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Green tea is a popular worldwide beverage, and its potential beneficial effects such as anti-cancer and anti-oxidant properties are believed to be mediated by epigallocatechin-3-gallate (EGCG), a major constituent of polyphenols. Recently, it was reported that EGCG might be useful in the prevention or treatment of androgenetic alopecia by selectively inhibiting 5alpha-reductase activity. However, no report has been issued to date on the effect of EGCG on human hair growth. This study was undertaken to measure the effect of EGCG on hair growth in vitro and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. EGCG promoted hair growth in hair follicles ex vivo culture and the proliferation of cultured DPCs. The growth stimulation of DPCs by EGCG in vitro may be mediated through the upregulations of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax ratio. Similar results were also obtained in in vivo dermal papillae of human scalps. Thus, we suggest that EGCG stimulates human hair growth through these dual proliferative and anti-apoptotic effects on DPCs. [ABSTRACT FROM AUTHOR]

Various organisms produce several products to defend themselves from the environment and enemies. These natural products have pharmacological and biological activities and are used for therapeutic purposes, retaining bitter taste because of chemical defense mechanisms. Cnicin is a plant-derived bitter sesquiterpene lactone with pharmacological characteristics such as anti-bacterial, anti-myeloma, anti-cancer, anti-tumor, anti-oxidant, anti-inflammatory, allelopathic, and cytotoxic properties. Although many studies have focused on cnicin detection, they have limitations and novel cnicin-detecting strategies are required. In this study, we developed the bioelectronics for screening cnicin using its distinct taste. hTAS2R46 was produced using an Escherichia coli expression system and reconstituted into nanodiscs (NDs). The binding sites and energy between hTAS2R46 and cnicin were investigated using biosimulations. hTAS2R46-NDs were combined with a side-gated graphene micropatterned field-effect transistor (SGMFET) to construct hTAS2R46-NDs bioelectronics. The construction was examined by chemical and electrical characterization. The developed system exhibited unprecedented performance, 10 fM limit of detection, rapid response time (within 10 s), 0.1354 pM -1 equilibrium constant, and high selectivity. Furthermore, the system was stable as the sensing performance was maintained for 15 days. Therefore, the hTAS2R46-NDs bioelectronics can be utilized to screen cnicin from natural products and applied in the food and drug industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Resistance to chemotherapy drugs, which commonly occurs during the treatment of colorectal cancer (CRC), can lead to tumor recurrence and metastasis, so combinational treatment strategies according to the cancer cell type are urgently needed to overcome drug resistance and increase therapeutic efficiency. To this end, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer strategy. Some CRC cell lines such as SW620 have low sensitivity to TRAIL, so additional sensitizers are required to make the strategy effective. Therefore, we focused on the apoptotic effect of combinational metformin and TRAIL treatment on TRAIL-resistant SW620 cells. Treatment with TRAIL alone did not induce apoptosis whereas combined treatment with metformin and TRAIL significantly increased it. TRAIL activated caspases through an extrinsic pathway but increased resistance to apoptosis through the protein kinase B or AKT (PKB/AKT)/mammalian target of rapamycin (mTOR) pathway. On the other hand, metformin reduced the inhibitory effect of X-linked inhibitor of apoptosis (XIAP) by blocking the AKT and nuclear factor kappa B (NF-κB) pathways and activated CCAAT-enhancer-binding protein homologous protein (CHOP) via endoplasmic reticulum (ER) stress but without inducing apoptosis. In addition, metformin induced cell-cycle arrest, thereby blocking cell proliferation and growth. These results were also confirmed through an in vivo mouse xenograft CRC model, in which combined treatment with metformin and TRAIL induced tumor cell death, thus demonstrating the anticancer effect of their coadministration. Therefore, cotreatment of metformin and TRAIL could be an effective anticancer treatment strategy for TRAIL-resistant CRC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Collagen is a complex, large protein molecule that presents a challenge in delivering it to the skin due to its size and intricate structure. However, conventional collagen delivery methods are either invasive or may affect the protein's structural integrity. This study introduces a novel approach involving the encapsulation of collagen monomers within zwitterionic nanoliposomes, termed Lip-Cols, and the controlled formation of collagen fibrils through electric fields (EF) stimulation. The results reveal the self-assembly process of Lip-Cols through electroporation and a pH gradient change uniquely triggered by EF, leading to the alignment and aggregation of Lip-Cols on the electrode interface. Notably, Lip-Cols exhibit the capability to direct the orientation of collagen fibrils within human dermal fibroblasts. In conjunction with EF, Lip-Cols can deliver collagen into the dermal layer and increase the collagen amount in the skin. The findings provide novel insights into the directed formation of collagen fibrils via electrical stimulation and the potential of Lip-Cols as a non-invasive drug delivery system for anti-aging applications., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

It would be clinically valuable if the efficacy of antiarrhythmic drugs could be simulated in advance. We developed a digital twin to predict amiodarone efficacy in high-risk atrial fibrillation (AF) patients post-ablation. Virtual left atrium models were created from computed tomography and electroanatomical maps to simulate AF and evaluate its response to varying amiodarone concentrations. As the amiodarone concentration increased in the virtual setting, action potential duration lengthened, peak upstroke velocities decreased, and virtual AF termination became more frequent. Patients were classified into effective (those with virtually terminated AF at therapeutic doses) and ineffective groups. The one-year clinical outcomes after AF ablation showed significantly better results in the effective group compared to the ineffective group, with AF recurrence rates of 20.8% vs. 45.1% (log-rank p = 0.031, adjusted hazard ratio, 0.37 [0.14-0.98]; p = 0.046). This study highlights the potential of a digital twin-guided approach in predicting amiodarone's effectiveness and improving personalized AF management. Clinical Trial Registration Name: The Evaluation for Prognostic Factors After Catheter Ablation of Atrial Fibrillation: Cohort Study, Registration number: NCT02138695. The date of registration: 2014-05. URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02138695., (© 2024. The Author(s).)

Chalaniline A, an aminofulveno[1,2- b ]chromone derivative previously isolated from a vorinostat-treated ascomycete Chalara sp., was prepared in nine steps from orcinol (3,5-dihydroxytoluene). In a key transformation, the tricyclic ring system of the target was generated by a pyrrolidine-catalyzed double annulation between α-(methylsulfinyl)-2,6-dihydroxy-4-methylacetophenone and the ketaldoester, methyl 2,5-dioxopentanoate. The resulting tertiary alcohol (coniochaetone H) was further converted to chalaniline A by operations including dehydration (to yield a hydroxyfulvene), Vilsmeier reaction, and enamine exchange.

This study explores novel approaches to enhance photocatalysis efficiency by introducing a photonic crystal (PC)-enhanced, multi-layered sub-bandgap photocatalytic reactor. The design aims to effectively utilize sub-bandgap photons that might otherwise go unused. The device consists of three types of layers: (1) two polymeric triplet-triplet annihilation upconversion (TTA-UC) layers converting low-energy green photons (λ Ex = 532 nm, 2.33 eV) to high-energy blue photons (λ Em = 425 nm, 2.92 eV), (2) a platinum-decorated WO 3 layer (E g = 2.8 eV) serving as a visible-light photocatalyst, and (3) a PC layer optimizing both TTA-UC and photocatalysis. The integration of the PC layer resulted in a 1.9-fold increase in UC emission and a 7.9-fold enhancement in hydroxyl radical (•OH) generation, achieved under low-intensity sub-bandgap irradiation (17.6 mW cm -2 ). Consequently, the combined layered structure of TTA/Pt-WO 3 /TTA/PC achieved a remarkable 38.8-fold improvement in •OH production, leading to outstanding degradation capability for various organic pollutants (e.g., 4-chlorophenol, bisphenol A, and methylene blue). This multi-layered sub-bandgap photocatalytic structure, which uniquely combines TTA-UC and PC layers, offers valuable insights into designing efficient photocatalytic systems for future solar-driven environmental remediation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although biocides are important materials in modern society and help protect human health and the environment, increasing exposure to combined biocides can cause severe side effects in the human body, such as lung fibrosis. In this study, we developed a receptonics system to screen for biocides in combined household chemical products based on biocides. The system contains transient receptor potential ankyrin 1 (TRPA1) nanovesicles (NVs) to sense biocides based on pain receptors and a side-gated field-effect transistor (SGFET) using a single-layer graphene (SLG) micropattern channel. The binding affinities between the TRPA1 receptor and the various biocides were estimated by performing biosimulation and using a calcium ion (Ca 2+ ) assay, and the sensitivity of the system was compared with that of TRPA1 NV receptonics systems. Based on the results of the TRPA1 NV receptonics system, the antagonistic and potentiation effects of combined biocides and household chemical products depended on the concentration. Finally, the TRPA1 NV receptonics system was applied to screen for biocides in real products, and its performance was successful. Based on these results, the TRPA1 NV receptonics system can be utilized to perform risk evaluations and identify biocides in a simple and rapid manner., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The application of artificial intelligence (AI) algorithms to 12-lead electrocardiogram (ECG) provides promising age prediction models. We explored whether the gap between the pre-procedural AI-ECG age and chronological age can predict atrial fibrillation (AF) recurrence after catheter ablation. We validated a pre-trained residual network-based model for age prediction on four multinational datasets. Then we estimated AI-ECG age using a pre-procedural sinus rhythm ECG among individuals on anti-arrhythmic drugs who underwent de-novo AF catheter ablation from two independent AF ablation cohorts. We categorized the AI-ECG age gap based on the mean absolute error of the AI-ECG age gap obtained from four model validation datasets; aged-ECG (≥10 years) and normal ECG age (<10 years) groups. In the two AF ablation cohorts, aged-ECG was associated with a significantly increased risk of AF recurrence compared to the normal ECG age group. These associations were independent of chronological age or left atrial diameter. In summary, a pre-procedural AI-ECG age has a prognostic value for AF recurrence after catheter ablation., (© 2024. The Author(s).)

Background and Aim: Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3 cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics., Methods: This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3 cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10 years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy., Results: One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7 months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8 months, P = 0.001). Median RFS was 19.1 months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2 cm) were poor prognostic factors of OS., Conclusions: The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3 cm) HCC in CTP class A patients., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The healing process after acne lesion extraction provides a miniature model to study skin wound repair mechanisms. In this study, we aimed to identify solutions for acne scars that frequently occur on our faces. We performed acne scar cytokine profiling and found that Interleukin 8 (IL8) and Tissue inhibitor of metalloproteinases 2 (TIMP2) were significant factors at the wounded site. The effect of chlorogenic acid and taurine on human epidermal cells and irritated human skin was investigated. Chlorogenic acid and taurine regulated IL8 and TIMP2 expression and accelerated keratinocyte proliferation. Moreover, tight junction protein expression was upregulated by chlorogenic acid and taurine synergistically. Further, these compounds modulated the expression of several inflammatory cytokines (IL1α, IL1β, and IL6) and skin hydration related factor (hyaluronan synthase 3; HAS3). Thus, chlorogenic acid and taurine may exert their effects during the late stages of wound healing rather than the initial phase. In vivo experiments using SLS-induced wounds demonstrated the efficacy of chlorogenic acid and taurine treatment compared to natural healing, reduced erythema, and restored barrier function. Skin ultrasound analysis revealed their potential to promote denser skin recovery. Therefore, the wound-restoring effect of chlorogenic acid and taurine was exerted by suppression of inflammatory cytokines, and induction of cell proliferation, tight junction expression, and remodeling factors.

As online news increasingly include data journalism, there is a corresponding increase in the incorporation of visualization in article thumbnail images. However, little research exists on the design rationale for visualization thumbnails, such as resizing, cropping, simplifying, and embellishing charts that appear within the body of the associated article. Therefore, in this paper we aim to understand these design choices and determine what makes a visualization thumbnail inviting and interpretable. To this end, we first survey visualization thumbnails collected online and discuss visualization thumbnail practices with data journalists and news graphics designers. Based on the survey and discussion results, we then define a design space for visualization thumbnails and conduct a user study with four types of visualization thumbnails derived from the design space. The study results indicate that different chart components play different roles in attracting reader attention and enhancing reader understandability of the visualization thumbnails. We also find various thumbnail design strategies for effectively combining the charts' components, such as a data summary with highlights and data labels, and a visual legend with text labels and Human Recognizable Objects (HROs), into thumbnails. Ultimately, we distill our findings into design implications that allow effective visualization thumbnail designs for data-rich news articles. Our work can thus be seen as a first step toward providing structured guidance on how to design compelling thumbnails for data stories.

With recent advances in adeno-associated virus (AAV)-based gene therapy, efficacy and toxicity screening have become essential for developing gene therapeutic drugs for retinal diseases. Retinal organoids from human pluripotent stem cells (hPSCs) offer a more accessible and reproducible human test platform for evaluating AAV-based gene therapy. In this study, hPSCs were differentiated into retinal organoids composed of various types of retinal cells. The transduction efficiencies of AAV2 and AAV8, which are widely used in clinical trials of inherited retinal diseases, were analyzed using retinal organoids. These results suggest that retinal organoids derived from hPSCs serve as suitable screening platforms owing to their diverse retinal cell types and similarity to the human retina. In summary, we propose an optimal stepwise protocol that includes the generation of retinal organoids and analysis of AAV transduction efficacy, providing a comprehensive approach for evaluating AAV-based gene therapy for retinal diseases.

Background/Aims: Well-known risk factors for gallbladder polyps include metabolic syndrome, age, and dyslipidemia. Jeju Island is approximately 80 km from the Korean peninsula and is divided into two administrative regions (Jeju City and Seogwipo City), with Mount Halla intervening in the center. Jeju City has higher employment and birth rates than Seogwipo City. Age and alcohol consumption differ between the two regions, and these factors may affect the prevalence of gallbladder polyps (GBPs). Therefore, we investigated the prevalence of GBPs and compared various factors, including alcohol consumption habits and age, associated with GBPs among residents in the two regions. Methods: This study included 21,734 residents who visited the Health Screening and Promotion Center of Jeju National University Hospital between January 2009 and December 2019. We investigated the prevalence and associated factors of GBPs among residents of Jeju City and Seogwipo City. Results: The prevalence of GBPs in Jeju City and Seogwipo City was 9.8% and 8.9% ( p = 0.043), respectively. The mean age and rate of high-risk alcohol intake were higher in Seogwipo City. The mean body mass index and levels of fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase were lower in Jeju City. Conclusions: This study demonstrated a significant difference in GBP prevalence between the two regions of Jeju Island. Age and alcohol consumption might contribute to this difference; however, further prospective cohort studies are warranted to confirm our findings.

The perceived duration of time does not veridically reflect the physical duration but is distorted by various factors, such as the stimulus magnitude or the observer's emotional state. Here, we showed that knowledge about an event's termination time is another significant factor. We often experience time passage differently when we know that an event will terminate soon. To quantify this, we asked 33 university students to report a rotating clock hand's duration with or without a termination cue that indicated the position at which the clock hand disappeared. The results showed that the presence of the termination cue dilated perceived durations, and the dilating effect was larger when the stimulus duration was longer, or the speed of the rotating stimulus was slower. A control experiment with a start-cue excluded the possibility that the cue's mere existence caused the results. Further computational analyses based on the attention theory-of-time perception revealed that the size of dilation is best explained by neither an event's duration nor the distance traveled by the clock hand, but by how long the clock hand spends time near the termination cue. The results imply that an event-termination cue generates a field in which the perceived time dilates., (© 2023. The Psychonomic Society, Inc.)

Although pulmonary vein isolation (PVI) gaps and extrapulmonary vein triggers contribute to recurrence after atrial fibrillation (AF) ablation, their precise mechanisms remain unproven. Our study assessed the impact of PVI gaps on rhythm outcomes using a human AF digital twin. We included 50 patients (76.0% with persistent AF) who underwent catheter ablation with a realistic AF digital twin by integrating computed tomography and electroanatomical mapping. We evaluated the final rhythm status, including AF and atrial tachycardia (AT), across 600 AF episodes, considering factors including PVI level, PVI gap number, and pacing locations. Our findings revealed that antral PVI had a significantly lower ratio of AF at the final rhythm (28% vs. 56%, p = 0.002) than ostial PVI. Increasing PVI gap numbers correlated with an increased ratio of AF at the final rhythm (p < 0.001). Extra-PV induction yielded a higher ratio of AF at the final rhythm than internal PV induction (77.5% vs. 59.0%, p < 0.001). In conclusion, our human AF digital twin model helped assess AF maintenance mechanisms. Clinical trial registration: https://www.clinicaltrials.gov ; Unique identifier: NCT02138695., (© 2024. The Author(s).)

Background: TB-500 (Ac-LKKTETQ), derived from the active site of thymosin β4 (Tβ4), has various biological functions in its unacetylated form, LKKTETQ. These functions include actin binding, dermal wound healing, angiogenesis, and skin repair. The biological effects of TB-500, however, have not been documented. And the analysis of TB-500 and its metabolites have been neither simultaneously quantified nor structurally identified using synthesized authentic standards., Methods: This study was aimed to investigating simultaneous analytical methods of TB-500 and its metabolites in in-vitro and urine samples by using UHPLC-Q-Exactive orbitrap MS, and to comparing the biological activity of its metabolites with the parent TB-500. The metabolism of TB-500 was investigated in human serum, various in-vitro enzyme systems, and urine samples from rats treated with TB-500, and their biological activities measured by cytotoxicity and wound healing experiments were also evaluated in fibroblasts., Results: The simultaneous analytical method for TB-500 and its metabolites was developed and validated. The study found that Ac-LK was the primary metabolite with the highest concentration in rats at 0-6 h intervals. Also, the metabolite Ac-LKK was a long-term metabolite of TB-500 detected up to 72 hr. No cytotoxicity of the parent and its metabolites was found. Ac-LKKTE only showed a significant wound healing activity compared to the control., Conclusion: The study provides a valuable tool for quantifying TB-500 and its metabolites, contributing to the understanding of metabolism and potential therapeutic applications. Our results also suggest that the previously reported wound-healing activity of TB-500 in literature may be due to its metabolite Ac-LKKTE rather than the parent form., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: High-power short-duration (HPSD) ablation creates wide, shallow lesions using radiofrequency (RF) heating. It is uncertain if adjusting RF energy based on atrial wall thickness provides extra benefits. We studied the safety and effectiveness of tailored HPSD energy based on left atrial (LA) wall thickness (LAWT) for circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (PAF)., Methods: We enrolled 212 patients (68.4% male, mean age: 59.5 ± 11.0 years) and randomly assigned them to two groups: LAWT-guided CPVI (WT, n  = 108) and conventional CPVI (control, n  = 104). Both groups used an open irrigated-tip deflectable catheter to apply 50 W for 10 s to the posterior LA, while controls used 60 W for 15 s on other LA regions. RF delivery time in WT was titrated (15 s at LAWT > 2.1 mm, 13 s at 1.4-2.1 mm, and 11 s at <1.4 mm) according to the computed tomogram-myocardial thickness color map., Results: After a mean follow-up of 13.4 ± 7.0 months, the WT and control groups showed no significant difference regarding clinical recurrence rate (13.9% vs. 5.8%, respectively; p  = .061) and major complication rate (4.6% vs. 3.8%, respectively; p  > .999). The total procedure time, cardioversion rate, and post-procedural AAD prescription rates did not significantly differ between the groups., Conclusions: The LAWT-guided energy titration strategy did not result in improved procedural safety and efficacy compared to the conventional 50-60 W-HPSD CPVI in patients with PAF., Competing Interests: We previously developed automated customized software (AMBER, LaonMed, Korea) to measure myocardial thickness from cardiac CT. We registered the patent for the above technology on June 2, 2022, and had the patent number (10‐2022‐0067621). The authors declare no conflict of interest, except for the patent related to wall thickness measurement software., (© 2024 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Introduction: Anterior cruciate ligament (ACL) injury is frequently accompanied by quadriceps muscle atrophy, a process closely linked to mitochondrial health and mitochondria-specific autophagy. However, the temporal progression of key quadricep atrophy-mediating events following ACL injury remains poorly understood. To advance our understanding, we conducted a longitudinal study to elucidate key parameters in quadriceps autophagy and mitophagy. Methods: Long-Evans rats were euthanized at 7, 14, 28, and 56 days after non-invasive ACL injury that was induced via tibial compression overload; controls were not injured. Vastus lateralis muscle was extracted, and subsequent immunoblotting analysis was conducted using primary antibodies targeting key proteins involved in autophagy and mitophagy cellular processes. Results: Our findings demonstrated dynamic changes in autophagy and mitophagy markers in the quadriceps muscle during the recovery period after ACL injury. The early response to the injury was characterized by the induction of autophagy at 14 days (Beclin1), indicating an initial cellular response to the injury. Subsequently, at 14 days we observed increase in the elongation of autophagosomes (Atg4B), suggesting a potential remodeling process. The autophagosome flux was also augmented between 14- and 28 days (LC3-II/LC3-I ratio and p62). Notably, at 56 days, markers associated with the elimination of damaged mitochondria were elevated (PINK1, Parkin, and VDAC1), indicating a possible ongoing cellular repair and restoration process. Conclusion: These data highlight the complexity of muscle recovery after ACL injury and underscore the overlooked but crucial role of autophagy and mitophagy in promoting the recovery process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Noh, Ahn, Davi, Lepley and Kwon.)

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., (© 2023 Wiley-VCH GmbH.)

Objective: The objective of this article is to evaluate near-infrared spectroscopy (NIRS), a non-invasive technique to assess tissue oxygenation and mitochondrial function, as a diagnostic tool for statin-associated muscle symptoms (SAMS)., Methods: We verified SAMS in 39 statin-treated patients (23 women) using a double-blind, placebo-controlled, cross-over protocol. Subjects with suspected SAMS were randomised to simvastatin 20 mg/day or placebo for 8 weeks, followed by a 4-week no treatment period and then assigned to the alternative treatment, either simvastatin or placebo. Tissue oxygenation was measured before and after each statin or placebo treatment using NIRS during handgrip exercise at increasing intensities of maximal voluntary contraction (MVC)., Results: 44% (n=17) of patients were confirmed as having SAMS (11 women) because they reported discomfort only during simvastatin treatment. There were no significant differences in percent change in tissue oxygenation in placebo versus statin at all % MVCs in all subjects. The percent change in tissue oxygenation also did not differ significantly between confirmed and unconfirmed SAMS subjects on statin (-2.4% vs -2.4%, respectively) or placebo treatment (-1.1% vs -9%, respectively). The percent change in tissue oxygenation was reduced after placebo therapy in unconfirmed SAMS subjects (-10.2%) (p≤0.01) suggesting potential measurement variability., Conclusions: NIRS in the forearm cannot differentiate between confirmed and unconfirmed SAMS, but further research is needed to assess the usability of NIRS as a diagnostic tool for SAMS., Trial Registration Number: NCT03653663., Competing Interests: Competing interests: Hartford Hospital through Dr. Thompson has received research funds from Norvatis and Esperion for studies of lipid metabolism., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To provide a synthesis of randomized controlled trials (RCTs) investigating statin-associated muscle symptoms (SAMS) in adults who underwent exercise training intervention., Patients and Methods: We systematically searched 5 electronic databases for placebo-controlled RCTs through January 31, 2023. We included short-term and long-term exercise interventions that compared the efficacy and safety of exercise+statin vs exercise+placebo in healthy adults and reported SAMS preintervention and postintervention. Publication bias and methodological study quality assessments were performed., Results: Five of 454 potentially qualifying RCTs met the inclusion criteria, all short-term exercise RCTs. Participants were predominantly physically inactive young to middle-aged (M=37.2 y) men (57%), 252 (49%) who were on statin therapy, and 271 (53%) on placebo. Of the 3 RCTs providing qualitative SAMS results, 19 (9%) out of 220 participants reported SAMS on exercise+statin and 10 (4%) out of 234 reported SAMS on exercise+placebo. There was no difference between exercise+statin vs exercise+placebo for maximal oxygen consumption ( d =-0.18; 95% CI, -0.37 to 0.00; P =.06) or creatine kinase after short-term exercise ( d =0.59; 95% CI, -0.06 to 1.25; P =.08). Participants in the exercise+statin group reduced low-density lipoprotein cholesterol vs exercise+placebo ( d =-1.84; 95% CI, -2.28 to -1.39; P <.001). Most of the RCTs exhibited low levels of risk of bias ( k =4, 80%) and achieved moderate methodological study quality (75.0%±5.2%)., Conclusion: Self-reported SAMs tended to be 5% greater after short-term exercise in statin users compared with placebo, although this difference did not achieve statistical significance. There remains an important need for placebo-controlled RCTs investigating the prevalence of statin-induced SAMS during exercise training., Competing Interests: LSP is founder and sole proprietor of P3-EX, LLC, which potentially could benefit from this research., (© 2024 The Authors.)

We developed a novel strategy for discriminative detection of SARS-CoV-2 variants based on the plasmonic photothermal effect of gold nanofilms and digital polymerase chain reaction (dPCR) technology. This method consists of the gold nanofilm-based dPCR chip fabrication for ultrafast heating and cooling cycles by the plasmonic photothermal effect, the LED quencher immobilization through the interfacing compound on the surface of the gold nanofilm to prevent photoquenching of PCR signaling dye, and the discriminative detection of the variant viruses from the COVID-19 clinical samples by photothermal cycles with fabricated dPCR chips and a portable plasmonic PCR device. Compared to conventional sequencing or RT-qPCR-based variant detection methods, this technology can be effectively applied to point-of-care testing by enabling ultrafast quantitative analysis with a small device. With this method, we successfully detected the delta variant and the omicron variant with a high sensitivity of 10 copies from COVID-19 patients' clinical samples within 25 min, including reverse transcription. This method can be applied universally to rapid and accurate point-of-care testing for various pandemic viruses as well as the coronavirus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lifestyle modification including exercise training is often the first line of defense in the treatment of obesity and hypertension (HTN), however, little is known regarding how these potentially compounding disease states impact vasodilatory and hemodynamic responses at baseline and exercise. Therefore, this study sought to compare the impact of obesity on vascular function and hemodynamics at baseline and during handgrip (HG) exercise among individuals with HTN. Non-obese (13M/7F, 56 ± 16 yr, 25 ± 4 kg/m 2 ) and obese (17M/4F, 50 ± 7 yr, 35 ± 4 kg/m 2 ) middle-aged individuals with HTN forwent antihypertensive medication use for ≥2 wk before assessment of vascular function by brachial artery flow-mediated dilation (FMD) and exercise hemodynamics during progressive HG exercise at 15-30-45% maximal voluntary contraction (MVC). FMD was not different between Non-Obese (4.1 ± 1.7%) and Obese (5.2 ± 1.9%, P = 0.11). Systolic blood pressure (SBP) was elevated by ∼15% during the supine baseline and during HG exercise in the obese group. The blood flow response to HG exercise at 30% and 45% MVC was ∼20% greater ( P < 0.05) in the obese group but not different after normalizing for the higher, albeit, nonsignificant differences in workloads (MVC: obese: 24 ± 5 kg, non-obese: 21 ± 5 kg, P = 0.11). Vascular conductance and the brachial artery shear-induced vasodilatory response during HG were not different between groups ( P > 0.05). Taken together, despite elevated SBP during HG exercise, obesity does not lead to additional impairments in vascular function and peripheral exercising hemodynamics in patients with HTN. Obesity may not be a contraindication when prescribing exercise for the treatment of HTN among middle-aged adults, however, the elevated SBP should be appropriately monitored. NEW & NOTEWORTHY This study examined vascular function and handgrip exercise hemodynamics in obese and nonobese individuals with hypertension. Obesity, when combined with hypertension, was neither associated with additional vascular function impairments at baseline nor peripheral hemodynamics and vasodilation during exercise compared with nonobese hypertension. Interestingly, systolic blood pressure and pulse pressure were greater in the obese group during supine baseline and exercise. These findings should not be ignored and may be particularly important for rehabilitation strategies.

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.

Objectives: This study sought to uncover whether having a gastrointestinal (GI) hospitalist available during weekday daytime hours results in higher-quality medical care compared to care provided by a team of residents., Methods: Our hospitalist GI team consisted of two gastroenterologists working weekday daytime hours and two physician assistants. The team of conventional care headed by thirteen professors, comprised twelve residents and eight physician assistants. We conducted a retrospective cohort study in South Korea between March 2 and December 9, 2020 The hospitalist team treated 528 patients, while the conventional care team treated 2,335. We assessed the medical parameters of length of stay (LOS), rates of in-hospital mortality, transfer to the intensive care unit, and readmission rate within 30 days. Furthermore, we gathered feedback from nurses working with both teams., Results: The study found that there was no significant difference in LOS between infections ( P  = 0.422) and other GI diseases like bleeding ( P  = 0.226). There was no significant difference in the rates of in-hospital mortality ( P  = 0.865) and transfer to the intensive care unit ( P  = 0.486) between the two teams. However, the hospitalist team had notably lower readmission rates than the conventional care team ( P  = 0.002) as well as a lower unscheduled readmission rate ( P  = 0.046). Furthermore, the survey results indicated that nurses who worked with the hospitalist team had significantly better responses than those who worked with the conventional care team ( P  < 0.001)., Conclusions: This study indicates that having GI hospitalists work weekday daytime hours improves patient care, and treatment and reduces readmission rates.

Non-invasive brain-computer interfaces (BCIs) based on an event-related potential (ERP) component, P300, elicited via the oddball paradigm, have been extensively developed to enable device control and communication. While most P300-based BCIs employ visual stimuli in the oddball paradigm, auditory P300-based BCIs also need to be developed for users with unreliable gaze control or limited visual processing. Specifically, auditory BCIs without additional visual support or multi-channel sound sources can broaden the application areas of BCIs. This study aimed to design optimal stimuli for auditory BCIs among artificial (e.g., beep) and natural (e.g., human voice and animal sounds) sounds in such circumstances. In addition, it aimed to investigate differences between auditory and visual stimulations for online P300-based BCIs. As a result, natural sounds led to both higher online BCI performance and larger differences in ERP amplitudes between the target and non-target compared to artificial sounds. However, no single type of sound offered the best performance for all subjects; rather, each subject indicated different preferences between the human voice and animal sound. In line with previous reports, visual stimuli yielded higher BCI performance (average 77.56%) than auditory counterparts (average 54.67%). In addition, spatiotemporal patterns of the differences in ERP amplitudes between target and non-target were more dynamic with visual stimuli than with auditory stimuli. The results suggest that selecting a natural auditory stimulus optimal for individual users as well as making differences in ERP amplitudes between target and non-target stimuli more dynamic may further improve auditory P300-based BCIs., Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-022-09901-3., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Renal cancer therapies are challenging owing to the extensive spreading of this cancer to other organs and its ability to pose resistance to current medications. Therefore, drugs targeting novel targets are urgently required to overcome these challenges. The cholesterol side-chain cleavage enzyme (CYP11A1) is closely associated with steroidogenesis, and its downregulation is linked to adrenal dysfunction and several types of carcinoma. We previously found that overexpression of CYP11A1 inhibited epithelial-mesenchymal transition and induced G2/M arrest in the kidney cancer Caki-1 cell line. In this context, natural compounds that exhibit potent CYP11A1 stimulation activity can be promising therpaeutic agents for kidney cancer., Methods: We screened a panel of 1374 natural compounds in a wound-healing assay using CYP11A1-transfected Caki-1 cells. Of these, 167 promising biologically active compounds that inhibited cancer cell migration by more than 75% were selected, and their half-maximal inhibitory concentrations (IC 50 ) were determined. The IC 50 of 159 compounds was determined and 38 compounds with IC 50 values less than 50 µM were selected for further analysis. Steroid hormones (cholesterol and pregnenolone) levels in cells treated with the selected compounds were quantitated using LC-MS/MS to determine their effect on CYP11A1 activity. Western blotting for CYP11A1, autophagy signaling proteins, and ferroptosis regulators were performed to ivestigate the mechanisms underlying the action of the selected compounds., Results: We screened five promising natural lead compounds that inhibited cancer cell proliferation after three screening steps. The IC 50 of these compounds was determined to be between 5.9 and 14.6 μM. These candidate compounds increased the expression of CYP11A1 and suppressed cholesterol levels while increasing pregnenolone levels, which is consistent with the activation of CYP11A1. Our results showed that CYP11A1 activation inhibited the migration of cancer cells, promoted ferroptosis, and triggered autophagy signaling., Conclusions: This study indicates that the CYP11A1-overexpressing Caki-1 cell line is useful for screening drugs against kidney cancer. The two selected compounds could be utilized as lead compounds for anticancer drug discovery, and specifically for the development of antirenal cancer medication., (© 2023. The Author(s).)

Introduction: Since the analgesic effect of acupuncture stimulation is derived from different mechanisms depending on the type of pain, it is important to know which acupuncture points to stimulate. In this study, to confirm the effect of acupuncture stimulation on acute pain from a neurological point of view, somatosensory evoked potential and sensory threshold changes were evaluated to identify the nerve range that is affected by acupuncture stimulation on LI4 (Hapgok acupuncture point, of the radial nerve) during acute pain., Methods: The subjects were 40 healthy men and women aged 19-35 years. The study was designed as a randomly controlled, crossover trial with acupuncture stimulation at LI4 as the intervention. The washout period for acupuncture stimulation was 2 weeks, and the subjects were divided into two groups, i.e., an acupuncture stimulation group and a nonstimulation group, with 10 men and 10 women in each group. Somatosensory evoked potential measurement was carried out for 5 min by alternately applying 2 HZ-pulse electrical stimulation to the thumb and the little finger of the hand acupunctured with a 64-channel electroencephalogram. The verbal rating scale was used before and after each acupuncture stimulation session., Result and Discussion: The results of the study confirmed that the somatosensory evoked potential amplitude value of the thumb was significantly decreased and that the intensity of sensory stimulation corresponding to a verbal rating scale score of 6 was significantly increased only in the thumb after acupuncture stimulation. Therefore, the results show that acupuncture treatment for acute pain is more effective when direct acupuncture stimulation is applied to the painful area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Choi, Cho, Kim, Kwon, Kang, Seo, Bang and Ryu.)

Bolasterone (7α,17α-dimethyltestosterone) and anabolic androgenic steroids are included in the World Anti-Doping Agency's Prohibited list of substances. This study aimed to evaluate the metabolism of bolasterone through in vitro experiments using rat liver microsomes and in vivo experiments using rat urine after oral administration. Urine samples were collected over a 168-h period. Bolasterone and its metabolites were detected by liquid chromatography coupled with a Q-Exactive Obitrap mass spectrometry (LC-HRMS). Ultimately 16 hydroxylated metabolites (M1-M16), one metabolite from the reduction of the 3-keto function and 4-ene (M17), and one glucuronic acid conjugated metabolite (M18) were detected. Metabolites M17 and M18 were confirmed by comparison with available reference or authentic standards. Metabolic modifications in the structure of the parent bolasterone result in different fragmentation patterns. Based on the sensitivity of the HRMS data, characteristic ions such as m/z 121.064 (C 8 H 9 O) generated from ring A of the mono-hydroxylated metabolites and 121.101 (C 9 H 13 ) generated from ring D of the di-hydroxylated metabolites were observed that helped differentiate between the obtained metabolites. The structures of fragment ions were tentatively proposed based on their fragmentation pathways, where the significant ions were correlated to the possible structural fragments. In conclusion, new metabolites of bolasterone were detected and characterized by the use of the full-scan and dd-MS/MS using LC-HRMS, and this data can be useful for providing metabolite information for the interpretation of mass spectra of anabolic bolasterone analogues for doping screening tests., (© 2023 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Thymosin β4 (Tβ4) was reported to exert various beneficial bioactivities such as tissue repair, anti-inflammation, and reduced scar formation, and it is listed on the prohibited substances in sports by the World Anti-Doping Agency. However, no metabolism studies of Tβ4 were reported yet. Previously, our lab reported in in vitro experiment that a total of 13 metabolites were found by using multiple enzymes, and six metabolites (Ac-Tβ 31-43 , Ac-Tβ 17-43 , Ac-Tβ 1-11 , Ac-Tβ 1-14 , Ac-Tβ 1-15 , and Ac-Tβ 1-17 ) were confirmed by comparing with the synthetic standards. This study was aimed at identifying new metabolites of Tβ4 leucine aminopeptidase (LAP), human kidney microsomes (HKM), cultured huvec cells, and rats after administration of Tβ4 protein to develop biomarkers for detecting doping drugs in sports. A method for detecting and quantifying Ac-Tβ 1-14 was developed and validated using Q-Exactive orbitrap mass spectrometry. The limit of detection (LOD) and limit of quantification (LOQ) of the Ac-Tβ 1-14 were 0.19 and 0.58 ng/mL, respectively, and showed a good linearity (r 2  = 0.9998). As a result, among the six metabolites above, Ac-Tβ 1-14 , as a common metabolite, was found in LAP, HKM, huvec cells exposed to Tβ4, and the urine of rats intraperitoneally treated with 20-mg/kg Tβ4. And the metabolite Ac-Tβ 1-14 was quantitatively determined by 48 h in rats, with the highest concentration occurring between 0 and 6 h. Ac-Tβ 1-14 was not detected in non-treated control groups, including human blank urine. These results suggest that Ac-Tβ 1-14 in urine is a potential biomarker for screening the parent Tβ4 in doping tests., (© 2023 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)