Fecal Microbiota and Its Correlation With Fatty Acids and Free Amino Acids Metabolism in Piglets After a Lactobacillus Strain Oral Administration

Lactobacillus has a positive effect on the host intestinal microbiota. In piglets, dietary supplementation with Lactobacillus affects general health and plays an important role in nutrient digestion and fermentation. However, this association requires further investigation. Here, we studied newborn piglets from 12 litters. The nursed piglets were given a creep feed beginning on day 10 post-partum and weaned at day 30. Piglets were fed either a control basic diet or a diet including supplementation with Lactobacillus reuteri ZLR003 at 6.0 × 106 CFU/g feed. At day 30 and 60, feces samples were taken and used for sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. At day 60, feces samples and serum samples were also taken and used to measure the short chain fatty acids (SCFAs) and to detect long chain fatty acids (LCFAs) and free amino acids (FAAs), respectively. The results revealed that L. reuteri ZLR003 could improve piglet fecal microbiota composition, especially at the end of weaned period. The concentrations of lactic acid and butyric acid in feces were higher, and acetic acid concentration was lower in the L. reuteri ZLR003 group compared with the control group (P < 0.05). The serum polyunsaturated fatty acids C18:2n6c, C18:3n3, C20:4n6, and C22:6n3 were significantly higher (P < 0.05), as were the serum FAAs Gly, Ala, Val, Iso, Asn, Asp, Glu, Met, Phe, and Leu (P < 0.05), in the L. reuteri group compared with the control group. A correlation analysis revealed that the genera Ruminococcaceae_UCG-010 and Ruminococcaceae_UCG-014 had a negative correlation with the SCFAs content in feces, the genus Prevotella_9 had a higher positive correlation with C18:2n6c, and the genera Megasphaera and Mitsuokella had a more positive significant effect on the serum FAAs content in weaned piglets in the L. reuteri ZLR003 group compared with the control group. In conclusion, L. reuteri ZLR003 influenced the fecal microbiota composition of piglets, and its effects were related to the metabolism of SCFAs, LCFAs, and FAAs. Our findings will help facilitate the application of Lactobacillus strains in pig production

Iterative optimization of the cyclic peptide SFTI-1 yields potent inhibitors of neutrophil proteinase 3

Neutrophils produce at least four serine proteases that are packaged within azurophilic granules. These enzymes contribute to antimicrobial defense and inflammation but can be destructive if their activities are not properly regulated. Accordingly, they represent therapeutic targets for several diseases, including chronic obstructive pulmonary disease, cystic fibrosis, and rheumatoid arthritis. In this study, we focused on proteinase 3 (PR3), a neutrophil protease with elastase-like specificity, and engineered potent PR3 inhibitors based on the cyclic peptide sunflower trypsin inhibitor-1 (SFTI-1). We used an iterative optimization approach to screen targeted substitutions at the P1, P2, P2', and P4 positions of SFTI-1, and generated several new inhibitors with values in the low nanomolar range. These SFTI-variants show high stability in human serum and are attractive leads for further optimization

Elemental Precursor Solution Processed (Cu_1–<i>x</i>Ag_<i>x</i>)₂ZnSn(S,Se)₄ Photovoltaic Devices with over 10% Efficiency

The partial substitution of Cu⁺ with Ag⁺ into the host lattice of Cu₂ZnSn­(S,Se)₄ thin films can reduce the open-circuit voltage deficit (<i>V</i>_oc,deficit) of Cu₂ZnSn­(S,Se)₄ (CZTSSe) solar cells. In this paper, elemental Cu, Ag, Zn, Sn, S, and Se powders were dissolved in solvent mixture of 1,2-ethanedithiol (edtH₂) and 1,2-ethylenediamine (en) and used for the formation of (Cu_1–<i>x</i>Ag_<i>x</i>)₂ZnSn­(S,Se)₄ (CAZTSSe) thin films with different Ag/(Ag + Cu) ratios. The key feature of this approach is that the impurity atoms can be absolutely excluded. Further results indicate that the variations of grain size, band gap, and depletion width of the CAZTSSe layer are generally determined by Ag substitution content. Benefiting from the <i>V</i>_oc enhancement (∼50 mV), the power conversion efficiency is successfully increased from 7.39% (<i>x</i> = 0) to 10.36% (<i>x</i> = 3%), which is the highest efficiency of Ag substituted devices so far

Engineering the Cyclization Loop of MCoTI-II Generates Targeted Cyclotides that Potently Inhibit Factor XIIa

Factor XIIa (FXIIa) is a promising target for developing new drugs that prevent thrombosis without causing bleeding complications. A native cyclotide (MCoTI-II) is gaining interest for engineering FXIIa-targeted anticoagulants as this peptide inhibits FXIIa but not other coagulation proteases. Here, we engineered the native biosynthetic cyclization loop of MCoTI-II (loop 6) to generate improved FXIIa inhibitors. Decreasing the loop length led to gains in potency up to 7.7-fold, with the most potent variant having five residues in loop 6 (Ki = 25 nM). We subsequently examined sequence changes within loop 6 and an adjacent loop, with substitutions at P4 and P2′ producing a potent FXIIa inhibitor (Ki = 2 nM) that displayed more than 700-fold selectivity, was stable in human serum, and blocked the intrinsic coagulation pathway in human plasma. These findings demonstrate that engineering the biosynthetic cyclization loop can generate improved cyclotide variants, expanding their potential for drug discovery

Tuning the Se Content in Cu₂ZnSn(S, Se)₄ Absorber to Achieve 9.7% Solar Cell Efficiency from a Thiol/Amine-Based Solution Process

The Se content in a Cu₂ZnSn­(S, Se)₄ absorber layer has a significant impact on the electronic properties, but it is rather challenging to control the Se/(S + Se) ratio due to a complicated selenization process. Here, a low-toxicity thiol/amine-based solution process was developed to tune the Se content in a Cu₂ZnSn­(S, Se)₄ absorber layer to an optimal value by ingeniously controlling the SeO₂ in the precursor solution. We demonstrated that the crystal growth and the band gap of Cu₂ZnSn­(S, Se)₄ thin films are affected by the Se/(S + Se) ratio. By this approach, the open-circuit voltage deficit (<i>V</i>_oc,def) of the device was effectively decreased, and the short-circuit density (<i>J</i>_sc) and fill factor (FF) were remarkably improved; thus, the power conversion efficiency of the Cu₂ZnSn­(S, Se)₄ solar cells was successfully increased from 5.6% to 9.7% for the optimal band gap (<i>E</i>_g = 1.13 eV)

Engineering the Cyclization Loop of MCoTI-II Generates Targeted Cyclotides that Potently Inhibit Factor XIIa

Factor XIIa (FXIIa) is a promising target for developing new drugs that prevent thrombosis without causing bleeding complications. A native cyclotide (MCoTI-II) is gaining interest for engineering FXIIa-targeted anticoagulants as this peptide inhibits FXIIa but not other coagulation proteases. Here, we engineered the native biosynthetic cyclization loop of MCoTI-II (loop 6) to generate improved FXIIa inhibitors. Decreasing the loop length led to gains in potency up to 7.7-fold, with the most potent variant having five residues in loop 6 (Ki = 25 nM). We subsequently examined sequence changes within loop 6 and an adjacent loop, with substitutions at P4 and P2′ producing a potent FXIIa inhibitor (Ki = 2 nM) that displayed more than 700-fold selectivity, was stable in human serum, and blocked the intrinsic coagulation pathway in human plasma. These findings demonstrate that engineering the biosynthetic cyclization loop can generate improved cyclotide variants, expanding their potential for drug discovery

Additional file 2 of Chemotherapy induces ACE2 expression in breast cancer via the ROS-AKT-HIF-1α signaling pathway: a potential prognostic marker for breast cancer patients receiving chemotherapy

Additional file 2: Figure S1. (A) qRT-PCR analysis showed no significant changes in ACE2 expression in colorectal and pancreatic cancer cells after exposure to EPI, PTX or 5-FU. All data are shown as mean ± SD; *P  0.05 versus control, N = 3

Additional file 1 of Chemotherapy induces ACE2 expression in breast cancer via the ROS-AKT-HIF-1α signaling pathway: a potential prognostic marker for breast cancer patients receiving chemotherapy

Additional file 1: Table S1. The primers used for qRT-PCR in this study. Table S2. The sequence of siRNAs target ACE2 and HIF-1α used in this study. Table S3. The sequence for shACE2 used in this study. Table S4. Clinicopathological characteristics of healthy donors and breast cancer patients enrolled in this study. Table S5. IC50 of breast cancer, colorectal cancer and pancreatic cancer cell lines in GDSC