[Metabonomic study of biochemical changes in serum of PCPA-induced insomnia rats after treatment with Suanzaoren Decoction].

Suanzaoren Decoction(SZRD) is a classical formula for the clinical treatment of insomnia. This study analyzed the effect of SZRD on endogenous metabolites in insomnia rats based on metabonomics and thereby explored the anti-insomnia mechanism of SZRD. To be specific, DL-4-chlorophenylalanine(PCPA) was used to induce insomnia in rats. Then pathological changes of the liver and brain were observed and biochemical indexes such as 5-hydroxytryptamine(5-HT), dopamine(DA), glutamate(Glu), γ-aminobutyric acid(GABA), and norepinephrine(NE) in the hippocampus and prostaglandin D2(PGD2), tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and IL-6 in the serum of rats were detected. On this basis, the effect of SZRD on PCPA-induced insomnia rats was preliminarily assessed. The metabolic profile of rat serum samples was further analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were combined with t-test and variable importance in projection(VIP) to identify differential metabolites, and MetaboAnalyst 5.0 was employed for pathway analysis. The results showed that SZRD could improve the pathological changes of brain and liver tissues, increase the levels of neurotransmitters 5-HT, DA, and GABA in hippocampus and the level of PGD2 in hypothalamic-pituitary-adrenal axis(HPA axis), and reduce the levels of IL-1ß and TNF-α in serum of insomnia rats. Metabonomics analysis yielded 12 significantly changed potential metabolites: 5-aminovaleric acid, N-acetylvaline, L-proline, L-glutamate, L-valine, DL-norvaline, D(-)-arginine, pyroglutamic acid, 1-methylguanine, L-isoleucine, 7-ethoxy-4-methylcoumarin, and phthalic acid mono-2-ethylhexyl ester(MEHP), which were related with multiple biochemical processes including metabolism of D-glutamine and D-glutamate, metabolism of alanine, aspartate, and glutamate, metabolism of arginine and proline, arginine biosynthesis, glutathione metabolism. These metabolic changes indicated that SZRD can improve the metabolism in insomnia rats by regulating amino acid metabolism.

[Mechanism of Suanzaoren Decoction in improving insomnia rats by integrating metabolomics and intestinal flora analysis].

To explore the mechanism of Suanzaoren Decoction(SZRD) in improving the insomnia rat model induced by DL-4-chlorophenylalanine(PCPA). The insomnia model was established by single intraperitoneal injection with PCPA(400 mg·kg~(-1)), UPLC-Q-TOF-MS/MS was used to analyze the profile of metabolites in rat hippocampus samples, combined with multivariate statistical analysis and screening of differential metabolites, and related metabolic pathways were constructed with MetaboAnalyst 5.0. The high-throughput sequencing of V3-V4 regions of 16 S rRNA gene was used to predict the structure and relative abundance of intestinal flora by LEfSe, OPLS-DA and PICRUSt2. A total of 22 differential hippocampus metabolites were identified by metabolomics analysis, including amino acids, fatty acids, nucleosides, organic acids, vitamins, and others. Pathway analysis showed that alanine, aspartate and glutamic metabolism, D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis were the main pathways. 16 S rRNA gene sequencing showed that Ruminococcus and Eubacterium were the differences between SZRD group and model group. Ruminococcus might be the sign of SZRD improving PCPA insomnia on analysis of PICRUSt2 and LEfSe. Furthermore Spearman correlation analysis showed that the differential metabolites 2-oxo-4-methylthiobutyric acid and palmitic acid intervened by SZRD were significantly positively correlated with the differential flora. In conclusion, SZRD indirectly improves insomnia by affecting metabolic pathways such as amino acids metabolic pathways and regulating the structure of flora. The results of this study provide a new mechanism and new idea for elucidating the mechanism of classic famous prescription SZRD in improving insomnia from the perspective of intestinal flora.

Ultrastable Anti-Acid "Shield" in Layered Silver Coordination Polymers.

Surface passivation technology provides noble-metal materials with limited chemical stability, especially under highly acidic condition. To design effective strategy to enhance stability of noble-metal particles, an understanding of their surface anticorrosion mechanism at the atomic level is desirable by using two-dimensional (2D) noble-metal coordination polymer (CP) as an ideal model for their interfacial region. With the protection of 2-thiobenzimidazole (TBI), we isolated two Ag-based 2D CPs, {Ag14 (TBI)12 X2 }n (S-X, where S denotes sheet and X=Cl or Br). These compounds exhibited excellent chemical stability upon immersion in various common solvents, boiling water, boiling ethanol, 10 % hydrogen peroxide, concentrated acid (12 M HCl), and concentrated alkali (19 M NaOH). Systematic characterization and DFT analyses demonstrate that the superior stability of S-X was attributed to the hydrophobic organic shell and dynamic proton buffer layer acting as a double protective "shield".

GM1 Ameliorates Neuronal Injury in Rats after Cerebral Ischemia and Reperfusion: Potential Contribution of Effects on SPTBN1-mediated Signaling.

Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg·kg-1·d-1, tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NFκB/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1-knockdown SH-SY5Y cells, the treatment with GM1 (20 µM) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1-overexpressed SH-SY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke.

The interface microenvironment mediates the emission of a semiconductor nanocluster via surface-dopant-involving direct charge transfer.

The interface microenvironment of doped quantum dots (QDs) is crucial in optimizing the properties associated with the photogenerated excitons. However, the imprecision of QDs' surface structures and compositions impedes a thorough understanding of the modulation mechanism caused by the complex interface microenvironment, particularly distinguishing the contribution of surface dopants from inner ones. Herein, we investigated interface-mediated emission using a unique model of an atomically precise chalcogenide semiconductor nanocluster containing uniform near-surface Mn2+ dopants. Significantly, we discovered that Mn2+ ions can directly transfer charges with hydrogen-bonding-bound electron-rich alkylamines with matched molecular configurations and electronic structures at the interface. This work provides a new pathway, the use of atomically precise nanoclusters, for analyzing and enhancing the interface-dependent properties of various doped QDs, including chalcogenides and perovskites.

Effects of cysteine addition to low-fishmeal diets on the growth, anti-oxidative stress, intestine immunity, and Streptococcus agalactiae resistance in juvenile golden pompano (Trachinotus ovatus).

As the precursor of taurine, cysteine serves physiological functions, such as anti-oxidative stress and immune improvement. Investigation of cysteine and its derivatives has made positive progress in avian and mammalian species, yet the study and application of cysteine in aquatic animals are relatively rare. Therefore, we evaluated the effects of supplementing a low-fishmeal diet with various levels of cysteine on the growth, antioxidant capacity, intestine immunity, and resistance against Streptococcus agalactiae of the juvenile golden pompano (Trachinotus ovatus). According to our study, exogenous supplementation with 0.6-1.2% cysteine greatly increased the final body weight (FBW) and specific growth rate (SGR) of golden pompano compared to the control group. Under the present conditions, the optimum dietary cysteine supplementation level for golden pompano was 0.91% based on the polynomial regression analysis of SGR. Meanwhile, we found that the Nrf2/Keap1/HO-1 signaling pathway was notably upregulated with the increase of exogenous cysteine, which increased antioxidant enzyme activity in serum and gene expression in the intestine and reduced the level of reactive oxygen species (ROS) in the serum of golden pompano. In addition, morphological analysis of the midgut demonstrated that exogenous cysteine improved muscle thickness and villi length, which suggested that the physical barrier of the intestine was greatly strengthened by cysteine. Moreover, cysteine increased the diversity and relative abundance of the intestinal flora of golden pompano. Cysteine suppressed intestinal NF-κB/IKK/IκB signaling and pro-inflammatory cytokine mRNA levels. Conversely, intestinal anti-inflammatory cytokine gene expression and serum immune parameters were upregulated with the supplementary volume of cysteine and improved intestine immunity. Further, exogenous cysteine supplementation greatly reduced the mortality rate of golden pompano challenged with S. agalactiae. In general, our findings provide more valuable information and new insights into the rational use of cysteine in the culture of healthy aquatic animals.

Effects of exogenous taurine supplementation on the growth, antioxidant capacity, intestine immunity, and resistance against Streptococcus agalactiae in juvenile golden pompano (Trachinotus ovatus) fed with a low-fishmeal diet.

Taurine has various biological functions in fish, playing an essential role in growth, resistance to oxidative stress, and intestine immunity. Here, we evaluated the effects of exogenous taurine added to low-fishmeal diets on the growth, anti-oxidative stress, intestine immunity, and Streptococcus agalactiae resistance in juvenile golden pompano (Trachinotus ovatus). Our study showed that exogenous taurine supplementation of 1.2% (T3 group) greatly enhanced the weight gain rate and specific growth rate (SGR) of juvenile golden pompano, significantly upregulating growth-related factor expression in the brain and liver, as well as the levels of growth-related parameters in the serum. Polynomial regression analysis using SGR estimated the optimal dietary taurine level for golden pompano at 1.18%. Moderate exogenous taurine also increased the muscular thickness and villus length within the intestine, maintained intestinal physical barrier stability, activated the Nrf2/Keap-1/HO-1 signaling pathway, increased intestinal antioxidant enzyme gene expression and antioxidant enzyme activity in the serum, and upregulated immunoglobulin and complement levels in parallel with declining reactive oxygen species (ROS) levels in the serum. Antioxidant factor expression was also upregulated in the intestine. Furthermore, supplementation suppressed NF-κB signaling and intestinal pro-inflammatory cytokine gene expression, increased anti-inflammatory cytokine gene expression, and improved intestine immunity. Finally, taurine supplementation improved the survival rate of golden pompano challenged with S. agalactiae. Overall, our findings provide additional information and support for the rational use of taurine in healthy aquatic animal farming.

Acoustic Change Complex Evoked by Horizontal Sound Location Change in Young Adults With Normal Hearing.

Acoustic change complex (ACC) is a cortical auditory-evoked potential induced by a change of continuous sound stimulation. This study aimed to explore: (1) whether the change of horizontal sound location can elicit ACC; (2) the relationship between the change of sound location and the amplitude or latency of ACC; (3) the relationship between the behavioral measure of localization, minimum audible angle (MAA), and ACC. A total of 36 normal-hearing adults participated in this study. A 180° horizontal arc-shaped bracket with a 1.2 m radius was set in a sound field where participants sat at the center. MAA was measured in a two-alternative forced-choice setting. The objective electroencephalography recording of ACC was conducted with the location changed at four sets of positions, ±45°, ±15°, ±5°, and ±2°. The test stimulus was a 125-6,000 Hz broadband noise of 1 s at 60 ± 2 dB SPL with a 2 s interval. The N1'-P2' amplitudes, N1' latencies, and P2' latencies of ACC under four positions were evaluated. The influence of electrode sites and the direction of sound position change on ACC waveform was analyzed with analysis of variance. Results suggested that (1) ACC can be elicited successfully by changing the horizontal sound location position. The elicitation rate of ACC increased with the increase of location change. (2) N1'-P2' amplitude increased and N1' and P2' latencies decreased as the change of sound location increased. The effects of test angles on N1'-P2' amplitude [F(1.91,238.1) = 97.172, p < 0.001], N1' latency [F(1.78,221.90) = 96.96, p < 0.001], and P2' latency [F(1.87,233.11) = 79.97, p < 0.001] showed a statistical significance. (3) The direction of sound location change had no significant effect on any of the ACC peak amplitudes or latencies. (4) Sound location discrimination threshold by the ACC test (97.0% elicitation rate at ±5°) was higher than MAA threshold (2.08 ± 0.5°). The current study results show that though the ACC thresholds are higher than the behavioral thresholds on MAA task, ACC can be used as an objective method to evaluate sound localization ability. This article discusses the implications of this research for clinical practice and evaluation of localization skills, especially for children.

5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Early Warning Biomarkers for COVID-19 Progression and Myocardial Injury.

Background: The symptoms of coronavirus disease 2019 (COVID-19) range from moderate to critical conditions, leading to death in some patients, and the early warning indicators of the COVID-19 progression and the occurrence of its serious complications such as myocardial injury are limited. Methods: We carried out a multi-center, prospective cohort study in three hospitals in Wuhan. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles in plasma cell-free DNA (cfDNA) was used to identify risk factors for COVID-19 pneumonia and develop a machine learning model using samples from 53 healthy volunteers, 66 patients with moderate COVID-19, 99 patients with severe COVID-19, and 38 patients with critical COVID-19. Results: Our warning model demonstrated that an area under the curve (AUC) for 5hmC warning moderate patients developed into severe status was 0.81 (95% CI 0.77-0.85) and for severe patients developed into critical status was 0.92 (95% CI 0.89-0.96). We further built a warning model on patients with and without myocardial injury with the AUC of 0.89 (95% CI 0.84-0.95). Conclusion: This is the first study showing the utility of 5hmC as an accurate early warning marker for disease progression and myocardial injury in patients with COVID-19. Our results show that phosphodiesterase 4D and ten-eleven translocation 2 may be important markers in the progression of COVID-19 disease.

Stimulation of osteogenic differentiation in bone marrow stromal cells via Wnt/ß-catenin pathway by Qili Jiegu-containing serum.

A capsule of Qili Jiegu, a traditional Chinese medicine with numerous biological activities, may exert a protective eff ;ect against postmenopausal bone loss. However, it remains unclear whether Qili Jiegu-containing serum regulates the osteogenic diff ;erentiation of bone marrow stromal cells (BMSCs) in vitro. In this study, BMSCs were treated with medium and Qili Jiegu-containing serum over a 14-day period. We found that Qili Jiegu-containing serum promoted the BMSC proliferation and alkaline phosphatase (ALP) activities, as well as stimulated the expression of osteogenic markers and Wnt/ß-catenin pathway-related genes, i.e., runt-related transcription factor 2 (Runx2), osteocalcin (OCN), ß-catenin and Wnt4a, in BMSCs. Finally, we found that Qili Jiegu-containing serum activated the Wnt/ß-catenin pathway. An addition of Dickkopf-related protein-1 (an inhibitor of the Wnt/ß-catenin signaling pathway) to the Qili Jiegu-containing serum could decrease the stimulatory osteogenic effect of Qili Jiegu-containing serum on BMSCs. Therefore, Qili Jiegu-containing serum could promote the osteogenic diff ;erentiation of BMSCs, and the potential mechanism may involve regulation of Wnt/ß-catenin signaling.

Selective Hydrodeoxygenation of 5-Hydroxymethylfurfural to 2,5-Dimethylfuran over Heterogeneous Iron Catalysts.

This work provided the first example of selective hydrodeoxygenation of 5-hydroxymethylfurfural (HMF) to 2,5-dimethylfuran (DMF) over heterogeneous Fe catalysts. A catalyst prepared by the pyrolysis of an Fe-phenanthroline complex on activated carbon at 800 °C was demonstrated to be the most active heterogeneous Fe catalyst. Under the optimal reaction conditions, complete conversion of HMF was achieved with 86.2 % selectivity to DMF. The reaction pathway was investigated thoroughly, and the hydrogenation of the C=O bond in HMF was demonstrated to be the rate-determining step during the hydrodeoxygenation, which could be accelerated greatly by using alcohol solvents as additional H-donors. The excellent stability of the Fe catalyst, which was probably a result of the well-preserved active species and the pore structure of the Fe catalyst in the presence of H2 , was demonstrated in batch and continuous flow fixed-bed reactors.

Complete Genome Sequence of the Fish Pathogen Yersinia ruckeri Strain SC09, Isolated from Diseased Ictalurus punctatus in China.

Yersinia ruckeri SC09 is a Gram-negative bacterium isolated from a moribund Ictalurus punctatus collected in Jianyang, China. Here, we report the complete genome sequence of this microorganism to facilitate the investigation of its pathogenicity and to reevaluate its taxonomic position.