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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aim
The presence of periodontal disease (PD) at a single time point has been suggested as a predictor of diabetes risk, but whether changes in PD status are associated with altered risk of diabetes ...is yet to be reported on a population scale. This study investigated whether recovery from or development of PD in a population is associated with an altered risk of diabetes occurrence.
Materials and Methods
Data of subjects who received health screening from 2002 to 2007 were obtained from the National Health Insurance Service–National Health Screening cohort database of Korea. Patients with a history of diabetes were excluded. Changes in PD status were determined from the first two health screenings. Study subjects were divided into four groups according to the changes in PD status: PD‐free, PD‐recovered, PD‐developed, and PD‐chronic. The outcome was the occurrence of diabetes.
Results
Overall, 111,611 subjects were included for analysis. During a median follow‐up of 9.10 years, diabetes developed in 6102 subjects. The adjusted hazard ratios (HRs) for incident diabetes across various PD change groups (in reference to the PD‐free group) were as follows: PD‐chronic group = 1.096 (95% confidence interval CI 1.026–1.170, p = .006); PD‐developed group = 1.073 (95% CI 0.993–1.159, p = .075); and PD‐recovered group = 1.019 (95% CI 0.945–1.100, p = .622). The subjects who recovered from PD had a lower diabetes risk than those who had consistent PD (adjusted HR 0.930, 95% CI 0.865–1.000, p = .050), whereas those who developed PD had a higher risk of diabetes than those who remained PD‐free.
Conclusion
The longitudinal change in PD status is associated with incident diabetes risk. Future intervention studies are necessary to determine whether PD treatment can prevent incident diabetes.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, ...pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
We have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes ...with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP
mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.
Various wearable electronic devices have been developed for extensive outdoor activities. The key metrics for these wearable devices are high touch sensitivity and good mechanical and thermal ...stability of the flexible touchscreen panels (TSPs). Their dielectric constants (k) are important for high touch sensitivities. Thus, studies on flexible and transparent cover layers that have high k with outstanding mechanical and thermal reliabilities are essential. Herein, an unconventional approach for forming flexible and transparent cellulose nanofiber (CNF) films is reported. These films are used to embed ultralong metal nanofibers that serve as nanofillers to increase k significantly (above 9.2 with high transmittance of 90%). Also, by controlling the dimensions and aspect ratios of these fillers, the effects of their nanostructures and contents on the optical and dielectric properties of the films have been studied. The length of the nanofibers can be controlled using a stretching method to break the highly aligned, ultralong nanofibers. These nanofiber‐embedded, high‐k films are mechanically and thermally stable, and they have better Young's modulus and tensile strength with lower thermal expansion than commercial transparent plastics. The demonstration of highly sensitive TSPs using high‐k CNF film for smartphones suggests that this film has significant potential for next‐generation, portable electronic devices.
Transparent and flexible cellulose films with a high dielectric performance using ultralong metal nanofibers are key attributes for flexible touchscreen panels (TSPs). High‐dielectric‐constant (k) CNF films using ultralong silver nanofibers have outstanding optical transmittance (≈90%) with high‐k values (k = 9.2 at 120 kHz). A TSP that is protected with a high‐k CNF film shows high touch sensitivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The interaction between histones and DNA is important for eukaryotic gene expression. A loose interaction caused, for example, by the neutralization of a positive charge on the histone surface by ...acetylation, induces a less compact chromatin structure, resulting in feasible accessibility of RNA polymerase and increased gene expression. In contrast, the formation of a tight chromatin structure due to the deacetylation of histone lysine residues on the surface by histone deacetylases enforces the interaction between the histones and DNA, which minimizes the chance of RNA polymerases contacting DNA, resulting in decreased gene expression. Therefore, the balance of the acetylation of histones mediated by histone acetylases (HATs) and histone deacetylases (HDACs) is an issue of transcription that has long been studied in relation to posttranslational modification. In this review, current knowledge of HDACs is briefly described with an emphasis on recent progress in research on HDACs, especially on class IIa HDACs.
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.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The hospitalist system has been introduced to improve the quality and safety of inpatient care. As its effectiveness has been confirmed in previous studies, the hospitalist system is spreading in ...various fields. However, few studies have investigated the feasibility and value of hospitalist-led care of patients with cancer in terms of quality and safety measures. This study aimed to evaluate the efficacy of the Hospitalist-Oncologist co-ManagemEnt (HOME) system.
Between January 1, 2019, and January 31, 2021, we analyzed 591 admissions before and 1068 admissions after the introduction of HOME system on January 1, 2020. We compared the length of stay and the types and frequencies of safety events between the conventional system and the HOME system, retrospectively. We also investigate rapid response system activation, cardiopulmonary resuscitation, unplanned intensive care unit transfer, all-cause in-hospital mortality, and 30-day re-admission or emergency department visits.
The average length of stay (15.9 days vs. 12.9 days, P < 0.001), frequency of safety events (5.6% vs. 2.8%, P = 0.006), rapid response system activation (7.3% vs. 2.2%, P < 0.001) were significantly reduced after the HOME system introduction. However, there was no statistical difference in frequencies of cardiopulomonary resuscitation and intensive care unit transfer, all-cause in-hospital morality, 30-day unplanned re-admission or emergency department visits.
The study suggests that the HOME system provides higher quality of care and safer environment compared to conventional oncologist-led team-based care, and the efficiency of the medical delivery system could be increased by reducing the hospitalization period without increase in 30-day unplanned re-admission.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A major challenge for implantable medical systems is the inclusion or reliable delivery of electrical power. We use ultrasound to deliver mechanical energy through skin and liquids and demonstrate a ...thin implantable vibrating triboelectric generator able to effectively harvest it. The ultrasound can induce micrometer-scale displacement of a polymer thin membrane to generate electrical energy through contact electrification. We recharge a lithium-ion battery at a rate of 166 microcoulombs per second in water. The voltage and current generated ex vivo by ultrasound energy transfer reached 2.4 volts and 156 microamps under porcine tissue. These findings show that a capacitive triboelectric electret is the first technology able to compete with piezoelectricity to harvest ultrasound in vivo and to power medical implants.
Alcoholic liver disease (ALD) refers to the damages to the liver and its functions due to alcohol overconsumption. It consists of fatty liver/steatosis, alcoholic hepatitis, steatohepatitis, chronic ...hepatitis with liver fibrosis or cirrhosis, and hepatocellular carcinoma. However, the mechanisms behind the pathogenesis of alcoholic liver disease are extremely complicated due to the involvement of immune cells, adipose tissues, and genetic diversity. Clinically, the diagnosis of ALD is not yet well developed. Therefore, the number of patients in advanced stages has increased due to the failure of proper early detection and treatment. At present, abstinence and nutritional therapy remain the conventional therapeutic interventions for ALD. Moreover, the therapies which target the TNF receptor superfamily, hormones, antioxidant signals, and MicroRNAs are used as treatments for ALD. In particular, mesenchymal stem cells (MSCs) are gaining attention as a potential therapeutic target of ALD. Therefore, in this review, we have summarized the current understandings of the pathogenesis and diagnosis of ALD. Moreover, we also discuss the various existing treatment strategies while focusing on promising therapeutic approaches for ALD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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