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The Cephalotaxus genus is well-known owing to the numerous complex, biologically relevant natural products that can be obtained from its constituent species. The successful identification of various Cephalotaxus alkaloids and natural, structurally diverse cephalotane diterpenoids that exhibit antitumor activities and excellent pharmacological properties has encouraged the discovery of previously undescribed compounds from this genus. The present review summarizes the different strategies for the total synthesis of cephalotane diterpenoids as well as their diverse chemical structures, antitumor activities, structure–activity relationships (SARs), and biosynthetic pathways. [Display omitted] • Novel cephalotane diterpenoids are important active components in Cephalotaxus genus. • The chemical structure classification of cephalotane diterpenoids are summarized. • The total synthesis of some cephalotane diterpenoids are summarized. • The pharmacological effects and structure-activity relationships are introduced. [ABSTRACT FROM AUTHOR]

• In this study, a forced degradation test combined with LC–MS/MS high-resolution mass spectrometry was used to quickly determine the source of cetrorelix methylene dimer impurity in cetrorelix, and determined the reaction site of cetrorelix methylene dimer impurity. • The determined of impurity named cetrorelix methylene dimer, which is synthesized for the first time. • The structure of cetrorelix methylene dimer was elucidated in detail by using liquid chromatography mass spectrometry (LC–MS/MS) method. • We found that the cetrorelix was highly unstable in formaldehyde conditions. Therefore, the methods of formaldehyde fumigation and sterilization in the workshop are not suitable for the production of such products, and sufficient attention must be paid. Cetrorelix, a potent third generation of luteinizing hormone releasing hormone (LHRH) antagonist, is a synthetic decapeptide used for treatment of infertility, prostatic hypertrophy and sexual hormone-dependent tumors. The approved drug of cetrorelix (Cetrotide, Asta Medica AG, Frankfurt, Germany.), was used for prevention of premature ovulation in patients undergoing a controlled ovarian stimulation (COS), followed by oocyte pick-up and assisted reproductive techniques, and has been shown safe and effective in controlled ovarian stimulation. Nevertheless, the study of aggregation products of cetrorelix was rarely reported. A simple liquid chromatography mass spectrometry (LC–MS/MS) method was developed for separation, identification and characterization of a new cetrorelix methylene dimer impurity in cetrorelix. The chromatographic separation was achieved on an XSelect Peptide CSH ™C 18 column (150 × 4.6 mm, 3.5 μm particle size) using gradient elution with a mobile phase of ammonium formate buffer (pH 3.0, 20 mM), acetonitrile at a flow rate 1.0 mL min−1, and an ultraviolet detection wavelength of 226 nm. The new cetrorelix methylene dimer impurity was characterized by LC–MS/MS and it characteristic fragment ions were summarized. A simple, fast and accurate method was established for the determination of the molecular weight and structure of the new cetrorelix methylene dimer impurity. In this study, the results showed that the cetrorelix was highly unstable in formaldehyde conditions. In addition, it is proposed that the impact of formaldehyde in the environment on the quality of cetrorelix acetate for Injection should be evaluated during the production process. [ABSTRACT FROM AUTHOR]

Background: Liver fibrosis is a prevalent pathological process in chronic liver diseases characterized by excessive extracellular matrix (ECM) deposition and abnormal angiogenesis. Notably, hepatic stellate cells (HSCs) are the primary source of ECM. Activated HSCs not only secrete numerous pro-fibrotic cytokines but also are endowed with a pro-angiogenic phenotype to promote pathological angiogenesis. Therefore, targeted modulation of HSCs has emerged as a pivotal strategy for addressing liver fibrosis. Hydroxysafflor yellow A (HSYA) is a homology of medicine and food colourant with good pharmacological activity. However, the precise mechanisms of HSYA against liver fibrosis remain unclear., Purpose: The objective of this study was to elucidate the impact of HSYA on liver fibrosis and pathological angiogenesis, as well as the underlying mechanisms in vitro and in vivo studies., Methods: The efficacy and mechanisms of HSYA on TGF-β1-induced HSCs and VEGFA-induced endothelial cells were investigated by MTT assay, EdU cell proliferation assay, cell scratch assay, Elisa assay, immunofluorescence assay, molecular docking, cell transfection assay, western blot analysis and RT-qPCR analysis. In CCl 4 -induced liver fibrosis mice model, H&E, Masson, and Sirius red staining were used to observe histopathology. Serum transaminase activity and liver biochemical indexes were tested by biochemical kit. Immunohistochemical, fluorescence in situ hybridization (FISH), western blot analysis and RT-qPCR analysis were implemented to determine the mechanism of HSYA in vivo., Results: Herein, our findings confirmed that HSYA inhibited the proliferation, migration and activation of HSCs, as evidenced by a reduction in cell viability, relative migration rate, EdU staining intensity, and pro-fibrotic mRNAs and proteins expression in vitro. Mechanistically, HSYA played an anti-fibrotic and anti-angiogenic role by partially silencing PDGFRB in activated HSCs, thereby disrupting PDGFRB/MEK/ERK signal transduction and inhibiting the expression of HIF-1α, VEGFA and VEGFR2 proteins. Importantly, PDGFRB was a target gene of miR-29a-3p. Treatment with HSYA reversed the down-regulation of miR-29a-3p and antagonized PDGFRB signaling pathway in TGF-β1-induced HSCs transfected with miR-29a-3p inhibitor. Consistent with our in vitro study, HSYA exhibited a good hepatoprotective effect in CCl 4 -induced liver fibrosis mice by reducing serum ALT and AST levels, decreasing the contents of four fibrosis indicators (HA, PIIIP, ColIV and LN) and hydroxyproline, and inhibiting the TGF-β1/TGFBR signaling pathway. In terms of mechanisms, HSYA alleviated pathological angiogenesis in fibrotic liver by deactivating PDGFRB signaling pathway and impairing the positive expression of CD31. Subsequently, FISH results further corroborated HSYA affected the activation of HSCs and angiogenesis achieved by the concurrent upregulation of miR-29a-3p and downregulation of α-SMA and VEGFA. Additionally, treatment with HSYA also forged a link between HSCs and endothelial cells, as supported by inhibiting the aberrant proliferation of endothelial cells., Conclusion: Fundamentally, the current study has illustrated that HSYA ameliorates liver fibrosis by repressing HSCs-mediated pro-fibrotic and pro-angiogenic processes, which is contingent upon the regulatory effect of HSYA on the miR-29a-3p/PDGFRB axis. These findings provide compelling evidence bolstering the potential of HSYA as a therapeutic agent in liver fibrosis., Competing Interests: Declaration of competing interest I promise no conflict of interest exists in submitting this manuscript, and all authors approve the manuscript for publication. On behalf of my co-authors, I would like to declare that the work described was original research that has not been published previously and not under consideration for publication elsewhere, in whole or in part., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Hepatic fibrosis (HF), a precursor to cirrhosis and hepatocellular carcinoma, is caused by abnormal proliferation of connective tissue and excessive accumulation of extracellular matrix in the liver. Notably, activation of hepatic stellate cells (HSCs) is a key link in the development of HF. Phillygenin (PHI, C 21 H 24 O 6 ) is a lignan component extracted from the traditional Chinese medicine Forsythiae Fructus, which has various pharmacological activities such as anti-inflammatory, antioxidant and anti-tumour effects. However, whether PHI can directly inhibit HSC activation and ameliorate the mechanism of action of HF has not been fully elucidated. Therefore, the aim of the present study was to investigate the in vitro anti-HF effects of PHI and the underlying molecular mechanisms. Transforming growth factor-β1 (TGF-β1)-activated mouse HSCs (mHSCs) and human HSCs (LX-2 cells) were used as an in vitro model of HF and treated with different concentrations of PHI for 24 h. Subsequently, cell morphological changes were observed under the microscope, cell viability was analyzed by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and the mechanism of anti-fibrotic effect of PHI was explored by immunofluorescence, ELISA, RT-qPCR and western blot. The results showed that PHI suppressed the proliferation of TGF-β1-activated mHSCs and LX-2 cells, arrested the cell cycle at the G0/G1 phase, decreased the levels of α-SMA, Collagen I, TIMP1 and MMP2 genes and proteins, and promoted apoptosis in activated mHSCs and LX-2 cells. Besides, PHI reduced the expression of inflammatory factors in activated mHSCs and LX-2 cells, suggesting a potential anti-inflammatory effect. Mechanically, PHI inhibited TGF-β1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/β-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study aimed to explore the longitudinal associations of rumination with suicidal ideation and suicide attempts in individuals with major depressive disorder (MDD)., Methods: Participants were derived from the Depression Cohort in China study (DCC). Those who completed at least one follow-up visit during the 12 months were included in the analysis. Dimensions of rumination including brooding and reflection were each measured using five items of the Ruminative Responses Scale. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation. Suicide attempts were also assessed and all were analyzed with generalized estimating equations., Results: Our final sample included 532 participants aged 18 to 59 years (mean [SD], 26.91 [6.94] years) consisting of 148 (27.8%) males and 384 (72.2%) females. After adjusting for temporal trend and potential confounders, individuals with higher levels of reflection were more likely to report suicidal ideation (AOR =1.11, 95% CI:1.01-1.22). However, no statistically significant association was found between brooding and suicidal ideation (AOR =1.06, 95% CI:0.96-1.17). Conversely, individuals with higher levels of brooding were more likely to report suicide attempts (AOR =1.13, 95% CI:1.02-1.24), while no statistically significant association was observed between reflection and suicide attempts (AOR =0.91, 95% CI:0.82-1.01)., Conclusion: Rumination reflects a disturbance in cognitive emotional processing and manifests in different dimensions. Our findings suggest that high levels of reflection and brooding may be associated with a higher likelihood of having suicidal ideation and suicide attempts, respectively. However, it should be interpreted with caution, given that effect sizes are small., Competing Interests: Declaration of competing interest Dr. Roger S. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals,Viatris, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. Other authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: The American Heart Association recently issued a substantial update to the definition and scoring of cardiovascular health (CVH), now called "Life's Essential 8" (LE8). We aimed to assess the trends in overall and individual LE8 CVH metrics among adolescents in the United States., Methods: A total of 6,999 United States adolescents aged 12-19 years from six cycles of the National Health and Nutrition Examination Survey from 2007-2008 to 2017-2018 were included in this study. The individual LE8 metrics included diet, physical activity, nicotine exposure, sleep health, body mass index (BMI), blood lipids, blood glucose, and blood pressure (BP). A higher CVH score indicates better CVH health., Results: The mean score of overall CVH significantly increased from 72.8 (95% confidence interval: 71.2-74.3) in 2007-2008 to 77.3 (76.1-78.5) in 2017-2018 in US adolescents (p-trend < .001). From 2007-2008 to 2017-2018, the mean scores increased from 75.5 (72.0-79.1) to 90.0 (88.0-91.9) for nicotine exposure, from 65.2 (61.6-68.8) to 73.3 (69.9-76.8) for sleep health, from 69.9 (67.1-72.8) to 73.0 (69.1-76.9) for blood lipids, and from 94.4 (93.0-95.9) to 96.2 (95.2-97.3) for BP (all p-trend < .05). However, the mean scores for diet, physical activity, and blood glucose did not significantly change (all p-trend > .05), whereas the mean score decreased from 81.4 (78.9-84.0) to 78.6 (76.4-80.8) for BMI (p-trend = .023)., Discussion: In United States adolescents, the overall CVH and four components (nicotine exposure, sleep health, blood lipids, and BP) significantly improved over time, diet, physical activity, and blood glucose remained unchanged, whereas BMI worsened., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

A stereodivergent synthesis of β- and α- O -glycosides using 3- O -quinaldoyl glucals was developed by palladium catalysis at 60 and 110 °C respectively. Various alcohols, monosaccharides, and amino acid were glycosylated to form β- and α- products in good yields with high stereoselectivity. Mechanistic studies indicated no classic Pd-N (quinoline) coordination, but π-π stacking interactions promoted the anomeric stereodiversity. The practicality was demonstrated by glycosylating natural products/drugs and synthesizing a complex tetrasaccharide.

microRNAs (miRNAs), a class of non-coding RNA with 20-24 nucleotides, are defined as the powerful regulators for gene expression. miR-21 is a multifunctional miRNA enriched in the circulatory system and multiple organs, which not only serves as a non-invasive biomarker in disease diagnosis, but also participates in many cellular activities. In various chronic liver diseases, the increase of miR-21 affects glycolipid metabolism, viral infection, inflammatory and immune cell activation, hepatic stellate cells activation and tissue fibrosis, and autophagy. Moreover, miR-21 is also a liaison in the deterioration of chronic liver disease to hepatocellular carcinoma (HCC), and it impacts on cell proliferation, apoptosis, migration, invasion, angiogenesis, immune escape, and epithelial-mesenchymal transformation by regulating target genes expression in different signaling pathways. In current research on miRNA therapy, some natural products can exert the hepatoprotective effects depending on the inhibition of miR-21 expression. In addition, miR-21-based therapeutic also play a role in regulating intracellular miR-21 levels and enhancing the efficacy of chemotherapy drugs. Herein, we systemically summarized the recent progress of miR-21 on biosynthesis, biomarker function, molecular mechanism and miRNA therapy in chronic liver disease and HCC, and looked forward to outputting some information to enable it from bench to bedside., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: Accumulating evidence suggests that low grip strength (GS) is associated with a faster cognitive decline, but most previous studies have measured GS at a single time point, ignoring changes in GS. We aimed to explore the association of the GS loss rate with the sequent cognitive decline, as well as the moderating role of social isolation in older adults., Research Design and Methods: Data were from the English Longitudinal Study of Ageing. Absolute and relative GS loss rates were calculated as the annual losses from Wave 2 (2004-05) to Wave 4 (2008-09). Participants were divided into 3 groups according to the tertiles of GS loss rates. Linear mixed models were used to assess the association of the GS loss rate during Waves 2-4 with the cognitive decline rate during Waves 4-9 (Wave 9, 2018-19)., Results: Of the 4 356 participants included in analyses, 1 938 (44.5%) were men, with a mean age of 68.4 ( SD : 8.4) years. Compared with Tertile 1 of the absolute GS loss rate, Tertile 2 (β = -0.009 [95% CI: -0.018 to -0.001] SD /year) and Tertile 3 (β = -0.018 [95% CI: -0.027 to -0.010] SD /year) were associated with a faster cognitive decline rate. The results of relative GS were similar to those of absolute GS. Social isolation was a significant modifier in the associations of the absolute GS loss rate with decline rates in global cognition and episodic memory, but not in temporal orientation. We did not observe that social isolation moderated the association of the relative GS loss rate with the cognitive decline rate., Discussion and Implications: Both absolute and relative GS loss rates were positively associated with the cognitive decline rate in older adults. Low social isolation scores attenuated the association of the absolute GS loss rate with the cognitive decline rate., Competing Interests: None., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

We experimentally investigated the coalescence-induced droplet-particle jumping phenomenon on a submillimeter scale in symmetric and asymmetric particle arrangements with poly(methyl methacrylate) (PMMA) particles and stainless steel (SS) particles. Coalescence-induced droplet-particle jumping exhibited excellent capability and interesting behavior for both droplet jumping enhancement and particle transport. The particle increased the normalized droplet jumping velocity from 0.250 for no particle case to 0.315 and 0.320 for symmetric and asymmetric particle cases. Compared with similar-sized macrostructures fixed between droplets, better jumping performance with particles may be attributed to avoiding the work of adhesion during droplet-macrostructure separation. Besides, all particles always sunk at the bottom in the symmetric cases, while the stick mode for PMMA particles and sink, wander, and jet modes for SS particles appeared in the asymmetry cases. We revealed that the asymmetric particle arrangement induces an unbalanced surface tension force, which may provide a driving force in the vertical direction. Additionally, a small enough resistive force caused by hydrophobic particles is another necessary condition for the wonder and jet mode. Finally, we realized a significantly superior particle transport in the asymmetric SS particle cases with maximum particle height reaching ∼2.1 mm, ∼12.4 times the particle radius, the most significant vertical self-propelled transport distance currently.

Amidst a global rise in lung cancer occurrences, conventional therapies continue to pose substantial side effects and possess notable toxicities while lacking specificity. Counteracting this, the incorporation of nanomedicines can notably enhance drug delivery at tumor sites, extend a drug's half-life and mitigate inadvertent toxic and adverse impacts on healthy tissues, substantially influencing lung cancer's early detection and targeted therapy. Numerous studies signal that while the nano-characteristics of lung cancer nanomedicines play a pivotal role, further interplay with immune, photothermal, and genetic factors exist. This review posits that the progression towards multimodal combination therapies could potentially establish an efficacious platform for multimodal targeted lung cancer treatments. Current nanomedicines split into active and passive targeting. Active therapies focus on a single target, often with unsatisfactory results. Yet, developing combination systems targeting multiple sites could chart new paths in lung cancer therapy. Conversely, low drug delivery rates limit passive therapies. Utilizing the EPR effect to bind specific ligands on nanoparticles to tumor cell receptors might create a new regime combining active-passive targeting, potentially elevating the nanomedicines' concentration at target sites. This review collates recent advancements through the lens of nanomedicine's attributes for lung cancer therapeutics, the novel carrier classifications, targeted therapeutic modalities and their mechanisms, proposing that the emergence of multi-target nanocomposite therapeutics, combined active-passive targeting therapies and multimodal combined treatments will pioneer novel approaches and tools for future lung cancer clinical therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Li, Guo, Zhang, Fang and Wang.)

Background: The development trajectories of children's SER remain unknown. This study aimed to characterize spherical equivalent refraction (SER) trajectories during grades 1-4 in Chinese children., Methods: This prospective cohort study included 1226 first-grade non-myopic children from 12 public primary schools, randomly selected in two districts in Guangzhou, China. From November 2018 to March 2022, four-wave ocular examinations and questionnaire surveys have been completed. The group-based trajectory modeling was used to explore SER trajectories in grades 1-4., Results: All five trajectories showed an upward trend and rose faster after grade 2. Children in the sharp-developing (n = 44), high-developing (n = 136), and rapid-developing (n = 237) myopia groups developed myopia before grades 2, 3, and 4, respectively. Their SER development speed remained at a relatively high level after myopia, almost consistent with that before myopia. Children in the moderate-developing (n = 418) and low-developing (n = 391) non-myopia groups did not develop myopia before grade 4. Some characteristics in grade 1 were independently associated with SER trajectories, including sex, axial length, number of parents with myopia, residence, academic achievement, and the duration of outdoor activity. Based on the baseline characteristics, we established the model predicting the probability of children belonging to each group., Conclusions: Myopia interventions are best started in grade 1 or preschool age. If interventions are not taken in time, the latest intervention window might be in grades 1, 2, and 3 for children with a high probability of belonging to the sharp-developing, high-developing, and rapid-developing myopia groups, respectively. The above probabilities might be predicted using the model we established. Moreover, the interventions for myopic children shouldn't be ignored., (© 2023. The Author(s).)

Importance: It remains unclear whether pet ownership is associated with cognitive decline and to what extent pet ownership mitigates the association between living alone and cognitive decline., Objective: To explore the association of pet ownership with cognitive decline, the interaction between pet ownership and living alone, and the extent to which pet ownership mitigates the association between living alone and cognitive decline in older adults., Design, Setting, and Participants: This cohort study used data from waves 5 (June 2010 to July 2011) to 9 (from June 2018 to July 2019) in the English Longitudinal Study of Ageing. Participants included adults 50 years and older. Data were analyzed from April 1 to June 30, 2023., Exposures: Pet ownership and living alone in wave 5., Main Outcomes and Measures: In waves 5 to 9, verbal memory and verbal fluency were assessed, and composite verbal cognition was further calculated., Results: Of the 7945 participants included, the mean (SD) age was 66.3 (8.8) years, and 4446 (56.0%) were women. Pet ownership was associated with slower rates of decline in composite verbal cognition (β = 0.008 [95% CI, 0.002-0.014] SD/y), verbal memory (β = 0.006 [95% CI, 0.001-0.012] SD/y), and verbal fluency (β = 0.007 [95% CI, 0.001-0.013] SD/y). Three-way interaction tests showed that living alone was a significant modifier in all 3 associations. Stratified analyses showed that pet ownership was associated with slower rates of decline in composite verbal cognition (β = 0.023 [95% CI, 0.011-0.035] SD/y), verbal memory (β = 0.021 [95% CI, 0.008-0.034] SD/y), and verbal fluency (β = 0.018 [95% CI, 0.005-0.030] SD/y) among individuals living alone, but not among those living with others. Joint association analyses showed no significant difference in rates of decline in composite verbal cognition, verbal memory, or verbal fluency between pet owners living alone and pet owners living with others., Conclusions and Relevance: In this cohort study, pet ownership was associated with slower rates of decline in verbal memory and verbal fluency among older adults living alone, but not among those living with others, and pet ownership offset the associations between living alone and declining rates in verbal memory and verbal fluency. Further studies are needed to assess whether pet ownership slows the rate of cognitive decline in older adults living alone.

Inhibiting the Leidenfrost effect has drawn extensive attention due to its detrimental impact on heat dissipation in high-temperature industrial applications. Although hierarchical structures have improved the Leidenfrost point to over 1000 °C, the current performance of single-scale structures remains inadequate. Herein, we present a facile high-temperature treatment method to fabricate superhydrophilic nickel foams that demonstrate ultrafast droplet permeation within tens of milliseconds, elevating the Leidenfrost point above 500 °C. Theoretical analysis based on the pressure balance suggests that these remarkable features arise from the superhydrophilic property, high porosity, and large pore diameter of nickel foams that promote capillary wicking and vapor evacuation. Compared to solid nickel surfaces with a Leidenfrost temperature of approximately 235 °C, nickel foams nucleate boiling at high superheat, triggering an order of magnitude higher heat flux. The effects of the pore diameter and surface temperature on droplet permeation behaviors and heat transfer characteristics are also elucidated. The results indicate that droplet permeation is dominated by inertial and capillary forces at low and high superheat, respectively, and moderate pore diameters are more conducive to facilitating droplet permeation. Furthermore, our heat transfer model reveals that pore diameter plays a negligible role in the heat flux at high surface temperatures due to the trade-off between effective thermal conductivity and specific surface area. This work provides a new strategy to address the Leidenfrost effect by metal foams, which may promise great potential in steel forging and nuclear reactor safety.

Objective: Some older adults with loneliness might have transient loneliness, followed by full remission, while others might have persistent loneliness. Such different courses might differ in predicting the risk of dementia, but most previous studies assessed short-term loneliness at a single time point, ignoring the long-term changes of loneliness. This study aimed to explore the association between 8-year trajectories of late-life loneliness and incident dementia., Methods: Data were from the English Longitudinal Study of Ageing (waves 2-9). This study included 6,722 older adults measured for loneliness greater than or equal to three times from wave 2 (2004-2005) to wave 6 (2012-2013) and free from dementia in wave 6. Loneliness was assessed using the short 1980 version of the University of California, Los Angeles Loneliness Scale. Group-based trajectory modeling was used to explore loneliness trajectories during waves 2-6. Cox proportional hazard models were used to investigate the association of loneliness trajectories with incident dementia during waves 6-9., Results: Five distinct loneliness trajectories were identified: long-term low, persistently decreasing, persistently increasing, long-term moderate, and long-term high. Compared with long-term low loneliness, the HRs (95% confidence intervals) for persistently decreasing, persistently increasing, long-term moderate, and long-term high loneliness were 1.29 (0.83-2.00), 1.55 (1.04-2.31), 1.56 (1.03-2.38), and 3.35 (1.89-5.91), respectively., Conclusion: The elderly show distinct patterns of loneliness over time, which cannot be captured by a single assessment of loneliness. The elderly with long-term loneliness and persistently increasing loneliness might be the high-risk group for dementia. Further studies are needed to determine whether reducing loneliness can prevent dementia., (Copyright © 2022 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: To explore the mediating role of personality traits in the correlation between multi-dimensional adverse childhood experiences (ACEs) and depressive symptoms in older adults., Methods: This cohort study used data from the English Longitudinal Study of Ageing, and included 4050 older adults without depressive symptoms in 2010-2011. Multi-dimensional ACEs were evaluated in 2006-2007. Personality traits were assessed using the Midlife Development Inventory in 2010-2011. Depressive symptoms were measured using the 8-item version of the Center for Epidemiologic Studies Depression Scale during 2012-2019. Cox proportional hazard model was used to explore the associations between ACEs and depressive symptoms. The package named "mediation" in R was used to test mediating role of personality traits., Results: ACEs in each dimension significantly increased the risk of depressive symptoms (all P-values < 0.05). The association of maltreatment (18.18 %) and household dysfunction (19.69 %) with depressive symptoms was significantly mediated by neuroticism. The correlation between poor parent-child bonding and depressive symptoms was significantly mediated by neuroticism (19.43 %), conscientiousness (4.84 %), and extroversion (8.02 %)., Limitations: ACEs were retrospectively assessed based on participants' memories, which may induce recall bias., Conclusions: Maltreatment and household dysfunction may induce depressive symptoms by increasing neuroticism. Poor parent-child bonding may induce depressive symptoms by increasing neuroticism and reducing conscientiousness and extraversion. In addition to reducing the occurrence of ACEs, reducing neuroticism of individuals with maltreatment and household dysfunction in childhood, and reducing neuroticism, and increasing conscientiousness and extraversion of individuals with poor parent-child bonding in childhood might help to decrease their risk of depressive symptoms., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The recently published "Life's Essential 8" (LE8) by the American Heart Association has overcome some limitations in evaluating cardiovascular health (CVH) in the previous "Life's Simple 7.", Objective: We aimed to examine the secular trends in CVH, as assessed by the LE8, in US adults from 2005 to 2018., Methods: Using cross-sectional data from the National Health and Nutrition Examination Survey between 2005-2006 and 2017-2018, we calculated the age-standardized mean scores of overall CVH and each of the LE8 components, where a higher score (range 0-100 points) means a better health status. A total of 21,667 adults aged 20-79 years were included in this analysis., Results: The overall CVH did not significantly change between 2005-2006 and 2017-2018 (65.5, 95% CI 63.9-67.1 to 65.0, 95% CI 62.8-67.1; P=.82). The individual metrics did not significantly change for diet (41.0, 95% CI 38.0-43.9 to 41.5, 95% CI 36.5-46.6; P=.94), physical activity (57.5, 95% CI 53.0-61.9 to 53.0, 95% CI 48.7-57.3; P=.26), and blood pressure (68.4, 95% CI 65.2-71.5 to 68.6, 95% CI 65.3-71.9, P=.35), improved for nicotine exposure (64.7, 95% CI 61.1-68.4 to 71.9, 95% CI 67.7-76.2; P<.001), sleep health (83.7, 95% CI 81.6-85.7 to 84.1, 95% CI 81.2-87.1; P=.006), and blood lipids (61.6, 95% CI 59.1-64.0 to 67.0, 95% CI 63.5-70.4; P<.001), and worsened for BMI (63.4, 95% CI 59.7-67.1 to 56.2, 95% CI 52.5-59.9; P<.001) and blood glucose (83.9, 95% CI 82.4-85.4 to 77.4, 95% CI 74.5-80.3; P<.001)., Conclusions: According to the LE8, the overall CVH did not change among US adults from 2005 to 2018, as well as 3 components (diet, physical activity, and blood pressure). Other metrics such as nicotine exposure, blood lipids, and sleep health improved, while BMI and blood glucose deteriorated over time., (©Cheng Li, Yanzhi Li, Min Zhao, Cheng Zhang, Pascal Bovet, Bo Xi. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 08.05.2023.)

Forsythia fruit, edible fruit of Forsythia suspensa (Thunb.) Vahl, which has been found to be effective in treating cholestasis. However, its key component for alleviating cholestasis has not been determined. In this study, four representative active ingredients in forsythia fruit were selected. Through network pharmacology and molecular docking technology, we tried to find the key component for its treatment of cholestasis. Furthermore, the model of cholestasis in mice was established to verify the protective effect of the key component on cholestasis. Network pharmacology and molecular docking showed that forsythoside A (FTA) is the key component of forsythia fruit in the treatment of cholestasis. In vivo experiments revealed that FTA treatment could alleviate liver injury, dysfunction, and collagen deposition induced by cholestasis in mice. At the same time, FTA treatment inhibited inflammatory factor release and fibrosis-related factor expression. In addition, FTA treatment also reduced MMP-2, TLR4, MYD88, NF-κB p65, and p -NF-κB p65 protein expression. In conclusion, FTA, a key component of forsythia fruit, alleviated liver damage and fibrosis caused by cholestasis via inhibiting the TLR4/NF-κB pathway, extracellular matrix accumulation, and inflammatory cytokine expression. The research results could provide a scientific reference for the development of forsythia fruit as a drug or functional food to prevent and treat cholestasis.

Background: The American Heart Association recently updated its construct of what constitutes cardiovascular health (CVH), called Life's Essential 8. We examined the association of total and individual CVH metrics according to Life's Essential 8 with all-cause and cardiovascular disease (CVD)-specific mortality later in  life., Methods: Data were from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 at baseline linked to the 2019 National Death Index records. Total and individual CVH metric scores including diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure were classified as 0-49 (low level), 50-74 (intermediate level), and 75-100 (high level) points. The total CVH metric score (the average of the 8 metrics) as a continuous variable was also used for dose-response analysis. The main outcomes included all-cause and CVD-specific mortality., Results: A total of 19,951 US adults aged 30-79 years were included in this study. Only 19.5% of adults achieved a high total CVH score, whereas 24.1% had a low score. During a median follow-up of 7.6 years, compared with adults with a low total CVH score, those with an intermediate or high total CVH score had 40% (adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.51-0.71) and 58% (adjusted HR 0.42, 95% CI 0.32-0.56) reduced risk of all-cause mortality. The corresponding adjusted HRs (95%CIs) were 0.62 (0.46-0.83) and 0.36 (0.21-0.59) for CVD-specific mortality. The population-attributable fractions for high (score ≥ 75 points) vs. low or intermediate (score < 75 points) CVH scores were 33.4% for all-cause mortality and 42.9% for CVD-specific mortality. Among all 8 individual CVH metrics, physical activity, nicotine exposure, and diet accounted for a large proportion of the population-attributable risks for all-cause mortality, whereas physical activity, blood pressure, and blood glucose accounted for a large proportion of CVD-specific mortality. There were approximately linear dose-response associations of total CVH score (as a continuous variable) with all-cause and CVD-specific mortality., Conclusions: Achieving a higher CVH score according to the new Life's Essential 8 was associated with a reduced risk of all-cause and CVD-specific mortality. Public health and healthcare efforts targeting the promotion of higher CVH scores could provide considerable benefits to reduce the mortality burden later in life., (© 2023. The Author(s).)

Background: Thymomas and thymic carcinoma are thymic epithelial tumors (TETs) of the anterior mediastinum. On the basis of The AJCC 8th Edition of TNM classification, no prognostic prediction model has been established for TETs patients undergoing surgical resection. In this study, based on data from Qilu Hospital of Shandong University, we identified prognostic factors and developed a nomogram to predict the prognosis for TETs patients undergoing extended thymectomy., Methods: Patients with TETs who underwent thymectomy between 2010 and 2020 were consecutively enrolled. An analysis of multivariate Cox regression and stepwise regression using the Akaike information criterion (AIC) was conducted to identify prognostic factors, and a nomogram for TETs was derived from the results of these analyses. The model was validated internally with the Kaplan-Meier curves, ROC curves and calibration curves., Results: There were 350 patients with TETs enrolled in the study, and they were divided into a training group (245,0.7) and a validation group (105,0.3). Age, histological type, tumor size, myasthenia gravis, and TNM stage were independent prognostic factors for CSS. The Kaplan-Meier curves showed a significant difference between high nomorisk group and low nomorisk group. A nomogram for CSS was formulated based on the independent prognostic factors and exhibited good discriminative ability as a means of predicting cause-specific mortality, as evidenced by the area under the ROC curves (AUCs) of 3-year, 5-year, and 10-year being 0.946, 0.949, and 0.937, respectively. The calibration curves further revealed excellent consistency between the predicted and actual mortality when using this nomogram., Conclusion: There are several prognostic factors for TETs. Based on TNM stage and other prognostic factors, the nomogram accurately predicted the 3-, 5-, and 10-year mortality rates of patients with TETs in this study. The nomogram could be used to stratify risk and optimize therapy for individual patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Li, Tang, Zhu and Tian.)

Previous studies have shown a relationship between fine particulate matter (PM 2.5 ) exposure and an increased risk of neonatal disorders. Considering the huge burden of neonatal disorders, we assessed spatiotemporal trends of neonatal disorders burden caused by ambient and household PM 2.5 at the global, regional, and national levels from 1990 to 2019. The number, rate, and population attributable fraction (PAF) of ambient and household PM 2.5 -related neonatal disorders disability-adjusted life years (DALYs) in 204 countries and territories from 1990 to 2019 were obtained from the Global Burden of Disease Study 2019 to measure the related neonatal disorders burden by age, sex, subtype, and region. Estimated annual percentage change (EAPC) was estimated to quantify temporal trends. In 2019, approximately a fifth of the global neonatal disorders burden was attributable to PM 2.5 exposure, with 7.54% for ambient PM 2.5 and 13.23% for household PM 2.5 . Although the global neonatal disorders burden attributable to household PM 2.5 has decreased substantially in the past 30 years, that attributable to ambient PM 2.5 has increased, especially in lower sociodemographic index (SDI) regions. The highest rate and PAF of ambient PM 2.5 -related neonatal disorders DALYs in 2019 were in South Asia and East Asia, respectively, and the fastest increases were in Eastern Sub-Saharan Africa (for rate: EAPC = 2.55, 95% CI: 2.37-2.73) and South Asia (for PAF: EAPC = 3.88, 95% CI: 3.68-4.08). In addition, we found an inverted V-shaped between rates and PAFs of ambient PM 2.5 -related neonatal disorders DALYs in 2019, as well as corresponding EAPCs, and SDI, while rates and PAFs of household PM 2.5 -related neonatal disorders DALYs in 2019 were highly negatively correlated with SDI. In the past three decades, the global ambient PM 2.5 -related neonatal disorders burden largely increased, especially in lower SDI regions. Comparatively, the household PM 2.5 -related neonatal disorders burden decreased but still accounted for about two-thirds of the PM 2.5 -related neonatal disease burden., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Although observational studies have suggested associations between circulating antioxidants and many mental disorders, causal inferences have not been confirmed. Mendelian randomization (MR) analyses were conducted using summary-level statistics from genome-wide association studies (GWASs) to explore whether genetically determined absolute circulating antioxidants (i.e., ascorbate, retinol, β-carotene, and lycopene) and metabolites (i.e., α- and γ-tocopherol, ascorbate, and retinol) were causally associated with the risk of six major mental disorders, including anxiety disorders (AD), major depressive disorder (MDD), bipolar disorder (BIP), schizophrenia (SCZ), post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). MR analyses were performed per specific-outcome databases, including the largest GWAS published to date (from 9725 for OCD to 413,466 for BIP participants), UK Biobank (over 370,000 participants), and FinnGen (over 270,000 participants), followed by meta-analyses. We found no significant evidence that genetically determined diet-derived circulating antioxidants were significantly causally associated with the risk of the six above-mentioned major mental disorders. For absolute antioxidant levels, the odds ratios (ORs) ranged from 0.91 (95% CI, 0.67-1.23) for the effect of β-carotene on OCD to 1.18 (95% CI, 0.90-1.54) for the effect of ascorbate on OCD. Similarly, for antioxidant metabolites, ORs ranged from 0.87 (95% CI, 0.55-1.38) for the effect of ascorbate on MDD to 1.08 (95% CI, 0.88-1.33) for the effect of ascorbate on OCD. Our study does not support significant causal associations of genetically determined diet-derived circulating antioxidants with the risk of major mental disorders.

Hypothesis: The unbalanced capillary force provided by wettability patterns, non-uniform/asymmetric microtextures enables directional droplet transport, while macrotextures have shown potentials in reducing the contact time. Inspired by these findings, we design millimeter superhydrophobic stepped surfaces to simultaneously achieve highly steerable directional bouncing and contact time reduction of impacting droplets., Experiments: The stepped surfaces are fabricated by computerized numerical control, chemical oxidation, hydrophobic treatment. Systematic impact experiments are conducted under Weber number ranging from 10.5 to 20.5, two step heights (0.5 mm and 1.0 mm) and extensive impact positions., Findings: Compared with known microtextured surfaces, the stepped surfaces exhibit excellent performance with the maximum lateral movement distance about 8 times of droplet radius, controllable rebound angle ranging from ∼ 32 ° to ∼ 90 ° and up to ∼ 30 % reduction in contact time. Particularly, we divide the directional bouncing characteristics into six regimes and attribute the variation of rebound velocity by the synergistic effects of viscous dissipation, excess surface energy, excess kinetic energy. It is demonstrated that the contact time is reduced by liquid mass redistribution and asymmetry enhancement. Predictive models of contact time that incorporate the coupling effects of impact position, impact velocity and step height are also established., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Adolescent idiopathic scoliosis (AIS) is the most common type of idiopathic scoliosis, affecting approximately 0.61%-6.15% adolescents worldwide. To date, the results on the relationship between moderate-to-vigorous physical activity (MVPA) and AIS were inconsistent, and the association between screen time (ST) and AIS remained unclear. This study aimed to describe MVPA and ST among adolescents, and to explore the independent and joint associations between PA, ST, and AIS., Methods: A frequency-matched case-control study based on the 2021 Chinese School-based Scoliosis Screening Program in Shenzhen city, south China, was conducted. The research involved 494 AIS patients (aged 9-17 years) and 994 sex- and age-matched healthy controls. MVPA and ST were measured using a self-administered questionnaire. Logistic regression models estimated associations between PA, ST, and AIS., Results: Compared to subjects meeting the recommended 60-min daily of MVPA, adolescents reporting daily MVPA time less than 60 min had 1.76 times higher odds of experiencing AIS (95% CI: 1.32-2.35) and adolescents reporting daily MVPA in inactive status had 2.14 times higher odds of experiencing AIS (95% CI: 1.51-3.03). Moreover, participants reporting ST for 2 hours or more had 3.40 times higher odds of AIS compared with those reporting ST less than 2 hours (95% CI: 2.35-4.93). When compared with the adolescents reporting both ST and MVPA meeting the guidelines recommended times (ST < 2 h and MVPA ≥ 60 min/day), those reporting both ST ≥ 2 h and MVPA in inactive status are 8.84 times more likely to develop AIS (95% CI: 3.99-19.61)., Conclusions: This study reported that the insufficient MVPA, especially MVPA in inactive status, and excessive ST were risk factors for AIS. Additionally, the joint effects of insufficient MVPA and excessive ST probably increase the risk of AIS.

Anthocyanins as natural pH-sensitive material can be used to determine the freshness of largemouth bass (Micropterus salmoides) fillets. However, it is easily degraded. Using zein as the protective layer to improve the light blocking ability of the film, gellan gum (GG) and black rice extracts (BRE) as the sensing layer, a bilayer colorimetric indicator film for monitoring fish spoilage was developed. The functionality and stability of bilayer film and GG single film were compared. As compared to GG single film, Zein/GG bilayer film had stronger intermolecular interactions, higher mechanical properties, and higher optical barrier properties. Notably, Zein/GG-8 % BRE bilayer film exhibited higher stability than GG-8 % BRE film when the films were exposed to room temperature for 30 days. Zein/GG-8 % BRE bilayer film were further used to monitor freshness of largemouth bass fillets during storage. Zein/GG-8 % BRE bilayer film demonstrated a noticeable color change from red to brown when largemouth bass fillets spoiled. Moreover, the ∆E of films showed a good correlation with TVB-N of largemouth bass fillets (R 2  = 0.985). Our research results show that the Zein/GG-BRE bilayer indicator film has great potential application prospects in monitoring fish freshness., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Described herein is the first application of perfluorinated solvent in the stereoselective formation of O -/ S -glycosidic linkages that occurs via a Ferrier rearrangement of acetylated glycals. In this system, the weak interactions between perfluoro- n -hexane and substrates could augment the reactivity and stereocontrol. The initiation of transformation requires only an extremely low loading of resin-H + and the mild conditions enable the accommodation of a broad spectrum of glycal donors and acceptors. The 'green' feature of this chemistry is demonstrated by low toxicity and easy recovery of the medium, as well as operational simplicity in product isolation.

Single measurements of waist circumference (WC) can predict the incident hypertension, while dynamic change patterns of WC during young adulthood and their association with the incidence of hypertension are poorly demonstrated. This study aimed to identify the longitudinal WC trajectories during young adulthood and explore their association with the risk of incident hypertension. We utilized the data from the China Health and Nutrition Survey (1993-2015) and included 6604 participants aged 18-50 years with repeated WC measurements of 3-8 times and information on incident hypertension. The group-based trajectory model was used to identify WC trajectories. Cox proportional hazard model was conducted to evaluate the association of WC trajectories with the risk of incident hypertension. We identified four distinct WC trajectories during young adulthood. Participants with the low-increasing and the moderate-increasing trajectories had increasing but normal WC, while those with the high-increasing and the sharp-increasing trajectories developed from non-abdominal obesity to abdominal obesity. Compared with the low-increasing trajectory, the adjusted hazard ratios (95% confidence intervals) were 1.48 (1.16-1.89), 2.50 (1.84-3.40), and 3.86 (2.40-6.21) for the moderate-increasing, the high-increasing, and the sharp-increasing trajectories, respectively. After further excluding participants with obesity at baseline, this association did not alter substantially. The gender-specific trajectory analyses yielded similar results. WC trajectories during young adulthood were significantly associated with the risk of incident hypertension in Chinese. Moreover, even the increasing WC trajectory within the normal range during young adulthood might increase the risk of hypertension., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Key Message: Two 4-coumarate: CoA ligase genes in tea plant involved in phenylpropanoids biosynthesis and response to environmental stresses. Tea plant is rich in flavonoids benefiting human health. Lignin is essential for tea plant growth. Both flavonoids and lignin defend plants from stresses. The biosynthesis of lignin and flavonoids shares a key intermediate, 4-coumaroyl-CoA, which is formed from 4-coumaric acid catalyzed by 4-coumaric acid: CoA ligase (4CL). Herein, we report two 4CL paralogs from tea plant, Cs4CL1 and Cs4CL2, which are a member of class I and II of this gene family, respectively. Cs4CL1 was mainly expressed in roots and stems, while Cs4CL2 was mainly expressed in leaves. The promoter of Cs4CL1 had AC, nine types of light sensitive (LSE), four types of stress-inducible (SIE), and two types of meristem-specific elements (MSE). The promoter of Cs4CL2 also had AC and nine types of LSEs, but only had two types of SIEs and did not have MSEs. In addition, the LSEs varied in the two promoters. Based on the different features of regulatory elements, three stress treatments were tested to understand their expression responses to different conditions. The resulting data indicated that the expression of Cs4CL1 was sensitive to mechanical wounding, while the expression of Cs4CL2 was UV-B-inducible. Enzymatic assays showed that both recombinant Cs4CL1 and Cs4CL2 transformed 4-coumaric acid (CM), ferulic acid (FR), and caffeic acid (CF) to their corresponding CoA ethers. Kinetic analysis indicated that the recombinant Cs4CL1 preferred to catalyze CF, while the recombinant Cs4CL2 favored to catalyze CM. The overexpression of both Cs4CL1 and Cs4CL2 increased the levels of chlorogenic acid and total lignin in transgenic tobacco seedlings. In addition, the overexpression of Cs4CL2 consistently increased the levels of three flavonoid compounds. These findings indicate the differences of Cs4CL1 and Cs4CL2 in the phenylpropanoid metabolism., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: This study aimed to assess the relationship between waist-to-height (WHtR) and estimated glomerular filtration rate (eGFR) in men, non-menopausal, and postmenopausal women among middle-aged and elderly Chinese., Methods: This study analyzed the data of 7,807 participants in a cross-sectional survey, ie, the third wave of the China Health and Retirement Longitudinal Study. Restrictive cubic-spline regression with three knots was used to assess the dose-response association of WHtR with eGFR. Piecewise linear regression models were further established to calculate the slope of each segment and their 95% confidence interval (CI)., Results: After adjusting for potential confounders, an inverse L-shaped dose-response relationship was found between WHtR and eGFR among men (Pnonlinear = 0.024, threshold = 0.513) and postmenopausal women (Pnonlinear = 0.009, threshold = 0.503). The slopes on the right sides of the threshold were statistically significant among men (β2 = -33.77, 95% CI: -53.23 to -14.31) and postmenopausal women (β2 = -36.53, 95% CI: -49.71 to -23.35), respectively. A weak negative linear relationship existed between WHtR and eGFR in non-menopausal women., Conclusions: The relationship between WHtR and eGFR tended to be inverse-L-shaped in men and postmenopausal women, but may vary with postmenopausal status in women., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2020 by The North American Menopause Society.)

Objective: The aim of this study was to assess the association of early menopause with diabetes and the mediating effect of abdominal obesity., Methods: This cross-sectional study was conducted among 5,693 participants. The data from the second follow-up (2015) of the China Health and Retirement Longitudinal Study were used. Participants self-reported their age at menopause and were divided into three age groups (<45, 45-54, and >54 years) according to the 10th, 10th to 90th, and 90th percentiles, with a menopausal age of 45 to 54 years serving as reference. The total effect was decomposed into direct and indirect (mediating) effects using logistic regression based on the Karlson-Holm-Breen method., Results: Compared to the menopausal age of 45 to 54 years, early menopause (<45 years) was associated with diabetes (odds ratio  = 2.19, 95% CI: 1.29-3.69) among Chinese women. The mediating effect of early menopause (<45 years) on diabetes was 4.98% (P = 0.321) for abdominal obesity., Conclusions: Early menopause may be associated with diabetes among Chinese women. Moreover, the mediating effect of abdominal obesity makes up a small percentage and has no statistical significance. Further studies are needed to examine other mechanisms behind the association of early menopause with diabetes.

Objective: The aim of this paper was to identify shapes of the curves between weekly working hours (WWH) and mental health status (MHS) and determine WWH for the best MHS in 13 occupations., Methods: This cross-sectional study applied public data of the 2015 to 2016 California Health Interview Survey. Restricted cubic spline regression was used to determine non-linear trends., Results: A statistically significant nearly V-shaped curve was demonstrated between WWH and MHS in total population, men and management, business and finance occupations. WWH for the best MHS were 42, 45, and 46 hours, respectively., Conclusion: These results suggest MHS be susceptible to WWH in total population, men and management, business and finance occupations. WWH for the best MHS for relevant populations could provide evidence for better work hours regulations in California.

Main Conclusion: LARs promoted the biosynthesis of catechin monomers and inhibited their polymerization. The accumulation of catechin monomers and polymers was increased by up-regulating the expression of NtLAR and NtANR s in CsMYB5b transgenic tobacco. Tea is rich in polyphenolic compounds, and catechins are the major polyphenols in tea. The biosynthesis of polyphenols is closely related to the expression of the leucoanthocyanidin reductase (LAR) and anthocyanidin reductase (ANR) genes. In this paper, an evolutionary analysis and functional characterization of three CsLARs were performed. The phylogenetic tree showed that plant LARs could be grouped into three, including gymnosperms, monocotyledons and dicotyledons (clusters I and II). The eighth amino acid residue in a conserved LAR-specific motif is changeable due to a transversion (G → T) and transition (G → C) that occur in the corresponding codon. Therefore, plant LARs can be classified as G-type, A-type and S-type LARs due to this variable amino acid residue. Although (2R, 3S)-trans-flavan-3-ols were the products of recombinant CsLARs proteins expressed in Escherichia coli, both (2R, 3S)-trans and (2R, 3R)-cis-flavan-3-ols were detected in tobacco overexpressing CsLARs. However, a butanol/HCl hydrolysis assay indicated that overexpression of the CsLARs caused a decrease in polymerized catechins. A hybridization experiment with CsLARc + AtPAP1 also showed that no polymers other than epicatechin, catechin and glycoside were detected, although the accumulation of anthocyanins was markedly decreased. CsMYB5b promoted the biosynthesis of both flavan-3-ols and proanthocyanidins (PAs). Therefore, LARs promoted the biosynthesis of catechin monomers and inhibited their polymerization. The accumulation of catechin monomers and polymers was increased by up-regulating the expression of the NtLAR and NtANRs in CsMYB5b transgenic tobacco.

A Gram-stain-positive, aerobic, non-motile, rod-shaped bacterium, designated strain CF5-4(T), was isolated from iron mining powder. 16S rRNA gene sequence analysis grouped strain CF5-4(T) in a single cluster with Actinotalea fermentans DSM 3133(T) (97.6% similarity). The major fatty acids (>5%) of strain CF5-4(T) were anteiso-C(15:0), anteiso-C(15:1) A, C(16:0), iso-C(16:0), iso-C(15:0) and anteiso-C(17:0). The predominant respiratory quinone was MK-10(H₄) and the genomic DNA G+C content was 74.7 mol%. The major polar lipids were diphosphatidylglycerol and one unidentified phosphoglycolipid. The peptidoglycan type of strain CF5-4(T) was A4β, containing L-Orn-D-Ser-D-Asp. The cell-wall sugars were rhamnose, fucose, mannose and galactose. The results of DNA-DNA hybridization in combination with the comparison of phenotypic and phylogenetic characteristics among strain CF5-4(T) and related micro-organisms revealed that the isolate represents a novel species of the genus Actinotalea, for which the name Actinotalea ferrariae sp. nov. is proposed. The type strain is CF5-4(T) ( =KCTC 29134(T) =CCTCC AB2012198(T)).

Dramatic progress has occurred in neonatal intensive care in tertiary centers in mid-eastern China. We investigated the characteristics of neonatal respiratory failure (NRF) including the incidence, management, outcomes and costs in 14 neonatal intensive care units (NICUs) of Hebei, a province at an intermediate economic level in China. Over a period of 12 consecutive months in 2007-2008, perinatal data were collected prospectively from all NICU admissions (n = 11,100). NRF was defined as severe hypoxemia requiring respiratory support for more than 24 h, and was diagnosed in 1,875 newborns (16.9%). The average birth weight of newborns with NRF was 2,200 g (range 600-5,500 g), with 60.9% <2,500 g, and 2% <1,000 g. The male:female ratio was 2.6:1. The leading diagnosis was respiratory distress syndrome; 58.3% of newborns with respiratory distress syndrome received surfactant. Continuous positive airway pressure was used more than ventilation (73.3 vs. 49.1%,p < 0.001). Overall, the mortality rate until discharge was 31.4% (583/1,859). Most deaths (432, 74.1%) followed a parental decision to withdraw care. NRF mortality varied in association with different gross domestic product levels, family annual income and nurse-to-bed ratios. The median cost of a hospital stay was 10,169 CNY (interquartile range: 6,745-16,386) for NRF survivors. We conclude that, despite the available respiratory support in these emerging NICUs, the mortality of NRF remains. This was associated with prematurity, standard of care but also with socioeconomic factors affecting treatment decisions. Assessment of efficacy of respiratory support for NRF in such emerging neonatal services should account for both standard of care and socioeconomic conditions., (Copyright © 2010 S. Karger AG, Basel.)