Sodium acetate and sodium butyrate attenuate diarrhea in yak calves by regulating gut microbiota and metabolites.

Diarrhea is a severe issue in calves that causes fertility problems and economic issues worldwide. Sodium acetate/sodium butyrate (SA/SB) alleviates diarrhea in mice; however, little information is available about the preventive effect of SA/SB on diarrheic yak calves living on the Tibet plateau. Yak calves (n = 19) of age ≥4 months and weight 37 ± 2 Kg were randomly divided into control (C, n = 10) and supplement groups (S, n = 9). Yaks belonging to the supplement group were given sodium butyrate (10 g/kg) and sodium acetate (5 g/kg) for 28 days, along with normal feed, seasonal grasses, pasture, and water. The blood and fecal samples from yak calves were collected for assessment of antioxidant capacity, inflammatory cytokines, microbiome, and short-chain fatty acids (SCFAs) concentration analysis. Results of this study revealed that a lower diarrhea rate, higher weight, and net weight gain were recorded in yaks belonging to group S supplemented with SA/SB. Similarly, increased antioxidant capacity with higher levels of T-AOC, SOD, and GSH-px and decreased inflammatory reactions by decreasing both TNF-α and IL-1ß concentrations were recorded in yaks of group S. The concentration of SCFAs was significantly higher (p < 0.05) in yaks from group S than group C. Microbiome analysis revealed that 8 phyla and 54 genera were significantly different (p < 0.05) in both yak groups, with increased probiotics (Akkermansia, Oscillospira), SCFAs producing genera (Oscillospira, ASF356, Anaerosporobacter and Phascolarctobacterium), and decreased inflammatory related genus (Flavonifractor, Fournierella) and harmful bacteria (Oscillibacter, Achromobacter) in group S. In conclusion, the results demonstrated that SA and SB could decrease diarrhea rates in yak calves on the plateau via increasing antioxidant ability and SCFAs, while decreasing inflammatory responses in yaks by moderating gut microbiota. The current results provide new insights for the prevention and treatment of diarrhea in yaks.

Rational Synthesis of Core-Shell-Structured Nickel Sulfide-Based Nanostructures for Efficient Seawater Electrolysis.

Versatile electrocatalysis at higher current densities for natural seawater splitting to produce hydrogen demands active and robust catalysts to overcome the severe chloride corrosion, competing chlorine evolution, and catalyst poisoning. Hereto, the core-shell-structured heterostructures composed of amorphous NiFe hydroxide layer capped Ni3 S2 nanopyramids which are directly grown on nickel foam skeleton (NiS@LDH/NF) are rationally prepared to regulate cooperatively electronic structure and mass transport for boosting oxygen evolution reaction (OER) performance at larger current densities. The prepared NiS@LDH/NF delivers the anodic current density of 1000 mA cm-2 at the overpotential of 341 mV in 1.0 m KOH seawater. The feasible surface reconstruction of Ni3 S2 -FeNi LDH interfaces improves the chemical stability and corrosion resistance, ensuring the robust electrocatalytic activity in seawater electrolytes for continuous and stable oxygen evolution without any hypochlorite production. Meanwhile, the designed Ni3 S2 nanopyramids coated with FeNi2 P layer (NiS@FeNiP/NF) still exhibit the improved hydrogen evolution reaction (HER) activity in 1.0 m KOH seawater. Furthermore, the NiS@FeNiP/NF||NiS@LDH/NF pair requires cell voltage of 1.636 V to attain 100 mA cm-2 with a 100% Faradaic efficiency, exhibiting tremendous potential for hydrogen production from seawater.

Interface Metal Oxides Regulating Electronic State around Nickel Species for Efficient Alkaline Hydrogen Electrocatalysis.

Heterogeneous electrocatalysis typically depends on the surface electronic states of active sites. Modulating the surface charge state of an electrocatalysts can be employed to improve performance. Among all the investigated materials, nickel (Ni)-based catalysts are the only non-noble-metal-based alternatives for both hydrogen oxidation and evolution reactions (HOR and HER) in alkaline electrolyte, while their activities should be further improved because of the unfavorable hydrogen adsorption behavior. Hereto, Ni with exceptional HOR electrocatalytic performance by changing the d-band center by metal oxides interface coupling formed in situ is endowed. The resultant MoO2 coupled Ni heterostructures exhibit an apparent HOR activity, even approaching to that of commercial 20% Pt/C benchmark, but with better long-term stability in alkaline electrolyte. An exceptional HER performance is also achieved by the Ni-MoO2 heterostructures. The experiment results are rationalized by the theoretical calculations, which indicate that coupling MoO2 with Ni results in the downshift of d-band center of Ni, and thus weakens hydrogen adsorption and benefits for hydroxyl adsorption. This concept is further proved by other metal oxides (e.g., CeO2 , V2 O3 , WO3 , Cr2 O3 )-formed Ni-based heterostructures to engineer efficient hydrogen electrocatalysts.

Sodium acetate/sodium butyrate alleviates lipopolysaccharide-induced diarrhea in mice via regulating the gut microbiota, inflammatory cytokines, antioxidant levels, and NLRP3/Caspase-1 signaling.

Diarrhea is a word-widely severe disease coupled with gastrointestinal dysfunction, especially in cattle causing huge economic losses. However, the effects of currently implemented measures are still not enough to prevent diarrhea. Previously we found that dropped short-chain fatty acids in diarrhea yaks, and butyrate is commonly known to be related to the epithelial barrier function and intestinal inflammation. However, it is still unknown whether sodium acetate/sodium butyrate could alleviate diarrhea in animals. The present study is carried out to explore the potential effects of sodium acetate/sodium butyrate on lipopolysaccharide-induced diarrhea in mice. Fifty ICR mice were randomly divided into control (C), LPS-induced (L), and sodium acetate/sodium butyrate (D, B, A)-treated groups. Serum and intestine samples were collected to examine inflammatory cytokines, antioxidant levels, relative gene expressions via real-time PCR assay, and gut microbiota changes through high-throughput sequencing. Results indicated that LPS decreased the villus height (p < 0.0001), increased the crypt depth (p < 0.05), and lowered the villus height to crypt depth ratio (p < 0.0001), while sodium acetate/sodium butyrate supplementation caused a significant increase in the villus height (p < 0.001), decrease in the crypt depth (p < 0.01), and increase in the villus height to crypt depth ratio (p < 0.001), especially. In mice treated with LPS, it was found that the serum level of IL-1ß, TNF-α (p < 0.001), and MDA (p < 0.01) was significantly higher; however, sodium acetate/sodium butyrate supplementation significantly reduced IL-1ß (p < 0.001), TNF-α (p < 0.01), and MDA (p < 0.01), respectively. A total of 19 genera were detected among mouse groups; LPS challenge decreased the abundance of Lactobacillus, unidentified F16, unidentified_S24-7, Adlercreutzia, Ruminococcus, unclassified Pseudomonadales, [Ruminococcus], Acetobacter, cc 1, Rhodococcus, unclassified Comamonadaceae, Faecalibacterium, and Cupriavidus, while increased Shigella, Rhodococcus, unclassified Comamonadaceae, and unclassified Pseudomonadales in group L. Interestingly, sodium acetate/sodium butyrate supplementation increased Lactobacillus, unidentified F16, Adlercreutzia, Ruminococcus, [Ruminococcus], unidentified F16, cc 115, Acetobacter, Faecalibacterium, and Cupriavidus, while decreased Shigella, unclassified Enterobacteriaceae, unclassified Pseudomonadales, Rhodococcus, and unclassified Comamonadaceae. LPS treatment upregulated the expressions of ZO-1 (p < 0.01) and NLRP3 (p < 0.0001) genes in mice; however, sodium acetate/sodium butyrate solution supplementation downregulated the expressions of ZO-1 (p < 0.05) and NLRP3 (p < 0.05) genes in treated mice. Also, the LPS challenge clearly downregulated the expression of Occludin (p < 0.001), Claudin (p < 0.0001), and Caspase-1 (p < 0.0001) genes, while sodium acetate/sodium butyrate solution supplementation upregulated those gene expressions in treated groups. The present study revealed that sodium acetate/sodium butyrate supplementation alleviated LPS-induced diarrhea in mice via enriching beneficial bacterium and decreasing pathogens, which could regulate oxidative damages and inflammatory responses via NLRP3/Caspase-1 signaling. The current results may give insights into the prevention and treatment of diarrhea.

Characterization of Bacterial Microbiota Composition in Healthy and Diarrheal Early-Weaned Tibetan Piglets.

The occurrence of diarrhea in Tibetan piglets is highly notable, but the microorganisms responsible are yet unclear. Its high incidence results in serious economic losses for the Tibetan pig industry. Moreover, the dynamic balance of intestinal microflora plays a crucial role in maintaining host health, as it is a prime cause of diarrhea. Therefore, the present study was performed to analyze the characteristics of bacterial microbiota structure in healthy, diarrheal and treated weaned piglets in Tibet autonomous region for providing a theoretical basis to prevent and control diarrhea. The study was based on the V3-V4 region of the 16S rRNA gene and gut microbiota functions following the metagenome analysis of fresh fecal samples (n = 5) from different groups. The Shannon and Simpson indices differed substantially between diarrheal and treated groups (p < 0.05). According to our findings, the beta diversities, especially between healthy and diarrheal groups, were found different. Firmicutes, Bacteroidetes and Proteobacteria were the dominant phyla in three groups. Furthermore, the abundance of Fusobacteria in the diarrheal group was higher than the other groups. The dominant genera in the diarrheal group were Fusobacterium, Butyricimonas, Sutterella, Peptostreptococcus, and Pasteurella. Moreover, Lactobacillus, Megasphaera and Clavibacter were distinctly less abundant in this group. It is noteworthy that the specific decrease in the abundance of pathogenic bacteria after antibiotic treatment in piglets was noticed, while the level of Lactobacillus was evidently increased. In conclusion, fecal microbial composition and structure variations were discovered across the three groups. Also, the ecological balance of the intestinal microflora was disrupted in diarrheal piglets. It might be caused by a reduction in the relative number of beneficial bacteria and an increase in the abundance of pathogenic bacteria. In the context of advocating for non-resistant feeding, we suspect that the addition of probiotics to feed may prevent early-weaning diarrhea in piglets. Moreover, our findings might help for preventing diarrhea in weaned Tibetan piglets with a better understanding of microbial population dynamics.

Circ_0075804 promotes the malignant behaviors of retinoblastoma cells by binding to miR-138-5p to induce PEG10 expression.

BACKGROUND: It has been gradually recognized that circular RNAs (circRNAs) are important modulators in multiple malignancies. Here, we analyzed the function of circ_0075804 and explored its associated mechanism in regulating retinoblastoma (RB) progression. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were utilized to measure RNA and protein expression, respectively. Cell proliferation was analyzed by Cell counting kit-8 (CCK8) assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was assessed by flow cytometry. Cell migration and invasion abilities were analyzed by wound healing assay and transwell invasion assay. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to verify intermolecular target relations. Xenograft tumor model was used to analyze the role of circ_0075804 in tumor growth in vivo. RESULTS: Circ_0075804 expression was markedly up-regulated in RB tissues and cell lines. Circ_0075804 knockdown restrained the proliferation, migration and invasion whereas promoted the apoptosis of RB cells. Circ_0075804 acted as a molecular sponge for microRNA-138-5p (miR-138-5p), and circ_0075804 silencing-induced effects were partly reversed by miR-138-5p knockdown in RB cells. MiR-138-5p interacted with the 3' untranslated region (3'UTR) of paternally expressed 10 (PEG10). Circ_0075804 positively regulated PEG10 level by sponging miR-138-5p in RB cells. PEG10 overexpression largely overturned miR-138-5p overexpression-mediated effects in RB cells. Circ_0075804 knockdown blocked xenograft tumor growth in vivo. CONCLUSION: Circ_0075804 promoted RB progression via miR-138-5p-dependent regulation of PEG10, which provided new insight in RB therapy.

Characterization of fungal microbial diversity in Tibetan sheep, Tibetan gazelle and Tibetan antelope in the Qiangtang region of Tibet.

Due to the high crude fiber content, straw of various crops is difficult to become a high quality forage resource. The degradation of cellulose in nature mainly depends on the cellulase secreted by microbes, which degrade cellulose into small molecular substances through chemical action, and the microbes that secrete cellulase mainly include some bacteria, fungi and actinomycetes, etc. The large and diverse microbial population contained in the mammalian gastrointestinal tract plays an important role in nutrient digestion. At present, many cellulose-degrading strains have been screened and obtained from animal digestive system and feces, such as Bacillus subtilis from the feces of Panda, Bacillus amyloliquefaciens from the cecum of goose. In this study, the fungal diversity was analysed in the fresh faeces of Tibetan sheep, Tibetan gazelle and Tibetan antelope in Qiangtang, Tibet. Results showed that the structure and species of gut fungi are different in three animals, which may be related to the different physiological functions among different animals, e.g., Tibetan antelope and Tibetan gazelle have stronger tolerance to rough feeding than Tibetan sheep. This study will lay a foundation for cellulose-degrading fungal development and provides technical support for improving rough feeding tolerance of Tibetan sheep.

Preventive effect of Terminalia bellirica (Gaertn.) Roxb. extract on mice infected with Salmonella Typhimurium.

Terminalia bellirica (Gaertn.) Roxb. (TB) is a traditional herbal combination used in Chinese medicine for the treatment of a broad range of diseases. In this study, thirty KM mice were randomly divided into control (N), infection group (NS), and the TB protection group (HS). Based on its digestive feature, intestinal physical barrier, immunological barrier and gut microbiota effects in vivo on challenged with S.typhimurium mice were investigated after oral administration of 600 mg/kg b.wt of TB for 13 days. The results show that the extract could improve the level of serum immunoglobulins (IgA and IgG), decrease the intestinal cytokine secretion to relieve intestinal cytokine storm, reinforce the intestinal biochemical barrier function by elevating the sIgA expression, and strengthen the intestinal physical barrier function. Simultaneously, based on the V3-V4 region of the 16S rRNA analyzed, the results of the taxonomic structure of the intestinal microbiota demonstrated that the TB prevention effect transformed the key phylotypes of the gut microbiota in S. Typhimurium-challenged mice and promoted the multiplication of beneficial bacteria. Furthermore, the abundance of Firmicutes and Deferribacteres increased, while that of Bacteroidetes and Actinobacteria decreased. At the genus level, the abundance of Ruminococcus and Oscillospira was substantially enhanced, while the other dominant genera showed no significant change between the vehicle control groups and the TB prevention groups. In summary, these results provide evidence that the administration of TB extract can prevent S. Typhimurium infection by alleviating the intestinal physical and immunological barriers and normalizing the gut microbiota, highlighting a promising application in clinical treatment. Thus, our results provide new insights into the biological functions of TB for the preventive effect of intestinal inflammation.

Characterization of fungal microbial diversity in healthy and diarrheal Tibetan piglets.

BACKGROUND: Diarrhea is an important ailment limiting the production of the Tibetan pig industry. Dynamic balance of the intestinal microbiota is important for the physiology of the animal. The objective of this work was to study fungal diversity in the feces of early weaning Tibetan piglets in different health conditions. RESULTS: In the present study, we performed high-throughput sequencing to characterize the fungal microbial diversity in healthy, diarrheal and treated Tibetan piglets at the Tibet Autonomous Region of the People's Republic of China. The four alpha diversity indices (Chao1, ACE, Shannon and Simpson) revealed no significant differences in the richness across the different groups (P > 0.05). In all samples, the predominant fungal phyla were Ascomycota, Basidiomycota and Rozellomycota. Moreover, the healthy piglets showed a higher abundance of Ascomycota than the treated ones with a decreased level of Basidiomycota. One phylum (Rozellomycota) showed higher abundance in the diarrheal piglets than in the treated. At genus level, compared with that to the healthy group, the proportion of Derxomyces and Lecanicillium decreased, whereas that of Cortinarius and Kazachstania increased in the diarrheal group. The relative abundances of Derxomyces, Phyllozyma and Hydnum were higher in treated piglets than in the diarrheal ones. CONCLUSIONS: A decreased relative abundance of beneficial fungi (e.g. Derxomyces and Lecanicillium) may cause diarrhea in the early-weaned Tibetan piglets. Addition of probiotics into the feed may prevent diarrhea at this stage. This study presented the fungal diversity in healthy, diarrheal and treated early-weaned Tibetan piglets.

Protective effects of IFN-γ on the kidney of type- 2 diabetic KKAy mice.

BACKGROUND: Development of novel therapeutic strategies that specifically target diabetic kidney disease (DKD) is urgently needed. METHODS: Male KKAy mice were divided randomly into three equal groups - KK, KI, and KF; Male C57BL/6 mice were the control group. All KKAy mice were fed a high-fat diet. From the 16th week, the KI group was given IFN-γ, and the KF group was assigned to be treated with fludarabine. C57BL/6 mice were always fed a normal mouse diet. Every 4 weeks, body weight, random blood sugar, urine albumin and urea of all mice were measured. At the 20th week, all mice were killed, renal tissue was obtained to observe the pathological manifestations and extract proteins, and transforming growth factor- beta1 (TGF-ß1), collagen IV and Janus kinase 2/signal transducers and activators of transcription 1 (JAK2/STAT1) pathway proteins were measured by western blot. RESULTS: The present study showed that all KKAy mice appeared obese and hyperglycaemic from 12 weeks old and exhibited an increased urine albumin-to-creatinine ratio (ACR) from 16 weeks old. At the 20th week, compared to the KK group, the KI group showed lower ACR, more overexpression of P-STAT1 and less expression of TGF-ß1 and collagen IV proteins in renal tissue. The KI group mice showed less accumulation of glomerular mesangial matrix than those in the KK group. CONCLUSIONS: Our results indicate that IFN-γ might activate STAT1 to suppress the overexpression of TGF-ß1 and collagen IV proteins and attenuate the excessive accumulation of mesangial matrix under DKD conditions in KKAy mice.

Factors Determining Effective Orthokeratology Treatment for Controlling Juvenile Myopia Progression.

BACKGROUND: We aimed to identify factors influencing the therapeutic outcome of orthokeratology on controlling juvenile myopia progression, and the risk factors for complications. METHODS: Myopic patients (n=724) in Shenzhen Second Hospital from Jan 2011 to Jan 2016 fitted with orthokeratology lenses and followed-up for 6-65 months were reviewed retrospectively. Univariate and multivariate logistic regression analyses were used to screen for the factors that can improve treatment outcome and prevent the development of complications. RESULTS: Patients where the orthokeratology treatment was effective displayed a shorter myopia time, smaller diopter and corneal curvature, larger corneal endothelium density, high proportion of overnight wear and longer wearing times compared with patients whose treatments were ineffective. Additionally, wearing Ortho-k for 6 or 12 months yielded improved corrective effect and achieved higher comfort level. Logistic regression analyses showed that myopia time, diopter, corneal curvature e value, corneal endothelium density, time with Ortho-k and corrective effect after wearing Ortho-k for 6 or 12 months were all independent factors influencing the treatment effects. Results showed corneal curvature, anterior chamber depth and central corneal thickness were independent risk factors. CONCLUSION: This study systematically identified the factors leading to effective treatments, and those carrying a risk for complications, to provide guidance for the prescription and follow-up of orthokeratology in the treatment of juvenile myopia.

Changes of hemoglobin expression in response to hypoxia in a Tibetan schizothoracine fish, Schizopygopsis pylzovi.

Fishes endemic to the Qinghai-Tibetan Plateau are comparatively well adapted to aquatic environments with low oxygen partial pressures (hypoxia). Here, we cloned the complete cDNA of hemoglobin (Hb) α and ß from the Tibetan schizothoracine fish Schizopygopsis pylzovi, and then investigated changes in Hb mRNA and protein levels in spleen, liver and kidney in response to hypoxia. We applied severe hypoxia (4 h at PO2 = 0.6 kPa) and moderate hypoxia (72 h at PO2 = 6.0 kPa) to adult S. pylzovi. Changes of Hb expression under hypoxia, together with the investigations of spleen somatic index, kidney somatic index and Hb concentration in circulation, suggest that the kidney may not only serve as the erythropoietic organ, but also act as the major blood reservoir in S. pylzovi. From this perspective, the transcriptional activity of Hb in S. pylzovi, as reflected in the kidney, was turned down quickly after the onset of severe hypoxia, while under moderate hypoxia the transcriptional activity of Hb showed upregulation for a short time, but then the transcriptional machinery was turned down slowly on prolonged exposure. Notably, the changes in Hb protein levels in spleen, liver and kidney in response to severe and moderate hypoxia were not in line with the changes in mRNA levels, which are related with the blood reservoir in the kidney. Tibetan schizothoracine fish, at least S. pylzovi, show a particular response of the transcription regulation of Hb to moderate hypoxia, which is different from that of other fish species.