High expression of PD-L1 on conventional dendritic cells in tumour-draining lymph nodes is associated with poor prognosis in oral cancer.

INTRODUCTION: Oral squamous cell carcinoma (OSCC), while common and with a favorable prognosis in early stages, presents a marked reduction in survival rate upon metastasis to lymph nodes. Early detection of lymph node metastasis via biomarkers could enhance the therapeutic strategy for OSCC. Here, we explored dendritic cells (DCs) and cytotoxic T-cells in tumour-draining lymph nodes (TDLNs) as potential biomarkers. METHOD: Dendritic cells and cytotoxic T-cells in 33 lymph nodes were analyzed with multi-parameter flow cytometry in TDLNs, regional non-TDLNs surgically excised from 12 OSCC patients, and compared to 9 lymph nodes from patients with benign conditions. RESULTS: Our results displayed a higher proportion of conventional cDC1s with immunosuppressive features in TDLN. Further, high PD-L1 expression on cDC1 in TDLNs was associated with metastasis and/or recurrent disease risk. Also, elevated levels of memory CD8+ T-cells and terminally exhausted PD-1+TCF-1-CD8+ T-cells were observed in TDLNs and non-TDLNs compared to healthy lymph nodes. CONCLUSIONS: We conclude that TDLNs contain cells that could trigger an anti-tumor adaptive response, as evidenced by activated cDC1s and progenitor-like TCF-1+ T-cells. The detection of high PDL1 expression on cDC1s was indicative of TDLN metastasis and an adverse prognosis, proposing that PD-L1 on dendritic cells in TDLN could serve as a predictive biomarker of OSCC patients with a worse prognosis.

Functional and Effective Connectivity Underlying Semantic Verbal Fluency.

Semantic verbal fluency (SVF) impairment is present in several neurological disorders. Although activation in SVF-related areas has been reported, how these regions are connected and their functional roles in the network remain divergent. We assessed SVF static and dynamic functional connectivity (FC) and effective connectivity in healthy participants using functional magnetic resonance imaging. We observed activation in the inferior frontal (IFG), middle temporal (pMTG) and angular gyri (AG), anterior cingulate (AC), insular cortex, and regions of the superior, middle, and medial frontal gyri (SFG, MFG, MidFG). Our static FC analysis showed a highly interconnected task and resting state network. Increased connectivity of AC with the pMTG and AG was observed for the task. The dynamic FC analysis provided circuits with connections similarly modulated across time and regions related to category identification, language comprehension, word selection and recovery, word generation, inhibition of speaking, speech planning, and articulatory planning of orofacial movements. Finally, the effective connectivity analysis provided a network that best explained our data, starting at the AG and going to the pMTG, from which there was a division between the ventral and dorsal streams. The SFG and MFG regions were connected and modulated by the MidFG, while the inferior regions formed the ventral stream. Therefore, we successfully assessed the SVF network, exploring regions associated with the entire processing, from category identification to word generation. The methodological approach can be helpful for further investigation of the SVF network in neurological disorders.

Payment perception in the emergency department: The mediating role of perceived quality of healthcare and patient satisfaction.

The aim of this research is to identify the main factors associated with patients' payment perception and the effects of these factors on payment perception. Patients admitted between January and December 2016 at an emergency department of a public hospital in Lisbon, Portugal, were included in this study, with a representative sample size of 382 patients. A 5% margin of error and a 95% confidence interval were used, and all the data were collected between May and November 2017. To test the mediation models, stepwise multiple linear regression analysis was used. The effect of doctors on payment perception through satisfaction and through perceived quality of healthcare (PQHC) is explained by 3% and 4% of the variation, respectively, with statistically significant results (P < .01). Moreover, the effect of privacy and meeting expectations on payment perception through PQHC is explained by 4% and 4% of the variation, with statistically significant results (P < .01). Doctors play a crucial role in understanding the patients' payment perception (with direct and indirect effects). Mediators, in turn, strengthen this effect, in which the contribution of PQHC is more significant than that of satisfaction.

Coastal natural products: a review applied to antimycobacterial activity.

Despite the many advances in drug research, natural products are still being explored as a promising source for discovering new bioactive compounds to treat global diseases such as tuberculosis. However, there is a lack of studies and information about coastal natural products, which thrive in the transitional environment between two different ecosystems and produce unique secondary metabolites. Mangroves, estuaries, and mudflats make up areas for coastal species and have shown promising results in antituberculosis research, some of them are present in hotspot areas. This review focuses on research conducted in coastal environments and explores the reasons why these natural products tend to outperform non-coastal ones against the causative agent of tuberculosis, Mycobacterium tuberculosis.

Lippia alba essential oil: A powerful and valuable antinociceptive and anti-inflammatory medicinal plant from Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases. AIM OF THE STUDY: to evaluate the chemical composition, antinociceptive, and anti-inflammatory activities of Lippia alba essential oil and its major compound geraniol. MATERIAL AND METHODS: Lippia alba leaves were collected in Pará state, Brazil. The leaf essential oil was obtained using a modified Clevenger-type extractor. Then, the oil was analyzed by GC and GC-MS analyses. To evaluate the toxicity of LaEO and geraniol, the doses of 50, 300, and 2000 mg/kg were used in a mouse model. For antinociception tests, abdominal contortion, hot plate, and formalin tests were used; all groups were treated with LaEO and geraniol at doses of 25, 50, and 100 mg/kg; and to evaluate inflammation using the ear edema model. RESULTS: The constituents identified in the highest content were oxygenated monoterpenes: geraniol (37.5%), geranial (6.7%) and neral (3.8%). The animals treated with LaEO and geraniol demonstrated atypical behaviors with aspects of lethargy and drowsiness, characteristics of animals in a state of sedation; the relative weights showed no significant difference compared to the controls. In the abdominal contortion test, LaEO at 25 mg/kg, 50 mg/kg doses, and 100 mg/kg reduced the number of contortions, representing a percentage reduction of 84.64%, 81.23%, and 66.21% respectively. In the hot plate test, LaEO and geraniol increased the latency time at doses of 25, 50, and 100 mg/kg in all test periods; there was no statistical difference between LaEO and geraniol. In the first phase of the formalin test, only doses of 25 mg/kg and 100 mg/kg of LaEO showed significant activity, reducing the latency time by 53.40% and 58.90%. LaEO at doses of 25 mg/kg and 100 mg/kg reduced the size of the edema, demonstrating an anti-inflammatory activity of 59.38% (25 mg/kg) and 50% (100 mg/kg). CONCLUSION: Lippia alba essential oil and geraniol showed central/peripheral analgesic and anti-inflammatory potential and can be used as an alternative or complementary treatment to conventional drugs. More studies are needed to evaluate its action mechanisms and its analgesic effects.

Scissor-assisted vs. conventional endoscopic submucosal dissection for colorectal lesions: Systematic review and meta-analysis.

OBJECTIVES: Colorectal endoscopic submucosal dissection (ESD) is a technically complex procedure. The scissor knife mechanism may potentially provide easier and safer colorectal ESD. The aim of this meta-analysis is to evaluate the efficacy and safety of scissor-assisted vs. conventional ESD for colorectal lesions. METHODS: A search strategy was conducted in MEDLINE, Embase, and Lilacs databases from January 1990 to November 2023 according to PRISMA guidelines. Fixed and random-effects models were used for statistical analysis. Heterogeneity was assessed using I2 test. Risk of bias was assessed using the ROBINS-I and RoB-2 tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: A total of five studies (three retrospective and two randomized controlled trials, including a total of 1575 colorectal ESD) were selected. The intraoperative perforation rate was statistically lower (risk difference [RD] -0.02; 95% confidence interval [CI] -0.04 to -0.01; P = 0.001; I2 = 0%) and the self-completion rate was statistically higher (RD 0.14; 95% CI 0.06, 0.23; P = 0.0006; I2 = 0%) in the scissor-assisted group compared with the conventional ESD group. There was no statistical difference in R0 resection rate, en bloc resection rate, mean procedure time, or delayed bleeding rate between the groups. CONCLUSION: Scissor knife-assisted ESD is as effective as conventional knife-assisted ESD for colorectal lesions with lower intraoperative perforation rate and a higher self-completion rate.

Yttrium immobilization through biomineralization with phosphate by the resistant strain Mesorhizobium qingshengii J19.

AIMS: Yttrium (Y) holds significant industrial and economic importance, being listed as a critical element on the European list of critical elements, thus emphasizing the high priority for its recovery. Bacterial strategies play a crucial role in the biorecovery of metals, offering a promising and environmentally friendly approach. Therefore, gaining a comprehensive understanding of the underlying mechanisms behind bacterial resistance, as well as the processes of bioaccumulation and biotransformation, is of paramount importance. METHODS AND RESULTS: A total of 207 Alphaproteobacteria strains from the University of Coimbra Bacteria Culture Collection were tested for Y-resistance. Among these, strain Mesorhizobium qingshengii J19 exhibited high resistance (up to 4 mM Y) and remarkable Y accumulation capacity, particularly in the cell membrane. Electron microscopy revealed Y-phosphate interactions, while X-ray diffraction identified Y(PO3)3·9H2O biocrystals produced by J19 cells. CONCLUSION: This study elucidates Y immobilization through biomineralization within phosphate biocrystals using M. qingshengii J19 cells.

Detection of Mtb and NTM: preclinical validation of a new asymmetric PCR-binary deoxyribozyme sensor assay.

Tuberculosis (TB) and infectious diseases caused by non-tuberculous mycobacteria (NTM) are global concerns. The development of a rapid and accurate diagnostic method, capable of detecting and identifying different mycobacteria species, is crucial. We propose a molecular approach, the BiDz-TB/NTM, based on the use of binary deoxyribozyme (BiDz) sensors for the detection of Mycobacterium tuberculosis (Mtb) and NTM of clinical interest. A panel of DNA samples was used to evaluate Mtb-BiDz, Mycobacterium abscessus/Mycobacterium chelonae-BiDz, Mycobacterium avium-BiDz, Mycobacterium intracellulare/Mycobacterium chimaera-BiDz, and Mycobacterium kansasii-BiDz sensors in terms of specificity, sensitivity, accuracy, and limit of detection. The BiDz sensors were designed to hybridize specifically with the genetic signatures of the target species. To obtain the BiDz sensor targets, amplification of a fragment containing the hypervariable region 2 of the 16S rRNA was performed, under asymmetric PCR conditions using the reverse primer designed based on linear-after-the-exponential principles. The BiDz-TB/NTM was able to correctly identify 99.6% of the samples, with 100% sensitivity and 0.99 accuracy. The individual values of specificity, sensitivity, and accuracy, obtained for each BiDz sensor, satisfied the recommendations for new diagnostic methods, with sensitivity of 100%, specificity and accuracy ranging from 98% to 100% and from 0.98 to 1.0, respectively. The limit of detection of BiDz sensors ranged from 12 genome copies (Mtb-BiDz) to 2,110 genome copies (Mkan-BiDz). The BiDz-TB/NTM platform would be able to generate results rapidly, allowing the implementation of the appropriate therapeutic regimen and, consequently, the reduction of morbidity and mortality of patients.IMPORTANCEThis article describes the development and evaluation of a new molecular platform for accurate, sensitive, and specific detection and identification of Mycobacterium tuberculosis and other mycobacteria of clinical importance. Based on BiDz sensor technology, this assay prototype is amenable to implementation at the point of care. Our data demonstrate the feasibility of combining the species specificity of BiDz sensors with the sensitivity afforded by asymmetric PCR amplification of target sequences. Preclinical validation of this assay on a large panel of clinical samples supports the further development of this diagnostic tool for the molecular detection of pathogenic mycobacteria.

Binding Evolution of the Dengue Virus Envelope Against DC-SIGN: A Combined Approach of Phylogenetics and Molecular Dynamics Analyses Over 30 Years of Dengue Virus in Brazil.

The Red Queen Hypothesis (RQH), derived from Lewis Carroll's "Through the Looking-Glass", postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host-pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus-cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus-host systems and noted patterns of co-evolution. As viruses evolved receptor-binding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co-evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this ever-evolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time.

Neurocognition and brain functional connectivity in a non-clinical population-based sample with psychotic experiences.

We characterized the neurocognitive profile of communed-based individuals and unaffected siblings of patients with psychosis from Brazil reporting psychotic experiences (PEs). We also analyzed associations between PEs and the intra and inter-functional connectivity (FC) in the Default Mode Network (DMN), the Fronto-Parietal Network (FPN) and the Salience Network (SN) measured by functional magnetic resonance imaging. The combined sample of communed-based individuals and unaffected siblings of patients with psychosis comprised 417 (neurocognition) and 85 (FC) volunteers who were divided as having low (<75th percentile) and high (≥75th percentile) PEs (positive, negative, and depressive dimensions) assessed by the Community Assessment of Psychic Experiences. The neurocognitive profile and the estimated current brief intellectual quotient (IQ) were assessed using the digit symbol (processing speed), arithmetic (working memory), block design (visual learning) and information (verbal learning) subtests of Wechsler Adult Intelligence Scale-third edition. Logistic regression models were performed for neurocognitive analysis. For neuroimaging, we used the CONN toolbox to assess FC between the specified regions, and ROI-to-ROI analysis. In the combined sample, high PEs (all dimensions) were related to lower processing speed performance. High negative PEs were related to poor visual learning performance and lower IQ, while high depressive PEs were associated with poor working memory performance. Those with high negative PEs presented FPN hypoconnectivity between the right and left lateral prefrontal cortex. There were no associations between PEs and the DMN and SN FC. Brazilian individuals with high PEs showed neurocognitive impairments like those living in wealthier countries. Hypoconnectivity in the FPN in a community sample with high PEs is coherent with the hypothesis of functional dysconnectivity in schizophrenia.

Cellular energy regulates mRNA degradation in a codon-specific manner.

Codon optimality is a major determinant of mRNA translation and degradation rates. However, whether and through which mechanisms its effects are regulated remains poorly understood. Here we show that codon optimality associates with up to 2-fold change in mRNA stability variations between human tissues, and that its effect is attenuated in tissues with high energy metabolism and amplifies with age. Mathematical modeling and perturbation data through oxygen deprivation and ATP synthesis inhibition reveal that cellular energy variations non-uniformly alter the effect of codon usage. This new mode of codon effect regulation, independent of tRNA regulation, provides a fundamental mechanistic link between cellular energy metabolism and eukaryotic gene expression.

Agency in urgency and uncertainty. Vaccines and vaccination in European media discourses.

Although Covid-19 was not the first pandemic, it was unique in the scale and intensity with which societies responded. Countries reacted differently to the threat posed by the new virus. The public health crisis affected European societies in many ways. It also influenced the way the media portrayed vaccines and discussed factors related to vaccine hesitancy. Europeans differed in their risk perceptions, attitudes towards vaccines and vaccine uptake. In European countries, Covid-19-related discourses were at the centre of media attention for many months. This paper reports on a media analysis which revealed significant differences as well as some similarities in the media debates in different countries. The study focused on seven European countries and considered two dimensions of comparison: between the pre-Covid period and the beginning of the Covid pandemic period, and between countries. The rich methodological approach, including linguistics, semantic field analysis and discourse analysis of mainstream news media, allowed the authors to explore the set of meanings related to vaccination that might influence actors' agency. This approach led the authors to redefine vaccine hesitancy in terms of characteristics of the "society in the situation" rather than the psychological profile of individuals. We argue that vaccine hesitancy can be understood in terms of agency and temporality. This dilemma of choice that transforms the present into an irreversible past and must be taken in relation to an uncertain future, is particularly acute under the pressure of urgency and when someone's health is at stake. As such, it is linked to how vaccine meaning is co-produced within public discourses.

Designing, development and validation of an app to reduce the response time of the emergency medical services.

INTRODUCTION: Delays in prehospital care attributable to the call-taking process can often be traced back to miscommunication, including uncertainty around the call location. Geolocation applications have the potential to streamline the call-taking process by accurately identifying the caller's location. OBJECTIVE: To develop and validate an application to geolocate emergency calls and compare the response time of calls made via the application with those of conventional calls made to the Brazilian Medical Emergency System (Serviço de Atendimento Médico de Urgência-SAMU). METHODS: This study was conducted in two stages. First, a geolocating application for SAMU emergency calls (CHAMU192) was developed using a mixed methods approach based on design thinking and subsequently validated using the System Usability Scale (SUS). In the second stage, sending time of the geolocation information of the app was compared with the time taken to process information through conventional calls. For this, a hypothetical case control study was conducted with SAMU in the Maringá, Paraná, Brazil. A control group of 350 audio recordings of emergency calls from 2019 was compared to a set of test calls made through the CHAMU192 app. The CHAMU192 group consisted of 201 test calls in Maringá. In test calls, the location was obtained by GPS and sent to the SAMU communication system. Comparative analysis between groups was performed using the Mann-Whitney test. RESULTS: CHAMU192 had a SUS score of 90, corresponding to a "best imaginable" usability rating. The control group had a median response time of 35.67 seconds (26.00-48.12). The response time of the CHAMU192 group was 0.20 (0.15-0.24). CONCLUSION: The use of the CHAMU192 app by emergency medical services could significantly reduce response time. The results demonstrate the potential of app improving the quality and patient outcomes related to the prehospital emergency care services.

Physiological evaluation of yeast strains under anaerobic conditions using glucose, fructose, or sucrose as the carbon source.

The aim of this study was to evaluate the physiology of 13 yeast strains by assessing their kinetic parameters under anaerobic conditions. They included Saccharomyces cerevisiae CAT-1 and 12 isolated yeasts from different regions in Brazil. The study aimed to enhance understanding of the metabolism of these strains for more effective applications. Measurements included quantification of sugars, ethanol, glycerol, and organic acids. Various kinetic parameters were analyzed, such as specific substrate utilization rate (qS), maximum specific growth rate (µmax), doubling time, biomass yield, product yield, maximum cell concentration, ethanol productivity (PEth), biomass productivity, and CO2 concentration. S. cerevisiae CAT-1 exhibited the highest values in glucose for µmax (0.35 h-1), qS (3.06 h-1), and PEth (0.69 gEth L-1 h-1). Candida parapsilosis Recol 37 did not fully consume the substrate. In fructose, S. cerevisiae CAT-1 stood out with higher values for µmax (0.25 h-1), qS (2.24 h-1), and PEth (0.60 gEth L-1 h-1). Meyerozyma guilliermondii Recol 09 and C. parapsilosis Recol 37 had prolonged fermentation times and residual substrate. In sucrose, only S. cerevisiae CAT-1, S. cerevisiae BB9, and Pichia kudriavzevii Recol 39 consumed all the substrate, displaying higher PEth (0.72, 0.51, and 0.44 gEth L-1 h-1, respectively) compared to other carbon sources.

Identification of Peptides in Spider Venom Using Mass Spectrometry.

Spider venoms are composed of hundreds of proteins and peptides. Several of these venom toxins are cysteine-rich peptides in the mass range of 3-9 kDa. Small peptides (<3 kDa) can be fully characterized by mass spectrometry analysis, while proteins are generally identified by the bottom-up approach in which proteins are first digested with trypsin to generate shorter peptides for MS/MS characterization. In general, it is sufficient for protein identification to sequence two or more peptides, but for venom peptidomics it is desirable to completely elucidate peptide sequences and the number of disulfide bonds in the molecules. In this chapter, we describe a methodology to completely sequence and determine the number of disulfide bonds of spider venom peptides in the mass range of 3-9 kDa by multiple enzyme digestion, mass spectrometry of native and digested peptides, de novo analysis, and sequence overlap alignment.

Trust matters: The Addressing Vaccine Hesitancy in Europe Study.

This article presents the design of a seven-country study focusing on childhood vaccines, Addressing Vaccine Hesitancy in Europe (VAX-TRUST), developed during the COVID-19 pandemic. The study consists of (a) situation analysis of vaccine hesitancy (examination of individual, socio-demographic and macro-level factors of vaccine hesitancy and analysis of media coverage on vaccines and vaccination and (b) participant observation and in-depth interviews of healthcare professionals and vaccine-hesitant parents. These analyses were used to design interventions aimed at increasing awareness on the complexity of vaccine hesitancy among healthcare professionals involved in discussing childhood vaccines with parents. We present the selection of countries and regions, the conceptual basis of the study, details of the data collection and the process of designing and evaluating the interventions, as well as the potential impact of the study. Laying out our research design serves as an example of how to translate complex public health issues into social scientific study and methods.

Exploring the impact of seasonal variations on the chemical composition, antinociceptive, and anti-inflammatory properties of Pogostemon heyneanus Benth. essential oil.

Background: Pogostemon heyneanus leaves infusions are relevant in ethnopharmacology for treating colds, coughs, headaches, and asthma. Purpose: The essential oil chemical composition of a Pogostemon heyneanus specimen was monthly monitored from October 2021 to July 2022 to evaluate the climatic influences on its yield and chemical composition and antinociceptive, andanti-inflammatory properties. Methods: The leaves, collected monthly over a 10-month period, were submitted to hydrodistillation. The oils obtained were analyzed by gas chromatography coupled to a mass spectrometer and gas chromatography coupled to flame ionization detector. The P. heyneanus essential oil (PhEO) was tested in vivo to evaluate its peripheral analgesic actions through the abdominal writhing test induced by acetic acid, and peripheral analgesia by tail immersion. Neurogenic and inflammatory pain were evaluated by formalin test, and acute oral toxicity of the oil was also verified. Results: PhEO presented 27 chemical constituents with the highest predominance of patchoulol (43.6%-76.9%), α-bulnesene (0.2%-12.7%), α-guaiene (0.4%-8.9%), seychellene (3.8%-5.1%) and pogostol (0.0%-8.2%). The climatic parameters insolation, humidity, rainfall, and temperature did not influence the essential oil yield or the main chemical constituents, except for pogostol, which presented a strong (r = 0.73) and statistically significant (p < 0.05) correlation with temperature. PhEO did not display toxicity at the maximum 300 mg/kg dosage. The oil showed low peripheral and central analgesic action at 100 mg/kg, while in the neurogenic and inflammatory pain inhibition tests, no actions related to PhEO were observed. In the carrageenan-induced peritonitis test, PhEO did not reduce the migration of leukocytes to the peritoneal cavity compared to the control group. Conclusion: Pogostemon heyneanus is a resistant plant to seasonal influences and a source of patchoulol. Despite ethnopharmacological indications, no in-vivo biological activities such as neurogenic or inflammatory pain were identified in the present work. So, the low influence of the climatic parameters on chemical composition can infer that the low pharmacological activity is also not subject to climatic variations, that is, it does not change due to the climate.

Novel Aphid-Repellent Fiber Mats Based on Poly(lactic acid)-Containing Ionic Liquids.

To protect crops as well as human and animal health, the development of novel repellents based on biopolymers is critical for a growing world population. Here, novel aphid-repellent electrospun mats containing epoxidized ionic liquids (ILs) covalently bonded to the carboxyl or hydroxyl groups of poly(lactic acid) (PLA) were designed to produce nonwoven mats. First, di-, tri-, and tetra-epoxidized imidazolium ILs were synthesized and incorporated in different weight fractions (3, 5, and 10 wt %) into the PLA solution. Then, the effect of ILs' microstructure, thermal properties, mechanical performance, and hydrophobic behavior were investigated. It was found that the incorporation of ILs resulted in a reduction of the fiber diameters while the mechanical properties of the mats, i.e., the three-dimensional fibrous porous structure, were maintained. Finally, the effect of these three ILs against the pea aphid Acyrthosiphon pisum (Harris) was evaluated for the first time, showing an attractive effect for the diepoxidized IL and a repellent effect for the tri- and tetra-epoxidized ILs. By exploiting the chemical nature of ILs, an environmentally friendly strategy can be developed to limit the need for chemical pesticides and petroleum-based polymers.

Impaired biogenesis of basic proteins impacts multiple hallmarks of the aging brain.

Aging and neurodegeneration entail diverse cellular and molecular hallmarks. Here, we studied the effects of aging on the transcriptome, translatome, and multiple layers of the proteome in the brain of a short-lived killifish. We reveal that aging causes widespread reduction of proteins enriched in basic amino acids that is independent of mRNA regulation, and it is not due to impaired proteasome activity. Instead, we identify a cascade of events where aberrant translation pausing leads to reduced ribosome availability resulting in proteome remodeling independently of transcriptional regulation. Our research uncovers a vulnerable point in the aging brain's biology - the biogenesis of basic DNA/RNA binding proteins. This vulnerability may represent a unifying principle that connects various aging hallmarks, encompassing genome integrity and the biosynthesis of macromolecules.

2,3,5-triphenyl tetrazolium chloride as colorimetric indicator for drug susceptibility testing against nontuberculous mycobacteria.

This study aimed to propose and evaluate a drug susceptibility testing (DST) using the 2,3,5-triphenyl tetrazolium chloride (TTC) as a colorimetric indicator against Mycobacterium abscessus complex (MABC), M. avium complex (MAC), and M. kansasii strains, main nontuberculous mycobacteria (NTM) of clinical relevance. Our results demonstrated that the assay using TTC and the broth microdilution method recommended by the Clinical and Laboratory Standards Institute had essential agreement above 91%, 92%, and 100%, for drugs tested against MABC, MAC, and M. kansasii strains, respectively. Categorical agreement above 91% was obtained for most drugs tested against MABC, except to cefoxitin (76.5%). For drugs tested against MAC and M. kansasii, categorical agreement above 92% and 100% was observed, respectively. TTC showed to be a promising colorimetric indicator of growth to be used in DST for NTM, allowing an easier reading of results.