Direct Synthesis of Aryloxy Phosphonamidate Nucleotide Prodrugs Using the Cross Metathesis Assisted by Ultrasonic Irradiation.

A direct synthetic strategy of aryloxy phosphonamidate nucleotide prodrugs (A, G, C, and U) was developed with the CM reaction assisted by ultrasonic irradiation and partitioned addition of 12 mol % of Hoveyda-Grubbs (H-G) II catalyst in 61-82% yields as a mixture of E-/Z-isomers (∼2:1) from aryloxy vinylphosponamidate and 5'-vinyl nucleoside moieties.

Association between depressive symptoms and dynamic balance among young adults in the community.

Background: Detecting and addressing depression symptoms at their outset can reduce the burden on individuals and society; however, it has a limitation in that such evaluations mainly rely on self-reports. Several studies have demonstrated a strong association between motor symptoms and early depression. We aimed to associate body balance measured by the Lower Quarter Y Balance Test (YBT-LQ) with depressive symptoms among young adults in the community, to confirm the current evidence that depression negatively influences body balance. Research question: Is the YBT-LQ an objective tool for measuring and evaluating young adults' depression risks, as well as assessing whether depression negatively influences body balance? Methods: Our participants comprised 36 young adults. We assessed their depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D) via a Google survey, measured their body balance with the YBT-LQ, and analyzed data with Spearman's rank-order correlation coefficient test, using SPSS version 27.0. Results: We found that the right leg's anterior, posteromedial, and posterolateral scores- Z = -2.129, p = .033; Z = -2.181, p = .029; and Z = -2.250, p = .024, respectively-and composite scores-Z = 73.00, p = .027 -were significantly lower in the group with risk for clinical depression compared to the normal group. The CES-D total score had a negative association with all YBT-LQ scores, except for the anterior score of the left leg. Among the CES-D sub-factors, somatic and retarded activity showed negative correlations with all the YBT-LQ scores. Significance: Our findings revealed that depressive symptoms have a negative association with balance, and that the YBT-LQ can be a reliable tool for measuring motor symptoms of depression, specifically among young adults.

Synthesis and biological evaluation of new ß-D-N4-hydroxycytidine analogs against SARS-CoV-2, influenza viruses and DENV-2.

Drug repurposing approach was applied to find a potent antiviral agent against RNA viruses such as SARS-CoV-2, influenza viruses and dengue virus with a concise strategy of small change in parent molecular structure. For this purpose, ß-D-N4-hydroxycytidine (NHC, 1) with a broad spectrum of antiviral activity was chosen as the parent molecule. Among the prepared NHC analogs (8a-g, and 9) from uridine, ß-D-N4-O-isobutyrylcytidine (8a) showed potent activity against SARS-CoV-2 (EC50 3.50 µM), Flu A (H1N1) (EC50 5.80 µM), Flu A (H3N2) (EC50 7.30 µM), Flu B (EC50 3.40 µM) and DENV-2 (EC50 3.95 µM) in vitro. Furthermore, its potency against SARS-CoV-2 was >5-fold, 3.4-fold, and 3-fold compared to that of NHC (1), MK-4482 (2), and remdesivir (RDV) in vitro, respectively. Ultimately, compound 8a was expected to be a potent inhibitor toward RNA viruses as a viral mutagenic agent like MK-4482.

Protective Effect of Avenanthramide-C on Auditory Hair Cells against Oxidative Stress, Inflammatory Cytokines, and DNA Damage in Cisplatin-Induced Ototoxicity.

Cisplatin-induced ototoxicity leads to hearing impairment, possibly through reactive oxygen species (ROS) production and DNA damage in cochlear hair cells (HC), although the exact mechanism is unknown. Avenanthramide-C (AVN-C), a natural, potent antioxidant, was evaluated in three study groups of normal adult C57Bl/6 mice (control, cisplatin, and AVN-C+cisplatin) for the prevention of cisplatin-induced hearing loss. Auditory brainstem responses and immunohistochemistry of outer hair cells (OHCs) were ascertained. Cell survival, ROS production, Phospho-H2AX-enabled tracking of DNA damage-repair kinetics, and expression levels of inflammatory cytokines (TNF-α, IL-1ß, IL6, iNOS, and COX2) were assessed using House Ear Institute-Organ of Corti 1 (HEI-OC1 Cells). In the in vivo mouse model, following cisplatin-induced damage, AVN-C decreased the hearing thresholds and sheltered all cochlear turns' OHCs. In HEI-OC1 cells, AVN-C preserved cell viability and decreased ROS production, whereas cisplatin enhanced both ROS levels and cell viability. In HEI-OC1 cells, AVN-C downregulated IL6, IL-1ß, TNF-α, iNOS, and COX2 production that was upregulated by cisplatin treatment. AVN-C attenuated the cisplatin-enhanced nuclear H2AX activation. AVN-C had a strong protective effect against cisplatin-induced ototoxicity through inhibition of ROS and inflammatory cytokine production and DNA damage and is thus a promising candidate for preventing cisplatin-induced sensorineural hearing loss.

Neutral but not in the middle: cross-cultural comparisons of negative bias of "neutral" emotional stimuli.

Previous studies have shown that the perception of neutral emotion stimuli can be negative rather than absolutely neutral. In the current study, we examined the negative bias of both neutral faces and scenes, cross-culturally between East Asians (e.g. Koreans) and Caucasian Americans. In all experiments, participants performed a Go/No-go task, by either executing or withholding a response toward neutral stimuli presented in the context of positive or negative stimuli. Differentiating neutral stimuli from negative stimuli was less accurate, measured in d', than doing so from positive stimuli. This negative bias was evident with both faces (Experiments 1 and 2) and scenes (Experiment 3). In all experiments, while both ethnic groups demonstrated significant negative biases, there was a subtle modulation of the bias by cultural background. For example, for Korean faces and IAPS scenes, Koreans showed a mitigated negative bias and Caucasian Americans demonstrated a greater negative bias. However, for Caucasian faces, bias was comparable between the two groups. With the possibility of cultural modulation, the prevalent negative bias of neutral emotion questions the validity of the neutrality assumption of the neutral emotion. The study discusses the necessity of methodological and theoretical reconsiderations for the utilisation of neutral emotion stimuli.