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The discovery of SARS-CoV-2 RNA in the periodontal tissues of patients who tested positive for COVID-19, 24 days post the initial symptom onset, indicates the oral cavity could serve as a viral reservoir. This research aims to investigate the antiviral capabilities of Ovatodiolide, introducing a novel periodontal ligament organoid model for the study of SARS-CoV-2. We have successfully established a reliable and expandable organoid culture from the human periodontal ligament, showcasing characteristics typical of epithelial stem cells. This organoid model enables us to delve into the lesser-known aspects of dental epithelial stem cell biology and their interactions with viruses and oral tissues. We conducted a series of in vitro and ex vivo studies to examine the inhibitory impacts of Ova on SARS-CoV-2. Our findings indicate that Ovatodiolide molecules can bind effectively to the NRP1 active domain. Our study identifies potential interaction sites for Ovatodiolide (OVA) within the b1 domain of the NRP1 receptor. We generated point mutations at this site, resulting in three variants: Y25A, T44A, and a double mutation Y25A/T44A. While these mutations did not alter the binding activity of the spike protein, they did impact the concentration of OVA required for inhibition. The inhibitory concentrations for these variants are 15 μM for Y25A, 15.2 μM for T44A, and 25 μM for the double mutant Y25A/T44A. In addition, in vitro inhibition experiments demonstrate that the EC50 of Ova against the main protease (Mpro) of the SARS-CoV-2 virus is 7.316 μM. Our in vitro studies and the use of the periodontal ligament organoid model highlight Ovatodiolide's potential as a small molecule therapeutic agent that impedes the virus's ability to bind to the Neuropilin-1 receptor on host cells. The research uncovers various pathways and biochemical strategies through which Ovatodiolide may function as an effective antiviral small molecule drug. [Display omitted] • Ovatodiolide as a potential drug inhibiting SARS-CoV- 2 infiltration of host cells. • Ovatodiolide inhibits the binding of SARS-CoV-2 spike S1 to human NRP1 receptor. • Ovatodiolide blocks the interaction between SARS-CoV-2 S1 and the human neuropilin-1 (NRP1) receptor Ex vivo. [ABSTRACT FROM AUTHOR]

Research presents evidence for the mammalian mitochondrial DNA replication, which occurs by a strand-coupled mechanism involving incorporation of ribonucleotides. Furthermore, the mitochondrial DNA replication intermediates are in duplex form and with treatment of ribonuclease H, they yield partial single-stranded DNA molecules.

Cytomegalovirus (CMV) gastritis is occasionally reported in case reports and limited case series. Up to now, it is the largest and most comprehensive retrospective study of CMV gastritis. All patients who were histologically diagnosed with CMV gastritis at Linkou Chang Gung Memorial Hospital between January 2000 and April 2020 were included. Patients were divided into two groups according to immunity. Between-group differences in characteristics, manifestations, endoscopic features, prognostic factors, and outcomes were analyzed. The main endpoint was 3-month mortality. A total of 54 patients (34 immunocompromised, 20 immunocompetent) were enrolled. Common presentations included gastrointestinal bleeding (35.2%), abdominal pain (33.3%) and fever (31.5%). The endoscopic features included ulcer (88.9%) and inflammation (11.1%). The 3-month mortality rate was 20.4% and overall mortality rate was 40.7%. Acute kidney injury was the only independent risk factor for 3-month mortality (OR 53.89, 95%CI 1.56–1861.73, p = 0.027). Anti-viral therapy and host immune status did not affect 3-month mortality. Both immunocompromised and immunocompetent patients with CMV gastritis have high mortality rates, without significant between-group differences. Acute kidney injury is the only independent predictive factor for 3-month mortality. Prevention of acute kidney injury may possibly improve the 3-month mortality rate. [ABSTRACT FROM AUTHOR]

We propose a nested negative curvature hollow-core fiber that can stably transmit a single-mode (LP 11 mode) dark hollow beam with low loss. A pair of resonant tubes is nested inside the cladding tubes in the horizontal direction to enhance the confinement loss of the fundamental mode LP 01. Two pairs of glass sheets at different positions within the four cladding tubes in the non-horizontal direction are introduced to suppress the comparatively low loss higher-order modes LP 21 and LP 02. The numerical simulation results indicate that the loss ratio between the fundamental mode and LP 11 mode can reach 28703 when the transmission wavelength is 1.54 µm, and the LP 11 mode has the lowest confinement loss of 0.0049 dB/m. Meanwhile, the loss ratios of higher-order modes such as LP 21 , LP 02 , and LP 31 with the target LP 11 mode are above 100. The effective bandwidth of single-mode dark hollow beam transmission can reach 5 nm. This provides an optical fiber solution for single-mode dark hollow beam transmission, which has potential applications in atomic optics, quantum information, and nonlinear optics. [ABSTRACT FROM AUTHOR]

Abstract This work develops a unique layered structural composite to prevent the device from internal electromagnetic (EM) waves' self-disturbance and external EM wave interference. The composite is composed of two layers, the inner layer is a hybrid composite, using MWCNTs and NdFeB powders as fillers and epoxy as matrix, which is designed as absorbent layer, and the outer is MWCNT-coated non-woven fabric, which is treated as reflection layer. The inner layer containing MWCNTs and magnetic powder of NdFeB can firstly absorb parts of EM waves generating from inside devices, and when the rest EM waves transmit through the inner layer and impinge to the outer layer, almost all of the waves will be reflected back. The reflected waves will go through the inner layer and be absorbed again. In the meanwhile, as the external EM waves impinge to the outer layer, they will be reflected immediately. The optimal combination of this study is able to achieve over 92% (−23.09 dB) absorption and leave least than 8% (−11 dB) reflection of internal EM waves, and over 99.99% reflection of external EM waves. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Background/purpose: The diagnostic and therapeutic benefits of double-balloon enteroscopy (DBE) in adults are established, but few data are available on pediatric patients. The aim of this study was to evaluate the clinical efficacy and safety of DBE in pediatric patients in Taiwan.Methods: From April 2005 to September 2015, DBE procedures performed for diagnosis or therapy of small-bowel disease in children less than 18 years of age at Linkou Chang Gung Memorial Hospital, Taiwan were evaluated. The clinical decision to perform DBE via the oral or anal approach was based on the patient's primary clinical presentation. Data on indications, endoscopic findings, treatment outcome, and complications associated with the procedure were collected and reviewed retrospectively.Result: In total, 20 pediatric patients underwent a total of 29 DBEs due to suspicion of small-bowel disease. Among them, nine patients were evaluated for suspected small-bowel bleeding, six for Peutz-Jeghers syndrome, two for chronic abdominal pain, two for chronic diarrhea, and one for suspected protein-losing enteropathy. After excluding the six Peutz-Jeghers syndrome patients, 9 of the 14 patients (64%) got a positive endoscopic finding and diagnosis in 8 of the 14 patients (57%). DBE resulted in a further therapeutic intervention (endoscopic or surgical) in 50% of the patients (10/20) without serious complications.Conclusion: DBE has a high diagnostic yield and leads to therapeutic interventions in pediatric patients and shows promise for assessment and treating small-intestinal diseases in children in Taiwan. [ABSTRACT FROM AUTHOR]

Implications of plasminogen activator inhibitor-1 (PAI-1) in colonic polyps remain elusive. A prospective study was conducted with 188 consecutive subjects who underwent colonoscopy at a tertiary referral center. Biochemical parameters, serum PAI-1 levels, PAI-1 single-nucleotide polymorphisms (rs-1799889), and colonic polyp profiles were analyzed at baseline and 24 and 48 weeks postpolypectomy. Of 188 patients (mean age: 56.8 years), 78.7% had adenomas; the median polyp number and size were 2 and 1.2cm, respectively. Multivariate analyses revealed the following baseline associations: PAI-1 levels (95% confidence interval [CI] for estimated β: 0.012-0.223) and polyp pathology (0.294-0.63) with polyp size; polyp size (0.085-0.498) and platelet count (0.013-0.027) with PAI-1 levels. At 24 weeks postpolypectomy, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and platelet count were independently associated with PAI-1 levels. Among patients with colonic adenomas, baseline PAI-1 levels (95% CI odds ratio: 1.06-1.686; cut-off value: >10.65 ng/mL, area under curve: 0.662, P = 0.032) and the PAI-1-rs-17998894G/4G genotype (0.036-0.912) were associated with high-grade dysplasia. Compared with baseline levels, repeated measures analysis of variance showed that PAI-1 levels increased, with concurrent increased HOMA-IR indexes, but decreased alanine transaminase levels and polyp size in follow-up colonoscopies at 24 weeks postpolypectomy. PAI-1 returned to baseline levels, and HOMA-IRs and triglyceride/high-density lipoprotein-cholesterol ratios decreased at 48 weeks postpolypectomy. Taken together, serum PAI-1 levels were positively associated with colonic polyp size and high-grade dysplasia, which was modulated by the PAI-1-rs-17998894G/4G genotype. The beneficial postpolypectomy inflammatory and metabolic alterations might be transiently counter regulated by elevated PAI-1 levels, with a link to HOMA-IR. [ABSTRACT FROM AUTHOR]

Valvular heart diseases in pulmonary valves may exhibit different degrees of aortic stenosis or congenital defects. Valve repair or replacement surgery is one of the important procedures commonly performed to relieve valvular dysfunction and improve the significant regurgitation. Hence, it is necessary to assess pulmonary valve insufficiency for pre-surgery decision-making and post-surgery outcome evaluation. This study proposes an assistive technology to quantify regurgitation using the regurgitation fraction (RF) and heart pump efficiency (HPE). In signal preprocessing stage, the detrending and zero-crossing processes are used to remove the unwanted flow fluctuations and identify the end-systolic and end-diastolic periods per each cardiac cycle. The fractional-order integrations are employed to calculate the stroke volume (SV) and regurgitation volume (RV). Then, the regurgitation flow can be quantified that indicates the high correlation with HPE. For a mimicking pulmonary circulation loop system, the proposed screening model can be validated to assess the valve stent efficacy. Experimental results also indicate that pulmonary valve replacement, such as handmade trileaflet valves, can improve severe pulmonary regurgitations. Combining the noninvasive measurement device and the proposed screening model can provide an accurate assessment in clinical applications. [ABSTRACT FROM AUTHOR]

Aortic dissection (AD) is a catastrophic disease with high mortality and morbidity, characterized with fragmentation of elastin and loss of smooth muscle cells. Although AD has been largely attributable to polymorphisms defect in the elastin-coding gene, tropoelastin (TE), other undermined factors also appear to play roles in AD onset. Here, we investigated the effects of post-transcriptional control of TE by microRNAs (miRNAs) on elastin levels in aortic smooth muscle cells (ASMC). We found that miR-144-3p is a miRNA that targets TE mRNA in both human and mouse. Bioinformatics analyses and dual luciferase reporter assay showed that miR-144-3p inhibited protein translation of TE, through binding to the 3'-UTR of the TE mRNA. Interestingly, higher miR-144-3p levels and lower TE were detected in the ASMC obtained from AD patients, compared to those from non-AD controls. In a mouse model for human AD, infusion of adeno-associated viruses (serotype 6) carrying antisense for miR-144-3p (asmiR-144-3p) under CAG promoter significantly reduced the incidence and severity of AD, seemingly through enhancement of TE levels in ASMC. Thus, our data suggest an essential role of miR-144-3p on the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

The redox reaction of vanadium ions (V 2+↔3+↔4+↔5+ ) on well-developed nitrogen-doped ordered mesoporous carbon (NOMC) was extensively investigated in different electrolyte solutions by electrochemical methods. It is found that both the electronic structure modulated by nitrogen doping and the enriched electrochemically active functional groups on NOMC favor the three electrochemical transitions between the adjacent couples, viz . V 2+↔3+↔4+↔5+ , as compared with Vulcan XC72 carbon black. Salient findings are as follows. First, the transition of V 3+↔2+ is the same on the two distinctly different carbons, which indicates that this reaction is an outer-sphere charge transfer reaction. The concomitant hydrogen evolution reaction makes NOMC unsuitable to be used as a negative electrode material in flow batteries. Second, the transition of V 5+↔4+ shows a quasi-reversible behavior, indicating that NOMC can be used as a positive electrode material. Simulation of cyclic voltammogram (CV) reveals that the standard rate constant and the adsorption equilibrium constant are (7.0 ± 0.9)*10 −3 cm s −1 and 0.70 ± 0.09 (both V 4+ and V 5+ ), respectively. Third, the transition of V 4+↔3+ is recognized in the CV curve, which proceeds in a quasi-reversible reaction. The preceding adsorption of the symmetrical ions (V 3+ ) is found to play a key role in determining the kinetics. Finally, for the two latter transitions, the content of dopant nitrogen yields a negligible effect on the electrochemical activity, excluding the possibility of its direct involvement in electrocatalysis. The above findings not only reveal the applicability of the nitrogen-doped carbon to be used as an electrode material in flow batteries, but also offer an in-depth understanding of the reaction mechanism of vanadium redox couples. [ABSTRACT FROM AUTHOR]

Experiencing everyday discrimination can have a significant negative impact on an individual's wellbeing. While much attention has been paid to the physical and mental health consequences of discrimination, less is known about how discrimination can affect cognitive health, and most existing work has been conducted in laboratory settings where participants recall discrimination retrospectively. Given the artificial environment and susceptibility to recall bias in such procedures, the current study utilised two daily diary studies, consisting of young adults in Singapore (Study 1; N = 484) and midlife adults from the US (Study 2; N = 3577), to examine the association between discrimination and cognitive failures in daily life. Multilevel modelling revealed consistent evidence that experiencing discrimination was associated with poorer cognitive health at both the within- and between-person levels. These associations between discrimination and cognitive health remained robust even after controlling for demographic covariates previously found to affect cognitive health, as well as daily stressor exposure. These findings suggest that the experiences of everyday discrimination may lead to poorer daily cognitive functioning regardless of whether discrimination was experienced in a daily context or across the lifespan, and indicate importance of raising awareness on the harmful cognitive consequences of discrimination. [ABSTRACT FROM AUTHOR]

Activation of mitogen-activated protein kinase (MAPK) and PI3K signaling confers resistance against sorafenib, a mainstay treatment for advanced hepatocellular carcinoma (HCC). Antrocin and ovatodiolide constitute as the most potent secondary metabolites isolated from Antrodia camphorata and Anisomeles indica, respectively. Both natural compounds have recently gained a lot of attention due to their putative inhibition of MAPK and PI3K signaling in various solid cancers. However, whether their combination is effective in HCC remains unknown. Here, we investigated their effect, alone or in various combinations, on MAPK and PI3K signaling pathways in HCC cells. An array of in vitro study were used to investigate anticancer and stemness effects to treat HCC, such as cytotoxicity, drug combination index, migration, invasion, colony formation, and tumor sphere formation. Drug effect in vivo was evaluated using mouse xenograft models. In this study, antrocin and ovatodiolide synergistically inhibited the SNU387, Hep3B, Mahlavu, and Huh7 cell lines. Sequential combination treatment of Huh7 and Mahlavu with ovatodiolide followed by antrocin resulted stronger cytotoxic effect than did treatment with antrocin followed by ovatodiolide, their simultaneous administration, antrocin alone, or ovatodiolide alone. In the Huh7 and Mahlavu cell lines, ovatodiolide→antrocin significantly suppressed colony formation and proliferation as well as markedly downregulated ERK1/2, Akt, and mTOR expression. Inhibition of ERK1/2 and Akt/mTOR signaling by ovatodiolide→antrocin suppressed ribosomal biogenesis, autophagy, and cancer stem cell-like phenotypes and promoted apoptosis in Huh7 and Mahlavu cells. The sorafenib-resistant clone of Huh7 was effectively inhibited by synergistic combination of both compound in vitro. Eventually, the ovatodiolide→antrocin combination synergistically suppressed the growth of HCC xenografts. Taken together, our findings suggested that ovatodiolide→antrocin combination may represent potential therapeutic approach for patients with advanced HCC. [ABSTRACT FROM AUTHOR]

The effect of the pore structure of SBA-15, which is tuned by varying the hydrothermal temperature (90–150 °C), is investigated on nitrogen-doped ordered mesoporous carbon. It is found that the pore structure of SBA-15 yields effects on both the composition and the pore structure of carbon, which thereby affecting its electrocatalytic activity for the oxygen reduction reaction (ORR). XPS reveals that the nitrogen content of the template-free carbon is 2.79 at.%, while dramatically increases to 4.48, 5.01 and 4.16 at.% for the three template-aided carbon catalysts with SBA-15 synthesized at 90, 130 and 150 °C, respectively. Nitrogen ad/desorption isotherms show that the specific surface area of the template-free carbon is 257 m 2 g −1 , which increases to 724, 731 and 691 m 2 g −1 for the above three carbons. Such changes correlate well with the electrochemical results. RRDE results show that the template-aided carbon catalysts yield better activity and selectivity for the ORR than does the template-free one. And the best performance is achieved for the carbon catalyst with SBA-15 synthesized at 130 °C, which coincidentally has the highest nitrogen content and surface area. [ABSTRACT FROM AUTHOR]

The dynamic performance of vertical cylindrical storage tanks under lateral impact of explosive fragments is important for its safe loading. In this paper, the method of combining experiments and numerical simulation is employed. Based on the simplified scaled model of thin-walled cylindrical containers, the lateral impact model experiments are carried out by using the drop hammer impact tester. Typical deformations and failure modes of the structure are then obtained. After processing the experimental data to obtain the load-deformation curve and the absorption energy curve, the curves are analyzed to study the dynamical response characteristics for cylindrical containers under impact as well as the influences for container length and impact velocity on the structural dynamical response. Then, the LS-DYNA program is applied for simulating the impact procedure and its dynamic response. With the reliability of the numerical model being verified, the stress distribution of the cylindrical container during the impact process is analyzed. Through finite element parametric analyses, combined with experimental results, the influences of impact velocity, length-to-radius ratio and radius-to-thickness ratio on dynamical responses as well as failure modes of the structure are investigated. It is shown that the failure mode of the cylindrical container changes with impact velocity and radius-to-thickness ratio, but is not affected by length-to-radius ratio. The variation of peak deformation and average force of the structure with parameters such as impact velocity are obtained. • Dynamic performance of cylindrical tank under lateral impact of explosive fragments is obtained. • Dynamic response of a thin-walled cylindrical container subjected to lateral impact can be divided into four stages. • Polygonal depressed region appear in the middle of container wall with a dividing line and local wrinkles at both ends. • Failure mode of container changes with impact velocity and R/t ratio, but not affected by L/R ratio. [ABSTRACT FROM AUTHOR]

To assess whether drinking tea can effectively prevent smoking-induced atherosclerosis, a clinical trial ex vivo study was performed. The volunteers were randomly allocated to two groups (n = 55 per group) that received either Pu-erh tea powder or a cellulose placebo (0.5 g/capsule, T.I.D.) for two months. The circulating monocytes were isolated from the tested individuals after 0, 1, and 2 months of tea-capsule administration. We found that monocytes displaying high α9-nicotinic-acetylcholine-receptor (α9-nAchR) expression that were isolated from heavy smokers before consuming tea capsules tended to form foam cells in response to nicotine (1 µL for 24 h, * P  < 0.001). In contrast, long-term tea consumption significantly downregulated the monocytic α9-nAchR expression (0 months vs. 1 and 2 months; # P  = 0.013 and ## P  = 0.004, respectively) which causes circulating monocytes to resist nicotine-induced foam cell formation even in heavy-smokers (* P  < 0.001). This study suggests that tea-drinking effectively attenuates the initial step (foam-cell formation) of smoking-induced atherosclerosis in circulating monocytes. [ABSTRACT FROM AUTHOR]

The orbital angular momentum (OAM) carried by vortex beams provides new possibilities for optical communication multiplexing. OAM modes can also carry information due to their helical-phase wave fronts, providing a new mechanism for optical fiber sensing. In this paper, a novel image detection scheme based on OAM intermodal interference in few-mode fibers is proposed. Temperature and strain are measured simultaneously based on components with different azimuthal distributions in the interference pattern. The sensing mechanism and demodulation principle of the proposed sensor are studied, and the linear response range and anti-interference capability are analyzed. Simulation results show that the variations in temperature and strain can be simultaneously demodulated by using a single image obtained at the output of the sensing fiber at a single working wavelength. External optical noise and the internal modal intensity fluctuations, have little effect on the temperature and strain sensitivities of the proposed sensor. The intermodal sensors based on OAM modes have a larger linear response range and better anti-interference capabilities than intermodal sensors based on linear polarization modes. [ABSTRACT FROM AUTHOR]

Abstract: Effects of the phenicol antibiotic, florfenicol (0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 mg/L), on marine diatom Skeletonema costatum were investigated in this study. Florfenicol was found to stimulate algal growth at concentrations of 0.5, 1.0 and 2.0 mg/L, and significantly inhibit algal growth at >2.0 mg/L. The highest inhibition rate was up to 86% at 16.0 mg/L and the IC50 for 96 h growth was 5.043 mg/L. The chlorophyll a and effective quantum yield () were significantly inhibited at 6, 24 and 96 h when florfenicol concentrations were ≥4.0 mg/L. Intracellular reactive oxygen species (ROS) production was enhanced significantly over the control when florfenicol concentrations were ≥1.0 mg/L at 6 h with the dose-dependent trends possibly due to the inhibition of photosynthesis. Since the membrane is highly prone to ROS attack, overproduction of ROS may cause deteriorated integrity and permeability of the cell membrane. Consequently, intracellular pH was found to increase with the increases in dosage; cell size swelled significantly when alga was exposed to florfenicol concentrations up to 8.0 mg/L. These deteriorations finally led to the decrease of cell viability as indicated by both fluorescein diacetate (FDA) assay and propidium iodide (PI) staining, in which viability was shown to decrease significantly at higher doses (4.0, 8.0, 16.0 mg/L). It can be concluded that S. costatum was vulnerable to florfenicol. [Copyright &y& Elsevier]

Abstract: Linear instability method has been adopted in this analysis to predict the Forming Limit Diagrams (FLDs), and the traditional instability analysis has been modified to account for strain rate effect. The initiation and growth of instability have been considered by examining the role of material work-hardening and strain rate sensitivity in affecting the limit strains. It is found that the initiation of the deformation instability is independent of the strain rate-sensitivity, while it affects the quasi-static stage of deformation. After the initiation of the deformation instability, the perturbation growth rate is different for different deformation conditions. For strain rate independent materials, the perturbation can grow into an observable neck just after the critical strain is reached when the strain ratio is negative; while the perturbation growth rate decreases with the increase of the strain ratio for the right hand side of forming limit diagrams. Material strain rate sensitivity reduces this perturbation growth rate, and it is expected that the deformation has longer quasi-stable deformation with strain rate sensitivity. For the left hand side of forming limit diagrams, the predicted angle is in the zero extension direction which coincides with that obtained by Hill in 1952; while the instability will take place along the minor strain direction for the positive strain ratio. The present predictions correlate well with experimental observations. [Copyright &y& Elsevier]