Activation of ERß hijacks the splicing machinery to trigger R-loop formation in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with aggressive behavior and poor prognosis. Current therapeutic options available for TNBC patients are primarily chemotherapy. With our evolving understanding of this disease, novel targeted therapies, including poly ADP-ribose polymerase (PARP) inhibitors, antibody-drug conjugates, and immune-checkpoint inhibitors, have been developed for clinical use. Previous reports have demonstrated the essential role of estrogen receptor ß (ERß) in TNBC, but the detailed molecular mechanisms downstream ERß activation in TNBC are still far from elucidated. In this study, we demonstrated that a specific ERß agonist, LY500307, potently induces R-loop formation and DNA damage in TNBC cells. Subsequent interactome experiments indicated that the residues 151 to 165 of U2 small nuclear RNA auxiliary factor 1 (U2AF1) and the Trp439 and Lys443 of ERß were critical for the binding between U2AF1 and ERß. Combined RNA sequencing and ribosome sequencing analysis demonstrated that U2AF1-regulated downstream RNA splicing of 5-oxoprolinase (OPLAH) could affect its enzymatic activity and is essential for ERß-induced R-loop formation and DNA damage. In clinical samples including 115 patients from The Cancer Genome Atlas (TCGA) and 32 patients from an in-house cohort, we found a close correlation in the expression of ESR2 and U2AF1 in TNBC patients. Collectively, our study has unraveled the molecular mechanisms that explain the therapeutic effects of ERß activation in TNBC, which provides rationale for ERß activation-based single or combined therapy for patients with TNBC.

Association between alcohol consumption and sleep traits: observational and mendelian randomization studies in the UK biobank.

Previous studies have shown that excessive alcohol consumption is associated with poor sleep. However, the health risks of light-to-moderate alcohol consumption in relation to sleep traits (e.g., insomnia, snoring, sleep duration and chronotype) remain undefined, and their causality is still unclear in the general population. To identify the association between alcohol consumption and multiple sleep traits using an observational and Mendelian randomization (MR) design. Observational analyses and one-sample MR (linear and nonlinear) were performed using clinical and individual-level genetic data from the UK Biobank (UKB). Two-sample MR was assessed using summary data from genome-wide association studies from the UKB and other external consortia. Phenotype analyses were externally validated using data from the National Health and Nutrition Examination Survey (2017-2018). Data analysis was conducted from January 2022 to October 2022. The association between alcohol consumption and six self-reported sleep traits (short sleep duration, long sleep duration, chronotype, snoring, waking up in the morning, and insomnia) were analysed. This study included 383,357 UKB participants (mean [SD] age, 57.0 [8.0] years; 46% male) who consumed a mean (SD) of 9.0 (10.0) standard drinks (one standard drink equivalent to 14 g of alcohol) per week. In the observational analyses, alcohol consumption was significantly associated with all sleep traits. Light-moderate-heavy alcohol consumption was linearly linked to snoring and the evening chronotype but nonlinearly associated with insomnia, sleep duration, and napping. In linear MR analyses, a 1-SD (14 g) increase in genetically predicted alcohol consumption was associated with a 1.14-fold (95% CI, 1.07-1.22) higher risk of snoring (P < 0.001), a 1.28-fold (95% CI, 1.20-1.37) higher risk of evening chronotype (P < 0.001) and a 1.24-fold (95% CI, 1.13-1.36) higher risk of difficulty waking up in the morning (P < 0.001). Nonlinear MR analyses did not reveal significant results after Bonferroni adjustment. The results of the two-sample MR analyses were consistent with those of the one-sample MR analyses, but with a slightly attenuated overall estimate. Our findings suggest that even low levels of alcohol consumption may affect sleep health, particularly by increasing the risk of snoring and evening chronotypes. The negative effects of alcohol consumption on sleep should be made clear to the public in order to promote public health.

Establishment of self-reported hearing cut-off value on the Chinese version of short form of speech, spatial and qualities of hearing scale (SSQ12).

OBJECTIVE: The aim of this study was to evaluate the efficacy of the Chinese version of Speech, Spatial and Qualities of Hearing Scale (C-SSQ12) in the Chinese Mandarin-speaking population and to determine its screening cut-off value by comparing measured pure-tone average (PTA), the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S) scores and C-SSQ12 scores. DESIGN: All participants completed the C-SSQ12 questionnaire and underwent the pure-tone audiometry. Older subjects aged ≧ 60 years completed the HHIE-S questionnaire. The optimal cut-off value for the C-SSQ12 as a hearing screening tool was calculated by comparing different cut-offs and hearing thresholds. STUDY SAMPLE: A total of 300 subjects were recruited. RESULTS: There was a negative correlation between C-SSQ12 scores and HHIE-S scores (r = -0.749). C-SSQ12 scores were negatively correlated with PTA (r = -0.507; r = -0.542). The best cut-off value for the C-SSQ12 was 6.0, with a sensitivity of 78.2%, specificity of 80.3%, positive predictive value of 63.7% and negative predictive value of 97.0% (PTA > 40dBHL for bilateral ears). CONCLUSIONS: Compared to mild hearing loss, the C-SSQ12 is a reliable and validated hearing screening tool with increased sensitivity for detecting moderate-to-severe hearing loss.

Metabolomics analysis reveals cytotoxic effects of ouabain towards psoriatic keratinocytes via impairment of glutathione metabolism.

Ouabain is a cardiac glycoside long studied for treating heart diseases, but the attempts to evaluate its anti-psoriatic activity have not been reported. We aimed to explore the effects of ouabain on proliferation and metabolism towards psoriatic keratinocytes. In human HaCaT keratinocytes, ouabain potently decreased viability, promoted apoptosis and caused G2/M cycle arrest. Metabolomics analysis indicated that ouabain markedly impaired glutathione metabolism. The solute carrier family 7 member 11 (SLC7A11) is an amino acid transporter highly specific to cysteine, which is critical for glutathione synthesis. Ouabain downregulated SLC7A11, reduced cysteine uptake and subsequently inhibited glutathione synthesis, probably through inhibiting Akt/mTOR/beclin axis that regulate protein activity of SLC7A11. The impaired glutathione synthesis and oxidative stress caused by ouabain may contribute to its cytotoxicity towards psoriatic keratinocytes. Our results provide experimental evidence supporting further study of ouabain as a potential anti-psoriatic agent.

Dual-mode tunable absorber based on quasi-bound states in the continuum.

In this Letter, we propose a novel, to the best of our knowledge, dual-mode tunable absorber that utilizes quasi-bound states in the continuum (q-BIC) based on the periodically arranged silicon cylinders tetramer. By introducing asymmetry perturbation through manipulating the diameters of diagonal cylinders in the all-dielectric structure, the symmetry-protected BIC (SP-BIC) transforms into q-BIC, leading to the emergence of one transmission and one reflection Fano-like resonant mode. The relationship between the quality factor of each mode and the asymmetry parameter α is analyzed, revealing an exponential dependence with an exponent of -1.75, i.e., Q ∝ α-1.75. To explain the underlying physics, multipole decomposition analysis and Aleksandra's theory are applied. Subsequently, a monolayer graphene is introduced to the all-dielectric structure to demonstrate the application of the dual-mode tunable absorber. When the critical coupling condition is satisfied, each mode can achieve the theoretical maximum absorption, demonstrating the distinctive capability of our proposed absorber for tuning and efficient light absorption. This research provides valuable insights into light-matter interactions and opens up possibilities for optical modulation and the development of graphene-based devices.

Effects of peripheral blood leukocyte count and tumor necrosis factor-alpha on early death in acute promyelocytic leukemia.

BACKGROUND: Early death remains a major factor in survival in APL. We aimed to analyze the risk factors for differentiation syndrome and early death in acute promyelocytic leukemia (APL). METHODS: The clinical data of APL patients who were newly diagnosed at Mianyang Central Hospital from January 2013 to January 2022 were retrospectively analyzed. RESULTS: Eighty-six newly diagnosed APL patients (37 males and 49 females) were included in this study. The median age was 46 (17-75) years. Sixty-one patients (70.9%) had low/intermediate-risk APL, and 25 patients (29.1%) had high-risk APL. The incidence of differentiation syndrome (DS) was 62.4%. The multivariate analysis showed that a peak white blood cell (WBC) count ≥16 × 10^9/L was an independent risk factor (OR = 11.000, 95% CI: 2.830-42.756, P = 0.001) for DS in all APL patients, while a WBC count ≥10 × 10^9/L on Day 5 was an independent risk factor for DS in low-intermediate risk APL patients (OR = 9.114, 95% CI: 2.384-34.849, P = 0.001). There were 31 patients (36.5%) with mild DS and 22 patients (25.9%) with severe DS. The multivariate analysis showed that WBC count ≥23 × 10^9/L at chemotherapy was an independent risk factor for severe DS (OR = 10.500, 95% CI: 2.344-47.034, P = 0.002). The rate of early death (ED) was 24.4% (21/86). The multivariate analysis showed that male gender (OR = 7.578,95% CI:1.136-50.551, P = 0.036), HGB < 65 g/L (OR = 16.271,95% CI:2.012-131.594, P = 0.009) and WBC count ≥7 × 10^9/L on Day 3(OR = 23.359,95% CI:1.825-298.959, P = 0.015) were independent risk factors for ED. The WBC count at diagnosis, WBC count on Day 3 and WBC count on Day 5 had moderate positive correlations with tumor necrosis factor-α (TNF-α) at diagnosis, and the correlation coefficients were 0.648 (P = 0.012), 0.615 (P = 0.033), and 0.609 (P = 0.035), respectively. The WBC count had no correlation with IL-6. CONCLUSION: During induction treatment, cytotoxic chemotherapy may need to be initiated to reduce the risk of DS for APL patients with a low-intermediate risk WBC count ≥10 × 10^9/L on Day 5 or for all patients with a peak WBC count ≥16 × 10^9/L. Patients with WBC > 7 × 10^9/L on Day 3 have a higher risk of ED. Leukocyte proliferation is associated with TNF-α rather than IL-6, and TNF-α may be a potential biomarker for predicting ED.

A novel PEGylated form of granulocyte colony-stimulating factor, mecapegfilgrastim, for peripheral blood stem cell mobilization in patients with hematologic malignancies.

BACKGROUND: The Pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) has longer half-life and is given once only, which is more comfortable for patients. We aimed to evaluate the efficacy of mecapegfilgrastim for hematopoietic stem cell (HSC) mobilization in patients with hematologic malignancies and to explore the potential factors related to HSC mobilization. METHODS: A retrospective analysis was performed on patients who underwent HSC mobilization in the hematology department of Mianyang Central Hospital from April 2016 to November 2022. The number of CD34 + cells collected was compared between the patients receiving mecapegfilgrastim (PEG group) and those receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF group), and the possible factors for mobilization failure were analyzed. RESULTS: The success rates of collecting CD34 + cells in the PEG group and rhG-CSF group were 80.6% and 67.7%, respectively (χ = 1.444, P = 0.229). The median CD34 + cell counts were 3.62 × 10^6/kg and 2.92 × 10^6/kg (P = 0.178), respectively. After combination with plerixafor for mobilization, the median number of CD34 + cells collected in the PEG group and rhG-CSF group were 3.64 × 10^6/kg and 3.92 × 10^6/kg, respectively, with no significant difference (P = 0.754). There was no significant difference in hematopoietic cell recovery or infection between the groups (P > 0.05). Multivariate analysis showed that more than 5 cycles of chemotherapy (OR = 15.897, 95% CI: 1.766-143.127, P = 0.014), a precollection WBC count < 32 × 10^9/L (OR = 14.441, 95% CI: 2.180-95.657, P = 0.006) and a precollection to premobilization lymphocyte ratio < 1.7 (OR = 11.388, 95% CI: 2.129-60.915, P = 0.004) were independent risk factors for HSC mobilization failure. CONCLUSIONS: The HSC mobilization efficacy of mecapegfilgrastim in patients with hematologic malignancies was comparable to that of rhG-CSF, and combination with plerixafor for mobilization was feasible and effective. Patients with more than 5 cycles of chemotherapy before HSC mobilization, a precollection WBC count lower than 32 × 10^9/L, and a precollection lymphocyte count less than 1.7 times the premobilization lymphocyte count have a high probability of HSC mobilization failure.

Diseases, health behaviors, psychological health and associated factors among women aged 50-70 years: a cross-sectional study in Hunan Province, China.

This cross-sectional study identified 2, 585 women aged 50-70 with certain diseases, health behaviors and psychological health problems among a representative and community-conducted sample of women in Hunan Province of China. It disclosed their poor health status: 51.0% had chronic diseases, 49.6% had gynecopathy, 23.6% had mastopathy, 57.1% failed to avoid secondhand smoke, less than 50% completed periodic health examinations, and 3.1% were anxious. Chronic diseases are expected to be serious health problems in the next 10 years, emphasizing the importance of women discussing their health status. Common diseases should be managed via public health service projects, and free screening and treatment of common diseases should be provided. To enhance women's health knowledge and awareness, targeted health education is necessary in accordance with their physiological and psychological characteristics.

[Application of Mecapegfilgrastim for Peripheral Blood Hematopoietic Stem Cell Mobilization in Patients With Hematologic Neoplasms and Analysis of Predictors for Poor Mobilization].

Objective: To evaluate the efficacy of applying mecapegfilgrastim for peripheral blood hematopoietic stem cell (PBSC) mobilization in patients with hematologic neoplasms, and to investigate the influencing factors of PBSC collection. Methods: Patients who underwent PBSC mobilization in the Department of Hematology, Mianyang Central Hospital between April 2016 and May 2022 were retrospectively analyzed. The CD34 + cell collection results of two groups, the mecapegfilgrastim group ( n=28), or the PEG group, and the recombinant human granulocyte colony-stimulating factor (rhG-CSF) group ( n=30), were compared, and the influencing factors of collection failure were analyzed. Results: The success rates of CD34 + cells collection in the PEG group and the rhG-CSF group were 75.0% and 63.3%, respectively ( P>0.05). The median CD34 + cell counts were 3.37×10 6/kg and 2.68×10 6/kg, respectively, showing no significant difference. After combined mobilization with plerixafor, the median counts of CD34 + cells collected in the PEG group and rhG-CSF group were 4.23×10 6/kg and 3.26×10 6/kg, respectively, showing no significant difference ( P>0.05). There was no significant difference in hematopoietic system reconstruction and infections between the two groups ( P>0.05). Multivariate analysis found non-plasma cell disease (odds ratio [ OR]=19.697, 95% confidence interval [ CI] : 1.501-258.537, P=0.023), anemia before collection ( OR=18.571, 95% CI: 1.354-254.775, P=0.029) and white blood cell count before collection under 32×10 9 L -1 ( OR=85.903, 95% CI: 4.947-1491.807, P=0.002) to be independent risk factors for PBSC collection failure. Conclusion: The effect of PBSC mobilization with mecapegfilgrastim was comparable to that of rhG-CSF in patients with hematologic neoplasms. Furthermore, combined mobilization with plerixafor was feasible and effective. Patients with leukemia or lymphoma, anemia, and WBC<32×10 9 L -1 before stem cell collection have a high probability of PBSC collection failure.

Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve.

BACKGROUND: The emerging epitranscriptome plays an essential role in female fertility. As the most prevalent internal mRNA modification, N6-methyladenine (m6A) methylation regulate mRNA fate and translational efficiency. However, whether m6A methylation was involved in the aging-related ovarian reserve decline has not been investigated. Herein, we performed m6A transcriptome-wide profiling in the ovarian granulosa cells of younger women (younger group) and older women (older group). RESULTS: m6A methylation distribution was highly conserved and enriched in the CDS and 3'UTR region. Besides, an increased number of m6A methylated genes were identified in the older group. Bioinformatics analysis indicated that m6A methylated genes were enriched in the FoxO signaling pathway, adherens junction, and regulation of actin cytoskeleton. A total of 435 genes were differently expressed in the older group, moreover, 58 of them were modified by m6A. Several specific genes, including BUB1B, PHC2, TOP2A, DDR2, KLF13, and RYR2 which were differently expressed and modified by m6A, were validated using qRT-PCR and might be involved in the decreased ovarian functions in the aging ovary. CONCLUSIONS: Hence, our finding revealed the transcriptional significance of m6A modifications and provide potential therapeutic targets to promote fertility reservation for aging women.

Sexual Activity and Related Factors of Older Women in Hunan, China: A Cross-Sectional Study.

BACKGROUND: Sexuality has an important impact on people's physical and mental health, but current research on the sexual activity of older Chinese women has many limitations and more detailed studies are needed. AIM: The objective was to determine the prevalence of sexual activity and related factors in women aged 55 to 85 years in Hunan, China. METHODS: Based on the data from the Hunan Provincial Women Health Needs Survey in 2018, we conducted a secondary analysis of 2,401 older women aged 55 and above. The dependent variable was sexual activity, and independent variables included sociodemographic characteristics, health behaviors, reproductive and chronic medical history, and psychological characteristics. All statistical analyses were performed using SPSS 26.0. Chi-square test was used to assess the association between categorical variables, and binary logistic regression was used to examine factors related to sexual activity. OUTCOMES: Sexual activity and related factors. RESULTS: The prevalence of sexual activity among older women was 12.5% (301/2401) in the past month. Having a partner (OR = 1.484; 95% CI, 1.048-2.101; P = .026), jogging (OR = 2.061; 95% CI, 1.391-3.054; P < .001), dancing (OR = 1.477; 95% CI, 1.106-1.974; P = .008), vegetarian-based diet (OR = 2.197; 95% CI, 1.334-3.618; P = .002), meat-based diet (OR = 2.196; 95% CI, 1.144-4.216; P = .018) were positively associated with being sexually active. Whereas, aging (OR = 0.781; 95% CI, 0.647-0.942; P = .010), living in the urban (OR = 0.628; 95% CI, 0.488-0.808; P < .001), hypertension (OR = 0.702; 95% CI, 0.520-0.949; P = .021), and anxiety (OR = 0.680; 95% CI, 0.475-0.972; P = .034) were negatively associated with being sexually active. CLINICAL IMPLICATIONS: Health care workers need to be aware that older women still have sexual activity and understand the needs of older women for sex education, take the initiative to discuss safe sex with them, and solve their sexual problems. STRENGTHS AND LIMITATIONS: This is one of the largest studies to determine the prevalence of sexual activity among older women in China and its related factors. In addition, new factors such as exercise types and eating habits related to sexual activity were discovered. The limitation of this study is that it did not use a specific questionnaire to assess the sexual activity and did not consider physical tenderness other than sexual intercourse. CONCLUSIONS: Some older women still have had sexual activity in the past month and factors such as lifestyles that can be changed and chronic diseases that can be self-managed were found to predict sexual activity. Li T, LuoY, Meng Y, et al. Sexual Activity and Related Factors of Older Women in Hunan, China: A Cross-Sectional Study. J Sex Med 2022;19:302-310.

Workforce situation of the Chinese mental health care system: results from a cross-sectional study.

BACKGROUND: High-quality mental health services can improve outcomes for people with mental health problems and abate the burden of mental disorders. We sought to identify the challenges the country's mental health system currently faces and the human resource situation related to psychological services and to provide recommendations on how the mental health workforce situation could be addressed in China. METHODS: This study used a cross-sectional survey design. A web-based questionnaire approach and a convenience sampling method were adopted. It was carried out from September 2020 to January 2021 in China, and we finally included 3824 participants in the analysis. Descriptive statistical analysis of the characteristics of the study sample was performed. The risk factors for competence in psychological counseling/psychotherapy were assessed using multiple linear regression analysis. RESULTS: Workforce related to psychotherapy is scarce in China, especially in Western China and community mental health sectors. Psychiatrists (39.1%) and nurses (38.9%) were the main service providers of psychotherapy in psychiatric hospitals, and clinical psychologists (6.9%) and counsellors (5.0%) were seriously scarce in mental health care sectors. A total of 74.2% of respondents had no systematic psychological training, and 68.4 and 69.2% of them had no self-experience and professional supervision, respectively. Compared with clinical psychologists and counselors, psychiatrists and nurses had less training. Systematic psychological training (ß = - 0.88), self-experience (ß = - 0.59) and professional supervision (ß = - 1.26) significantly influenced psychotherapy capacity (P<0.001). CONCLUSIONS: Sustained effort will be required to provide a high-quality, equitably distributed psychotherapy workforce in China, despite challenges for community mental health sectors and western China being likely to continue for some time. Because mental illness is implicated in so many burgeoning social ills, addressing this shortfall could have wide-ranging benefits.

Parental chest computerized tomography examination before IVF/ICSI has no impact on pregnancy and neonatal outcomes: a cohort study of 2680 fresh transfer cycles.

BACKGROUND: Some concern has been expressed regarding the negative effects of low-level ionizing radiation exposure in the context of radiological evaluation prior to IVF/ICSI treatment, but the available evidence is limited and conflicting. The aim of this study is to evaluate pregnancy and neonatal outcomes of couples who did chest computed tomography (CT) prior to IVF/ICSI. METHODS: This was a retrospective cohort study of 2680 IVF/ICSI fresh embryo transfer cycles conducted from January 2019 - August 2020. Fertility outcomes were compared between couples that had or had not undergone CT examination within 3 months prior to the date of oocyte retrieval and sperm collection. Miscarriage was the primary study outcome, while secondary outcomes included the number of oocytes collected, oocyte maturation, normal fertilization, number of good quality cleavage stage embryos, blastocyst formation, implantation, clinical pregnancy, ectopic pregnancy, live birth, multiple birth, Cesarean section rates, gestational weeks, maternal obstetric complications, birth weight, newborn sex ratio, and birth defect incidence. Propensity score matching was used to control for potential confounding variables. RESULTS: Of the 2680 cycles included in this study, couples underwent CT examination in 731 cycles. After 1:1 propensity score matching, 670 cycles were included in each group. When comparing demographic and fertility-related variables between groups that had and had not undergone CT examination after propensity score matching, we detected no significant differences in miscarriage rates (16.99% vs. 15.77%, OR = 1.10, 95CI% = 0.74 to 1.68). Similarly, both groups exhibited comparable oocyte and embryonic development, implantation rates (41.99% vs. 40.42%, OR = 1.07, 95%CI = 0.87 to 1.31), clinical pregnancy rates (45.67% vs. 44.48%, OR = 1.05, 95%CI = 0.85 to 1.30), ectopic pregnancy rates (2.94% vs. 1.68%, OR = 1.78, 95%CI = 0.59 to 5.36), live birth rates (36.57% vs. 35.67%, OR = 1.04, 95%CI = 0.83 to 1.30), multiple birth rates, Cesarean section rates, gestational weeks, maternal obstetric complication rates, and neonatal outcomes. CONCLUSIONS: Chest CT examination before IVF/ICSI has no impact on pregnancy and neonatal outcomes associated with fresh embryo transfer. TRIAL REGISTRATION: Not applicable.

Treatment of status epilepticus in pediatrics: curriculum learning combined with in-situ simulations.

BACKGROUND: Appropriate and timely treatment of status epilepticus (SE) reduces morbidity and mortality. Therefore, skill-based identification and management are critical for emergency physicians. PURPOSE: To assess whether the ability of training physicians, residents, nurses, and others to respond to SE as a team could be improved by using curriculum learning [Strategies and Tools to Enhance Performance and Patient Safety of Team (TeamSTEPPS) course training] combined with in-situ simulations of emergency department (ED) staff. APPROACH: A pre-training-post-training design was used on SE skills and teamwork skills. Emergency training, residents, and N1 and N2 nurses completed the SE skill and teamwork assessments (pre-training) through in-situ simulation. Next, the participating physicians and nurses attended the SE course [Strategies and Tools to Enhance Performance and Patient Safety of Team (TeamSTEPPS) course training], followed by conscious skill practice, including in-situ simulation drills every 20 days (eight times total) and deliberate practice in the simulator. The participants completed the SE skill and teamwork assessments (post-training) again in an in-situ simulation. Pre-training-post-training simulated SE skills and teamwork performance were assessed. The simulation training evaluation showed that the training process was reasonable, and the training medical staff had different degrees of benefit in increasing subject interest, improving operational skills, theoretical knowledge, and work self-confidence. FINDINGS: Sixty doctors and nurses participated in the intervention. When comparing the SE skills of 10 regular training physicians pre-training and post-training, their performance improved from 40% (interquartile range (IQR): 0-1) before training to 100% (IQR: 80.00-100) after training (p < 0.001). The teamwork ability of the 10 teams improved from 2.43 ± 0.09 before training to 3.16 ± 0.08 after training (p < 0.001). CONCLUSION: SE curriculum learning combined with in-situ simulation training provides the learners with SE identification and management knowledge in children and teamwork skills.

The effect of perceived social support on frailty and depression: A multicategorical multiple mediation analysis.

The mediating effects of three sources of perceived social support on frailty severity and depression were examined. Conducted in rural China, data on 570 frail older women were studied. Results showed that significant others' support (mainly daughters) (ß = 0.177 for frailty score = 3) mediated the relationship between frailty severity and depression, and the 95 % bias-corrected bootstrap confidence intervals did not straddle zero (0.013-0.419), while the mediating effects of family support (mainly sons) and friends support were not observed. Support from daughters contributes to frail mothers' mental health.

Coevolving spreading dynamics of negative information and epidemic on multiplex networks.

The widespread dissemination of negative information on vaccine may arise people's concern on the safety of vaccine and increase their hesitancy in vaccination, which can seriously impede the progress of epidemic control. Existing works on information-epidemic coupled dynamics focus on the suppression effects of information on epidemic. Here we propose a negative information and epidemic coupled propagation model on two-layer multiplex networks to study the effects of negative information of vaccination on epidemic spreading, where the negative information propagates on the virtual communication layer and the disease spreads on the physical contact layer. In our model, an individual getting an adverse event after vaccination will spread negative information and an individual affected by the negative information will reduce his/her willingness to get vaccinated and spread the negative information. By using the microscopic Markov chain method, we analytically predict the epidemic threshold and final infection density, which agree well with simulation results. We find that the spread of negative information leads to a lower epidemic outbreak threshold and a higher final infection density. However, the individuals' vaccination activities, but not the negative information spreading, has a leading impact on epidemic spreading. Only when the individuals obviously reduce their vaccination willingness due to negative information, the negative information can impact the epidemic spreading significantly.

Isolation and identification of endophytic fungi from Dendrobium huoshanense with their antibacterial and anti-inflammatory activities.

To examine the symbiotic relationship between Dendrobium huoshanense and its endophytic fungi, a total of 168 endophytic fungi were isolated and classified into 18 genera and 36 species via using pure culture and techniques of molecular biology. Among them, Stagonosporopsis oculihominis, Alternaria eichhorniae, Phyllosticta aristolochiicola, Aspergillus flavus and Fusarium lactis were the dominant genera. Further, the secondary metabolites produced by the dominant genera were screened for antibacterial and anti-inflammatory activities. The secondary metabolites of Stagonosporopsis oculihominis showed good inhibitory activity against Staphylococcus aureus and the release of nitric oxide (NO). Three benzene ring derivatives were also identified using chromatographic and spectroscopic techniques, including (Z)-1- hydroxy-4-(2-nitroethenyl)-benzene (1), p-hydroxybenzaldehyde (2) and p-hydroxyphenylacetic acid (3). These findings indicated that the endophytic fungi of Dendrobium huoshanense are diverse and their dominant genera exert similar anti-inflammatory and antibacterial effects as those of the host plant, which provided a scientific basis for the subsequent investigation of the medicinal value of Dendrobium huoshanense.

Investigating Lysosomal Autophagy via Surface-Enhanced Raman Scattering Spectroscopy.

Autophagy plays a critical role in many vitally important physiological and pathological processes, such as the removal of damaged and aged organelles and redundant proteins. Although autophagy is mainly a protective process for cells, it can also cause cell death. In this study, we employed in situ and ex situ surface-enhanced Raman scattering (SERS) spectroscopies to obtain chemical information of lysosomes of HepG2 cells. Results reveal that the SERS profiles of the isolated lysosomes are different from the in situ spectra, indicating that lysosomes lie in different microenvironments in these two cases. We further investigated the molecular changes of isolated lysosomes according to the autophagy induced by starvation via ex situ SERS. During autophagy, the conformation of proteins and the structures of lipids have been affected, and autophagy-related molecular evidence is given for the first time in the living lysosomes. We expect that this study will provide a reference for understanding the cell autophagy mechanism.

Ultrasensitive detection of trypsin in serum via nanochannel device.

A highly sensitive trypsin sensing system in serum was developed by using an anodic alumina oxide (AAO)-based, trypsin substrate-decorated hybrid ion permeation membrane. Owing to the trypsin-triggered peptide hydrolyzation reaction, the surface electrical feature of the peptide-decorated hybrid ion membrane changed. The electric double layer effect reduces the effective ion current diameter in the AAO nano unit, so that the ion current rectification ratio will be enhanced, realizing the quantitative detection of trypsin. The lowest detection concentration can be achieved as low as 0.1 pM. This method is no need for sample pre-preparation, easy to operate, highly sensitive, and also applicable to other enzyme evaluation systems by changing corresponding substrates. This study provides a new idea for selective measurements of proteases in complex biological samples.

Prevalence and associated factors of depression, anxiety, and stress among Hubei pediatric nurses during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is putting healthcare workers across the world in an unprecedented situation. The purpose of this study was to evaluate the levels of depression, anxiety, and stress among Hubei pediatric nurses during the COVID-19 pandemic and to analyze the potential factors associated with them. MATERIALS AND METHODS: A self-designed online questionnaire survey, which consisted of the demographic and selected features, the occupational protection knowledge, attitudes, and practices of COVID-19, and the Chinese version of Depression, Anxiety, and Stress Scale, were used to assess the levels of depression, anxiety, and stress among Hubei pediatric nurses during COVID-19 pandemic. The logistic regression analyses were performed to analyze the potential factors associated with depression, anxiety, and stress. RESULTS: A total of 617 pediatric nurses were included in the survey. A considerable proportion of pediatric nurses reported symptoms of depression (95 [15.4%]), anxiety (201 [32.6%]), and stress (111 [18.0%]). Results of multivariable logistic regression analyses indicated that the good occupational protection practices (for depression: OR = 0.455, 95%CI: 0.281 to 0.739; for anxiety: OR = 0.597, 95%CI: 0.419 to 0.851; for stress: OR = 0.269, 95%CI: 0.166 to 0.438) and the personal protective equipment (PPE) meeting work requirements (for depression: OR = 0.438, 95%CI: 0.246 to 0.778; for anxiety: OR = 0.581, 95%CI: 0.352 to 0.959; for stress: OR = 0.504, 95%CI: 0.283 to 0.898) were independent protective factors against depression, anxiety, and stress, respectively. Yet, working in an isolation ward or fever clinic was an independent risk factor associated with depression, anxiety, and stress, respectively (for depression: OR = 1.809, 95%CI: 1.103 to 2.966; for anxiety: OR = 1.864, 95%CI: 1.221 to 2.846; for stress: OR = 2.974, 95%CI: 1.866 to 4.741). Having suspected or confirmed COVID-19 patients in the departments (OR = 1.554, 95%CI: 1.053 to 2.294) and coming in contact with the patient's bodily fluids or blood (OR = 1.469, 95%CI: 1.031 to 2.095) were independent risk factors for anxiety, while >3 times of training for COVID-19 related information was an independent protective factor for depression (OR = 0.592, 95%CI: 0.360 to 0.974). Moreover, >10 years of working was an independent risk factor for stress (OR = 1.678, 95%CI: 1.075 to 2.618). CONCLUSION: During the COVID-19 outbreak, a considerable proportion of Hubei pediatric nurses had psychological problems. The pediatric nurses endorsing the higher number of risk factors should be given special attention and necessary psychological intervention. Improving the levels of PPE so as to meet the work requirements and intensifying occupational protection practices might help safeguard pediatric nurses from depression, anxiety, and stress.