The effects of wearing KF94 masks on cardiorespiratory function and hemorheological response during moderate intensity exercise in adult males

The purpose of this study was to examine the effect of wearing a Korea filter 94 (KF94) mask on cardiorespiratory function and hemorheological responses during moderate intensity exercise in men during the Coronavirus disease 2019 (COVID-19) pandemic. 12 healthy males aged 20 to 29 years (28.3 ± 3.6 yr) were recruited for this study. The exercise intensity corresponding to the anaerobic threshold level was determined following a maximum graded exercise test, and exercise was performed for 40 minutes with a cycle ergometer at the target exercise intensity. Cardiorespiratory function, blood pressure, and hemorheological responses were measured every 10 minutes at rest and during exercise. Our results indicated no differences between conditions in respiratory frequency (Rf), tidal volume (TV), minute ventilation (VE), carbon dioxide production (V̇CO2), and partial pressure of arterial oxygen (PaO2). However, oxygen consumption (V̇O2) was significantly lower in the KF94 mask group compared to the control. There were no differences in systolic blood pressure (SBP), diastolic blood pressure (DBP), rate pressure product (RPP), aggregation index (AI), and blood critical stress (BCS) between the two groups. The mask group had a significant respiratory exchange ratio (R) at rest and during 10 minutes exercise compared to the control. The elongation index was higher at rest, 10 minutes, and 30 minutes in the mask group than control group (p < 0.05). Overall, our results suggest that although V̇O2 was decreased and R values were increased, the effects of other physiological parameters and hemorheological responses imposed by face masks during moderate intensity exercise are small. Thus, although negative effects of using face masks affect exercise capacity (i.e., exercise tolerance), our findings suggest that individuals wearing KF94 could safely exercise and get some health benefits from physical activities during the COVID-19 pandemic

Vocal Analysis Related to Changes in Frequency of Pure Tone Auditory Feedback

Purpose: Many studies have shown that subjects show a change of vocal fundamental frequency (F0) when phonating subjects hear their vocal pitch feedback shifted upward or downward. This study was performed to demonstrate whether vocal parameters [F0, intensity, jitter, shimmer, and noise to harmonic ratio (NHR)] in normal males respond to changes in frequency of pure tone masking. Materials and Methods: Twenty healthy male subjects participated in this study. Subjects vocalized /a / vowel sounds while listening to a pitchshift pure tone through headphones (upward pitch-shift in succession: 1kHz to 2 kHz and 1 kHz to 4 kHz at 50 dB or 80 dB, respectively, downward pitch-shift in succession: 1 kH

Hepatocyte Differentiation from Human ES Cells using the Simple Embryoid Body Formation Method and the Staged-Additional Cocktail

To induce hepatocytes from human embryonic stem (hES) cells easily and effectively, a simple suspension culture method that separates ES colonies with a scraper and transfers them into newly developed, nonadherent MPC (2-methacryloyloxyethyl phosphorylcholine) plates, and the staged-additional cocktail method, including growth factors, cytokines, and Lanford serum-free medium, were developed and evaluated mainly by morphological analysis. The formed embryoid bodies (EBs) showed compact cellular agglomeration until day 4 and later formed coeloms in their interior. RT-PCR (reverse transcriptase-polymerase chain reaction) analysis showed that they are gene markers of the three germ layers. Mesenchymal cells with rough endoplasmic reticulum (rER) and extracellular matrix (ECM), and without junctions, were recognized in the interior of the EBs by transmission electron microscopy (TEM) in addition to epithelial cells. When they were stimulated by the staged-additional cocktail, they expressed albumin-positive immunoreactivity, indocyanine green (ICG) uptake, and typical ultrastructures of the hepatocytes, including bile canaliculi. These results indicate that these combined methods promote EB formation and hepatocyte differentiation from hES cells

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

Initial Catalyst−Substrate Association Step in Enyne Metathesis Catalyzed by Grubbs Ruthenium Complex Probed by Time-Dependent Fluorescence Quenching

This communication introduces an FRET-based simple and efficient method for monitoring kinetics and thermodynamics of organic reactions and describes its application to studies on the initial catalyst-substrate association step in the enyne metathesis catalyzed by a Grubbs Ru complex to probe the reaction initiation on the alkyne versus the alkene. The kinetic and thermodynamic parameters of alkene and alkyne with the first generation Grubbs Ru complex, determined by the time-dependent fluorescence quenching of the dye-conjugated substrate by the Ru catalyst, strongly support the dominance of the reaction initiation on alkene over alkyne in the reaction both kinetically and thermodynamically.1122sciescopu

Human papillomavirus 16 (HPV16) enhances tumor growth and cancer stemness of HPV-negative oral/oropharyngeal squamous cell carcinoma cells via miR-181 regulation

High-risk human papillomaviruses (e. g., HPV16, HPV18) are closely associated with the development of head and neck cancers including oral/oropharyngeal squamous cell carcinoma (OSCC). We previously demonstrated immortalization of normal human oral keratinocytes by introducing high-risk HPV whole genome, suggesting that HPV infection plays an important role in the early stage of oral carcinogenesis. Although HPV infection may occur in different stages of cancer development, roles of HPV in exacerbating malignant phenotypes in already-transformed cells in the context of cancer stemness are not clearly defined. In this study, we investigated the role of HPV16 in promoting the virulence of HPV-negative OSCC. Introducing HPV16 whole genome in HPV-negative OSCC increased malignant growth and self-renewal capacity, a key characteristic of cancer stem cells (CSCs). HPV16 also enhanced other CSC properties, including aldehyde dehydrogenase 1 (ALDH1) activity, migration/invasion, and CSC-related factor expression. Mechanistically, we found that HPV16 inhibited the expression of miR-181a and miR-181d (miR-181a/d) at the transcriptional level. Ectopic expression of miR-181a/d decreased anchorage independent growth and CSC phenotype of HPV16-transfected OSCC. Furthermore, silencing of miR-181a/d target genes, i. e., K-ras and ALDH1, abrogated the effects of HPV16 in HPV16-transfected OSCC, supporting the functional importance of HPV16/miR-181a/d axis in HPV-mediated oral carcinogenesis. Our study suggests that high-risk HPV infection further promotes malignancy in HPV-negative OSCC by enhancing cancer stemness via miR-181a/d regulation. Consequently, miR-181a/d may represent a novel therapeutic agent for the treatment of HPV-positive OSCC. Keywords: HPV, OSCC, cancer stem cells, miR-18

Orai3 Calcium Channel Contributes to Oral/Oropharyngeal Cancer Stemness through the Elevation of ID1 Expression

Emerging evidence indicates that intracellular calcium (Ca2+) levels and their regulatory proteins play essential roles in normal stem cell proliferation and differentiation. Cancer stem-like cells (CSCs) are subpopulations of cancer cells that retain characteristics similar to stem cells and play an essential role in cancer progression. Recent studies have reported that the Orai3 calcium channel plays an oncogenic role in human cancer. However, its role in CSCs remains underexplored. In this study, we explored the effects of Orai3 in the progression and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC). During the course of OSCC progression, the expression of Orai3 exhibited a stepwise augmentation. Notably, Orai3 was highly enriched in CSC populations of OSCC. Ectopic Orai3 expression in non-tumorigenic immortalized oral epithelial cells increased the intracellular Ca2+ levels, acquiring malignant growth and CSC properties. Conversely, silencing of the endogenous Orai3 in OSCC cells suppressed the CSC phenotype, indicating a pivotal role of Orai3 in CSC regulation. Moreover, Orai3 markedly increased the expression of inhibitor of DNA binding 1 (ID1), a stemness transcription factor. Orai3 and ID1 exhibited elevated expression within CSCs compared to their non-CSC counterparts, implying the functional importance of the Orai3/ID1 axis in CSC regulation. Furthermore, suppression of ID1 abrogated the CSC phenotype in the cell with ectopic Orai3 overexpression and OSCC. Our study reveals that Orai3 is a novel functional CSC regulator in OSCC and further suggests that Orai3 plays an oncogenic role in OSCC by promoting cancer stemness via ID1 upregulation