Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation.

The mechanistic understanding of nascent RNAs in transcriptional control remains limited. Here, by a high sensitivity method methylation-inscribed nascent transcripts sequencing (MINT-seq), we characterized the landscapes of N6-methyladenosine (m6A) on nascent RNAs. We uncover heavy but selective m6A deposition on nascent RNAs produced by transcription regulatory elements, including promoter upstream antisense RNAs and enhancer RNAs (eRNAs), which positively correlates with their length, inclusion of m6A motif, and RNA abundances. m6A-eRNAs mark highly active enhancers, where they recruit nuclear m6A reader YTHDC1 to phase separate into liquid-like condensates, in a manner dependent on its C terminus intrinsically disordered region and arginine residues. The m6A-eRNA/YTHDC1 condensate co-mixes with and facilitates the formation of BRD4 coactivator condensate. Consequently, YTHDC1 depletion diminished BRD4 condensate and its recruitment to enhancers, resulting in inhibited enhancer and gene activation. We propose that chemical modifications of eRNAs together with reader proteins play broad roles in enhancer activation and gene transcriptional control.

Detection of terbinafine-resistant Trichophyton indotineae isolates within the Trichophyton mentagrophytes species complex isolated from patients in Hue City, Vietnam: A comprehensive analysis.

The Trichophyton mentagrophytes complex comprises a group of dermatophyte fungi responsible for various dermatological infections. The increasing drug resistance of this species complex, especially terbinafine resistance of Trichophyton indotineae, is a major concern in dermatologist practice. This study provides a comprehensive analysis of T. mentagrophytes complex strains isolated from patients in Hue City, Vietnam, focusing on their phenotypic and genetic characteristics, antifungal susceptibility profiles, and molecular epidemiology. Keratinophilic fungi from dermatophytosis culture samples were identified morphologically and phenotypically, with species and genotypes confirmed by internal transcribed spacer sequencing and phylogenetic analysis. Antifungal susceptibility testing was carried out to evaluate their susceptibility to itraconazole, voriconazole, and terbinafine. The 24% (n = 27/114) of superficial mycoses were phenotypically attributed to T. mentagrophytes complex isolates. Trichophyton interdigitale, mainly genotype II*, was predominant (44.4%), followed by T. mentagrophytes genotype III* (22.2%), T. indotineae (14.8%), T. tonsurans (11.2%), and T. mentagrophytes (7.4%). While all isolates were susceptible to itraconazole and voriconazole, half of T. indotineae isolates exhibited resistance to terbinafine, linked to the Phe397Leu mutation in the SQLE protein. This study highlighted the presence of terbinafine-resistant T. indotineae isolates in Vietnam, emphasizing the need to investigate dermatophyte drug resistance and implement effective measures in clinical practice.

Species diversity within the Trichophyton mentagrophytes complex isolated from dermatophytosis in Hue City, Vietnam, was observed. Terbinafine-resistant T. indotineae isolates were detected for the first time in Vietnam, emphasizing the importance of implementing antifungal susceptibility testing to effectively manage and prevent the spread of resistant isolates.

Physicochemical Characterization, Antioxidant and Tyrosinase Inhibitory Activities of Coffea Robusta Monofloral Honey from Dak Lak Province, Vietnam.

Robusta coffee blossom honey stands as a key regional product in Dak Lak province, Vietnam. Despite its significance, there exists a dearth of scientific data for assessing its quality. This study aims to fill this gap by characterizing the physicochemical properties and biological activities of coffee blossom honeys from three distinct sub-regions within Dak Lak province, Vietnam. These activities include ferric reducing power (FRP), DPPH and ABTS radical scavenging, as well as tyrosinase inhibitory activities. Moreover, the study compares these honey samples with other popular varieties in Vietnam, such as Lychee and Longan honeys. The physicochemical parameters of the honey samples meet the standards set by Codex Alimentarius 2001. Through UPLC analysis, eleven compounds were identified, with caffeine serving as a marker for coffee honey. Furthermore, by employing multiple factor analysis (MFA), it was observed that certain physicochemical properties correlate positively with tyrosinase inhibitory, DPPH, ABTS free radicals scavenging activities, and FRP. Notably, tyrosinase inhibitory activity exhibited a positive correlation with antioxidant activity. These findings underscore the high quality of Coffea robusta honey, showcasing its potent antioxidant and tyrosinase inhibitory activities.

Phytochemical Profiles and Biological Activities of Five Wild Camellia Species from Ta Dung, Vietnam.

The C. luuana Orel & Curry (TD3), C. furfuracea (Merr.) Cohen-Stuard (TD4), C. bidoupensis Truong, Luong & Tran (TD6), C. sinensis (L.) Kuntze (TD7), and C. kissii var. spp (TD8), have been traditionally used as a health-promoting beverage by local people in Ta Dung, Dak Nong. Despite their potential health benefits, further scientific data on biological and phytochemical properties of these plants is needed. To address this issue, this study was conducted to investigate phytochemical and biological properties of five Camellia species extracts, using DPPH, ABTS radical scavenging, copper chelating (Cu-chelator), and tyrosinase inhibition (TI), α-amylase (Al-AI), and α-glucosidase (Al-GI) analyses. As results, ten compounds were identified using UPLC method, in which catechins (mainly EGCG and catechin (Cat)), were the most prevalent, and followed by chlorogenic acid (ChlA), quercitrin (Querci), rutin, and quercetin (Querce). Additionally, multiple factor analysis (MFA) also revealed that TD7, TD3, and TD4 containing high TPC, TFC, high concentrations of EGCG, ChlA, and caffeine were responsible for their high DPPH, ABTS radical scavenging activities, as well asTI, Al-AI and Al-GI. Furthemore, TD6 and TD8, possessing elevated levels of Apig, Querci, Rutin, Querce, Cat, and EA, exhibited a high Cu-chelator property, but a weak enzyme inhibition. From all above-mentioned results, the antioxidative and enzyme inhibitory potentials of Camellia species extracts collected in Dak Nong province in Vietnam were scientifically demonstrated paving a pathway to develop health supplement in further studies.

Hippocampal motor memory network reorganization depends on familiarity, not time.

There is debate as to whether a time-dependent transformation of the episodic-like memory network is observed for nonepisodic tasks, including procedural motor memory. To determine how motor memory networks reorganize with time and practice, mice performed a motor task in a straight alley maze for 1 d (recent), 20 d of continuous training (continuous), or testing 20 d after the original training (remote), and then regional c-Fos expression was assessed. Elevated hippocampal c-Fos accompanied remote, but not continuous, motor task retrieval after 20 d, suggesting that the hippocampus remains engaged for nonhabitual remote motor memory retrieval.

Time-course cross-species transcriptomics reveals conserved hepatotoxicity pathways induced by repeated administration of cyclosporine A.

Cyclosporine A (CsA) has shown efficacy against immunity-related diseases despite its toxicity in various organs, including the liver, emphasizing the need to elucidate its underlying hepatotoxicity mechanism. This study aimed to capture the alterations in genome-wide expression over time and the subsequent perturbations of corresponding pathways across species. Six data from humans, mice, and rats, including animal liver tissue, human liver microtissues, and two liver cell lines exposed to CsA toxic dose, were used. The microtissue exposed to CsA for 10 d was analyzed to obtain dynamically differentially expressed genes (DEGs). Single-time points data at 1, 3, 5, 7, and 28 d of different species were used to provide additional evidence. Using liver microtissue-based longitudinal design, DEGs that were consistently up- or down-regulated over time were captured, and the well-known mechanism involved in CsA toxicity was elucidated. Thirty DEGs that consistently changed in longitudinal data were also altered in 28-d rat in-house data with concordant expression. Some genes (e.g. TUBB2A, PLIN2, APOB) showed good concordance with identified DEGs in 1-d and 7-d mouse data. Pathway analysis revealed up-regulations of protein processing, asparagine N-linked glycosylation, and cargo concentration in the endoplasmic reticulum. Furthermore, the down-regulations of pathways related to biological oxidations and metabolite and lipid metabolism were elucidated. These pathways were also enriched in single-time-point data and conserved across species, implying their biological significance and generalizability. Overall, the human organoids-based longitudinal design coupled with cross-species validation provides temporal molecular change tracking, aiding mechanistic elucidation and biologically relevant biomarker discovery.

Neuronal loss and inflammation preceding fibrillary tau pathology in a rat model with early human-like tauopathy.

In tauopathies such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), the microtubule associated protein tau undergoes conformational and posttranslational modifications in a gradual, staged pathological process. While brain atrophy and cognitive decline are well-established in the advanced stages of tauopathy, it is unclear how the early pathological processes manifest prior to extensive neurodegeneration. For these studies we have applied a transgenic rat model of human-like tauopathy in its heterozygous form, named McGill-R955-hTau. The goal of the present study was to investigate whether lifelong accumulation of mutated human tau could reveal the earliest tau pathological processes in a context of advanced aging, and, at stages before the overt aggregated or fibrillary tau deposition. We characterized the phenotype of heterozygous R955-hTau rats at three endpoints, 10, 18 and 24-26 months of age, focusing on markers of cognitive capabilities, progressive tau pathology, neuronal health, neuroinflammation and brain ultrastructural integrity, using immunohistochemistry and electron microscopy. Heterozygous R955-hTau transgenic rats feature a modest, life-long accumulation of mutated human tau that led to tau hyperphosphorylation and produced deficits in learning and memory tasks after 24 months of age. Such impairments coincided with more extensive tau hyperphosphorylation in the brain at residues pThr231 and with evidence of oligomerization. Importantly, aged R955-hTau rats presented evidence of neuroinflammation, detriments to myelin morphology and detectable hippocampal neuronal loss in the absence of overt neurofibrillary lesions and brain atrophy. The slow-progressing tauopathy of R955-hTau rats should allow to better delineate the temporal progression of tau pathological events and therefore to distinguish early indicators of tauopathy as having the capability to induce degenerative events in the aged CNS.

The influences of stomatal size and density on rice abiotic stress resilience.

A warming climate coupled with reductions in water availability and rising salinity are increasingly affecting rice (Oryza sativa) yields. Elevated temperatures combined with vapour pressure deficit (VPD) rises are causing stomatal closure, further reducing plant productivity and cooling. It is unclear what stomatal size (SS) and stomatal density (SD) will best suit all these environmental extremes. To understand how stomatal differences contribute to rice abiotic stress resilience, we screened the stomatal characteristics of 72 traditionally bred varieties. We found significant variation in SS, SD and calculated anatomical maximal stomatal conductance (gsmax ) but did not identify any varieties with SD and gsmax as low as transgenic OsEPF1oe plants. Traditionally bred varieties with high SD and small SS (resulting in higher gsmax ) typically had lower biomasses, and these plants were more resilient to drought than low SD and large SS plants, which were physically larger. None of the varieties assessed were as resilient to drought or salinity as low SD OsEPF1oe transgenic plants. High SD and small SS rice displayed faster stomatal closure during increasing temperature and VPD, but photosynthesis and plant cooling were reduced. Compromises will be required when choosing rice SS and SD to tackle multiple future environmental stresses.

Pathway-level multi-omics analysis of the molecular mechanisms underlying the toxicity of long-term tacrolimus exposure.

Tacrolimus (TAC)-based treatment is associated with nephrotoxicity and hepatotoxicity; however, the underlying molecular mechanisms responsible for this toxicity have not been fully explored. This study elucidated the molecular processes underlying the toxic effects of TAC using an integrative omics approach. Rats were sacrificed after 4 weeks of daily oral TAC administration at a dose of 5 mg/kg. The liver and kidney underwent genome-wide gene expression profiling and untargeted metabolomics assays. Molecular alterations were identified using individual data profiling modalities and further characterized by pathway-level transcriptomics-metabolomics integration analysis. Metabolic disturbances were mainly related to an imbalance in oxidant-antioxidant status, as well as in lipid and amino acid metabolism in the liver and kidney. Gene expression profiles also indicated profound molecular alterations, including in genes associated with a dysregulated immune response, proinflammatory signals, and programmed cell death in the liver and kidney. Joint-pathway analysis indicated that the toxicity of TAC was associated with DNA synthesis disruption, oxidative stress, and cell membrane permeabilization, as well as lipid and glucose metabolism. In conclusion, our pathway-level integration of transcriptome and metabolome and conventional analyses of individual omics profiles, provided a more comprehensive picture of the molecular changes resulting from TAC toxicity. This study also serves as a valuable resource for subsequent investigations aiming to understand the mechanism underlying the molecular toxicology of TAC.

Pyrimido[1,2-a]benzimidazoles as inhibitors of oncoproteins ubiquitin specific protease 5 and MYCN in the childhood cancer neuroblastoma.

The MYCN oncogene and histone deacetylases (HDACs) are key driver genes in the childhood cancer, neuroblastoma. We recently described a novel pyridobenzimidazole analogue, SE486-11, which enhanced the therapeutic effectiveness of HDAC inhibitors by increasing MYCN ubiquitination through effects on the deubiquitinase, ubiquitin-specific protease 5 (USP5). Here we describe the synthesis of a novel series of pyrimido[1,2-a]benzimidazole derivatives, and an evaluation of their cytopathic effects against non-malignant and human neuroblastoma cell lines. Among the tested analogues, 4-(4-methoxyphenyl)benzo[4,5]imidazo[1,2-a]pyrimidine (3a) was the most active compound against neuroblastoma cells (IC50 ≤ 2 µM), with low cytotoxicity (IC50 ≥ 15 µM) to normal cells. We show compound 3a bound to USP5 protein (Kd = 0.47 µM) in vitro and synergistically enhanced the efficacy of HDAC inhibitors against neuroblastoma cells. Moreover, knockdown of USP5 and MYCN in treated neuroblastoma cells showed that both USP5 and MYCN expression was necessary for the cytopathic activity of compound 3a, thus providing a clinically relevant rationale for further development of this of pyrimido[1,2-a]benzimidazole.

ClusTRace, a bioinformatic pipeline for analyzing clusters in virus phylogenies.

BACKGROUND: SARS-CoV-2 is the highly transmissible etiologic agent of coronavirus disease 2019 (COVID-19) and has become a global scientific and public health challenge since December 2019. Several new variants of SARS-CoV-2 have emerged globally raising concern about prevention and treatment of COVID-19. Early detection and in-depth analysis of the emerging variants allowing pre-emptive alert and mitigation efforts are thus of paramount importance. RESULTS: Here we present ClusTRace, a novel bioinformatic pipeline for a fast and scalable analysis of sequence clusters or clades in large viral phylogenies. ClusTRace offers several high-level functionalities including lineage assignment, outlier filtering, aligning, phylogenetic tree reconstruction, cluster extraction, variant calling, visualization and reporting. ClusTRace was developed as an aid for COVID-19 transmission chain tracing in Finland with the main emphasis on fast screening of phylogenies for markers of super-spreading events and other features of concern, such as high rates of cluster growth and/or accumulation of novel mutations. CONCLUSIONS: ClusTRace provides an effective interface that can significantly cut down learning and operating costs related to complex bioinformatic analysis of large viral sequence sets and phylogenies. All code is freely available from https://bitbucket.org/plyusnin/clustrace/.

Introduction and Rapid Spread of SARS-CoV-2 Omicron Variant and Dynamics of BA.1 and BA.1.1 Sublineages, Finland, December 2021.

Multiple introductions of SARS-COV-2 Omicron variant BA.1 and BA.1.1. lineages to Finland were detected in early December 2021. Within 3 weeks, Omicron overtook Delta as the most common variant in the capital region. Sequence analysis demonstrated the emergence and spread through community transmission of a large cluster of BA.1.1 virus.

Characterization of Clofazimine as a Potential Substrate of Drug Transporter.

In this study, we explored clofazimine (CFZ) as a potential substrate of uptake and efflux transporters that might be involved in CFZ disposition, using transporter gene overexpressing cell lines in vitro. The intracellular concentrations of CFZ were significantly increased in the presence of selective inhibitors of P-gp and BCRP, which include verapamil, cyclosporine-A, PSC-833, quinidine, Ko143, and daunorubicin. In a bidirectional transport assay using transwell cultures of cell lines overexpressing P-gp and BCRP, the mean efflux ratios of CFZ were found to be 4.17 ± 0.63 and 3.37 ± 1.2, respectively. The Km and maximum rate of uptake (Vmax) were estimated to be 223.3 ± 14.73 µM and 548.8 ± 87.15 pmol/min/mg protein for P-gp and 381.9 ± 25.07 µM and 5.8 ± 1.22 pmol/min/mg protein for BCRP, respectively. Among the uptake transporters screened, the CFZ uptake rate was increased 1.93 and 3.09-fold in HEK293 cell lines overexpressing OAT1 and OAT3, respectively, compared to the control cell lines, but no significant uptake was observed in cell lines overexpressing OCT1, OCT2, OATP1B1, OATP1B3, OATP2B1, or NTCP. Both OAT1- and OAT3-mediated uptake was inhibited by the selective inhibitors diclofenac, probenecid, and butanesulfonic acid. The Km and Vmax values of CFZ were estimated to be 0.63 ± 0.15 µM and 8.23 ± 1.03 pmol/min/mg protein, respectively, for OAT1 and 0.47 ± 0.1 µM and 17.81 ± 2.19 pmol/min/mg protein, respectively, for OAT3. These findings suggest that CFZ is a novel substrate of BCRP, OAT1, and OAT3 and a known substrate of P-gp in vitro.

Characterization of Clofazimine Metabolism in Human Liver Microsomal Incubation In Vitro.

Clofazimine [N,5-bis(4-chlorophenyl)-3-[(propane-2-yl)rimino]-3,5-dihydrophenazin-2-amine] is an antimycobacterial agent used as a second-line antituberculosis (anti-TB) drug. Nonetheless, little information is known about the metabolic routes of clofazimine, and the enzymes involved in metabolism. This study aimed to characterize the metabolic pathways and enzymes responsible for the metabolism of clofazimine in human liver microsomes. Eight metabolites, including four oxidative metabolites, three glucuronide conjugates, and one sulfate conjugate were identified, and their structures were deduced based on tandem mass spectrometry (MS/MS) spectra. Hydroxylated clofazimine and hydrated clofazimine was generated even in the absence of the NADPH generating system presumably via a nonenzymatic pathway. Hydrolytic-dehalogenated clofazimine was catalyzed mainly by CYP1A2 whereas hydrolytic-deaminated clofazimine was formed by CYP3A4/A5. In case of glucuronide conjugates, UGT1A1, UGT1A3, and UGT1A9 showed catalytic activity toward hydroxylated and hydrated clofazimine glucuronide whereas hydrolytic-deaminated clofazimine glucuronide was catalyzed by UGT1A4, UGT1A9, UGT1A3, and UGT2B4. Our results suggested that CYP1A2 and CYP3A are involved in the formation of oxidative metabolites while UGT1A1, 1A3, 1A4, 1A9, and 2B4 are involved in the formation of glucuronide conjugates of oxidative metabolites of clofazimine.

Multiple Early-Life Seizures Alters Neonatal Communicative Behavior in Fmr1 Knockout Mice.

Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and a significant contributor to Autism Spectrum Disorder. Individuals with FXS are subject to developing numerous comorbidities, one of the most prevalent being seizures. In the present study, we investigated how seizures affected neonatal communicative behavior in the FXS mouse model. On postnatal day (PD) 7 through 11, we administered 3 flurothyl seizures per day to both Fmr1 knockout and wild-type C57BL/6J male mice. Ultrasonic vocalizations were recorded on PD12. Statistically significant alterations were found in both spectral and temporal measurements across seizure groups. We found that induction of seizures across PD7-11 resulted in an increased fundamental frequency (pitch) of ultrasonic vocalizations produced (p < 0.05), a longer duration of calls (p < 0.05), and a greater cumulative duration of calls (p < 0.05) in both genotypes. Induction of seizures across PD7-11 also resulted in a decreased latency to the first emitted vocalization (p < 0.05) and a decrease in mean power (loudness) for their vocalizations (p < 0.05). Early-life seizures also resulted in an increase in the number of downward and frequency step call types (p < 0.05). There was a significant increase in the number of chevron calls emitted from the Fmr1 knockout mice that received seizures compared to knockout control and wild-type seizure mice (p < 0.05). Overall, this study provides evidence that early-life seizures result in communication impairments and that superimposing seizures in Fmr1 knockout mice does produce an additional deficit in vocalization.

Long-term outcomes of crossmatch positive simultaneous liver-kidney transplantations in the United States.

The long-term outcomes of positive crossmatch (+XM) simultaneous liver-kidney (SLK) transplantations are conflicting. We examined the association between crossmatch status and SLK outcomes in recipients discharged on tacrolimus and mycophenolate with or without steroids. We analyzed the Scientific Registry of Transplant Recipients for all primary SLK recipients between 2003 and 2020 with available crossmatch and induction data. We grouped recipients according to the crossmatch status: negative crossmatch (-XM; n = 3040) and +XM (n = 407). Kaplan-Meier curves were generated to examine recipient, death-censored liver, and death-censored kidney survival by crossmatch status. Cox proportional hazard models were used to investigate the association between crossmatch status and outcomes of interest with follow-up censored at 10 years. Models were adjusted for recipient age, sex, diabetes mellitus, Model for End-Stage Liver Disease score, duration on the liver waiting list, induction immunosuppression, steroid maintenance, hepatitis C infection, donor age and sex, local vs. shared organ, cold ischemia time, and previous liver transplantation status. In the univariable analysis, crossmatch status was not associated with recipient survival (log-rank p = 0.63), death-censored liver graft survival (log-rank p = 0.05), or death-censored kidney graft survival (log-rank p = 0.11). Compared with -XM, +XM recipients had a similar 1-year liver rejection rate, but higher kidney rejection rate (4.6% vs. 8.9%, p = 0.002). In the multivariable models, +XM status was not associated with deleterious long-term recipient, liver, or kidney grafts survival. -XM and +XM SLK transplantations have comparable long-term recipient, liver graft, and kidney survival with a slightly increased risk of early kidney allograft rejection in the +XM group. Crossmatch positivity in SLK transplantations should not influence the decision to use organs from a specific donor.

Delineation of the molecular mechanisms underlying Colistin-mediated toxicity using metabolomic and transcriptomic analyses.

The mechanisms underlying colistin-induced toxicity are not fully understood. This study used untargeted metabolomics and transcriptomics to elucidate the molecular processes occurring in the liver and kidney of rats after treatment with colistin methanesulfonate (CMS). Rats were treated with 50 mg/kg CMS (high-dose), 25 mg/kg CMS (low-dose), or vehicle control, either as a single dose or once daily for 1 or 4 weeks. We found that metabolic alterations were dose- and treatment duration-dependent in the kidney, whereas mild changes were noted in the liver. Metabolic profiles in the high-dose, low-dose, and control groups of both tissues could be classified using partial least-squares discriminant analysis. Metabolic alterations were associated with the citric acid cycle and related processes, disrupted balance between pro-oxidants and antioxidants, inflammatory responses, and amino acid and nucleic acid metabolism. Gene expression profiles further showed that high-dose treatment was associated with disrupted metabolism, oxidative stress, and proinflammatory signals in the kidney. The expression levels of genes related to the cell cycle, DNA replication, and programmed cell death were also predominantly upregulated. These findings suggested that high-dose treatment was associated with a dramatic increase in cellular kidney injury, while only minor effects were observed in the low-dose group. Almost no significant gene expression was changed in the liver, even with high-dose CMS. In conclusion, untargeted metabolomics and transcriptomics provided better insights into the biological mechanisms underlying colistin-induced nephrotoxicity.

Biological Activities of Lichen-Derived Monoaromatic Compounds.

Lichen-derived monoaromatic compounds are bioactive compounds, associated with various pharmacological properties: antioxidant, antifungal, antiviral, cytotoxicity, and enzyme inhibition. However, little is known about data regarding alpha-glucosidase inhibition and antimicrobial activity. Very few compounds were reported to have these activities. In this paper, a series of monoaromatic compounds from a lichen source were isolated and structurally elucidated. They are 3,5-dihydroxybenzoic acid (1), 3,5-dihydroxybenzoate methyl (2), 3,5-dihydroxy-4-methylbenzoic acid (3), 3,5-dihydroxy-4-methoxylbenzoic acid (4), 3-hydroxyorcinol (5), atranol (6), and methyl hematommate (7). To obtain more derivatives, available compounds from the previous reports such as methyl ß-orsellinate (8), methyl orsellinate (9), and D-montagnetol (10) were selected for bromination. Electrophilic bromination was applied to 8-10 using NaBr/H2O2 reagents to yield products methyl 5-bromo-ß-orsellinate (8a), methyl 3,5-dibromo-orsellinate (9a), 3-bromo-D-montagnetol (10a), and 3,5-dibromo-D-montagnetol (10b). Compounds were evaluated for alpha-glucosidase inhibition and antimicrobial activity against antibiotic-resistant, pathogenic bacteria Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii. Compound 4 showed stronger alpha-glucosidase inhibition than others with an IC50 value of 24.0 µg/mL. Synthetic compound 9a exhibited remarkable activity against Staphylococcus aureus with a MIC value of 4 µg/mL. Molecular docking studies were performed to confirm the consistency between in vitro and in silico studies.

Intentions to use ride-sourcing services in Vietnam: What happens after three months without COVID-19 infections?

The COVID-19 pandemic has brought new risks and stress for paid transport users worldwide. COVID-19 has changed mobility dynamics worldwide, including low- and middle-income countries (e.g., Vietnam). The present study aims to provide an in-depth understanding of ride-sourcing passengers' behavioural intentions when COVID-19 pandemic management successfully prevented community transmission by extending the TPB with two constructs: perceived virus infection risk and problem-focused coping. Using self-administered questionnaires, data were collected from ride-sourcing customers in Ho Chi Minh City (Vietnam). A total of 540 responses were used for validating the proposed theorethical model. The structural equation model results indicate that problem-focused coping is a multi-faceted construct with two dimensions: problem-solving and self-protection. Also, problem-focused coping has the highest total effect on the intention to use ride-sourcing services following a period of COVID-19 suppression (3 months without identified cases). The findings also reveal that attitude partially mediates the link between problem-focused coping and behavioural intention. The results of this study could be used to develop strategies to promote ride-sourcing services in the aftermath of the COVID-19 pandemic.

Care competencies in adolescents: Development of a new measure and relationships with well-being.

Worldwide, we observe an increasing focus on fostering well-being in adolescents. This is reflected in growing research in the field of care. However, empirical research is lacking that focuses on the relationship between components of care: receiving care, self-care and extending care. This lack of research is mirrored in the lack of valid measures for assessing care competencies in educational contexts. The present research, therefore, has four goals: 1) to create a valid and reliable scale assessing levels of care competencies based on the multifaceted and multidimensional concept of care; 2) to explore the relationship between socio-demographic characteristics and care competencies in adolescents; 3) to examine the psychological outcomes associated with different levels of care competencies in adolescents; 4) to explore the interaction of the three care dimensions in predicting adolescents' well-being. Based on data from 742 adolescents, a reliable and valid scale could be developed with six subscales: Receiving care, self-care and extending care, with each of them falling apart in care competencies and care failures. Gender, age and academic achievement were related to care competencies/failures. Findings support the link between adolescents' well-being and care competencies/failures. These results have implications for promoting adolescents' well-being through school-based care-cultivation programs.