Search

Abstract Lipid nanoparticles (LNPs) have emerged as promising platforms for efficient in vivo mRNA delivery owing to advancements in ionizable lipids. However, maintaining the thermostability of mRNA/LNP systems remains challenging. While the importance of only a small amount of lipid impurities on mRNA inactivation is clear, a fundamental solution has not yet been proposed. In this study, we investigate an approach to limit the generation of aldehyde impurities that react with mRNA nucleosides through the chemical engineering of lipids. We demonstrated that piperidine-based lipids improve the long-term storage stability of mRNA/LNPs at refrigeration temperature as a liquid formulation. High-performance liquid chromatography analysis and additional lipid synthesis revealed that amine moieties of ionizable lipids play a vital role in limiting reactive aldehyde generation, mRNA–lipid adduct formation, and loss of mRNA function during mRNA/LNP storage. These findings highlight the importance of lipid design and help enhance the shelf-life of mRNA/LNP systems.

This study evaluates the potential deleterious impact of untreated waste water discharged into an unlined pit by the Nigerian National Petroleum Company (NNPC) on the groundwater quality of Umuakpara community in Osisioma, Abia state. Its overarching objective is to assess potential contaminant sources, distribution in groundwater using diverse techniques. Water samples collected from 14 domestic wells in two contrasting seasons (Rainy and Dry) were analyzed for Polynuclear Aromatic Hydrocarbons (PAHs) using Gas chromatography (GC). Vertical Electric Sounding (VES) technique was employed to determine the depth to water table and soil lithological layers required for good understanding of contaminants behavior along groundwater flow path. Pearson product moment correlation coefficient (r) and One-way ANOVA were used to define the interactions of detected PAHs and spatial variation in means of the PAHs components (p

Objectives: Evaluating the adherence to HIV Pre-Exposure Prophylaxis (PrEP) is essential for increasing its utilization and decreasing the risk of HIV transmission among Davao City's vulnerable groups. Methods: The research method utilized in the study is a quantitative, retrospective, descriptive research design. This method was employed to retrospectively review the de-identified data, which involved the fill and refill dates of PrEP and tablets supplied, to calculate the Proportion of Days Covered (PDC) among individuals in Davao City from January 2021 to December 2023. The study also included some demographic characteristics such as age and gender. Results: From 178 data entries collected, the age group of 25 to 34 years old was found to have the highest HIV PrEP use (52.3%), followed by those between 18 to 24 (30.9%), 35 to 44 (13.5%), and 45 years old and older (3.4%). Out of 178, only 2 clients were female. Furthermore, 73.6% of the 178 entries in the pharmacy records were identified to be taking PrEP daily. Descriptive statistics showed that the frequency of adherent clients across the years were 36.4%, 44.7% and 38.5%, respectively. Furthermore, the average PDC through the years was found to be 70.13%, 80.48%, and 72.8%. Age did not significantly affect adherence to PrEP during the years investigated (p-values > 0.05). Conclusion: Adherence to PrEP improved consistently in 2022 but declined in 2023, showing erratic adherence rates. Furthermore, adherence to HIV PrEP in Davao City was found to be suboptimal and while there are clients who are adherent, many are not. The results emphasize the need for targeted interventions and suggest that other socio-behavioral factors may play a role in this. To improve adherence and prevent HIV contractions, both short-term actions like public education campaigns about HIV PrEP and long-term plans like incorporating PrEP into the community pharmacies can be contributive.

Résumé : Œuvre de Trifonia Melibea Obono, La bastarda (2016) est essentiellement une traduction en espagnol de données sociologiques et anthropologiques fàŋ vers l'espagnol de Guinée-Équatoriale. En 2020, ce roman a été traduit de l'espagnol au français par Anne-Laure Bonvalot, ce qui contribue à accroître sa visibilité car elle permet aux multiples lecteurs de pénétrer cet univers socioculturel subsaharien. Cette étude n'est pas une critique de la traduction de l'œuvre dans son ensemble, mais celle des titres en espagnol La bastarda et français La bâtarde. L’étude consiste donc en un essai titrologique contrastif dans le domaine de l'ethnotraductologie qui convoque convoque l’horizon d’attente de la théorie de la réception. Il nous intéresse de savoir si, à travers ces deux titres, la société du roman est caractéristique de la société de référence ou si les deux auteurs naviguent à contre-courant de la pensée fàŋ. Mots-clés : Traduction – Culture – Titrologie - La bastarda - Guinée équatoriale.

Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case–control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at −80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher (p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher (p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes’ degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP.

This scientific article aims to identify the most optimal healthcare financing model suitable for a country's unique healthcare context while focusing on overcoming the fragmented and costly way in which healthcare is traditionally delivered. The tasks set for this research include evaluating and benchmarking different countries and environments to identify the most efficient model, reducing transaction costs, and analysing the agents and their motivations and decision situations using agent theory and game theory. To achieve the goal and tasks, the author conducted a comprehensive study based on the transaction cost theory, which explains how inefficient contracts can lead to an inefficient healthcare system. Additionally, the author used agent theory to understand the motivations of various stakeholders involved in healthcare financing and game theory to analyse decision-making processes leading to socially and individually beneficial outcomes. The empirical segment of the research utilised data from the OECD annual healthcare database for 2016-2019. A range of analytical tools, including descriptive analysis, data visualization, correlation analysis, and hypothesis testing were employed to examine the dataset for this study. The analysis results revealed four healthcare financial models with various indicators with different levels of influence. This research provides valuable insights for senior healthcare managers and policymakers to make informed decisions and lead their organisations toward more efficient and effective healthcare financing models. In conclusion, this study fills the research gap and addresses the central research question by comprehensively analysing healthcare financing models. The results emphasize the importance of reducing transaction costs and understanding the motivations of different stakeholders for achieving more efficient and effective healthcare outcomes. Countries can move towards a more integrated and cost-effective healthcare system by implementing the most efficient model identified in this study

Stomatal pores close rapidly in response to low-air-humidity-induced leaf-to-air vapor pressure difference (VPD) increases, thereby reducing excessive water loss. The hydroactive signal-transduction mechanisms mediating high VPD-induced stomatal closure remain largely unknown. The kinetics of stomatal high-VPD responses were investigated by using time-resolved gas-exchange analyses of higher-order mutants in guard-cell signal-transduction branches. We show that the slow-type anion channel SLAC1 plays a relatively more substantial role than the rapid-type anion channel ALMT12/QUAC1 in stomatal VPD signaling. VPD-induced stomatal closure is not affected in mpk12/mpk4GC double mutants that completely disrupt stomatal CO2 signaling, indicating that VPD signaling is independent of the early CO2 signal-transduction pathway. Calcium imaging shows that osmotic stress causes cytoplasmic Ca2+ transients in guard cells. Nevertheless, osca1-2/1.3/2.2/2.3/3.1 Ca2+-permeable channel quintuple, osca1.3/1.7-channel double, cngc5/6-channel double, cngc20-channel single, cngc19/20crispr-channel double, glr3.2/3.3-channel double, cpk-kinase quintuple, cbl1/4/5/8/9 quintuple, and cbl2/3rf double mutants showed wild-type-like stomatal VPD responses. A B3-family Raf-like mitogen-activated protein (MAP)-kinase kinase kinase, M3Kδ5/RAF6, activates the OST1/SnRK2.6 kinase in plant cells. Interestingly, B3 Raf-kinase m3kδ5 and m3kδ1/δ5/δ6/δ7 (raf3/6/5/4) quadruple mutants, but not a 14-gene raf-kinase mutant including osmotic stress-linked B4-family Raf-kinases, exhibited slowed high-VPD responses, suggesting that B3-family Raf-kinases play an important role in stomatal VPD signaling. Moreover, high VPD-induced stomatal closure was impaired in receptor-like pseudokinase GUARD CELL HYDROGEN PEROXIDE-RESISTANT1 (GHR1) mutant alleles. Notably, the classical transient "wrong-way" VPD response was absent in ghr1 mutant alleles. These findings reveal genes and signaling mechanisms in the elusive high VPD-induced stomatal closing response pathway.

Chemokine G-protein coupled receptors are validated drug targets for many diseases, including cancer, neurological, and inflammatory disorders. Despite much time and effort spent on therapeutic development, very few chemokine receptor antagonists are approved for clinical use. Among potential reasons for the slow progress in developing chemokine receptor inhibitors, antagonist tolerance, a progressive reduction in drug efficacy after repeated administration, is likely to play a key role. The mechanisms leading to antagonist tolerance remain poorly understood. In many cases, antagonist tolerance is accompanied by increased receptor concentration on the cell surface after prolonged exposure to chemokine receptor antagonists. This points to a possible role of altered receptor internalization and presentation on the cell surface, as has been shown for agonist (primarily opioid) tolerance. In addition, examples of antagonist tolerance in the context of other G-protein coupled receptors suggest the involvement of noncanonical signal transduction in opposing the effects of the antagonists. In this review, we summarize the available progress and challenges in therapeutic development of chemokine receptor antagonists, describe the available knowledge about antagonist tolerance, and propose new avenues for future investigation of this important phenomenon. Furthermore, we highlight the modern methodologies that have the potential to reveal novel mechanisms leading to antagonist tolerance and to propel the field forward by advancing the development of potent “tolerance-free” antagonists of chemokine receptors.

Abstract Background Direct-access physiotherapy practice has led to a global review of the use of differential-diagnostic modalities such as musculoskeletal imaging (MI) in physiotherapy. Objective To explore the MI authority, levels of training, attitude, utilisation, and competence among clinical physiotherapists in Nigeria. Methods This national cross-sectional study analysed a voluntary response sample of 400 Nigerian physiotherapists that completed the online version of the Physiotherapist’s Musculoskeletal Imaging Profiling Questionnaire (PMIPQ), using descriptive statistics, Spearman’s correlation, Mann-Whitney U, Kruskal-Wallis, and Friedman’s ANOVA tests. Results Of the 400 participants, 93.2% believed that physiotherapists should use MI in clinical practice. However, only 79.8% reported having MI authority in their practice settings. The participants’ median (interquartile range) levels of training =10 (24) and competence =16 (24) were moderate. Nonetheless, levels of training (χ2 [15] = 1285.899, p = 0.001), and competence (χ2 [15] = 1310.769, p

El presente trabajo tenemos por objetivo el análisis de los memes de la política chaqueña. Para el abordaje del tema estudiaremos aquellos memes que circulen a través de distintas redes sociales y que hayan aparecido entre 2019 y 2020. Nuestro propósito es contribuir al conocimiento de los modos de producción de sentido en los medios de comunicación en la provincia del Chaco.La palabra meme fue acuñada por el biólogo Richard Dawkins (1993) para definir a aquellos transmisores de información cultural (paralelos a los genes que transmiten información genética). Nosotros consideramos a los memes como un discurso social (Verón, 1993), cuya forma de comunicación es inmediata y, usualmente, anónima; y que cuenta, además, con una combinación de materiales verbales, escritos y orales, e imágenes, entre otros lenguajes, que demuestran la heterogeneidad que los caracteriza. Los memes circulan por las redes sociales y pueden abarcar distintas temáticas, entre ellas, la política, es por esto que actualmente podemos encontrar varios actores de la política chaqueña siendo protagonistas de estos discursos. Para su estudio nos valdremos del Análisis del discurso, en tanto metodología interdisciplinar (Arnoux, 2009); asimismo, observaremos la evolución de los medios de masas hasta la actualidad en que se encuentra los nuevos medios (Carlón, 2018), lugar por donde circulan los memes y, también, describiremos las características que estos discursos poseen. Luego analizaremos brevemente tres memes, uno surgido en el 2019 previo a las elecciones, y dos publicados durante la cuarentena del 2020.

Environmental conditions and photoperiod length drive the seasonal variability of gas exchange in plants. Still, little is known about trees' adaptation to climate change, expressed as a delay in decreasing photosynthetic capacity at the end of the growing season. We investigated the effect of elevated air humidity (RH) and sampling period (from July to September) on the variability of net photosynthesis ([A.sub.n]), dark respiration (R), daytime ([g.sub.l_day]) and night-time ([g.sub.l_night]) leaf conductance, an index of leaf chlorophyll content (SPAD), and [A.sub.n]:SPAD ratio in cut shoots of silver birch (Betula pendula Roth). Measurements of cut shoots were conducted in a climate chamber to eliminate the direct effect of field conditions. The [A.sub.n], [A.sub.n]:SPAD ratio, and [g.sub.l_day] were higher in the humidification treatment (H) than in the control (C) (P < 0.05) in autumn. The R was higher in the control than in the humidification treatment across the study period. The [g.sub.l_night] increased considerably in September in both treatments (P < 0.05) and was significantly correlated with R. Our findings suggest that autumnal leaf conductance and gas exchange in silver birch are considerably influenced by long-term exposure to elevated RH and are probably related to a complex of leaf senescence processes, including nitrogen retranslocation. Key words: abscisic acid, global climate change, leaf senescence, night-time, photoperiod. Les conditions environnementales et la duree de la photoperiode influencent la variabilite saisonniere de l'echange gazeux des plantes. Nous en savons toutefois tres peu sur l'adaptation des arbres aux changements climatiques exprimee comme un retard dans la diminution de la capacite photosynthetique a la fin de la saison de croissance. Nous avons examine l'effet de l'humidite elevee de l'air (RH) et la periode d'echantillonnage (de juillet a septembre) sur la variabilite de la photosynthese nette ([A.sub.n]), la respiration nocturne (R), la conductance des feuilles le jour ([g.sub.l_day]) et la nuit ([g.sub.l_night]) et l'indice du contenu de chlorophylle dans les feuilles (SPAD) ainsi que le taux de l'[A.sub.n]:SPAD dans les tiges coupees du bouleau verruqueux (Betula pendula Roth). Les mesures des tiges coupees ont ete effectuees dans une chambre climatique afin d'eliminer l'effet direct des conditions du terrain. L'[A.sub.n], le taux de l'[A.sub.n]:SPAD et le [g.sub.l_day] etaient plus eleves dans l'humidification (H) que dans le traitement (P < 0,05) de controle (C) en automne. La R etait plus elevee dans le controle que dans le traitement d'humidification tout au long de la periode de l'etude. Le [g.sub.l_night] a augmente considerablement en septembre dans les deux traitements (P < 0,05) et etait largement correle avec notre R. Nos conclusions suggerent que la conductance des feuilles automnales et l'echange gazeux dans le bouleau verruqueux sont considerablement influences par l'exposition a long terme a une RH elevee et sont probablement relies a des processus complexes de senescence des feuilles, y compris la retranslocation de l'azote. [Traduit par la Redaction] Mots-cles: acide abscissique, changements climatiques a l'echelle mondiale, senescence des feuilles, periode nocturne, photoperiode., Introduction Global climate change leads to longer growing seasons at high latitudes and is responsible for changes in the functionality and productivity of forest ecosystems. Moreover, climate change creates considerable [...]

Abstract Background S100B is an established biomarker of brain development and damage. Lutein (LT) is a naturally occurring xanthophyll carotenoid mainly concentrated in the central nervous system (CNS), but its neurotrophic role is still debated. We investigated whether LT cord blood concentrations correlate with S100B in a cohort of preterm and term healthy newborns. Methods We conducted a prospective study on the distribution of LT and S100B in arterial cord blood of healthy preterm (n = 50) and term (n = 50) newborns. Results S100B and LT showed a pattern of concentration characterized by higher levels (P

Abstrak. Tujuan dari penelitian ini adalah mengetahui pengaruh yang ditimbulkan dari pemberian penguatan verbal (verbal reinforcement) pada saat pembelajaran berlangsung terhadap motivasi belajar siswa. Jenis penelitian ini adalah penelitian kuantitatif ex-post facto dengan desain regresi yaitu mencari pengaruh variabel pemberian penguatan verbal (X) terhadap variabel motivasi belajar (Y). Penelitian ini dilaksanakan di SD 24 Pakkana, Kabupaten Sengkang. Sebanyak 30 orang siswa kelas V sebagai sampel. Pengumpulan data menggunakan teknik angket dan dokumentasi. Data dianalisis dengan teknik statistik deskriptif dan statistik inferensial. Hasil penelitian ini yaitu terdapat pengaruh positif dan signifikan pemberian penguatan verbal terhadap motivasi belajar siswa kelas V di SD 24 Pakkana, Kabupaten Sengkang. Besarnya nilai koefisien korelasi yang dilambangkan dengan R yaitu sebesar 0.955. Sedangkan besarnya persentase (%) pengaruh yang ditimbulkan variabel bebas (pemberian penguatan verbal) terhadap variabel terikat (motivasi belajar siswa) yang dilambangkan dengan R square (R2) yaitu 0.911, artinya bahwa pengaruh variabel pemberian penguatan verbal (X) terhadap variabel motivasi belajar siswa (Y) adalah sebesar 91.1%, sedangkan sisanya dipengaruhi oleh variabel lain diluar dari yang diteliti. Jadi, konstribusi pemberian penguatan verbal terhadap motivasi belajar siswa sebesar 91.1%. Kata Kunci: pengaruh, penguatan verbal, motivasi belajar

Stomatal pore apertures are narrowing globally due to the continuing rise in atmospheric [CO2]. CO2 elevation and the plant hormone abscisic acid (ABA) both induce rapid stomatal closure. However, the underlying signal transduction mechanisms for CO2/ABA interaction remain unclear. Two models have been considered: (i) CO2 elevation enhances ABA concentrations and/or early ABA signaling in guard cells to induce stomatal closure and (ii) CO2 signaling merges with ABA at OST1/SnRK2.6 protein kinase activation. Here we use genetics, ABA-reporter imaging, stomatal conductance, patch clamp, and biochemical analyses to investigate these models. The strong ABA biosynthesis mutants nced3/nced5 and aba2-1 remain responsive to CO2 elevation. Rapid CO2-triggered stomatal closure in PYR/RCAR ABA receptor quadruple and hextuple mutants is not disrupted but delayed. Time-resolved ABA concentration monitoring in guard cells using a FRET-based ABA-reporter, ABAleon2.15, and ABA reporter gene assays suggest that CO2 elevation does not trigger [ABA] increases in guard cells, in contrast to control ABA exposures. Moreover, CO2 activates guard cell S-type anion channels in nced3/nced5 and ABA receptor hextuple mutants. Unexpectedly, in-gel protein kinase assays show that unlike ABA, elevated CO2 does not activate OST1/SnRK2 kinases in guard cells. The present study points to a model in which rapid CO2 signal transduction leading to stomatal closure occurs via an ABA-independent pathway downstream of OST1/SnRK2.6. Basal ABA signaling and OST1/SnRK2 activity are required to facilitate the stomatal response to elevated CO2 These findings provide insights into the interaction between CO2/ABA signal transduction in light of the continuing rise in atmospheric [CO2].

Abstract The emergence of green materials has attracted considerable attention in the field of optoelectronics. Copper-based lead-free metal halide (with a near-unity quantum yield) obtained from Cs3Cu2I5 nanocrystals (NCs) can exhibit blue emission with a wavelength of 440 nm and provide outstanding stability for various applications. However, in practical applications, colloidal dispersion purity and film quality are inadequate toward a high-performance device. In this study, antisolvent-free gel permeation chromatography is used to purify Cs3Cu2I5 NCs. The purified Cs3Cu2I5 NCs exhibit a high photoluminescent quantum yield and provide a highly oriented single-crystal film. Density functional theory calculation results indicate that the iodide-rich surface in the NCs makes them highly stable. In addition, it has been demonstrated for the first time that the mixture of polymethyl methacrylate (PMMA) and Cs3Cu2I5 NCs has waterproofing capabilities. The composite film consisting of Cs3Cu2I5 NCs and PMMA can survive in water for several days. This result opens up more possibilities for the application of these green material.

The measurement of blood pH and gas analytes (BPGA), soon after birth, constitutes the first-line standard of care procedure in high-risk newborns. However, no data is available in capillary blood on perinatal bias such as gestational age (GA), weight at birth (BW), delivery mode, and gender. The aims of the present study were to investigate whether in a cohort of healthy preterm (PT) and term (T) infants BPGA were GA, BW, delivery mode and gender dependent, thus affecting BPGA reliability as diagnostic test.We performed a prospective case-control study in 560 healthy infants (PT: n=115, T: n=445). BPGA was measured within 24-h from birth. Perinatal characteristics, outcomes, and clinical examination were also recorded.PT infants showed higher (p<0.001) carbon dioxide partial pressure (pCO2), fraction of fetal hemoglobin (HbF), base excess (BE), bicarbonate (HCO3), and lower lactate (Lac) levels. When corrected for delivery mode, higher (p<0.001) HbF, BE, HCO3, and lower Lac levels were found. Similarly, higher (p<0.05, for all) pCO2, HbF, BE, HCO3 and lower Lac levels were found between female and male PT and T infants. Repeated multiple logistic regression analysis showed that BPGA was GA, BW, delivery mode and gender dependent.The present results showing that BPGA can be affected by a series of perinatal outcomes open the way to further investigations providing longitudinal BPGA reference curves in the transitional phase, thus empowering BPGA role as a reliable diagnostic and therapeutic strategies efficacy marker. [ABSTRACT FROM AUTHOR]