ABSTRACT
Cellular senescence, which is triggered by various stressors, manifests as irreversible cell cycle arrest, resulting in the disruption of multiple nuclear condensates. One of the affected structures is the nucleolus, whose tripartite layout, separated into distinct liquid phases, allows for the stepwise progression of ribosome biogenesis. The dynamic properties of dense fibrillar components, a sub-nucleolar phase, are crucial for mediating pre-rRNA processing. However, the mechanistic link between the material properties of dense fibrillar components and cellular senescence remains unclear. We established a significant association between cellular senescence and alterations in nucleolar materiality and characteristics, including the number, size, and sphericity of individual subphases of the nucleolus. Senescent cells exhibit reduced fibrillarin dynamics, aberrant accumulation of high-order protein assemblies, such as oligomers and fibrils, and increased dense fibrillar component density. Intriguingly, the addition of RNA-interacting entities mirrored the diminished diffusion of fibrillarin in the nucleolus during cellular senescence. Thus, our findings contribute to a broader understanding of the intricate changes in the materiality of the nucleolus associated with cellular senescence and shed light on nucleolar dynamics in the context of aging and cellular stress.
ABSTRACT
3D printing has been widely used for on-demand prototyping of complex three-dimensional structures. In biomedical applications, PEDOT:PSS has emerged as a promising material in versatile bioelectronics due to its tissue-like mechanical properties and suitable electrical properties. However, previously developed PEDOT:PSS inks have not been able to fully utilize the advantages of commercial 3D printing due to its long post treatment times, difficulty in high aspect ratio printing, and low conductivity. We propose a one-shot strategy for the fabrication of PEDOT:PSS ink that is able to simultaneously achieve on-demand biocompatibility (no post treatment), structural integrity during 3D printing for tall three-dimensional structures, and high conductivity for rapid-prototyping. By using ionic liquid-facilitated PEDOT:PSS colloidal stacking induced by a centrifugal protocol, a viscoplastic PEDOT:PSS-ionic liquid colloidal (PILC) ink was developed. PILC inks exhibit high-aspect ratio vertical stacking, omnidirectional printability for generating suspended architectures, high conductivity (~286 S/cm), and high-resolution printing (~50 µm). We demonstrate the on-demand and versatile applicability of PILC inks through the fabrication of 3D circuit boards, on-skin physiological signal monitoring e-tattoos, and implantable bioelectronics (opto-electrocorticography recording, low voltage sciatic nerve stimulation and recording from deeper brain layers via 3D vertical spike arrays).
Subject(s)
Biocompatible Materials , Colloids , Electric Conductivity , Ionic Liquids , Polystyrenes , Printing, Three-Dimensional , Ionic Liquids/chemistry , Colloids/chemistry , Biocompatible Materials/chemistry , Animals , Polystyrenes/chemistry , Rats , Ink , Polymers/chemistry , Thiophenes/chemistry , Neurons/physiology , Bridged Bicyclo Compounds, Heterocyclic/chemistryABSTRACT
Metal-organic frameworks (MOFs) are of great interest for energy applications due to their high porosity, high charge storage capacity, and large number of active redox sites. It is important to enhance the performance of metal-organic frameworks through modification in order to increase their potential applications. Unique Fe nanoparticle (NP) in the Materials of Institute Lavoisier (MIL) series embedded in the carbon nanotube (CNT), FeNP@MIL-101(Fe)/CNT-based, nanocomposites have been synthesized using suitable hierarchical micromesoporous structures. These were fabricated by simple and straightforward solvothermal methods, and their electrochemical charge storage performance was investigated. The energy storage application using the FeNP@MIL -101(Fe)/CNT composite as a supercapacitor electrode was implemented for the first time. Various techniques were used to characterize this composite. It has excellent electrochemical properties when used as electrode material in 1 M KOH solution, including a high capacitance of up to 1305 F g-1 at 1 A g-1 and a long cycling stability of 95.7% capacitance retention after 10,000 cycles. Moreover, symmetric two-electrode electrochemical experiments showed that the composite achieved an energy density of 98.65 Wh kg-1 and a power density of 9000 W kg-1, The combination of microporous and mesoporous structures, increased surface area, and higher electrical conductivity are the main reasons for the high performance. The integration of FeNP@MIL-101(Fe) with the CNT creates new ion diffusion pathways, improves the hierarchical pore properties, and exposes the FeNP@MIL-101(Fe) cluster to more redox active sites, which improves the charge storage performance.
ABSTRACT
Mild, metal-free, and operationally simple three-component coupling reactions involving arynes, phosphites, and acrylates have been achieved. The reaction proceeded well with α- or ß-substituted acrylates. Additionally, various functional groups were tolerated under these reaction conditions, resulting in diverse ortho-3-propanoate-substituted aryl phosphonates. Moreover, the reaction can be used to synthesize a range of organophosphorus compounds present in natural products, materials, and biologically active compounds.
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Viral pathogens, particularly influenza and SARS-CoV-2, pose a significant global health challenge. Given the immunomodulatory properties of human milk oligosaccharides, in particular 2'-fucosyllactose and 3-fucosyllactose (3-FL), we investigated their dietary supplementation effects on antiviral responses in mouse models. This study revealed distinct immune modulations induced by 3-FL. RNA-sequencing data showed that 3-FL increased the expression of interferon receptors, such as Interferon Alpha and Beta Receptor (IFNAR) and Interferon Gamma Receptor (IFNGR), while simultaneously downregulating interferons and interferon-stimulated genes, an effect not observed with 2'-fucosyllactose supplementation. Such modulation enhanced antiviral responses in both cell culture and animal models while attenuating pre-emptive inflammatory responses. Nitric oxide concentrations in 3-FL-supplemented A549 cells and mouse lung tissues were elevated exclusively upon infection, reaching 5.8- and 1.9-fold increases over control groups, respectively. In addition, 3-FL promoted leukocyte infiltration into the site of infection upon viral challenge. 3-FL supplementation provided protective efficacy against lethal influenza challenge in mice. The demonstrated antiviral efficacy spanned multiple influenza strains and extended to SARS-CoV-2. In conclusion, 3-FL is a unique immunomodulator that helps protect the host from viral infection while suppressing inflammation prior to infection.
Subject(s)
Trisaccharides , Animals , Mice , Humans , Trisaccharides/pharmacology , Trisaccharides/immunology , A549 Cells , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/drug therapy , Female , SARS-CoV-2/immunology , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , COVID-19/immunology , Mice, Inbred BALB C , Disease Models, Animal , Dietary Supplements , Nitric Oxide/metabolism , Influenza, Human/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Lung/immunology , Lung/virology , OligosaccharidesABSTRACT
BACKGROUND: Due to the increasing proportion of older adults in Korea and growing interest in aging, the concepts of oral aging and oral hypofunction have recently been introduced. Thus, it is necessary to investigate the age-specific oral function levels of Korean older adults and develop expert intervention methods for healthy aging. METHODS: Dysphagia, independence of daily living, and oral hypofunction were assessed in 206 older adults living in Wonju, Gangwon State, South Korea. Subjective dysphagia was assessed through self-report questionnaires using the Dysphagia Handicap Index (DHI), the Korean version of Eating Assessment Tool-10, and the Korean version of the Modified Barthel Index. In addition, the oral hypofunction assessment items included decreased chewing ability, occlusal pressure, tongue pressure, oral dryness, and oral cleanliness. RESULTS: DHI increased significantly with age, with those in their 80 s reporting the most difficulty swallowing. Oral function in terms of chewing ability (maximum occlusal pressure and number of remaining teeth), maximum occlusal pressure, and maximum tongue pressure also declined with increasing age. While there was no significant difference in oral dryness by age, those in their 80 s had dry mouth according to the criteria of the oral moisture checking device. CONCLUSIONS: In an assessment of oral function in community-dwelling, independent Korean older adults, the number of items that were assessed as oral hypofunction increased with age. The findings can be used to standardize the oral hypofunction assessment item and develop age-based individualized intervention plans for the early management of oral health and individual oral myofunctional rehabilitation in Korean community-dwelling older adults.
Subject(s)
Deglutition Disorders , Xerostomia , Humans , Aged , Independent Living , Pressure , Tongue , Oral Health , Geriatric AssessmentABSTRACT
Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, predicting and preventing PTB are important. In this study, we investigated the potential of using short-chain fatty acid (SCFA) levels, specific vaginal microbiota-derived metabolites, as a biomarker in predicting PTB using gas chromatography/mass spectrometry. Cervicovaginal fluid (CVF) was collected from 89 pregnant women (29 cases of PTB vs. 60 controls) without evidence of other clinical infections, and SCFA levels were measured. Furthermore, the PTB group was divided into two subgroups based on birth timing after CVF sampling: delivery ≤ 2 days after sampling (n = 10) and ≥2 days after sampling (n = 19). The concentrations of propionic acid, isobutyric acid, butyric acid, valeric acid, hexanoic acid, and heptanoic acid were significantly higher in the PTB group than in the term birth (TB) group (p < 0.05). In particular, the concentrations of propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid were continuously higher in the PTB group than in the TB group (p < 0.05). In the delivery ≤ 2 days after sampling group, the propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid levels were significantly higher than those in the other groups (p < 0.05). This study demonstrated a significant association between specific SCFAs and PTB. We propose these SCFAs as potential biomarkers for the prediction of PTB.
Subject(s)
Caproates , Isobutyrates , Premature Birth , Propionates , Pregnancy , Female , Infant, Newborn , Humans , Premature Birth/metabolism , Mass Spectrometry , Fatty Acids, Volatile , Biomarkers/metabolismABSTRACT
PURPOSE: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17ß-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). MATERIALS AND METHODS: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague-Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17ß-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. RESULTS: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. CONCLUSIONS: CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.
ABSTRACT
PURPOSE: The primary goal of this study is to evaluate the effect of the non-invasive radiofrequency hyperthermia (RFHT) device on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) rat model and investigate the underlying mechanism. MATERIALS AND METHODS: In this study, Sprague-Dawley rats were randomly distributed into three groups: (1) normal control group, (2) CP/CPPS group, and (3) RFHT group. CP/CPPS rat models were induced by 17ß-estradiol and dihydrotestosterone for 4 weeks and RFHT was administered for 5 weeks after model establishment. During RFHT administration, core body temperatures were continuously monitored with a rectal probe. After administering RFHT, we assessed pain index for all groups and collected prostate tissues for Western blot analysis, immunofluorescence, and immunohistochemistry. We also collected adjacent organs to the prostate including urinary bladder, testes, and rectum for safety assessment via H&E staining along with a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. RESULTS: After administering RFHT, pain in rats was significantly alleviated compared to the CP/CPPS group. RFHT reduced high-mobility group box 1 (HMGB1) expression and improved inflammation by downregulating subsequent proinflammatory cytokines through inhibition of the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. In prostate-adjacent organs, no significant histological alteration or inflammatory infiltration was detected. The area of cell death also did not increase significantly after RFHT. CONCLUSIONS: In conclusion, RFHT demonstrated anti-inflammatory effects by inhibiting the HMGB1-TLR4-NF-κB pathway in CP/CPPS rat models. This suggests that RFHT could serve as a safe and promising therapeutic strategy for CP/CPPS.
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The decreasing efficacy of antiviral drugs due to viral mutations highlights the challenge of developing a single agent targeting multiple strains. Using host cell viral receptors as competitive inhibitors is promising, but their low potency and membrane-bound nature have limited this strategy. In this study, the authors show that angiotensin-converting enzyme 2 (ACE2) in a planar membrane patch can effectively neutralize all tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that emerged during the COVID-19 pandemic. The ACE2-incorporated membrane patch implemented using nanodiscs replicated the spike-mediated membrane fusion process outside the host cell, resulting in virus lysis, extracellular RNA release, and potent antiviral activity. While neutralizing antibodies became ineffective as the SARS-CoV-2 evolved to better penetrate host cells the ACE2-incorporated nanodiscs became more potent, highlighting the advantages of using receptor-incorporated nanodiscs for antiviral purposes. ACE2-incorporated immunodisc, an Fc fusion nanodisc developed in this study, completely protected humanized mice infected with SARS-CoV-2 after prolonged retention in the airways. This study demonstrates that the incorporation of viral receptors into immunodisc transforms the entry gate into a potent virucide for all current and future variants, a concept that can be extended to different viruses.
Subject(s)
Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing , COVID-19 , SARS-CoV-2 , Animals , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/chemistry , Humans , Mice , COVID-19/virology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Chlorocebus aethiops , Vero Cells , Virus Internalization/drug effects , HEK293 Cells , Antibodies, Viral/immunologyABSTRACT
OBJECTIVES: This study aimed to establish the validity-specifically, the sensitivity and specificity-of the screening questionnaire and diagnostic criteria for oral frailty proposed by the Korean Academy of Geriatric Dentistry (KAGD) among community-dwelling older adults. METHODS: This study enrolled 100 participants. Among various definitions of oral frailty, this study used the criteria proposed by Tanaka as the reference test. The screening questionnaire consisted of 11 items for screening physical frailty, chewing ability, swallowing difficulties, oral dryness, and tongue and lip motor function. Each question had a different scoring weight, and if the total score was 1 or higher, an oral frailty diagnostic examination proposed by the KAGD would be recommended. The diagnostic test was the oral frailty diagnostic criteria proposed by the KAGD including 6 measures: chewing ability, occlusal force, tongue pressure, oral dryness, swallowing difficulty, and oral hygiene. If a participant exhibited 2 or more positive measures, this participant was classified as "oral frail." The screening questionnaire was analyzed using a cut-off value of 1 or higher, while the diagnostic criteria utilized a cut-off of 2 or more positive measures. Sensitivity and specificity were calculated. RESULTS: The screening questionnaire showed significant power for screening oral frailty (area under the receiver operating characteristic curve, 0.783; sensitivity, 87.8%; specificity, 52.5%). The diagnostic accuracy of the newly proposed diagnostic criteria was acceptable (sensitivity, 95.1%; specificity, 42.4%). CONCLUSIONS: The newly proposed screening questionnaire and diagnostic criteria in Korea appear to be a useful tool to identify oral frailty in community-dwelling older adults.
Subject(s)
Frailty , Humans , Aged , Frailty/diagnosis , Independent Living , Frail Elderly , Geriatric Dentistry , Pressure , Cross-Sectional Studies , Geriatric Assessment , Tongue , Surveys and Questionnaires , Republic of KoreaABSTRACT
PURPOSE: To evaluate the anti-inflammatory and antioxidative effects of extracorporeal shockwave therapy (ESWT) on prostatitis and explore the mechanism of alleviating pain. MATERIALS AND METHODS: For in vitro testing, RWPE-1 cells were randomly divided into 5 groups: (1) RWPE-1 group (normal control), (2) LPS group (lipopolysaccharide inducing inflammation), (3) 0.1ESWT group (treated by 0.1 mJ/mm² energy level), (4) 0.2ESWT group (treated by 0.2 mJ/mm² energy level), and (5) 0.3ESWT group (treated by 0.3 mJ/mm² energy level). After ESWT was administered, cells and supernatant were collected for ELISA and western blot. For in vivo testing, Sprague-Dawley male rats were randomly divided into 3 groups: (1) normal group, (2) prostatitis group, and (3) ESWT group (n=12 for each). Prostatitis was induced by 17 beta-estradiol and dihydrotestosterone (DHT) administration. Four weeks after ESWT, the pain index was assessed for all groups and prostate tissues were collected for immunohistochemistry, immunofluorescence, apoptosis analysis and, western blot. RESULTS: Our in vitro studies showed that the optimal energy flux density of ESWT was 0.2 mJ/mm². In vivo, ESWT ameliorated discomfort in rats with prostatitis and inflammation symptoms were improved. Compared to normal rats, overexpressed NLRP3 inflammasomes triggered apoptosis in rats with prostatitis and this was improved by ESWT. TLR4-NFκB pathway was overactive after experimental prostatitis, compared to normal and ESWT groups, and prostatitis induced alterations in BAX/BAK pathway were inhibited by ESWT. CONCLUSIONS: ESWT improved CP/CPPS by reducing NLRP3 inflammasome and ameliorated apoptosis via inhibiting BAX/BAK pathway in a rat model. TLR4 may play a key role in bonding NLRP3 inflammasome and BAX/BAK pathways. ESWT might be a promising approach for the treatment of CP/CPPS.
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The transmission and pathogenesis of highly contagious fatal respiratory viruses are increasing, and the need for an on-site diagnostic platform has arisen as an issue worldwide. Furthermore, as the spread of respiratory viruses continues, different variants have become the dominant circulating strains. To prevent virus transmission, the development of highly sensitive and accurate on-site diagnostic assays is urgently needed. Herein, a facile diagnostic device is presented for multi-detection based on the results of detailed receptor-ligand dynamics simulations for the screening of various viral strains. The novel bioreceptor-treated electronics (receptonics) device consists of a multichannel graphene transistor and cell-entry receptors conjugated to N-heterocyclic carbene (NHC). An ultrasensitive multi-detection performance is achieved without the need for sample pretreatment, which will enable rapid diagnosis and prevent the spread of pathogens. This platform can be applied for the diagnosis of variants of concern in clinical respiratory virus samples and primate models. This multi-screening platform can be used to enhance surveillance and discriminate emerging virus variants before they become a severe threat to public health.
Subject(s)
Biological Assay , Graphite , Animals , Ligands , ElectronicsABSTRACT
PURPOSE: The purpose of this study was to evaluate the efficacy and safety of red ginseng oil (RXGIN) in men with lower urinary tract symptoms. MATERIALS AND METHODS: Men aged between 40 and 75 years with a total International Prostate Symptom Score (IPSS) of 8 to 19 points were recruited from April 2020 to December 2020. Subjects were randomly assigned to either the RXGIN group or the control group in a 1:1 ratio and received either RXGIN or placebo daily for 12 weeks. For the primary outcome, changes in IPSS scores at 6 and 12 weeks from baseline were analyzed. The secondary outcomes were changes in International Index of Erectile Function (IIEF), maximum urinary flow rate, and post-void residual volume at weeks 6 and 12 compared to baseline. Urine analysis and blood tests were additionally performed for safety assessment. RESULTS: A total of 88 subjects (RXGIN group, 46; control group, 42) completed the study. The total IPSS and IPSS subscores (residual urine sensation, frequency, intermittency, urgency, weak stream, straining, nocturia, and quality of life) were significantly improved in the RXGIN group compared to the control group at weeks 6 and 12. Total IIEF and sexual desire were significantly improved in the RXGIN group at week 6 and week 12, respectively, but there were no significant changes in the level of serum testosterone or dihydrotestosterone. The serum prostate-specific antigen showed significant decrease at weeks 12. No serious adverse events leading to discontinuation of the study drug were observed in the RXGIN group. CONCLUSIONS: Red ginseng oil (RXGIN) appears to be safe and effective in improving lower urinary tract symptoms in men and may also improve some aspects of sexual function.
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INTRODUCTION: Many countries have enacted indoor smoke-free policies, and some have established outdoor non-smoking areas. However, no clear standard for determining the optimal distance for these outdoor non-smoking zones remains. This study aimed to evaluate outdoor tobacco smoke (OTS) exposure up to a distance of 21 m and to identify factors influencing OTS levels. METHODS: To assess OTS levels, PM2.5 concentrations were measured at distances of 6, 12, 15, 18, and 21 m using real-time aerosol monitors. Between August and October 2022, a total of 164 measurements were undertaken. The background PM2.5 concentration was gauged for 5 minutes before smoking commenced and then re-measured 3 minutes during smoking. OTS levels were determined by calculating the difference between the average background PM2.5 and the average PM2.5 concentrations during smoking. A one-sample t-test was employed to ascertain if the OTS levels at each distance were significantly elevated compared to 0 µg/m3. Furthermore, a multiple linear regression analysis was conducted to determine the factors influencing OTS levels. RESULTS: The mean OTS levels recorded at all specified distances significantly surpassed 0 µg/m3. The regression analysis revealed that the OTS levels correlated significantly with distance and wind speed. Specifically, OTS levels diminished as distance expanded and wind speed reduced. CONCLUSIONS: OTS levels, even at 21 m, were significantly greater than 0 µg/m3. Our results provide robust evidence supporting the establishment of outdoor non-smoking zone up to 21 m. IMPLICATIONS: Outdoor tobacco smoke (OTS) level was determined by PM2.5 concentration. The OTS levels significantly exceeded 0 µg/m3 at every measured distance up to 21 m. In the regression model, OTS levels notably correlated with distance and wind speed. OTS levels diminished as distance expanded and wind speed reduced.
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γ-Hydroxybutyrate (GHB), a date-rape drug, causes certain symptoms, such as amnesia, confusion, ataxia, and unconsciousness, when dissolved in beverages and consumed by a victim. Commonly, assailants use GHB in secret for the crime of drug-facilitated sexual assault because it is tasteless, odorless, and colorless when dissolved in beverages. Generally, GHB detection methods are difficult to use promptly and secretly in situ and in real life because of the necessary detection equipment and low selectivity. To overcome this problem, we have developed a fast, simple, and easy-to-use second skin platform as a confidential self-protection platform that can detect GHB in situ or in real life without equipment. The second skin platform for naked-eye detection of GHB is fabricated with poly(vinyl alcohol) (PVA), polyurethane (PU), and polyacrylonitrile (PAN) included in the chemical receptor 2-(3-bromo-4-hydroxystyryl)-3-ethylbenzothiazol-3-ium iodide (BHEI). PAN conjugated with BHEI nanofibers (PB NFs) has various characteristics, such as ease of use, high sensitivity, and fast color change. PB NFs rapidly detected GHB at 0.01 mg/mL. Furthermore, the second-skin platform attached to the fingertip and wrist detected both 1 and 0.1 mg/mL GHB in solution within 50 s. The color changes caused by the interaction of GHB and the second skin platform cannot be stopped due to strong chemical reactions. In addition, a second skin platform can be secretly utilized in real life because it can recognize fingerprints and object temperatures. Therefore, the second skin platform can be used to aid daily life and prevent drug-facilitated sexual assault crime when attached to the skin because it can be exposed anytime and anywhere.
Subject(s)
Rape , Sodium Oxybate , EthanolABSTRACT
This study focuses on InGaZnO-based synaptic devices fabricated using reactive radiofrequency sputtering deposition with highly uniform and reliable multilevel memory states. Electron trapping and trap generation behaviors were examined based on current compliance adjustments and constant voltage stressing on the ITO/InGaZnO/ITO memristor. Using O2 + N2 plasma treatment resulted in stable and consistent cycle-to-cycle memory switching with an average memory window of ~95.3. Multilevel resistance states ranging from 0.68 to 140.7 kΩ were achieved by controlling the VRESET within the range of -1.4 to -1.8 V. The modulation of synaptic weight for short-term plasticity was simulated by applying voltage pulses with increasing amplitudes after the formation of a weak conductive filament. To emulate several synaptic behaviors in InGaZnO-based memristors, variations in the pulse interval were used for paired-pulse facilitation and pulse frequency-dependent spike rate-dependent plasticity. Long-term potentiation and depression are also observed after strong conductive filaments form at higher current compliance in the switching layer. Hence, the ITO/InGaZnO/ITO memristor holds promise for high-performance synaptic device applications.
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BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) are approved for the treatment of BRCA-mutated breast cancer (BC), including triple-negative BC (TNBC) and ovarian cancer (OvCa). A key challenge is to identify the factors associated with PARPi resistance; although, previous studies suggest that platinum-based agents and PARPi share similar resistance mechanisms. METHODS: Olaparib-resistant (OlaR) cell lines were analyzed using HTG EdgeSeq miRNA Whole Transcriptomic Analysis (WTA). Functional assays were performed in three BRCA-mutated TNBC cell lines. In-silico analysis were performed using multiple databases including The Cancer Genome Atlas, the Genotype-Tissue Expression, The Cancer Cell Line Encyclopedia, Genomics of Drug Sensitivity in Cancer, and Gene Omnibus Expression. RESULTS: High miR-181a levels were identified in OlaR TNBC cell lines (p = 0.001) as well as in tumor tissues from TNBC patients (p = 0.001). We hypothesized that miR-181a downregulates the stimulator of interferon genes (STING) and the downstream proinflammatory cytokines to mediate PARPi resistance. BRCA1 mutated TNBC cell lines with miR-181a-overexpression were more resistant to olaparib and showed downregulation in STING and the downstream genes controlled by STING. Extracellular vesicles derived from PARPi-resistant TNBC cell lines horizontally transferred miR-181a to parental cells which conferred PARPi-resistance and targeted STING. In clinical settings, STING levels were positively correlated with interferon gamma (IFNG) response scores (p = 0.01). In addition, low IFNG response scores were associated with worse response to neoadjuvant treatment including PARPi for high-risk HER2 negative BC patients (p = 0.001). OlaR TNBC cell lines showed resistance to platinum-based drugs. OvCa cell lines resistant to platinum showed resistance to olaparib. Knockout of miR-181a significantly improved olaparib sensitivity in OvCa cell lines (p = 0.001). CONCLUSION: miR-181a is a key factor controlling the STING pathway and driving PARPi and platinum-based drug resistance in TNBC and OvCa. The miR-181a-STING axis can be used as a potential marker for predicting PARPi responses in TNBC and OvCa tumors.
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PURPOSE: Slow speech rate and abnormal temporal prosody are primary diagnostic criteria for differentiating between people with aphasia who do and do not have apraxia of speech. We sought to identify appropriate cutoff values for abnormal word syllable duration (WSD) in a word repetition task, interpret them relative to a data set of people with chronic aphasia, and evaluate the extent to which manually derived measures could be approximated through an automated process that relied on commercial speech recognition technology. METHOD: Fifty neurotypical participants produced 49 multisyllabic words during a repetition task. Audio recordings were submitted to an automated speech recognition (ASR) service (IBM Watson) to measure word duration and generate an orthographic transcription. The transcribed words were compared to a lexical database, and the number of syllables was identified. Automatic and manual measures were compared for 50% of the sample. Results were interpreted relative to WSD scores from an existing data set of 195 people with mostly chronic aphasia. RESULTS: ASR correctly identified 83% of target words and 98% of target syllable counts. Automated word duration calculations were longer than manual measures due to imprecise cursor placement. Upon applying regression coefficients to the automated measures and examining the frequency distributions for both manual and estimated measures, a WSD of 303-316 ms was found to indicate longer-than-normal performance (corresponding to the 95th percentile). With this cutoff, 40%-45% of participants with aphasia in our comparison sample had an abnormally long WSD. CONCLUSIONS: We recommend using a rounded WSD cutoff score between 303 and 316 ms for manual measures. Future research will focus on customizing automated WSD methods to speech samples from people with aphasia, identifying target words that maximize production and measurement reliability, and developing WSD standard scores based on a large participant sample with and without aphasia.
Subject(s)
Aphasia , Apraxias , Stroke , Humans , Reproducibility of Results , Aphasia/diagnosis , Aphasia/etiology , Apraxias/diagnosis , Stroke/complications , Stroke/diagnosis , Speech , SurvivorsABSTRACT
The sense of spiciness is related to the stimulation of vanilloid compounds contained in the foods. Although, the spiciness is commonly considered as the part of taste, it is more classified to the sense of pain stimulated on a tongue, namely, pungency, which is described as a tingling or burning on the tongue. Herein, first, a reusable electronic tongue based on a transient receptor potential vanilloid 1 (TRPV1) nanodisc conjugated graphene field-effect transistor is fabricated and spiciness-related pain evaluation with reusable electrode is demonstrated. The pungent compound reactive receptor TRPV1 is synthesized in the form of nanodiscs to maintain stability and reusability. The newly developed platform shows highly selective and sensitive performance toward each spiciness related vanilloid compound repeatably: 1 aM capsaicin, 10 aM dihydrocapsaicin, 1 fM piperine, 10 nM allicin, and 1 pM AITC. The binding mechanism is also examined by simulation. Furthermore, the elimination of the burning sensation on the tongue after eating spicy foods is not investigated. Based on the synthesis of micelles composed of casein protein (which is contained in skim milk) that remove pungent compounds bound to TRPV1 nanodisc, the deactivation of TRPV1 is investigated, and the electrode is reusable that mimics electronic tongue.