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• Vupanorsen, an ASO targeting ANGPTL3, reduced TGs but increased hepatic fat. • 227 patients randomized to vupanorsen or placebo were included in this analysis. • Increases in hepatic fat related to ANGPTL3 inhibition and baseline risk factors. • Hepatic fat changes with vupanorsen only moderately correlated with AST and ALT. • Hepatic fat should be monitored in trials of triglyceride-lowering therapies. Angiopoietin-like protein 3 (ANGPTL3) is a novel therapeutic target for hyperlipidemia. Vupanorsen, an antisense oligonucleotide targeting ANGPTL3, reduced triglycerides up to 57% in a phase 2b trial, but caused dose-dependent increases in hepatic fat fraction (HFF). To determine the degree of HFF progression with escalating doses of vupanorsen, differential HFF increases in key patient subgroups, and the correlation between changes in HFF and liver enzymes. TRANSLATE-TIMI 70 was a randomized, placebo-controlled trial testing 7 dosing regimens of vupanorsen in 286 adults with hyperlipidemia. A total of 227 patients had HFF measured at baseline and 24 weeks and were included in this analysis. The median HFF at baseline was 8.5%. Vupanorsen led to dose-dependent relative increases in HFF of up to 76% at 24 weeks (p < 0.001), corresponding to an absolute increase of up to 7.0% at the highest dose (p < 0.001). Increases in HFF were numerically greater in patients who had elevated baseline HFF, body mass index, triglycerides, or diabetes. Vupanorsen also increased liver enzymes in a dose-dependent manner, and changes in HFF were moderately positively correlated with changes in aspartate transaminase (AST) (rho = 0.49, p < 0.001) and alanine transaminase (ALT) (rho = 0.50, p < 0.001). Vupanorsen, an inhibitor of ANGPTL3 protein synthesis, caused dose-dependent increases in HFF. Increases in HFF were only moderately correlated with elevations in AST and ALT, suggesting that liver enzymes are an imperfect indicator to detect increases in hepatic fat. These results highlight the need to monitor HFF in clinical trials of therapies targeting intracellular ANGPTL3 inhibition, especially those that are targeted to the liver. [ABSTRACT FROM AUTHOR]

Maternal exposure to dibutyl phthalate (DBP) may result in obesity in female offspring. However, the underlying mechanisms remain elusive. Sprague-Dawley rats were intraperitoneally injected with different doses of DBP and corn oil from gestational day 7 until the end of lactation. The weights, visceral fat percentage, serum lipid, insulin and glucose, protein levels of PI3K signal pathway in muscle were detected in F1 female offspring. Although the birth weight of F1 female offspring was not different among groups, the weights were heavier in DBP groups from postnatal day 7 to adult (P < 0.001). The visceral adipose percentage in adult female offspring was increased by perinatal exposure to DBP (P < 0.001). Decreased serum level of triglyceride (P = 0.001) in F1 female offspring was found in DBP group as compared to control, especially in medium and high DBP. However, none difference was found for fasting glucose, prolactin, HOMA-IR, fasting insulin, total cholesterol, adiponectin. Different protein levels of GPR30 were observed in muscle of female offspring among four groups (P = 0.016). The protein level of AKT seemed higher in DBP group but without statistical significance (P = 0.05). None difference was observed for the protein levels of PI3K, p-AKT, pAKT/AKT, PTEN, GLUT4, InsR, IRS. Maternal perinatal exposure to DBP might induce obesity and accumulation of visceral adipose tissue for the adult female offspring. Serum glucolipid and local signal transduction of PTEN/PI3K/AKT pathway in muscle were not adversely affected by perinatal exposure to DBP for adult female offspring. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency poses a global public health burden; however, there are limited studies on the relationship between vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) concentration in Koreans with a special focus on seasonal variables. We hypothesized that the relationship between serum 25(OH)D and vitamin D intake levels in Korean adults would change with the seasons, and that the distribution of food sources for vitamin D would vary according to sex and age. We established a new version of the food vitamin D database, analyzed the Korean National Health and Nutrition Examination Survey 2013 to 2014 data (n = 3257), and calculated the vitamin D intake of Koreans using a complex sample model. We found that the daily vitamin D intakes of men and women were 4.09 ± 0.26 µg and 2.87 ± 0.17 µg and their 25(OH)D levels were 16.98 ± 0.24 ng/mL and 15.62 ± 0.21 ng/mL, respectively. A significant positive correlation was observed between vitamin D intake and serum 25(OH)D levels in all participants. Serum 25(OH)D levels in the spring and winter (low ultraviolet irradiation seasons) were significantly higher in the 3rd tertile of vitamin D intake than in the first tertile. Fish and shellfish were the main sources of vitamin D for Koreans, the consumption of which was the least in the 19- to 29-year-old group; additionally, their serum 25(OH)D level was the lowest. In conclusion, insufficient vitamin D intake during low ultraviolet irradiation seasons is associated with lower levels of serum 25(OH)D. Serum 25-hydroxyvitamin D levels in the spring and winter (low ultraviolet irradiation seasons) were significantly higher in the third tertile of vitamin D intake than in the first tertile. However, the summer and fall (high ultraviolet irradiation seasons) were not significant. In this case, the median value of vitamin D intake was 0.97 to 2.59 µg/d. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aims to carry out a meta-analysis of attitudes, knowledge, and skills level of nursing students and nurses in EBP, providing a reference for optimizing EBP education strategies. At present, no meta-analysis has been performed to quantitatively synthesize the attitudes, knowledge and skill levels of nursing students and nurses toward EBP. This makes it difficult to precisely identify the true level of EBP among nurses, implying that there is no evidence to support the adoption of EBP teaching strategies approaches. A total of 9 Chinese and English databases including CNKI, Wan fang, VIP, CBM, PubMed, Embase, Web of Science, Cochrane Library and CINAHL were used to search cross-sectional quantitative articles on EBP attitudes, knowledge and skills level of nurses and nursing students. The search time limit was from the inception of the database to September 2023. Two researchers independently screened the literature and extracted the data. The Agency for Healthcare Research and Quality (AHRQ) was used to assess the quality of the included studies. Stata15.0 software was used for statistical analysis to summarize the scores of EBP attitude, knowledge and skills level of nursing students and nurses included in the study. A total of 25 cross-sectional studies from 13 countries were included, involving 11363 nursing students and nurses. The meta-analysis results revealed that nursing students and nurses lacked evidence-based practical knowledge and skills, with pooled mean scores of 3.06 (95 % CI: 2.72, 3.39), 2.91 (95 % CI: 2.60, 3.22), 4.31 (95 % CI: 4.08, 4.54) and 4.45 (95 % CI: 4.20, 4.70). In contrast, nursing students and nurses revealed a positive attitude towards EBP, with pooled mean scores of 3.57 (95 % CI: 3.28, 3.86) and 5.11 (95 % CI: 4.80, 5.42). Subgroup analysis revealed that senior nursing students and nurses with master's degree or above had higher attitudes, knowledge and skills. In summary, nursing students and nurses have a positive attitude towards EBP. However, they seem to lack the necessary knowledge and skills. Therefore, nursing educators should consider this as an opportunity to strengthen the teaching of their evidence-based practical knowledge and skills. This will lay a reference for developing nursing discipline. • A positive attitude towards EBP and better knowledge and skills contribute to the development of the nursing discipline. • In recent years, there are more and more researches on EBP among nurses and nursing students. • A total of 25 studies involving 4557 nursing students and 6806 nurses from 13 countries were included in this review, and the results of the meta-analysis suggest that nursing students and nurses have positive attitudes towards EBP, but appear to lack the necessary knowledge and skills. • In view of the above problems, nursing educators need to take advantage of the positive attitude of nurses and nursing students towards EBP and adopt innovative teaching strategies, and lay a foundation for the development of nursing disciplines. [ABSTRACT FROM AUTHOR]

Prinsepia utilis Royle, native to the Himalayan region, has a long history of use in traditional medicine for its heat-clearing, detoxification, anti-inflammatory, and analgesic properties. Oils extracted from P. utilis seeds are also used in cooking and cosmetics. With the increasing market demand, this extraction process generates substantial industrial biowastes. Recent studies have found many health benefits with using aqueous extracts of these biowastes, which are also rich in polysaccharides. However, there is limited research related to the reparative effects of the water extracts of P. utilis oil cakes (WEPUOC) on disruptions of the skin barrier function. This study aimed to evaluate the reparative efficacy of WEPUOC in both acute and chronic epidermal permeability barrier disruptions. Furthermore, the study sought to explore the underlying mechanisms involved in repairing the epidermal permeability barrier. Mouse models with induced epidermal disruptions, employing tape-stripping (TS) and acetone wiping (AC) methods, were used. The subsequent application of WEPUOC (100 mg/mL) was evaluated through various assessments, with a focus on the upregulation of mRNA and protein expression of Corneocyte Envelope (CE) related proteins, lipid synthase-associated proteins, and tight junction proteins. The polysaccharide was the major phytochemicals of WEPUOC and its content was determined as 32.2% by the anthranone-sulfuric acid colorimetric method. WEPUOC significantly reduced transepidermal water loss (TEWL) and improved the damaged epidermal barrier in the model group. Mechanistically, these effects were associated with heightened expression levels of key proteins such as FLG (filaggrin), INV (involucrin), LOR (loricrin), SPT, FASN, HMGCR, Claudins-1, Claudins-5, and ZO-1. WEPUOC, obtained from the oil cakes of P. utilis , is rich in polysaccharides and exhibits pronounced efficacy in repairing disrupted epidermal barriers through increased expression of critical proteins involved in barrier integrity. Our findings underscore the potential of P. utilis wastes in developing natural cosmetic prototypes for the treatment of diseases characterized by damaged skin barriers, including atopic dermatitis and psoriasis. [Display omitted] • The water extract of Prinsepia utilis oil cakes (WEPUOC) can repair epidermal barriers. • WEPUOC upregulates corneocyte envelope protein expression in the stratum corneum. • WEPUOC upregulates the expression of lipid synthases among corneocytes. • WEPUOC enhances the expression of tight junction proteins. [ABSTRACT FROM AUTHOR]

Tibetan Patent Medicines (TPMs) have unique advantages in the treatment of ischemic stroke (IS) with the features of multi-component, multi-channel, and multi-target. In China, five TPMs mainly consisting of precious medicinal materials such as gold, pearls, and agate are widely utilized to treat IS and have achieved good results according to the current clinical practice. To systematically evaluate the efficacy and safety of the five TPMs orally in treating IS and provide a reference for future clinical application and research. We searched the following 24 databases up to December 11, 2022: China National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database, Chinese Biomedical Database (CBM), PubMed, Embase, Web of Science, MEDLINE, Scopus, the Cochrane Library, ScienceDirect, etc. Comprehensive searches for randomized controlled trials (RCTs) of the five TPMs for IS were conducted. Outcome measures included clinical effective rate, neurological impairment score, activities of daily living (ADL), hematologic indices, and adverse events (AEs). The meta-regression, subgroup analyses, and sensitivity analyses were conducted to explore the sources of heterogeneity. We assessed the evidence grade of outcomes via the GRADE system. TSA software was used for trial sequential analyses of the clinical effective rate, neurological impairment score, and ADL. 17 RCTs (1603 patients) met our criteria. Compared with the control groups, the five TPMs showed greater improvement in clinical effective rate (RR = 1.23, 95% CI 1.17 to 1.29, P < 0.00001), neurological impairment score (SMD = −1.71, 95% CI -2.31 to −1.10, P < 0.00001), ADL (SMD = 1.97, 95% CI 1.26 to 2.68, P < 0.00001), hematocrit (MD = −1.56, 95% CI -2.83 to −0.29, P = 0.02), and hypersensitive-c-reactive-protein (MD = −2.96, 95% CI -3.30 to −2.61, P < 0.00001). AEs were reported in four RCTs and there was no statistical difference between groups (RD = −0.00, 95% CI -0.04 to 0.03, P = 0.82). The quality of evidence of the outcomes was rated as low to very low according to the GRADE system. The results of TSA provided firm evidence for the significant effect of the five TPMs on clinical effective rate, neurological impairment score, and ADL. This review showed that the five TPMs were beneficial in improving clinical effective rate, neurological impairment scores, and ADL. However, no definite conclusions for hematologic indices and AEs were drawn due to insufficient studies. Further high-quality clinical trials are required to confirm these findings. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aims to explore the effect of organizational justice on young nurses' turnover intention and the roles of organizational climate and emotional labour in this relationship. The shortage of nursing resources has become a growing problem in countries worldwide. As the main representatives of the nursing force, young nurses have high turnover intentions, which aggravates the possibility of nursing shortages. As an important variable affecting the turnover intention of young nurses, the mechanism underlying the impact of organizational justice should be studied in depth. A descriptive cross-sectional design was employed. From November to December 2022, an online questionnaire survey was conducted among 1160 young clinical nurses from 5 hospitals in Henan Province, China. The scales used in this study include the organizational justice scale, the turnover intention scale, the organizational climate scale and the emotional labour scale. AMOS 26.0 was used for model drawing and mediation path testing, and SPSS 25.0 was used for data analysis. This study complies with the STROBE Statement of Observational Studies. In general, the young nurses surveyed had high turnover intentions (14.82 +/- 4.44). Organizational justice has a negative predictive effect on young nurses' turnover intention (r = −0.465, P ＜0.01). Organizational climate and emotional labour play a chain mediating role in the relationship between organizational justice and young nurses' turnover intention (β = −0.051). Organizational justice is significantly related to the turnover intention of young nurses, and organizational climate and emotional labour play a chain mediating role in the relationship between organizational justice and turnover intention. Therefore, nursing managers should pay attention not only to organizational justice but also to the influence of organizational climate and emotional labour on the turnover intention of young nurses. [ABSTRACT FROM AUTHOR]

The spreading of COVID-19 misinformation paralleled increasing fear towards the pandemic reported worldwide in its early stages. Yet research on the emotional basis for misinformation susceptibility and how emotional appeals may help reduce COVID-19 related misperceptions remains limited. To address this gap, we conducted a 2 (threat from COVID-19: yes vs. no) × 4 (correction conditions: none vs. factual correction vs. factual correction + words of optimistic outlook & individual efficacy vs. factual correction + words of optimistic outlook & collective efficacy) between-participant factorial experiment among an online sample of Chinese residents (N = 836) in June 2020. Misinformation about COVID-19 treatments and mitigation was presented in all conditions. Across five misinformation topics, threat information induced more misperceptions while all three types of corrections mitigated threat information's deleterious impact and improved belief accuracy. Importantly, corrections incorporating hope appeals showed enhanced effectiveness in improving belief accuracy when threat information was present whereas factual corrections absent hope appeals did not show similar sensitivity towards threat information. For hope appeal corrections, their indirect effects on desirable downstream behavioral intentions through corrected beliefs were stronger with than without preceding threat information. Our study thus demonstrated the potential of deploying hope appeals to fight the COVID-19 infodemic in China and beyond when threat information is prevalent, while highlighting the importance of studying the roles of emotional appeals in health misperception formation and correction. • Fear-inducing threat information increases COVID-19 misperceptions. • Hope appeal corrections can decrease COVID-19 misperceptions. • Self- and collective-efficacy can both serve as promising hope appeal components. • Hope appeals are more likely to correct misperceptions when threat is salient. [ABSTRACT FROM AUTHOR]

Academic motivation is the psychological factor that promotes learning activities. The persistence of learning activities in nursing education is directly influenced by academic motivation. However, there are currently no specialist instruments for nursing students in China. To translate the Motivation for nursing student scale (MNSS) into Chinese and evaluate its validity and reliability among nursing students in China. A quantitative and cross-sectional design. The survey was conducted at a medical university in Jinzhou, China between March and May 2022. A total of 688 Chinese nursing students were surveyed by questionnaire in this study. The Chinese version of MNSS adopted Brislin's transition model and conducted expert consultations to validate the facial validity and testing of the transition version. Reliability and validity were tested using exploratory factor analysis, confirmatory factor analysis, and internal consistency reliability. Nursing experts confirm the high content validity of the Chinese version of the 20-item scale. An exploratory factorial analysis revealed a four-factor solution, with a total variance of 64.1% and confirmatory factor analysis results showed a satisfactory fit (χ2/df=2.738, RMSEA =0.073, SRMR = 0.0719, CFI = 0.914, IFI = 0.915, NFI =0.872, RFI =0.849,). Cronbach's alpha coefficient for the scale was 0.869, and the split-half reliability is 0.727. The Chinese version of MNSS has satisfactory reliability and validity and is a reliable instrument to assess the academic motivation of Chinese nursing students. [ABSTRACT FROM AUTHOR]

Numerous scholars have investigated the prevalence of cyber dating abuse (CDA) and recognize that CDA is a widespread phenomenon among adolescents and emerging adults. However, to date, there is no consensus on the extent to which adolescents and emerging adults perpetrate and experience CDA. Based on the PRISMA and MOOSE guidelines, the present work performed separate meta-analyses for studies involving adolescents and emerging adults. This study aims to estimate the pooled prevalence of CDA perpetration and victimization and try to explain discrepancies in the literature. In all, 69 publications (25 adolescent and 44 emerging adult studies) on CDA were identified through a systematic literature search, including 74 independent samples with a total of 62,376 participants. The results showed that the overall prevalence of CDA perpetration was 24.0% and victimization was 36.9% among adolescents, while 44.6% and 43.4% for CDA perpetration and victimization among emerging adults. Moderator analyses revealed that higher rates of CDA perpetration and victimization were found for older adolescents. In addition, control dimension had higher rates of CDA perpetration and victimization compared to direct aggression dimension among emerging adults. Finally, the assessed lifetime prevalence of CDA perpetration was higher than that assessed in the last year in emerging adults, whereas unpublished studies showed a higher prevalence of CDA victimization compared to published studies in adolescents. In sum, current evidence contributes to a better understanding of the prevalence and influencing factors for CDA among adolescents and emerging adults. Prevention and intervention programs are urgently required to reduce CDA behaviors in adolescents and emerging adults. • We performed separate meta-analyses for studies involving adolescents and emerging adults. • Meta-analytic combination produced an overall prevalence of CDA perpetration was 24.0% and victimization was 36.9% among adolescents, while 44.6% and 43.4% for CDA perpetration and victimization among emerging adults. • Moderator analyses revealed that the high heterogeneity in the prevalence of CDA perpetration and/or victimization among adolescents and emerging adults could be accounted for by age, dimension of CDA, time frame, and publication status. • Prevention and intervention programs are urgently required to reduce CDA behaviors in adolescents and emerging adults. [ABSTRACT FROM AUTHOR]

Two new polyketides versicolorones A-B (1 – 2), one new diketopiperazine derivative aspergiamide B methyl ester (3), along with twenty known compounds 4 – 23 , were obtained from the EtOAc extract of the Cordyceps -colonizing fungus Aspergillus versicolor ZJUTE2. The structures of 1 – 3 were established by detailed interpretation of the spectroscopic data and their absolute configurations were established by comparative analyses of the calculated and experimental ECD spectra. In the in-vitro bioassay, compounds 8 and 21 exhibited significant inhibitory activity against the Escherichia coli β -glucuronidase (EcGUS) with IC 50 values of 54.73 ± 2.69 and 56.59 ± 1.77 μM, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Dragon׳s blood, a traditional Chinese herb, has been used to “panacea of blood activating” and its major biological activity appears to be from phenolic compounds. In this study, our research aims to examine the effects of Dragon׳s blood (DB) and its extracts (DBE) on radiation-induced myelosuppressive mice. Materials and methods: Adult BALB/C mice were exposed to the whole body irradiation with 4Gy 60Co γ-rays. DB and DBE were respectively administered orally for 5 constitutive days prior to irradiation treatment. The radioprotective effects and relevant mechanisms of DB and DBE in radiation-induced bone marrow injury were investigated by ex vivo examination. Results: We found that the administration of DB and DBE significantly increased the numbers of peripheral blood cells and colony forming unit of bone marrow-derived stem/progenitor cells. Interestingly, compared with the irradiation group, the administration of DB and DBE significantly decreased the levels of the inflammatory cytokines such as IL-6, TNF-α and IFN-γ and oxidative stress injury such as SOD, CAT, GSH, MDA in serum of mice. Furthermore, DBE markedly improved the morphology of bone marrow histopathology. Conclusions: Our data suggest that DB and DBE effectively attenuate radiation-induced damage in bone marrow, which is likely associated with the anti-oxidative and anti-inflammatory properties of DB and DBE. [Copyright &y& Elsevier]

Abstract: A rapid, sensitive and selective high-performance liquid chromatography mass spectrometric method has been developed and validated for the simultaneous determination of oxymatrine and its active metabolite matrine in human plasma after administration of oxymatrine oral solution. Analytes were extracted from the plasma by liquid-liquid extraction with chloroform. The chromatographic separation was accomplished on a Venusil C18 column (150mm×4.6mm, 5μm) protected by a C18 guard column (4.0mm×2.0nm; Phenomenex, Torrance, CA, USA). Analytes were detected on a single quadruple mass spectrometer by selected ion monitoring mode via electrospray ionization source. The assay had a lower limit of quantification of 1.5ng·mL−1 for oxymatrine and 3ng·mL−1 for matrine in plasma. The calibration curves were linear in the measured range. The overall precision and accuracy for all concentrations of quality controls and standards were within ±15%. The proposed method enabled unambiguous identification and quantification of oxymatrine and its active metabolite matrine in vivo. The results provided a meaningful basis for evaluating the clinical applications of the oxymatrine oral solution. [Copyright &y& Elsevier]

Background: An understudied component of the diet, branchedchain fatty acids (BCFAs) are distinctive saturated fatty acids that may have an important influence on health. Human-milk fatty acid composition is known to differ worldwide, but comparative data are lacking on BCFAs. Objective: We tested the hypotheses that concentrations of BCFAs in human milk differ between populations and are associated with maternal diet. Design: We surveyed the BCFA composition of samples collected as part of a standardized, prospective study of human-milk composition. Mothers were enrolled from 3 urban populations with differing diets: Cincinnati, Ohio; Shanghai, China; and Mexico City, Mexico. Enrollment was limited to healthy mothers of term singleton infants. We undertook a cross-sectional analysis of milk from all women with samples at postpartum week 4 (n = 359; ~ 120 women/site). Fatty acids were extracted from milk by using a modified Bligh-Dyer technique and analyzed by gas chromatography. Statistical analysis was performed by ANOVA and Tobit regression. For Cincinnati mothers, 24-h diet recalls were analyzed in relation to the individual BCFA concentrations measured in milk samples. Results: Total BCFAs in milk differed by site, with the highest concentration in Cincinnati followed by Mexico City and Shanghai (mean ± SE: 7.90 ± 0.41, 6.10 ± 0.36, and 4.27 ± 0.25 mg/100 mL, respectively; P < 0.001). Site differences persisted after delivery mode, maternal age, and body mass index were controlled for. The individual concentrations of iso-14:0, iso-16:0, iso-18:0, anteiso-15:0, and anteiso-17:0 also differed between sites. Milk concentrations of iso-14:0 and anteiso-15:0 were associated with maternal intake of dairy; iso-16:0 was associated with maternal intakes of dairy and beef. Conclusions: BCFA concentrations in milk at 4 wk postpartum differed between mothers from Cincinnati, Shanghai, and Mexico City. Variations in human-milk BCFAs are influenced by diet. The impact of BCFAs on infant health warrants investigation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Ginsenosides are natural product steroid glycosides and triterpene saponins obtained from the Panax species. Panax ginseng has been widely used as a traditional Chinese medicine (TCM) for around a thousand years, especially in East Asian countries. Ginseng, the root and rhizome of the most popular species P. ginseng , used as tonic, prophylactic agent and restorative. In TCM, ginseng is highly valued herb and has been applied to a variety of pathological conditions and illnesses such as hypodynamia, anorexia, shortness of breath, palpitation, insomnia, impotence, hemorrhage and diabetes. Aim of the study The basic aim of this study was to evaluate the anti-Alzheimer's disease activities of selected ginsenosides (Rb1, Rb2, Rc, Re, Rg1, and Rg3) according to peroxynitrite (ONOO ‒ ) scavenging activity and inhibitory activity of ONOO − -mediated nitrotyrosine formation as a measure of changes in oxidative stress. In addition, molecular docking simulation studies were performed to predict binding energies of the ginsenosides with β-site amyloid precursor protein cleaving enzyme 1 (BACE1, β-secretase) and identify the interacting residues. Materials and methods In vitro cholinesterase enzyme assays by using acetylcholinesterase (AChE), butyrylcholinesterase ( BChE), and BACE1 were performed. In vitro authentic peroxynitrite scavenging activity and inhibitory activity against ONOO − -mediated nitrotyrosine formation were also performed. Molecular docking simulation studies were performed with Autodock Vina software and Discovery studio 4.1. Results In vitro enzyme assays demonstrated that ginsenosides have significant inhibitory potential against AChE, BChE, and BACE1, as well as ONOO − and nitrotyrosine formation. Most importantly, significant AChE inhibitory activities were observed for Re; BChE for Rg3; and BACE1 for Rc, with IC 50 values of 29.86±3.20, 16.80±0.36, and 59.81±2.74 μg/mL, respectively. Among the tested ginsenosides, Rb1 exhibited a higher scavenging activity against ONOO − with an IC 50 value of 27.86±1.34 μg/mL, while Rc and Rg3 exhibited impressive inhibitory activity against the formation of nitrotyrosine. In addition, molecular docking studies revealed potential BACE1 inhibitory activity of ginsenosides, especially Rb1 and Rb2, which exhibited good binding affinities towards BACE1, with docking scores of −10 kcal/mol. Conclusion The findings of the present study suggest the potential of ginsenosides (Rb1, Rb2, Rc, Re, Rg1, and Rg3) for use in the development of therapeutic or preventive agents for Alzheimer's disease, especially through inhibition of AChE, BChE and BACE1 activities, as well as scavenging of ONOO − and inhibition of nitrotyrosine formation. [ABSTRACT FROM AUTHOR]

Testing for SARS-CoV-2 infection has been a key strategy to mitigate and control the COVID-19 pandemic. Wide spatial and racial/ethnic disparities in COVID-19 outcomes have emerged in US cities. Previous research has highlighted the role of unequal access to testing as a potential driver of these disparities. We described inequities in spatial accessibility to COVID-19 testing locations in 30 large US cities. We used location data from Castlight Health Inc corresponding to October 2021. We created an accessibility metric at the level of the census block group (CBG) based on the number of sites per population in a 15-minute walkshed around the centroid of each CBG. We also calculated spatial accessibility using only testing sites without restrictions, i.e., no requirement for an appointment or a physician order prior to testing. We measured the association between the social vulnerability index (SVI) and spatial accessibility using a multilevel negative binomial model with random city intercepts and random SVI slopes. Among the 27,195 CBG analyzed, 53% had at least one testing site within a 15-minute walkshed, and 36% had at least one site without restrictions. On average, a 1-decile increase in the SVI was associated with a 3% (95% Confidence Interval: 2% - 4%) lower accessibility. Spatial inequities were similar across various components of the SVI and for sites with no restrictions. Despite this general pattern, several cities had inverted inequity, i.e., better accessibility in more vulnerable areas, which indicates that some cities may be on the right track when it comes to promoting equity in COVID-19 testing. Testing is a key component of the strategy to mitigate transmission of SARS-CoV-2 and efforts should be made to improve accessibility to testing, particularly as new and more contagious variants become dominant. • There is wide heterogeneity in spatial accessibility to COVID-19 testing. • Areas of high (vs. low) social vulnerability have lower accessibility to testing. • Inequity in spatial accessibility varied greatly by city. • For some cities, accessibility was better in more vulnerable areas. [ABSTRACT FROM AUTHOR]

Billions of people play Internet games and some of them may develop Internet gaming disorder (IGD), yet the differences between IGD and non-disordered but heavy Internet gaming use behavior remain unclear. We used multiple behaviors and multimodal functional magnetic resonance imaging (fMRI) to examine the specificity of impulse control to differentiate IGD from non-disordered but heavy Internet gaming use. One hundred sixty subjects, including patients with IGD (PIGD), non-disordered but heavy Internet gaming participants (NIGP), and healthy controls rated Barratt Impulsiveness Scale, and 141 out of them completed delay-discounting task and resting-state during fMRI. The PIGD but not the NIGP showed altered impulsiveness and delay discounting behavior as compared to healthy controls. Moreover, the PIGD but not the NIGP showed altered activity pattern in the frontoparietal network as compared to healthy controls. The PIGD but not the NIGP showed altered functional connectivity in the frontoparietal network during delay discounting and resting-state as compared to healthy controls. Furthermore, impulse control-related behavioral and fMRI measures significantly classified PIGD from NIGP. This study provides consistent evidence supporting the specificity of impulse control for distinguishing IGD from non-disordered but heavy Internet gaming use. • The IGD but not the non-disordered but heavy Internet gaming participants (NIGP) showed altered impulsive behaviors. • The IGD but not the NIGP showed altered activity pattern in the frontoparietal network. • The PIGD but not the NIGP showed altered functional connectivity in the frontoparietal network during the delay discounting. • The PIGD but not the NIGP showed altered resting-state functional connectivity in the frontoparietal network. • Impulse control-related behavioral and fMRI measures significantly classified IGD from NIGP. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to investigate whether vitamin A combined with iron supplementation for preschool children resulted in improved changes in children's infectious morbidity. Method: In this randomized placebo-controlled and blinded field intervention trial, totally 445 preschoolers, ages 3 to 6 y old, were randomly selected. All children were randomly divided into four groups: vitamin A supplement-only group (group I), iron supplement-only group (group II), vitamin A and iron supplement group (group III), and no vitamin A and ferrous sulfate as placebo-control (group IV) for 6 mo. The morbidity of diarrhea and respiratory infections, were collected during supplementation. Results: There was evidence of the lowest incidence rate of respiratory-related illnesses and fewest symptoms of runny nose, cough, and fever for children in group III compared with children in groups I, II and IV (P < 0.05). Moreover, despite the undistinguished incidence rate of vomiting, nausea, and stomach pain, the rate of diarrhea-related illness was significantly lower for children in group III than for those in the other three groups. Conclusion: The beneficial affects on infectious morbidity over 6 mo, highlight the potential of vitamin A plus an iron supplement for preschool-aged children. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Artemisia capillaris Thunberg (Compositae) have been used as traditional medicine as a diuretic, liver protective agent, and for amelioration of inflammatory and analgesic disorders. The present study was carried out to establish the scientific rationale for treating inflammation and to find active principles from A. capillaris. The aim of the present study is to investigate the possible anti-inflammatory mechanism of the major component (capillarisin) isolated from A. capillaris via inhibition of MyD88/TIRAP inflammatory signaling both in vitro and in vivo models. Materials and methods: The nitrite, PGE2, and TNF-α productions were evaluated by Griess reagent and ELISA kits. The protein and mRNA expression levels were investigated by Western blot and RT-PCR. The NF-κB and AP-1 DNA-binding was performed by electrophoretic mobility shift assay. The CFA- and carrageenan-induced paw edema was performed in ICR mice in which 20 and 80mg/kg body weight of capillarisin was administered intraperitoneally (i.p.). Results: The results demonstrated that pretreatment with capillarisin effectively inhibited the LPS-induced activation of NF-κB, Akt, and MAP kinase-activated inflammatory genes, which is mediated by MyD88 and TIRAP. Treatment with capillarisin reduced the mRNA and protein levels of iNOS and COX-2 in RAW 264.7 cells as assessed by RT-PCR and Western blot. Capillarisin suppressed LPS-induced inhibitory kappa kinase (IKK) phosphorylation and the degradation of inhibitory kappa B (IκBα) and prevented the nuclear translocation of p65 and p50. Capillarisin also exhibited a promising inhibitory effect on the LPS-induced NF-κB and AP-1 DNA binding activity based on an electrophoretic mobility shift assay. The LPS-induced activation of p-JNK, p-p38, p-ERK, and p-Akt was significantly inhibited. In addition, the TNF-α level in the media was effectively reduced by capillarisin. In vivo experimental analysis revealed that capillarisin (20 and 80mg/kg, i.p.) inhibited complete Freund''s adjuvant (CFA)-and carrageenan-induced paw edema, nitrite production in plasma, and TNF-α, a pro-inflammatory cytokine production. Conclusion: The results presented here demonstrate that capillarisin has consistent anti-inflammatory properties and acts by inhibiting inflammatory mediators in in vitro and in vivo experimental models, and suggest its potential utility in the control of inflammatory disorders. [Copyright &y& Elsevier]

Abstract: Aims of the study: We recently reported the potential antioxidant and anti-inflammatory activities of umbelliferone 6-carboxylic acid (UMC) isolated from the whole plants of Angelica decursiva. In this study, we elucidated the anti-inflammatory mechanisms of UMC in vitro and in vivo. Methods: The inhibitory effects of UMC on the production of nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α), the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the activation of nuclear factor kappa B (NF-κB) were evaluated using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The reactive oxygen species (ROS) generation inhibitory activity of UMC was evaluated using t-butyl hydroperoxide (t-BHP)-induced RAW 264.7 cells. Furthermore, the in vivo anti-inflammatory activity of UMC was evaluated using carrageenan induced mouse paw edema model. Results: UMC dose-dependently inhibited NO and PGE2 production by down-regulating iNOS and COX-2 protein expression in LPS-stimulated RAW 264.7 macrophages. UMC also suppressed the production of the proinflammatory cytokine TNF-α in LPS stimulated RAW 264.7 cells in a concentration dependent manner. In addition, UMC dose-dependently prevented LPS-induced nuclear translocation of NF-κB in RAW 264.7 macrophages. Furthermore, UMC exhibited the inhibitory activity against t-BHP-induced ROS generation in RAW 264.7 cells with an IC50 value of 705.1μg/ml. Moreover, UMC inhibited λ-carrageenan induced mouse paw edema by 70.40 and 60.20% at doses of 50 and 25mg/kg body weight, respectively. Conclusion: The combined results of this study indicate that UMC is an important anti-inflammatory constituent of A. decursiva and its anti-inflammatory effect was due to its ability to inhibit the production of inflammatory mediators via inhibition of NF-κB activation pathway. [Copyright &y& Elsevier]

Background: Body energy homeostasis is largely regulated by the interactions between appetite-related brain regions and gut hormones. Objective: We hypothesized that the sensitivity of appetite-related brain regions [eg, hypothalamus, insula, thalamus, parahippocampal/ hippocampal cortex, caudate, putamen, amygdala, and orbitofrontal cortex (OFC)] varies for each macronutrient, and the differential sensitivity is associated with gut hormone concentrations in humans. Design: Brain activation responses to ingested fat, glucose, protein, and water in the above-mentioned 8 brain regions of 14 healthy men were investigated by using functional magnetic resonance imaging. Fasting and postprandial plasma glucose, insulin, ghrelin, cholecystokinin (CCK), and glucagon-like peptide 1 (GLP-1) concentrations were measured. The relation of the blood oxygen level-dependent (BOLD) signal with plasma glucose and hormone concentrations was assessed by using Pearson's correlation analysis. Results: Ingested macronutrients similarly reduced the BOLD signal in the middle insula, thalamus, parahippocampal cortex, caudate, and lateral OFC. Protein ingestion reduced the BOLD signal in the amygdala more effectively than did fat and glucose ingestion. BOLD signal changes were positively correlated with circulating ghrelin concentrations and were negatively correlated with circulating insulin, CCK, and GLP-1 concentrations. The findings indicate variations in the correlation between brain activation and plasma hormone concentrations after ingestion of different macronutrients. Conclusions: The middle insula, thalamus, parahippocampal cortex, caudate, and lateral OFC, but not the amygdala, have similar sensitivities, to isocaloric and isovolumetric macronutrient solutions. Differential correlations exist between BOLD signal changes in activated brain regions and postprandial changes in plasma concentrations' of different gut hormones in response to the ingestion of different macronutrients. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The dried root of Sophora flavescens Aiton (Sophorae radix, SR) has long been used in traditional medicine for the treatment of fever and swelling in eastern countries. Materials and methods: The present study investigated the anti-allergic and anti-inflammatory effects of SR using 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis mouse model and in vitro using RBL-2H3 cells. Results: In mice, the topical application of 10mg/mL of SR effectively inhibited enlargement of ear thickness and weight induced by repeated painting with DNFB. Topical application of SR also inhibited hyperplasia, edema, spongiosis and infiltration of mononuclear cells in ear tissue. In addition, production levels of interferon-gamma and tumor necrosis factor-alpha were decreased by SR in vivo. Finally, the release of histamine and β-hexosaminidase, and migration were inhibited by treatment with SR. Conclusions: These data indicate the potential of SR in treating patients with allergic skin diseases and also suggest that related mechanisms are involved in anti-inflammatory action on the Th 1 skewing reaction and inhibition against recruitment and degranulation of mast cells. [Copyright &y& Elsevier]

• The value of PowerPlex®18D used for forensic purpose in Guizhou Miao was evaluated. • Comprehensive population genetic comparisons of 174 Asian populations were conducted. • The genetic affiliations varied among Guizhou Miao tribes and other nationalities. • The possible routes of southward migration for Miao nationality were suggested. Genetic polymorphism of 17 autosomal short tandem repeat (STR) loci, included in the PowerPlex®18D amplification kit, were analyzed in Miao tribes from 58 different sampling microareas (N = 5255) of Guizhou as well as two cities (N = 151) of Hunan, China. Allele frequencies and forensic efficiency parameters were calculated. Moreover, comprehensive population genetic comparisons among 91 nationwide populations and 174 Asian populations were conducted based on raw genotype data and allele frequency data, respectively. Our results of forensic efficiency parameters showed that the panel was a robust tool in forensic individual identification and paternity cases for this population. Genetic affinities were observed among most of the Miao tribes revealed by multidimensional scaling plot, principal component analysis, and neighboring-joining tree. The genetic distance between Miao tribes and Han nationalities were varies by different geographical positions. Some of the Miao tribes were genetically closer to the Hmong-Mien populations living in southeastern contiguous regions and even the Indochina. The result coincided with the migration or reverse migration routes for Miao nationality in modern history. This study of the Miao tribes from plenty of microareas in Guizhou would be useful in reconstructing the population history and establishing a more comprehensive forensic reference database. [ABSTRACT FROM AUTHOR]

Psychological resilience is characterized as the ability to respond to extreme stress or trauma or adverse experience successfully. While the relation between public emergencies and psychological distress is well known, research on therelationship between psychological resilience and mental health is very limited during the outbreak of public health emergencies. This research investigated the relationship between psychological resilience and mental health (depression, anxiety, somatization symptoms) among the general population in China. Psychological resilience, depression, anxiety, and somatization symptoms of 1770 Chinese citizens were investigated during the epidemic peak of coronavirus disease 2019 (COVID-19) (23rd February 2020 to 2nd March 2020). The analyses were done through the Connor-Davidson Resilience Scale (CD-RISC), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7) scale, and the Patient Health Questionnaire-15 (PHQ-15) scale. The prevalence of depression, anxiety, somatization symptoms was found to be 47.1%, 31.9%, 45.9%, respectively, among all participants. From them, 18.2% showed moderate to severe symptoms of depression, 8.8% showed moderate to severe symptoms of anxiety, and 16.6% showed moderate to severe symptoms of somatization. Psychological resilience was negatively correlated with depression (standardized β = −0.490, P < 0.001), anxiety (standardized β = −0.443, P < 0.001), and somatization symptom scores (standardized β = −0.358, P < 0.001), while controlling for confounding factors. Analysis of the three-factor resilience structure showed that strength and tenacity were correlated with depression (standardized β = −0.256, P < 0.001; standardized β = −0.217, P < 0.001), anxiety (standardized β = −0.268, P < 0.001; standardized β = −0.147, P < 0.001), and somatization symptoms (standardized β = −0.236, P < 0.001; standardized β = −0.126, P < 0.01). Our results suggest that there is a high prevalence of psychological distresses among the general population at the peak of the COVID-19 epidemic in China, which is negatively correlated with resilience. Psychological resilience represents an essential target for psychological intervention in a public health emergency. • Investigated mental health and resilience in response to COVID-19. • The study took place at the peak of the COVID-19 epidemic in China. • In total, 18.2% had depression, 8.8% had anxiety, and 16.6% had somatic symptoms. • Resilience negatively correlated with depression, anxiety, and somatic symptoms. • Resilience represents an essential target for psychological interventions. [ABSTRACT FROM AUTHOR]

Although the health benefits of exercise for older adults are widely recognized, physical inactivity is still common among older adults. Further clarification of the factors affecting exercise adherence is needed to develop more effective exercise interventions in community-dwelling older adults. The purposes of this study were to identify (1) barriers and facilitators of exercise adherence in community-dwelling older adults and (2) behavior change techniques (BCTs) and implementation strategies that are potentially effective in improving adherence. A total of eight databases were searched: PubMed, Web of Science, EMBASE, CENTRAL, PsycINFO, SPORTDiscus, MEDLINE, and Scopus. Studies published from database inception to April 2023 were searched. The quality of the included studies was assessed using the Mixed Methods Appraisal Tool (MMAT). The Capabilities, Opportunities, Motivations, Behavior (COM-B) model and the Theoretical Domain Framework (TDF) were used to identify potential barriers and facilitators. The BCTs were used to identify potential intervention implementation strategies. A total of 64 studies were included, including 30 qualitative studies, 12 randomized controlled trials, 12 mixed methods studies, 6 quantitative descriptive studies, and 5 non-randomized trials. 54 factors influencing adherence and 38 potentially effective BCTs were identified from the included studies. The 38 BCTs were further categorized into 8 areas of implementation strategies (tailored exercise program, appropriate exercise environment, multidimensional social support, monitoring and feedback, managing emotional experiences and issues, participants education, enhancing self-efficacy, and exerting participants' autonomy). This study identified 54 influential factors affecting exercise adherence and identified 8 areas of intervention strategies (containing 38 BCTs). Further refinement, evaluation, and validation of these factors and strategies are needed in future studies. [ABSTRACT FROM AUTHOR]

Previous studies have reported the relationship between educational attainment and attention deficit hyperactivity disorder (ADHD). However, the mechanism of this relationship remains unknown. It is well known that educational attainment correlates with income. Therefore, based on summary data from a genome-wide association study we used two-step Mendelian randomization (MR) to explore the role of income between education and ADHD. The inverse variance weighted (IVW) method was used in our analysis. The IVW results suggested that educational attainment and income were protective factors against ADHD. Educational attainment affects ADHD through income [ADHD: Beta = −0.68, 95% confidence interval (CI) = −0.87, −0.49; female: Beta = −0.87, 95% CI = −1.28, −0.47; male: Beta = −1.01, 95% CI = −1.34, −0.68; childhood: Beta = −0.52, 95% CI = −0.74, −0.30; late-diagnosed: Beta = −0.78, 95% CI = −1.11, −0.47; persistent: Beta = −0.82, 95% CI = −1.33, −0.31]. Income also affected ADHD through educational attainment [female: Beta = −1.08, 95% CI = −1.35, −0.83; male: Beta = −1.16, 95% CI = −1.57, −0.77; persistent: Beta = −1.48, 95% CI = −2.09, −0.94]. In the final analysis, data with heterogeneity were analyzed using IVW random effects results. The mechanism is that income will mediate the relationship between educational attainment and ADHD. • Educational attainment affects the risk of attention deficit hyperactivity disorder (ADHD) through income and that this effect is causal. • Income affects the risk of ADHD through educational attainment. • These findings were significant across sexes and diagnostic periods for ADHD. [ABSTRACT FROM AUTHOR]

Healthy aging is an important means of promoting the well-being of older individuals. However, no studies have examined the relationship between eHealth literacy and healthy aging or its mechanism. Therefore, this study aimed to examine the relationship between eHealth literacy and healthy aging and the mediating effect of health behaviors in older Chinese individuals. Cross-sectional study. We recruited 2144 older individuals from Jinan, Shandong Province, China. We used the eHealth Literacy Scale to assess eHealth literacy. Healthy aging was evaluated based on multimorbidity, functional limitations, mild cognitive impairment, depressive symptoms, and social isolation. Moreover, health behaviors were assessed using the Health-Promoting Lifestyle Profile. Logistic and linear regression models were used to analyze the relationships between eHealth literacy, healthy aging, and its components. Finally, a structural equation model was used to analyze the mediation. High eHealth literacy was associated with all healthy aging components (P <.05), including the absence of multimorbidity [odds ratio (OR), 1.014; 95% CI, 1.002–1.025], no functional limitation (OR, 1.035; 95% CI, 1.022–1.047), no mild cognitive impairment (OR, 1.042; 95% CI, 1.024–1.061), no depressive symptoms (OR, 1.049; 95% CI, 1.027–1.072), and no social isolation (OR, 1.033; 95% CI, 1.018–1.048). In the adjusted model, eHealth literacy (β = 0.174; 95% CI, 0.132–0.217) was positively correlated with healthy aging. Health behaviors had a partial mediating effect on the relationship between eHealth literacy and healthy aging. Higher eHealth literacy was associated with better healthy aging in older Chinese individuals, and health behaviors mediated this relationship. Improving eHealth literacy may be an effective intervention for achieving healthy aging. [ABSTRACT FROM AUTHOR]

To investigate the appropriate timing of radiotherapy (RT) after mastectomy and adjuvant chemotherapy for women with high-risk breast cancer. Post hoc analyses of 584 patients with stage II and III breast cancer from a randomised controlled clinical trial were performed. All patients underwent mastectomy followed by sequential chemotherapy and RT. The optimal cut-off values for the surgery-RT interval (SRI) and the chemotherapy-RT interval (CRI) for overall survival (OS) were determined using the hazard ratio for continuous predictors. The locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and OS rates were estimated using the Kaplan–Meier method. Multivariate analyses were performed using Cox proportional hazards regression. Median follow-up time was 83.5 months. Median SRI and CRI were 168 and 27 days, respectively. An SRI of >210 days was independently associated with higher DM (HR 2.65, 95% CI: 1.49–4.71; HR 2.78, 95% CI 1.51–5.26), lower OS (HR 2.44, 95% CI: 1.28–4.54; HR 2.50, 95% CI: 1.41–4.35), and lower DFS (HR 2.57, 95% CI: 1.45–4.57; HR 2.70, 95% CI: 1.45–5.00) than SRI of <180 or 180–210 days. Furthermore, a CRI of more than 42 days was independently associated with higher DM (HR 1.89, 95% CI: 1.17–3.06; HR 1.96, 95% CI: 1.19–3.22), lower OS (HR 2.44, 95% CI: 1.41–4.35; HR 1.92, 95% CI: 1.10–3.33), and lower DFS (HR 1.84, 95% CI: 1.14–2.96; HR 1.82, 95% CI: 1.12–2.94) than a CRI of <28 or 28–42 days. However, SRI and CRI had no significant effect on LRR. Based on the present findings, the timing of the initiation of RT both after mastectomy and after the completion of adjuvant chemotherapy is crucial for patients with high-risk breast cancer. • Delays in initiating PMRT compromise distant control and survival. • Up to 210 days after mastectomy and 42 days after chemotherapy may be acceptable. • Studies on RT should evaluate endpoints beyond locoregional recurrence. [ABSTRACT FROM AUTHOR]

Nine new sesquiterpenes ( 1 – 9 ), together with seventeen known ones ( 10 – 26 ), were isolated from Chinese eaglewood. Their structures were established by extensive spectroscopic analysis, and the absolute configuration of 6 was determined by the modified Mosher's method. Compounds 7 , 10 , 14 , 15 , and 21 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC 50 values in the range 7.1–53.8 μM. [ABSTRACT FROM AUTHOR]

Although studies have indicated that physical activity (PA) is related to cardiovascular disease, the specific association between PA and incident cerebrovascular disease (CBVD) remains uncertain. The current study aimed to investigate the associations between PA levels and the CBVD incidence or all-cause mortality. Prospective cohort study. Older participants (aged >60 years) from the UK Biobank. The baseline PA was classified as total, light, moderate, and vigorous PA based on the metabolic equivalent–minutes per week (MET-min/wk) and considered as exposures, whereas CBVD incidence and all-cause mortality were considered as the outcomes. Cox proportional hazards were used to calculate the hazard ratios (HRs) and 95% CIs for the influence of the association between PA and CBVD incidence and all-cause mortality. A total of 146,742 participants aged 60 years and older were included. During a median follow-up period of 13.5 years (interquartile range of 12.8-14.2), 9338 older individuals developed CBVD and 3033 death were recorded (including 767 CBVD-related deaths). High volumes of PA were consistently associated with lower risks of CBVD and all-cause mortality. The lowest risk of CBVD incidence was observed at 2001-2500 MET-min/wk of total PA (HR 0.61, 95% CI 0.53-0.70), and the lowest risk of all-cause mortality was observed at 2501-5000 MET-min/wk (HR 0.52, 95% CI 0.43-0.63) in older adults. Total PA at 2001-2500 MET-min/wk significantly reduced the CBVD incidence in older women (HR 0.57, 95% CI 0.46-0.71), which was more pronounced than that in older men (HR for 2001-2500 MET-min/wk: 0.64, 95% CI 0.50-0.77). Total PA at 2001-2500 MET-min/wk significantly reduced the risk of incident CBVD and all-cause mortality in adults aged >60 years, although the extents of risk reduction vary in men and women. [ABSTRACT FROM AUTHOR]

• This is the first study to explore the relationship between family socioeconomic status, suicide ideation, effortful control, irritability, and future orientation among adolescents, particularly in the Chinese context. • 25.6% (last week) and 45.4% (worst) of adolescents reported suicide ideation, with a significantly higher rate of suicide ideation among girls than boys (both last week and worst) and higher rates of suicide ideation among older grades (worst). • The external objective environment (e.g., family SES) may not be directly related to the mental health of adolescents (e.g., irritability, suicide ideation) but can indirectly affect the healthy development of adolescents through internal factors (e.g., effortful control). • The results suggest that we should pay attention to the positive effects of effortful control and future orientation on suicide prevention and intervention and suppress the negative effect of irritability on suicide. Traditionally, most researchers believe that low family socioeconomic status (SES) is closely related to high suicide ideation, but this view remains controversial in empirical studies. Meanwhile, less is known about the mechanisms underlying this association. Moreover, previous studies on the relationship between family SES and suicide ideation have mostly focused on adults rather than adolescents and relatively lacked support from Chinese samples. Therefore, this study is based on the integrated motivational–volitional model of suicide behaviour and the context-process-outcomes model, aiming to determine whether and how family SES is associated with adolescents' suicide ideation and to evaluate the chain-mediating effect of effortful control and irritability, as well as the moderating effect of future orientation on this association. Data were extracted from 1058 girls and 855 boys, aged 11 to 19 years (14.86 ± 1.61 years), who completed a self-reported online survey. Descriptive statistics, t -test, chi-square test, bivariate correlations, and regression analysis were performed using IBM SPSS version 25. The conditional process model (CPM) was examined using SPSS PROCESS Macro 4.0. The results showed that there were differences in some demographic factors and the main study variables between adolescents with and without suicide ideation. In addition, the results suggested that family SES was not directly related to suicide ideation in adolescents, but it could indirectly effect suicide ideation through the chain-mediating effect of effortful control and irritability. Furthermore, future orientation moderated the relationship between irritability and suicide ideation. These findings provide evidence for current debates and conflicting conclusions, reveal the effect mechanism of family SES on suicide ideation, and add to empirical support for the prevention and intervention of adolescent suicide ideation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Paeonia suffruticosa Andrews (PSE) is a well-known Chinese medicine that has been widely used as an anti-tumor, anti-oxidative and anti-inflammatory agent. cis - and trans -gnetin H are two resveratrol oligomers isolated from the seeds of PSE. Although resveratrol is widely considered to be one of the most valuable natural chemopreventive agents and there are numerous studies on the antitumor activities of resveratrol, little is known about the antitumor properties of cis - and trans -gnetin H. Materials and methods The inhibitory effects of cis - and trans -gnetin H in different human cancer cell lines were assessed using fluorescent viability tests. Cytotoxicity in human lung and breast cancer cells was detected via nuclear condensation, cell permeability, and changes in the mitochondrial membrane potential (∆ψm). Apoptosis in human lung and breast cancer cells was assessed by flow cytometry, a luminescence assay and high-content screening analysis. Finally, a xenograft mice model was used to examine the efficacy of cis -gnetin H on lung tumors. Results cis - and trans -gnetin H have superior activity in inhibiting the proliferation of four human cancer cell lines, A549 (lung), BT20 (breast), MCF-7 (breast) and U2OS (osteosarcoma), and promote cell apoptosis, while having a minimal effect on two normal human epithelial cell lines, HPL1A (lung) and HMEC (breast) used as controls. cis - and trans -gnetin H promote apoptosis by releasing mitochondria cytochrome c , activating caspase 3/7 and inhibiting NF-κB activation. Flow cytometry analysis shows that cis - or trans -gnetin H arrested the cell cycle of cancer cells at the G0–G1 phase. Moreover, cis -gnetin H suppressed the growth of xenograft lung tumors in mice. Conclusion Collectively, our findings demonstrate the promise of the natural compounds cis - and trans -gnetin H as candidates for cancer chemotherapy agents. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance: Nepal, a mountainous country having diversified topographic and climatic conditions, gives rise to a wide range of flora and fauna. In villages ethnic people, including Magar and Majhi highly depend on medicinal plants for their primary healthcare. Due to overexploitation, encroachment in forest for arable land and destruction of natural habitat, potentially useful medicinal plants are going to be threatened in their natural environment. There is a strong need to enlist highly valuable medicinal plants and use traditional knowledge to protect, utilize and manage them in ex-situ and in-situ conservation. The present research investigates and documents traditional knowledge on medicinal plants utilization as natural medicine by two ethnic communities Magar and Majhi of Parbat district in Western Nepal. Methods Ethnomedicinal data was collected during 2012–2013 by the following standard ethnobotanical methods. Data about medicinal uses of herbs, shrubs and trees were collected using semi-structured questionnaire, field observation, personal interview and group discussion with 334 (130 men and 204 women) pre-identified local informants, among which 13 male and 2 female were local healers. Statistical tool, informant consensus factors ( F IC ) and fidelity level (FL) values were used to analyze the importance of ethnomedicinal plants. Results A total of 132 ethnomedicinal plant species belonging to 99 genera and 67 families have been documented. These plants are used to treat various diseases and disorders grouped under 12 disease categories, with the highest number of species (61) being used for gastro-intestinal, parasitic and hepatobiliary disorders ( F IC =0.78%), followed by blood and lymphatic system ( F IC =0.76%) category. The highest fidelity level (FL) values recorded in Paris polyphylla (FL=96.0%) followed by Bergenia ciliata (FL=95.0%) confirms that these plants are the best plant species with medicinal properties. Conclusions The two ethnic communities, Magar and Majhi, in Parbat district are rich in ethnomedicinal knowledge. The high degree of consensus among the informants suggests that current use and knowledge are still strong, and thus the preservation of indigenous knowledge would show good foresight in acting before much has been lost. [ABSTRACT FROM AUTHOR]

Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC. The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC. Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by LC-MS/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and Western blot to explore the key pathway of WMW in preventing CAC. WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1β, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4+ T cells and CD8+ T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM + DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM + DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC. WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM + DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs. [Display omitted] [ABSTRACT FROM AUTHOR]

Mild cognitive impairment affects 36% of people aged ≥65 years in China, around 50% of whom will develop dementia within 3 years. Early intervention can slow disease progression and delay the onset of dementia; however, whether a multicomponent intervention can decelerate the progression of mild cognitive impairment remains unknown. To evaluate the effects of a multicomponent intervention to slow mild cognitive impairment progression in Chinese patients. Randomized controlled trial. This study was conducted in two large regional communities in Guangzhou, China. Patients aged ≥ 65 years diagnosed with mild cognitive impairment were included. A total of 112 eligible participants were assigned to receive either a 6-month multicomponent intervention or usual care from September 2019 until January 2021. Data were collected at the beginning of the study and at 1, 3, and 6 months thereafter. The primary outcomes were cognitive function, comprehensive physical capacity, depression, and quality of life. Analysis followed the intention-to-treat principle. A generalized estimating equation was used to determine intervention effects. At baseline, clinical characteristics did not differ significantly between groups. Significant interaction effects between time and group were detected (p < 0.001), indicating that the scores of five outcomes (cognitive function, short physical performance battery, timed up and go test, quality of life, and depression) of intervention and control groups changed differently over time. Participants in the intervention group were found to have a significantly greater improvement in cognitive function, physical function, quality of life, and fewer depression symptoms compared with the control group at baseline and follow-up periods. This study demonstrates the beneficial effects of a multicomponent intervention on cognitive function, physical function, depression symptoms, and quality of life in people with mild cognitive impairment in the East Asia region. The effectiveness and feasibility of this intervention program suggest that its application should be promoted in community settings to delay the progression of disease in people with mild cognitive impairment. Registration number: ChiCTR1900026042 Tweetable abstract: The multicomponent intervention improves cognitive/physical function, depression, and quality of life, slowing cognitive impairment progression. [ABSTRACT FROM AUTHOR]

In monarchE, abemaciclib demonstrated a sustained benefit in invasive disease-free survival and a tolerable safety profile at 42-months median follow-up. With no expected disease-related symptoms, therapies in the adjuvant setting should preserve quality of life (QoL). With all patients off abemaciclib, we report updated patient-reported outcomes (PROs) for the full 2-year treatment period and follow-up. Patients completed PROs including FACT-B, FACT-ES, and FACIT-Fatigue at baseline, 3, 6, 12, 18, and 24 months during treatment, and 1, 6, and 12 months after treatment discontinuation. Mixed effects repeated measures model estimated changes from baseline within and between arms for QoL scales and individual items. Meaningful changes were prespecified and no statistical testing was performed. Frequencies of responses to items associated with relevant adverse events and treatment bother were summarized. At baseline, completion rates for PRO instruments were >96 %. Mean changes from baseline for all QoL scales were numerically similar within and between arms (ie, less than prespecified thresholds). The same was observed for all individual items, except diarrhea. Within abemaciclib arm, meaningful differences for diarrhea were observed at 3 and 6 months (mean increases of 1.19 and 1.03 points on 5-point scale, respectively). During treatment, most patients in both arms (69–78 %) reported being bothered "a little bit" or "not at all" by side effects. Overall, patterns for fatigue were similar between arms. During post-treatment follow-up, PROs in both arms were similar to baseline. PRO findings confirm a tolerable and reversible toxicity profile for abemaciclib. QoL was preserved with the addition of adjuvant abemaciclib to endocrine therapy, supporting its use in patients with HR+, HER2-, high-risk early breast cancer. • Quality of life was well preserved with the addition of abemaciclib to ET in EBC. • No clinically meaningful differences across arms in bothered by side effects and fatigue. • Differences in diarrhea at 3-6 months did not impact overall quality of life. • No residual symptoms reported after completion of abemaciclib. • Common ET symptoms (hot flush, joint pain) were less frequent in abemaciclib arm. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The leaves of Sapium sebiferum have long been used in Traditional Chinese Medicine (TCM) for the treatment of eczema, shingles, edema, swelling, ascites, scabs, and snakebites, among other maladies. Aim of this study: The present study aimed to investigate the antioxidant and anti-inflammatory effects of the phenolic extracts of Sapium sebiferum leaves using in vitro and in vivo models. Materials and methods: The in vitro antioxidant activities of the extracts were measured using common chemical methods (total phenolic content; total flavonoid content; scavenging of DPPH·, ABTS+·, superoxide, and nitrite radicals; reducing power; β-carotene bleaching; and FTC assays). The in vivo topical anti-inflammatory activities were tested using the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis animal model. The SOD and CAT activities and the GSH content of ear tissue were also determined using test kits. Results: The extracts of Sapium sebiferum leaves exhibited strong in vitro antioxidant activities. They also showed significant (P<0.001) and dose-dependent anti-inflammatory activities in an acute dermatitis model at the doses of 0.03mg/ear, 0.1mg/ear, and 0.3mg/ear. The application of Sapium sebiferum leaf extracts increased the SOD and CAT activities and the GSH content relative to those of the TPA treatment group. The anti-inflammatory effect of the Sapium sebiferum leaf extract was positively correlated with its antioxidant activity. Conclusion: These results demonstrate that Sapium sebiferum leaf extract is an effective anti-inflammatory agent in the TPA-induced dermatitis model, and its anti-inflammatory effect is related, at least in part, to its antioxidant activity. [Copyright &y& Elsevier]

Abstract: Four new sesquiterpenes, chlorajapolides F–I (1–4), along with nine known terpenoids (5–13) were isolated from the aerial part of Chloranthus japonicus. Their structures were elucidated on the basis of spectroscopic analysis, and a lindenane sesquiterpene, named 9-hydroxy-heterogorgiolide, previously isolated from the C. japonicus, was revised as its 8-epimer (1a). Moreover, methanol extract (ME), EtOAc fraction (EF), water fraction (WF), and all isolates (1a, 1–13) were evaluated for their cytotoxicities using two human cancer cell lines. [Copyright &y& Elsevier]

This study considers whether secure and insecure attachment styles acquired in the early stages of life are related to adults' patterns of devotion to their favorite sport team by examining these patterns after exposure to the object of devotion. In addition, the study examines whether the desire to reinforce self-esteem and the ability of those with a secure attachment style to utilize their favorite team as a source of increasing their self-esteem can explain a person's devotion patterns. The entire study was conducted online and measured participants' attachment style, self-esteem, and extent of their devotion to their team through exposure or non-exposure to the object of their devotion. The study participants included 185 men aged 18 to 49 who are fans of various football teams. According to the results, fans with a secure attachment style exhibit higher levels of self-esteem and devotion than fans with an insecure attachment style. Moreover, fans with a secure attachment style who watched a video of their team (object of devotion) were found to exhibit higher levels of devotion than fans with a secure attachment style who were not exposed to their object of devotion. On the other hand, participants with an insecure attachment style demonstrated a reverse pattern, so that fans who watched a video of their team reported lower levels of devotion than those with insecure attachment style who had not been exposed to such content. • Fans with a secure attachment style exhibited higher self-esteem and team devotion than fans with an insecure attachment style. • Fans with a secure attachment style who watched a video of their team (object of devotion) exhibited higher levels of team devotion than fans with a secure attachment style who were not exposed to their object of devotion. • Not only do fans with insecure attachment style exhibit lower levels of devotion, but their exposure to content related to their favorite team (object of devotion) lowers their level of interest and involvement. [ABSTRACT FROM AUTHOR]

Tenuigenin (TNG) is an extract obtained from Polygalae Radix. It possesses anti-inflammatory, antioxidant, and neuroprotective properties. However, the potential mechanism of TNG in intracerebral hemorrhage (ICH) has not been well studied. In the present study, we aimed to identify the prospective mechanism of TNG in treating ICH. A total of 120 mice were divided into five groups: Sham group, ICH + vehicle group, ICH + TNG(8 mg/kg), ICH + TNG(16 mg/kg), and ICH + TNG(32 mg/kg). The modified Garcia test and beam walking test were carried out at 24 h and 72 h after ICH. Brain water content, haematoma volume and hemoglobin content examinations were performed at 72 h after ICH. TMT-based quantitative proteomics combined with bioinformatics analysis methods was used to distinguish differentially expressed proteins (DEPs) to explore potential pharmacological mechanisms. Western blotting was performed to validate representative proteins. Our results showed that the optimal dose of TNG was 16 mg/kg, which could markedly improve neurological functions, and reduce cerebral oedema, haematoma volume and hemoglobin levels 72 h after ICH. A total of 404 DEPs (353 up-and 51 downregulated) were identified in the ICH + vehicle vs. sham group, while 342 DEPs (306 up-and 36 downregulated) and 76 DEPs (28 up-and 48 downregulated) were quantified in the TNG vs. sham group and TNG vs. ICH + vehicle group, respectively. In addition, a total of 26 DEPs were selected according to strict criteria. Complement and coagulation cascades were the most significantly enriched pathways, and two proteins (MBL-C and Car1) were further validated as hub molecules. Our results suggested that the therapeutic effects of TNG on ICH were closely associated with the complement system, and that MBL-C and Car1 might be potential targets of TNG for the treatment of ICH. [Display omitted] [ABSTRACT FROM AUTHOR]

Carex baccans , known as Shan-Bai-Zi or Ye-Gao-Liang in China, is a traditional medicinal herb used by several ethnic groups in Yunnan Province. It is utilized for the treatment of wound infections, ulcers, and dysentery. However, there is currently a dearth of research reports on its antimicrobial potential. The substance basis of the antimicrobial activity of C. baccans will be unveiled, and the in vitro and in vivo antibacterial activities against multidrug-resistant bacteria of its major active compounds, as well as their preliminary mechanisms of action, will be investigated. An antibacterial bioactivity-guided isolation method was used to isolate and identify the active compound curcusinol from C. baccans. UPLC-DAD-MS was employed for the quantitative analysis of curcusinol. The antibacterial activity, resistance profile, synergistic effects, anti-biofilm activity, and potential mechanisms of action of curcusinol against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and other multidrug-resistant bacteria (Escherichia coli , Pseudomonas aeruginosa , Acinetobacter baumannii) were investigated using various methods, including the broth microdilution method, scanning electron microscopy, time kill assay, multi-generational resistance induction assay, checkerboard synergy assay, anti-biofilm assay, and metabolomics. Furthermore, the therapeutic efficacy of curcusinol was assessed in vivo by establishing an animal skin wound infection model of MRSA. Curcusinol was isolated from the fruit of C. baccans , which accounts for 3.1% of the dry weight of the fruit. Curcusinol exhibited significant bactericidal and anti-biofilm activities against antibiotic-resistant Gram-positive bacteria in vitro. Furthermore, curcusinol acted as an antibiotic adjuvant to enhance the activity of various commonly used antibiotics against both Gram-positive and Gram-negative antibiotic-resistant bacteria without cytotoxicity to mammalian cells (A549 and RAW264.7) at 64 μM. Moreover, curcusinol affected arginine biosynthesis, cysteine and methionine metabolism, and alanine, aspartate, and glutamate metabolism significantly in MRSA cells under stress. Additionally, curcusinol effectively treated MRSA-infected mouse skin wounds and accelerated wound healing in vivo. The results of this study not only support the traditional uses of C. baccans but also demonstrate that its major active compound, curcusinol, is an effective plant-derived bactericidal agent and antibacterial adjuvant with potential applications in the treatment of skin infections. [Display omitted] • The antibacterial substance, curcusinol from the ulcer healing ethnomedicine Carex baccans was identified for the first time. • Curcusinol kills multidrug-resistant Gram-positive bacteria in vitro and in vivo , with low resistance potential. • Curcusinol showed a broad synergistic antibacterial effect in combination with a wide spectrum of antibiotics. • Curcusinol disrupts resistant bacteria biofilm, inhibiting bacterial proliferation within it. [ABSTRACT FROM AUTHOR]

Long-term complications are becoming more important as the survival rate of breast cancer improves. Treatment-related myeloid neoplasm is an important long-term complication in breast cancer survivors as it has a poor prognosis. We evaluated the incidence and risk factors for the development of treatment-related acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS) in patients treated with early breast cancer. We accessed the national Korean database to identify 153,565 patients diagnosed with breast cancer between January 2007 and October 2016 who underwent surgery for breast cancer. We estimated the cumulative incidence of AML/MDS and analysed the risk factors for developing AML/MDS. Of 153,575 patients, 79,321 received anthracycline-based adjuvant therapy, 14,317 received adjuvant therapy without anthracyclines and 46,657 did not receive adjuvant chemotherapy. Overall, 120 developed AML (105 in the anthracycline group, 9 in the non-anthracycline group and 6 in the control group), and 128 developed MDS (96, 9 and 23 in each group). The 10-year cumulative incidence of AML/MDS was the highest in the anthracycline group (0.221% and 0.199%), followed by the non-anthracycline group (0.122% and 0.163%) and the control group (0.024% and 0.089%). The risk of developing AML/MDS was significantly higher in patients treated with anthracyclines (hazard ratio [HR] 9.531; p < 0.0001 for AML and HR 2.559; p < 0.0001 for MDS) compared to patients in the control group. This study found that anthracycline-based adjuvant therapy significantly increased the risk of AML/MDS in Korean breast cancer patients, with the risk persisting for at least 10 years. While the cumulative incidence was low, the long-term risks of AML/MDS should be taken into account considering the poor outcomes associated with these neoplasms. • Therapy-related myeloid neoplasms are increasing as survival rates for breast cancer improve. • Anthracyclines increased the risk of AML/MDS in breast cancer patients. • Chemotherapy without anthracycline also increased the risk of AML. • Despite the low incidence, therapy-related AML/MDS should be kept in mind. [ABSTRACT FROM AUTHOR]

β -Alanine (BA) supplementation results in elevated intramuscular carnosine content, enhancing buffering capacity during intense exercise. Although men have greater muscle carnosine content than women, elevations still appear to occur despite high baseline levels. Recent research has suggested that BA supplementation may also reduce muscle l -histidine. Thus, the purpose of this investigation was to compare 28 days of BA (6 g·d −1 ) supplementation in men and women on performance and muscle carnosine, l -histidine, and BA. We hypothesized that supplementation would result in similar elevations in carnosine and performance between sexes and decrease l -histidine. Twenty-six men and women were assigned either BA or placebo (PLA). At baseline, a trend toward greater carnosine ( P = .069) was observed in men, and intramuscular BA content was significantly ( P ≤ .05) greater in men. Statistical analysis was performed using magnitude-based inferences. Changes in muscle carnosine were likely and very likely greater after BA supplementation compared with PLA in men and women, respectively, but changes were unclear between sexes (mean sex difference: 2.50 ± 4.30 mmol·kg −1 ww). The attenuation of exercise fatigue was likely greater in BA compared with PLA, but the change was unclear between sexes (mean sex difference: 14.0 ± 39.0 Nm). Changes in muscle BA following supplementation was unclear in men, likely elevated in women, but unclear between sexes (mean sex difference: 0.03 ± 0.42 mmol·kg −1 ww). Changes in muscle l -histidine were unclear in men and women, and unclear between sexes (mean sex difference: 0.09 ± 0.13 mmol·kg −1 ww). In conclusion, BA supplementation increased muscle carnosine and attenuated fatigue in men and women similarly but did not reduce muscle l -histidine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Many Chinese medicinal materials (CMMs) have changed over centuries of use, particularly in terms of their botanical identity and processing methods. In some cases, these changes have important implications for safety and efficacy in modern clinical practice. As most previous research has focused on clarifying the evolution of CMMs by analyzing traditional Chinese materia medica (“ bencao ”) literature, assessments of historical collections are needed to validate these conclusions with material evidence. Aim of the study Historical collections of Chinese medicines reveal the market materials in circulation at a given moment in time, and represent an underexploited resource for analyzing the evolution of Chinese herbal medicines. This study compares specimens from a rare collection of CMMs from the 1920s with contemporary market materials; by highlighting examples of changes in botanical identity and processing that remain relevant for safe clinical practice in the modern era, this work aims to stimulate further research into previously unexplored historical collections of Chinese medicines. Materials and methods 620 specimens of CMMs that were collected from Chinese pharmacies in the Malay peninsula in the 1920s were examined macroscopically and compared with current pharmacopoeia specifications and authentic contemporary samples. These historical specimens, which are stored in the UK in the Economic Botany Collections (EBC) of Royal Botanic Gardens Kew, were morphologically examined, photographed, and compared to authentic CMMs stored at the Bank of China (Hong Kong) Chinese Medicines Center at Hong Kong Baptist University, as well as authentic herbarium-vouchered specimens from the Leon Collection (LC) at the Kew EBC. Case studies were selected to illustrate examples of historical changes in botanical identity, used plant parts, and processing methods. Results This investigation confirmed that confusion due to shared common names and regional variations in the botanical identity of certain CMMs has been a persistent issue over time. Additionally, historical changes in processing methods and the plant parts used were observed for some CMMs. In some cases, these changes have direct implications for the safe clinical practice of Chinese medicine. Conclusions This preliminary assessment illustrated the significant potential of collections for clarifying historical changes in CMMs. More research is needed to investigate pre-modern collections of CMMs, including a more comprehensive assessment of the holdings in the Kew EBC and other European collections that have not yet been explored from the perspective of Chinese medicine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Triptolide is a most important active ingredient extracted from traditional Chinese medicine Tripterygium, which has been widely used to treat glomerulonephritis as well as immune-mediated disorders, likely for its immunosuppressive, anti-proliferative and anti-inflammatory effects. Aim of the study In this study, we have investigated the potential protective effects of triptolide against diabetic cardiomyopathy (DCM) by regulating immune system, attenuating inflammatory response, thus resulting in decreased cardiac fibrosis and improved left ventricle function. Materials and methods Sprague-Dawley rats were randomly divided into 5 groups: normal group, diabetic group and diabetic rats treated with triptolide (50, 100, or 200 μg/kg/day resp) for 8 weeks. Cardiac function was performed by echocardiography and histopathology of the hearts was examined with HE, Masson staining and scanning electron microscopy. Immune regulation mediator, macrophage infiltration, inflammatory response and cardiac fibrosis related cytokines were measured by RT-PCR, Western blot and Immunohistochemistry staining. Results In the diabetic group, the expressions of TLR4 and NF-κB p65 were both up-regulated, which was associated with increased pro-inflammatory cytokines, coupled with cardiac fibrosis and impaired left ventricular function. Interestingly, pathological structure and function of left ventricle were both significantly improved in the triptolide treated groups. Furthermore, the immune mediator TLR4, downstream activator NF-κB p65, macrophage infiltration (CD68+), pro-inflammatory cytokines (TNF-α, IL-1β), cell adhesion molecule (VCAM-1) and chemokine (MCP-1) were significantly suppressed when treated with medium and high dosage triptolide compared with the diabetic group. Moreover, cardiac fibrosis pathway including α-SMA, TGF-β1, vimentin and collagen accumulations were observed significantly decreased in the triptolide treated groups. Conclusions Our data demonstrated that the protective effects of triptolide against DCM might attribute to inhibition of TLR4-induced NF-κB/IL-1β immune pathway, suppression of NF-κB/TNF-α/VCAM-1 inflammatory pathway and down-regulation of TGF-β1/α-SMA/Vimentin fibrosis pathway. [ABSTRACT FROM AUTHOR]

Hypericum perforatum L. has a long history in many countries of being used as a herbal medicine. It is also widely used in Chinese herbal medicine for the treatment of infections. Hypericin, a main component extracted from Hypericum perforatum L., has attracted the attention of many researchers for its remarkable antiviral, antitumor and antidepressant effects. To find plant molecules that inhibit the alkaline nuclease (AN) of herpes simplex virus type 1 (HSV-1) and suppress viral replication. Bioinformatics methods were used to determine which compounds from a variety of natural compounds in our laboratory interact with AN. By this means we predicted that hypericin may interact with AN and suppress HSV-1 replication. Experiments were then carried out to verify whether hypericin inhibits the bioactivity of AN. The Pichia pastoris expression system was used to obtain recombinant AN. The exonuclease and endonuclease activity of AN treated with hypericin were tested by electrophoresis. Immunohistochemical staining of the HSV-1 nucleocapsids was used to find out whether hypericin inhibits the intracellular function of AN. Real-time PCR and western blotting analysis were performed to test viral gene expression and viral protein synthesis. The extent of viral replication inhibited by hypericin was determined by a plaque assay and a time of addition assay. Recombinant AN was obtained by Pichia pastoris expression system. The exonuclease and endonuclease activity of recombinant AN were inhibited by hypericin in the electrophoresis assay. Hypericin showed no inhibitory effect on BeyoZonase™ Super Nuclease or DNase I. T5 Exonuclease activity was inhibited partially by10 μM hypericin, and was completely suppressed by 50 μM hypericin. Hind Ⅲ was inhibited by hypericin at concentrations greater than 100 μM, but EcoR I, BamH I, and Sal I were not inhibited by hypericin. HSV-1 nucleocapsids gathered in the nucleus when the viruses were treated with hypericin. Plaque formation was significantly reduced by hypericin (EC 50 against HSV-1 F is 2.59 ± 0.08 μM and EC 50 against HSV-1 SM44 is 2.94 ± 0.10 μM). UL12 , ICP27 , ICP8 , gD , and UL53 gene expression (P < 0.01, 4.0 μM hypericin treated group vs control group) and ICP4 (P < 0.05, 6.0 μM hypericin treated group vs control group), ICP8 and gD (P < 0.05, 2.0 μM hypericin treated group vs control group) protein synthesis were inhibited by hypericin. In the time of addition assay, HSV-1 was suppressed by hypericin in the early stages of viral replication. Hypericin exhibits potent virucidal activity against HSV-1 and inhibits the adsorption and penetration of HSV-1. Hypericin inhibits the bioactivity of AN and suppresses HSV-1 replication. The data revealed a novel mechanism of the antiherpetic effect of hypericin. [Display omitted] • The study provided the first evidence that hypericin blocks the function of HSV-1 UL12. • The study demonstrated that hypericin is very effective in blocking HSV-1 replication. • Until now, to our knowledge, no previous study reported the intracellular anti-HSV activity of hypericin. • The study report that hypericin inhibits the viral adsorption and viral penetration of HSV-1. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Zhi-Zi-Da-Huang decoction (ZZDHD), a classic traditional Chinese medicine (TCM) formula composed of four herbal medicines, has been widely used to treat various hepatobiliary disorders for a long time in China. However, the pharmacological effect of ZZDHD on liver injury with cholestasis is unrevealed. Aim of the study To investigate the hepatoprotective effect of ZZDHD against α-naphthylisothiocyanate (ANIT)-induced liver injury with cholestasis in rats. Materials and methods The rats were intragastrically (i.g.) given ZZDHD at doses of 1, 2 and 4 g/kg (crude drug/body weight) once a day for seven days and treated with ANIT (75 mg/kg via i.g.) to cause liver injury at 12 h after the fifth administration. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GTP), total bilirubin (TBIL), direct bilirubin (DBIL) and total bile acid (TBA), as well as bile flow were measured at 48 h after ANIT treatment to evaluate the protective effect of ZZDHD. Moreover, the possible protective mechanisms were elucidated by assays of liver enzyme activities and component contents including malondialdehyde (MDA), myeloperoxidase (MPO), lipid peroxide (LPO), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). The biochemical observations were supplemented by histopathological examination. Ultra fast liquid chromatography–mass spectrometry (UFLC–MS) was used for the phytochemical analysis of ZZDHD. Results The high dose (4 g/kg) and middle dose (2 g/kg) of ZZDHD exhibited significant and dose-dependent protective effect on ANIT-induced liver injury with cholestasis by reversing the changes in bile flow, the serum and hepatic enzymes, and histopathology of the liver tissue. Meanwhile, it was found that the low dose (1 g/kg) of ZZDHD did not improve the biochemical indexes except serum TBIL, DBIL and TBA, which showed little protective effect. Phytochemical analysis revealed the presence of sixteen compounds in ZZDHD. Conclusions This study indicates that ZZDHD exerted a hepatoprotective effect on ANIT-induced liver injury with cholestasis in rats, and the mechanism of this activity is possibly related to its antioxidant properties. [ABSTRACT FROM AUTHOR]

Ethnopharmacologic relevance Rhizoma Coptidis (the rhizome of Coptis chinensis Franch) has commonly been used for treatment of diabetes mellitus in traditional Chinese medicine due to its blood sugar-lowering properties and therapeutic benefits which highly related to the alkaloids therein. However, a limited number of studies focused on the Coptis alkaloids other than berberine. Materials and methods In the present study, we investigated the anti-diabetic potential of Coptis alkaloids, including berberine ( 1 ), epiberberine ( 2 ), magnoflorine ( 3 ), and coptisine ( 4 ), by evaluating the ability of these compounds to inhibit protein tyrosine phosphatase 1B (PTP1B), and ONOO − -mediated protein tyrosine nitration. We scrutinized the potentials of Coptis alkaloids as PTP1B inhibitors via enzyme kinetics and molecular docking simulation. Results The Coptis alkaloids 1 – 4 exhibited remarkable inhibitory activities against PTP1B with the IC 50 values of 16.43, 24.19, 28.14, and 51.04 μM, respectively, when compared to the positive control ursolic acid. These alkaloids also suppressed ONOO − -mediated tyrosine nitration effectively in a dose dependent manner. In addition, our kinetic study using the Lineweaver-Burk and Dixon plots revealed that 1 and 2 showed a mixed-type inhibition against PTP1B, while 3 and 4 noncompetitively inhibited PTP1B. Moreover, molecular docking simulation of these compounds demonstrated negative binding energies (Autodock 4.0=−6.7 to −7.8 kcal/mol; Fred 2.0=−59.4 to −68.2 kcal/mol) and a high proximity to PTP1B residues, including Phe182 and Asp181 in the WPD loop, Cys215 in the active sites and Tyr46, Arg47, Asp48, Val49, Ser216, Ala217, Gly218, Ile219, Gly220, Arg221 and Gln262 in the pocket site, indicating a higher affinity and tighter binding capacity of these alkaloids for the active site of the enzyme. Conclusion Our results clearly indicate the promising anti-diabetic potential of Coptis alkaloids as inhibitors on PTP1B as well as suppressors of ONOO − -mediated protein tyrosine nitration, and thus hold promise as therapeutic agents for the treatment of diabetes and related disease. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance St John׳s Wort ( Hypericum perforatum , SJW) is a widely used herbal medicine in western countries but also an important Uygur drug in China. Hypericin (HY) is the main components in SJW extracts, which is used to treat fatigue, weakness, and mild depression. The aim of this study was to investigate the anti-depression effects of HY on chronic unpredictable mild stress (CUMS) model rats and identify the possible mechanisms. Materials and methods In this study, the protective effects of HY on CUMS-induced depression in rats were investigated by using a combination of behavioral assessments and urinary metabolites analysis. Urinary metabolites analyses were performed using LC–MS/MS in conjunction with principal components analysis (PCA) after oral administration of either HY or Venlafaxine (VF) for 27 days. During the procedure of experiment, food consumption, body weight, adrenal gland, thymus and spleen indices, behavior scores, sucrose consumption, and stress hormone levels were measured. Results Changes in the classic behavioral tests and pharmacological biochemical indices reflected that HY alleviated the symptoms of depression in a shorter period than VF, which was used as positive control for antidepression. Metabolites analysis of urine revealed that HY affected excitatory amino acids and monoamine neurotransmitter metabolites. Remarkably, urinary valine was increased remarkably by HY, even much higher than CUMS group. These results provide important mechanistic insights into the protective effects of HY against CUMS-induced depression and metabolic dysfunction. Conclusion As the most important active ingredient in SJW extracts, HY possesses the better protective effect against CUMS-induced depression symptoms and metabolic disturbances. [ABSTRACT FROM AUTHOR]

Background Dietary patterns that are considered healthy (eg, the Dietary Approaches to Stop Hypertension diet and Mediterranean diet) may be more successful in reducing typical cardiovascular disease risks compared to dietary patterns considered unhealthy (eg, energy-dense diets such as the typical American diet). Objective This study assessed the effects of a Korean diet, the 2010 Dietary Guidelines for Americans (DGA), and a typical American diet on cardiometabolic risk factors, including lipid levels and blood pressure, in overweight, non-Asian individuals in the United States with elevated low-density lipoprotein cholesterol. Design/intervention The study was a three-period crossover, controlled-feeding study from January 2012 to May 2012. Thirty-one subjects were randomly allocated to one of six possible sequential orders for consuming the three diets for 4 weeks, each separated by a 10-day break. Data analysis included 27 subjects on the Korean diet periods and 29 in the DGA and typical American diet periods. Subjects remained weight stable. Main outcome measures Lipid profile, blood pressure, insulin, glucose, and 24-hour urinary sodium were determined at baseline and at the end of each diet period. Statistical analyses performed The additive main effects multiplicative interactions model was used to test for a subject by diet interaction. Differences among diets were determined using a mixed-models procedure (PROC MIXED) with random intercept for each subject. Results Total cholesterol and low-density lipoprotein cholesterol significantly decreased on Korean ( P <0.0001 and P <0.01, respectively) and DGA ( P <0.01 and P <0.05, respectively) diets, but not on the typical American diet. Although an unfavorable outcome, high-density lipoprotein cholesterol significantly decreased on all three diets (Korean: P <0.0001; DGA: P <0.0001; typical American: P <0.05). No diet had a significant effect on serum triglycerides, but a slight increase in triglycerides in the Korean and decrease in the DGA resulted in a significant difference between these two diets ( P <0.01). All three diets caused modest decreases in systolic and diastolic blood pressure, which reached statistical significance for DGA only ( P <0.05 and P <0.01, respectively). No diet had significant effect on fasting insulin, whereas fasting glucose decreased significantly on the Korean ( P <0.01) and typical American ( P <0.05) diets only. Urinary sodium output decreased significantly on DGA ( P <0.0001). Conclusions After a 4-week feeding period, Korean and DGA diet patterns resulted in positive changes in cardiovascular disease risk factors. [ABSTRACT FROM AUTHOR]