Influenza virus and coronavirus, belonging to enveloped RNA viruses, are major causes of human respiratory diseases. The aim of this study was to investigate the broad spectrum antiviral activity of ...a naturally existing sulfated polysaccharide, lambda-carrageenan (λ-CGN), purified from marine red algae. Cell culture-based assays revealed that the macromolecule efficiently inhibited both influenza A and B viruses with EC
values ranging from 0.3 to 1.4 μg/ml, as well as currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an EC
value of 0.9 ± 1.1 μg/ml. No toxicity to the host cells was observed at concentrations up to 300 μg/ml. Plaque titration and western blot analysis verified that λ-CGN reduced expression of viral proteins in cell lysates and suppressed progeny virus production in culture supernatants in a dose-dependent manner. This polyanionic compound exerts antiviral activity by targeting viral attachment to cell surface receptors and preventing virus entry. Moreover, its intranasal administration to mice during influenza A viral challenge not only alleviated infection-mediated reductions in body weight but also protected 60% of mice from virus-induced mortality. Thus, λ-CGN could be a promising antiviral agent for preventing infection with several respiratory viruses.
Electrospun polymeric piezoelectric fibers have a considerable potential for shape‐adaptive mechanical energy harvesting and self‐powered sensing in biomedical, wearable, and industrial applications. ...However, their unsatisfactory piezoelectric performance remains an issue to be overcome. While strategies for increasing the crystallinity of electroactive β phases have thus far been the major focus in realizing enhanced piezoelectric performance, tailoring the fiber morphology can also be a promising alternative. Herein, a design strategy that combines the nonsolvent‐induced phase separation of a polymer/solvent/water ternary system and electrospinning for fabricating piezoelectric poly(vinylidene fluoride‐trifluoroethylene) (P(VDF‐TrFE) fibers with surface porosity under ambient humidity is presented. Notably, electrospun P(VDF‐TrFE) fibers with higher surface porosity outperform their smooth‐surfaced counterparts with a higher β phase content in terms of output voltage and power generation. Theoretical and numerical studies also underpin the contribution of the structural porosity to the harvesting performance, which is attributable to local stress concentration and reduced dielectric constant due to the air in the pores. This porous fiber design can broaden the application prospects of shape‐adaptive energy harvesting and self‐powered sensing based on piezoelectric polymer fibers with enhanced voltage and power performance, as successfully demonstrated in this work by developing a communication system based on self‐powered motion sensing.
Structural porosity significantly affects the overall piezoelectric performance to a larger extent than the crystalline β‐phase content, which has been the sole focus thus far. The key to fabricating porous fibers lies in the combination of a nonsolvent‐induced phase separation method based on the thermodynamics of the polymer solution and the electrospinning process that controls the kinetics of fiber formation.
Many studies have reported the effect of hypertension on microcirculation of the retina. Advance of optical coherence tomography angiography (OCTA) allows us more detailed observations of ...microcirculation of the retina. Therefore, we compared OCTA parameters between chronic hypertension (disease duration of at least 10 yrs; Group A, 45 eyes), relieved hypertensive retinopathy (grade IV HTNR < 1 yr prior; Group B, 40 eyes), and normal controls Group C (50 eyes) ≥ 50 yrs old and Group D (50 eyes) < 50 yrs old. A 3 × 3 mm macular scan was performed in each group by OCTA. In vessel density of 3 mm full, group A and B were significantly decreased compared to normal control group (Group A vs. C; 19.4 mm
vs. 20.1 mm
, Group B vs. D; 19.8 mm
vs. 21.8 mm
, all p < 0.05). In foveal avascular zone, group A and B were significantly increased compared to normal control group (Group A vs. C; 0.35 mm
vs. 0.30 mm
, Group B vs. D; 0.36 mm
vs. 0.29 mm
, all p < 0.05). OCTA is useful for examining retinal microcirculatory changes in hypertension and we confirmed that hypertension affects the OCTA parameters. Considering the effect of hypertension on the change of microvasculature, care is required in the interpretation of OCTA parameters in various ophthalmic condition.
Soluble epoxide hydrolase (sEH) is an enzyme targeted for the treatment of inflammation and cardiovascular diseases. Activated inflammatory cells produce nitric oxide (NO), which induces oxidative ...stress and exacerbates inflammation. We identify an inhibitor able to suppress sEH and thus NO production. Five flavonoids
-
isolated from
flowers were evaluated for their abilities to inhibit sEH with IC
values of 12.1 ± 0.1 to 62.8 ± 1.8 µM and for their effects on enzyme kinetics. A simulation study using computational chemistry was conducted as well. Furthermore, five inhibitors (
-
) were confirmed to suppress NO levels at 10 µM. The results showed that flavonoids
-
exhibited inhibitory activity in all tests, with compound
exhibiting the most significant efficacy. Thus, in the development of anti-inflammatory inhibitors, compound
is a promising natural candidate.
Objectives
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry into the host cells depends on the expression of angiotensin‐converting enzyme 2 (ACE2) and transmembrane protease serine ...2 (TMPRSS2). We investigated the distribution of ACE2‐ and TMPRSS2‐expressing cells in various oral tissues to identify the underlying mechanism of oral manifestations in patients with coronavirus disease 2019.
Subjects
We analyzed the expression patterns of ACE2 and TMPRSS2 in the oral mucosa (tongue, palate, and buccal mucosa), trigeminal ganglion, vessels, and salivary glands of 9 Sprague‐Dawley rats using immunohistochemistry and immunofluorescence.
Results
ACE2 and TMPRSS2 were strongly expressed in the intermediate layer of the squamous epithelia of tongue papillae and buccal mucosa. ACE2‐ and TMPRSS2‐positive cells were observed in the taste buds of the tongue. Additionally, ACE2 and TMPRSS2 were co‐expressed in the ductal epithelium and acinar cells of salivary glands. Furthermore, both ACE2 and TMPRSS2 were stained in the neuronal cell body of trigeminal ganglia, but not in Schwann cells. Moreover, ACE2 and TMPRSS2 were expressed in capillaries, but not in venules/arterioles.
Conclusions
SARS‐CoV‐2 can spread the suprabasal area of squamous epithelia of the oral mucosa, invades taste bud, trigeminal nerve, parotid gland, and microvessel, resulting in oral manifestations.
Lanthanide-doped upconverting nanoparticles (UCNPs) have recently attracted enormous attention in the field of biological imaging owing to their unique optical properties: (1) efficient upconversion ...photoluminescence, which is intense enough to be detected at the single-particle level with a (nonscanning) wide-field microscope setup equipped with a continuous wave (CW) near-infrared (NIR) laser (980 nm), and (2) resistance to photoblinking and photobleaching. Moreover, the use of NIR excitation minimizes adverse photoinduced effects such as cellular photodamage and the autofluorescence background. Finally, the cytotoxicity of UCNPs is much lower than that of other nanoparticle systems. All these advantages can be exploited simultaneously without any conflicts, which enables the establishment of a novel UCNP-based platform for wide-field two-photon microscopy. UCNPs are also useful for multimodal in vivo imaging because simple variations in the composition of the lattice atoms and dopant ions integrated into the particles can be easily implemented, yielding various distinct biomedical activities relevant to magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). These multiple functions embedded in a single type of UCNPs play a crucial role in precise disease diagnosis. The application of UCNPs is extended to therapeutic fields such as photodynamic and photothermal cancer therapies through advanced surface conjugation schemes.
•Ischemic brain injury impaired cognitive function at 28 days post-stroke in mice.•Ischemic brain injury triggered AIM2 inflammasome-mediated inflammation within 7 days post-stroke.•Microglia- or ...endothelial cell-induced AIM2 production mediated PSCI pathogenesis.•AIM2 inflammasome-induced pyroptosis may contribute to acute and chronic neuronal death after stroke.•AIM2 KO and administration of the caspase-1 inhibitor, Ac-YVAD-CMK, attenuated long-term cognitive deficits.
Although over one-third of stroke patients may develop post-stroke cognitive impairment (PSCI), the mechanisms underlying PSCI remain unclear. We explored here, the involvement of post-stroke inflammasomes in long-term PSCI development, using a 45 min-middle cerebral artery occlusion (MCAO)/reperfusion-induced PSCI model. Immunohistological assessment on day 1, 3, and 7 was followed by cognitive function test 28 days post-stroke. Evaluation of inflammasome sensor gene expression in aged mouse brains showed dominant expression of absent in melanoma 2 (Aim2) in 6-, 12-, and 18-month-old mouse brains. AIM2 mRNA and protein increased until 7 days post-stroke. PSCI decreased anxiety in elevated plus maze test and impaired spatial learning and memory functions in Morris water maze test 28 days post-stroke. AIM2 and other inflammasome subunit immunoreactivities, including those for caspase-1, interleukin (IL)-1β, and IL-18, were higher in the hippocampus and cortex of the PSCI than in those of the sham group 7 days post-stroke. AIM2 immunoreactivity of the PSCI group was primarily co-localized with Iba-1 (microglial marker) and CD31 (endothelial cell marker) immunoreactivities but not NeuN (neuronal marker) and GFAP (astrocyte marker) immunoreactivities, suggesting that microglia or endothelial cell-induced AIM2 production mediated PSCI pathogenesis. Additionally, inflammasome-induced pyroptosis might contribute to acute and chronic neuronal death after stroke. AIM2 knockout (KO) and Ac-YVAD-CMK-induced caspase-1 inhibition in mice significantly improved cognitive function and reversed brain volume in the hippocampus relative to those in stroke mice. Conclusively, AIM2 inflammasome-mediated inflammation and pyroptosis likely aggravated PSCI; therefore, targeting and controlling AIM2 inflammasome could potentially treat PSCI.
Assessment of functional independence and residual disability is very important for measuring treatment outcome after stroke. The modified Rankin Scale (mRS) and the modified Barthel Index (MBI) are ...commonly used scales to measure disability or dependence in activities of daily living (ADL) of stroke survivors. Lack of consensus regarding MBI score categories has caused confusion in interpreting stroke outcomes. The purpose of this study was to identify the optimal corresponding MBI and modified Rankin scale (mRS) grades for categorization of MBI. The Korean versions of the MBI (K-MBI) and mRS were collected from 5,759 stroke patients at 3 months after onset of stroke. The sensitivity and specificity were calculated at K-MBI score cutoffs for each mRS grade to obtain optimally corresponding K-MBI scores and mRS grades. We also plotted receiver operating characteristic (ROC) curves of sensitivity and specificity and determined the area under the curve (AUC). The K-MBI cutoff points with the highest sum of sensitivity and specificity were 100 (sensitivity 0.940; specificity 0.612), 98 (sensitivity 0.904; specificity 0.838), 94 (sensitivity 0.885; specificity 0.937), 78 (sensitivity 0.946; specificity, 0.973), and 55 (sensitivity 937; specificity 0.986) for mRS grades 0, 1, 2, 3, and 4, respectively. From this result, the K-MBI cutoff score range for each mRS grade can be obtained. For mRS grade 0, the K-MBI cutoff score is 100, indicating no associated score range. For mRS grades 1, 2, 3, 4, and 5, the K-MBI score ranges is from 99 to 98, 97 to 94, 93 to 78, 77 to 55, and under 54, respectively.The AUC for the ROC curve was 0.791 for mRS grade 0, 0.919 for mRS grade 1, 0.970 for mRS grade 2, 0.0 for mRS grade 3, and 0.991 for mRS grade 4. The K-MBI cutoff score ranges for representing mRS grades were variable; mRS grades 0, 1, and 2 had narrow K-MBI score ranges, while mRS grades 3, 4, and 5 exhibited broad K-MBI score ranges. mRS grade seemed to sensitively differentiate mild residual disability of stroke survivors, whereas K-MBI provided more specific information of the functional status of stroke survivors with moderate to severe residual impairment.
Solution studies have proposed that crystal nucleation can take more complex pathways than previously expected in classical nucleation theory, such as formation of prenucleation clusters or densified ...amorphous/liquid phases. These findings show that it is possible to separate fluctuations in the different order parameters governing crystal nucleation, that is, density and structure. However, a direct observation of the multipathways from aqueous solutions remains a great challenge because heterogeneous nucleation sites, such as container walls, can prevent these paths. Here, we demonstrate the existence of multiple pathways of nucleation in highly supersaturated aqueous KH₂PO₄ (KDP) solution using the combination of a containerless device (electrostatic levitation), and in situ micro-Raman and synchrotron X-ray scattering. Specifically, we find that, at an unprecedentedly deep level of supersaturation, a high-concentration KDP solution first transforms into a metastable crystal before reaching stability at room temperature. However, a low-concentration solution, with different local structures, directly transforms into the stable crystal phase. These apparent multiple pathways of crystallization depend on the degree of supersaturation.
Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a ...label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients ('at risk brains') from those with better prognosis or to discriminate Alzheimer's disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing.
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