There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. ...Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3′ sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.
Middle East respiratory syndrome‐coronavirus (MERS‐CoV) is a zoonotic virus transmitted between animals and human beings. It causes MERS with high mortality rate. However, no vaccine or specific ...treatment is currently available. Since antiviral activity of some flavonoids is known, we applied a flavonoid library to probe inhibitory compounds against MERS‐CoV 3C‐like protease (3CLpro). Herbacetin, isobavachalcone, quercetin 3‐β‐d‐glucoside and helichrysetin were found to block the enzymatic activity of MERS‐CoV 3CLpro. The binding of the four flavonoids was also confirmed independently using a tryptophan‐based fluorescence method. The systematic comparison of the binding affinity of flavonoids made it possible to infer their scaffolds and functional groups required to bind with MERS‐CoV 3CLpro. An induced‐fit docking analysis revealed that S1 and S2 sites play a role in interaction with flavonoids. The experimental and computational study showed that flavonol and chalcone are favourite scaffolds to bind with the catalytic site of MERS‐CoV 3CLpro. It was also deduced that some flavonoid derivatives with hydrophobic or carbohydrate attached to their core structures have a good inhibitory effect. Therefore, we suggest that flavonoids with these characteristics can be used as templates to develop potent MERS‐CoV 3CLpro inhibitors.
MERS‐CoV 3CLpro was assayed with a flavonoid library and some chalcone derivatives represented promising inhibitory activity. The docking study confirmed the experimental measurement of the better efficacy of helichrysetin than cardamonin. This study showed the antiviral effect of flavonoids in the atomic level.
Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, ...previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses.
Coronavirus disease 2019 (COVID-19) has been a pandemic disease of which the termination is not yet predictable. Currently, researches to develop vaccines and treatments is going on globally to cope ...with this disastrous disease. Main protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the good targets to find antiviral agents before vaccines are available. Some flavonoids are known to inhibit 3CLpro from SARS-CoV which causes SARS. Since their sequence identity is 96%, a similar approach was performed with a flavonoid library. Baicalin, herbacetin, and pectolinarin have been discovered to block the proteolytic activity of SARS-CoV-2 3CLpro. An in silico docking study showed that the binding modes of herbacetin and pectolinarin are similar to those obtained from the catalytic domain of SARS-CoV 3CLpro. However, their binding affinities are different due to the usage of whole SARS-CoV-2 3CLpro in this study. Baicalin showed an effective inhibitory activity against SARS-CoV-2 3CLpro and its docking mode is different from those of herbacetin and pectolinarin. This study suggests important scaffolds to design 3CLpro inhibitors to develop antiviral agents or health-foods and dietary supplements to cope with SARS-CoV-2.
The aims of this study are to evaluate the cost-effectiveness of early dental visits (EDVs) and to investigate how regional deprivation impacts the economic evaluation.
This study used the South ...Korea National Health Insurance database, which included medical claim data and voluntary-based oral examination data. The subjects of this study included whole participants for oral examinations for infants and toddlers of the National Health Insurance Corporation. A retrospective cohort study was designed and measured all oral treatments, costs, and number of visits for 208,969 children (experimental group, 101,768; non- experimental group, 107,201) who underwent oral examination for infants and toddlers from 2007 to 2014. The cost-effectiveness was measured using the incremental cost-effectiveness ratio, and the T-health index was used as the measurement for effectiveness. In addition, the difference in the effect according to the level of regional deprivation was confirmed.
The findings of this study showed that EDVs were cost-effective and that children who participated in EDVs had better oral health (T-health-2 index difference 0.32 point in most deprived regions) and needed 5 USD less costly dental treatments than those who did not have EDVs. The cost-effectiveness of EDVs varied according to the level of regional deprivation and was the highest in the most deprived regions.
The study findings suggested that the provision of oral examination for infants and toddlers was a cost-effective dental policy. Additionally, EDVs were more effective in children who resided in the most deprived regions, a finding that will lead to the development of policy intervention to improve dental care despite spatial inequality for disadvantaged population groups. Regarding the distribution of dental hospitals/clinics, incentive based dental polices for either dental providers or patients are needed that will assure the delivery of dental care despite spatial inequality.
Transparent and stretchable electronics with remarkable bendability, conformability, and lightness are the key attributes for sensing or wearable devices. Transparent and stretchable field‐effect ...transistor sensors using graphene–metal nanowire hybrid nanostructures have high mobility (≈3000 cm2 V−1 s−1) with low contact resistance, and they are transferrable onto a variety of substrates. The integration of these sensors for RLC circuits enables wireless monitoring.
Transparent electrodes that can remain electrically conductive and stable under large mechanical deformations are highly desirable for applications in flexible and wearable electronics. This paper ...describes a comprehensive study of the electrical, optical, and mechanical properties of hybrid nanostructures based on two-dimensional graphene and networks of one-dimensional metal nanowires, and their use as transparent and stretchable electrodes. Low sheet resistance (33 Ω/sq) with high transmittance (94% in visible range), robust stability against electric breakdown and oxidation, and superb flexibility (27% in bending strain) and stretchability (100% in tensile strain) are observed, and these multiple functionalities of the hybrid structures suggest a future promise for next generation electronics. The use of hybrid electrodes to fabricate oxide semiconductor transistors and single-pixel displays integrated on wearable soft contact lenses with in vivo tests are demonstrated.
Sensory axons degenerate following separation from their cell body, but partial injury to peripheral nerves may leave the integrity of damaged axons preserved. We show that an endogenous ligand for ...the natural killer (NK) cell receptor NKG2D, Retinoic Acid Early 1 (RAE1), is re-expressed in adult dorsal root ganglion neurons following peripheral nerve injury, triggering selective degeneration of injured axons. Infiltration of cytotoxic NK cells into the sciatic nerve by extravasation occurs within 3 days following crush injury. Using a combination of genetic cell ablation and cytokine-antibody complex stimulation, we show that NK cell function correlates with loss of sensation due to degeneration of injured afferents and reduced incidence of post-injury hypersensitivity. This neuro-immune mechanism of selective NK cell-mediated degeneration of damaged but intact sensory axons complements Wallerian degeneration and suggests the therapeutic potential of modulating NK cell function to resolve painful neuropathy through the clearance of partially damaged nerves.
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•Cytotoxic NK cells infiltrate the damaged peripheral nerve within days of injury•Injured sensory axons express NKG2D ligand RAE1 to signal degeneration by NK cells•Clearance of damaged axons reduces development of chronic pain after nerve injury•NK cells complement Wallerian degeneration to aid functional regeneration of PNS
Pain following nerve damage can be mitigated by cytotoxic natural killer cells that selectively clear out partially damaged nerves.
Replication-Factor-C (RFC) and RFC-like complexes (RLCs) mediate chromatin engagement of the proliferating cell nuclear antigen (PCNA). It remains controversial how RFC and RLCs cooperate to regulate ...PCNA loading and unloading. Here, we show the distinct PCNA loading or unloading activity of each clamp loader. ATAD5-RLC possesses the potent PCNA unloading activity. ATPase motif and collar domain of ATAD5 are crucial for the unloading activity. DNA structures did not affect PCNA unloading activity of ATAD5-RLC. ATAD5-RLC could unload ubiquitinated PCNA. Through single molecule measurements, we reveal that ATAD5-RLC unloaded PCNA through one intermediate state before ATP hydrolysis. RFC loaded PCNA through two intermediate states on DNA, separated by ATP hydrolysis. Replication proteins such as Fen1 could inhibit the PCNA unloading activity of Elg1-RLC, a yeast homolog of ATAD5-RLC in vitro. Our findings provide molecular insights into how PCNA is released from chromatin to finalize DNA replication/repair.
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