Synthesis and medicinal chemical characterisation of antiproliferative O,N-functionalised isopulegol derivatives.

Benzylation of isopulegol furnished O-benzyl-protected isopulegol, which was transformed into aminodiols via epoxidation followed by ring opening of the corresponding epoxides and subsequent hydrogenolysis. On the other hand, (-)-isopulegol was oxidised to a diol, which was then converted into dibenzyl-protected diol derivatives. The products were then transformed into aminotriols by using a similar method. The antiproliferative activity of aminodiol and aminotriol derivatives was examined. In addition, structure-activity relationships were also explored from the aspects of substituent effects and stereochemistry on the aminodiol and aminotriol systems. The drug-likeness of the compounds was assessed by in silico and experimental physicochemical characterisations, completed by kinetic aqueous solubility and in vitro intestinal-specific parallel artificial membrane permeability assay (PAMPA-GI) measurements.

Artemisia argyi ethanol extract ameliorates nonalcoholic steatohepatitis-induced liver fibrosis by modulating gut microbiota and hepatic signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi (AA), a herbal medicine traditionally used in Asian countries, to treat inflammatory conditions such as eczema, dermatitis, arthritis, allergic asthma and colitis. However, the mechanism of action of this plant with regard to hepatitis and other liver-related diseases is still unclear. AIM: This study aimed to investigate the effects of AA ethanol extract on NASH-related fibrosis and gut microbiota in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model. METHODS: Male C57BL/6J mice were fed CDAHFD, with or without AA ethanol extract treatment. Biochemical markers, lipid profiles, hepatic mRNA expression levels of key genes, and the fibrosis area were assessed. In vitro, TGF-ß-stimulated human hepatic stellate LX-2 cells and mouse primary hepatic stellate cells (mHSCs) were used to elucidate the effects of AA ethanol extract on fibrosis and steatosis. 16S rRNA sequencing, QIIME2, and PICRUST2 were employed to analyze gut microbial diversity, composition, and functional pathways. RESULTS: Treatment with the AA ethanol extract improved plasma and liver lipid profiles, modulated hepatic mRNA expression levels of antioxidant, lipolytic, and fibrosis-related genes, and significantly reduced CDAHFD-induced hepatic fibrosis. Gut microbiota analysis revealed a marked decrease in Acetivibrio ethanolgignens abundance upon treatment with the AA ethanol extract, and its functional pathways were significantly correlated with NASH/fibrosis markers. The AA ethanol extract and its active components (jaceosidin, eupatilin, and chlorogenic acid) inhibited fibrosis-related markers in LX-2 and mHSC. CONCLUSION: The AA ethanol extract exerted therapeutic effects on CDAHFD-induced liver disease by modulating NASH/fibrosis-related factors and gut microbiota composition. Notably, AA treatment reduced the abundance of the potentially profibrotic bacterium (A. ethanolgignens). These findings suggest that AA is a promising candidate for treating NASH-induced fibrosis.

Vortex of regret: How positive and negative coping strategies correlate with feelings of guilt.

Bad coping behavior and guilt may reinforce each other as a negative feedback loop. Social contexts and expectations may also create cognitive dissonance in coping individuals and affect the effectiveness of coping styles. This study examines the associations between the feeling of guilt and specific coping styles belonging to both groups of positive and negative coping styles. We conducted Bayesian Multiple Regression analyses on secondary data from 3784 high school students in China. Positive coping is associated more with reduced feelings of guilt compared to negative coping. However, some positive coping styles were found to be positively associated with a sense of guilt, especially those involving confrontation against or conformity to social expectations. Most negative coping styles are positively associated with guilt, and substance use has the strongest influence among the examined negative coping styles. The findings suggest that the consideration of sociocultural contexts is very important in supporting those with guilt issues, especially adolescents in societies with dominant traditional East Asian values.

Physicochemical Characterization, Antioxidant and Tyrosinase Inhibitory Activities of Coffea Robusta Monofloral Honey from Dak Lak Province, Vietnam.

Robusta coffee blossom honey stands as a key regional product in Dak Lak province, Vietnam. Despite its significance, there exists a dearth of scientific data for assessing its quality. This study aims to fill this gap by characterizing the physicochemical properties and biological activities of coffee blossom honeys from three distinct sub-regions within Dak Lak province, Vietnam. These activities include ferric reducing power (FRP), DPPH and ABTS radical scavenging, as well as tyrosinase inhibitory activities. Moreover, the study compares these honey samples with other popular varieties in Vietnam, such as Lychee and Longan honeys. The physicochemical parameters of the honey samples meet the standards set by Codex Alimentarius 2001. Through UPLC analysis, eleven compounds were identified, with caffeine serving as a marker for coffee honey. Furthermore, by employing multiple factor analysis (MFA), it was observed that certain physicochemical properties correlate positively with tyrosinase inhibitory, DPPH, ABTS free radicals scavenging activities, and FRP. Notably, tyrosinase inhibitory activity exhibited a positive correlation with antioxidant activity. These findings underscore the high quality of Coffea robusta honey, showcasing its potent antioxidant and tyrosinase inhibitory activities.

Cornflower Extract and Its Active Components Alleviate Dexamethasone-Induced Muscle Wasting by Targeting Cannabinoid Receptors and Modulating Gut Microbiota.

Sarcopenia, a decline in muscle mass and strength, can be triggered by aging or medications like glucocorticoids. This study investigated cornflower (Centaurea cyanus) water extract (CC) as a potential protective agent against DEX-induced muscle wasting in vitro and in vivo. CC and its isolated compounds mitigated oxidative stress, promoted myofiber growth, and boosted ATP production in C2C12 myotubes. Mechanistically, CC reduced protein degradation markers, increased mitochondrial content, and activated protein synthesis signaling. Docking analysis suggested cannabinoid receptors (CB) 1 and 2 as potential targets of CC compounds. Specifically, graveobioside A from CC inhibited CB1 and upregulated CB2, subsequently stimulating protein synthesis and suppressing degradation. In vivo, CC treatment attenuated DEX-induced muscle wasting, as evidenced by enhanced grip strength, exercise performance, and modulation of muscle gene expression related to differentiation, protein turnover, and exercise performance. Moreover, CC enriched gut microbial diversity, and the abundance of Clostridium sensu stricto 1 positively correlated with muscle mass. These findings suggest a multifaceted mode of action for CC: (1) direct modulation of the muscle cannabinoid receptor system favoring anabolic processes and (2) indirect modulation of muscle health through the gut microbiome. Overall, CC presents a promising therapeutic strategy for preventing and treating muscle atrophy.

Stereoselective synthesis and antiproliferative activity of allo-gibberic acid-based 1,3-aminoalcohol regioisomers.

A new library of allo-gibberic acid-based aminoalcohol regioisomers was synthesised stereoselectively starting from commercially available gibberellic acid, which yields allo-gibberic acid under mild acidic conditions. The successful formation of hydroxymethyl ketone derivative 5, by acid-mediated rearrangement of previously prepared epoxide, paved the way to obtain the desired 1,3-aminoalcohols through Schiff base formation. To obtain the desired regioisomers, the primary alcohol functionality of 5 was subjected to mesylation, then replaced with either primary amine or sodium azide. The formed azide derivative was subjected to either CuAAC reaction to obtain 1,2,3-triazoles or underwent Pd-catalysed hydrogenolysis to obtain primary aminoalcohol, which was further transformed into 1,3-aminoalcohols by reductive alkylation. All prepared aminoalcohols were identified in a satisfactory manner using modern spectroscopic techniques and assessed for their antiproliferative activity against a panel of human cancer cell lines. The antiproliferative effects of the prepared compounds were assayed by in vitro MTT method against a panel of human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231). A significant difference was observed in the antiproliferative activity between the regioisomers. Some compounds exerted outstanding activities against the malignant cells with limited action on fibroblasts, indicating considerable cancer selectivity.

High-performance liquid chromatographic enantioseparation of azole analogs of monoterpene lactones and amides focusing on the separation characteristics of polysaccharide-based chiral stationary phases.

High-performance liquid chromatography-based enantioseparation of newly prepared azole analogs of monoterpene lactones and amides was studied. Effects of additives and mobile phase composition were evaluated both in normal and polar organic modes. Applying amylose tris-(3,5-dimethylphenylcarbamate) selector in normal and polar organic modes acid and base additives were found to affect the peak profiles, without significantly influencing the enantiorecognition ability of the studied selector. In most cases, differences observed in retention times and enantioselectivities were lower than 10 and 20 % under normal phase and polar organic conditions, respectively. Under normal phase conditions decreased retention was observed for all the studied analytes with increased eluent polarity. Interestingly, enantioselectivity was only slightly (<10 %) influenced by the variation in the n-hexane/2-propanol ratio between 80/20 and 20/80 v/v. In polar organic mode, five different neat solvents (acetonitrile, methanol, ethanol, 1-propanol, and 2-propanol) were tested, and the best results were obtained with acetonitrile and ethanol in the case of Lux Amylose-1 column with enantioresolutions most often above 2. Based on results obtained with amylose and cellulose-based columns the amylose tris-(3,5-dimethylphenylcarbamate) selector is found to offer a superior performance both in normal and polar organic modes. When evaluating the possible effects of the selector immobilization, no striking differences were found in the normal phase. Usually, enantioselectivities and resolutions were higher (10-20 %), while retention factors of the first peaks were lower (20-30 %), on the coated-type column. In contrast, in polar organic mode, the retention characteristics and enantiorecognition ability of the coated and immobilized selectors were heavily affected by the nature of the polar solvent. Special attention has been paid to the history-dependent behavior of polysaccharide-based selectors. A confidence interval-based evaluation is suggested to help comparison of the histereticity observed in different systems. Several examples are shown to confirm that the recently discovered hysteresis is a common characteristic of polysaccharide-based selectors.

Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation.

BACKGROUND: Atopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development. METHODS: We analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell-type-specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti-inflammatory effects of FVE were investigated. The anti-inflammatory effects of FVE were validated using a DNCB-induced mouse model of AD. Anti-inflammatory activity of compounds isolated from FVE was validated in each immune cell type. RESULTS: FVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro-inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL-33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti-inflammatory FVE compound. CONCLUSION: Forsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them.

Lithospermum erythrorhizon Siebold & Zucc. extract reduces the severity of endotoxin-induced uveitis.

BACKGROUND: Uveitis is an inflammatory eye condition that threatens vision, and effective anti-inflammatory treatments with minimal side effects are necessary to treat uveitis. PURPOSE: This study aimed to investigate the effects of Lithospermum erythrorhizon Siebold & Zucc. against endotoxin-induced uveitis in rat and mouse models. METHODS: Endotoxin-induced uveitis models of rats and mice were used to evaluate the effects of l. erythrorhizon treatment. Clinical inflammation scores and retinal thickness were assessed in the extract of l. erythrorhizon-treated rats. Histopathological examination revealed inflammatory cell infiltration into the ciliary body. Protein concentration, cellular infiltration, and prostaglandin-E2 levels were measured in the aqueous humor of the extract of l. erythrorhizon-treated rats. Protective effects of l. erythrorhizon on the anterior segment of the eye were examined in mice with endotoxin-induced uveitis. Additionally, we investigated the effect of l. erythrorhizon on the expression of pro-inflammatory cytokines [tumor necrosis factor alpha, interleukin-6, and interleukin-8] in lipopolysaccharide-stimulated THP1 human macrophages and examined the involvement of nuclear factor kappaB/activator protein 1 and interferon regulatory factor signaling pathways. Furthermore, three components of l. erythrorhizon were identified and assessed for their inhibitory effects on LPS-induced inflammation in RAW264.7 macrophage cells. RESULTS: Treatment of the extract of l. erythrorhizon significantly reduced clinical inflammation scores and retinal thickening in rats with endotoxin-induced uveitis. Histopathological examination revealed decreased inflammatory cell infiltration into the ciliary body. The extract of l. erythrorhizon effectively reduced the protein concentration, cellular infiltration, and PG-E2 levels in the aqueous humor of rats with endotoxin-induced uveitis. In mice with endotoxin-induced uveitis, the extract of l. erythrorhizon demonstrated a protective effect on the anterior segment of the eye by reducing inflammation and retinal thickening. The extract of l. erythrorhizon suppressed the expression of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-6, and interleukin-8) in lipopolysaccharide-induced inflammation in THP1 human macrophages, by modulating nuclear factor kappaB/activator protein 1 and interferon regulatory factor signaling pathways. Moreover, shikonin, acetylshikonin, and ß, ß-dimethylacryloylshikonin showed dose-dependent inhibition of nitric oxide, tumor necrosis factor alpha and interleukin-6 production in RAW264.7 macrophage cells. CONCLUSION: The extract of l. erythrorhizon is a potential therapeutic agent for uveitis management. Administration of the extract of l. erythrorhizon led to reduced inflammation, retinal thickening, and inflammatory cell infiltration in rat and mouse models of uveitis. The compounds (shikonin, acetylshikonin, and ß, ß-dimethylacryloylshikonin) identified in this study played crucial roles in mediating the anti-inflammatory effects of l. erythrorhizon. These findings indicate that the extract of l. erythrorhizon and its constituent compounds are promising candidates for further research and development of novel treatment modalities for uveitis.

Trust Is for the Strong: How Health Status May Influence Generalized and Personalized Trust.

In the trust-health relationship, how trusting other people in society may promote good health is a topic often examined. However, the other direction of influence-how health may affect trust-has not been well explored. In order to investigate this possible effect, we employed the Bayesian Mindsponge Framework (BMF) analytics to go deeper into the information processing mechanisms underlying the expressions of trust. Conducting a Bayesian analysis on a dataset of 1237 residents from Cali, Colombia, we found that general health status is positively associated with generalized trust, but recent experiences of illnesses/injuries have a negative moderating effect. Personalized trust is largely unchanged across different general health conditions, but the trust level becomes higher with recent experiences of illnesses/injuries. Psychophysiological mechanisms of increasing information filtering intensity toward unfamiliar sources during a vulnerable state of health is a plausible explanation of found patterns in generalized trust. Because established personal relationships are reinforced information channels, personalized trust is not affected as much. Rather, the results suggest that people may rely even more on loved ones when they are in bad health conditions. This exploratory study shows that the trust-health relationship can be examined from a different angle that may provide new insights.

Serum CA-125 as a predictor in the early diagnosis of ectopic pregnancy in Vietnam - A case-control study.

INTRODUCTION: This study aimed to determine the predictive value of cancer antigen-125 (CA-125) in combination with serum beta-human chorionic gonadotropin (ß-hCG) and progesterone in the early detection of ectopic pregnancy (EP). METHODS: Between May 2019 and May 2020, the cross-sectional study recruited 42 cases of EP and 42 cases of IUP at the same gestational age who visited the Department of Obstetrics and Gynecology, Hospital of Hue University of Medicine and Pharmacy. EP was diagnosed based on surgical (laparoscopy) and postoperative pathology examination. RESULTS: There were significant differences of mean level of ß-hCG (2570 mUI/mL vs. 18357.7 mUI/mL), progesterone (10.79 ± 8.16 ng/ml vs. 27.42 ± 4.17 ng/ml) and CA-125 (26.90 ± 10.26 U/mL vs. 70.61 ± 20.89 U/mL) between the EP and the IUP groups (p < 0.001). In the prediction of early diagnosis of EP, the cut-off value of CA-125 at 30.94 U/mL has a sensitivity of 89.3% and a specificity of 87,9%; the cut-off value of ß hCG at 2750mIU/ml has the sensitivity of 75%, specificity of 78,8%; the cut-off value of progesterone at 10.24 ng/mL has the sensitivity of 85.7%, specificity of 81.8%. A combination of CA-125, ß hCG, and progesterone had a sensitivity of 92.8% and a specificity of 90.9% in early diagnosis of EP. DISCUSSION: Serum CA-125 levels can be used independently or in combination with other markers in the early diagnosis of EP.

Examining the Influence of Exploration and Parental Education Attainment on Students' Acceptance of Collectivist Values.

Exploration can help students access a wider range of information and make connections among values within the natural and social world. This study investigated the relationship between students' previous exploration of their surroundings and their acceptance of collectivist values in the context of China. A sample of 343 college students was analyzed based on the Bayesian Mindsponge Framework to explore this relationship. The results revealed a positive association between students' prior exploration of surroundings and their degree of collectivist orientation. Furthermore, parental education attainment was found to negatively moderate this association, albeit with a small effect size. These findings contribute to the understanding of how information acquisition influences students' acceptance of collectivist values and highlight the potential role of the family infosphere in shaping this relationship.

A dataset of Chinese drivers' driving behaviors and socio-cultural factors related to driving.

Given the high fatality rate due to road traffic accidents in China, understanding the factors influencing aggressive driving behaviors among Chinese drivers is essential to alleviate the problem. The paper describes a dataset of 1039 Chinese drivers' driving behaviors and the socio-cultural factors associated with the behaviors. The dataset was collected through an online survey. The dataset comprises five main categories: 1) driving information, 2) aggressive driving behaviors, 3) friend/peer influence, 4) family influence, and 5) socio-demographic information. The dataset is valuable for public health and transportation researchers to explore factors influencing drivers' driving behaviors and public safety in China. The dataset's construct validity was confirmed by the Bayesian Mindsponge Framework (BMF) analytics. Specifically, the analysis shows that safe driving behaviors are affected by information promoting safe driving that is passively and actively absorbed from friends/peers (friends/peers being role models and friends'/peers' support, respectively). The result is consistent with the Mindsponge Theory's information-processing mechanism in human minds.

Roles for the Synechococcus elongatus RNA-Binding Protein Rbp2 in Regulating the Circadian Clock.

The cyanobacterial circadian oscillator, consisting of KaiA, KaiB, and KaiC proteins, drives global rhythms of gene expression and compaction of the chromosome and regulates the timing of cell division and natural transformation. While the KaiABC posttranslational oscillator can be reconstituted in vitro, the Kai-based oscillator is subject to several layers of regulation in vivo. Specifically, the oscillator proteins undergo changes in their subcellular localization patterns, where KaiA and KaiC are diffuse throughout the cell during the day and localized as a focus at or near the pole of the cell at night. Here, we report that the CI domain of KaiC, when in a hexameric state, is sufficient to target KaiC to the pole. Moreover, increased ATPase activity of KaiC correlates with enhanced polar localization. We identified proteins associated with KaiC in either a localized or diffuse state. We found that loss of Rbp2, found to be associated with localized KaiC, results in decreased incidence of KaiC localization and long-period circadian phenotypes. Rbp2 is an RNA-binding protein, and it appears that RNA-binding activity of Rbp2 is required to execute clock functions. These findings uncover previously unrecognized roles for Rbp2 in regulating the circadian clock and suggest that the proper localization of KaiC is required for a fully functional clock in vivo.

How AI's Self-Prolongation Influences People's Perceptions of Its Autonomous Mind: The Case of U.S. Residents.

The expanding integration of artificial intelligence (AI) in various aspects of society makes the infosphere around us increasingly complex. Humanity already faces many obstacles trying to have a better understanding of our own minds, but now we have to continue finding ways to make sense of the minds of AI. The issue of AI's capability to have independent thinking is of special attention. When dealing with such an unfamiliar concept, people may rely on existing human properties, such as survival desire, to make assessments. Employing information-processing-based Bayesian Mindsponge Framework (BMF) analytics on a dataset of 266 residents in the United States, we found that the more people believe that an AI agent seeks continued functioning, the more they believe in that AI agent's capability of having a mind of its own. Moreover, we also found that the above association becomes stronger if a person is more familiar with personally interacting with AI. This suggests a directional pattern of value reinforcement in perceptions of AI. As the information processing of AI becomes even more sophisticated in the future, it will be much harder to set clear boundaries about what it means to have an autonomous mind.

Near-Suicide Phenomenon: An Investigation into the Psychology of Patients with Serious Illnesses Withdrawing from Treatment.

Patients with serious illnesses or injuries may decide to quit their medical treatment if they think paying the fees will put their families into destitution. Without treatment, it is likely that fatal outcomes will soon follow. We call this phenomenon "near-suicide". This study attempted to explore this phenomenon by examining how the seriousness of the patient's illness or injury and the subjective evaluation of the patient's and family's financial situation after paying treatment fees affect the final decision on the treatment process. Bayesian Mindsponge Framework (BMF) analytics were employed to analyze a dataset of 1042 Vietnamese patients. We found that the more serious the illnesses or injuries of patients were, the more likely they were to choose to quit treatment if they perceived that paying the treatment fees heavily affected their families' financial status. Particularly, only one in four patients with the most serious health issues who thought that continuing the treatment would push themselves and their families into destitution would decide to continue the treatment. Considering the information-filtering mechanism using subjective cost-benefit judgments, these patients likely chose the financial well-being and future of their family members over their individual suffering and inevitable death. Our study also demonstrates that mindsponge-based reasoning and BMF analytics can be effective in designing and processing health data for studying extreme psychosocial phenomena. Moreover, we suggest that policymakers implement and adjust their policies (e.g., health insurance) following scientific evidence to mitigate patients' likelihood of making "near-suicide" decisions and improve social equality in the healthcare system.

An analytical framework-based pedagogical method for scholarly community coaching: A proof of concept.

Working in academia is challenging, even more so for those with limited resources and opportunities. Researchers around the world do not have equal working conditions. The paper presents the structure, operation method, and conceptual framework of the SM3D Portal's community coaching method, which is built to help Early Career Researchers (ECRs) and researchers in low-resource settings overcome the obstacle of inequality and start their career progress. The community coaching method is envisioned by three science philosophies (cost-effectiveness, transparency spirit, and proactive attitude) and established and operated based on the Serendipity-Mindsponge-3D knowledge (SM3D) management framework (i.e., mindsponge thinking and Bayesian Mindsponge Framework analytics serve as the coaching program's foundational theory and analytical tools). The coaching method also embraces Open Science's values for lowering the cost of doing science and encouraging the trainees to be transparent, which is expected to facilitate the self-correcting mechanism of science through open data, open review, and open dialogue. Throughout the training process, members are central beneficiaries by gaining research knowledge and skills, acquiring publication as the training's product, and shifting their mindsets from "I can't do it" to "I can do it," and at the same time transforming a mentee to be ready for a future mentor's role. The coaching method is thus one of the members, for the member, by the members.•The paper provides the structure, operation method, and conceptual framework of the SM3D Portal's community coaching method, which is built to help Early Career Researchers (ECRs) and researchers in low-resource settings overcome the obstacle of inequality and start their career progress.•The paper presents three major science philosophies envisioning the establishment and operation of scholarly community coaching.•The paper employs the mindsponge theory and BMF analytics to construct a conceptual framework explaining how an environment is created to help shift members' mindsets from "I can't do it" to "I can do it."

Predicting the severity of COVID-19 patients using the CD24-CSF1R index in whole blood samples.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has become one of the most serious public health crises worldwide. Most infected people are asymptomatic but are still able to spread the virus. People with mild or moderate illnesses are likely to recover without hospitalization, while critically ill patients face a higher risk of organ injury or even death. In this study, we aimed to identify a novel biomarker that can predict the severity of COVID-19 patients. Clinical information and RNA-seq data of leukocytes from whole blood samples with and without a COVID-19 diagnosis (n = 100 and 26, respectively) were retrieved from the National Center for Biotechnology Information Gene Expression Omnibus database. Raw data were processed using the Transcripts Per Million (TPM) method and then transformed using log2 (TPM+1) for normalization. The CD24-CSF1R index was established. Violin plots, Kaplan-Meier curves, ROC curves, and multivariate Cox proportional hazards regression analyses were performed to evaluate the prognostic value of the established index. The CD24-CSF1R index was significantly associated with ICU admission (n = 50 ICU, 50 non-ICU) and ventilatory status (n = 42 ventilation, 58 non-ventilation) with p = 4.186e-11 and p = 1.278e-07, respectively. The ROC curve produced a relatively accurate prediction of ICU admission with an AUC of 0.8524. Additionally, patients with a high index had significantly fewer mechanical ventilation-free days than patients with a low index (p = 6.07e-07). Furthermore, the established index showed a strong prognostic ability for the risk of using a ventilator in the multivariate Cox regression model (p < 0.001). The CD24-CSF1R index was significantly associated with COVID-19 severity. The established index could have potential implications for prognosis, disease severity stratification, and clinical management.

Neuroprotective Effects of Ethanol Extract of Polyscias fruticosa (EEPF) against Glutamate-Mediated Neuronal Toxicity in HT22 Cells.

In traditional herbal medicine, the Polyscias fruticosa has been frequently used for the treatment of ischemia and inflammation. Oxidative stress mediated by elevated glutamate levels cause neuronal cell death in ischemia and various neurodegenerative diseases. However, so far, the neuroprotective effects of this plant extract against glutamate-mediated cell death have not been investigated in cell models. The current study investigates the neuroprotective effects of ethanol extracts of Polyscias fruticosa (EEPF) and elucidates the underlying molecular mechanisms of EEPFs relevant to neuroprotection against glutamate-mediated cell death. The oxidative stress-mediated cell death was induced by 5 mM glutamate treatment in HT22 cells. The cell viability was measured by a tetrazolium-based EZ-Cytox reagent and Calcein-AM fluorescent dye. Intracellular Ca2+ and ROS levels were measured by fluorescent dyes, fluo-3 AM and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA), respectively. Protein expressions of p-AKT, BDNF, p-CREB, Bax, Bcl-2, and apoptosis-inducing factor (AIF) were determined by western blot analysis. The apoptotic cell death was measured by flow cytometry. The in vivo efficacy of EEPF was evaluated using the Mongolian gerbil mouse by surgery-induced brain ischemia. EEPF treatment showed a neuroprotective effect against glutamate-induced cell death. The EEPF co-treatment reduced the intracellular Ca2+ and ROS and apoptotic cell death. Furthermore, it recovered the p-AKT, p-CREB, BDNF, and Bcl-2 levels decreased by glutamate. The EEPF co-treatment suppressed the activation of apoptotic Bax, the nuclear translocation of AIF, and mitogen-activated protein kinase (MAPK) pathway proteins (ERK1/2, p38, JNK). Further, EEPF treatment significantly rescued the degenerative neurons in the ischemia-induced Mongolian gerbil in vivo model. EEPF exhibited neuroprotective properties that suppress glutamate-mediated neurotoxicity. The underlying mechanism of EEPF is increasing the level of p-AKT, p-CREB, BDNF, and Bcl-2 associated with cell survival. It has therapeutic potential for the treatment of glutamate-mediated neuropathology.

Biomedical materials for wound dressing: recent advances and applications.

Wound healing is vital to maintain the physiological functions of the skin. The most common treatment is the use of a dressing to cover the wound and reduce infection risk and the rate of secondary injuries. Modern wound dressings have been the top priority choice for healing various types of wounds owing to their outstanding biocompatibility and biodegradability. In addition, they also maintain temperature and a moist environment, aid in pain relief, and improve hypoxic environments to stimulate wound healing. Due to the different types of wounds, as well as the variety of advanced wound dressing products, this review will provide information on the clinical characteristics of the wound, the properties of common modern dressings, and the in vitro, in vivo as well as the clinical trials on their effectiveness. The most popular types commonly used in producing modern dressings are hydrogels, hydrocolloids, alginates, foams, and films. In addition, the review also presents the polymer materials for dressing applications as well as the trend of developing these current modern dressings to maximize their function and create ideal dressings. The last is the discussion about dressing selection in wound treatment and an estimate of the current development tendency of new materials for wound healing dressings.