MELK aggravates lung adenocarcinoma by regulating EZH2 ubiquitination and H3K27me3 histone methylation of LATS2.

We tried to elucidate the possible roles of maternal embryonic leucine pull chain kinase (MELK) in lung adenocarcinoma (LUAD) growth and metastasis. Differentially expressed genes in LUAD samples were analysed by the GEPIA database. Clinical tissue samples and cells were collected for MELK, EZH2 and LATS2 expression determination. Co-IP assay was used to verify the interaction between EZH2 and MELK; CHX tracking assay and ubiquitination assay detected the degradation of MELK on EZH2 ubiquitination. ChIP assay detected the enrichment of EZH2 and H3K27me3 on the LATS2 promoter region. LUAD cells were selected for in vitro validation, and the tumorigenic ability of LUAD cells was also observed in a transplantation tumour model of LUAD nude mice. MELK and EZH2 were highly expressed in LUAD samples, while LATS2 was lowly expressed. MELK interacted with EZH2 to inhibit its ubiquitination degradation; EZH2 elevated H3K27me3 modification in the LATS2 promoter to lower LATS2 expression. Silencing MELK or EZH2 or overexpressing LATS2 restrained LUAD cell proliferation and invasion, and facilitated their apoptosis. Silencing MELK or EZH2 or overexpressing LATS2 suppressed tumour formation in nude mice. This study demonstrated that MELK aggravated LUAD by upregulating EZH2 and downregulating LATS2.

Characterizing the Role of AosfgA and AofluG in Mycelial and Conidial Development in Arthrobotrys oligospora and Their Role in Secondary Metabolism.

Arthrobotrys oligospora, a widespread nematode-trapping fungus which can produce conidia for asexual reproduction and form trapping devices (traps) to catch nematodes. However, little is known about the sporulation mechanism of A. oligospora. This research characterized the functions and regulatory roles of the upstream spore-producing regulatory genes, AosfgA and AofluG, in A. oligospora. Our analysis showed that AosfgA and AofluG interacted with each other. Meanwhile, the AofluG gene was downregulated in the ΔAosfgA mutant strain, indicating that AosfgA positively regulates AofluG. Loss of the AosfgA and AofluG genes led to shorter hyphae and more septa, and the ΔAosfgA strain responded to heat and chemical stresses. Surprisingly, the number of nuclei was increased in the mycelia but reduced in the conidia of the ΔAosfgA and ΔAofluG mutants. In addition, after nematode induction, the number and volume of vacuoles were remarkably increased in the ΔAosfgA and ΔAofluG mutant strains. The abundance of metabolites was markedly decreased in the ΔAosfgA and ΔAofluG mutant strains. Collectively, the AosfgA and AofluG genes play critical roles in mycelial development, and they are also involved in vacuole assembly, the stress response, and secondary metabolism. Our study provides distinct insights into the regulatory mechanism of sporulation in nematode-trapping fungi.

USP14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the HK2/AKT/P62 axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with strong invasiveness and poor prognosis. Previous studies have demonstrated the significant role of USP14 in various solid tumors. However, the role of USP14 in the regulation of HCC development and progression remains unclear. METHODS: We discovered through GEO and TCGA databases that USP14 may play an important role in liver cancer. Using bioinformatics analysis based on the Cancer Genome Atlas (TCGA) database, we screened and identified USP14 as highly expressed in liver cancer. We detected the growth and metastasis of HCC cells promoted by USP14 through clone formation, cell counting kit 8 assay, Transwell assay, and flow cytometry. In addition, we detected the impact of USP14 on the downstream protein kinase B (AKT) and epithelial-mesenchymal transition (EMT) pathways using western blotting. The interaction mechanism between USP14 and HK2 was determined using immunofluorescence and coimmunoprecipitation (CO-IP) experiments. RESULTS: We found that sh-USP14 significantly inhibits the proliferation, invasion, and invasion of liver cancer cells, promoting apoptosis. Further exploration revealed that sh-USP14 significantly inhibited the expression of HK2. Sh-USP14 can significantly inhibit the expression of AKT and EMT signals. Further verification through immunofluorescence and CO-IP experiments revealed that USP14 co-expressed with HK2. Further research has found that USP14 regulates the glycolytic function of liver cancer cells by the deubiquitination of HK2. USP14 regulates the autophagy function of liver cancer cells by regulating the interaction between SQSTM1/P62 and HK2. CONCLUSIONS: Our results indicate that USP14 plays a crucial role in the carcinogenesis of liver cancer. We also revealed the protein connections between USP14, HK2, and P62 and elucidated the potential mechanisms driving cancer development. The USP14/HK2/P62 axis may be a new therapeutic biomarker for the diagnosis and treatment of HCC.

AoPrdx2 Regulates Oxidative Stress, Reactive Oxygen Species, Trap Formation, and Secondary Metabolism in Arthrobotrys oligospora.

Prdx2 is a peroxiredoxin (Prx) family protein that protects cells from attack via reactive oxygen species (ROS), and it has an important role in improving the resistance and scavenging capacity of ROS in fungi. Arthrobotrys oligospora is a widespread nematode-trapping fungus that can produce three-dimensional nets to capture and kill nematodes. In this study, AoPrdx2, a homologous protein of Prx5, was investigated in A. oligospora via gene disruption, phenotypic analysis, and metabolomics. The deletion of Aoprdx2 resulted in an increase in the number of mycelial septa and a reduction in the number of nuclei and spore yield. Meanwhile, the absence of Aoprdx2 increased sensitivity to oxidative stresses, whereas the ∆Aoprdx2 mutant strain resulted in higher ROS levels than that of the wild-type (WT) strain. In particular, the inactivation of Aoprdx2 severely influenced trap formation and pathogenicity; the number of traps produced by the ∆Aoprdx2 mutant strain was remarkably reduced and the number of mycelial rings of traps in the ∆Aoprdx2 mutant strain was less than that of the WT strain. In addition, the abundance of metabolites in the ∆Aoprdx2 mutant strain was significantly downregulated compared with the WT strain. These results indicate that AoPrdx2 plays an indispensable role in the scavenging of ROS, trap morphogenesis, and secondary metabolism.

TMEM43 promotes the development of hepatocellular carcinoma by activating VDAC1 through USP7 deubiquitination.

Background: Transmembrane protein 43 (TMEM43), a member of the TMEM subfamily, is encoded by a highly conserved gene and widely expressed in most species from bacteria to humans. In previous studies, TMEM43 has been found to play an important role in a variety of tumors. However, the role of TMEM43 in cancer remains unclear. Methods: We utilized the RNA sequencing (RNA-seq) and The Cancer Genome Atlas (TGCA) databases to explore and identify genes that may play an important role in the occurrence and development of hepatocellular carcinoma (HCC), such as TMEM43. The role of TMEM43 in HCC was explored through Cell Counting Kit-8 (CCK-8) cloning, flow cytometry, and Transwell experiments. The regulatory relationship between TMEM43 and voltage-dependent anion channel 1 (VDAC1) was investigated through coimmunoprecipitation (co-IP) and western blot (WB) experiments. WB was used to study the deubiquitination effect of ubiquitin-specific protease 7 (USP7) on TMEM43. Results: In this study, we utilized the RNA-seq and TGCA databases to mine data and found that TMEM43 is highly expressed in HCC. The absence of TMEM43 in cancer cells was shown to inhibit tumor development. Further research detected an important regulatory relationship between TMEM43 and VDAC1. In addition, we found that USP7 affected the progression of HCC by regulating the ubiquitination level of TMEM43 through deubiquitination. Conclusions: Our study demonstrated that USP7 participates in the growth of HCC tumors through TMEM43/VDAC1.Our results suggest that USP7/TMEM43/VDAC1 may have predictive value and represent a new treatment strategy for HCC.

Identification of a transcription factor AoMsn2 of the Hog1 signaling pathway contributes to fungal growth, development and pathogenicity in Arthrobotrys oligospora.

INTRODUCTION: Arthrobotrys oligospora has been utilized as a model strain to study the interaction between fungi and nematodes owing to its ability to capture nematodes by developing specialized traps. A previous study showed that high-osmolarity glycerol (Hog1) signaling regulates the osmoregulation and nematocidal activity of A. oligospora. However, the function of downstream transcription factors of the Hog1 signaling in the nematode-trapping (NT) fungi remains unclear. OBJECTIVE: This study aimed to investigate the functions and potential regulatory network of AoMsn2, a downstream transcription factor of the Hog1 signaling pathway in A. oligospora. METHODS: The function of AoMsn2 was characterized using targeted gene deletion, phenotypic experiments, real-time quantitative PCR, RNA sequencing, untargeted metabolomics, and yeast two-hybrid analysis. RESULTS: Loss of Aomsn2 significantly enlarged and swollen the hyphae, with an increase in septa and a significant decrease in nuclei. In particular, spore yield, spore germination rate, traps, and nematode predation efficiency were remarkably decreased in the mutants. Phenotypic and transcriptomic analyses revealed that AoMsn2 is essential for fatty acid metabolism and autophagic pathways. Additionally, untargeted metabolomic analysis identified an important function of AoMsn2 in the modulation of secondary metabolites. Furtherly, we analyzed the protein interaction network of AoMsn2 based on the Kyoto Encyclopedia of Genes and Genomes pathway map and the online website STRING. Finally, Hog1 and six putative targeted proteins of AoMsn2 were identified by Y2H analysis. CONCLUSION: Our study reveals that AoMsn2 plays crucial roles in the growth, conidiation, trap development, fatty acid metabolism, and secondary metabolism, as well as establishes a broad basis for understanding the regulatory mechanisms of trap morphogenesis and environmental adaptation in NT fungi.

Metaproteomics analysis of anaerobic digestion of food waste by the addition of calcium peroxide and magnetite.

Adding trace calcium peroxide and magnetite into a semi-continuous digester is a new method to effectively improve the anaerobic digestion of food waste. However, the microbial mechanism in this system has not been fully explored. Metaproteomics further revealed that the most active and significantly regulated genus u_p_Chloroflexi had formed a good cooperative relationship with Methanomicrobiales and Methanothrix in the system. u_p_Chloroflexi decomposed more organic compounds into CO2, acetate, amino acids, and other substances by alternating between short aerobic-anaerobic respiration. It perceived and adapted to the surrounding environment by producing biofilm, extracellular enzymes, and accelerating substrate transport, formed a respiratory barrier, and enhanced iron transport capacity by using highly expressed cytochrome C. The methanogens formed reactive oxygen species scavengers and reduced iron transport to prevent oxidative damage. This study provides new insight for improving the efficiency of anaerobic digestion of food waste and identifying key microorganisms and their regulated functional proteins in the calcium peroxide-magnetite digestion system.IMPORTANCEPrevious study has found that the combination of calcium peroxide and magnetite has a good promoting effect on the anaerobic digestion process of food waste. Through multiple omics approaches, information such as microbial population structure and changes in metabolites can be further analyzed. This study can help researchers gain a deeper understanding of the digestion pathway of food waste under the combined action of calcium peroxide and magnetite, further elucidate the impact mechanisms of calcium peroxide and magnetite at the microbial level, and provide theoretical guidance to improve the efficiency and stability of anaerobic digestion of food waste, as well as reduce operational costs. This research contributes to improving energy recovery efficiency, promoting sustainable management and development of food waste, and is of great significance to environmental protection.

Integrating External Controls by Regression Calibration for Genome-Wide Association Study.

Genome-wide association studies (GWAS) have successfully revealed many disease-associated genetic variants. For a case-control study, the adequate power of an association test can be achieved with a large sample size, although genotyping large samples is expensive. A cost-effective strategy to boost power is to integrate external control samples with publicly available genotyped data. However, the naive integration of external controls may inflate the type I error rates if ignoring the systematic differences (batch effect) between studies, such as the differences in sequencing platforms, genotype-calling procedures, population stratification, and so forth. To account for the batch effect, we propose an approach by integrating External Controls into the Association Test by Regression Calibration (iECAT-RC) in case-control association studies. Extensive simulation studies show that iECAT-RC not only can control type I error rates but also can boost statistical power in all models. We also apply iECAT-RC to the UK Biobank data for M72 Fibroblastic disorders by considering genotype calling as the batch effect. Four SNPs associated with fibroblastic disorders have been detected by iECAT-RC and the other two comparison methods, iECAT-Score and Internal. However, our method has a higher probability of identifying these significant SNPs in the scenario of an unbalanced case-control association study.

p21-activated kinase is involved in the sporulation, pathogenicity, and stress response of Arthrobotrys oligospora under the indirect regulation of Rho GTPase-activating protein.

The p21-GTPase-activated protein kinases (PAKs) participate in signal transduction downstream of Rho GTPases, which are regulated by Rho GTPase-activating proteins (Rho-GAP). Herein, we characterized two orthologous Rho-GAPs (AoRga1 and AoRga2) and two PAKs (AoPak1 and AoPak2) through bioinformatics analysis and reverse genetics in Arthrobotrys oligospora, a typical nematode-trapping (NT) fungus. The transcription analyses performed at different development stages suggested that Aopaks and Aorga1 play a crucial role during sporulation and trap formation, respectively. In addition, we successfully deleted Aopak1 and Aorga1 via the homologous recombination method. The disruption of Aopak1 and Aorga1 caused a remarkable reduction in spore yield and the number of nuclei per cell, but did not affect mycelial growth. In ∆Aopak1 mutants, the trap number was decreased at 48 h after the introduction of nematodes, but nematode predatory efficiency was not affected because the extracellular proteolytic activity was increased. On the contrary, the number of traps in ∆Aorga1 mutants was significantly increased at 36 h and 48 h. In addition, Aopak1 and Aorga1 had different effects on the sensitivity to cell-wall-disturbing reagent and oxidant. A yeast two-hybrid assay revealed that AoPak1 and AoRga1 both interacted with AoRac, and AoPak1 also interacted with AoCdc42. Furthermore, the Aopaks were up-regulated in ∆Aorga1 mutants, and Aorga1 was down-regulated in ∆Aopak1 mutants. These results reveal that AoRga1 indirectly regulated AoPAKs by regulating small GTPases.

Improving mesophilic anaerobic digestion of food waste by side-stream thermophilic reactor: Activation of methanogenic, key enzymes and metabolism.

Anaerobic digestion (AD) is a favorable way to convert organic pollutants, such as food waste (FW), into clean energy through microbial action. This work adopted a side-stream thermophilic anaerobic digestion (STA) strategy to improve a digestive system's efficiency and stability. Results showed that the STA strategy brought higher methane production as well as higher system stability. It quickly adapted to thermal stimulation and increased the specific methane production from 359 mL CH4/g·VS to 439 mL CH4/g·VS, which was also higher than 317 mL CH4/g·VS from single-stage thermophilic anaerobic digestion. Further exploration of the mechanism of STA using metagenomic and metaproteomic analysis revealed enhanced activity of key enzymes. The main metabolic pathway was up-regulated, while the dominant bacteria were concentrated, and the multifunctional Methanosarcina was enriched. These results indicate that STA optimized organic metabolism patterns, comprehensively promoted methane production pathways, and formed various energy conservation mechanisms. Further, the system's limited heating avoided adverse effects from thermal stimulation, and activated enzyme activity and heat shock proteins through circulating slurries, which improved the metabolic process, showing great application potential.

Molecular mechanism of the miR-7/BCL2L1/P53 signaling axis regulating the progression of hepatocellular carcinoma.

Background: To investigate the roles of miR-7 and its potential mechanisms in hepatocellular carcinoma (HCC). Methods: The functions of miR-7 were identified and measured by MTT [3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide], colony formation, transwell, and flow cytometry assays. A luciferase assay was applied to verify the direct binding of miR-7 on BCL2L1 3'untranslated region (3'UTR). An in vitro experiment was then used to investigate the biological effects of miR-7 and BCL2L1. A co-immunoprecipitation (COIP) assay was used to detect the protein interaction between BCL2L1 and P53. Results: We found that miR-7 overexpression suppressed cell proliferation, migration, and invasion in HCC. BCL2L1 was also demonstrated as a direct target gene of miR-7. This study showed that BCL2L1 could partially rescue the inhibitory effect of miR-7 on the proliferation, migration, and invasion of HCC cells. Our research showed that miR-7 could inhibit the epithelial-mesenchymal transition (EMT) pathway by regulating BCL2L1. We also further confirmed that miR-7 inhibits the proliferation, migration, and invasion of Hep3B and Huh7 cells by targeting BCL2L1. Furthermore, we observed that the BCL2L1 protein interacts with the P53 protein and BCL2L1 affects the development of liver cancer through P53. We also found that BCL2L1 could promote the invasion and migration of liver cancer cells through P53 inhibition. BCL2L1 also inhibited the expression of Caspase 3/7 in hepatoma cells by inhibiting the expression of P53. Conclusions: Our study demonstrated that miR-7/BCL2L1/P53 may serve as a regulatory molecular axis for HCC treatment. Our results suggest that miR-7/BCL2L1/P53 may have predictive value and represent a new treatment strategy for liver cancer.

Clinical study of the value of shear wave elastography in evaluating the degree of liver fibrosis in children.

OBJECTIVES: To explore the clinical application of shear wave elastography (SWE) in evaluating the degree of liver fibrosis in children. METHODS: To explore the value of SWE in assessing liver fibrosis in children, the correlation between elastography values and the METAVIR grade of liver fibrosis in children with biliary system or liver diseases was studied. Children with significant liver enlargement were enrolled, and the fibrosis grade was analyzed to explore the value of SWE in assessing the degree of liver fibrosis in the presence of significant liver enlargement. RESULTS: A total of 160 children with bile system or liver diseases were recruited. The areas under the receiver operating characteristic curve (AUROCs) for liver biopsy from stage F1 to F4 were 0.990, 0.923, 0.819, and 0.884. According to the degree of liver fibrosis at liver biopsy, there was a high correlation between the SWE value and the degree of liver fibrosis (correlation coefficient 0.74). There was no significant correlation between the Young's modulus value of the liver and the degree of liver fibrosis (correlation coefficient 0.16). CONCLUSIONS: Supersonic SWE can generally accurately evaluate the degree of liver fibrosis in children with liver disease. However, When the liver is significantly enlarged, SWE can only evaluate liver stiffness based on Young's modulus values, and the degree of liver fibrosis must still be determined by pathologic biopsy.

The Application of Carbon Nanomaterials in Sensing, Imaging, Drug Delivery and Therapy for Gynecologic Cancers: An Overview.

Gynecologic cancers are one of the main health concerns of women throughout the world, and the early diagnosis and effective therapy of gynecologic cancers will be particularly important for the survival of female patients. As a current hotspot, carbon nanomaterials have attracted tremendous interest in tumor theranostics, and their application in gynecologic cancers has also been developed rapidly with great achievements in recent years. This Overview Article summarizes the latest progress in the application of diverse carbon nanomaterials (e.g., graphenes, carbon nanotubes, mesoporous carbon, carbon dots, etc.) and their derivatives in the sensing, imaging, drug delivery, and therapy of different gynecologic cancers. Important research contributions are highlighted in terms of the relationships among the fabrication strategies, architectural features, and action mechanisms for the diagnosis and therapy of gynecologic cancers. The current challenges and future strategies are discussed from the viewpoint of the real clinical application of carbon-based nanomedicines in gynecologic cancers. It is anticipated that this review will attract more attention toward the development and application of carbon nanomaterials for the theranostics of gynecologic cancers.

IL-10 alleviates radicular pain by inhibiting TNF-α/p65 dependent Nav1.7 up-regulation in DRG neurons of rats.

BACKGROUND: Lumbar disc herniation (LDH) may induce radicular pain, the upregulation of voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) contributes to radicular pain by generating ectopic discharge of neurons, but the mechanism is unclear. Previously, we reported pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) up-regulated VGSCs in diabetic neuropathy. In this study, we explored the effect of anti-inflammatory cytokine interleukin-10 (IL-10) on radicular pain and the possible mechanisms. METHODS: Rat model of LDH was induced by implanting autologous nucleus pulposus (NP). Mechanical and thermal pain thresholds were assessed by von Frey filaments and hotplate test respectively. IL-10 and TNF-α level in DRG and cerebrospinal fluid (CSF) were assessed by Enzyme-linked immunosorbent assay (ELISA). IL-10 was intrathecally delivered for 12 days. The expression of IL-10R1 and sodium channel Nav1.7 was displayed by immunofluorescence staining. The protein level of TNF-α and p-p65 was measured by western blotting. RESULTS: NP implantation increased Nav1.7 expression in DRG neurons, decreased IL-10 level and increased TNF-α level in DRG and CSF. IL-10 significantly alleviated pain behaviors of rats with NP. IL-10R1 was co-localized with neurons but not with satellite cells in DRG. IL-10 decreased Nav1.7 and TNF-α/p-p65 expression in DRG of rats with NP. Co-administration of TNF-α with IL-10 counteracted the effect of IL-10 on pain behaviors, Nav1.7 and TNF-α/p-p65 expression of rats with NP. CONCLUSIONS: The study revealed that IL-10 alleviated radicular pain by inhibiting TNF-α/p-p65 dependent Nav1.7 up-regulation in DRG neurons.

Nitrogen and phosphorus emissions to water in agricultural crop-animal systems and driving forces in Hainan Island, China.

The NUFER (Nutrient Flow in food chains, Environment and Resources) model has been used to reliably quantify nitrogen (N) and phosphorus (P) emissions from agriculture land to water bodies. However, factors impacting agricultural N and P emissions at the island scale have rarely been studied due to the lack of high-resolution spatialization tools, which are critical for exploring mitigation options. Here, a high-resolution NUFER model was constructed based on geology, meteorology, land-use data, statistical data, and field investigation. The spatial characteristics of N and P emissions in Hainan Island, China, were quantified, and the driving forces were analyzed. We also explored effective measures to reduce emissions by 2035 using scenario analysis. Overall, 98 Gg N from agriculture entered water bodies in 2018, of which crop system contributed 70%; 15 Gg P entered water bodies, of which, animal system contributed 78%. Nitrate (NO3-) leaching (65%) and direct discharge of animal manure (69%) accounted for most of the N and P emissions, respectively. Plains contributed 89% of N and 92% of P emissions. Spatial overlay analysis showed that high N and P emissions were mainly concentrated in the western and northeastern plain areas. At the sub-basin scale, the Nandu River basin had the largest agricultural N and P emissions, accounting for more than 20% of all emissions. Scenario analysis showed that N and P emissions were significantly correlated with natural (e.g., elevation, slope, and soil texture) and anthropogenic (e.g., rural income, population density, planting structure, and livestock density) factors. We further analyzed the emissions of N and P can be reduced by 71 Gg and 14 Gg by 2035, respectively, via reducing food chain waste and consumption, importing more food, and improving production efficiency, but especially prohibiting the direct discharge of livestock manure. This high-resolution quantification of agricultural N and P emissions to the water bodies provides an exploration of the most effective options for reducing agricultural non-point source (ANPS) pollution at the island scale.

Strategy to enhance semi-continuous anaerobic digestion of food waste by combined use of calcium peroxide and magnetite.

Optimizing methane production from food waste (FW) efficiently is always a hot topic in the field of anaerobic digestion (AD). In this study we aimed to improve the conversion of organics to methane by using CaO2 and magnetite to enhance the semi-continuous AD of food waste. Under the organic load of 2.5 g VS/L·d-1, the specific methane yield was increased from 333.9 mL CH4/g·VS to 423.4 mL CH4/g·VS by adding 0.01 g/L CaO2 with 0.4 g/L magnetite, improving the production of methane from FW. We assessed reactor performance, ORP changes, mass balance, enzyme activities and characterized the metagenomic profile of microorganisms involved in digestion. These microorganisms showed rapid conversion of volatile fatty acids and increased expression of genes related to hydrolysis and acid production. Thus, the addition of CaO2 and magnetite optimized the relationship between fermentation bacteria and methanogenic archaea to enhance the overall production of methane. Microorganisms evolved unique adaptive mechanisms in the co-operative environment of CaO2 and magnetite, as their energy metabolism patterns combined those controlled by individual CaO2 and magnetite addition. This method of combining a micro-aeration environment with conductive materials provides a new perspective for optimizing the AD of FW.

Effect of elevated carbon dioxide on chicken eggs during the early and late incubation periods.

Carbon dioxide (CO2) is always maintained at ambient levels by ventilation in commercial egg incubators. However, elevated CO2 levels during the early and late periods have been reported to improve the quality of chicks and shorten the hatch window. This study investigated the effect of precise CO2 supplementation during the early and late periods of incubation on embryo growth and incubation performance by developing and using a CO2 supplementation system to increase the CO2 level in an experimental egg incubator. The CO2 level was maintained at 1% in the early period (from the beginning to the 10th day of incubation, E0-E10) and in the late period (from internal pipping (IP) to the 21st day of incubation (E21), IP-E21) in an incubator for the treatment group, whereas the CO2 level was maintained at the ambient level in the other incubators for the control group. A comparative assessment of embryonic development, hatching characteristics, and hormone and nutrient levels was conducted for each trial. The experiment comprised three trials, with 300 Jing Hong No. 1 breeding eggs in each incubator. The elevated CO2 treatment significantly shortened the chick hatching time (H0) by 4 h (P < 0.05) and the hatch window by 3 h (P < 0.05) without affecting hatchability, chick weight at 1 d of age, brooding period, or quality score. At external pipping (EP), the heart weight, intestinal weight, relative intestinal weight, and relative heart weight in the treatment group were significantly higher than those in the control group (P < 0.05). In addition, the embryonic intestine, relative intestine, and relative heart weights of the newly hatched chicks in the treatment group were significantly higher than those in the control group (P < 0.05) at H0. The treatment significantly increased the concentration of corticosterone in the embryonic plasma during the period from IP to EP (P < 0.05), promoted the secretion of triiodothyronine and tetraiodothyronine (P < 0.05), and increased the glycogen content of the embryonic liver on E21 (P < 0.05). This result indicates that elevated CO2 (1%) during the early and late periods of incubation accelerated embryonic organ development and shortened the chick hatching time and hatch window without affecting hatchability or hatchling quality, which can be explained by the synergistic functions of the secretion of plasma corticosterone and thyroid hormones and the accumulation of liver glycogen between the early and late periods of incubation.

Status of medication literacy and its related factors among undergraduate students in Shanxi Province, China: A cross-sectional study.

WHAT IS KNOWN AND OBJECTIVE: Medication safety problem has always been the focus of healthcare providers and public health community scholars. As the backbone of the future society, the mastery of college students' knowledge to use medicine will directly affect the level of medication literacy (ML) of the public in the future. The purpose of this study was to investigate the current ML of college students in Shanxi Province and to identify its related factors. METHODS: A cluster random sampling method was utilized to select 800 college students from 10 universities in Shanxi province as participants from 21 March to 10 April 2020. After quality control, 763 valid questionnaires were collected (effective rate 95.4%). This study applied the ML scale adapted from the 14-item health literacy scale (HLS-14) to estimate ML, which contains functional ML, communicative ML and critical ML dimensions to estimate the ML situation. Then, we used structural equation modelling (SEM) to test the hypothesized relationship among three dimensions of ML, self-evaluated health status and safety medication science popularization activities on campus. RESULTS AND DISCUSSION: The results showed that the reliability and validity of the ML scale were good. The average score of ML level of college students in Shanxi Province was 44 points, and the interquartile range was 40-48 points (full score is 65 points). The proportion of high ML level was estimated at as low as 26.7%. 73.1% participants had an average level, and only 1 participant (0.1%) had a low level of ML. Univariate analysis showed that the ML level was significantly influenced by gender, universities, field of study, academic performance and ethnic group (p < 0.05). SEM showed that functional ML (λ = 0.01) and communicative ML (λ = 0.75) had a direct positive association with critical ML. Meanwhile, the model also had a mediating effect. Functional ML had an indirect positive association with critical ML through the mediating effect of communicative ML (λ = 0.11). In addition, both self-evaluated health status and safety medication science popularization activities on campus had an indirect positive association with critical ML through the mediating effect of functional ML and communicative ML. WHAT IS NEW AND CONCLUSION: The study revealed that the ML of most college students in Shanxi Province was at the average level. Among them, medical college student (including pharmacy, nursing, public health, preventive medicine, basic medicine and clinical medicine students), the Han nationality students (the students of China's majority ethnic group), students of good self-evaluated health status, and students who were more exposed to safety medication science popularization activities had a relatively higher ML level. Moreover, it highlighted the importance of self-evaluated health status and safety medication science popularization activities on campus to ML.

The Effect of Melatonin on Radicular Pain in a Rat Model of Lumbar Disc Herniation.

STUDY DESIGN: Controlled, randomized, animal study. OBJECTIVE: To investigate the effect of melatonin and its receptors on radicular pain and the possible mechanisms. SUMMARY OF BACKGROUND DATA: Lumbar disc herniation (LDH) may induce radicular pain, but the mechanism is not clear and therapeutic effect is still poor. Previously we report central sensitization meaning potentiation of spinal nociceptive synaptic transmission is the critical cause of radicular pain. Melatonin (Mel) has been reported to promote hippocampal synaptic transmission and thus improve learning ability. But the effect of Mel on spinal synaptic transmission and radicular pain are not clear. METHODS: Rat LDH model was induced by autologous nucleus pulposus (NP) implantation. Melatonin was delivered intraperitoneally four times a day, from day 1 to day 3 after surgery. Melatonin receptor agonist and antagonists were delivered intrathecally for 3 days as well. Mechanical and thermal pain thresholds were assessed by von Frey filaments and hotplate test respectively. Electrophysiological recording was employed for survey C-fiber evoked field potentials. The protein level of N- methyl-D-aspartate submit 2A (NR2A), NR2B, melatonin receptor 1 (MT1), and receptor 2 (MT2) was evaluated by western blotting. Spinal expression of calcitonin gene related peptides (CGRP), isolectin b4 (IB4), and neurofilament-200 (NF200) was displayed by immunofluorescence staining. RESULTS: Melatonin significantly increased mechanical and thermal pain thresholds, lasting at least to day 5 after surgery. Melatonin decreased C-fiber evoked field potentials; decreased spinal NR2B protein level; reduced spinal CGRP, and IB4 expression. MT2 was upregulated after NP implantation and was co-localized with neuron and microglia. MT2 receptor agonist simulated the effect of Mel, and both MT receptor broadspectrum antagonist and MT2 specific antagonist abolished the effect of MT2 receptor agonist. CONCLUSION: Melatonin alleviates radicular pain from LDH by inhibiting central sensitization via binding with its receptor 2, decreasing spinal CGRP, IB4, and NR2B expression.

A systemic review and meta-analysis on the efficacy and safety of ferumoxytol for anemia in chronic kidney disease patients.

PURPOSE: To evaluate the efficacy of ferumoxytol, relative to conventional iron supplement formulations, on hemoglobin levels, ferritin level, and adverse event incidence in chronic kidney disease patients. METHODS: We performed a systematic search of six academic databases (EMBASE, CENTRAL, Scopus, PubMed, Web of sciences, and MEDLINE), adhering to PRISMA guidelines. We performed a meta-analysis on relevant studies to evaluate the overall influence of ferumoxytol, relative to conventional iron supplement formulations, on hemoglobin levels, ferritin level, and treatment related treatment emergent adverse events (TEAEs) incidence in chronic kidney disease patients. RESULTS: Seven eligible studies were identified from a total of 1397 studies. These studies contained data on 3315 participants with chronic kidney disease (mean age: 59.2 ± 4.6 years). A meta-analysis revealed that ferumoxytol administration had positive effects on hemoglobin levels (Hedge's g statistic: 0.51) and ferritin level (0.88), transferrin saturation (0.39). Besides, we also report reduced incidence of treatment related TEAEs (-0.24) for patients consuming ferumoxytol as compared conventional iron supplement formulations. CONCLUSIONS: This meta-analysis provides preliminary evidence that ferumoxytol use exerts beneficial effects on the overall hematological outcomes in patients with chronic kidney disease. This study also reports improved treatment related safety profile for ferumoxytol when compared with conventional iron formulations. The findings from this study can have direct implications in forming best practice guidelines for managing anemia in patients with chronic kidney disease.