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The classification and extraction of valuable components from coal gangue is a way to improve the comprehensive utilization of coal gangue. However, the stable structure of kaolinite in coal gangue makes silicon and aluminum closely combined in minerals, which is difficult to separate by simple physical or chemical methods, and hinders its hierarchical extraction. In this study, a method of calcination activation acid leaching combined with reduction treatment of coal gangue was developed, and an aluminum iron enriched acidic solution and a silicon enriched material were prepared. The activation effect and mechanism of calcined coal gangue and the conversion mechanism of acid leaching extraction of metal aluminum were systematically studied. The results showed that the optimal calcination activation acid leaching process parameters were as follows: calcination temperature: 600 ℃, calcination time: 4 h, acid leaching time: 2 h, solid–liquid ratio of activated coal gangue and hydrochloric acid solution (g:ml): 1:12. After calcination under the optimal conditions, the layered structure of Kaolinite was destroyed and some layered silicate minerals, Berlinite (AlPO4), FeS, which were soluble in hydrochloric acid solution, were formed. These minerals are dissolved in hydrochloric acid solution and then separated by solid–liquid separation after reaction. An acidic solution rich in aluminum and iron and a material rich in silicon were prepared, which made the recovery of Al and Fe reach 90.84 % and 97.68 %, respectively. And the enrichment rate of Si (SiO2) reached 83.90 %.This provides a new solution for the comprehensive utilization and sustainable utilization of coal gangue.

Objectives The current status of patient and visitor violence (PVV) reporting among nurses has proven insufficient. Therefore, we explored the barriers and facilitators in nurses’ reporting of PVV.Design Cross-sectional study.Setting General and specialised hospitals in Jiangsu Province, China.Participants A convenience sampling of 3363 nurses in Jiangsu Province was collected between January and July 2023.Main outcome measure The reporting rate of PVV was assessed by the hospital workplace violence questionnaire-revised version; multivariable logistic regression analyses were performed to determine factors associated with PVV reporting at the 5% significance level.Results Out of the 3363 surveyed nurses, 1813 (53.9%) reported experiencing PVV within the past year. Notably, only 16.1% of these nurses proactively reported PVV incidents after encountering them. Factors that facilitated reporting of PVV comprised being male (OR 1.832, 95% CI 1.083 to 3.101), working in specialised hospitals (OR 2.335, 95% CI 1.517 to 3.594), serving in emergency (OR 1.788, 95% CI 1.105 to 2.892), outpatient (OR 3.153, 95% CI 1.697 to 5.860), paediatrics (OR 3.808, 95% CI 1.976 to 7.338), possessing agreeableness personality (OR 2.112, 95% CI 1.140 to 3.911), prior hearing of PVV (OR 1.749, 95% CI 1.305 to 2.346) and having hospitals that actively encouraged reporting (OR 2.700, 95% CI 1.848 to 3.946) while safeguarding staff interests (OR 2.072, 95% CI 1.010 to 4.248) and emphasising nurses more (OR 2.109, 95% CI 1.123 to 3.958). Conversely, factors impeding nurses from reporting PVV included having night shifts 5–9 times per month (OR 0.481, 95% CI 0.282 to 0.819) and selectively reporting based on the severity of the violence (OR 0.550, 95% CI 0.344 to 0.878).Conclusion The reporting rate of PVV among nurses was notably low. Nursing managers should consider implementing comprehensive measures that address both the facilitating and blocking factors identified in the study. This strategic approach aims to enhance the reporting rate of PVV incidents among nurses, fostering a safer and more supportive environment within healthcare settings.

Abstract The analysis of cardiac wall mechanics is of importance for understanding coronary heart diseases (CHD). The inhalation of ultrafine particles could deteriorate CHD. The aim of the study is to investigate the effects of cardiac wall mechanics on rats of myocardial infarction (MI) after long-term inhalation of ultrafine Zn particles. Cardiac wall stresses and strains were computed, based on echocardiographic and hemodynamic measurements. It was found that MI resulted in the significantly elevated stresses and the reduced strains. The short-term inhalation of ultrafine Zn particles decreased stresses and increased strains in MI rats, but the long-term inhalation had the opposite effects. Hence, the short-term inhalation of ultrafine Zn particles could alleviate the MI-induced LV dysfunction while the long-term inhalation impaired it.

Abstract Background Culex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear. Results In total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P

The escalating human pressures on natural ecosystems necessitate urgent and effective conservation strategies to safeguard biodiversity and ecosystem functions. This review explored current techniques for mapping human pressure, with a particular focus on their application in nature conservation, especially within protected areas (PAs). Specifically, we analyzed the impacts of seven major types of human pressures on nature conservation within PAs. Additionally, we discussed four key methods for mapping human pressure, including land use intensity, human footprint, digital human footprint, and other proxies, examining their distinct characteristics and respective advantages and disadvantages. Additionally, our research explored the application of human pressure mapping for nature conservation, assessing its suitability for conservation applications and delineating directions for future work. These insights contributed to better support nature conservation and the management of PAs.

Abstract Background Workplace violence among nurses has emerged as a critical issue, posing a significant threat to their occupational safety. Education and training are the primary measures employed to prevent and respond to workplace violence. However, the current approaches have proven ineffective, possibly due to a lack of consideration for the specific needs of clinical nurses. Therefore, it is essential to explore the effectiveness of an informational education and training platform tailored to nurses' requirements. This study aimed to investigate the impact of such a platform on the incidence, severity, and coping resources of WPV in nurses. Methods This research was a quasi-experimental study. An information-based education and training platform focused on nurse workplace violence was developed through literature reviews, expert meetings, consultations with software development companies, and a trial run. A tertiary general hospital in Suzhou was selected, in which hospital district A was the intervention group and hospital district B was the control group. A total of 276 nurses were recruited, 140 in the intervention group and 136 in the control group. The nurses' incidence, severity, coping resources status, and evaluation of the application were measured before the intervention and at 1, 3, and 6 months after the intervention. Results The overall incidence of workplace violence, verbal aggression, and verbal threat among nurses showed statistically significant differences (P

Abstract Background Workplace violence (WPV) poses a significant occupational hazard for nurses. The efficacy of current education and training programs in mitigating WPV incidence among nurses remains uncertain, possibly due to insufficient consideration of clinical contexts and nurses’ specific needs. Therefore, this study developed a WPV prevention strategy based on the actual requirements of clinical nurses and situational prevention theory and aimed to explore its application effects. Methods Under the guidance of situational prevention theory, a WPV prevention strategy for nurses was constructed through literature review, semi-structured interviews and focus group discussion. This study adopted a self-controlled research design, and trained 130 nurses selected from a comprehensive tertiary grade A hospital in Suzhou in this WPV prevention strategy. Data were collected through structured questionnaires, including the revised WPV questionnaire, WPV severity grading scale, and hospital WPV coping resources scale. The WPV incidence, severity, and WPV coping resource scores of nurses were collected before the intervention, as well as at 3 months, 6 months, and 9 months after training. Results The WPV prevention strategy comprised 11 prevention plans based on 11 high-risk situational elements of WPV. Each prevention plan included the WPV prevention flowchart, treatment principle, and communication strategy. The strategy demonstrated excellent feasibility and practicality. Following the intervention, the overall incidence of WPV among nurses significantly decreased from 63.85% (baseline) to 46.15% (9 months after training) (P

Abstract Background Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. Methods Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. Results After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI

In this work, a novel ternary nanocomposite of PEI/RuSi-MWCNTs was designed and synthesized for the first time, which an ultrasensitive and self-enhanced electrochemiluminescent (ECL) aptasensor was developed for the detection of profenofos residues in vegetables. The self-enhanced complex PEI-Ru (II) enhanced the emission and stability of ECL, and the multi-walled carbon nanotubes (MWCNTs) acted as an excellent carrier and signal amplification. The PEI/RuSi-MWCNTs were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM) and energy dispersive spectrometer (EDS). The incorporation of gold nanoparticles (AuNPs) improved the performance of the sensor and provided a platform for the immobilization of the aptamer. The results of the experiment showed that the presence of profenofos significantly suppressed the electrochemiluminescence intensity of the sensor. The detection sensitivity of the aptamer sensor was in the range of 1 × 10−2 to 1 × 103 ng/mL. Under optimal conditions, the limit of detection (LOD) of the sensor for profenofos was 1.482 × 10−3 ng/mL. The sensor had excellent stability, reproducibility and specificity. The recoveries of the sensor ranged from 92.29 % to 106.47 % in real sample tests.

Abstract Background Mosquitoes are important vectors for a range of diseases, contributing to high rates of morbidity and mortality in the human population. Culex pipiens pallens is dominant species of Culex mosquito in northern China and a major vector for both West Nile virus and Bancroftian filariasis. Insecticide application were largely applied to control the mosquito-mediated spread of these diseases, contributing to increasing rates of resistance in the mosquito population. The voltage-gated sodium channel (Vgsc) gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr). While these kdr mutations are known to be critical to pyrethroid resistance, their evolutionary origins remain poorly understood. Clarifying the origins of these mutations is potential to guide further vector control and disease prevention efforts. Accordingly, the present study was designed to study the evolutionary genetics of kdr mutations and their association with the population structure of Cx. p. pallens in Shandong province, China. Methods Adult Culex females were collected from Shandong province and subjected to morphological identification under a dissection microscope. Genomic DNA were extracted from the collected mosquitoes, the Vgsc gene were amplified via PCR and sequenced to assess kdr allele frequencies, intron polymorphisms, and kdr codon evolution. In addition, population genetic diversity and related population characteristics were assessed by amplifying and sequencing the mitochondrial cytochrome C oxidase I (COI) gene. Results Totally, 263 Cx. p. pallens specimens were used for DNA barcoding and sequencing analyses to assess kdr allele frequencies in nine Culex populations. The kdr codon L1014 in the Vgsc gene identified two non-synonymous mutations (L1014F and L1014S) in the analyzed population. These mutations were present in the eastern hilly area and west plain region of Shandong Province. However, only L1014F mutation was detected in the southern mountainous area and Dongying city of Shandong Province, where the mutation frequency was low. Compared to other cities, population in Qingdao revealed significant genetic differentiation. Spatial kdr mutation patterns are likely attributable to some combination of prolonged insecticide-mediated selection coupled with the genetic isolation of these mosquito populations. Conclusions These data suggest that multiple kdr alleles associated with insecticide resistance are present within the Cx. p. pallens populations of Shandong Province, China. The geographical distributions of kdr mutations in this province are likely that the result of prolonged and extensive insecticide application in agricultural contexts together with frequent mosquito population migrations. In contrast, the low-frequency kdr mutation detected in central Shandong Province populations may originate from the limited selection pressure in this area and the relative genetic isolation. Overall, the study compares the genetic patterns revealed by a functional gene with a neutral marker and demonstrates the combined impact of demographic and selection factors on population structure.

Abstract Background Future distribution of dengue risk is usually predicted based on predicted climate changes using general circulation models (GCMs). However, it is difficult to validate the GCM results and assess the uncertainty of the predictions. The observed changes in climate may be very different from the GCM results. We aim to utilize trends in observed climate dynamics to predict future risks of Aedes albopictus in China. Methods We collected Ae. albopictus surveillance data and observed climate records from 80 meteorological stations from 1970 to 2021. We analyzed the trends in climate change in China and made predictions on future climate for the years 2050 and 2080 based on trend analyses. We analyzed the relationship between climatic variables and the prevalence of Ae. albopictus in different months/seasons. We built a classification tree model (based on the average of 999 runs of classification and regression tree analyses) to predict the monthly/seasonal Ae. albopictus distribution based on the average climate from 1970 to 2000 and assessed the contributions of different climatic variables to the Ae. albopictus distribution. Using these models, we projected the future distributions of Ae. albopictus for 2050 and 2080. Results The study included Ae. albopictus surveillance from 259 sites in China found that winter to early spring (November–February) temperatures were strongly correlated with Ae. albopictus prevalence (prediction accuracy ranges 93.0–98.8%)—the higher the temperature the higher the prevalence, while precipitation in summer (June–September) was important predictor for Ae. albopictus prevalence. The machine learning tree models predicted the current prevalence of Ae. albopictus with high levels of agreement (accuracy > 90% and Kappa agreement > 80% for all 12 months). Overall, winter temperature contributed the most to Ae. albopictus distribution, followed by summer precipitation. An increase in temperature was observed from 1970 to 2021 in most places in China, and annual change rates varied substantially from -0.22 ºC/year to 0.58 ºC/year among sites, with the largest increase in temperature occurring from February to April (an annual increase of 1.4–4.7 ºC in monthly mean, 0.6–4.0 ºC in monthly minimum, and 1.3–4.3 ºC in monthly maximum temperature) and the smallest in November and December. Temperature increases were lower in the tropics/subtropics (1.5–2.3 ºC from February–April) compared to the high-latitude areas (2.6–4.6 ºC from February–April). The projected temperatures in 2050 and 2080 by this study were approximately 1–1.5 °C higher than those projected by GCMs. The estimated current Ae. albopictus risk distribution had a northern boundary of north-central China and the southern edge of northeastern China, with a risk period of June–September. The projected future Ae. albopictus risks in 2050 and 2080 cover nearly all of China, with an expanded risk period of April–October. The current at-risk population was estimated to be 960 million and the future at-risk population was projected to be 1.2 billion. Conclusions The magnitude of climate change in China is likely to surpass GCM predictions. Future dengue risks will expand to cover nearly all of China if current climate trends continue.

Chronic cadmium (Cd) exposure causes severe adverse health effects on the human body, especially the kidney tissue. Studies have demonstrated oxidative stress to be involved in renal pathological variations after exposure to Cd, but few effective treatments are available for the disease yet. Therefore, the present study was carried out to investigate the potential therapeutic intervention and its underlying molecular mechanisms of melatonin (MT), a natural antioxidant with multiple biological activities, against renal injury caused by Cd exposure in mice. C57BL/6 male mice (eight-week-old) were intragastrically administered with CdCl2, MT, or both for 30 days. Biochemical analysis showed that MT intervention significantly improved the SOD, GSH, and CAT activities while markedly decreasing the kidney MDA content of the mice exposed to Cd. Histological examination indicated that Cd exposure resulted in the atrophy of the renal glomerular, the degeneration and dilation of tubules, and the accumulation of fibrocytes. By contrast, MT administration effectively ameliorated the histological outcome of the injured kidney tissue. Moreover, administrating MT significantly inhibited proinflammatory cytokines TNF-α and iNOS expression in Cd-treated mice. Further, MT treatment markedly suppressed the expressions of renal fibrosis-related factors TGF-β1, α-SMA, and collagen Ⅰ in the injured renal tissue and the accumulation and development of renal fibrosis. In addition, the administration of MT significantly reduced the expression of caspase-3 and cell apoptotic death in the kidney tissue of Cd-exposed mice. In all, the data showed that MT has a compelling therapeutic potential in alleviating the pathological variations of renal injury caused by Cd exposure.

Abstract Background Workplace violence (WPV) among nurses has become an increasingly serious public health issue worldwide. Investigating the status quo and characteristics of WPV among nurses in different time periods can help hospital managers understand the current status of WPV and its trends over time. This study aimed to understand the current situation of WPV among nurses in Suzhou general hospitals from 2010 to 2019 and analyze changes over time. Methods A cross-sectional study was conducted to investigate 942, 2,110 and 2,566 nurses in 6 fixed polyclinic hospitals in Suzhou in 2010, 2015 and 2019, respectively. This study used the revised version of the hospital WPV questionnaire. The count data are described as frequencies and percentages, and the measurement data are represented as means and standard deviations. The general data of nurses during different time periods, the incidence of WPV, nurses’ cognition and attitudes toward WPV and the attitudes and measures of hospitals regarding WPV were analyzed by the chi-square test. Results The incidence of WPV among nurses in Suzhou general hospitals in 2015 (69.0 %) and in 2019 (68.4 %) was higher than the incidence of 62.4 % in 2010 (P

BackgroundHorizontal violence is common in nurses. Most published studies have focused on horizontal violence and higher turnover rates in nurses; however, it lacks systematic reviews and meta-analyses. The purpose of this review is to quantitatively assess the correlation between horizontal violence and turnover intention in nurses.MethodsSystematic review and meta-analysis were performed in accordance with PRISMA guidelines. The relationship between horizontal violence and turnover intention in nurses was obtained by systematically searching related literature in four English databases (Cochrane, PubMed, Embase, and CINAHL) and three Chinese databases (SinoMed, CNKI, and Wanfang) (up to 6 March 2022). The relationship between horizontal violence and turnover intention was evaluated using Fisher's z-value, which was then converted to r. STATA 16.0 was used to perform statistical analysis. The random-effects model was performed to synthesize data.ResultsA total of 14 studies with 6,472 nurses were included. A low-positive correlation of horizontal violence with turnover intention was found (pooled r=0.32 [0.29–0.34]). Subgroup analysis showed that sample size and quality were not the source of heterogeneity. Measurement tool was the source of heterogeneity. Although geographic region might not be the source of heterogeneity, further subgroup analysis of the country reveals heterogeneity. The funnel plot and Egger's test showed no publication bias.ConclusionHorizontal violence had a low positive correlation with turnover intention in nurses. Nurses who experienced horizontal violence were more likely to leave or change careers than those who did not experience horizontal violence. This finding helps to draw attention to horizontal violence by nursing managers and implement effective interventions for nurses, so as to reduce nurses' turnover.

Vanadium dioxide nanoparticles (VO2 NPs) have been massively produced due to their excellent metal-insulator transition characteristics for various applications. Pilot studies indicated the toxicity of VO2 NPs to bacteria and mammalian cells, but the environmental hazards of VO2 NPs to plants have been unrevealed to date. In this study, we reported the inhibitive effects of VO2 NPs to the growth and photosynthesis of pea seedlings. Laboratory synthesized monoclinic VO2 NPs (N-VO2), commercial nanosized VO2 NPs (S-VO2), and commercial microsized VO2 particles (M-VO2) were carefully characterized for environmental toxicity evaluations. VO2 particles were supplemented to culture medium for seed germination and seedling growth. All three VO2 samples did not affect the germination rates of pee seeds, while serious growth inhibition of pea seedlings was observed at 10 mg/L for S-VO2 and N-VO2, and 100 mg/L for M-VO2. VO2 particles had no impact on the chlorophyll contents, but the photosynthesis of leaf was significantly decreased following the consequence of N-VO2 > S-VO2 > M-VO2. The inhibition of photosynthesis was attributed to the damage of acceptor side of photosystem II by VO2 particles at high concentrations. Abundant bioaccumulations of vanadium in roots aroused oxidative damage and changed the root structure. Our results collectively indicated that the phytotoxicity of VO2 NPs was related to the concentration, size and crystalline degree.

Photon upconversion with near-infrared excitation and ultraviolet emission has many applications, but suffers from low quantum efficiency. Here, the authors report a six-photon upconversion process in nanoparticles with heterogeneous core-multishell structure, that regulate the energy transfer pathway.

Both biomedical applications and safety assessments of manufactured nanomaterials require a thorough understanding of the interaction between nanomaterials and cells, including how nanomaterials enter cells, transport within cells, and leave cells. However, compared to the extensively studied uptake and trafficking of nanoparticles (NPs) in cells, less attention has been paid to the exocytosis of NPs. Yet exocytosis is an indispensable process of regulating the content of NPs in cells, which in turn influences, even decides, the toxicity of NPs to cells. A comprehensive understanding of the mechanisms and influencing factors of the exocytosis of NPs is not only essential for the safety assessment of NPs but also helpful for guiding the design of safe and highly effective NP-based materials for various purposes. Herein, we review the current status and progress of studies on the exocytosis of NPs. Firstly, we introduce experimental procedures and considerations. Then, exocytosis mechanisms/pathways are summarized with a detailed introduction of the main pathways (lysosomal and endoplasmic reticulum/Golgi pathway) and the role of microtubules; the patterns of exocytosis kinetics are presented and discussed. Subsequently, the influencing factors (initial content and location of intracellular NPs, physiochemical properties of NPs, cell type, and extracellular conditions) are fully discussed. Although there are inconsistent results, some rules are obtained, like smaller and charged NPs are more easily excreted. Finally, the challenges and future directions in the field have been discussed.

Summary: Molecular conformational engineering is to engineer flexible non-functional molecules into unique conformations to create novel functions just like natural proteins fold. Obviously, it is a grand challenge with tremendous opportunities. Based on the facts that natural proteins are only marginally stable with a net stabilizing energy roughly equivalent to the energy of two hydrogen bonds, and the energy barriers for the adatom diffusion of some metals are within a similar range, we propose that metal nanoparticles can serve as a general replacement of protein scaffolds to conformationally engineer protein fragments on the surface of nanoparticles. To prove this hypothesis, herein, we successfully restore the antigen-recognizing function of the flexible peptide fragment of a natural anti-lysozyme antibody on the surface of silver nanoparticles, creating a silver nanoparticle-base artificial antibody (Silverbody). A plausible mechanism is proposed, and some general principles for conformational engineering are summarized to guide future studies in this area.

Abstract Background The Saiga antelope (Saiga tatarica) is native to Eurasia and is a member of the family Bovidae. Prior to 1920, the antelope had been extensively hunted for its horns, which were used in traditional Chinese medicine. Since 1920, the Saiga antelope has been protected because of this extensive hunting, which nearly led to its extinction. Objective The study evaluated haematological and biochemical parameters to provide references for the Calf Saiga antelope (S. tatarica). The study also sought to explore the mechanisms affecting these parameters in both genders of the Calf Saiga antelope. Methods Haematological and biochemical parameters were collected from the Calf Saiga antelope. Haematological and biochemical parameters were analysed by the Coulter counter and Automatic analyser, respectively. Results The average concentrations of female triglyceride levels showed significantly higher values than the significant concentrations of male. Female red blood cells and platelets concentrations were statistically significant than the significant concentrations of males. Magnesium female concentrations were also significantly higher than male values. Other parameters showed differences between males and females. Conclusion The reported results show that haematological and biochemical characteristics varied among Calf Saiga antelope and other animals. The study results suggest that regardless of the factors, breed, the breeding environment, and climatic variables, haematological and biochemical variations can be triggered that can result in a reduction in the heat production needed for maintenance of homeothermy.

Abstract Background Leguminous plants alter patterns of gene expression in response to symbiotic colonization and infection by their cognate rhizobial bacteria, but the extent of the transcriptomic response has rarely been examined below the species level. Here we describe the identification of 12 rhizobial biotypes of Ensifer meliloti, which form nitrogen-fixing nodules in the roots of alfalfa (Medicago sativa L.), followed by a comparative RNA-seq analysis of four alfalfa cultivars each inoculated with two E. meliloti strains varying in symbiotic performance and phylogenetic relatedness. Results Rhizobial biotypes were identified on the basis of their symbiotic performance, particularly shoot dry weight. Differentially expressed genes (DEGs) and metabolic pathways were determined by comparing the RNA-seq data with that of the uninoculated control plant. Significant differences were found between DEGs generated in each cultivar with the inoculation of two rhizobial strains in comparison (P

Astaxanthin (AX) is a naturally occurring carotenoid often used as a dietary supplement in the Pacific white shrimp (Litopenaeus vannamei) culture industry. This study evaluated the effects of chemically synthesized astaxanthin on growth performance, survival, stress resistance, immune responses, and pigmentation of the Pacific white shrimp fed diets supplemented with five dietary levels of AX containing 0, 20, 40, 80, and 160 mg kg−1. The feeding trial was conducted for 8 weeks. The results showed the individuals fed diets supplemented with AX exhibited better growth performance, whose final body weight (FBW), body weight gain (BWG), specific growth ratio (SGR), and Myostatin (MSTN) showed a dose-dependent increase in Astaxanthin levels. Following acute hypoxia and ammonia stress test, the survival rate (SR) of shrimp fed with 40, 80 and 160 mg kg−1 diets were higher than that of the control group. AX diet groups improved their capacity of antioxidant defense to prevent oxidative damage, including increasing the activities of acid phosphatase (ACP), total antioxidant capacity (T-AOC), and decreasing the activities of superoxide dismutase (SOD) and catalase (CAT), the content of malondialdehyde (MDA) compared to the control group. In addition, the gene expression of various antioxidant enzymes in the hepatopancreas of shrimp was significantly upregulated higher such as manganese superoxide dismutase (MnSOD) and glutathione S-transferase (GST). High expression of hypoxia-inducible factor-1α (HIF-1α) and glutamate dehydrogenase (GDH-β), glutamine synthetase (GS) in 80 and 160 mg kg−1 group indicated their effect on glycolysis possibly, which is vital on energy production required. Quadratic regression analysis indicated that the optimal levels for growth and pigmentation were 126.94 mg kg−1 and 138.96 mg kg−1 diet, respectively. In conclusion, Astaxanthin can enhance growth performance, alleviate oxidative and ammonia stress, improving the immunity of Pacific white shrimp.

Background The increasing insecticide resistance of Aedes albopictus puts many countries in Asia and Africa, including China, at great risk of a mosquito-borne virus epidemic. To date, a growing number of researches have focused on the relationship between intestinal symbiotic bacteria and their hosts’ resistance to insecticides. This provides a novel aspect to the study of resistant mechanisms. Methods/Findings This study reveals significant composition and dynamic changes in the intestinal symbiotic bacteria of Ae. albopictus between the resistant and susceptible strains based on full-length sequencing technology. The relative abundance of Serratia oryzae was significantly higher in the resistance strain than in the susceptible strains; also, the relative abundance of S. oryzae was significantly higher in deltamethrin-induced Ae. albopictus than in their counterpart. These suggested that S. oryzae may be involved in the development of insecticide resistance in Ae. albopictus. To explore the insecticide resistance mechanism, adult mosquitoes were fed with GFP-tagged S. oryzae, which resulted in stable bacterial enrichment in the mosquito gut without affecting the normal physiology, longevity, oviposition, and hatching rates of the host. The resistance measurements were made based on bioassays as per the WHO guidelines. The results showed that the survival rate of S. oryzae-enriched Ae. albopictus was significantly higher than the untreated mosquitoes, indicating the enhanced resistance of S. oryzae-enriched Ae. albopictus. Also, the activities of three metabolic detoxification enzymes in S. oryzae-enriched mosquitoes were increased to varying degrees. Meanwhile, the activity of extracellular enzymes released by S. oryzae was measured, but only carboxylesterase activity was detected. HPLC and UHPLC were respectively used to measure deltamethrin residue concentration and metabolite qualitative analysis, showing that the deltamethrin degradation efficiency of S. oryzae was positively correlated with time and bacterial amount. Deltamethrin was broken down into 1-Oleoyl-2-hydroxy-sn-glycero-3-PE and 2’,2’-Dibromo-2’-deoxyguanosine. Transcriptome analysis revealed that 9 cytochrome P450s, 8 GSTs and 7 CarEs genes were significantly upregulated. Conclusions S. oryzae can be accumulated into adult Ae. albopictus by artificial feeding, which enhances deltamethrin resistance by inducing the metabolic detoxification genes and autocrine metabolic enzymes. S. oryzae is vertically transmitted in Ae. albopictus population. Importantly, S. oryzae can degrade deltamethrin in vitro, and use deltamethrin as the sole carbon source for their growths. Therefore, in the future, S. oryzae may also be commercially used to break down the residual insecticides in the farmland and lakes to protect the environment. Author summary This work, for the first time, isolated intestinal symbiotic bacteria S. oryzae from Ae. albopictus and verified its role in enhancing insecticide resistance in vivo and in vitro. We show that S. oryzae enhances deltamethrin resistance by inducing the metabolic detoxification genes and autocrine metabolic enzymes. This work highlights a new aspect of mosquito resistance. Moreover, S. oryzae’s capacity to high-effectively degrade insecticide in vitro may contribute to environmental protection by degrading the residual insecticide in the farmland and lakes.

Background The prevalence of inter-nurse lateral violence (LV) reported in current studies is inconsistent, ranging from 7% to 83%. The purpose of this study is to quantify the prevalence of LV in nurses’ workplaces.Methods Systematic review and meta-analysis. Cochrane, PubMed, Embase, CINAHL, CNKI and Wanfang databases were searched for relevant studies (up to 27 January 2021). We included cross-sectional, case–control or cohort studies in which both abusers and victims were nurses. Studies that did not provide specific data on abusers were excluded. Stata V.16.0 was used for statistical analysis. Fixed-effect or random-effect model was adopted according to heterogeneity, which was evaluated by Cochran’s Q and I2 values. The main indicator was LV prevalence. Sensitivity analysis, subgroup analysis and meta-regression were performed to investigate the sources of heterogeneity.Results A total of 14 studies with 6124 nurses were included. Further, 13 articles with 5745 nurses were included in the meta-analysis, and the pooled prevalence of LV among nurses was 33.08% (95% CI: 23.41% to 42.75%, p

Cadmium (Cd) is a widespread environmental heavy metal pollutant that has high toxicity to human health. Cd accumulates in the liver and results in oxidative stress and inflammatory reactions. Melatonin (MT), a hormone exhibiting strong antioxidative properties, has been proved to have hepatoprotective effect against both acute and chronic liver injury. However, the molecular mechanism underlying MT's hepatoprotective effect against Cd-induced liver injury remain not fully understood. In this study, the potential protective effect of MT on Cd-induced hepatic injury was investigated. Adult male C57BL/6 mice were randomly divided into four groups: control, CdCl2, MT, and CdCl2 plus MT groups. Animals were daily treated with either CdCl2 (5 mg/kg) or MT (10 mg/kg) or both through intragastric administration for 30 consecutive days. Serum enzymatic analysis indicated that treatment mice with Cd significantly increased AST, ALT, LDH and ALP levels, by contrast, MT treatment resulted in significant decreases of AST, ALT, LDH and ALP levels in the serum of Cd treated mice. By biochemical analysis, it was found that MT treatment significantly increased the activities of SOD, GSH, GST, CAT and GR, while significantly decreased the contents of MDA in the liver tissue of Cd treated mice. Moreover, MT treatment also suppressed the Cd-induced inflammation by reducing the inflammatory mediators, including IL-1β, IL-6, TNF-α and iNOS. Furthermore, MT treatment ameliorated the Cd-induced histopathological variations of liver tissue, which was confirmed by the biochemical and molecular data. It is clear from the results of this study that MT exerts hepatoprotective effect by improving the redox state, suppressing inflammatory reaction and cell apoptosis as well as ameliorating the performance of liver tissue histopathology, which is eventually reflected by the improvement of liver function in mice.

Multidimensional landscapes of regulatory genes in neuronal phenotypes at whole-brain levels in the vertebrate remain elusive. We generated single-cell transcriptomes of ~67,000 region- and neurotransmitter/neuromodulator-identifiable cells from larval zebrafish brains. Hierarchical clustering based on effector gene profiles (‘terminal features’) distinguished major brain cell types. Sister clusters at hierarchical termini displayed similar terminal features. It was further verified by a population-level statistical method. Intriguingly, glutamatergic/GABAergic sister clusters mostly expressed distinct transcription factor (TF) profiles (‘convergent pattern’), whereas neuromodulator-type sister clusters predominantly expressed the same TF profiles (‘matched pattern’). Interestingly, glutamatergic/GABAergic clusters with similar TF profiles could also display different terminal features (‘divergent pattern’). It led us to identify a library of RNA-binding proteins that differentially marked divergent pair clusters, suggesting the post-transcriptional regulation of neuron diversification. Thus, our findings reveal multidimensional landscapes of transcriptional and post-transcriptional regulators in whole-brain neuronal phenotypes in the zebrafish brain.

Nanoplastics, one component of plastic pollution, can enter human bodies via inhalation and thus threaten human health. However, the knowledge about the uptake and exocytosis of nanoplastics in cells of human lung organs is still very limited. Herein, we investigated the endocytosis, distribution, and exocytosis of polystyrene nanoparticles (PS NPs) of 50 nm (G50PS) and 100 nm (R100PS) in A549 cells and BEAS-2B cells. We found that both the cellular uptake of PS NPs increased positively with exposure time and dose, and A549 cells ingested more PS NPs than BEAS-2B cells did. In addition, the intracellular content of G50PS was higher than that of R100PS except at a higher dose and longer time. The ingested PS NPs were distributed mainly in lysosomes, while many G50PS appeared around the cell membrane, and R100PS also accumulated in mitochondria in BEAS-2B cells. As for the exocytosis, R100PS was more difficult to excrete than G50PS. Lysosomes in A549 cells and actin and microtubule in BEAS-2B cells were involved in the exocytosis of the PS NPs. These findings provide detailed information about the translocation of nanoplastics in lung cells, which is valuable for the safety assessment of nanoplastics in the environment.

Abstract Background Drug resistance is a major obstacle to treating cancers because it desensitizes cancer cells to chemotherapy. Recently, attention has been focused on changes in the tumor immune landscape after the acquisition of drug resistance. Programmed death-ligand-1 (PD-L1) is an immune suppressor that inhibits T cell-based immunity. Evidence has shown that acquired chemoresistance is associated with increased PD-L1 expression in cancer cells. However, the underlying mechanism is still largely unknown. Methods PD-L1 expression in three drug-resistant A549/CDDP, MCF7/ADR and HepG2/ADR cell lines was detected by qRT-PCR, western blotting and flow cytometry, and a T cell proliferation assay was performed to test its functional significance. Then, the potential roles of JNK/c-Jun, histone H3 acetylation, histone deacetylase 3 (HDAC3) and the E3 ligase COP1 in the PD-L1 increase were explored through ChIP assays and gain- and loss-of-function gene studies. Furthermore, murine xenograft tumor models were used to verify the role of JNK/c-Jun and HDAC3 in PD-L1 expression in A549/CDDP cells in vivo. Finally, the correlations of PD-L1, c-Jun and HDAC3 expression in clinical cisplatin-sensitive and cisplatin-resistant non-small cell lung cancer (NSCLC) tissues were analyzed by immunohistochemistry and Pearson’s correlation coefficient. Results PD-L1 expression was significantly increased in A549/CDDP, MCF7/ADR and HepG2/ADR cells and was attributed mainly to enhanced JNK/c-Jun signaling activation. Mechanistically, decreased COP1 increased c-Jun accumulation, which subsequently inhibited HDAC3 expression and thereby enhanced histone H3 acetylation of the PD-L1 promoter. Furthermore, PD-L1 expression could be inhibited by JNK/c-Jun inhibition or HDAC3 overexpression in vivo, which could largely reverse inhibited CD3+ T cell proliferation in vitro. PD-L1 expression was significantly increased in the cisplatin-resistant clinical NSCLC samples and positively correlated with c-Jun expression but negatively correlated with HDAC3 expression. Conclusions Enhanced histone H3 acetylation of the PD-L1 promoter via the COP1/c-Jun/HDAC3 axis was crucial for the PD-L1 increase in drug-resistant cancer cells. Our study reveals a novel regulatory network for the PD-L1 increase in drug-resistant cancer cells and that combined PD-L1-targeting strategies could improve T cell-based immunity in drug-resistant cancers.

Abstract Background Dengue fever outbreaks tend to spread northward in China, and Jining is the northernmost region where local dengue fever cases have been detected. Therefore, it is important to investigate the density of Aedes albopictus and its resistance to deltamethrin. Methods The Breteau index (BI) and container index (CI) were calculated to assess the larval density of Ae. albopictus and human-baited double net trap (HDN) surveillance was performed in six subordinate counties (Rencheng, Yanzhou, Sishui, Liangshan, Zoucheng and Jiaxiang) of Jining City in 2017 and 2018. The resistance of Ae. albopictus adults to deltamethrin was evaluated using the World Health Organization (WHO) standard resistance bioassay. The mutations at Vgsc codons 1532 and 1534 were also analysed to determine the association between kdr mutations and phenotypic resistance in adult mosquitoes. Results The average BI, CI and biting rate at Jining were 45.30, 16.02 and 1.97 (female /man/hour) in 2017 and 15.95, 7.86 and 0.59 f/m/h in 2018, respectively. In August 26, 2017, when the first dengue fever case was diagnosed, the BI at Qianli village in Jiaxiang County was 107.27. The application of prevention and control measures by the government sharply decreased the BI to a value of 4.95 in September 3, 2017. The mortality of field-collected Ae. albopictus females from Jiaxiang was 41.98%. I1532T, F1534L and F1534S mutations were found in domain III of the Vgsc gene. This study provides the first demonstration that both I1532T and F1534S mutations are positively correlated with the deltamethrin-resistant phenotype. Conclusions Mosquito density surveillance, resistance monitoring and risk assessment should be strengthened in areas at risk for dengue to ensure the sustainable control of Ae. albopictus and thus the prevention and control of dengue transmission.

Abstract Background Culex pipiens pallens is the most abundant Culex mosquito species in northern China and is an important vector of bancroftian filariasis and, potentially, West Nile virus. Insecticides, particularly pyrethroids, are widely used for adult mosquito control. Insecticide resistance has become common in several mosquito species, and vector control is the main method currently available to prevent disease transmission. The voltage-gated sodium channel (Vgsc) gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr). Methods Culex pipiens pallens larvae were collected from May to November over two decades, from 1992 to 2018, in four cities in Shandong Province, China. The World Health Organization (WHO) standard resistance bioassay was applied to test the resistance levels of Cx. p. pallens larvae to five different insecticides and to test deltamethrin resistance in adults, using the F1 generation. Mutations at Vgsc codon 1014 were also screened in 471 adult samples collected in 2014 to determine the association between kdr mutations and phenotypic resistance. Results Larval resistance against deltamethrin showed an increasing trend from the 1990s until 2018, which was statistically significant in all populations; resistance to cypermethrin increased significantly in mosquitoes from the Zaozhuang population. However, larval resistance to other insecticides remained relatively stable. Larval resistance against deltamethrin was consistent with adult bioassays in 2014, in which all tested populations were highly resistant, with mortality rates ranging from 39.4 to 55.23%. The L1014S and L1014F mutations were both observed in five Cx. p. pallens populations, with L1014F significantly associated with deltamethrin resistance. Conclusions The long-term dataset from Shandong demonstrates major increases in pyrethroid resistance over a 20-year period. The L1014F kdr mutation may be considered a viable molecular marker for monitoring pyrethroid resistance in Cx. p. pallens.

[This corrects the article DOI: 10.1371/journal.pbio.3000435.].

Abstract The intestinal symbiotic bacteria of Aedes albopictus play a potential role in host resistance to insecticides. In this study, we sequenced the full‐length of 16S rRNA and analyzed the differences in the intestinal microbiota between deltamethrin‐resistant and ‐sensitive Ae. albopictus. Symbiotic bacteria were cultured and analyzed using six types of culture media in aerobic and anaerobic environments. We found significant differences in the diversity and abundance of the intestinal microbiota of the two strains of Ae. albopictus. The symbiotic bacteria cultured in vitro were found to be mainly facultative anaerobes. The cultured bacteria such as Serratia oryzae and Acinetobacter junii may function to promote the development of insecticide resistance. This work indicates that intestinal bacteria may contribute to the enhancement of insecticide resistance of Ae. albopictus It also highlights the analytical advantage of full‐length 16S rRNA sequencing to study the intestinal microbiota of mosquitoes.

As Jiaxiang County of Shandong province is an area with complex mosquito vector composition, it is necessary to investigate the relationship between bacterial diversity, physicochemical factors, and larval density. Therefore, the physicochemical properties of 46 breeding sites for six kinds of habitat types (small puddles, small water containers, paddy fields, large water containers, irrigation channels, and drainage ditches) were investigated by a multiparameter analyzer; the water’s bacterial diversity was analyzed by the 16S rRNA full-length sequencing method. Spearman correlation and multiple linear regression were used to analyze the correlation between larval density and variables. The variables analyzed were dissolved oxygen, pH, hardness, turbidity, conductivity, temperature, ammonia nitrogen, water depth, and distance from the nearest house. One-Way ANOVA was used to understand whether there are differences in bacterial diversity in different habitats. Pearson linear correlation model was used to analyze the effects of bacterial diversity and richness on mosquito densities in breeding sites. A total of 3291 larvae were captured, and a total of 6 species of 4 genera were identified. The identified species were Culex pipiens pallens, Aedes albopictus, Anopheles sinensis, Culex tritaeniorhynchus, Culex bitaeniorhynchus, and Mansonia uniformis. The density and species can be jointly affected by physicochemical properties and bacterial diversity, especially Shannon index and distance from the nearest house. In general, the physicochemical parameters and bacterial diversity of different habitats were significantly different. Even for the same habitat type, the physicochemical parameters varied greatly due to different environments.

The main stem cell niche for neurogenesis in the adult mammalian brain is the subventricular zone (SVZ) that extends along the cerebral lateral ventricles. We aimed at characterizing the initial molecular responses of the macaque monkey SVZ to transient, global cerebral ischemia. We microdissected tissue lining the anterior horn of the lateral ventricle (SVZa) from 7 day post-ischemic and sham-operated monkeys. Transcriptomics shows that in ischemic SVZa, 541 genes were upregulated and 488 genes were down-regulated. The transcription data encompassing the upregulated genes revealed a profile typical for quiescent stem cells and astrocytes. In the primate brain the SVZ is morphologically subdivided in distinct and separate ependymal and subependymal regions. The subependymal contains predominantly neural stem cells (NSC) and differentiated progenitors. To determine in which SVZa region ischemia had evoked transcriptional upregulation, sections through control and ischemic SVZa were analyzed by high-throughput in situ hybridization for a total of 150 upregulated genes shown in the www.monkey-niche.org image database. The majority of the differentially expressed genes mapped to the subependymal layers on the striatal or callosal aspect of the SVZa. Moreover, a substantial number of upregulated genes was expressed in the ependymal layer, implicating a contribution of the ependyma to stem cell biology. The transcriptome analysis yielded several novel gene markers for primate SVZa including the apelin receptor that is strongly expressed in the primate SVZa niche upon ischemic insult.

Background: We aimed to conduct a retrospective analysis of the epidemiological changes and prevention effects for malaria in Weifang, Shandong Peninsula, China from 1957 to 2017. Methods: The malaria data from a web-based reporting system were analyzed to explore malaria epidemiological characteristics and prevention effects in Weifang. Results: Overall, 1, 704, 890 malaria cases were reported in Weifang from 1957 to 2017, of which two major malaria epidemics occurred in 1961 (827.28/10, 000) and 1971 (366.14/10, 000). Prior to 1997, all malaria patients (1, 704, 829) were infected with Plasmodium vivax (P. vivax). After 2007, the cases of Plasmodium falciparum (P. falciparum) showed an upward trend (76.8%). The reported cases after the 21st century were mainly imported cases, and the last indigenous case was a patient that infected with P. vivax in 2006. Overall, 36 imported cases were reported from 2010 to 2017, of which 88.9% were acquired in Africa. Except for one 32-year-old woman, the rest were male (97.2%), in which laborers and farmers represented the vast majority (66.6%). From 1987 to 2017, there were 1, 224, 474 cases of fever with blood tests, and the average blood test rate was 4.9%. From 1957 to 2017, a total of 1, 704, 890 malaria patients were treated, 96 cases were treated during resting phase from 1987 to 2017. Conclusion: Weifang should continue to strengthen the management of the migrant population, making blood tests for fever patients and patient treatment as important means of malaria control and monitoring

The circadian clock is a cell-autonomous time-keeping mechanism established gradually during embryonic development. Here, we generated a transgenic zebrafish line carrying a destabilized fluorescent protein driven by the promoter of a core clock gene, nr1d1, to report in vivo circadian rhythm at the single-cell level. By time-lapse imaging of this fish line and 3D reconstruction, we observed the sequential initiation of the reporter expression starting at photoreceptors in the pineal gland, then spreading to the cells in other brain regions at the single-cell level. Even within the pineal gland, we found heterogeneous onset of nr1d1 expression, in which each cell undergoes circadian oscillation superimposed over a cell type-specific developmental trajectory. Furthermore, we found that single-cell expression of nr1d1 showed synchronous circadian oscillation under a light-dark (LD) cycle. Remarkably, single-cell oscillations were dramatically dampened rather than desynchronized in animals raised under constant darkness, while the developmental trend still persists. It suggests that light exposure in early zebrafish embryos has significant effect on cellular circadian oscillations.

Complete desorption of contaminants from electrode materials is required for the efficient utilization and long service life of capacitive deionization (CDI) but remains a major challenge. The electrodesorption capacity of CDI in the conventional electrode configuration is limited by the narrow electrochemical stability window of water, which lowers the operating potential to approximately 1.2 V. Here, we report a graphite anode–titanium cathode electrode configuration that extends the cathode potential to −1.7 V and provides an excellent (100%) electrodesorption performance, which is maintained after five cycles. The improvement of the cathode potential depends on the redox property of the electrode. The stronger the oxidizability of the anode and reducibility of the cathode, the wider the cathode potential. The complete desorption potential of SO42− predicted by theoretical electrochemistry was the foundation for optimizing the electrode configuration. The desorption efficiency of Cl− depended on the ionic strength and was negligibly affected by circulating velocities above 112 mL min−1. This work can direct the design optimizations of CDI devices, especially for reactors undergoing chemisorption during the electrosorption process.

Abstract Background Circadian rhythms are oscillating physiological and behavioral changes governed by an internal molecular clock, and dysfunctions in circadian rhythms have been associated with ageing and various neurodegenerative diseases. However, the evidence directly connecting the neurodegeneration-associated proteins to circadian control at the molecular level remains sparse. Methods Using meta-analysis, synchronized animals and cell lines, cells and tissues from FUS R521C knock-in rats, we examined the role of FUS in circadian gene expression regulation. Results We found that FUS, an oscillating expressed nuclear protein implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), exerted a novel feedback route to regulate circadian gene expression. Nr1d1-encoded core circadian protein REV-ERBα bound the Fus promoter and regulated the expression of Fus. Meanwhile, FUS was in the same complex as PER/CRY, and repressed the expression of E box-containing core circadian genes, such as Per2, by mediating the promoter occupancy of PSF-HDAC1. Remarkably, a common pathogenic mutant FUS (R521C) showed increased binding to PSF, and caused decreased expression of Per2. Conclusions Therefore, we have demonstrated FUS as a modulator of circadian gene expression, and provided novel mechanistic insights into the mutual influence between circadian control and neurodegeneration-associated proteins.

This study was conducted to explore the outcomes of starvation/re-feeding techniques on growth performance, liver antioxidant activities, and histological changes of the gastrointestinal organs of Gansu golden trout. A total of 225 juveniles were divided into 5 treatment groups; the control group (N0) was routinely fed every day while the other groups (N7, N14, N21, and N28) were starved for 7, 14, 21, and 28 days, respectively and after the starvation session, each group was re-fed for 28 days. Compensatory growth was statistically recorded in N14. Weight gain rate and feeding ratio were the highest in the N14 group, while specific growth rate and feeding conversion ratio showed significant increases in the fish groups exposed to longer starvation periods. Liver antioxidant activities showed a significant increase and decrease in malondialdehyde and superoxide dismutase levels in N21 and N28, respectively, which returned to normal levels after re-feeding. Stomach, intestine, and liver showed histological alterations in all groups and the severity was correlated with the fasting periods. Those changes were restored to a certain degree after feeding was resumed. The compensation by group N14 presents potential for economic usefulness of the fasting/re-feeding strategy in Gansu golden trout.

The utilization of extracellular vesicles (EVs) in clinical theranostics has rapidly advanced in the past decade. In November 2018, the International Society for Extracellular Vesicles (ISEV) held a workshop on “EVs in Clinical Theranostic”. Here, we report the conclusions of roundtable discussions on the current advancement in the analysis technologies and we provide some guidelines to researchers in the field to consider the use of EVs in clinical application. The main challenges and the requirements for EV separation and characterization strategies, quality control and clinical investigation were discussed to promote the application of EVs in future clinical studies.

BACKGROUND:To investigate mosquito larval habitats and resistance to common insecticides in areas with high incidence rates of mosquito-borne diseases in Jining, Shandong Province, and to provide a scientific basis for the future prevention and control of mosquito-borne diseases and the rational use of insecticides. METHODS AND RESULTS:From June to September 2018, mosquito habitat characteristics and species compositions in Jintun town were studied through a cross-sectional survey. Larvae and pupae were collected in different habitats using the standard dipping technique. A total of 7,815 mosquitoes, comprising 7 species from 4 genera, were collected. Among them, Culex pipiens pallens (n = 5,336, 68.28%) was the local dominant species and found in all four habitats (rice paddies, irrigation channels, water containers, drainage ditches). There were 1,708 Cx. tritaeniorhynchus (21.85%), 399 Anopheles sinensis (5.11%), 213 Armigeres subalbatus (2.72%), 124 Aedes albopictus (1.59%), and 35 other (Cx. bitaeniorhynchus and Cx. halifaxii) (0.45%) mosquito samples collected. Spearman correlation analysis was employed to evaluate the relationship between larval density and the physicochemical characteristics of the breeding habitat. It was found that the larval density of Cx. tritaeniorhynchus correlated positively with water depth (r = 0.927 p = 0.003), the larval density of An. sinensis correlated positively with dissolved oxygen (DO) (r = 0.775 p = 0.041) and the larval density of Cx. p. pallens correlated positively with ammonia nitrogen (r = 0.527 p = 0.002). Resistance bioassays were carried out on the dominant populations of Cx. p. pallens: mosquitoes presented very high resistance to cypermethrin and deltamethrin, moderate resistance to dichlorvos (DDVP), and low resistance to Bacillus thuringiensis israelensis (Bti), with decreased susceptibility to propoxur. CONCLUSION:We showed that mosquito species vary across habitat type and that the mosquito larval density correlated positively with certain physicochemical characteristics in different habitats. In addition, Cx. p. pallens developed different levels of resistance to five insecticides. Vector monitoring should be strengthened after an epidemic, and further research should be conducted to scientifically prevent and kill mosquitoes.

[This corrects the article DOI: 10.1371/journal.pone.0224822.].

The role of metabolomics in autoimmune diseases has been a rapidly expanding area in researches over the last decade, while its pathophysiologic impact on systemic lupus erythematosus (SLE) remains poorly elucidated. In this study, we analyzed the metabolic profiling of fecal samples from SLE patients and healthy controls based on ultra-high-performance liquid chromatography equipped with mass spectrometry for exploring the potential biomarkers of SLE. The results showed that 23 differential metabolites and 5 perturbed pathways were identified between the two groups, including aminoacyl-tRNA biosynthesis, thiamine metabolism, nitrogen metabolism, tryptophan metabolism, and cyanoamino acid metabolism. In addition, logistic regression and ROC analysis were used to establish a diagnostic model for distinguishing SLE patients from healthy controls. The combined model of fecal PG 27:2 and proline achieved an area under the ROC curve of 0.846, and had a good diagnostic efficacy. In the present study, we analyzed the correlations between fecal metabolic perturbations and SLE pathogenesis. In summary, we firstly illustrate the comprehensive metabolic profiles of feces in SLE patients, suggesting that the fecal metabolites could be used as the potential non-invasive biomarkers for SLE.

Lanthanide-doped upconversion nanoparticles can convert long wavelength excitation radiation to short wavelength emission. They have great potential in biomedical applications, such as bioimaging, biodetection, drug delivery, and theranostics. However, there is little information available on their bioavailability and biological effects after oral administration. In this study, we systematically investigated the bioavailability, biodistribution, and toxicity of silica-coated upconversion nanoparticles administrated by gavage. Our results demonstrate that these nanoparticles can permeate intestinal barrier and enter blood circulation by microstructure observation of Peyer's patch in the intestine. Comparing the bioavailability and the biodistribution of silica-coated upconversion nanoparticles with oral and intravenous administration routes, we found that the bioavailability and biodistribution are particularly dependent on the administration routes. After consecutive gavage for 14 days, the body weight, pathology, Zn and Cu level, serum biochemical analysis, oxidative stress, and inflammatory cytokines were studied to further evaluate the potential toxicity of the silica-coated upconversion nanoparticles. The results suggest that these nanoparticles do not show overt toxicity in mice even at a high dose of 100 mg/kg body weight.

Ankle sprain is a commonly recurring sports injury. This study aimed to compare the rehabilitation effects of resistance and balance training programs in patients with recurrent ankle sprain. Patients with recurrent lateral ankle sprain completed a home-based rehabilitation program comprising resistance training (RT; n = 27) or balance training (BT; n = 27). RT consisted of exercises using elastic tube bands, and BT consisted mainly of exercises performed using a variety of balance tools. Exercises were performed for 6 weeks, twice a day for 20 min, 5 days per week. Isokinetic eversion strength, Y-Balance test and hop tests, and foot and ankle outcome score (FAOS) were evaluated. Both RT and BT significantly improved strength and dynamic balance (p < 0.05). Compared to RT, BT also significantly improved the outcome of the crossover hop test (p = 0.008). The changes reflected group and time in pain (p = 0.022), sports (p = 0.027), and quality of life (p = 0.033) of FAOS were significantly greater in BT than RT.

BACKGROUND:The Saiga antelope (Saiga tatarica) is a critically endangered species, and there has been limited success in restoring the population by captive breeding. This study assessed the biochemical and physiological parameters of newborn Saiga antelope to provide reference information that can be used to evaluate their health. Comparisons have been made with parameters for horses and closely related members of the Bovidae family but there are no reference values for the newborn Saiga antelope. METHODS:Biochemical and physiological parameters were measured in 61 animals. An automatic analyzer (Hitachi Ltd. 7180 Serial, Tokyo, Japan) was used to analyze the biochemical parameters, while the Coulter counter (Model ZK) was used to analyze the physiological parameters. RESULTS:The results showed that the biochemical and physiological parameters differ considerably in range. The evaluation of parameters stratified by sex showed differences. Triglyceride and LDL cholesterol concentrations among male animals were significantly higher than those in female animals, while the creatine kinase concentrations were significantly higher in females than in males. Comparing this study's results with published data for horses showed many similarities and some differences. Cholesterol, magnesium and glucose levels were similar between Saiga antelope and horses, while albumin and hematocrit levels in Saiga antelope differed from the reference values in horses. CONCLUSION:The study has shown that horses and even closely related members of the Bovidae family are not suitable references when evaluating the biochemical and physiological properties of newborn Saiga antelope. These animals have unique stressors and warrant further study to inform efforts pertaining to their care and the future sustainability of the species.

Risk taking is imperative for the survival and fitness of animals since they constantly face innumerable threats from various sources. Indeed, the ability of the individual to balance between the costs and benefits of various options and adopt a wise decision is critical for the well-being of the animal. In the current study, we investigated gender differences in risk taking and decision making in male and female Smith's zokors (Eospalax smithii), a subterranean rodent species, in the defensive withdrawal apparatus (DWA) under novel, predator and conditioned contexts. Under novel context, males showed more exploratory and less hiding behavior than females especially during the first half of the testing session. However, under predator and conditioned contexts, non-significant sexually dimorphic behavioral differences were observed. Nevertheless, analysis of the performance of each gender separately across the three contexts revealed that males showed strong aversion to the predator and conditioned contexts. By contrast, females did not significantly vary their behavioral responses when exposed to the predator and conditioned cues. Our results suggest that males are more inclined to indulge in riskier exploratory activities while females may be regarded as risk-aversive. The current findings highlighted the functional significance of the trade-off between risk and exploration in the natural environment such that male and female zokors differed in how they gather and process information during risky confrontations that ultimately elicit significant variations in their decision-making and coping strategies to dangerous events. Keywords: Conditioning, Behavior, Sex differences, Risk-taking, Subterranean rodents

Background & objectives: Under certain ecological circumstances, pathogens are able to rapidly adapt to new vectors. The great capacity of Plasmodium spp. to adapt to new anopheline mosquito vectors on different continents and the continuous ecological changes attributed to humans might promote their adaptation to culicine vectors, which are known to infect humans. Based on our current knowledge, it is difficult to predict whether such adaptations will occur. This study was aimed to determine the infection susceptibility of Anopheles sinensis, Culex tritaeniorhynchus and Cx. pipiens pallens to Plasmodium vivax in Shandong Province of China. Methods: The susceptibility of the three predominant species of mosquitoes -An. sinensis, Cx. tritaeniorhynchus and Cx. pipiens pallens in Shandong Province was compared with a direct membrane feeding assay with 15 batches of Shandong strain mono-infected gametocyte-containing blood collected from Plasmodium vivax-infected patients. Infectivity was measured by dissecting the midguts and salivary glands of the mosquitoes. The presence of oocysts and sporozoites was determined by microscopy at 6 and 22 days post-blood feeding. Results: From the 15 batches of mosquitoes that were fed infected blood, oocysts and sporozoites were detected only in 7th, 13th and 15th batches of infection for An. sinensis, and no oocysts or sporozoites were detected in Cx. tritaeniorhynchus or Cx. pipiens pallens. The positive rate of An. sinensis infection was 21.2, 13 and 36.3% in the three batches of mosquitoes, with an average infection rate of 23.5%. Interpretation & conclusion: The susceptibility of An. sinensis to P. vivax was very high in Shandong Province. Cx. tritaeniorhynchus and Cx. pipiens pallens failed to exhibit susceptibility to P. vivax.

The Sonic hedgehog (Shh) signaling pathway is crucial for pattern formation in early central nervous system development. By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1- and Shh-Ptch1+. These two domains are associated respectively with Foxa2 and Gata3, two transcription factors that play key roles in specifying them. Gata3 ChIP-seq experiments and RNA-seq assays on Gata3-knockdown cells revealed that Gata3 up-regulates the genes that are enriched in the Shh-Ptch1+ domain. Important Gata3 targets include Slit2 and Slit3, which are involved in the process of axon guidance, as well as Slc18a1, Th and Qdpr, which are associated with neurotransmitter synthesis and release. By contrast, Foxa2 both up-regulates the genes expressed in the Shh+Ptch1- domain and down-regulates the genes characteristic of the Shh-Ptch1+ domain. From these and other data, we were able to reconstruct a gene regulatory network governing both domains. Our work provides the first genome-wide characterization of the gene regulatory network involved in the Shh pathway that underlies pattern formation in the early mouse brain.

In the study of circadian rhythms, it has been a puzzle how a limited number of circadian clock genes can control diverse aspects of physiology. Here we investigate circadian gene expression genome-wide using larval zebrafish as a model system. We made use of a spatial gene expression atlas to investigate the expression of circadian genes in various tissues and cell types. Comparison of genome-wide circadian gene expression data between zebrafish and mouse revealed a nearly anti-phase relationship and allowed us to detect novel evolutionarily conserved circadian genes in vertebrates. We identified three groups of zebrafish genes with distinct responses to light entrainment: fast light-induced genes, slow light-induced genes, and dark-induced genes. Our computational analysis of the circadian gene regulatory network revealed several transcription factors (TFs) involved in diverse aspects of circadian physiology through transcriptional cascade. Of these, microphthalmia-associated transcription factor a (mitfa), a dark-induced TF, mediates a circadian rhythm of melanin synthesis, which may be involved in zebrafish's adaptation to daily light cycling. Our study describes a systematic method to discover previously unidentified TFs involved in circadian physiology in complex organisms.

Circadian rhythm is fundamental in regulating a wide range of cellular, metabolic, physiological, and behavioral activities in mammals. Although a small number of key circadian genes have been identified through extensive molecular and genetic studies in the past, the existence of other key circadian genes and how they drive the genomewide circadian oscillation of gene expression in different tissues still remains unknown. Here we try to address these questions by integrating all available circadian microarray data in mammals. We identified 41 common circadian genes that showed circadian oscillation in a wide range of mouse tissues with a remarkable consistency of circadian phases across tissues. Comparisons across mouse, rat, rhesus macaque, and human showed that the circadian phases of known key circadian genes were delayed for 4-5 hours in rat compared to mouse and 8-12 hours in macaque and human compared to mouse. A systematic gene regulatory network for the mouse circadian rhythm was constructed after incorporating promoter analysis and transcription factor knockout or mutant microarray data. We observed the significant association of cis-regulatory elements: EBOX, DBOX, RRE, and HSE with the different phases of circadian oscillating genes. The analysis of the network structure revealed the paths through which light, food, and heat can entrain the circadian clock and identified that NR3C1 and FKBP/HSP90 complexes are central to the control of circadian genes through diverse environmental signals. Our study improves our understanding of the structure, design principle, and evolution of gene regulatory networks involved in the mammalian circadian rhythm.