Tailoring the Structure-Property Relationship of Ring-Opened Metathesis Copolymers for CO2-Selective Membranes.

In this work, we explore the use of ring-opening metathesis polymerization (ROMP) facilitated by a second-generation Grubbs catalyst (G2) for the development of advanced polymer membranes aimed at CO2 separation. By employing a novel copolymer blend incorporating 4,4'-oxidianiline (ODA), 1,6-hexanediamine (HDA), 1-adamantylamine (AA), and 3,6,9-trioxaundecylamine (TA), along with a CO2-selective poly(ethylene glycol)/poly(propylene glycol) copolymer (Jeffamine2003) and polydimethylsiloxane (PDMS) units, we have synthesized membranes under ambient conditions with exceptional CO2 separation capabilities. The strategic inclusion of PDMS, up to a 20% composition within the PEG/PPG matrix, has resulted in copolymer membranes that not only surpass the 2008 upper limit for CO2/N2 separation but also meet the commercial targets for CO2/H2 separation. Comprehensive analysis reveals that these membranes adhere to the mixing rule and exhibit percolation behavior across the entire range of compositions (0-100%), maintaining robust antiplasticization performance even under pressures up to 20 atm. Our findings underscore the potential of ROMP in creating precisely engineered membranes for efficient CO2 separation, paving the way for their application in large-scale environmental and industrial processes.

In Situ Changes in Mechanical Properties Based on Gas Saturation Inside Pressure Vessels.

In previous studies, difficulties were encountered in measuring changes within high-pressure vessels owing to limitations such as sensor connectors and sensor failures under high-pressure conditions. In addition, polymer-gas mixtures experience instantaneous gas desorption upon exiting high-pressure vessels owing to pressure differentials, leading to measurement errors. In this study, a device using magnetic sensors was developed to measure the real-time changes in gas-saturated polymers inside pressure vessels. Experiments on polymethyl methacrylate gas adsorption were conducted with parameters including pressure at 5 MPa and temperatures ranging from -20 to 40 °C for 60 and 180 min. It was observed that at -20 °C, the maximum magnetic field force density and deflection were 391.53 µT and 5.83 mm, respectively, whereas at 40 °C, deflection did not occur, with a value of 321.79 µT. Based on gas saturation experiments, a new model for deflection in high-pressure atmospheres is proposed. Additionally, an ANSYS analysis was conducted to predict the changes in Young's modulus based on gas saturation. In previous studies, mechanical properties were measured outside the pressure vessel, resulting in an error due to a pressure difference, while the proposed method is characterized by the ability to directly measure polymer behavior according to gas saturation in high-pressure vessels using a magnetic sensor in real time. Therefore, it is possible to predict polymer behavior, making it easy to control variables in high-pressure polymer processes.

Surgical outcome and risk scoring to predict survival after hepatic resection for hepatocellular carcinoma with portal vein tumor thrombosis.

Backgrounds/Aims: The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT. Methods: We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea. Results: The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA-II, neutrophil-to-lymphocyte ratio, and albumin-bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors-tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, p < 0.001). Conclusions: HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.

Exploring the feasibility of robotic liver resection in a limited resource setting.

The transition from open hepatectomy to minimally invasive techniques has reduced morbidity and mortality. However, laparoscopic liver resection (LLR) requires substantial expertise. Robotic liver resection (RLR) combines minimal invasiveness with open surgical precision. It may facilitate complex procedures without the learning required for LLR. We evaluated RLR outcomes in a limited resource setting and assessed its efficacy and practicality. This retrospective study analyzed 67 robotic hepatectomies conducted from 2020 to 2023. Demographic, perioperative factors, and surgical outcomes were analyzed. Major hepatectomies were required in 46/67 (68.7%) patients who underwent RLR. No open conversions, 30-day mortalities, or readmissions occurred. Complications occurred in 7.4% of patients; major complications occurred in 5.9%. Learning curve analysis showed a negative correlation between operation sequence and operative time. Effective use of robotic technology combined with the expertise of well-trained surgeons facilitates successful execution of RLR with feasible surgical outcomes, even at smaller centers.

External Validation of Deep Learning-Based Cardiac Arrest Risk Management System for Predicting In-Hospital Cardiac Arrest in Patients Admitted to General Wards Based on Rapid Response System Operating and Nonoperating Periods: A Single-Center Study.

OBJECTIVES: The limitations of current early warning scores have prompted the development of deep learning-based systems, such as deep learning-based cardiac arrest risk management systems (DeepCARS). Unfortunately, in South Korea, only two institutions operate 24-hour Rapid Response System (RRS), whereas most hospitals have part-time or no RRS coverage at all. This study validated the predictive performance of DeepCARS during RRS operation and nonoperation periods and explored its potential beyond RRS operating hours. DESIGN: Retrospective cohort study. SETTING: In this 1-year retrospective study conducted at Yonsei University Health System Severance Hospital in South Korea, DeepCARS was compared with conventional early warning systems for predicting in-hospital cardiac arrest (IHCA). The study focused on adult patients admitted to the general ward, with the primary outcome being IHCA-prediction performance within 24 hours of the alarm. PATIENTS: We analyzed the data records of adult patients admitted to a general ward from September 1, 2019, to August 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Performance evaluation was conducted separately for the operational and nonoperational periods of the RRS, using the area under the receiver operating characteristic curve (AUROC) as the metric. DeepCARS demonstrated a superior AUROC as compared with the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS), both during RRS operating and nonoperating hours. Although the MEWS and NEWS exhibited varying performance across the two periods, DeepCARS showed consistent performance. CONCLUSIONS: The accuracy and efficiency for predicting IHCA of DeepCARS were superior to that of conventional methods, regardless of whether the RRS was in operation. These findings emphasize that DeepCARS is an effective screening tool suitable for hospitals with full-time RRS, part-time RRS, and even those without any RRS.

Research status of east Asian traditional medicine treatment for chronic cough: A scoping review.

BACKGROUND: When patients continue to experience cough despite conventional treatment, East Asian traditional medicine (EATM) including herbal medicine and/or acupuncture has been frequently used. Previous systematic reviews of EATM treatment for chronic cough have been conducted mainly on herbal medicine, targeting patients with conditions that cause cough. In clinical practice, EATM interventions are not limited to herbal medicine, and considering that chronic cough is often caused by two or more conditions or unspecific causes, a comprehensive investigation is clinically relevant. We examined the current research status of EATM for chronic cough. METHODS: Based on Arksey and O'Malley's scoping review methodological framework, a total of six English, Chinese, Korean, and Japanese electronic databases were searched on August 2022. Any clinical studies on EATM targeting chronic cough patients (regardless of their cause) were included. RESULTS: Among 474 included studies, the study designs were mainly randomized controlled trials (72.4%), and the population was evenly distributed between children and adults. The cause of cough was not reported in most studies (56.1%). The common cause of cough was upper airway cough syndrome and post-respiratory infection (9.5%, each), followed by mixed cause (7.6%), nonspecific cause (5.9%), and gastroesophageal reflux disease (4.0%). EATM was conducted for a mean of 19.1 days, and herbal medicine was the most common (80.6%). Conventional medication was frequently used as a control (81.2%). For outcomes, the total effective rate was the most frequently utilized (94.3%), followed by cough severity (53.8%). EATM treatment showed positive outcomes in most studies. CONCLUSIONS: In future EATM studies, it is necessary to either specify the cause of chronic cough or to report that the study was targeting nonspecific chronic cough. In addition, high-quality studies assessing the efficacy of EATM with placebo control treatment should be conducted, using validated evaluation tools.

The Effectiveness and Safety of Chuna Manual Therapy Adjuvant to Western Medicine in Patients with Chronic Obstructive Pulmonary Disease: A Randomized, Single-Blind, Investigator-Initiated, Pilot Trial.

Recently, non-pharmacological treatments are gaining increasing importance for improving the quality of life in patients with chronic obstructive pulmonary disease (COPD). This pilot study aimed to evaluate the feasibility of conducting extensive research on Chuna manual therapy (CMT). This study investigated the effectiveness and safety of CMT adjuvant to Western medicine (WM) in patients with COPD. Forty patients with COPD were randomized into two groups in a 1:1 ratio: experimental (CMT plus WM) and control (WM only) groups. The CMT intervention was administered once a week for eight weeks. The primary outcome measured was the 6-min walk distance (6MWD). Secondary outcomes measured were: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), assessments using the modified Medical Research Council (mMRC) scale and Visual Analog Scale (VAS) for dyspnea, the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), and the EuroQoL five-dimensional questionnaire (EQ-5D). The mean differences in FEV1 (L) between Weeks 1 and 8 were statistically significant between the groups (p = 0.039). Additionally, the experimental group showed improved 6MWD, mMRC, VAS for dyspnea, CAT, SGRQ (total), and EQ-VAS scores than the control group. However, the differences between the two groups were not statistically significant. No adverse events were observed during this trial. CMT has the potential to alleviate symptoms, improve quality of life, and delay the decline in lung function in patients with COPD. The results of this pilot study could lead to large-scale clinical trials in the future.

Tuning Polarity in WSe2/AlScN FeFETs via Contact Engineering.

Recent advancements in ferroelectric field-effect transistors (FeFETs) using two-dimensional (2D) semiconductor channels and ferroelectric Al0.68Sc0.32N (AlScN) allow high-performance nonvolatile devices with exceptional ON-state currents, large ON/OFF current ratios, and large memory windows (MW). However, previous studies have solely focused on n-type FeFETs, leaving a crucial gap in the development of p-type and ambipolar FeFETs, which are essential for expanding their applicability to a wide range of circuit-level applications. Here, we present a comprehensive demonstration of n-type, p-type, and ambipolar FeFETs on an array scale using AlScN and multilayer/monolayer WSe2. The dominant injected carrier type is modulated through contact engineering at the metal-semiconductor junction, resulting in the realization of all three types of FeFETs. The effect of contact engineering on the carrier injection is further investigated through technology-computer-aided design simulations. Moreover, our 2D WSe2/AlScN FeFETs achieve high electron and hole current densities of ∼20 and ∼10 µA/µm, respectively, with a high ON/OFF ratio surpassing ∼107 and a large MW of >6 V (0.14 V/nm).

Phenolic changes in a combined herbal extract of Lithospermum erythrorhizon, Houttuynia cordata, and Spirodela polyrhiza and alleviation of DNCB-induced atopic dermatitis in BALB/c mice.

Atopic dermatitis (AD) is an inflammatory skin disease showing skin barrier dysfunction, eczematous lesions, severe itching, and abnormal immune responses. The aim of this study was to determine whether an herb combination of Lithospermum erythrorhizon (LE), Houttuynia cordata (HC), and Spirodela polyrhiza (SP) has a superior anti-AD effect. Forty-two compounds were identified in LE, HC, SP, and a combined herb extract of LE, HC, and SP (LHS) using ultra-high-pressure liquid chromatography (UHPLC)-Orbitrap mass spectrometer (MS). The concentration of flavonoid glycosides including orientin (luteolin-8-C-glucoside), quercetin-3-O-rhamnoside, and luteolin-7-O-glucoside in the LHS was increased than in individual extracts. Furthermore, the treatment of LHS most effectively inhibited the increase of epidermal thickness, the number of mast cells, and the release of immunoglobulin E compared with that with each extract. These results suggest that the potential anti-AD effects of the LHS are due to the changes of bioactive compounds by the combination of herbs. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01329-7.

Anti-photoaging effects of canola meal extract on human dermal fibroblasts against UVB-induced oxidative stress.

Canola meal, a by-product of canola oil processing, is a source of bioactive compounds that show antioxidant and skin anti-aging effects through upcycling (i.e., creative reuse). Here we describe the antioxidant and skin anti-aging effects of canola meal extract (CME) obtained by upcycling canola meal. The antioxidant capacity of CME is due in part to its antioxidative phenolics. Seven phenolics, including sinapine and sinapic acid, in CME were identified using ultra-high-performance liquid chromatography-Orbitrap mass spectrometry. Addition of CME (1000 µg/mL) to human dermal fibroblast neonatal cells  significantly (p < 0.05) reduced matrix metalloproteinase-12 production and increased pro-collagen Ι alpha 1 content in response to ultraviolet B-induced oxidative stress compared with cells without CME. These results suggest that CME can serve as a functional food ingredient with antioxidant capacity and anti-aging effects on the skin.

Intrahepatic Cholangiocarcinoma in Wilson's Disease: A Case Report.

BACKGROUND Wilson's disease is a rare autosomal recessive disorder characterized by excessive accumulation of copper in the liver, brain, and kidneys. Although it affects only approximately 1 in 30 000 individuals, it leads to progressive liver damage and neurological issue. Wilson's disease presents a wide spectrum of clinical manifestations related to hepatic disease, ranging from asymptomatic cases to acute liver failure. The occurrence of hepatobiliary malignancies, including intrahepatic cholangiocarcinoma, is relatively uncommon in Wilson's disease, even among patients with cirrhosis. Only 14 cases have been published so far, including the present report, and its etiology remains unclear. CASE REPORT We report the successful treatment of intrahepatic cholangiocarcinoma in a 39-year-old woman with Wilson's disease. Twenty-two years after being diagnosed with Wilson's disease, intrahepatic cholangiocarcinoma was diagnosed. She had an intrahepatic mass that was found to be a 4.3-cm ill-defined hypodense lesion in liver segment 3/4, with features suggesting infiltrative intrahepatic cholangiocarcinoma rather than hepatocellular carcinoma. Laboratory results showed slightly elevated liver enzymes and tumor markers. There was no evidence of metastasis on chest computed tomography or positron emission tomography, and the tumor was resectable, so surgery was the first-choice treatment option. Left hepatectomy was performed successfully, and the final pathology confirmed adenocarcinoma with clear resection margins. The patient received adjuvant chemotherapy with capecitabine. To date, the patient has been doing well without evidence of recurrence or metastasis. CONCLUSIONS Despite limited knowledge regarding hepatic malignancy in Wilson's disease, it is crucial to prioritize careful monitoring and develop suitable treatment strategies upon diagnosis to achieve favorable outcomes, considering the potential occurrence of intrahepatic cholangiocarcinoma in Wilson's disease.

Understanding experiences of cancer-related fatigue in patients with lung cancer after their cancer treatment: a qualitative content analysis.

PURPOSE: Cancer-related fatigue (CRF) is an important symptom affecting the quality of life of patients with lung cancer. However, research on the characteristics of CRF in lung cancer and their relationship to cancer treatment is limited. We aimed to explore the unique features of CRF in patients with lung cancer, and investigate the influencing factors. METHODS: Semi-structured interviews were conducted with 21 adult patients with lung cancer until data saturation was reached. The collected data were analyzed using qualitative content analysis. An inductive coding process and deductive content analysis incorporating the established CRF domains were employed. Patient data from electronic medical records were used for data triangulation. RESULTS: The analysis revealed five themes of CRF: (1) energy depletion, the double burden of illness and treatment, and daily life impediments; (2) feeling down and anxious; (3) neurovascular disturbances and changes in sensory perception; (4) cognitive impairment; and (5) personal and social isolation. CRF tended to improve over time, except for persistent emotional fatigue beyond 6 months. Patients who underwent surgery followed by adjuvant cancer treatment exhibited the most diverse CRF symptoms. The concurrent chemoradiation therapy group experienced significant physical fatigue, whereas the radiosurgery group reported distinct emotional fatigue. Certain factors, such as exercise, can serve as both alleviating and aggravating factors for CRF. CONCLUSION: Tailored interventions that take into account the multidimensional symptoms of CRF and patient characteristics are crucial. These findings will guide healthcare professionals when implementing patient-centered symptom management and patient education.

A pH-Responsive Virus-Like Particle as a Protein Cage for a Targeted Delivery.

A stimuli-responsive protein self-assembly offers promising utility as a protein nanocage for biotechnological and medical applications. Herein, the development of a virus-like particle (VLP) that undergoes a transition between assembly and disassembly under a neutral and acidic pH, respectively, for a targeted delivery is reported. The structure of the bacteriophage P22 coat protein is used for the computational design of coat subunits that self-assemble into a pH-responsive VLP. Subunit designs are generated through iterative computational cycles of histidine substitutions and evaluation of the interaction energies among the subunits under an acidic and neutral pH. The top subunit designs are tested and one that is assembled into a VLP showing the highest pH-dependent structural transition is selected. The cryo-EM structure of the VLP is determined, and the structural basis of a pH-triggered disassembly is delineated. The utility of the designed VLP is exemplified through the targeted delivery of a cytotoxic protein cargo into tumor cells in a pH-dependent manner. These results provide strategies for the development of self-assembling protein architectures with new functionality for diverse applications.

Propensity Score Matched Comparison of Robotic Single-Site and Laparoscopic Cholecystectomy.

Background and Objectives: To demonstrate the feasibility and potential of robotic single-site cholecystectomy, the study aimed to compare it with conventional laparoscopic cholecystectomy. Methods: In total, 791 consecutive patients underwent conventional laparoscopic cholecystectomy or robotic single-site cholecystectomy at our center between 2019 and 2022. After 1:1 propensity score matching, 117 patients for each group were selected. Results: After propensity score matching, the only statistically significant difference between conventional laparoscopic cholecystectomy and robotic single-site cholecystectomy was operative time, which was 29.15 ±11.45 min in the conventional laparoscopic cholecystectomy group versus 38.57 ± 12.59 min in the robotic single-site cholecystectomy group (P < 0.001). Because the difference in surgical time between the two groups was minimal, it has little clinical relevance. Using cumulative sum analysis, the maturation phase of the total operation and docking times occurred after the 53rd case. To reduce bias, a comparison of results with conventional laparoscopic cholecystectomy and cases of robotic single-site cholecystectomy was performed in the maturation phase, which revealed only total operative time as statistically significant (P < 0.001). Conclusion: Robotic single-site cholecystectomy is a technically feasible and safe method for treating benign gallbladder diseases, with a relatively short learning curve and reasonable operative time.

Acetylcorynoline Induces Apoptosis and G2/M Phase Arrest through the c-Myc Signaling Pathway in Colon Cancer Cells.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua Cham. et Schltdl tubers. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrate that ACN inhibited c-Myc expression through CNOT2 and MID1IP1, and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.

Herbal medicine for the treatment of chronic cough: a systematic review and meta-analysis.

Objectives: Chronic cough is a frequent condition worldwide that significantly impairs quality of life. Herbal medicine (HM) has been used to treat chronic cough due to the limited effectiveness of conventional medications. This study aimed to summarize and determine the effects of HM on patients with chronic cough. Methods: A comprehensive search of 11 databases was conducted to find randomized controlled clinical trials (RCTs) that reported the effects of HM for patients with chronic cough on 16 March 2023. The primary outcome was cough severity, and the secondary outcomes included cough-related quality of life, cough frequency, total effective rate (TER), and cough recurrence rate. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool, and the certainty of the evidence for effect estimates was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations tool. Results: A total of 80 RCTs comprising 7,573 patients were included. When HM was used as an alternative therapy to conventional medication, there were inconsistent results in improving cough severity. However, HM significantly improved cough-related quality of life and TER and significantly lowered the cough recurrence rate compared with conventional medication. When used as an add-on therapy to conventional medication, HM significantly improved cough severity, cough-related quality of life, and TER and significantly lowered the recurrence rate. In addition, HM had a significantly lower incidence of adverse events when used as an add-on or alternative therapy to conventional medication. The subgroup analysis according to age and cause of cough also showed a statistically consistent correlation with the overall results. The certainty of the evidence for the effect of HM was generally moderate to low due to the risk of bias in the included studies. Conclusion: HM may improve cough severity and cough-related quality of life, and lower the cough recurrence rate and incidence of adverse events in patients with chronic cough. However, due to the high risk of bias and clinical heterogeneity of the included studies, further high-quality placebo-controlled clinical trials should be conducted using a validated and objective assessment tool. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023418736, CRD42023418736.

Universal primers for rift valley fever virus whole-genome sequencing.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease causing acute hemorrhagic fever. Accurate identification of mutations and phylogenetic characterization of RVF virus (RVFV) require whole-genome analysis. Universal primers to amplify the entire RVFV genome from clinical samples with low copy numbers are currently unavailable. Thus, we aimed to develop universal primers applicable for all known RVFV strains. Based on the genome sequences available from public databases, we designed eight pairs of universal PCR primers covering the entire RVFV genome. To evaluate primer universality, four RVFV strains (ZH548, Kenya 56 (IB8), BIME-01, and Lunyo), encompassing viral phylogenetic diversity, were chosen. The nucleic acids of the test strains were chemically synthesized or extracted via cell culture. These RNAs were evaluated using the PCR primers, resulting in successful amplification with expected sizes (0.8-1.7 kb). Sequencing confirmed that the products covered the entire genome of the RVFV strains tested. Primer specificity was confirmed via in silico comparison against all non-redundant nucleotide sequences using the BLASTn alignment tool in the NCBI database. To assess the clinical applicability of the primers, mock clinical specimens containing human and RVFV RNAs were prepared. The entire RVFV genome was successfully amplified and sequenced at a viral concentration of 108 copies/mL. Given the universality, specificity, and clinical applicability of the primers, we anticipate that the RVFV universal primer pairs and the developed method will aid in RVFV phylogenomics and mutation detection.

Effects of herbal medicines (Eunkyosan/Yin qiao san and Samsoeum/Shen su yin) for treating the common cold: A randomized, placebo-controlled, multicenter clinical trial.

Background: Eunkyosan (EKS) and Samsoeum (SSE), which are called Yin qiao san and Shen su yin in Chinese, are commonly used herbal medicines for the common cold in East Asian countries. This study aimed to evaluate the effectiveness and safety of EKS and SSE for treating the common cold. Methods: A randomized, patient-assessor-blind, placebo-controlled, parallel, and multicenter clinical trial was conducted. Adult participants who had one or more cold within 48 h before screening, were randomly allocated to EKS, SSE, or placebo groups. The recruitment goal was planned to be 375 participants. They took an EKS, SSE, or placebo, thrice daily for up to 8 days. The primary outcome was the change in the total score of the Wisconsin Upper Respiratory Symptom Scale-21-Korean version (WURSS-21-K) on day 6 compared to the baseline. The secondary outcomes included visual analog scale (VAS) scores and the duration of symptoms was assessed throughout the trial. Results: A total of 128 participants were enrolled and 44, 42, and 42 were allocated to the EKS, SSE, and placebo groups, respectively. This study was prematurely terminated due to the COVID-19 pandemic, and we were unable to recruit all the planned participants (n = 375). EKS showed significant clinical effectiveness over the placebo group in the treatment of the common cold, as assessed by the total, symptom, and quality of life scores of WURSS-21-K and VAS, whereas SSE showed significant improvement over the placebo group in terms of WURSS-21-K symptom score. No severe adverse events were reported. Conclusions: Although EKS and SSE demonstrated statistically significant clinical effectiveness and safety in patients with the common cold, we failed to recruit our pre-planned number of participants. Future definitive full-scale studies are needed to confirm these results. Trial registration: ClinicalTrials. gov, registration number: NCT04073511. Registered on 29 August 2019.

Modafinil exerts anti-inflammatory and anti-fibrotic effects by upregulating adenosine A2A and A2B receptors.

Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression contributes to the development of fibrotic diseases and whether A2AAR and A2BAR upregulation inhibits fibrotic responses. Primary human lung fibroblasts (HLFs) from normal (NHLFs) or patients with idiopathic pulmonary fibrosis (DHLF) were used for in vitro testing. Murine models of fibrotic liver or pulmonary disease were developed by injecting thioacetamide intraperitoneally, by feeding a high-fat diet, or by intratracheal instillation of bleomycin. Modafinil, which activates cAMP signaling via A2AAR and A2BAR, was administered orally. The protein amounts of A2AAR, A2BAR, and exchange protein directly activated by cAMP (Epac) were reduced, while collagen and α-smooth muscle actin (α-SMA) were elevated in DHLFs compared to NHLFs. In liver or lung tissue from murine models of fibrotic diseases, A2AAR and A2BAR were downregulated, but A1AR and A3AR were not. Epac amounts decreased, and amounts of collagen, α-SMA, KCa2.3, and KCa3.1 increased compared to the control. Modafinil restored the amounts of A2AAR, A2BAR, and Epac, and reduced collagen, α-SMA, KCa2.3, and KCa3.1 in murine models of fibrotic diseases. Transforming growth factor-ß reduced the amounts of A2AAR, A2BAR, and Epac, and elevated collagen, α-SMA, KCa2.3, and KCa3.1 in NHLFs; however, these alterations were inhibited by modafinil. Our investigation revealed that A2AAR and A2BAR downregulation induced liver and lung fibrotic diseases while upregulation attenuated fibrotic responses, suggesting that A2AAR and A2BAR-upregulating agents, such as modafinil, may serve as novel therapies for fibrotic diseases.