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The objective of this review is to provide a comprehensive examination of the role of microbial metabolites in the progression of neurodegenerative diseases, as well as to investigate potential therapeutic interventions targeting the microbiota. A comprehensive literature search was conducted across the following databases: PubMed, Scopus, Web of Science, ScienceDirect, and Wiley. Key terms related to the gut microbiota, microbial metabolites, neurodegenerative diseases, and specific metabolic products were used. The review included both preclinical and clinical research articles published between 2000 and 2024. Short-chain fatty acids have been demonstrated to play a crucial role in modulating neuroinflammation, preserving the integrity of the blood–brain barrier, and influencing neuronal plasticity and protection. Furthermore, amino acids and their derivatives have been demonstrated to exert a significant influence on CNS function. These microbial metabolites impact CNS health by regulating intestinal permeability, modulating immune responses, and directly influencing neuroinflammation and oxidative stress, which are integral to neurodegenerative diseases. Therapeutic strategies, including prebiotics, probiotics, dietary modifications, and fecal microbiota transplantation have confirmed the potential to restore microbial balance and enhance the production of neuroprotective metabolites. Furthermore, novel drug developments based on microbial metabolites present promising therapeutic avenues. The gut microbiota and its metabolites represent a promising field of research with the potential to advance our understanding of and develop treatments for neurodegenerative diseases.

Parkinson’s Disease (PD) is a prevalent neurodegenerative disorder characterized by motor and non-motor symptoms. Emerging evidence suggests that gut microbiota alterations, specifically involving short-chain fatty acids (SCFAs) like butyrate, may influence PD pathogenesis and symptomatology. This Systematic Review aims to synthesize current research on the role of butyrate in modulating motor symptoms and its neuroprotective effects in PD, providing insights into potential therapeutic approaches. A systematic literature search was conducted in April 2024 across databases, including ScienceDirect, Scopus, Wiley, and Web of Science, for studies published between 2000 and 2024. Keywords used were “neuroprotective effects AND butyrate AND (Parkinson disease OR motor symptoms)”. Four authors independently screened titles, abstracts, and full texts, applying inclusion criteria focused on studies investigating butyrate regulation and PD motor symptoms. A total of 1377 articles were identified, with 40 selected for full-text review and 14 studies meeting the inclusion criteria. Data extraction was performed on the study population, PD models, methodology, intervention details, and outcomes. Quality assessment using the SYRCLE RoB tool highlighted variability in study quality, with some biases noted in allocation concealment and blinding. Findings indicate that butyrate regulation has a significant impact on improving motor symptoms and offers neuroprotective benefits in PD models. The therapeutic modulation of gut microbiota to enhance butyrate levels presents a promising strategy for PD symptom management.

Over the past few years, there has been a surge in the industrial production of recombinant enzymes from microorganisms due to their catalytic characteristics being highly efficient, selective, and biocompatible. l -asparaginase ( l -ASNase) is an enzyme belonging to the class of amidohydrolases that catalyzes the hydrolysis of l -asparagine into l -aspartic acid and ammonia. It has been widely investigated as a biologic agent for its antineoplastic properties in treating acute lymphoblastic leukemia. The demand for l -ASNase is mainly met by the production of recombinant type II l -ASNase from Escherichia coli and Erwinia chrysanthemi . However, the presence of immunogenic proteins in l -ASNase sourced from prokaryotes has been known to result in adverse reactions in patients undergoing treatment. As a result, efforts are being made to explore strategies that can help mitigate the immunogenicity of the drug. This review gives an overview of recent biotechnological breakthroughs in enzyme engineering techniques and technologies used to improve anti-leukemic l -ASNase, taking into account the pharmacological importance of l -ASNase. Graphical Abstract

Covalent attachment of therapeutic proteins to polyethylene glycol (PEG) is widely used for the improvement of its pharmacokinetic and pharmacological properties, as well as the reduction in reactogenicity and related side effects. This technique named PEGylation has been successfully employed in several approved drugs to treat various diseases, even cancer. Some methods have been developed to obtain PEGylated proteins, both in multiple protein sites or in a selected amino acid residue. This review focuses mainly on traditional and novel examples of chemical and enzymatic methods for site-selective PEGylation, emphasizing in N-terminal PEGylation, that make it possible to obtain products with a high degree of homogeneity and preserve bioactivity. In addition, the main assay methods that can be applied for the characterization of PEGylated molecules in complex biological samples are also summarized in this paper.

Background It has been documented that the parents’ highest level of education has an impact on their children’s access to oral health services and the frequency of their use.This study aimed to determine the association between time elapsed since peruvian children’s last dental care and head of household educational attainment. Methods Cross-sectional study using a database of children aged 0 to 11 years, with a final sample of 8012 participants. The dependent variable in this study was the time elapsed since last dental care and the independent variable was the head of household educational attainment. Other covariates considered were natural region, area of residence, place of residence, altitude, wealth index, health insurance coverage, sex and age. Descriptive, bivariate and multivariate statistical analyses were applied. Results Time elapsed since last dental care in the year 2021 was 5.68 years (SD = 5.25). A hierarchical multiple linear regression analysis was performed, analyzing the variables dimensions by separate and joint models. When head of household educational attainment was analyzed, there was no statistical significance (p = 0.262); however, other models did (p < 0.05). Model 4, which addresses all dimensions, was significant (p < 0.001) with an R 2 % of 0.011 and constant equal to 5.788; it showed significance with place of dental care, health insurance, altitude and age. Conclusions No association was found between head of household educational attainment and time elapsed since last dental care; however, the latter was associated with place of care, health insurance coverage, altitude and age in Peruvian children.

The process of examiner calibration is an essential step in all epidemiological research, as it aims to ensure uniform interpretation, understanding, and application of the instrument to be used. This ensures that the data collected will be valid and reliable. This study aimed to determine the differences in concordance in dental caries calibration across three dental specialties. The population consisted of 45 dentists, divided into three groups: 15 general dentists working in the public sector, 15 dentists specializing in Dental Public Health, and 15 dentists specializing in Restorative and Aesthetic Dentistry. The calibration process was carried out in three stages: theory, calibration using photographs, and calibration on natural teeth, performed by the gold standard. In the first validity process, a statistical difference was only found between the Kappa values of the inter-examiner calibration process using photographs. For the evaluation of teeth, in the second validity process, 33.33% (n = 15) of the participants achieved “almost perfect agreement.” Finally, only 75.56% (n = 34) of the examiners were considered for the reliability report; of this group, 52.94% (n = 18) were in “almost perfect agreement,” and 35.29% (n = 12) were in “substantial agreement.” The validity and reliability of the dental caries experience calibration process did not present significant statistical differences between general dentists in the public sector, dentists specializing in Dental Public Health, and dentists specializing in Restorative and Aesthetic Dentistry.

Historical and future projected changes in climatic patterns over the largest irrigated basin in the world, the Indus River Basin (IRB), threaten agricultural production and food security in Pakistan, in particular for vulnerable farming communities. To build a more detailed understanding of the impacts of climate change on agriculture s in the IRB, the present study analyzes (1) observed trends in average temperature, precipitation and related extreme indicators, as well as seasonal shifts over a recent historical period (1997–2016); and (2) statistically downscaled future projections (up to 2100) from a set of climate models in conjunction with crop-specific information for the four main crops of the IRB: wheat, cotton, rice and sugarcane. Key findings show an increasing trend of about over 0.1 °C/year in observed minimum temperature across the study area over the historical period, but no significant trend in maximum temperature. Historical precipitation shows a positive annual increase driven mainly by changes in August and September. Future projections highlight continued warming resulting in critical heat thresholds for the four crops analyzed being increasingly exceeded into the future, in particular in the Kharif season. Concurrently, inter-annual rainfall variability is projected to increase up to 10–20% by the end of the 21st century, augmenting uncertainty of water availability in the basin. These findings provide insight into the nature of recent climatic shifts in the IRB and emphasize the importance of using climate impact assessments to develop targeted investments and efficient adaptation measures to ensure resilience of agriculture in Pakistan into the future.

Objectives The primary objective of the study was to compare the postoperative complications following surgical removal of impacted third molars using panoramic radiography (PAN) images- and cone-beam computed tomography (CBCT)-based surgeries for “moderate-risk” cases of impacted third mandibular molars. The secondary objective was to compare the reliability of CBCT with that of PAN in preoperative radiographic determination of the position of the third molar, number of roots, and apical divergence. Materials and methods A randomized controlled multicenter trial was conducted to compare the surgical complications of PAN- and CBCT-based surgeries of impacted third molars. The sample consisted of impacted third molars from 256 patients with a close relation to the inferior alveolar nerve (IAN). Exclusion criteria were “no risk” and “high risk” of damage to the IAN based on the assessment of the panoramic radiograph. Patients were divided into two groups: the CBCT group ( n  = 126) and the PAN group ( n  = 130). The incidences of IAN sensory disturbance and other postoperative complications were recorded for each group at 7 days after surgery. Statistical analysis (kappa values) was used to compare the diagnoses of five trained dentomaxillofacial radiologists and to relate radiologic diagnoses to perioperative findings. Logistic regression was used to determine whether the imaging modality influenced occurrence of postoperative complications. Results Two extractions (1.5 %) in the CBCT group and five (3.8 %) in the PAN group resulted in IAN sensory disturbance ( p  = 0.45). Logistic regression models did not show that CBCT modality decreased postoperative complications following surgical removal of impacted third molars. Yet, CBCT revealed the number of roots and apical divergence of the roots more reliably than panoramic radiographs. Conclusions CBCT was not better than panoramic radiography in predicting postoperative complications for moderate-risk cases of impacted third mandibular molars. Nonetheless, a CBCT buccolingual view can accurately confirm the number of roots and root morphology of the third molar better than PAN. Clinical relevance For management of postoperative complications for moderate-risk cases of impacted mandibular third molars, careful preoperative radiographic planning followed by an atraumatic surgical approach seems to be valuable, irrespective of the 2D or 3D nature of the preoperative images.

Protein toxins are defense mechanisms and adaptations found in various organisms and microorganisms, and their use in scientific research as therapeutic candidates is gaining relevance due to their effectiveness and specificity against cellular targets. However, discovering these toxins is time-consuming and expensive. In silico tools, particularly those based on machine learning and deep learning, have emerged as valuable resources to address this challenge. Existing tools primarily focus on binary classification, determining whether a protein is a toxin or not, and occasionally identifying specific types of toxins. For the first time, we propose a novel approach capable of classifying protein toxins into 27 distinct categories based on their mode of action within cells. To accomplish this, we assessed multiple machine learning techniques and found that an ensemble model incorporating the Light Gradient Boosting Machine and Quadratic Discriminant Analysis algorithms exhibited the best performance. During the tenfold cross-validation on the training dataset, our model exhibited notable metrics: 0.840 accuracy, 0.827 F1 score, 0.836 precision, 0.840 sensitivity, and 0.989 AUC. In the testing stage, using an independent dataset, the model achieved 0.846 accuracy, 0.838 F1 score, 0.847 precision, 0.849 sensitivity, and 0.991 AUC. These results present a powerful next-generation tool called MultiToxPred 1.0, accessible through a web application. We believe that MultiToxPred 1.0 has the potential to become an indispensable resource for researchers, facilitating the efficient identification of protein toxins. By leveraging this tool, scientists can accelerate their search for these toxins and advance their understanding of their therapeutic potential.

Quinoa (Chenopodium quinoa Willd.) is a herbaceous C3 crop that has demonstrated resilience in regions concurrently affected by climate change and food insecurity, such as sub-Saharan Africa (SSA). The photosynthetic rate and productivity of C3 crops are enhanced under increasing CO₂ concentrations. We looked at future climate trends in SSA to estimate their impacts on quinoa yields in Burkina Faso. Climate projections show a temperature increase of 1.67–4.90°C under Representative Concentration Pathways (RCP) 4.5 and 8.5, respectively by the end of the century. We demonstrate that any further climate disturbances can either be beneficial or harmful for quinoa, and modulating climate risks will depend on the decisions made at the farm level (e.g. planting date and crop choice). Crop modelling supports the identification of the most suitable transplanting dates based on future climate conditions (RCP 4.5 and 8.5), agroclimatic zones (Sahel, Soudano-Sahelian and Soudanian) and time-horizons (2020, 2025, 2050 and 2075). We show that quinoa yields can improve—when grown under irrigated conditions and transplanted in November—by about 14–20% under RCP 4.5 and by 24–33% under RCP 8.5 by 2075 across the Sahel and Soudanian agroclimatic zones, respectively. For the Soudano-Sahelian zone, the highest yield improvements (19%) are obtained when transplanting is assumed in December under RCP 8.5 by 2075. Overall, the findings of this work encourage policymakers and agricultural extension officers to further promote climate-resilient and highly nutritious crops. Such possibilities are of much interest in SSA, thought to be highly vulnerable to climate change impacts where millions of people are already experiencing food insecurity.