Search Results (968)

D-tagatose is a high-value, low-calorie sweetener that can be produced from dairy lactose via a two-step enzymatic route: lactose hydrolysis to galactose followed by galactose isomerization to tagatose. Here, we combined genomics, in silico structural analysis, and biochemical assays to evaluate the lactose-to-tagatose conversion potential of an Antarctic isolate, L47, identified as Ewingella americana (NCBI accession SAMN54554459). Genome mining revealed one L-arabinose isomerase gene (araA) and three β-galactosidase genes (bgaA, bglY, lacZ), an uncommon combination in a single bacterium. Recombinant AraA was produced in Escherichia coli and biochemically characterized, showing Mn²⁺ dependence and measurable D-galactose isomerization, reaching ~18% tagatose from 100 mM galactose after 48 h under the tested conditions. In contrast, the β-galactosidases were predominantly recovered as insoluble aggregates in E. coli; therefore, β-galactosidase activity was assessed using washed inclusion-body preparations. Under these conditions, BgaA displayed the most consistent o-NPG hydrolyzing activity, whereas BglY and LacZ did not yield reproducible activity. Overall, our results identify BgaA as the most tractable lactose-hydrolyzing candidate from L47 in the current workflow and indicate that AraA performance is the principal bottleneck toward an efficient lactose-to-tagatose process, motivating future optimization at the enzyme and process levels. Full article

Powder flow is a constant concern in the production of solid dosage forms. Its concise and reliable determination and improvement are challenges for the pharmaceutical industry. Lactose (Lac) and microcrystalline cellulose (MCC) are both widely used pharmaceutical fillers either alone or mixed. In this study, flow determination was performed through methods described on the European Pharmacopoeia. The results obtained showed poor flow and cohesive behavior for Lac and MCC powders and their mixtures (co-processed excipients). The 50% Lac_MCC mixture, with colloidal silicon dioxide (CSD) as the glidant in different proportions, showed relevant improvements in flow. In addition, the effective angle of wall friction (φx), the effective angle of internal friction (φe), arching, and ratholing were also determined, demonstrating the flow behavior in the discharge equipment. Outlet diameters that prevent blockages or insufficient powder flow were also determined. With this study, it was concluded that it was possible to prepare a co-processed excipient with optimal flow behavior composed of Lac_MCC and CSD as a glidant. Full article

Carbon dioxide (CO₂) emissions are a major contributor to climate change, requiring sustainable carbon capture and utilization (CCU) strategies. This study employed density functional theory (DFT) to assess a choline chloride–lactic acid deep eutectic solvent (CHL–LAC DES) as a dual system for CO₂ capture and gingerol extraction. Using the wB97X-D functional theory for energy calculation with PM3-optimized geometries, the DES exhibited stronger CO₂ binding (–0.86 eV) than monoethanolamine (–0.234 eV) and a higher affinity for 6-gingerol (–1.87 eV). These results suggest that CHL–LAC DES can simultaneously capture CO₂ and extract bioactive compounds, advancing green pharmaceutical and integrated CCU applications. Full article

Background/Objectives: Screening instruments are relevant for assessing the mental health of older adults, favoring clinical practice and research. However, there is a need for instruments with sufficient evidence of validity for use in Latin America and the Caribbean (LAC), where they are growing. This scoping review aims to evaluate the existing evidence regarding the psychometric properties of mental health measurement instruments used with older adults from LAC. Methods: Eight databases (PubMed, CINAHL, Medline, Embase, Scielo, Scopus, Web of Science, PsycINFO) were searched to extract relevant articles about instruments to measure mental health outcomes in older adults in English, Spanish, and Portuguese. After the first screening and duplicate removal, 6307 were retrieved. Results: The full-text screening identified 312 articles for inclusion in the review. Most of the articles were from Brazil (49.04%). One hundred eighty instruments (52.79%) assessed cognition, mainly using the Mini-Mental State Examination (MMSE), followed by 11.14% for depression, most commonly with the Yesavage Depression Scale (GDS). The assessment of validity was predominantly based on two criteria (34%), and 56% of the evidence was published in the last 10 years. To improve usability, we have provided a practical guide to help LAC clinicians and researchers identify and select robustly validated and contextually appropriate assessment instruments. Conclusions: There is still little evidence of the validity of instruments that measure other aspects of mental health beyond cognitive functioning. There seems to be no unified set of criteria in Latin America for determining whether an instrument has sufficient valid evidence. More work is needed on cross-cultural validity evidence within the region. Full article

Pt-rare earth metal (Pt-RE) alloys are considered to be one of the most promising electrocatalysts for producing oxygen reduction reactions (ORRs) due to their compressively strained Pt overlayer and their exceptional negative-alloy formation energies, which result in excellent activity and stability. However, there are still great challenges in the chemical synthesis of Pt-RE nanoalloys. Herein, we report a simple method employing the nanopores of porous carbon as nanoreactors to synthesize a Pt₅La nanoalloy. The Pt₅La alloy nanoparticles are embedded in porous carbon (Pt₅La@C) with a particle size of around 1–3 nm and also exhibit a very narrow size distribution because of the confined-space effect. The as-prepared Pt₅La@C nanoalloy exhibits highly efficient ORR performance with a half-wave potential of 0.912 V in 0.1 M HClO₄, which is 56 mV higher than that of a commercial Pt/C catalyst. Moreover, it achieves an improved intrinsic activity of 0.69 mA cm⁻² and, a mass activity of 0.42 A mg_Pt⁻¹ at 0.90 V. In addition, it also delivers a very stable lifespan performance, with negligible decay in half-wave potential after accelerated stress testing for 10,000 cycles. This work also provides a new method for the development of promising Pt-RE nanoalloys with ultrasmall nanoparticles with a very narrow size distribution for various efficient energy-conversion devices. Full article

Intrinsically disordered regions enable transcription factors (TFs) to undergo structural changes upon ligand binding, facilitating the transduction of environmental signals into gene expression. In this study, we applied molecular modeling methods to explore the hypothesis that unstructured inter-domain and subdomain linkers in bacterial TFs can function as sensors for carbohydrate signaling molecules. We combined molecular dynamics simulations and carbohydrate docking to analyze six repressors with GntR-type DNA-binding domains, including UxuR, GntR and FarR from Escherichia coli, as well as AraR, NagR and YydK from Bacillus subtilis. Protein models obtained from different time points of the dynamic simulations were subjected to sequential carbohydrate docking. We found that the inter-domain linker of the UxuR monomer binds D-fructuronate, D-galacturonate, D-glucose, and D-glucuronate with an affinity comparable to nonspecific interactions. However, these ligands formed multimolecular clusters, a feature absent in the UxuR dimer, suggesting that protein dimerization may depend on linker occupancy by cellular carbohydrates. D-glucose interacted with linkers connecting subdomains of the LacI/GalR-type E-domains in GntR and AraR, forming hydrogen bonds that connected distant structural modules of the proteins, while in NagR, FarR and YydK, it bridged the inter-domain linkers and a β-sheet within the HutC-type E-domains. Hence, our results establish flexible linkers as pivotal metabolic sensors that directly integrate nutritional cues to alter gene expression in bacteria. Full article

This study presents the first systematic regional assessment of how the Historic Urban Landscape (HUL) approach has been understood and applied in Latin American and Caribbean (LAC) cities between 2011 and 2022. The HUL approach is framed as a socio-spatial perspective shaped by historical layering, cultural practices, ecological structures, and contemporary development pressures. A systematic review of academic publications and institutional gray literature (Scopus, Google Scholar, and municipal repositories) was conducted to evaluate both conceptual understanding and methodological implementation aligned with the six steps of the 2011 HUL Recommendation. Findings reveal a clear implementation gap: although awareness of the HUL approach has increased across the region, its practical application remains partial. Steps 1 and 2 focused on value identification and participatory engagement show the highest adoption, while steps 4 and 6 which require interinstitutional coordination and integration into statutory planning instruments exhibit limited progress. Academic and research institutions play a more prominent role than local governments in leading or supporting HUL-related actions, indicating persistent institutional and governance constraints. Results highlight the need to strengthen municipal capacities, integrate HUL-based diagnostics into urban planning systems, and consolidate participatory, interdisciplinary, and multilevel governance mechanisms to close the gap between conceptual uptake and operational implementation. Full article

Transmembrane facilitation of substrates by channels and secondary active transporters results in a defined steady-state concentration ratio across the membrane. Evidence is accumulating that asymmetry in the structural build of the transporters, or interaction with asymmetric partner proteins, can shift the position of the transmembrane equilibrium by biased transport directionality. For instance, the bacterial lactose transporter, LacY, and two amino acid transporters, i.e., the human excitatory amino acid carrier, EAAC1, and the yeast lysine permease, Lyp1, were reported to exhibit distinct transport kinetics in the inward and outward direction by protein-intrinsic properties. A recent example is transport modulation of human monocarboxylate transporters, MCT, by shedding of the extracellular domain of an ancillary protein, basigin. Loss of the domain selectively increases export of lactate from lung cancer cells by a factor of four, contributing to the Warburg effect and malignancy. Further, intrinsic properties of monocarboxylate transporters involving asymmetric affinities of substrate binding, or biased open probabilities were shown to generate preference for one transport direction. Here, we discuss molecular mechanisms and physiological contexts of asymmetric secondary active transmembrane transport. Focus is laid on experimentally established cases, and examples are given in which putative bias in transport directionality may have been overlooked. Full article

Group A rotaviruses (RVAs) remain the leading cause of acute gastroenteritis (AGE) in young children in low- and middle-income countries. In Brazil, the oral attenuated RVA vaccine (Rotarix^®), monovalent genotype G1P[8], is distributed by the national immunization program and has drastically reduced morbidity and mortality associated with RVA etiology. In this study, Rotarix^® G1P[8] was detected using specific qRT-PCR from the fecal shedding of children living in the Amazon region, and 18.3% (29/158) were positive and 75.8% (22/29) presented with AGE. The VP4 (VP8*) gene of these sheddings, submitted to Sanger nucleotide sequencing, showed an occurrence of mutations, including the silent mutation at 144C > G (one child) and the following missense mutations— 499T > C (F167L) (two children), 644G > C (C215S) (one child), and 787G > A (E263K) (one child). These mutations had no impact on the protein model structure in silico deduced from the VP4 (VP8*) mutants. The in silico protein model deduced from the VP4 (VP8*) nucleotide sequences, bound to type 1H sugar antigens (H1) and its precursor Lac-para-N-biose (LNB), had a stronger binding to the G1P[8] genotype, when compared to G3P[8]. Rotarix^® shedding was higher in HBGA secretors than in non-secretors (79.3%; 23/29). A total of 11.4% (18/158) of children with Rotarix^® G1P[8] shedding were unvaccinated, indicating the occurrence of indirect protection. Stability evidence of Rotarix^® VP4 (VP8*) spike protein from samples collected in vivo is presented. Full article

The lacquer tree (Toxicodendron vernicifluum) possesses significant economic value due to its capability to produce raw lacquer, lacquer wax, and lacquer oil. The fruit is the primary source of lacquer wax; the primary components of lacquer wax are fatty acids, yet the synthesis mechanisms of fatty acids and wax esters remain unclear. In this study, we employed RNA-seq to analyze differentially expressed genes (DEGs) across four developmental stages in the fruit of the lacquer tree. The results revealed that, compared to the T1 stage, there were 1736, 10,228, and 12,444 DEGs in the three developmental stages. Through KEGG enrichment analysis, DEGs associated with lacquer wax synthesis were found to be primarily enriched in fatty acid metabolism, degradation, and the biosynthesis of cutin, suberin, and wax esters pathways. Furthermore, analysis of DEGs expression patterns in fatty acid synthesis pathways revealed that ACC, KAS, KAR, FATB, and FAD were significantly differentially expressed. Additionally, LACS, WSD1, CER4, CER1, and MAH1 participated in wax biosynthesis. Moreover, one co-expression network among wax biosynthesis genes, hormone signal transduction genes, and transcription factors was established. These findings provide a theoretical foundation for identifying key genes involved in regulating fatty acid and lacquer wax synthesis in Toxicodendron vernicifluum. Full article

Since there is currently no cure for Parkinson’s disease, pharmacobiotic approaches based on gut microbiota—capable of producing pharmacologically active compounds—are under development. In this study, we propose LfU21, derived from the strain Limosilactobacillus fermentum U-21, as a candidate pharmacobiotic. To evaluate its efficacy, a combined LPS- and lactacystin (LAC)-induced Parkinson’s disease model was established in Wistar rats. Effects were assessed using behavioral, biochemical, immunomodulatory, and transcriptomic biomarkers. LfU21 administration reduced α-synuclein levels, altered motor performance in the “Rung ladder” test, and modulated bdnf gene expression in the right and left striata. Under LPS exposure, LfU21 prevented alterations in immune response markers, GSH levels, drd2 and bdnf gene expression, and intestinal goblet cell counts. In LAC and LAC + LPS groups, LfU21 mitigated the rise in α-synuclein, the decline in bdnf expression, and behavioral deficits in the “Open Field” and “Rung ladder” tests, respectively. The multifunctional activity of LfU21 in a combined Parkinson’s disease model underscores its therapeutic potential and helps identify a target patient cohort for future clinical trials. Full article

Objective: To provide a narrative overview of the scientific knowledge on Last Aid Courses and experiences from different countries. Background: The levels of death literacy, grief literacy, and knowledge about palliative care are low in many countries around the world. For many people, dying, death, and grief are still a taboo. Public Palliative Care Education (PPCE), the public knowledge approach, and the Last Aid Course (LAC) aim to increase death literacy, grief literacy, and public knowledge about palliative care. Methods: A literature search in the databases PubMed/Medline, CINAHL, and PsycInfo was undertaken. Other additional sources were found by hand searching, books, reference lists, and the internet. A narrative overview of the existing literature on LAC and Public Palliative Care Education (PPCE) is provided. Experiences with PPCE and LAC from different countries are presented. Based on the findings, a future agenda for research on PPCE and LAC is presented. Results and Discussion: PPCE and LAC have been introduced in 23 countries. A total of 17 articles and reviews on Last Aid were included. Research on the effects of LAC in different countries and cultural issues connected to LAC are ongoing. Conclusions: Since 2015, LACs have been introduced in 23 different countries. The LAC, the LAC-KT, and PPCE may enhance the public debate on dying, death, grief, and palliative care and may empower people to contribute to end-of-life care in the community. Future research on PPCE, the LAC, and the LAC-KT should focus on retention over time and the long-term effects of the courses. Full article

Background: Serum lactate is a key biomarker of tissue hypoperfusion and metabolic stress in sepsis. Although lactate clearance is widely recognized, many intensive care units record only a peak lactate within 24 h (pLac-24h). The prognostic value of pLac-24h among patients receiving blood purification therapy remains unclear in Asian intensive care settings. Methods: We retrospectively analyzed the 2018–2020 ICU dataset from MacKay Memorial Hospital, Taiwan. Among 16,693 adult ICU admissions, 2506 patients received continuous renal replacement therapy (CRRT) as blood purification for severe sepsis or septic shock. Of these, 1264 (50.4%) had available pLac-24h data, and 27 (1.1%) also required extracorporeal membrane oxygenation (ECMO). The primary outcome was 28-day all-cause mortality. Multivariate logistic regression adjusted for age, sex, APACHE II score, infection source, and CRRT/ECMO use. Discrimination was evaluated by receiver operating characteristic (ROC) curves and decision-curve analysis. This analysis was conducted as a predefined sub-analysis of an institutional ICU database. Results: The mean age of the cohort was 65.7 ± 13.4 years, and 64.8% were male. Median pLac-24h was 5.1 mmol/L (IQR 3.2–8.6). The overall 28-day mortality among CRRT patients was 47.3%. Mortality rose progressively across pLac-24h quartiles (Q1–Q4: 28.9%, 39.4%, 54.7%, and 68.1%; p < 0.001). Each 1 mmol/L increase in pLac-24h independently predicted higher mortality (adjusted OR 1.18, 95% CI 1.10–1.26, p < 0.001). The area under the ROC curve for pLac-24h predicting 28-day mortality was 0.78 (95% CI 0.74–0.82), outperforming the APACHE II score (AUC 0.69, p = 0.02). Conclusions: In critically ill patients with septic shock undergoing CRRT, peak lactate within 24 h was a strong, independent predictor of 28-day mortality. pLac-24h offers a pragmatic, readily available prognostic indicator when serial lactate measurements are unavailable, supporting its integration into bedside risk assessment in real-world Asian ICU practice. Full article

This study investigates the modulation effects of varying infill densities and phase angles on the radiation attenuation properties of three 3D-printed polymers: acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), and thermoplastic polyurethane (TPU). Using the EpiXS software for radiation attenuation calculations, the study assessed the linear attenuation coefficients (LACs) of the materials under different infill densities (30%, 50%, 70%, 90%, and 100%) and phase angles (0°, 30°, 45°, 60°, and 90°) for radiation in the 1–100 keV energy range, which corresponds to the X-ray spectrum. TPU demonstrated the highest attenuation values, with a baseline coefficient of 20.199 cm⁻¹ at 30% infill density, followed by PLA at 18.835 cm⁻¹, and ABS at 13.073 cm⁻¹. Statistical analysis via the Kruskal–Wallis test confirmed that infill density significantly impacts attenuation, while phase angle exhibited no significant effect, with p-values exceeding 0.05 across all materials. TPU showed the highest sensitivity to infill density, with a slope of 1.1194, compared to 0.7257 for ABS and 0.9251 for PLA, making TPU the most suitable candidate for radiation protection applications, particularly in applications where flexibility and high attenuation are required. The findings support the potential of 3D printing to produce customized, cost-effective radiation protection gear for medical and industrial applications. Future work can further optimize material designs by exploring more complex infill geometries and testing under broader radiation spectra. Full article

As a vital appearance quality trait of broccoli, curd-surface wax powder not only affects its commercial value but also plays a key role in plant resistance to abiotic stresses. However, its formation mechanism remains unclear. Using low-wax variety CK (‘QH18’) and high-wax variety T1 (‘QHMS4’) as materials, this study systematically elucidated the molecular mechanism of wax powder formation via physiological indexes, scanning electron microscopy (SEM), targeted metabolomics, and transcriptomics. Determination of fatty acid (FA) content in broccoli flower bud tissue showed a close association between FA content and wax deposition. SEM observation revealed that T1 had significantly denser wax crystals, mainly granular, than CK. Targeted metabolomics identified 25 fatty acids in the two varieties. And the linolenic and palmitic acids, with high content and significant differences, may be key metabolites regulating wax synthesis. Integrated transcriptomics and metabolomics indicated that BolfabG, BolLACS, BolKCS1, BolKCS2 and BolMAH1 genes are involved in wax biosynthesis. Moreover, AP2/ERF-ERF transcription factor (TF)-encoding genes (BolERF018, BolERF1F.1, BolERF1F.2 and BolERF1C) played the primary role in regulating wax biosynthesis, followed by NAC (BolNAC62.1), MYB (BolMYB44), and MADS-MIKC(BolPISTILLATA). These TFs may regulate BolfabG, BolLACS, BolKCS1, BolACOX2 and BolACAA1 to affect linolenic and palmitic acid balance, altering wax precursor synthesis and accumulation, and finally leading to differences in wax morphology and content. This study reveals a “Transcription Factors–Differentially Expressed Genes–Differentially Accumulated Metabolites–Fatty Acids” (TFs-DEGs-DAMs-FA) network, providing a basis for understanding broccoli wax formation. Full article