Dietary exposure to sulfamethazine alters fish intestinal homeostasis and promotes resistance gene transfer.

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.

Assessment of a training project of English as a media of instruction(EMI) using Kirkpatrick model.

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.

Ring- and diffuse-porous tree species from a cold temperate forest diverge in stem hydraulic traits, leaf photosynthetic traits, growth rate and altitudinal distribution.

In cold and humid temperate forests, low temperature, late frost and frequent freeze-thaw cycles are the main factors limiting tree growth and survival. Ring- and diffuse-porous tree species differing in xylem anatomy coexist in these forests, but their divergent adaptations to these factors have been poorly explored. To fill this knowledge gap, we compared four ring-porous and four diffuse-porous tree species from the same temperate forest in Northeast China by quantifying their leaf and stem functional traits, their stem growth rates using tree ring analysis and their resistance to cold represented by upper altitude species distribution borders from survey data. We found that the ring-porous trees were characterized by traits related to more rapid water transport, carbon gain and stem growth rates than those of the diffuse-porous species. Compared with the diffuse-porous species, the ring-porous species had a significantly higher shoot hydraulic conductance (Ks-shoot, 0.52 vs 1.03 kg m-1 s-1 MPa-1), leaf photosynthetic rate (An, 11.28 vs 15.83 µmol m-2 s-1), relative basal area increment (BAIr, 2.28 vs 0.72 cm year-1) and stem biomass increment (M, 0.34 vs 0.09 kg year-1 m-1). However, the observed upper elevational distribution limit of the diffuse-porous species was higher than that of the ring-porous species and was associated with higher values of conservative traits, such as longer leaf life span (R2 = 0.52). Correspondingly, BAIr and M showed significant positive correlations with acquisitive traits such as Ks-shoot (R2 = 0.77) and leaf photosynthetic rate (R2 = 0.73) across the eight species, with the ring-porous species occurring at the fast-acquisitive side of the spectrum and the diffuse-porous species located on the opposite side. The observed contrasts in functional traits between the two species groups improved our understanding of their differences in terms of growth strategies and adaptive capabilities in the cold, humid temperate forests.

Wideband reflective metasurface for independent control of mode and circular polarization of orbital angular momentum.

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.

[Environmental Process, Effects and Risks of Emerging Contaminants in the Estuary-Coastal Environment].

Human activities and global climate change have contributed substantially to the input of land-sourced pollutants into the aquatic environment, especially for emerging or newly identified contaminants, such as microplastics, emerging persistent organic pollutants, pharmaceuticals, and personal care products. The prevalence and toxicity of these emerging pollutants has raised continued concern for the health and safety of the public worldwide. A review of sources, distribution, interfacial transport processes of microplastics, per-and polyfluorinated compounds, antibiotics, and endocrine-disrupting chemicals and factors that influence their environmental behavior in the estuary-coastal environment have been included. The adverse ecological effects and health risks of these emerging contaminants to humans were also reviewed. Lastly, the direction of future research was provided regarding the environmental behavior of multiple emerging pollutants in the coastal environment and the health risks resulting from their interactions, supporting the prevention and control of marine pollution and the healthy development of the marine economy.

Metagenomic evidence for increasing antibiotic resistance in progeny upon parental antibiotic exposure as the cost of hormesis.

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.

Selective adsorption of antibiotics on aged microplastics originating from mariculture benefits the colonization of opportunistic pathogenic bacteria.

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.

[Hydraulics and non-structural carbohydrate contents of Ginkgo biloba under different environmental conditions in Shenyang City, China.] / 沈阳市区不同环境下银杏水力特征和非结构性碳水化合物含量.

Ginkgo biloba is an important urban ornamental tree species, but poor growth and damages often occur in urban environments. As a street tree species, the decline and death of G. biloba is particularly frequent, with the relevant physiological mechanism being unclear. In this study, we compared hydraulic characteristics, non-structural carbohydrate (NSC) contents and health status between G. biloba trees growing along the streets and those in parks in Shenyang City. The results showed that G. biloba growing along the streets showed higher degrees of branch and leaf mortality than those growing in the parks. Branches of G. biloba growing in both conditions showed lower degrees of xylem embolism. Branch hydraulic vulnerable curves of G. biloba under the two growing conditions also showed no significant difference, with the average P50 being lower than -2.8 MPa. G. biloba growing along the streets had lower leaf area specific conductivity, smaller tracheid diameter, smaller hydraulic diameter, lower soluble sugar content and total NSC than those growing in parks. Hydraulic failure was not the direct reason for the decline and mortality of G. biloba growing along streets. Under the more stressed growth conditions along the streets, G. biloba had smaller tracheid diameters in stems and lower Huber values, which limited the ability of water transport and photosynthetic carbon assimilation at the whole branch level. In addition, in order to deal with more serious stress such as greater heat and drought stresses, G. biloba might need to invest more NSC to repair damage, which further decreaded NSC contents in branches and increased the risk of carbon imbalance. At the same habitat (street or park), xylem hydraulics and NSC contents of G. biloba also showed relatively large difference among sampling sites, which reflected large heterogeneity of urban environment for tree growth.

Hydraulic vulnerability segmentation in compound-leaved trees: Evidence from an embolism visualization technique.

The hydraulic vulnerability segmentation (HVS) hypothesis implies the existence of differences in embolism resistance between plant organs along the xylem pathway and has been suggested as an adaptation allowing the differential preservation of more resource-rich tissues during drought stress. Compound leaves in trees are considered a low-cost means of increasing leaf area and may thus be expected to show evidence of strong HVS, given the tendency of compound-leaved tree species to shed their leaf units during drought. However, the existence and role of HVS in compound-leaved tree species during drought remain uncertain. We used an optical visualization technique to estimate embolism occurrence in stems, petioles, and leaflets of shoots in two compound-leaved tree species, Manchurian ash (Fraxinus mandshurica) and Manchurian walnut (Juglans mandshurica). We found higher (less negative) water potentials corresponding to 50% loss of conductivity (P50) in leaflets and petioles than in stems in both species. Overall, we observed a consistent pattern of stem > petiole > leaflet in terms of xylem resistance to embolism and hydraulic safety margins (i.e. the difference between mid-day water potential and P50). The coordinated variation in embolism vulnerability between organs suggests that during drought conditions, trees benefit from early embolism and subsequent shedding of more expendable organs such as leaflets and petioles, as this provides a degree of protection to the integrity of the hydraulic system of the more carbon costly stems. Our results highlight the importance of HVS as an adaptive mechanism of compound-leaved trees to withstand drought stress.

Perinatal outcomes after selective feticide via umbilical cord occlusion in complicated monochorionic pregnancies: A systematic review and meta-analysis.

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.

Effects of SARS-CoV-2 Infection During Late Pregnancy on Early Childhood Development: A Prospective Cohort Study.

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.

Roles of RAGE/ROCK1 Pathway in HMGB1-Induced Early Changes in Barrier Permeability of Human Pulmonary Microvascular Endothelial Cell.

Background: High mobility group box 1 (HMGB1) causes microvascular endothelial cell barrier dysfunction during acute lung injury (ALI) in sepsis, but the mechanisms have not been well understood. We studied the roles of RAGE and Rho kinase 1 (ROCK1) in HMGB1-induced human pulmonary endothelial barrier disruption. Methods: In the present study, the recombinant human high mobility group box 1 (rhHMGB1) was used to stimulate human pulmonary microvascular endothelial cells (HPMECs). The endothelial cell (EC) barrier permeability was examined by detecting FITC-dextran flux. CCK-8 assay was used to detect cell viability under rhHMGB1 treatments. The expression of related molecules involved in RhoA/ROCK1 pathway, phosphorylation of myosin light chain (MLC), F-actin, VE-cadherin and ZO-1 of different treated groups were measured by pull-down assay, western blot and immunofluorescence. Furthermore, we studied the effects of Rho kinase inhibitor (Y-27632), ROCK1/2 siRNA, RAGE-specific blocker (FPS-ZM1) and RAGE siRNA on endothelial barrier properties to elucidate the related mechanisms. Results: In the present study, we demonstrated that rhHMGB1 induced EC barrier hyperpermeability in a dose-dependent and time-dependent manner by measuring FITC-dextran flux, a reflection of the loss of EC barrier integrity. Moreover, rhHMGB1 induced a dose-dependent and time-dependent increases in paracellular gap formation accompanied by the development of stress fiber rearrangement and disruption of VE-cadherin and ZO-1, a phenotypic change related to increased endothelial contractility and endothelial barrier permeability. Using inhibitors and siRNAs directed against RAGE and ROCK1/2, we systematically determined that RAGE mediated the rhHMGB1-induced stress fiber reorganization via RhoA/ROCK1 signaling activation and the subsequent MLC phosphorylation in ECs. Conclusion: HMGB1 is capable of disrupting the endothelial barrier integrity. This study demonstrates that HMGB1 activates RhoA/ROCK1 pathway via RAGE, which phosphorylates MLC inducing stress fiber formation at short time, and HMGB1/RAGE reduces AJ/TJ expression at long term independently of RhoA/ROCK1 signaling pathway.

Determinants of exclusive breastfeeding for the first six months in China: a cross-sectional study.

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.

China's antenatal care promoting early childhood development: evidence from a cross-sectional survey.

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.

Acute exposure of di(2-ethylhexyl) phthalate (DEHP) induces immune signal regulation and ferroptosis in oryzias melastigma.

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.

Prevalence of mental health problems during the COVID-19 pandemic: A systematic review and meta-analysis.

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.

MicroRNA-34a Inhibition Alleviates Lung Injury in Cecal Ligation and Puncture Induced Septic Mice.

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-1ß, 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.

The intergenerational toxic effects on offspring of medaka fish Oryzias melastigma from parental benzo[a]pyrene exposure via interference of the circadian rhythm.

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 N6-methyladenosine (m6A) 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.

Amelioration of clinical course and demyelination in the cuprizone mouse model in relation to ketogenic diet.

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 1ß (IL-1ß) 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.

Influence of Long-Chain/Medium-Chain Triglycerides and Whey Protein/Tween 80 Ratio on the Stability of Phosphatidylserine Emulsions (O/W).

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.