A novel donor-acceptor structured diketopyrrolopyrrole-based conjugated polymer synthesized by direct arylation polycondensation (DArP) for highly efficient antimicrobial photothermal therapy.

A novel donor (D)-acceptor (A) structured conjugated polymer (PDPP-TP), which contains two alternating D-A pairs, namely thiophene (T)-diketopyrrolopyrrole (DPP) and thiophenen (T)-thieno[3,4-b]pyrazine (TP) along the main chain of the polymer, was synthesized by direct arylation polycondensation (DArP) for a highly efficient photothermal antibacterial treatment. The hydrophilic PDPP-TP-based nanoparticles (PTNPs) with a hydration diameter of about 120 nm were obtained by self-assembly using DSPE-mPEG2000 as the polymer matrix. PTNPs show strong near-infrared (NIR) absorbance with a λmax at 910 nm (ε = 2.25 × 104 L mol-1 cm-1) and NIR light-triggered photoactivity with a high photothermal conversion efficiency (PTCE) of 52.8% under 880 nm laser irradiation. Keeping the merits of excellent biocompatibility and photostability, PTNPs exhibited remarkable bacterial inhibition efficiency of almost 100% against Gram-negative E. coli and Gram-positive S. aureus with the help of an 880 nm laser (0.7 W cm-2, 6 min), demonstrating its great potential as photothermal materials with a broad spectrum of activity for the effective treatment of microbial infections.

13-Methyl-palmatrubine shows an anti-tumor role in non-small cell lung cancer via shifting M2 to M1 polarization of tumor macrophages.

BACKGROUND: Previous studies have substantiated that M2-activated tumor-associated macrophages (M2-TAMs) are involved in multiple malignancies. Presently, we probe the impact and related mechanisms of 13-methyl-palmatrubine (13MP), the Corydalis yanhusuo extract, on M2-TAM-mediated non-small cell lung cancer (NSCLC) development. METHODS: IL-4 and IL-13 were adopted to induce M2-TAMs. The polarization state of TAMs was evaluated by quantitative reverse transcription PCR (qRT-PCR), Western blot (WB) and cellular immunofluorescence. NSCLC cells (A549 and NCL-H1975) were co-cultured with the conditioned medium (CM) of M2-TAMs. Followed by 13MP treatment, cell viability, proliferation, invasion, epithelial-mesenchymal transition (EMT), and in-vivo growth of NSCLC cells were determined. Additionally, human umbilical vein endothelial cells (HUVECs) were co-cultured with the CM of M2-TAMs. The tube formation assay was made to test the tube formation capacity of HUVECs, and the expression of MMP3, MMP9, and VEGF was assessed by WB in the co-culture model. Mechanistically, WB was performed to validate the expression of the PI3K/AKT and JAK/STAT3 pathways in NSCLC cells (A549 and NCL-H1975) as well as in endothelial cell lines co-cultured with M2-TAMs. RESULTS: 13MP inhibited the proliferation, invasion, EMT, growth and enhanced apoptosis of NSCLC cells. 13MP dose-dependently boosted the polarization of TAM from M2 to M1 state. M2-TAMs enhanced the malignant behaviors of NSCLC cells, whereas 13MP hindered M2-TAM-mediated NSCLC cell proliferation and invasion. Meanwhile, 13MP weakened the M2-TAM-mediated angiogenesis. Moreover, 13MP inactivated the PI3K/AKT and JAK/STAT3 signaling in A549 cells, NCL-H1975 cells and HUVECs. CONCLUSION: 13MP suppresses TAM-mediated NSCLC progression via transforming the polarization of TAM from M2 to M1.

Combined yeast culture and organic selenium supplementation during late gestation and lactation improve preweaning piglet performance by enhancing the antioxidant capacity and milk content in nutrient-restricted sows.

This study was conducted to investigate the effects of dietary supplementation with yeast culture (YC) and organic selenium (Se) during late gestation and lactation on reproductive performance, milk quality, piglet preweaning performance, antioxidant capacity, and secretion of immunoglobulin in multiparous sows. A total of 160 healthy cross-bred sows (Landrace × Yorkshire, mean parity 4.1 ± 0.3) were randomly assigned to 4 groups as follows: 1) high nutrient (HN), 3,420 kcal/kg digestible energy (DE) and 18.0% crude protein (CP); 2) low nutrient (LN), 3,240 kcal/kg DE and 16.0% CP; 3) LN + YC, LN diet + 10 g/kg YC; 4) LN + YC + Se, LN diet + 10 g/kg YC + organic Se (1 mg/kg Se). Feeding trials of sows started from d 85 of pregnancy to d 35 of lactation. Compared with sows in the LN group, sows fed the LN + YC + Se diet had greater litter weaning weight, average litter gain, and milk fat content (14-d and 25-d milk) (P < 0.05). The content of malonaldehyde (MDA) (colostrum and 14-d milk) was lesser, and the activity of glutathione peroxidase (GSH-Px) (colostrum and 25-d milk) was greater when sows were fed the LN + YC + Se diet, compared with sows fed the LN diet (P < 0.05). Supplementation of YC and organic Se in the nutrient-restricted diet improved sows' reproductive performance and pig weaning body weight by enhancing the antioxidant capacity and fat content in milk.

Penochalasin K, a new unusual chaetoglobosin from the mangrove endophytic fungus Penicillium chrysogenum V11 and its effective semi-synthesis.

A new chaetoglobosin, penochalasin K (1) bearing an unusual six-cyclic 6/5/6/5/6/13 fused ring system, along with the known analogues, chaetoglobosin C (2), penochalasin I (3), and chaetoglobosin A (4) were isolated from the solid culture of the mangrove endophytic fungus Penicillium chrysogenum V11. Their structures were elucidated by 1D, 2D NMR spectroscopic analysis and high resolution mass spectroscopic data. The absolute configuration of compound 1 was determined by comparing the theoretical and experimental electronic circular dichroism curves. Compound 1 displayed significant inhibitory activities against Colletotrichum gloeosporioides and Rhizoctonia solani (MICs=6.13, 12.26µM, respectively), which was better than those of carbendazim, and exhibited potent cytotoxicity against MDA-MB-435, SGC-7901 and A549 cells (IC50<10µM). An effective biomimetic transformation of chaetoglobosin C (2)/chaetoglobosin A (4) into penochalasin K (1)/penochalasin I (3) was developed, which provided a simple method for the semi-synthesis of chaetoglobosins with a six-cyclic 6/5/6/5/6/13 fused system formed by the connectivity of C-5 and C-2' from their corresponding epoxide analogues.