Hundred-Fold Enhancement in the Anomalous Hall Effect Induced by Hydrogenation.

The anomalous Hall effect (AHE) is one of the most fascinating transport properties in condensed matter physics. However, the AHE magnitude, which mainly depends on net spin polarization and band topology, is generally small in oxides and thus limits potential applications. Here, we demonstrate a giant enhancement of AHE in a LaCoO3-induced 5d itinerant ferromagnet SrIrO3 by hydrogenation. The anomalous Hall resistivity and anomalous Hall angle, which are two of the most critical parameters in AHE-based devices, are found to increase to 62.2 µΩ·cm and 3%, respectively, showing an unprecedentedly large enhancement ratio of ∼10000%. Theoretical analysis suggests the key roles of Berry curvature in enhancing AHE. Furthermore, the hydrogenation concomitantly induces the significant elevation of Curie temperature from 75 to 160 K and 40-fold reinforcement of coercivity. Such giant regulation and very large AHE magnitude observed in SrIrO3 could pave the path for 5d oxide devices.

Nanozyme-Based Biofuel Cell Ingeniously Coupled with Luminol Chemiluminescence System through In Situ Co-Reactant Generation for Dual-Signal Biosensing.

Classical luminol-based chemiluminescence (CL) is the process of emitting light enhanced by the addition of coreactant hydrogen peroxide (H2O2). To address the instability issue of H2O2 decomposition, herein, we proposed a nanozyme-based biofuel cell (BFC) ingeniously coupled with a luminol CL system via in situ generation of H2O2. Specifically, the gold nanoparticle (AuNP) nanozyme with glucose oxidase-like activity can act as the anodic enzyme of BFC to catalyze the oxidation of glucose to produce H2O2 and electrons. In this case, H2O2 as a coreactant enhanced the CL intensity and the cathode of the BFC obtained electrons to generate the open circuit voltage (EOCV) signals. As a result, a dual-signal biosensing platform was successfully constructed. Interestingly, the AuNPs-catalyzed system operates in an alkaline medium, which precisely meets the pH requirement for luminol luminescence. Such a BFC-CL system not only greatly lessens the effect of unstable exogenous H2O2 on the signal stability but also enhances the CL of luminol. Furthermore, both CL and EOCV signals present a positive correlation with the glucose concentration. Therefore, this novel BFC-CL system shows good performance for dual-signal biosensing, which would serve as a valuable guideline for the design and application of BFC-based self-powered or CL biosensors.

Extracellular vesicles derived from hypoxia-preconditioned bone marrow mesenchymal stem cells ameliorate lower limb ischemia by delivering miR-34c.

Hypoxic mesenchymal stem cell-derived extracellular vesicles (EVs) have been suggested as a promising therapy for various diseases. This study aims to determine the effect of EVs derived from bone marrow mesenchymal stem cells (BMMSCs) under hypoxia on lower limb ischemia and the underlying mechanism. Human BMMSCs were subjected to hypoxia or normoxia followed by the isolation of EVs. Nanoparticle trafficking analysis (NTA), transmission electron microscopy (TEM), and Western Blotting using corresponding markers were performed to confirm the EVs. The EVs from BMMSCs under hypoxia condition (Hyp-EVs) or normoxia condition (Nor-EVs) were subjected to hindlimb ischemia (HI) mice. MiR-34c expression in BMMSCs and BMMSC-EVs was detected. The role of miR-34c in regulating M2 macrophage polarization, as well as the target of miR-34c, were explored. HI mice with Hyp-EV treatment, as compared to the Nor-EV or the PBS group, had better blood flow and higher capillary density. MiR-34c expression was increased in BMMSCs, BMMSC-EVs, and the adductor muscle of HI mice. Hyp-EVs promoted the M2 macrophage polarization and anti-inflammatory cytokine production, and enhanced the blood flow and capillary density in HI mice, while the knockdown of miR-34c partly reversed these effects. PTEN is a target of miR-34c, and the PTEN silencing facilitated M2 macrophage polarization, whereas the inhibition of AKT signaling partly abolished the effect. Hyp-EVs promoted M2 macrophage polarization by delivering miR-34c via PTEN/AKT pathway, which could be a promising therapeutic strategy to ameliorate lower limb ischemia.

Anisotropic thermoelectric properties in hydrogenated nitrogen-doped porous graphene nanosheets.

By using density functional theory calculations combined with the nonequilibrium Green's function method and machine learning, we systematically studied the thermoelectric properties of four kinds of porous graphene nanosheets (PGNS) before and after nitrogen doping. The results show that the thermoelectric performance of porous graphene nanosheets along the armchair or zigzag chiral direction is improved due to the dramatically enhanced power factor caused by nitrogen doping. The calculated ZT values of nitrogen-doped porous graphene nanosheets are boosted by about one order of magnitude compared with those of undoped porous graphene nanosheets at room temperature. More importantly, an anisotropic thermoelectric transport is found in the nitrogen-doped porous graphene nanosheets. The results show that the ZT values of nitrogen-doped porous graphene nanosheets along the zigzag transport direction are nearly 11 times larger than those of them along the armchair transport direction. These results reveal that the thermoelectric properties of porous graphene nanosheets can be well regulated by nitrogen doping, and provide a good theoretical guidance for their application in thermoelectric devices.

The relationship between role ambiguity, emotional exhaustion and work alienation among chinese nurses two years after COVID-19 pandemic: a cross-sectional study.

BACKGROUND: work alienation is receiving increasing attention as a psychological risk at work, and little is known about the mechanisms of role ambiguity and work alienation in nurses in the context of the COVID-19 pandemic. This article aims to examine how role ambiguity affects work alienation among Chinese nurses during the two years after COVID-19 pandemic and verify emotional exhaustion as mediators. METHODS: A cross-sectional study design was used to recruit 281 Chinese nurses. Nurses completed online questionnaires containing demographic characteristics, role ambiguity, emotional exhaustion, and work alienation, and SPSS 26.0 and AMOS 24.0 were used for data analysis and structural equation modelling. RESULTS: work alienation scores were (34.64 ± 10.09), work alienation was correlated with role ambiguity and emotional exhaustion (r1 = 0.521, r2 = 0.755; p < .01), and role ambiguity was positively correlated with emotional exhaustion (r = 0.512; p < .01). A mediating effect of emotional exhaustion between role ambiguity and work alienation held (mediating effect of 0.288, 95% CI: 0.221-0.369, accounting for 74.8% of the total effect). CONCLUSION: Role ambiguity has a significant direct effect on nurses' feelings of alienation and exacerbates alienation through emotional exhaustion. Clarifying roles at work and being less emotionally drained are effective ways to reduce nurses' feelings of alienation.

The magnetic resonance characteristics of sinonasal rhabdomyosarcoma in adults: analysis of 27 cases and comparison with pathological subtypes.

BACKGROUND: Sinonasal rhabdomyosarcoma (RMS) in adults is extremely rare, and early diagnosis and treatment are crucial to improve the patient's prognosis. The purpose of this study was to evaluate the magnetic resonance imaging (MRI) findings of sinonasal RMS in adults and analyze the correlations between the imaging features and pathological subtypes. METHODS: We reviewed 27 patients with pathologically proven RMS of the nasal cavity and paranasal sinuses, including embryonal RMS (ERMS) in 14 patients, alveolar RMS (ARMS) in seven patients, and mixed-type RMS in six patients. Conventional MRI was performed in all 27 patients, and high-resolution diffusion-weighted imaging was conducted in 25 patients. The tumor location, size, morphological features, signal intensity, texture, contrast enhancement characteristics, lymph node metastases, apparent diffusion coefficients (ADCs), and involvement of local soft tissues were independently assessed by two authors. RESULTS: On MR imaging, sinonasal RMS appeared isointense on T1-weighted imaging in 21 cases (77.8%) and heterogeneously hyperintense on T2-weighted imaging in 18 patients (66.7%). After enhancement, the tumors were heterogeneously enhanced in 24 cases (88.9%). Botryoid enhancement with multiple small rings resembling bunches of grapes was found in 15 cases (55.6%). Mucosal invasion of the maxillary sinus was identified in 51.9% patients. Skull and orbit involvement were found in 55.6% and 81.5% patients, respectively. Lymph node metastasis was seen in 18 cases (66.7%). There were significant differences in botryoid enhancement (P = 0.044) and skull involvement (P = 0.044) among different histological subtypes. The mean ADC value of RMS was 0.73 ± 0.082 × 10-3 mm2/s, and there was no significant difference among different histological subtypes. CONCLUSIONS: Some characteristic MRI findings such as botryoid enhancement in the ethmoid sinus, involvement of the orbit and skull, and a lower ADC value can provide important clues for preoperative diagnosis of sinonasal RMS in adults. Further, botryoid enhancement was more common in ERMS, while skull involvement was more common in ARMS.

Mapping Yearly Fine Resolution Global Surface Ozone through the Bayesian Maximum Entropy Data Fusion of Observations and Model Output for 1990-2017.

Estimates of ground-level ozone concentrations are necessary to determine the human health burden of ozone. To support the Global Burden of Disease Study, we produce yearly fine resolution global surface ozone estimates from 1990 to 2017 through a data fusion of observations and models. As ozone observations are sparse in many populated regions, we use a novel combination of the M3Fusion and Bayesian Maximum Entropy (BME) methods. With M3Fusion, we create a multimodel composite by bias-correcting and weighting nine global atmospheric chemistry models based on their ability to predict observations (8834 sites globally) in each region and year. BME is then used to integrate observations, such that estimates match observations at each monitoring site with the observational influence decreasing smoothly across space and time until the output matches the multimodel composite. After estimating at 0.5° resolution using BME, we add fine spatial detail from an additional model, yielding estimates at 0.1° resolution. Observed ozone is predicted more accurately (R2 = 0.81 at the test point, 0.63 at 0.1°, and 0.62 at 0.5°) than the multimodel mean (R2 = 0.28 at 0.5°). Global ozone exposure is estimated to be increasing, driven by highly populated regions of Asia and Africa, despite decreases in the United States and Russia.

Engineering of a ß-galactosidase from Bacillus coagulans to relieve product inhibition and improve hydrolysis performance.

Most ß-galactosidases reported are sensitive to the end product (galactose), making it the rate-limiting component for the efficient degradation of lactose through the enzymatic route. Therefore, there is ongoing interest in searching for galactose-tolerant ß-galactosidases. In the present study, the predicted galactose-binding residues of ß-galactosidase from Bacillus coagulans, which were determined by molecular docking, were selected for alanine substitution. The asparagine residue at position 148 (N148) is correlated with the reduction of galactose inhibition. Saturation mutations revealed that the N148C, N148D, N148S, and N148G mutants exhibited weaker galactose inhibition effects. The N148D mutant was used for lactose hydrolysis and exhibited a higher hydrolytic rate. Molecular dynamics revealed that the root mean square deviation and gyration radius of the N148D-galactose complex were higher than those of wild-type enzyme-galactose complex. In addition, the N148D mutant had a higher absolute binding free-energy value. All these factors may lead to a lower affinity between galactose and the mutant enzyme. The use of mutant enzyme may have potential value in lactose hydrolysis.

Knockouts of a late flowering gene via CRISPR-Cas9 confer early maturity in rice at multiple field locations.

KEY MESSAGE: OsGhd7 gene was discovered by screening our rice activation tagging population. CRISPR-Cas9 created knockouts of OsGhd7 conferred early flowering and early maturity in rice varieties across multiple geographical locations in China. Our research shows that OsGhd7 is a good target for breeding early maturity rice varieties, and an excellent example of the advantages of applying the CRISPR-Cas9 technology for trait improvement. Flowering time (heading date) is an important trait for crop cultivation and yield. In this study, we discovered a late flowering gene OsGhd7 by screening our rice activation tagging population, and demonstrated that overexpression of OsGhd7 delayed flowering time in rice, and the delay in flowering time depended on the transgene expression level. OsGhd7 is a functional allele of the Ghd7 gene family; knockouts of OsGhd7 generated by CRISPR-Cas9 significantly accelerated flowering time and the earliness of the flowering time depended on field location. The homozygous OsGhd7 knockout lines showed approximately 8, 10, and 20 days earlier flowering than controls at three different locations in China (Changsha City, Sanya City, and Beijing City, respectively) that varied from 18.25° N to 39.90° N. Furthermore, knockouts of OsGhd7 also showed an early flowering phenotype in different rice varieties, indicating OsGhd7 can be used as a common target gene for using the CRISPR technology to modulate rice flowering time. The importance of OsGhd7 and CRISPR technology for breeding early maturity rice varieties are discussed.

A cytokinin-activation enzyme-like gene improves grain yield under various field conditions in rice.

KEY MESSAGE: CRISPR-edited variants at the 3'-end of OsLOGL5's coding sequence (CDS), significantly increased rice grain yield under well-watered, drought, normal nitrogen, and low nitrogen field conditions at multiple geographical locations. Cytokinins impact numerous aspects of plant growth and development. This study reports that constitutive ectopic overexpression of a rice cytokinin-activation enzyme-like gene, OsLOGL5, significantly reduced primary root growth, tiller number, and yield. Conversely, mutations at the 3'-end of OsLOGL5 CDS resulted in normal rice plant morphology but with increased grain yield under well-watered, drought, normal nitrogen, and low nitrogen field conditions at multiple geographical locations. Six gene edited variants (Edit A to F) were created and tested in the field. Edit-B and Edit-F plants increased, but Edit-D and Edit-E plants decreased, the panicle number per plant. All OsLOGL5-edited plants significantly increased seed setting rate, total grain numbers, full-filled grain numbers per panicle, and thousand seed weight under drought conditions, suggesting that OsLOGL5 is likely involved in the regulation of both seed development and grain filling processes. Our results indicate that the C-terminal end of OsLOGL5 protein plays an important role in regulating rice yield improvement under different abiotic stress conditions, and OsLOGL5 is important for rice yield enhancement and stability.

Dynamic changes in rumen fermentation and bacterial community following rumen fluid transplantation in a sheep model of rumen acidosis: implications for rumen health in ruminants.

Over the years, rumen fluid transplantation (RT) has been successfully applied to treat acute rumen acidosis in ruminants, but how it functions in the ruminal microbial homeostasis and host function remains largely unknown. Here, we investigated the dynamic changes of rumen fermentation and bacterial communities following RT and its beneficial effects on rumen epithelial morphology and function in a sheep model of rumen acidosis. The results showed that RT resulted in dynamic changes in rumen fermentation and increased the concentrations of total volatile fatty acid, acetate, propionate, and butyrate, but it decreased the levels of lactate and LPS in the rumen. Illumina MiSeq Sequencing data showed that RT facilitated rapid rebuilt of ruminal bacterial homeostasis (8 d in control vs. 2 d in RT) from a markedly dysbiotic acidosis state to a healthy level (similar with those of donors). At the genus level, RT increased the relative abundance of unclassified Bacteroidales, unclassified Prevotellaceae, unclassified Ruminococcaceae, and Acetitomaculum. Additionally, RT also accelerated recovery of the predicted metagenomic function of ruminal bacteria. Rumen papillae morphology results showed that RT alleviated the damage of rumen epithelia induced by acute rumen acidosis and increased the length of rumen papillae. Furthermore, real-time PCR results showed that RT modulated mRNA expression of genes related to cytokines and tight junctions in the rumen epithelia. In summary, these results reveal that RT accelerates recovery of rumen fermentation and bacterial homeostasis and modulates rumen epithelial morphology and function for sheep suffering from rumen acidosis.-Liu, J., Li, H., Zhu, W., Mao, S. Dynamic changes in rumen fermentation and bacterial community following rumen fluid transplantation in a sheep model of rumen acidosis: implications for rumen health in ruminants.

Design, synthesis and biological evaluation of mogrol derivatives as a novel class of AMPKα2ß1γ1 activators.

Adenosine monophosphate-activated protein kinase (AMPK) has been considered as a promising drug target for its regulation in both glucose and lipid metabolism. Mogrol was originally identified from high throughput screening as a small molecule activator of AMPK subtype α2ß1γ1. In order to enhance its potency on AMPK and summarize the structure-activity relationships, a series of mogrol derivatives were designed, synthesized and evaluated in pharmacological AMPK activation assays. The results showed that the amine derivatives at the 24-position can improve the potency. Among them, compounds 3 and 4 exhibited the best potency (EC50: 0.15 and 0.14 µM) which was 20 times more potent than mogrol (EC50: 3.0 µM).

Comparison of Different Slice Thicknesses in Computed Tomography for Labyrinthine Fistula Evaluation.

OBJECTIVES: The aim of the present study is to assess the impact of different slice thicknesses in computed tomography for labyrinthine fistula evaluation and to determine the appropriate slice thickness. METHODS: A total of 258 patients who underwent mastoidectomy and tympanoplasty for chronic otitis media with cholesteatoma from 2010 to 2014 were reviewed. The radiological diagnoses were compared with intraoperative findings. Sensitivity and specificity of 2.0-, 1.5-, 1.0-, and 0.75-mm-thick computed tomographic (CT) images for the evaluation of labyrinthine fistulae were calculated. Cohen's κ coefficient was also calculated. RESULTS: The sensitivities of 2.0-, 1.5-, 1.0-, and 0.75-mm-thick CT images for the evaluation of labyrinthine fistulae were 76.9, 86.5, 90.4, and 93.3% (observer 1) and 67.3, 76.0, 79.8, and 87.5% (observer 2), respectively. The specificities of 2.0-, 1.5-, 1.0-, and 0.75-mm-thick CT images for labyrinthine fistula evaluation were 96.1, 94.8, 95.5, and 95.5% (observer 1) and 99.4, 97.4, 95.5, and 94.8% (observer 2), respectively. Cohen's κ coefficients were 0.790, 0.788, 0.876, and 0.911 in 2.0-, 1.5-, 1.0-, and 0.75-mm-thick CT images, respectively. CONCLUSIONS: The sensitivity of CT for labyrinthine fistula evaluation increases with decreasing slice thickness, while the specificity does not improve.

Dissipation of Emamectin Benzoate Residues in Rice and Rice-Growing Environments.

The experiment developed the ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method for testing emamectin benzoate, and studied the metabolism of emamectin benzoate in rice plants and rice-growing environments via application of this testing method. The dissipation curve of emamectin benzoate standard substance was good at 0.5-200 µg L-1, and its correlation coefficient was greater than 0.99. In the concentration range of 0.1-50 µg kg-1, the average recovery rate of plants, soil, and field water was 82 %-102 %, and relative standard deviation (RSD) was between 0.3 % and 15.9 %. Half-lives in rice plants and soil were 0.8-2.8 days and 1.9-3.8 days, respectively, and emamectin benzoate was not detected in rice or rice hull. The experiment showed that emamectin benzoate is harmless to human health at the concentration recommended by the manufacturer.

Down-regulation of insulin-like growth factor binding protein 5 is involved in intervertebral disc degeneration via the ERK signalling pathway.

It is obvious that epigenetic processes influence the evolution of intervertebral disc degeneration (IDD). However, its molecular mechanisms are poorly understood. Therefore, we tested the hypothesis that IGFBP5, a potential regulator of IDD, modulates IDD via the ERK signalling pathway. We showed that IGFBP5 mRNA was significantly down-regulated in degenerative nucleus pulposus (NP) tissues. IGFBP5 was shown to significantly promote NP cell proliferation and inhibit apoptosis in vitro, which was confirmed by MTT, flow cytometry and colony formation assays. Furthermore, IGFBP5 was shown to exert its effects by inhibiting the ERK signalling pathway. The effects induced by IGFBP5 overexpression on NP cells were similar to those induced by treatment with an ERK pathway inhibitor (PD98059). Moreover, qRT-PCR and Western blot analyses were performed to examine the levels of apoptosis-related factors, including Bax, caspase-3 and Bcl2. The silencing of IGFBP5 up-regulated the levels of Bax and caspase-3 and down-regulated the level of Bcl2, thereby contributing to the development of human IDD. Furthermore, these results were confirmed in vivo using an IDD rat model, which showed that the induction of Igfbp5 mRNA expression abrogated the effects of IGFBP5 silencing on intervertebral discs. Overall, our findings elucidate the role of IGFBP5 in the pathogenesis of IDD and provide a potential novel therapeutic target for IDD.

General-Purpose Quantum Circuit Simulator with Projected Entangled-Pair States and the Quantum Supremacy Frontier.

Recent advances on quantum computing hardware have pushed quantum computing to the verge of quantum supremacy. Here, we bring together many-body quantum physics and quantum computing by using a method for strongly interacting two-dimensional systems, the projected entangled-pair states, to realize an effective general-purpose simulator of quantum algorithms. The classical computing complexity of this simulator is directly related to the entanglement generation of the underlying quantum circuit rather than the number of qubits or gate operations. We apply our method to study random quantum circuits, which allows us to quantify precisely the memory usage and the time requirements of random quantum circuits. We demonstrate our method by computing one amplitude for a 7×7 lattice of qubits with depth (1+40+1) on the Tianhe-2 supercomputer.

A novel thermostable ß-galactosidase from Bacillus coagulans with excellent hydrolysis ability for lactose in whey.

ß-Galactosidase is one of the most important enzymes used in dairy industry. Here, a novel thermostable ß-galactosidase was cloned and overexpressed from Bacillus coagulans NL01 in Escherichia coli. The phylogenetic trees were constructed using neighbor-joining methods. Phylogeny and amino acid analysis indicated that this enzyme belonged to family 42 of glycoside hydrolases. The optimal pH and temperature were, respectively, 6.0 and 55 to 60°C. The purified enzyme had a 3.5-h half-life at 60°C. Enzyme activity was enhanced by Mn2+. Compared with other ß-galactosidases from glycoside hydrolase family 42, B. coagulans ß-galactosidase exhibited excellent hydrolysis activity. The Michaelis constant (Km) and maximum rate of enzymatic reaction (Vmax) values for p-nitrophenyl-ß-d-galactopyranoside and o-nitrophenyl-ß-d-galactopyranoside were 1.06 mM, 19,383.60 U/mg, and 2.73 mM, 5,978.00 U/mg, respectively. More importantly, the enzyme showed lactose hydrolysis ability superior to that of the commercial enzyme. The specific enzyme activity for lactose was 27.18 U/mg. A total of 104.02 g/L lactose in whey was completely hydrolyzed in 3 h with addition of 2.38 mg of pure enzyme per gram of lactose. In view of the high price of commercial ß-galactosidase, B. coagulans ß-galactosidase could be a promising prototype for development of commercial enzymes aimed at lactose treatment in the dairy industry.

Influence of application of manganese ore in constructed wetlands on the mechanisms and improvement of nitrogen and phosphorus removal.

Vertical up-flow constructed wetlands (CWs) with manganese ore (Mn ore) as media (M-CWs) were developed to treat simulated polluted river water. The results showed that the average removal efficiencies for NH4-N, NO3-N, TN and TP were 91.74%, 83.29%, 87.47% and 65.12% in M-CWs, respectively, which were only 79.12%, 72.90%, 75.85% and 43.23% in the CWs without Mn ore (C-CWs). Nutrient mass balance showed that nitrogen (N) removal was improved by enhanced microbial processes, media storage and plant uptake in M-CWs. Moreover, almost 50% of phosphorus (P) was retained by media storage because of the adsorption processes on Mn ore. It was found that addition of Mn ore enhanced denitrification as the relative abundance of denitrifying bacteria increased. The produced Mn(II) and more abundant Gammaproteobacteria confirmed alternative N removal pathways including anoxic nitrification coupled to Mn ore reduction and denitrification using Mn(II) as electron donor. Mn(II) concentration in the effluent of M-CWs was below the drinking water limit of 0.1 mg/L, which makes them environmentally-friendly.

Effects of starter feeding on caecal mucosal bacterial composition and expression of genes involved in immune and tight junctions in pre-weaned twin lambs.

The objective of this study was to explore the effects of starter feeding on caecal mucosal bacterial composition and the expression of genes involved in immune and tight junctions in pre-weaned lambs. Six pairs of new-born twin lambs were selected. From 10 days of age, one lamb of each pair received ewe's milk only (M group, n = 6), while the other one was fed ewe's milk plus starter feed (M + S group, n = 6). At 56 days of age, the lambs were sacrificed, and then cecum digesta was collected to measure pH values and concentrations of volatile fatty acid (VFA), and caecal mucosa were collected to determine the changes in bacterial communities and the mRNA expression of cytokines, toll-like receptors (TLRs) and tight junction proteins. The results showed the body weight and average daily gain were not significantly different between both groups. Starter feeding significantly (P < 0.05) increased the concentrations of propionate and butyrate; the proportions of acetate, propionate and butyrate to total concentrations of VFA; and decreased the ratio of acetate to propionate in caecal contents. Principal coordinate analysis showed that samples from the M + S group could be distinguished from those from the M group; starter feeding also increased the diversity of caecal mucosal bacteria. At the genus level, starter feeding significantly (FDR < 0.05) increased the relative abundance of Alistipes, Parabacteroides, Parasutterella and Butyricimonas, and caused a decreasing trend (FDR < 0.10) in the relative abundance of Campylobacter and Helicobacter. The real-time PCR results showed that starter feeding significantly (FDR < 0.05) decreased the relative mRNA expression level of IL-12, TNF-α and TLR4 and increased the relative mRNA expression level of claudin-4. These results indicate that starter feeding altered caecal mucosal bacterial communities and decreased the expression of inflammatory factors, which may be beneficial in alleviating the weaning stress of lambs.

Aspartame supplementation in starter accelerates small intestinal epithelial cell cycle and stimulates secretion of glucagon-like peptide-2 in pre-weaned lambs.

The objective of this study was to test the hypothesis that aspartame supplementation in starter diet accelerates small intestinal cell cycle by stimulating secretion and expression of glucagon-like peptide -2 (GLP-2) in pre-weaned lambs using animal and cell culture experiments. In vivo, twelve 14-day-old lambs were selected and allocated randomly to two groups; one was treated with plain starter diet (Con, n = 6) and the other was treated with starter supplemented with 200 mg of aspartame/kg starter (APM, n = 6). Results showed that the lambs received APM treatment for 35 d had higher (p < .05) GLP-2 concentration in the plasma and greater jejunum weight/live body weight (BW) and jejunal crypt depth. Furthermore, APM treatment significantly upregulated (p < .05) the mRNA expression of cyclin D1 in duodenum; and cyclin A2, cyclin D1, cyclin-dependent kinases 6 (CDK6) in jejunum; and cyclin A2, cyclin D1, CDK4 in ileum. Moreover, APM treatment increased (p < .05) the mRNA expression of glucagon (GCG), insulin-like growth factor 1 (IGF-1) in the jejunum and ileum and mRNA expression of GLP-2 receptor (GLP-2R) in the jejunum. In vitro, when jejunal cells were treated with GLP-2 for 2 hr, the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) OD, IGF-1 concentration, and the mRNA expression of IGF-1, cyclin D1 and CDK6 were increased (p < .05). Furthermore, IGF-1 receptor (IGF-1R) inhibitor decreased (p < .05) the mRNA expression of IGF-1, cyclin A2, cyclin D1 and CDK6 in GLP-2 treatment jejunal cells. These results suggest that aspartame supplementation in starter accelerates small intestinal cell cycle that may, in part, be related to stimulate secretion and expression of GLP-2 in pre-weaning lambs. Furthermore, GLP-2 can indirectly promote the proliferation of jejunal cells mainly through the IGF-1 pathway. These findings provide new insights into nutritional interventions that promote the development of small intestines in young ruminants.