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Background: Education is an important part of the work of most doctors. Clinical preceptors act as role models and supervisors. Preceptors' quality of supervision strongly influences the learning quality of clinical interns (Bartlett et al. BMC Med Educ 20:165, 2020). To ensure a consistent approach to every preceptorship experience, the competency of clinical preceptors should be assessed to ensure that the desired outcomes are achieved. This study aims to evaluate clinical preceptors' competency in learner-centered teaching, to provide constructive feedback to develop the preceptors' competency and improve supervisory skills and internship quality at Kunming Medical University (KMU) in Kunming of China., Methods: This is a cross-sectional study with a quantitative self-administered online questionnaire. The convenience sampling technique was employed. In the undergraduate internship stage of KMU, clinical preceptors (N = 340) and interns (N = 487) were invited to use the augmented Stanford Faculty Development Program questionnaire (SFDPQ) (Stalmeijer et al. Med Teach 30:e272-e277, 2008), to (self-) assess the preceptor's competency of learner-centered teaching on a five-point scale (1 = strongly disagree, 5 = strongly agree)., Results: Two hundred twenty-eight preceptors and two hundred thirty-six interns completed the questionnaire correctly. Overall, the assessment was positive, but the preceptors' self-assessment significantly higher than the interns' (p < 0.00). The overall mean of each category of preceptors' self-assessment was greater than 4.5, with no difference based on educational qualification. Male preceptors scored significantly higher in two categories than female preceptors. Preceptors under 30 years of age with less than 5 years of teaching experience rated "Teacher's knowledge and attitude" lower than those over 40 years of age with more than 5 years of experience (p < 0.05). There were statistically significant differences in the four categories across disciplines (p < 0.05). Undergraduate interns rated "Teachers' knowledge" as the highest category and "Learning climate" as the lowest, and interns of different genders are evaluated without distinction in all categories of SFDPQ., Conclusions: Employing the augmented SFDPQ to evaluate learner-centered teaching competency of clinical preceptors, offers potentially useful information for delivering constructive feedback. Combining self-evaluations with learner evaluation data can contribute to exploring preceptor competency development framework to guide them in targeted learner-centered teaching skill and acquisition and improvement, finally improving the overall quality of internships., (© 2024. The Author(s).)

Benzo[a]pyrene (BaP), a representative five-membered polycyclic aromatic hydrocarbon, has been extensively studied as a pollutant for decades. Despite this, sex-specific responses to BaP exposure remain poorly understood. This study employed a life-cycle exposure approach to investigate the effects of prolonged BaP exposure on marine medaka (Oryzias melastigma), highlighting sex-specific responses. After a 90-day exposure period, significant variations in biometric measurements and oxidative stress markers were observed between male and female fish. BaP exposure resulted in weak detoxification defense in males, while females exhibited an opposite response. Transcriptomic analysis revealed 13 significantly enriched pathways in males and 11 in females, with varying numbers of differentially expressed genes between the sexes, highlighting distinct biological responses. Host resistance assay showed higher mortality rates among BaP-exposed males, and suppressed immune gene expressions and lysozyme activity, while females demonstrated enhanced immune genes and lysozyme activity post-challenge, indicating a more resilient defense response. Furthermore, after a one-month depuration period following BaP exposure, male medaka demonstrated slower recoverability compared to females. These findings underscore sex-specific effects of BaP exposure on fish, with females displaying stronger resilience. Understanding these distinctions are crucial for accurately assessing the impact of environmental pollutants on the aquatic population and ecosystem maintenance., 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 Ltd. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) accumulate and integrate into aquatic environments, raising concerns about the well-being and safety of aquatic ecosystems. Benzo[a]pyrene (BaP), a persistent PAH commonly detected in the environment, has been extensively studied. However, the broader multifaceted toxicity potential of BaP on the early life stages of marine fish during chronic exposure to environmentally relevant concentrations needs further exploration. To fill these knowledge gaps, this study assessed the in vivo biotoxicity of BaP (1, 4, and 8 μg/L) in marine medaka (Oryzias melastigma) during early development over a 30-day exposure period. The investigation included morphological, biochemical, and molecular-level analyses to capture the broader potential of BaP toxicity. Morphological analyses showed that exposure to BaP resulted in skeletal curvatures, heart anomalies, growth retardation, elevated mortality, delayed and reduced hatching rates. Biochemical analyses revealed that BaP exposure not only created oxidative stress but also disrupted the activities of antioxidant enzymes. This disturbance in redox balance was further explored by molecular level investigation. The transcriptional profiles revealed impaired oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle pathways, which potentially inhibited the oxidative respiratory chain in fish following exposure to BaP, and reduced the production of adenosine triphosphate (ATP) and succinate dehydrogenase (SDH). Furthermore, this investigation indicated a potential connection to apoptosis, as demonstrated by fluorescence microscopy and histological analyses, and supported by an increase in the expression levels of related genes via real-time quantitative PCR. This study enhances our understanding of the molecular-level impacts of BaP's multifaceted toxicity in the early life stages of marine medaka, and the associated risks., 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.)

Pancharatnam-Berry (PB) phase, usually utilized for phase manipulation of circularly polarized (CP) waves, has inherent symmetrical response on left-handed polarized (LCP) and right-handed polarized (RCP) for orbital angular momentum (OAM), which severely hinders its application. By modulating both propagation and PB phase allows independent control of LCP and RCP of OAM, but increases the design difficulty. Here, we propose a phase compensation scheme to independent control the CP states of OAM only utilizing PB phase, where arbitrary topological charges and deflection directions of LCP and RCP beams can be realized. Two wideband metasurfaces are designed to independent control the mode, circular polarization and beam directions of OAM at the frequency range of 10-20 GHz. This work significantly motivates the development of polarization division multiplexing in wireless communication system.

The present study was undertaken to explore the effects of sulfamethazine (SMZ) dietary exposure on the enrichment of the intestine microbial structure, and antibiotic resistance gene (ARGs) transmission in marine medaka, with respect to antibiotic dose, duration, and sex. In male fish, a dietary exposure of 10 μg/L SMZ led to a heightened SMZ enrichment in the intestine, whereas metabolite (N-SMZ) levels were elevated at a higher exposure concentration (100 μg/L). Conversely, female fish exhibited stable levels of accumulation and metabolic rates across the exposure period. The composition of intestinal microorganisms revealed that exposure duration exerted a greater impact on the abundance and diversity of gut microbes, and microbial responses to SMZ varied across exposure time points. The expansion of Bacteroidetes and Ruegeria likely stimulated SMZ metabolism and contributed to the more balanced level of SMZ and N-SMZ observed in females. In males, short-term SMZ stress resulted in a disruption of intestinal homeostasis, while the rise in the abundance of the Fusobacteria and Propionigeniuma suggested a potential enhancement in intestinal anti-inflammatory capacity over time. Overall, female medaka exhibited greater adaptability to SMZ, and males appear to experience prolonged effects due to SMZ. A total of 11 ARGs and 5 mobile genetic elements (MGEs) were identified. Ruegeria is the main carrier of two types of MGEs (IS1247, ISSm2-Xanthob), and may serve as an indicator of ARG transmission. Therefore, it is rational to consider some fish breeding areas in natural waters as potential "reservoirs" of antibiotic resistance. This research will provide a valuable reference for the transmission of drug resistance along the food chain., 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. Published by Elsevier B.V.)

Background: English as a Media of Instruction (EMI) teacher development project is based upon the framework for teacher Continuing Professional Development (CPD) and aims to effectively improve both the confidence and overall capacity of EMI lecturers. Kunming Medical University(KMU) conducted the EMI training project to improve teachers' competence for MBBS education. This study aimed to assess teachers' changes following the implementation of this training project, via the Kirkpatrick evaluation model., Methods: A total of trainees (n = 84) were invited as the research objects. The effects of the EMI training project implemented in KMU were evaluated in terms of the reaction, learning, and behavior dimensions based on the Kirkpatrick model. The self-administered online anonymous questionnaires and observations of participants' EMI lectures were administered to all participants to collect the data. Furthermore, to understand participants' perceptions of the management and trainers of the training project, some open-ended questions were required to answer., Results: Based on 1-3 level of the Kirkpatrick model, all participants were highly satisfied with the EMI training implementation on the reaction level, and expressed positive comments about the management of the training and trainers. On the learning level, participants' scores on awareness of EMI teaching techniques increased significantly(t = 7.122, P < 0.001)with the training process. Concerning the behavior level, the participant's confidence as an EMI instructor increased dramatically at end of the whole training(p < 0.001). Moreover, trainees had applied some EMI skills in class and would like to make some commitment to implement learner-centered learning, to do more practice on EMI techniques., Conclusion: The findings of this study confirm that EMI training has an effective impact on the competence and confidence of participants as EMI instructors at levels 1-3 of the Kirkpatrick evaluation model. This training may be a potentially beneficial effect on the teaching quality of MBBS education., (© 2023. The Author(s).)

Antibiotics are widely consumed in the intensive mariculture industry. A better understanding of the effect of antibiotics on intergenerational antibiotic resistance in organisms is urgent since intergenerational transmission is crucial for the spread of antibiotic resistance genes (ARGs) in the environment. Herein, marine medaka (Oryzias melastigma) chronically exposed to low doses of sulfamethazine (SMZ) hormetically affected the progeny, characterized by increased richness and diversity of fecal microbiota and intestinal barrier-related gene up-regulation. Progeny immunity was modulated and caused by genetic factors due to the absence of significant SMZ accumulation in F1 embryos. In addition, some of the top genera in the progeny were positively correlated with immune diseases, while the expression of some immune-related genes, such as TNFα, IL1R2, and TLR3 changed significantly. This further indicated that the host selection caused by changes in progeny immunity was probably the primary determinant of progeny intestinal microbial colonization. Metagenomic analysis revealed that Proteobacteria represented the primary carriers of ARGs, while parental SMZ exposure facilitated the distribution and enrichment of multiple ARGs involved in the antibiotic inactivation in the progeny by promoting the diversity of Gammaproteobacteria and Bacteroidetes, further illustrating that antibiotic selection pressure persisted even if the offspring were not exposed. Therefore, SMZ induced hormesis in the progeny at the expense of increasing antibiotic resistance. Collectively, these findings provide a comprehensive overview of the intergenerational effect of antibiotics and serve as a reminder that the ARG transmission induced by the intergenerational impact of antibiotics on organisms should not be ignored., 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 Ltd. All rights reserved.)

Microplastics and antibiotics widely coexist in the aquatic environment, especially in mariculture regions. However, antibiotics adsorbed on microplastics and their role in the colonization of microorganisms on microplastics are poorly understood. Therefore, in-situ aging experiments were conducted to investigate the impact of antibiotics and microplastics co-occurrence on microorganisms and assess their potential risks to human health. Results showed that antibiotics were adsorbed selectively on microplastics, with 29 investigated antibiotics (n = 40) detected in surrounding water but only 6 investigated antibiotics were adsorbed on microplastics. The concentration of antibiotics accumulated on microplastics was controlled by microplastic types and environmental conditions. For example, aged polypropylene (PP) had more developed pore structures resulting in higher adsorption of antibiotics than other microplastic types. High-throughput sequencing showed higher diversity and distinct composition of microorganisms attached to the microplastics than the surrounding water. Opportunistic pathogenic bacteria such as Mycobacterium possessed positive relationships with tetracycline and doxycycline on aged microplastics, which showed adsorbed antibiotics on aged microplastics could benefit some specific pathogens colonized on the microplastics and spread into unaffected ecosystems, marine organisms even humans. The health risk quotient (HQ) implied the potential human health risk of consuming commercial seafood polluted by antibiotics and microplastic loaded with antibiotics. This study revealed the interaction of antibiotics and microorganisms with aged microplastics in aquaculture systems, providing a novel insight into their synergistic effects on ecological and human health., 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 Ltd. All rights reserved.)

Objective: We aimed to compare perinatal outcomes between umbilical cord occlusion techniques in monochorionic pregnancies, including umbilical cord ligation, fetoscopic laser coagulation, interstitial laser coagulation, bipolar cord occlusion, radiofrequency ablation, and microwave ablation., Methods: This study was registered with PROSPERO (CRD42020158861). PubMed, Web of Science, Cochrane Library, and Embase were searched for studies published up to May 2020. The DerSimonian-Laird random-effects model was used for the meta-analysis. Subgroup analyses were performed to compare the outcomes among the six techniques. Meta-regression was used to adjust for confounders., Results: Thirty-four studies with 1646 participants were included. The overall survival was 76.5% after umbilical cord ligation, 78.8% after fetoscopic laser coagulation, 60.3% after interstitial laser coagulation, 79.2% after bipolar cord occlusion, 77.5% after radiofrequency ablation, and 75.0% after microwave ablation. Subgroup comparison showed the rates of overall survival and preterm premature rupture of membranes were not significant different among six techniques. However, rates of fetal loss, premature birth, live birth, and neonatal death differed significantly among the six groups., Conclusions: The choice of umbilical cord occlusion techniques will affect perinatal outcomes. We suggested that the choice of umbilical cord occlusion techniques should fully consider these differences among techniques., (© 2021 John Wiley & Sons Ltd.)

Background: There is little direct or indirect evidence of the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on early childhood development. Methods: We conducted a prospective, observational cohort study in China from May 1 to October 31, 2020, that enrolled 135 mother-infant dyads: 57 dyads in the infection cohort and 78 in the non-infection cohort. Among all infants, 14.0% were preterm birth in the infection cohort and 6.4% in the non-infection cohort. Participants were followed by telephone interviews to collect demographic characteristics, medical records of coronavirus disease 2019, breastfeeding data, and early childhood development was assessed by the Age and Stage Questionnaire (ASQ-3) and Age and Stage Questionnaire Social-Emotional (ASQ:SE-2) Chinese versions at 3 months after childbirth. We used multivariable Poisson regression models to estimate the relative risk (RR) of SARS-CoV-2 infection. Multivariable linear regression models and a mediation model were used to test the direct and indirect associations between SARS-CoV-2 infection and the ASQ-3 score. This study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (No. IRB00006761-M2020127). Results: In the infection cohort, 13.6% of the children showed social-emotional developmental delay, and 13.5% showed overall developmental delay. The corresponding rates in the non-infection cohort were 23.4 and 8.1%. Compared with the non-infection cohort, SARS-CoV-2 infection during pregnancy did not increase the risk of social-emotional (RR = 0.87, 95% CI: 0.51-1.49) or overall (RR = 1.02, 95% CI: 0.60-1.73) developmental delay. The mediation model showed that SARS-CoV-2 infection indirectly affected the ASQ-3 score by increasing the length of mother-infant separation. Conclusions: SARS-CoV-2 during late pregnancy did not increase the risk of developmental delay of the offspring 3 months after delivery. However, SARS-CoV-2 may have indirect effects on early childhood development by increasing mother-infant separation., 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 © 2021 Wu, Chen, Wang, Shi, Niu, Yin, Li, Tan, Jiang, Zheng, Wei, Zhao, Wang and Qiao.)

The Chinese government has established a three-tier maternal care system covering the entire country and providing integrated antenatal care (ANC) for pregnancies. This study aimed to analyze the direct and indirect effects of ANC services on early childhood development. A community-based cross-sectional survey was conducted for mothers' ANC visits and assessments of early childhood development in Shanxi and Guizhou provinces, China. A total of 1660 mother-child dyads were included in current analyses: 29.2% of mothers did not receive any ANC (ANC1), 23.3% of mothers received ANC three or fewer times (ANC2), and 47.5% of mothers received ANC four or more times (ANC3). Children whose mothers received ANC services had a significantly lower risk of overall developmental delay (OR = 0.60, 95% CI: 0.44-0.81 for ANC2; and OR = 0.44, 95% CI: 0.34-0.59 for ANC3) and social-emotional developmental delay (OR = 0.68, 95% CI: 0.49-0.94 for ANC3). Furthermore, a significant pathway relationship mediated by maternal depression and nurturing care was found between ANC and developmental delay. This study showed ANC services significantly reduced the risk of developmental delay in offspring. We also suggest that a nationwide ANC system can be a good delivery platform for scaled-up early childhood development interventions., (© 2021 New York Academy of Sciences.)

Background: Breast milk is the best source of essential nutrients and bioactive components for infants under 6 months. However, little is known about what affects breastfeeding intentions and practices of Chinese mothers. With measures of individual, setting, and sociocultural factors, this study examined determinants of exclusive breastfeeding in the first 6 months of infancy in China., Methods: Data were obtained from a national cross-sectional survey in China in 2018 that included 5237 infants under 6 months with available measurements of breastfeeding. A 24-h reported food recall method was applied to assess breastfeeding and complementary food intake in the past 24 h. Potential breastfeeding determinants categorized into six aspects were measured: (1) infant health, (2) maternal sociodemographic characteristics, (3) maternal health, (4) breastfeeding support from family, friends, and workplace, (5) social support for breastfeeding, and (6) maternal breastfeeding experiences and knowledge. Reasons for non-commencement or early cessation of breastfeeding were evaluated for non-breastfed infants. For breastfed infants, multivariate logistic regression was used to explore the determinants of exclusive breastfeeding., Results: About 30 % (29.5%) of infants under 6 months were exclusively breastfed; 2.3% (2.3%) had never been breastfed and 3.2% had ceased breastfeeding. No breast milk (60.7%), maternal illness (13.9%), and infant illness (13.1%) were the top three reasons for non-commencement of breastfeeding. Insufficient breast milk was the reason given for ceasing breastfeeding early by almost two thirds of caregivers who had stopped breastfeeding. The following factors were associated with exclusive breastfeeding: maternal higher education, formal employment with ≥6 months of paid maternity leave, support of the husband and best friends for breastfeeding, a breastfeeding-supportive society, and better breastfeeding knowledge and experiences (a previous successful breastfeeding experience ≥6 months and early initiation of breastfeeding). Maternal age of ≥40 years, caesarean delivery, and infant disease history were associated with non-exclusive breastfeeding., Conclusions: The exclusive breastfeeding rate is still very low in China. Multidimensional barriers contribute to this situation. A comprehensive intervention framework is needed to increase optimal breastfeeding and achieve substantial public health gains.

Background: The global COVID-19 pandemic has generated major mental and psychological health problems worldwide. We conducted a meta-analysis to assess the prevalence of depression, anxiety, distress, and insomnia during the COVID-19 pandemic., Methods: We searched online biomedical databases (PubMed, Embase, Web of Science, Ovid, CNKI, and Wanfang Data) and preprint databases (SSRN, bioRxiv, and MedRxiv) for observational studies from January 1, 2020 to March 16, 2020 investigating the prevalence of mental health problems during the COVID-19 pandemic., Results: We retrieved 821 citations from the biomedical databases and 53 citations from the preprint databases: 66 studies with 221,970 participants were included in our meta-analysis. The overall pooled prevalence of depression, anxiety, distress, and insomnia was 31.4%, 31.9%, 41.1% and 37.9%, respectively. Noninfectious chronic disease patients, quarantined persons, and COVID-19 patients had a higher risk of depression (Q=26.73, p<0.01) and anxiety (Q=21.86, p<0.01) than other populations. The general population and non-medical staff had a lower risk of distress than other populations (Q=461.21, p< 0.01). Physicians, nurses, and non-medical staff showed a higher prevalence of insomnia (Q=196.64, p<0.01) than other populations., Limitations: All included studies were from the early phase of the global pandemic. Additional meta-analyses are needed to obtain more data in all phases of the pandemic., Conclusions: The COVID-19 pandemic increases the mental health problems of the global population, particularly health care workers, noninfectious chronic disease patients, COVID-19 patients, and quarantined persons. Interventions for mental health are urgently needed for preventing mental health problems., (Copyright © 2020. Published by Elsevier B.V.)

The plasticizer di (2-ethylhexyl) phthalate (DEHP) is becoming increasingly abundant throughout the global environment as plastic pollution becomes highly severe, especially in the ocean. The adverse effects of DEHP have garnered increasing concern as they are recognized as endocrine disruptors. However, information on the effects of DEHP in marine organisms remains limited. In this study, acute toxic effects on marine medaka (Oryzias melastigma) following DEHP exposure were investigated. Transcriptome analysis was performed on the livers of medaka exposed to DEHP for 6 and 24 h. Results showed that 1595 genes were affected in all the analyzed specimens, and several genes expressed variably according to sex. Some pathways associated with immunity, metabolism, and endocrine system were significantly enriched, with the complement system appearing to be the most affected immune pathway. Pathway enrichment indicated that, under acute DEHP exposure, the immune response of females tended to be more sensitive than that of males. In addition, ferroptosis occurred in response to DEHP exposure, which resulted in an enrichment of the ferroptosis pathway along with iron overload, an increase in malondialdehyde (MDA) and lipid peroxidation (LPO) content, and a decrease in glutathione (GSH) levels. These results indicate that a form of cell death characterized by iron-dependence occurred following DEHP exposure, but the underlying mechanism requires further analysis. This study implies that DEHP can alter some molecular regulation patterns within a short period and induce cell death through ferroptosis., 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 © 2020 Elsevier Ltd. All rights reserved.)

Benzo[a]pyrene (BaP), a widely existed polycyclic aromatic hydrocarbon pollutant in aquatic environment, has toxic effects on marine animals and their generations, but the intergenerational immunotoxic mechanism underlying has not been clearly understood. In the study, the offspring of marine medaka (oryzias melastigma) which were exposed to 0.5 μg L -1 BaP suffered from circadian rhythm oscillation disorders and severe DNA damage. Many clock-associated genes like per1 were significantly modulated in offspring, both per1 and p53 were significantly inhibited that altered the progression of cell cycle and inhibited DNA repair, which possibly resulted in the increased mortality of offspring. The hypermethylation of the per1 promotor and abnormal levels of N 6 -methyladenosine (m 6 A) suggested that the underlying mechanism was probably related to the epigenetic modification. Moreover, the offspring from paternal BaP exposure had more severe DNA damage and a higher degree of hypermethylation than those from maternal exposure. F1 larvae from BaP-exposed parents were more sensitive to BaP exposure, showing that the expression of immune and metabolism-related genes were significantly up-regulated. Taken together, the parental toxicity induced by BaP could be passed to F1 generation and the mechanism underlying was probably associated with a characteristic circadian rhythm disorder., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Sepsis is the leading cause of death in intensive care units. MicroRNA-34a (miR-34a) is involved in sepsis progression, while its underlying mechanisms on sepsis-induced lung injury remain obscure. Oxidative stress, pyroptosis, and inhibition of autophagy can result in organ injury. MiR-34a has been reported to regulate oxidative stress and autophagy via inhibiting silent information regulator T1 (SIRT1) and autophagy gene 4B (ATG4B) signaling. This study aimed at identifying the function of miR-34a in oxidative stress, inflammation, pyroptosis, and autophagy in sepsis-induced lung injury. Male 8-week-old C57BL/6 mice were subjected to cecal ligation and puncture and treated with miR-34a antagomir/agomir. Survival ( n = 10), histopathological changes ( n = 6), and lung wet-to-dry ratio ( n = 6) were recorded and assayed. Other detection ( n = 6) was performed to investigate the level of oxidative stress, inflammation, pyroptosis, and autophagy in lung tissues. Results showed that miR-34a down-regulation ameliorated lung injury in septic mice as reflected by decreased lung injury scores (decrease from 3.00 ± 0.32 to 2.00 ± 0.32) and wet-to-dry ratio (0.36-fold decrease). MiR-34a down-regulation also decreased reactive oxygen species accumulation (0.36-fold decrease), and promoted superoxide dismutase activity and the expression of SIRT1 (1.24-fold increase), heme oxygenase-1 and nuclear factor erythroid 2 like 2 to inhibit oxidative stress in septic mice. Moreover, miR-34a down-regulation suppressed inflammatory response and pyroptosis in septic mice, as evidenced by decreased level of pro-inflammatory factors including tumor necrosis factor α, interleukin-6 (IL-6), IL-1β, and IL-18, activity of caspase-1 (0.51-fold decrease) and expression of nucleotide-binding domain and leucine-rich repeat protein-3 (0.48-fold decrease), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D (0.36-fold decrease), and increased level of anti-inflammatory factors IL-10. MiR-34a down-regulation also enhanced autophagy in septic mice as evidenced by more autolysosomes and elevated expressions of ATG4B (0.90-fold increase), beclin1, ATG9, and LC3 II/I. Among these experiments, miR-34a up-regulation showed opposite effects on oxidative stress, inflammatory response, pyroptosis, and autophagy in septic mice. Additionally, miR-34a could bind to the 3'-untranslated region of SIRT1 and ATG4B. In conclusion, our findings demonstrated that miR-34a was implicated in oxidative stress, inflammation, pyroptosis, and autophagy in the development of sepsis. MiR-34a inhibition had a potential to alleviate sepsis-induced lung injury., (Copyright © 2020 Chen, Ding, Hu, Yin, Xiao, Zhang, Yan and Lv.)

Ketogenic diet (KD) is defined as a high-fat, low-carbohydrate diet with appropriate amounts of protein, which has broad neuroprotective effects. However, the mechanisms of ameliorating the demyelination and of the neuroprotective effects of KD have not yet been completely elucidated. Therefore, the present study investigated the protection mechanism of KD treatment in the cuprizone (bis-cyclohexanone oxalydihydrazone, CPZ)-induced demyelination mice model, with special emphasis on neuroinflammation. After the KD treatment, an increased ketone body level in the blood of mice was detected, and a significant increase in the distance traveled within the central area was observed in the open field test, which reflected the increased exploration and decreased anxiety of mice that received CPZ. The results of Luxol fast blue and myelin basic protein (MBP) immunohistochemistry staining for the evaluation of the myelin content within the corpus callosum revealed a noticeable increase in the number of myelinated fibers and myelin score after KD administration in these animals. Concomitant, the protein expressions of glial fibrillary acidic protein (GFAP, an astrocyte marker), ionized calcium-binding adaptor molecule 1 (Iba-1, a microglial marker), CD68 (an activated microglia marker) and CD16/32 (a M1 microglial marker) were down-regulated, while the expression of oligodendrocyte lineage transcription factor 2 (OLIG2, an oligodendrocyte precursor cells marker) was up-regulated by the KD treatment. In addition, the KD treatment not only reduced the level of the C-X-C motif chemokine 10 (CXCL10), which is correlated to the recruitment of activated microglia, but also inhibited the production of proinflammatory cytokines, including interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α), which are closely correlated to the M1 phenotype microglia. It is noteworthy, that the expression levels of histone deacetylase 3 (HADC3) and nod-like receptor pyrin domain containing 3 (NLRP3) significantly decreased after KD administration. In conclusion, these data demonstrate that KD decreased the reactive astrocytes and activated the microglia in the corpus callosum, and that KD inhibited the HADC3 and NLRP3 inflammasome signaling pathway in CPZ-treated mice. This suggests that the inhibition of the HADC3 and NLRP3 signaling pathway may be a novel mechanism by which KD exerts its protective actions for the treatment of demyelinating diseases.

Phosphatidylserine (PS) is a major anionic phospholipid constituent of membrane bilayers, which is specifically enriched in the cytoplasmic leaflet, has functions of regulating the intracellular signaling pathways of neuronal survival and differentiation, and acts as a neurotransmitter to control the activity of neurons. Oil-in-water (O/W) emulsions could improve the bio-availability of PS. Thus, there is a high level of interest in PS emulsion because of its purported health benefits. However, because of high viscosity and poor fluidity, it remains difficult to make the emulsion. A detailed analysis with suited biophysical methods would help to better understand the processes on a molecular level. Therefore, the main aim of the present study was to engineer and characterize a stable O/W phosphatidylserine emulsion. Furthermore, the effect of emulsifiers mixture, whey protein isolate (WPI), and Tween 80 (T80), as well as the oil phase was systematically evaluated. The key parameters were the chain length and the degree of nonsaturation (sunflower oil, a long-chain triglycerides [LCTs] or a medium-chain triglycerides [MCTs]). Small droplets of emulsions could be obtained by adjusting the type of emulsifier and the LCT/MCT ratio. A stable PS emulsion characterized by a smaller droplet size, higher negative zeta-potential, lower centrifugal stability constant, and longer storage time was produced by MCTs T80 (2.0%, w/w) with T80 (2.0%, w/w) as the emulsifier, and by LCTs with the WPI (0.5%, w/w)-T80 (1.5%, w/w) as the emulsifier, respectively. The PS emulsion with LCTs exhibited higher viscosity, when compared to the emulsion made by MCT at the same emulsifier concentration, while all emulsions exhibited a shear thinning behavior. The microstructure images revealed that the PS emulsions produced by MCTs and T80 (2.0%, w/w) or WPIs (0.5%, w/w)-T80 (1.5%, w/w) mixed with LCTs can form specific uniform networks, in order to prevent flocculation. After 28 days of storage, no visual phase separation was observed in the emulsions, except for the PS emulsion with the WPI (2.0%, w/w). It was concluded that the characteristics of the interfacial layer of particles in the PS emulsion system were not only dependent on the proportion of the applied emulsifiers, but also dependent on the oily phase features. These findings may provide indications for choosing the suitable process parameters when a stable PS emulsion is produced., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Background: Browning of white adipose tissues (WAT) is recognized as a novel way to combat obesity and its related comorbidities. Thus, a lot of dietary agents contributing to browning of WAT have been identified., Objective: In this study, we try to explore the mechanism of the browning of WAT induced by resveratrol (Res) in 3T3-L1 adipocytes., Methods: The levels of cell viability and lipid accumulation were evaluated under different concentrations of Res. Cell signaling pathway analysis was performed to investigate the possible mechanisms of the WAT browning effect of Res in 3T3-L1 cells., Results: We found that Res induced the brown fat-like phenotype by activating protein expressions of brown adipocyte-specific markers, such as peroxisome proliferator-activated receptor gamma (PPAR-γ), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and uncoupling protein 1 (UCP1). Besides, Res reduced lipid accumulation, as shown by Oil Red O staining. The increased small lipid droplets implied that Res-treated 3T3-L1 adipocytes had some features of brown adipocytes. The brown fat-like phenotype in 3T3-L1 adipocytes induced by Res was possibly mediated by activation of mammalian target of rapamycin (mTOR), as brown adipocyte-specific markers were decreased by rapamycin, an inhibitor of mTOR and the MHY1485 treatment, an activator of mTOR, showed the similar effect of Res on browning markers., Conclusions: Res induced brown-like adipocyte phenotype in 3T3-L1 adipocytes partly via mTOR pathway, which provided new insights into the utilization of Res to prevent obesity and related comorbidities., Competing Interests: The authors declare no conflict of interest. This research was supported by the Natural Science Foundation of Guangdong Province, China (No. 2014A030313097)., (© 2020 Zihui Liu et al.)

Promoting the browning of white fat may be a potential means of combating obesity. Therefore, in this study, we investigated the effect of resveratrol (RES) on the body weight and browning of white fat in high-fat diet (HFD)-induced obese mice and the potential associated mechanism in vivo. Eight-week-old male mice were randomized to receive different treatments: (1), chow without any additional treatment (chow); (2), chow plus 0.4% resveratrol (chow-RES); (3), HFD without any additional treatment (HFD); and (4), HFD plus 0.4% resveratrol (HFD-RES). After 4 weeks of feeding, additional 8-week-old male recipient mice were randomly allocated to the following 4 treatments: (5), HFD and received feces from chow-fed mice; (6), HFD and received feces from chow-RES-fed mice; (7), HFD and received feces from HFD-fed mice; and (8), HFD and received feces from HFD-RES-fed mice. RES treatment significantly inhibited increases in fat accumulation, promoted the browning of white adipose tissue (WAT) and alleviated gut microbiota dysbiosis in HFD-fed mice. Subsequent analyses showed that the gut microbiota remodeling induced by resveratrol had a positive role in WAT browning, and sirtuin-1 (Sirt1) signaling appears to be a key component of this process. Overall, the results show that RES may serve as a potential intervention to reduce obesity by alleviating dysbiosis of the gut microbiota.

Activation of protein C is greatly enhanced by the presence of thrombomodulin (TM) and endothelial protein C receptor (EPCR) on the endothelial surface. Impairment of the anticoagulant protein C system occurs during endotoxemia and contributes to sepsis-associated hypercoagulability. Previous studies have demonstrated that unfractionated heparin (UFH) can attenuate coagulation in endotoxemic mice. However, whether UFH has an effect on the protein C system remains to be elucidated. The current study evaluated the therapeutic effect of UFH on the protein C system in a mouse model of lipopolysaccharide (LPS)-induced sepsis, and further investigated the effect of UFH on the expression of TM and EPCR in vitro using human umbilical vein endothelial cells (HUVECs). The in vivo data indicated that UFH preconditioning attenuated the decline in circulating activated protein C following LPS administration, and also reduced LPS-induced shedding of TM and EPCR. In HUVECs, LPS stimulation led to the downregulation of TM and EPCR expression, and UFH dose-dependently restored the mRNA and protein levels of TM and EPCR. In addition, UFH inhibited the LPS-induced activation of mitogen-activated protein kinase 14, proto-oncogene tyrosine-protein kinase Src and nuclear factor κB signaling in HUVECs. In summary, these results suggest that UFH has a protective effect on the protein C system during sepsis. Thus, UFH may be a candidate therapeutic agent for the treatment of patients with sepsis.

So far, few data are available on the reproductive toxicological assessment of β-diketone antibiotics (DKAs), a class of ubiquitous pseudo-persistent pollutant, in zebrafish (Danio rerio). Herein, we reported the reproductive effects of DKAs by means of transcriptome analysis (F1-zebrafish), changes in a series of reproductive indices (F0-zebrafish) and histopathological observations. A total of 1170, 983 and 1399 genes were found to be differentially expressed when compared control vs. 6.25mg/L, control vs. 12.5mg/L and 6.25 vs. 12.5mg/L DKA-exposure treatments, respectively. Among three comparison groups, 670, 569 and 821 genes were respectively assigned for GO analyses based on matches with sequences of known functions. In 149 KEGG-noted metabolic pathways, the preferential one was the MAPK (mitogen-activated protein kinase) signaling pathway, followed by oxidative phosphorylation, neuroactive ligand-receptor interaction and so on. By qPCR verification, 6 genes (c6ast4, igfbp1b, mrpl42, tnnc2, emc4 and ddit4) showed consistent gene expression with those identified by transcriptome sequencing. Due to DKA-exposure, the concentrations of plasma estradiol and testosterone, and the gonado-somatic index were significantly dose-dependently declined. Also, DKA-exposure led to declining in zebrafish reproductive capacity, reflecting in fertilization, hatchability and egg production. Histopathological observations demonstrated that zebrafish ovary and testis suffered serious damage after DKA-exposure. The 4-oxo-TEMP signals increased obviously with increasing DKA-exposed concentrations, implying disruption of balance between generation and clearance of 1 O 2 . In summary, DKAs not only produce reproductive toxicological effects on F0-zebrafish, but also result in adverse consequences for growth and development of F1-zebrafish., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Heparanase, a heparan sulfate (HS)-specific endoglycosidase, plays an important role in inflammation and mediates acute pulmonary and renal injuries during sepsis. To explore its role in septic intestinal injury, a non-anticoagulant heparanase inhibitor, N-desulfated/re- N-acetylated heparin (NAH), was administrated to a mouse sepsis model induced by cecal ligation and puncture (CLP). Immunohistochemical staining revealed massive shedding of HS from the intestinal mucosal surfaces after CLP, and effective inhibition of heparanase by NAH was confirmed by markedly reduced HS shedding. Following CLP, intestinal expression of heparanase was increased, whereas pretreatment with NAH reduced the sepsis-induced upregulation of heparanase expression. Meanwhile, CLP led to shedding of syndecan-1 and upregulated expression of proteases such as matrix metalloprotease-9 and urokinase-type plasminogen activator in the intestine, whereas NAH markedly suppressed syndecan-1 shedding and protease upregulation following CLP. In addition, pretreatment with NAH attenuated intestinal injury, inhibited neutrophil infiltration and suppressed the production of inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6) in the intestine during sepsis, and it also significantly reduced the elevation of inflammatory cytokines in the serum 24 hr after CLP. Our findings demonstrate that the activation of intestinal heparanase contributes to intestinal injury during early sepsis by facilitating the destruction of mucosal epithelial glycocalyx and promoting inflammatory responses.

Transcriptome analysis is important for interpreting the functional elements of the genome and revealing the molecular constituents of cells and tissues. Herein, differentially transcribed genes were identified by deep sequencing after zebrafish (Danio rerio) were exposed to β-diketone antibiotics (DKAs); 23,129 and 23,550 mapped genes were detected in control and treatment groups, a total of 3238 genes were differentially expressed between control and treatment groups. Of these genes, 328 genes (213 up- and 115 down-regulation) had significant differential expression (p < 0.05) and an expression ratio (control/treatment) of >2 or <0.5. Additionally, we performed Gene Ontology (GO) category and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and found 266 genes in the treatment group with annotation terms linked to the GO category. A total of 77 differentially expressed transcriptional genes were associated with 132 predicted KEGG metabolic pathways. Serious liver tissue damage was reflected and consistent with the differences in genetic classification and function from the transcriptome analysis. These results enhance our understanding of zebrafish developmental processes under exposure to DKA stress. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1357-1371, 2016., (© 2015 Wiley Periodicals, Inc.)

Fluoroquinolones (FQs) and tetracyclines (TCs), the two β-diketone antibiotics (DKAs), are two frequently detected pollutants in the environment; however, little data are available on their combined toxicity to zebrafish (Danio rerio). This study reports that toxicologic effects of combined DKA (FQs-TCs) exposure on zebrafish were comparable with or slightly less than those of TCs alone, showing that TCs played a major toxicologic role in the mixtures. The effects of FQs, TCs, and DKAs on malformation rates of zebrafish were dose dependent, with EC50 values of 481.3, 16.4, and 135.1 mg/L, respectively. According to the combined effects of DKAs on zebrafish hatching, mortality, and malformation rates, the interaction between FQs and TCs was shown to be antagonistic based on three assessment methods: Toxic Unit, Additional Index, and Mixture Toxic Index. The 1.56 mg/L TC and 9.38 mg/L DKA treatments resulted in higher zebrafish basal swimming rate compared with the control group at 120 hours postfertilization (hpf). in both light and light-to-dark photoperiod experiments. Under conditions of no obvious abnormality in cardiac development, the heart beats were decreased significantly because of DKA exposure, such as decreasing by ∼20% at 150 mg/L DKAs. Transmission electron microscopy observation of myocytes from DKA-exposed hearts displayed prominent interruptions and myofibrillar disorganization of the normal parallel alignment of thick and thin filaments, and partial edematous and dissolved membranes of cell nuclear tissues. At 90 mg/L DKAs, the transcriptional levels of the acta1a, myl7, and gle1b genes, related to heart development and skeletal muscle formation, were significantly changed. This is consistent with the swimming behavior and histopathologic results obtained by transmission electron microscopy. In summary, the toxicity of the combined DKAs to zebrafish was comparable with or less than that of TCs alone and had the ability to impair individual behaviors that are of great importance in the assessment of their ecologic fitness. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 736-750, 2016., (© 2014 Wiley Periodicals, Inc.)

Objective: To investigate the effect of unfractionated heparin (UFH) on the expression of heme oxygenase-1 (HO-1) in intestinal mucosa of mice with sepsis., Methods: Thirty-six male C57BL/6J mice were randomly divided into sham group, cecal ligation and puncture (CLP) group and UHF group, n =12 in each group. Model of intestinal injury in sepsis was induced by CLP. In sham group, the mice were exposed without ligation of cecum. In UFH group, the mice were treated intravenously with 8 U of UFH via the tail vein half an hour before the operation and 12 hours after the surgery respectively. Six mice in each group were randomly chosen at 4 hours and 24 hours after operation to collect inferior vena venous blood samples and terminalileum tissues. The serum levels of interleukins (IL-1 β,IL-6),and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA).The serum level of D-lactate was determined by colorimetry.Pathological changes of ileum tissue and Chiu score were observed after hematoxylin eosin (HE) staining. The HO-1 expression was detected immunohistochemically., Results: In sham group, no significant changes in the serum levels of IL-1 β,IL-6,TNF-α and D-lactate were observed. Twenty-four hours after the operation, the structure of intestinal mucosa was basically normal without obvious pathology change and no HO-1 positive cells were found. The serum levels of IL-1 β,IL-6,TNF-α,and D-lactate in CLP group were gradually increased, and they were significantly increased as compared with sham group [IL-1 β (ng/L):40.87±2.88 vs.22.60±2.05 at 4 hours,113.73±3.96 vs.22.07±2.74 at 24 hours;IL-6 (ng/L):63.89±3.26 vs.44.89±3.38 at 4 hours,176.56±5.45 vs.45.76±4.02 at 24 hours; TNF-α (ng/L):194.62± 14.13 vs.152.05±6.22 at 4 hours,599.62± 10.20 vs.155.90± 14.18 at 24 hours; D-lactate (mmol/L):0.24± 0.02 vs.0.19 ± 0.01 at 4 hours,0.33 ± 0.04 vs.0.20 ± 0.02 at 24 hours, all P ＜ 0.05].Twenty-four hours after the operation, edema and inflammation in ileal mucosa, intestinal villi structural damage were observed, the Chiu score was significantly higher than those in the sham group [4.5 (3.0-5.0) vs.0 (0-1.0),P ＜ 0.05],and a small amount of HO-1 positive cells were localized in the intestinal mucosa. Compared with CLP group, the serum levels of IL-1 β,IL-6,TNF-α,and D-lactate of UFH group were significantly decreased [IL-1 β (ng/L):31.53 ± 2.90 vs.40.87 ± 2.88 at 4 hours,61.13 ± 2.80 vs.113.73 ± 3.96 at 24 hours;IL-6 (ng/L):51.16 ± 5.68 vs.63.89 ± 3.26 at 4 hours,81.16 ± 4.54 vs.176.56 ± 5.45 at 24 hours; TNF-α (ng/L):171.76± 5.60 vs.194.62± 14.13 at 4 hours,328.48 ± 10.79 vs.599.62± 10.20 at 24 hours; D-lactate (mmol/L):0.21 ±0.01 vs.0.24±0.02 at 4 hours,0.24±0.02 vs.0.33±0.04 at 24 hours, all P ＜ 0.05]. Twenty-four hours after the operation, intestinal injury was ameliorated, the Chiu score was significantly lower [1.5 (1.0-5.0) vs.4.5 (3.0-5.0),P ＜ 0.05],and HO-1 positive cells in the intestinal mucosa was remarkably increased., Conclusion: UFH can enhance the expression of HO-1 in intestinal mucosa, reduce the release of inflammatory factors, ameliorate the intestinal inflammatory response, and thus play a protective role in intestinal tissue in mice with sepsis.

Herein, we developed a novel integrated apparatus to perform phase separation based on magnetic-stirring, salt-induced, liquid-liquid microextraction for determination of five fluoroquinolones in animal-based foods by HPLC analysis. The novel integrated apparatus consisted of three simple HDPE (high density polyethylene) parts that were used to separate the solvent from the aqueous solution prior to retrieving the extractant. The extraction parameters were optimized using the response surface method based on central composite design: 791 μL of acetone solvent, 2.5 g of Na2SO4, pH 1.7, 3.0 min of stir time, and 5.5 min centrifugation. The limits of detection were 0.07-0.53 μg kg(-1) and recoveries were 91.6-105.0% for the five fluoroquinolones from milk, eggs and honey. This method is easily constructed from inexpensive materials, extraction efficiency is high, and the approach is compatible with HPLC analysis. Thus, it has excellent prospects for sample pre-treatment and analysis of fluoroquinolones in animal-based foods., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The removal efficiency of Cu(2+) by Spirulina platensis (strain FACHB-834), in viable and heat-inactivated forms, was investigated in the presence and absence of linear alkylbenzene sulfonate (LAS). When the initial Cu(2+) concentration was in the range of 0.5-1.5 mg · L(-1) , a slight increase in growth rate of FACHB-834 was observed. In contrast, when Cu(2+) or LAS concentrations were at or higher than 2.0 or 6.0 mg · L(-1) , respectively, the growth of FACHB-834 was inhibited and displayed yellowing and fragmentation of filaments. The presence of LAS improved Cu(2+) removal by ~20%, and accelerated attainment of Cu(2+) retention equilibrium. For the 2- mg · L(-1) Cu(2+) treatments, retention equilibrium occurred within 2 d and showed maximum Cu(2+) removal of 1.83 mg · L(-1) . In the presence of LAS, the ratio of extracellular bound Cu(2+) to intracellular Cu(2+) taken up by the cells was lower (1.05-2.26) than corresponding ratios (2.46-7.85) in the absence of LAS. The percentages of extracellular bound Cu(2+) to total Cu(2+) removal (both bound and taken up by cells) in the presence of LAS ranged from 51.2% to 69.3%, which was lower than their corresponding percentages (71.1%-88.7%) in the absence of LAS. LAS promoted biologically active transport of the extracellular bound form of Cu(2+) into the cell. In contrast, the addition of LAS did not increase the maximum removal efficiency of Cu(2+) (61.4% ± 5.6%) by heat-inactivated cells compared to that of living cells (59.6% ± 6.0%). These results provide a theoretical foundation for designing bioremediation strategies using FACHB-834 for use in surface waters contaminated by both heavy metals and LAS., (© 2014 Phycological Society of America.)

β-Diketone antibiotics (DKAs) can produce chronic toxicity in aquatic ecosystems due to their pseudo-persistent in the environment. In this study, after long-term DKA exposure to zebrafish (Danio rerio), 47 protein spots had greater than 2-fold differential expression as compared to the control; there were 26 positive proteins with 14 up-regulated and 12 down-regulated. The main functions of the differentially expressed proteins were related to signal transduction mechanisms and the cytoskeleton. Of the 26 target genes, 11 genes were consistent between their transcriptional and translational levels. Low dose DKA exposure (4.69 and 9.38 mg/L) stimulated spontaneous movement in zebrafish. Changes in both creatine kinase activity and creatine concentration showed a similar trend to zebrafish activity. There was no obvious change in SV-BA after DKA exposure, while a reduction of heart rate was concomitant with increasing DKA concentrations. DKAs also induced severe histopathological changes in zebrafish heart tissue, such as dissolution of cristae and vacuolation of mitochondria. These results demonstrated that trace-level DKA exposure affects a variety of cellular and biological processes in zebrafish.