On the Precise and Continuous Regulation of the Superatomic and Spectroscopic Behaviors of the Quasi-Cubic W4C4 Cluster by the Oriented External Electric Field.

Designing and realizing novel superatoms with controllable and tunable electronic properties is vital for their potential applications in cluster-assembly nanomaterials. Here, we investigated the effect of the oriented external electric field (OEEF) on the geometric and electronic structures as well as the spectroscopic properties of the quasi-cubic W4C4 cluster by utilizing the density functional theory (DFT) calculations. Compared with traditional models, the OEEF was observed to hold the special capability in continuously and precisely modulating the electronic properties of W4C4, that is, remarkably increasing its electron affinity (EA) (1.58 eV) to 5.61 eV under the 0.040 au OEEF (larger than any halogen atoms in the periodic table), which possesses the superhalogen behavior. Furthermore, the downward movement of the lowest unoccupied molecular orbital level of the cluster accompanied by the enhancement of the OEEF intensity was demonstrated to be the origin of the EA increment. Additionally, the photoelectron spectra (PES) of W4C4- were also simulated under different OEEF intensities, where the PES peaks move to a higher energy area following the enhancement of the OEEF strength, exhibiting the blue-shift behavior. These findings observed here open a new avenue in conveniently and precisely adjusting the electronic properties of clusters, which will be beneficial for the rational design of superatoms or superatom-assembled nanomaterials under the external field.

Exogenous administration of chronic corticosterone affects hepatic cholesterol metabolism in broiler chickens showing long or short tonic immobility.

Tonic immobility (TI) is an innate characteristic of animals related to fear or stress response. Animals can be classified into long TI (LTI) and short TI (STI) phenotypes based on TI test duration. In this study, effect of TI phenotype, chronic corticosterone administration (CORT), and their interaction on cholesterol metabolism in liver was evaluated in broilers. LTI broilers showed higher level of cholesterol in liver compared to STI chickens (p<0.05), and CORT significantly increased hepatic cholesterol content (p<0.01). Real-time PCR results showed that both TI and CORT potentially altered ABCA1 and CYP7A1 gene expressions (0.05

Cholesterol deregulation induced by chronic corticosterone (CORT) stress in pectoralis major of broiler chickens.

Chronic endogenous glucocorticoid (GC) excess in mammals is associated with metabolic dysfunction and dyslipidemia that are characterized by increased plasma triglyceride and total cholesterol (Tch) levels. However, the effects of chronic GC administration on cholesterol metabolism, particularly in muscle tissues of broiler chickens, are unknown. In this study, broiler chickens were treated chronically with vehicle (CON) or corticosterone (CORT) for 2 weeks. Chronic CORT treatment significantly increased Tch levels in pectoralis major muscle (PMC) (p<0.001) as well as in leg muscle (p<0.01), and CORT enhanced triglyceride levels in the PMC (p<0.001). Real-time PCR results showed that HMGCR (p<0.05) mRNA expression was up-regulated by CORT in PMC, and 11ß-HSD1 gene transcription (p=0.08) was not significantly downregulated, whereas glucocorticoid receptor (GR) mRNA expression, 11ß-HSD2, CYP7A1, CYP27A1, ApoB and LDLR were unchanged by CORT (p>0.05). Western blot results showed that the levels of total GR (p=0.08) tended to be increased and nuclear GR protein (p<0.05) was increased in PMC by CORT administration. Parallel to an increase in gene expression, HMGCR protein expression in PMC was significantly increased (p<0.05) by CORT. Moreover, LDLR (p<0.05), ApoA1 (p=0.06) and 11ß-HSD2 (p=0.07) protein expression in PMC tended to be increased by CORT compared to control. These results indicate that chronic CORT administration causes cholesterol accumulation in PMC tissues of broiler chickens by increasing cholesterol synthesis and uptake.

Effects of tonic immobility (TI) and corticosterone (CORT) on energy status and protein metabolism in pectoralis major muscle of broiler chickens.

Tonic immobility (TI), which can be divided into short (STI) or long (LTI) duration, is a character related to fear. Our previous study has demonstrated LTI phenotype and chronic corticosterone (CORT) administration retarded growth of breast muscle in broiler chickens. In order to investigate the mechanism behind the negative effects of LTI and CORT on growth, the level of mRNA transcription of several key genes linked to energy and protein metabolism was measured in muscle. LTI broilers showed lower levels of ATP, energy charge (EC) (p<0.01), and lower muscle glycogen content (p<0.05) but higher level of ADP (p = 0.08) than STI birds. CORT treatment elevated EC level (p<0.05) and reduced liver glycogen content (p<0.05). Real-time PCR results showed that STI chickens had higher mRNA expression of PPAR α (p = 0.06) and AMPK α (p = 0.09) than LTI. CORT significantly down-regulated α-enolase mRNA expression in breast muscle compared to control (p<0.05). Neither TI nor CORT altered gene expression in Akt/mTOR/p70s6k cascade pathway in muscle (p > 0.05). However, western blot results showed that LTI chickens exhibited higher protein content of total Akt (p = 0.05) and phosphorylated Akt (p = 0.06) than STI. CORT treatment decreased the total protein content of Akt (p = 0.09) and p70s6k (p = 0.08). These results suggest that the retardation of muscle growth by LTI and chronic CORT administration parallels a strong alternation in energy status but slight changes of Akt/mTOR/p70s6k cascade, indicating that a decrease in muscle growth induced by LTI and CORT might not be mediated through mTOR-dependent signaling pathways.

Comparative proteomic analysis of the breast muscle response to chronic corticosterone administration in broiler chickens showing long or short tonic immobility.

Broilers of the same genetic origin were classified as short or long tonic immobility duration (STI and LTI, respectively) phenotypes and treated chronically with vehicle (control) or corticosterone (CORT) dissolved in drinking water between 27 and 42 d of age. Differential expression of proteins and mRNA was examined using 2-dimensional gel electrophoresis and real-time PCR to elucidate the mechanism behind the severe retardation of broiler breast muscle growth caused by LTI and CORT. The majority of the 13 proteins found to be differentially expressed in breast muscle of STI and LTI broilers are involved in either glycolysis (5 proteins) or myofilament formation (5 proteins). Of the 16 proteins differentially expressed in breast muscle following CORT treatment, 6 are structural proteins, 5 are categorized as cellular defense and stress proteins, and 3 (pyruvate kinase, l-lactate dehydrogenase, and creatine kinase) are involved in responses to stress and muscle damage. Real-time PCR results indicated that expression of these proteins is transcriptionally and posttranscriptionally regulated. Protein synthesis capacity, estimated by the RNA-to-protein ratio, was significantly lower in the breast muscle of CORT-treated broilers than in untreated control broilers. The level of Leu, Gly, and Ser in serum was significantly higher in CORT-treated broilers than in the control birds. Therefore, we conclude that CORT treatment retards the growth of skeletal muscle by suppressing protein synthesis and augmenting protein catabolism, paralleling the response to severe stress and muscle damage, and the negative effect of LTI on muscle growth is likely mediated through glucose metabolism. No interaction was observed between CORT and tonic immobility affecting growth performance or any parameter examined in the current study.

An adolescent female African elephant (Loxodonta africana) gave birth to an abnormal calf.

Maternal nutrition and the uterine environment can influence placental development in mammals, leading to the birth of abnormal infants who often experience difficulties in independent standing. This article documents an adolescent female African elephant (Loxodonta africana) giving birth to an African elephant calf with a shoulder height below the mean, and its inability to stand for the first 10 h after birth, a time span that significantly exceeds the average duration for independent standing. Through the implementation of assisted feeding and assisted standing measures, the calf eventually achieved independent standing and nursing from its mother after 27 h and subsequent catch-up growth at 5 months of age. This study presents the first case report on the growth parameters during pregnancy of an adolescent African elephant, the birth and care (feeding, assisted standing) of a small African elephant calf with the inability to stand alone and nurse independently for several hours, highlighting pregnancy may influence the growth of cows during their ongoing growth and development phase, the calf's survival and subsequent catch-up growth at 5 months of age. These findings offer valuable insights into the care of abnormal African elephant calves.

Genome-wide investigation of HD-ZIP gene family and functional characterization of BnaHDZ149 and BnaHDZ22 in salt and drought response in Brassica napus L.

HD-ZIP proteins comprise a plant-specific transcription factor family, which play pivotal roles in plant development and adaptation to ever-changing environment. Although HD-ZIP family members have been identified in some plant species, so far our knowledge about HD-ZIP genes in rapeseed is still limited. In this study, 178 Brassica napus HD-ZIP (BnaHDZ) family members were identified in the rapeseed genome. The phylogenetic relationship, chromosomal locations, intron-exon structures, motif composition, and expression patterns of the BnaHDZ members were analyzed. The BnaHDZ family can be phylogenetically divided into four categories (Ⅰ, Ⅱ, Ⅲ and Ⅳ). Genome-wide transcriptome analysis revealed that most of the HD-ZIP I members respond to at least one abiotic stress. Two closely homologous stress-responsive HD-ZIP Ⅰ genes, BnaHDZ22 and BnaHDZ149, were identified to be involved in drought and salt responses, and selected for further functional characterization. Overexpressing BnaHDZ149 in rapeseed increased salt sensitivity of the transgenic plants, whereas overexpressing BnaHDZ22 increased sensitivity of the transgenic plants to polyethylene glycol (PEG)-simulated drought stress. This research provides not only a comprehensive landscape of BnaHDZ genes, but also a theoretical basis for elucidating the molecular mechanism of the abiotic stress responses of the HD-ZIP family in rapeseed.

Factors contributing to learning satisfaction with blended learning teaching mode among higher education students in China.

Blended learning has increasingly grown in importance as a method of classroom instruction in Chinese higher education classrooms in the context of fast-evolving network information technology, higher standards of educational informatization, and growing attention to the reform of teaching modes in higher education. The efficiency of blended learning can be increased by better understanding the students' learning satisfaction and its key influencing factors. Based on the theories of constructivism and phenomenology, the study constructs an index system of student satisfaction with blended learning in higher education, and conducts a questionnaire survey on 650 students with blended learning experience in 6 universities in Sichuan Province, China, obtaining 598 valid questionnaires after reviewing the collected questionnaires for missing values. This study uses descriptive statistical analysis (DSA), one-way ANOVA, Pearson correlation analysis, and multiple linear regression (MLR) to analyze the effects of each factor in the index system on satisfaction. Results indicate that the overall level of student satisfaction with blended learning in universities is moderately high, with students' self-satisfaction being the lowest, and that substantial disparities exist in the evaluation of satisfaction with blended learning on various online resources, online teaching forms, and offline teaching methods. This study applies multiple linear regression (MLR) to conclude that students' learning attitudes, curriculum design, and teachers' teaching methods are the most important factors influencing satisfaction with blended learning in universities. Results indicate that a blended learning system be built from the three dimensions of students, teachers, and curriculum, offering a theoretical foundation and point of reference for the ongoing reform of blended learning in higher education. The study is of great significance in optimizing teaching quality and deepening the reform of blended learning.

Research progress on source, risk assessment, and management of emerging pollutants in drinking water.

With the extensive production and use of various chemicals, emerging pollutants including environmental endocrine disrupting chemicals, perfluoro chemicals, antibiotics, and microplastics have been continuously entering the environment, and spread to water through multiple pathways. The pollution of these emerging pollutants raised continuous concerns for the safety of drinking water, threating the ecological environment and human health. In combination with international research progress, we discussed in detail about pollution, source, and risk assessment of emerging pollutants in drinking water. We further suggested and prospected the challenge of environmental management of emerging pollutants. This review could promote the public's understanding of emerging pollutants, and provide theoretical support for risk prevention and treatment of emerging pollutants in drinking water.

Unraveling the influence of human fecal pollution on antibiotic resistance gene levels in different receiving water bodies using crAssphage indicator gene.

Discharged wastewater treatment plant (WWTP) effluents can contaminate receiving water bodies with human feces and alter the abundance of antibiotic resistance genes (ARGs). In this study, we examined the co-occurrence of ARGs, human fecal pollution indicator crAssphage, and antibiotics in human feces and a series of connected receiving water bodies affected by human feces, including water from different treatment units of a WWTP, river, lake, and tap waters. Results showed that crAssphage was detected in 68.2 % of the studied water bodies, confirming widespread human fecal contamination. Both ARG and crAssphage abundances exhibited a distance-decay effect from the emission source to the receiving environment. Interestingly, the detected ARG abundance in the water bodies was significantly correlated with crAssphage abundance but not with the residual antibiotic concentration, demonstrating that the presence of ARG could largely be explained by the extent of fecal pollution, with no clear signs of antibiotic selection. In addition, 14 ARGs co-shared by human feces and water bodies were significantly correlated with crAssphage. Furthermore, a close evolutionary relationship was observed between the blaTEM-1 gene from human feces and aquatic environments. These results imply a potential ARG exchange between human feces and receiving water bodies. Overall, this study provides important insights into the distribution and sources of ARGs in water bodies affected by human fecal contamination.

RNA demethylase ALKBH5 suppresses tumorigenesis via inhibiting proliferation and invasion and promoting CD8+ T cell infiltration in colorectal cancer.

BACKGROUND: ALKBH5 belongs to the ALKB family consists of a Fe (II) and a-ketoglutarate-dependent dioxygenase. ALKBH5 directly catalyzes the oxidative demethylation of m6A-methylated adenosine. ALKBH5 involves in tumorigenesis and tumor progression, and is often dysregulated in a wide range of cancers, including colorectal cancer. Emerging evidence indicates that the expression of ALKBH5 is associated with the abundance of infiltrating immune cells in the microenvironment. However, how ALKBH5 affects immune cell infiltration in the microenvironment in colorectal cancer (CRC) has not been reported. The aim of this study was to identify how the expression of ALKBH5 affects the biological behaviors of CRC cell lines and regulates the effects on infiltrating CD8+ T cells in CRC microenvironment with its specific mechanism. METHODS: Firstly, the transcriptional expression profiles of CRC were downloaded from TCGA database and integrated via R software (4.1.2). Between CRC and normal colorectal tissues, ALKBH5 mRNA expressions were compared (Wilcoxon rank-sum). We further identified the expression levels of ALKBH5 in CRC tissues and cell lines through quantitative PCR, western blot, and immunohistochemistry. Then, how ALKBH5 affects the biological behaviors of CRC cells were confirmed by gain- and loss-of-function analysis. Furthermore, the relationship between ALKBH5 level and 22 tumor-infiltrating immune cells was examined through CIBERSORT in R software. Furthermore, we explored the correlation between ALKBH5 expression and tumor-infiltrated CD8+, CD4+ and regulatory T cells by utilizing the TIMER database. Finally, the association between chemokines and CD8+ T cells infiltration in CRC was analyzed using GEPIA online database. qRT-PCR, WB and IHC were used to further determine the effect of ALKBH5 on NF-κB-CCL5 signaling axis and CD8+ T cells infiltration. RESULTS: Clinically, ALKBH5 expression was downregulated in CRC and low levels of ALKBH5 expression were correlated with poor overall survival (OS). Functionally, overexpression of ALKBH5 reduced the proliferation, migration and invasion of CRC cells, and vice versa. Overexpression of ALKBH5 suppresses NF-κB pathway, thus reduces CCL5 expression and promotes CD8+ T cells infiltration in CRC microenvironment. CONCLUSIONS: ALKBH5 is poorly expressed in CRC, and overexpression of ALKBH5 attenuates CRC malignant progression by inhibiting CRC cell proliferation, migration, invasion and promoting CD8+ T cells infiltration in the tumor microenvironment through NF-κB-CCL5 axis.

The miR169n-NF-YA8 regulation module involved in drought resistance in Brassica napus L.

As an ancient and conserved plant microRNA (miRNA) family, miR169 targets nuclear factor Y subunit alpha (NF-YA) family members. The miR169-NF-YA module is associated with plant development and various stress responses. However, the function of miR169 in response to drought stress in rapeseed (Brassica napus L.) is unclear. In the present study, we showed that miR169n acted as a negative regulator of drought resistance in rapeseed by targeting a nuclear factor Y-A gene, NF-YA8. miR169n was strongly down-regulated by drought stress. Expression of a miR169n target mimicry construct (MIM169n) which functioned as a sponge to trap miR169n resulted in enhanced resistance of transgenic plants to both osmotic stress at the post-germination stage and drought stress at the seedling stage. MIM169n plants had a higher relative water content (RWC) and proline content, lower relative electrolyte leakage (REL), and showed higher antioxidative capability compared with those of control (CK) plants under drought stress. Moreover, NF-YA8 was verified as a target of miR169n, and overexpression of NF-YA8 led to improved tolerance of rapeseed to osmotic stress at the post-germination stage. Overall, our findings implied that the miR169n-NF-YA8 regulatory module could serve as a potential target for genetic improvement of drought resistance in B. napus.

Colistin and amoxicillin combinatorial exposure alters the human intestinal microbiota and antibiotic resistome in the simulated human intestinal microbiota.

Antibiotics treatment could cause the dysbiosis of human intestinal microbiota and antibiotic resistome. Fecal microbiota transplantation (FMT) has been an efficacious treatment to restore the dysbiosis of intestinal microbiota in a variety of intestinal diseases. However, to data, the effect of the combinatorial antibiotic treatment on microbiota, antibiotic resistome and the FMT for restoration affected by combinatorial antibiotic exposure in the human intestinal microbiota remain unclear. In this study, we systematically investigated the effect of the colistin and amoxicillin combinatorial exposure in the simulator of the human intestinal microbial ecosystem (SHIME) and found that this combinatorial exposure significantly altered (p < 0.05) the human intestinal microbiota and antibiotic resistome. The shift of bacterial community and antibiotic resistome could incompletely recovery to baseline by FMT treatment after combinatorial antibiotic exposure. Additionally, the variance of antibiotic resistome was dominantly driven by the bacterial community (41.18%-68.03%) after the combinatorial antibiotic exposure. Overall, this study first to investigate the influence of the colistin and amoxicillin combinatorial exposure on the intestinal microbiota and antibiotic resistome, and assess the FMT recovery in the simulated human intestinal microbiota, which may potentially provide a correct administration of antibiotics and application of FMT in the clinic.

The prolonged disruption of a single-course amoxicillin on mice gut microbiota and resistome, and recovery by inulin, Bifidobacterium longum and fecal microbiota transplantation.

The usages of antibiotics in treating the pathogenic infections could alter the gut microbiome and associated resistome, causing long term adverse impact on human health. In this study, mice were treated with human-simulated regimen 25.0 mg kg-1 of amoxicillin for seven days, and their gut microbiota and resistome were characterized using the 16S rRNA amplicons sequencing and the high-throughput qPCR, respectively. Meanwhile, the flora restorations after individual applications of inulin, Bifidobacterium longum (B. longum), and fecal microbiota transplantation (FMT) were analyzed for up to 35 days. The results revealed the prolonged negative impact of single course AMX exposure on mice gut microbiota and resistome. To be specific, pathobionts of Klebsiella and Escherichia-Shigella were significantly enriched, while prebiotics of Bifidobacterium and Lactobacillus were dramatically depleted. Furthermore, ß-lactam resistance genes and efflux resistance genes were obviously enriched after amoxicillin exposure. Compared to B. longum, FMT and inulin were demonstrated to preferably restore the gut microbiota via reconstituting microbial community and stimulating specific prebiotic respectively. Such variation of microbiome caused their distinct alleviations on resistome alteration. Inulin earned the greatest elimination on AMX induced ARG abundance and diversity enrichment. FMT and B. longum caused remove of particular ARGs such as ndm-1, blaPER. Network analysis revealed that most of the ARGs were prone to be harbored by Firmicutes and Proteobacteria. In general, gut resistome shift was partly associated with the changing bacterial community structures and transposase and integron. Taken together, these results demonstrated the profound disruption of gut microbiota and resistome after single-course amoxicillin treatment and different restoration by inulin, B. longum and FMT.

Occurrence and distribution of clinical and veterinary antibiotics in the faeces of a Chinese population.

Antibiotics ingested in the human gut may create selective pressure to change the composition of the gut microbiota, which could adversely effect the immune system of the host. However, the occurrence and distribution of antibiotics in the human gut remains unclear. A total population of 180 individuals, across three Chinses regions with different economic development levels, including children, adults, and elders, were sampled in 2017. A total of 19 representative antibiotics, including both clinical and veterinary antibiotics, were investigated in human faeces. While clinical use and prescriptions were the main exposure pathways for children, environmental media were the exposure pathway to adults. In addition, significant differences (P < 0.05) in antibiotic residues in human faeces were observed amongst various economic development levels, where human faeces from underdeveloped areas were mostly associated with higher levels of antibiotics. This study first to investigate the occurrence and distribution of typical antibiotics in the faeces of a Chinese population and thereby provide a reference for the intensive study of the effects and mechanisms of antibiotics on human gut microbiota.

Gut resistomes, microbiota and antibiotic residues in Chinese patients undergoing antibiotic administration and healthy individuals.

Human gut microbiota is an important reservoir of antibiotic resistance genes (ARGs). Although dysbacteriosis after the antibiotic course has been previously observed in the patient guts, a comprehensive comparison of gut resistomes, microbiota and antibiotic residues in healthy individuals and patients undergoing antibiotic administration is little. Using high-throughput qPCR, 16S rRNA gene amplicon sequencing and UPLC-MS/MS, we systematically examined the antibiotic resistome, gut microbiota, and antibiotic residues in fecal samples from both Chinese healthy individuals and patients receiving antibiotic therapy. Compared with healthy individuals, patients' guts harbored lower diverse gut resistome and microbiota, but higher concentrations of antibiotics and ARGs. Antibiotic concentration in human guts was positively correlated with ARG total abundance, but was negatively related to the diversity of both ARGs and bacterial communities, which demonstrated that antibiotic administration could shape the antibiotic resistomes and bacterial communities in the patient guts. Gene cfxA was evaluated as a potential biomarker to distinguish the patients receiving antibiotic therapy from the healthy individuals in China since its wide detection and significant enrichment in the guts of the patients. The detection of some veterinary antibiotics in human guts illustrated the potential transmission of antibiotic from the external environment to human via the food chain. The obtained results could help to better understand the influence of antibiotic therapy in shaping antibiotic reistomes and bacterial communities in Chinese individuals.

Human catalytic antibody Se-scFv-B3 with high glutathione peroxidase activity.

In order to generate catalytic antibodies with glutathione peroxidase (GPX) activity, we prepared GSH-S-2,4-dinitrophenyl t-butyl ester (GSH-S-DNPBu) as target antigen. Three clones (A11, B3, and D5) that bound specifically to the antigen were selected from the phage display antibody library (human synthetic VH + VL single-chain Fv fragment (scFv) library). Analysis of PCR products using gel electrophoresis and sequencing showed that only clone B3 beared intact scFv-encoding gene, which was cloned into the expression vector pPELB and expressed as soluble form (scFv-B3) in Escherichia coli Rosetta. The scFv-B3 was purified by Ni(2+)-immobilized metal affinity chromatography (IMAC). The yield of purified proteins was about 2.0-3.0 mg of proteins from 1 L culture. After the active site serines of scFv-B3 were converted into selenocysteines (Secs) with the chemical modification method, we obtained the human catalytic antibody (Se-scFv-B3) with GPX activity of 1288 U/micromol.