chitosan and Liverfree. The G10 and G11 groups were administered 2 g/L of sulfaquinoxaline. From the moment the chicks arrived at Foshan University (one-day-old chicks) until the completion of the experiment, all medications were given to them as a preventative measure. G8 did; however, receive chitosan and liver free as therapeutic supplements at 7 dpi. The current study showed that the combination of liver free and chitosan can achieve better prophylactic and therapeutic effects than either alone. In E. tenella challenged chickens, G8 and G9 chickens showed reduced oocyst shedding and lesion score, improved growth performance (body weight, body weight gain, feed intake, feed conversion ratio, and mortality rate), and cecal histology. The current study demonstrates that combining liver free and chitosan has superior preventive and therapeutic benefits than either alone, and they could also be used as alternative anticoccidial agents., (© 2024. The Author(s).)

Background: Neoadjuvant chemotherapy (NACT) has arisen as a treatment option for breast cancer (BC). However, the response to NACT is still unpredictable and dependent on cancer subtype. Metabolomics is a tool for predicting biomarkers and chemotherapy response. We used plasma to verify metabolomic alterations in BC before NACT, relating to clinical data., Methods: Liquid chromatography coupled to mass spectrometry (LC-MS) was performed on pre-NACT plasma from patients with BC ( n = 75). After data filtering, an SVM model for classification was built and validated with 75%/25% of the data, respectively., Results: The model composed of 19 identified metabolites effectively predicted NACT response for training/validation sets with high sensitivity (95.4%/93.3%), specificity (91.6%/100.0%), and accuracy (94.6%/94.7%). In both sets, the panel correctly classified 95% of resistant and 94% of sensitive females. Most compounds identified by the model were lipids and amino acids and revealed pathway alterations related to chemoresistance., Conclusion: We developed a model for predicting patient response to NACT. These metabolite panels allow clinical gain by building precision medicine strategies based on tumor stratification.

Dietary supplements are drastically growing as a category of consumer products all over the world. The abuse of supplements marketed for slimming purposes and physical fitness has been observed worldwide in recent years, which raises concerns in terms of public health. In this study, different types of dietary supplements marketed and delivered through the e -commerce were studied for the determination of thallium as a hazardous inorganic contaminant. The total content of thallium was determined by a sensitive voltammetric method after a microwave-assisted oxidative digestion of the sample. In addition, a comparative spectrometric method was applied for validation of the results in the samples. The maximum concentration found for thallium was found to be 2.89 mg kg -1 , which well agree with the comparative measurement. Considering the 32 studied formulations, it can be pointed out that ∼24% of the of dietary supplements presented Tl concentrations at concentrations higher than 1 mg kg -1 . The results permitted the assessment of the health risk related to thallium from contaminated samples, based on the calculation of the estimated daily intake (EDI) and the risk quotient (HQ). The highest daily intake of thallium was calculated as 82.0 µg day -1 in a protein-based supplement, which is equivalent to an EDI of 1.17 µg kg -1  day -1 . This work highlights the need to develop regulations on the limits of toxic elements such as thallium in widely consumed dietary supplements, as well as an in-depth look at the adverse effects caused by this element in the human body.

Trichoderma erinaceum is a filamentous fungus that was isolated from decaying sugarcane straw at a Brazilian ethanol biorefinery. This fungus shows potential as a source of plant cell wall-degrading enzymes (PCWDEs). In this study, we conducted a comprehensive multiomics investigation of T. erinaceum to gain insights into its enzymatic capabilities and genetic makeup. Firstly, we performed genome sequencing and assembly, which resulted in the identification of 10,942 genes in the T. erinaceum genome. We then conducted transcriptomics and secretome analyses to map the gene expression patterns and identify the enzymes produced by T. erinaceum in the presence of different substrates such as glucose, microcrystalline cellulose, pretreated sugarcane straw, and pretreated energy cane bagasse. Our analyses revealed that T. erinaceum highly expresses genes directly related to lignocellulose degradation when grown on pretreated energy cane and sugarcane substrates. Furthermore, our secretome analysis identified 35 carbohydrate-active enzymes, primarily PCWDEs. To further explore the enzymatic capabilities of T. erinaceum , we selected a β-glucosidase from the secretome data for recombinant production in a fungal strain. The recombinant enzyme demonstrated superior performance in degrading cellobiose and laminaribiose compared to a well-known enzyme derived from Trichoderma reesei . Overall, this comprehensive study provides valuable insights into both the genetic patterns of T. erinaceum and its potential for lignocellulose degradation and enzyme production. The obtained genomic data can serve as an important resource for future genetic engineering efforts aimed at optimizing enzyme production from this fungus.

Extreme environments, such as Antarctica, select microbial communities that display a range of evolutionary strategies to survive and thrive under harsh environmental conditions. These include a diversity of specialized metabolites, which have the potential to be a source for new natural product discovery. Efforts using (meta)genome mining approaches to identify and understand biosynthetic gene clusters in Antarctica are still scarce, and the extent of their diversity and distribution patterns in the environment have yet to be discovered. Herein, we investigated the biosynthetic gene diversity of the biofilm microbial community of Whalers Bay, Deception Island, in the Antarctic Peninsula and revealed its distribution patterns along spatial and temporal gradients by applying metagenome mining approaches and multivariable analysis. The results showed that the Whalers Bay microbial community harbors a great diversity of biosynthetic gene clusters distributed into seven classes, with terpene being the most abundant. The phyla Proteobacteria and Bacteroidota were the most abundant in the microbial community and contributed significantly to the biosynthetic gene abundances in Whalers Bay. Furthermore, the results highlighted a significant correlation between the distribution of biosynthetic genes and taxonomic diversity, emphasizing the intricate interplay between microbial taxonomy and their potential for specialized metabolite production.IMPORTANCEThis research on antarctic microbial biosynthetic diversity in Whalers Bay, Deception Island, unveils the hidden potential of extreme environments for natural product discovery. By employing metagenomic techniques, the research highlights the extensive diversity of biosynthetic gene clusters and identifies key microbial phyla, Proteobacteria and Bacteroidota, as significant contributors. The correlation between taxonomic diversity and biosynthetic gene distribution underscores the intricate interplay governing specialized metabolite production. These findings are crucial for understanding microbial adaptation in extreme environments and hold significant implications for bioprospecting initiatives. The study opens avenues for discovering novel bioactive compounds with potential applications in medicine and industry, emphasizing the importance of preserving and exploring these polyextreme ecosystems to advance biotechnological and pharmaceutical research., Competing Interests: The authors declare no conflicts of interest.

Objective: To assess the prevalence of chronic neutropenia (CN) and the clinical profile of patients with CN aged up to 18 years, followed in the pediatric hematology, rheumatology, or immunology outpatient clinic of a tertiary medical center from May 1, 2018, to 30 April 2019., Methods: Retrospective observational study carried out by collecting data from the patient's medical charts. CN was defined as absolute neutrophil count (ANC) below 1.5 × 10 9 /L lasting over three months. Autoimmune neutropenia (AIN) was defined by clinical criteria and an over twofold increase in ANC after glucocorticoid stimulation. AIN was considered secondary when associated with autoimmune or immunoregulatory disorders. Wilcoxon and Fisher's exact tests were used to compare variables; the significance level was 5 %., Results: A total of 1,039 patients were evaluated; 217 (20 %) presented CN. Twenty-one (2 %) had AIN, classified as primary in 57 % of the cases. The average age at the onset of symptoms was 38.6 months. During follow-up, patients had 4.2 infections on average; frequency was higher among patients with secondary AIN (p = 003). Isolated neutropenia occurred in 43 % of the patients with AIN. Neutropenia resolved in eight (38 %) of the 21 patients with AIN within 19.6 months on average. Eight patients with secondary AIN met the criteria for Inborn Errors of Immunity., Conclusion: AIN prevalence was 2 %. Most cases were first evaluated by a pediatric immunologist or rheumatologist rather than a pediatric hematologist. This study highlights the need for a multidisciplinary approach involving a pediatric immunologist, rheumatologist, and hematologist., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Editora Ltda.)

In the last decade, over 40% of bird species in Europe have experienced poor and bad conservation status, with more than 30% of bird species in mainland Portugal threatened with extinction. Along with anthropogenic factors, parasites and pathogens such as avian haemosporidians have been suggested to be responsible for these avian population declines. Wildlife rehabilitation centres play an essential role in species conservation and preservation. Moreover, animals admitted for rehabilitation can provide valuable information regarding transmission and pathogenicity of many diseases that affect wild birds that are rarely sampled in nature. However, reports of haemosporidians in captive birds are still limited. Here, we explored the prevalence and genetic diversity of avian haemosporidians in 89 birds from 29 species admitted to rehabilitation centres in Portugal, showing an overall infection prevalence of 30.3%. The prevalence of infection was higher in Strigiformes and in birds admitted to rehabilitation centres due to debilitating diseases. Remarkably, 30% of the infected bird species have not been found to harbour malaria parasites in preceding studies. We detected 15 different haemosporidian lineages infecting a third of bird species sampled. Notably, 2 out of these 15 detected haemosporidian lineages have not been obtained previously in other studies. Furthermore, we also identified nine new host-parasite interactions representing new host records for these haemosporidian parasites. Finally, our results revealed that birds infected with haemosporidians require longer rehabilitation treatments, which increase the economic costs for rehabilitation and may impair their survival prospects. These findings emphasise the importance of integrating haemosporidian infection considerations into rehabilitation protocols, highlighting the challenges posed by these infections in avian conservation and rehabilitation, including economic and logistical demands.

Two inbred strains, Lewis (LEW) and Spontaneously Hypertensive Rats (SHR), are well-known for their contrasting behavior related to anxiety/emotionality. Studies with these two strains led to the discovery of the Quantitative Trait Loci (QTL) on chromosome 4 (Anxrr16). To better understand the influences of this genomic region, the congenic rat strain SLA16 (SHR.LEW-Anxrr16) was developed. SLA16 rats present higher hyperactivity/impulsivity, deficits in learning and memory, and lower basal blood pressure than the SHR strain, even though genetic differences between them are only in chromosome 4. Thus, the present study proposed the alpha-synuclein and the dopaminergic system as candidates to explain the differential behavior of SHR and SLA16 strains. To accomplish this, beyond the behavioral analysis, we performed (I) the Snca gene expression and (II) quantification of the alpha-synuclein protein in the hippocampus (HPC), prefrontal cortex (PFC), and striatum (STR) of SHR and SLA16 strains; (III) sequencing of the 3'UTR of the Snca gene; and (IV) evaluation of miRNA binding in the 3'UTR site. A Single Nucleotide Polymorphism (SNP) was identified in the 3'UTR of the Snca gene, which exhibited upregulation in the HPC of SHR compared to SLA16 females. Alpha-synuclein protein was higher in the HPC of SHR males compared to SLA16 males. The results of this work suggested that differences in alpha-synuclein HPC content could be influenced by miRNA regulation and associated with behavioral differences between SHR and SLA16 animals., Competing Interests: Declarations of interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Alcohol withdrawal-induced hyperalgesia (AWH) is characterized as an increased pain sensitivity observed after cessation of chronic alcohol use. Alcohol withdrawal-induced hyperalgesia can contribute to the negative affective state associated with abstinence and can increase susceptibility to relapse. We aimed to characterize pain sensitivity in mice during withdrawal from two different models of alcohol exposure: chronic drinking in the dark (DID) and the Lieber-DeCarli liquid diet. We also investigated whether treatment with a histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), could ameliorate AWH in mice treated with the Lieber-DeCarli diet., Methods: Male and female C57BL/6J mice were used for these studies. In the DID model, mice received bottles of 20% ethanol or water during the dark cycle for 4 h per day on four consecutive days per week for 6 weeks. Peripheral mechanical sensitivity was measured weekly the morning of Day 5 using von Frey filaments. In the Lieber-DeCarli model, mice received ethanol (5% v/v) or control liquid diet for 10 days, along with a single binge ethanol gavage (5 g/kg) or control gavage, respectively, on Day 10. Peripheral mechanical sensitivity was measured during the liquid diet administration and at 24 and 72 h into ethanol withdrawal. An independent group of mice that received the Lieber-DeCarli diet were administered SAHA (50 mg/kg, i.p.) during withdrawal., Results: Male mice exhibited mechanical hypersensitivity after consuming ethanol for 5 weeks in the DID procedure. In the Lieber-DeCarli model, ethanol withdrawal led to hyperalgesia in both sexes. Suberoylanilide hydroxamic acid treatment during withdrawal from the ethanol liquid diet alleviated AWH., Conclusions: These results demonstrate AWH in mice after chronic binge drinking in males and after Lieber-DeCarli liquid diet administration in both sexes. Like previous findings in rats, HDAC inhibition reduced AWH in mice, suggesting that epigenetic mechanisms are involved in AWH., (© 2024 The Authors. Alcohol: Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.)

Background: The combined application of predatory fungi and antiparasitic drugs is a sustainable approach for the integrated control of animal gastrointestinal (GI) parasites. However, literature addressing the possible interference of antiparasitic drugs on the performance of these fungi is still scarce. This research aimed to assess the in vitro susceptibility of six native coccidicidal fungi isolates of the species Mucor circinelloides and one Mucor lusitanicus isolate to several antiparasitic drugs commonly used to treat GI parasites' infections in birds, namely anthelminthics such as Albendazole, Fenbendazole, Levamisole and Ivermectin, and anticoccidials such as Lasalocid, Amprolium and Toltrazuril (drug concentrations of 0.0078-4 µg/mL), using 96-well microplates filled with RPMI 1640 medium, and also on Sabouraud Agar (SA)., Results: This research revealed that the exposition of all Mucor isolates to the tested anthelminthic and anticoccidial drug concentrations did not inhibit their growth. Fungal growth was recorded in RPMI medium, after 48 h of drug exposure, as well as on SA medium after exposure to the maximum drug concentration., Conclusions: Preliminary findings from this research suggest the potential compatibility of these Mucor isolates with antiparasitic drugs for the integrated control of avian intestinal parasites. However, further in vitro and in vivo studies are needed to confirm this hypothesis., (© 2024. The Author(s).)

Whey protein concentrate (WPC) and maltodextrin were used to microencapsulate polyphenols extract from organic coffee husks by spray drying. The microparticles were characterized and evaluated for their influence on the release, bioaccessibility, and antioxidant capacity of polyphenols in the simulated gastrointestinal tract. WPC as a single encapsulating agent promoted better yield (54.8%) of microparticles. The microparticles showed solubility above 92%, and lower hygroscopicity when encapsulated with maltodextrin alone (7.4%). Smaller diameter (6.78 µm), better encapsulation efficiency (89.1%) and retention of compounds (74.4%) were observed in microparticles with WPC in the composition. Polyphenols were completely released from the microparticles during simulated gastric digestion. The microparticles influenced the bioaccessibility of over 70% of the polyphenols in the intestinal phase. The microparticles showed rapid gastrointestinal release effect but favored the increase of bioaccessibility and preservation of the antioxidant capacity of polyphenols, especially those from the microparticles with WPC compared to the free extract., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis., Method: A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol., Results: Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma., Conclusion: Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series., (© 2024. The Author(s).)

Background: The large quantities of by-products generated in the coffee industry are a problem. Studies related to the biological potential of organic coffee husks are still limited. The aim of this work was to investigate the occurrence of phenolic compounds in organic coffee husks and to evaluate their potential as a source of bioactive dietary components., Results: To achieve this objective, three extracts were prepared, namely extractable polyphenols (EPs), hydrolyzable non-extractable polyphenols (H-NEPs), and non-extractable polyphenols (NEPs). These extracts were characterized and evaluated for their bioactive properties after simulated gastrointestinal digestion. The results show that the extraction process affected the occurrence of phenols from coffee peels, especially for caffeic acid, gallic acid, and chlorogenic acid. The free and bound polyphenols found in the extracts and digests not only showed antioxidant properties against 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals but were also strongly bioavailable and had good anticoagulant potential., Conclusion: These results highlight the potential health benefits of phytochemicals from coffee husks and open new perspectives for the use of such compounds in dietary supplements. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

This article reports the first occurrence of Rhytidodes gelatinosus (Rudolphi, 1819) Looss, 1901 (Digenea: Rhytidodidae) in the olive-ridley turtle Lepidochelys olivacea (Testudines: Chelonidae), in an individual found in the State of Sergipe, Brazil. Although R. gelatinosus has already been described in other species of sea turtles in the world, this is the first report of this parasite in L. olivacea . We also present a list of hosts and locations where this helminth has already been identified., Competing Interests: Conflict of Interest Authors declare no conflict of interest., (© 2023 J. Da Cunha Fernandes et al., published by Sciendo.)

The article presents a framework for a Bioinformatics competition that focuses on 4 key aspects: structure, model, overview, and perspectives. Structure represents the organizational framework employed to coordinate the main tasks involved in the competition. Model showcases the competition design, which encompasses 3 phases. Overview presents our case study, the League of Brazilian Bioinformatics (LBB) 2nd Edition. Finally, the section on perspectives provides a brief discussion of the LBB 2nd Edition, along with insights and feedback from participants. LBB is a biannual team competition launched in 2019 to promote the ongoing training of human resources in Bioinformatics and Computational Biology in Brazil. LBB aims to stimulate ongoing training in Bioinformatics by encouraging participation in competitions, promoting the organization of future Bioinformatics competitions, and fostering the integration of the Bioinformatics and Computational Biology community in the country, as well as collaboration among participants. The LBB 2nd Edition was launched in 2021 and featured 251 competitors forming 91 teams. Knowledge competitions promote learning, collaboration, and innovation, which are crucial for advancing scientific knowledge and solving real-world problems. In summary, this article serves as a valuable resource for individuals and organizations interested in developing knowledge competitions, offering a model based on our experience with LBB to benefit all levels of Bioinformatics trainees., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Horácio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The helminth fauna of juvenile green sea turtles ( Chelonia mydas Linnaeus, 1758) is still poorly known. Herein, we study the gastrointestinal helminths of 28 juvenile green sea turtles found stranded on the north coast of Rio de Janeiro state, Brazil. All turtles were infected showing a rich helminth fauna. In total, 14802 trematodes belonging to 30 species and 5 families including Micros-caphidiidae, Plagiorchiidae, Pronocephalidae, Hapalotrematidae, and Telorchiidae were recovered. An unidentified nematode specimens was also found. The mean intensity was 536 (95% CI = 362 - 853) (range: 1 - 2831), and the species richness was 7.86 (95% CI = 6.46 - 9.21) (range: 1 - 17). The coast of Rio de Janeiro state represents new locality records for Angiodictyum posterovitellatum, Microscaphidium aberrans, M. warui, Octangium hyphalum, O. sagitta, Enodiotrema reductum and Pleurogonius laterouterus . This study confirms that the green sea turtle harbors the richest helminth fauna among sea turtle species and provides useful information on the gastrointestinal helminths of a poorly known stage in the life cycle of this endangered chelonian., Competing Interests: Conflict of Interest Authors state no conflict of interest., (© 2023 B. Cavaco et al., published by Sciendo.)

Cystic echinococcosis, also known as hydatid disease, is a significant parasitic zoonosis with public health implications, albeit often neglected. In Portugal, data on this zoonosis are scarce despite being a mandatory notifiable disease in both humans and animals. To assess the impact of cystic echinococcosis on both livestock and humans, we compiled data from slaughterhouse records of ruminants, human hospitalizations, and confirmed cases of human echinococcosis. Overall, a total of 298 cases of cystic echinococcosis were identified in ruminants slaughtered from national farms for human consumption in Portugal between 2008 and 2022, comprising 192 cases in ovines, 95 in bovines, and 11 in caprines. Echinococcosis led to 582 hospitalizations in Portuguese public hospitals, with an average hospital stay of 11 days (±15.66), and resulted in 13 deaths (2.23%) from 2008 to 2018. Each infected animal was associated with a 7% increase in the incidence rate of human hospitalization ( p = 0.002, IRR = 1.070, 95% CI: 1.025-1.117). Additionally, for every 100,000 person-years observed between 2008 and 2018, the total number of hospitalizations was 0.528. Residence in the Alentejo region was associated with a 5.3-fold increase in the incidence rate of human hospitalizations and an 8-fold higher risk of death from echinococcosis.

The control of gastrointestinal parasites in animals has become more challenging every year due to parasite resistance to conventional chemical control, which has been observed worldwide. Ovicidal or opportunistic fungi do not form traps to capture larvae. Their mechanism of action is based on a mechanical/enzymatic process, which enables the penetration of their hyphae into helminth eggs, with subsequent internal colonization of these. The biological control with the Pochonia chlamydosporia fungus has been very promising in the treatment of environments and prevention. When used in intermediate hosts of Schistosoma mansoni, the fungus promoted a high percentage decrease in the population density of aquatic snails. Secondary metabolites were also found in P. chlamydosporia. Many of these compounds can be used by the chemical industry in the direction of a commercial product. This review aims to provide a description of P. chlamydosporia and its possible use as a biological parasitic controller. The ovicidal fungus P. chlamydosporia is effective in the control of parasites and goes far beyond the control of verminosis, intermediate hosts, and coccidia. It can also be used not only as biological controllers in natura but also as their metabolites and molecules can have chemical action against these organisms. KEY POINTS: • The use of the fungus P. chlamydosporia is promising in the control of helminths. • Metabolites and molecules of P. chlamydosporia may have chemical action in control., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil., Patients and Methods: This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected., Results: Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses., Conclusion: The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t)., (© 2023. The Author(s).)

Honeys produced by stingless bees Cephalotrigona capitata and Scutellaris Latrelle in the Caatinga and Atlantic Forest biomes were characterized in terms of chemical composition, antioxidant activity and phenolic, volatile and sensory profile. 'Mombucão' honey showed higher water activity, acidity, % sucrose and % organic acids, while 'uruçu' honey showed the highest % fructose and glucose. Nineteen phenolic compounds and flavonoids were quantified, with emphasis on epicatechin gallate, myricetin, quercetin and procyanidin A2. 'Mombucão' honey stood out with the highest to antioxidant activity. A total of 133 volatile compounds were identified in honeys, with emphasis on terpenes (41) and esters (26). 'Mombucão' honey presented a differentiated sensory profile and was characterized by the prevalence of acid and citrus aroma and flavor, while 'uruçu' honey presented a more characteristic sweet and woody aroma and flavor. The variability in the composition of honeys probably resulted from bee species, floral species and geographic origins., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The effects of silver nano/microparticles (AgP) on juvenile Litopenaeus vannamei shrimp were evaluated through several responses, aiming to use it as a prophylactic and therapeutic method. Shrimps (3.19 ± 0.13 g) were exposed to clear water for 3 h with increasing concentrations of nanosilver (0; 25; 100; and 400 μg/l). After 3 h of exposure, they were transferred to water without nanosilver for 30 days (recovery). The weight gain and weekly growth were not affected by AgNP. Total antioxidant capacity (ACAP) increased in the hepatopancreas (exposure period) and gills (recovery) in shrimp exposed to AgNP. In muscle, ACAP was induced in shrimp exposed to 100 μg/l AgNP (exposure). In the gills, there was an increase in TBARS in shrimp exposed to 100 μg/l AgNP (recovery). In the concentration of protein-associated sulfhydryl groups (P-SH), a decrease was observed in the hepatopancreas (recovery) in the 100 μg/l AgNP treatment. In chromaticity parameters, an increase in reddish tones was observed in shrimp exposed to 100 μg/l AgNP (recovery). An increase in granular hemocytes was verified in shrimp exposed to 25 and 400 μg/l AgNP during exposure. Tissues analyzed histologically showed normal patterns without apoptosis or necrosis processes, and after 30 d of recovery, only in one muscle sample of shrimp exposed to μg/l of AgNP was silver detected. It is concluded that a prophylactic action of short duration (3 h) mostly did not affected the welfare of shrimp L. vannamei and can be considered its use as a therapeutic strategy., Competing Interests: Declaration of competing interest 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., (Copyright © 2022. Published by Elsevier Inc.)

At the end of the nineteenth century, massive population declines were observed in carnivores due to the emergence of infectious diseases. This study aims to investigate, by means of coprological analysis, the prevalence and intensity of the parasites that infect the endangered Iberian wolf Canis lupus signatus and two mesocarnivores (the red fox Vulpes vulpes and the stone marten Martes foina) in Central Portugal. In total, 67.2% of the samples screened were infected; Toxascaris leonina (40.6%) was the parasite with the highest prevalence, followed by Ancylostomatidae and Eimeria spp. (28.1%). Eimeria spp. was found in stone marten with the highest infection rate (37,800 OPG), followed by T. leonina (10,100 EPG) in a red fox sample. Moderate to high levels of parasitic infections were identified in 73.3% of red foxes from the western area. Our results highlight the possibility of cross-infection among these carnivore species and cross-contamination in the wildlife-livestock-human interface., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Compulsive alcohol drinking is a key symptom of alcohol use disorder (AUD) that is particularly resistant to treatment. An understanding of the biological factors that underly compulsive drinking will allow for the development of new therapeutic targets for AUD. One animal model of compulsive alcohol drinking involves the addition of bitter-tasting quinine to an ethanol solution and measuring the willingness of the animal to consume ethanol despite the aversive taste. Previous studies have demonstrated that this type of aversion-resistant drinking is modulated in the insular cortex of male mice by specialized condensed extracellular matrix known as perineuronal nets (PNNs), which form a lattice-like structure around parvalbumin-expressing neurons in the cortex. Several laboratories have shown that female mice exhibit higher levels of aversion-resistant ethanol intake but the role of PNNs in females in this behavior has not been examined. Here we compared PNNs in the insula of male and female mice and determined if disrupting PNNs in female mice would alter aversion-resistant ethanol intake. PNNs were visualized in the insula by fluorescent labeling with Wisteria floribunda agglutinin (WFA) and disrupted in the insula by microinjecting chondroitinase ABC, an enzyme that digests the chondroitin sulfate glycosaminoglycan component of PNNs. Mice were tested for aversion-resistant ethanol consumption by the addition of sequentially increasing concentrations of quinine to the ethanol in a two-bottle choice drinking in the dark procedure. PNN staining intensity was higher in the insula of female compared to male mice, suggesting that PNNs in females might contribute to elevated aversion-resistant drinking. However, disruption of PNNs had limited effect on aversion-resistant drinking in females. In addition, activation of the insula during aversion-resistant drinking, as measured by c-fos immunohistochemistry, was lower in female mice than in males. Taken together, these results suggest that neural mechanisms underlying aversion-resistant ethanol consumption differ in males and females.

The Eastern Amazon is rich in bauxite ore. The extraction and processing of bauxite lead to the mobilization of Aluminum (Al) and other metals in environmental. We evaluated the metals (Al, Mn, Ba, and Cr) concentration in tissue, water, and sediment associated with antioxidant and oxidative damage responses in Bryconops caudomaculatus. The samplings were done in two hydrological periods (post-rain and post-dry periods) and at three points, located at two rivers: one in the surroundings of the mining area (P1) and other inside the mining area, upstream (P2), and downstream (P3). Defense antioxidant system biomarkers analyzed were total antioxidant capacity (ACAP) and glutathione-S-transferase (GST) activity. As an oxidative damage biomarker, the lipoperoxidation (LPO) was evaluated. Metals concentrations in the water and sediment were higher in the post-rain period compared to post-dry period. The water samples were acidic, with dissolved Al concentrations above the values established by local legislation at all points. In the gills, the metals accumulation was higher in fish from in the surrounding and upstream sites, and in the liver, was higher in fish from downstream site. Fish from the surrounding had increased antioxidant defenses, with higher ACAP in all tissues and higher GST in the gills. Consequently, they had lower levels of LPO. Fish from the mining area had decreased antioxidant defenses, with lower ACAP in all tissues and lower GST in the gills. Consequently, they had higher levels of LPO, indicating oxidative stress. The fish muscle was not responsive to GST and LPO at all sites. We conclude that the oxidative stress observed in the gills and liver of B. caudomaculatus from the area modified by the mining activity reflected the local anthropogenic impact status., Competing Interests: Declaration of competing interest 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Infections caused by gastrointestinal parasites have been described worldwide as one of the most important issues impacting small ruminant production. The systematic administration of anthelmintic (AH) drugs without following good practice principles has led to an increase in anthelmintic resistance (AR). There is scarce information regarding AH efficacy in small ruminants in Portugal. This study aimed to characterize by in vivo methods the presence and level of AR in four farms in the region of Lisbon and Tagus Valley. All four farms kept small herds in extensive management systems and used different deworming protocols. The active substances used were fenbendazole and a combination of mebendazole plus closantel in a dosage according to the manufacturers' instructions. On day 0 (T0), fecal samples were collected from all study animals, and animals in the treatment group (n = 40) were dewormed with the AH previously chosen by the assistant veterinarian. Animals in the control group (n = 30) did not receive any AH drug. The fecal sample collection was repeated on day 15 (T15), and the control group was treated. Egg counts were performed using the McMaster method for the eggs per gram (EPG), and AR was evaluated by the fecal egg count reduction test (FECRT) with a 95% confidence level (CL). The results from this experiment indicated that the four farms presented AR with two farms to fenbendazole (FECRT of 48% and 85%) and two farms to mebendazole plus closantel (FECRT of 66% and 79%). These results indicate that the gastrointestinal parasites of the four studied Portuguese farms are resistant to benzimidazoles, which suggests an increase in AR regarding nematodes in small ruminant production systems in Portugal.

The antioxidant capacity of organic coffee husk extract (Coffee arabica L.) added to chicken burgers was evaluated. Two formulations were prepared: with addition of the extract (100 and 200 ppm CAE/kg), in addition to control formulations without the addition of antioxidant, and with the addition of synthetic antioxidant. The products were characterized by physical and chemical analysis and analyzed for oxidative stability during 45 days of storage under freezing. The addition of extract in the proportion of 200 ppm CAE/kg of hamburger revealed efficacy against lipid oxidation equivalent to treatment with a synthetic antioxidant. As for protein oxidation, there was no pro or antioxidant influence in the treatments. The addition of organic coffee husk extract to chicken hamburgers is thus indicated, being considered as a potential natural additive. In addition, the use of coffee husks helps to minimize the lager amounts of agro-industrial by-products generated by the coffee industry., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Spirometra infection is aneglected food- and waterborne disease with worldwide distribution., Objectives: The present study aims to estimate the global prevalence of Spirometra species in snakes, frogs, dogs and cats., Methods: Multiple databases (PubMed, Scopus, ProQuest, Web of Science and Google Scholar) were searched for relevant literatures published up to March 2022., Results: Among 131 data sets (including 113 articles) that met the inclusion, 15 investigations reported Spirometra infection in snakes, 23 in frogs, 41 in dogs and 52 in cats. The pooled prevalence (95% confidence interval) in intermediate hosts and definitive hosts was found to be 0.313% and 0.089%, respectively. Based on continent, the infection was most prevalent in Asia for studies on snakes (0.696%) and frogs (0.181%), while Africa (0.224%) and Oceania (0.203%) were the regions with the highest pooled prevalence rates of the infection in dogs and cats, respectively. Among different diagnostic methods, the highest pooled prevalence was related to morphological method for studies on snakes, frog and cats with rate of 0.665%, 0.189% and 0.104%, respectively. Regarding studies on dogs, the highest pooled prevalence was observed for molecular technique (0.101%)., Conclusions: The results presented here revealed the importance of establishing a prevention and control measure focused on protection of aquaculture systems from being contaminated with faeces of dogs and cats, and raising awareness of parasitic zoonotic diseases to decrease the transmission risk., (© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Chronic heavy alcohol consumption is associated with increased mortality and morbidity and often leads to premature aging; however, the mechanisms of alcohol-associated cellular aging are not well understood. In this study, we used DNA methylation derived telomere length (DNAmTL) as a novel approach to investigate the role of alcohol use on the aging process. DNAmTL was estimated by 140 cytosine phosphate guanines (CpG) sites in 372 individuals with alcohol use disorder (AUD) and 243 healthy controls (HC) and assessed using various endophenotypes and clinical biomarkers. Validation in an independent sample of DNAmTL on alcohol consumption was performed (N = 4219). Exploratory genome-wide association studies (GWAS) on DNAmTL were also performed to identify genetic variants contributing to DNAmTL shortening. Top GWAS findings were analyzed using in-silico expression quantitative trait loci analyses and related to structural MRI hippocampus volumes of individuals with AUD. DNAmTL was 0.11-kilobases shorter per year in AUD compared to HC after adjustment for age, sex, race, and blood cell composition (p = 4.0 × 10 -12 ). This association was partially attenuated but remained significant after additionally adjusting for BMI, and smoking status (0.06 kilobases shorter per year, p = 0.002). DNAmTL shortening was strongly associated with chronic heavy alcohol use (ps < 0.001), elevated gamma-glutamyl transferase (GGT), and aspartate aminotransferase (AST) (ps < 0.004). Comparison of DNAmTL with PCR-based methods of assessing TL revealed positive correlations (R = 0.3, p = 2.2 × 10 -5 ), highlighting the accuracy of DNAmTL as a biomarker. The GWAS meta-analysis identified a single nucleotide polymorphism (SNP), rs4374022 and 18 imputed ones in Thymocyte Expressed, Positive Selection Associated 1(TESPA1), at the genome-wide level (p = 3.75 × 10 -8 ). The allele C of rs4374022 was associated with DNAmTL shortening, lower hippocampus volume (p < 0.01), and decreased mRNA expression in hippocampus tissue (p = 0.04). Our study demonstrates DNAmTL-related aging acceleration in AUD and suggests a functional role for TESPA1 in regulating DNAmTL length, possibly via the immune system with subsequent biological effects on brain regions negatively affected by alcohol and implicated in aging., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)