Donor-Acceptor Copolymer with a Linear Backbone Induced Ordered and Robust Doping Morphology for Efficient and Stable Organic Electrochemical Devices.

Donor (D)-acceptor (A) copolymer-based organic mixed ionic-electronic conductors (OMIECs) exhibit intrinsic environmental stability for they have tailored energy levels. However, their figure-of-merit (µC*) is still falling behind the D-D polymers because of morphology deterioration during the electrochemical doping process. Herein, we developed two D-A copolymers with precisely regulated backbone curvature, namely PTBT-P and PTTBT-P. Compared to the curved PTBT-P and previously reported copolymers, PTTBT-P better keeps its backbone linear, leading to a long-range ordered doping morphology, which is revealed by the in operando X-ray technique. This optimized doping morphology enables a significantly improved operando charge mobility (µ) of 2.44 cm2 V-1 s-1 and a µC* value of 342 F cm-1 V-1 s-1, one of the highest values in D-A copolymer based on OECTs. Besides, we fabricated PTTBT-P-based electrochemical random-access memories and achieved ideal and robust conductance modulation. This study highlights the critical role of backbone curvature control in the optimization of doping morphology for efficient and robust organic electrochemical devices.

Maternal exposure to particulate matter from duck houses restricts fetal growth due to inflammatory damage and oxidative stress.

The composition of particulate matter (PM) in poultry farms differs significantly from that of atmospheric PM as there is a higher concentration of microbes on farms. To assess the health effects of PM from poultry farms on pregnant animals, we collected PM from duck houses using a particulate sampler, processed it via centrifugation and vacuum concentration, and subsequently exposed the mice to airborne PM at 0.48 mg/m3 (i.e., low concentration group) and 1.92 mg/m3 (i.e., high concentration group) on the fifth day of pregnancy. After exposure until the twentieth day of pregnancy or spontaneous delivery, mice were euthanized for sampling. The effects of PM from duck houses on the pregnancy toxicity of mice were analyzed using histopathological analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction (qPCR). The results showed that exposure to PM had adverse effects on pregnant mice that reduced their feed intake in both groups. Microscopic lesions were observed in the lungs and placentas of pregnant mice, and the lesions worsened with increased PM concentrations, as shown by alveolar wall thickening, the infiltration of inflammatory cells in pulmonary interstitium, congestion, edema, and cellular degeneration of placenta. In pregnant mice in the high concentration group, exposure to PM significantly increased the expression of inflammatory cytokines in the lungs and placentas, caused oxidative stress, and decreased estrogen level in the blood. Exposure to PM also resulted in the reduced litter sizes of pregnant mice and shorter body and tail lengths in the fetuses delivered. Beyond that, exposure to PM significantly downregulated the levels of antioxidant factor superoxide dismutase and neurotrophic factor Ngf in the brains of fetuses. Collectively, exposure to a high concentration of PM by inhalation among pregnant mice caused significant pregnancy toxicity that led to abnormal fetal development due to inflammatory damage and oxidative stress. These findings established a foundation for future studies on the underlying mechanisms of pregnancy toxicity induced by exposure to PM.

M1 polarization of chicken macrophage HD11 can be activated by duck Tembusu virus via MyD88-NF-κB-mediated signaling pathway.

Duck Tembusu virus (DTMUV) has caused significant economic losses to the global duck industry since its outbreak in 2010. The macrophages act as the key immune cell, and its polarization in different functional states is very important for host's immune responses and microbial infections. Avian macrophages are the main target cells of DTMUV, its polarization induced by DTMUV and the underlying mechanisms were explored in this study. Through quantitative real-time PCR, nitrite assay, and flow cytometry analysis, we found that DTMUV caused severe inflammatory responses in chicken macrophage line HD11 by reprogramming the expression of M1- and M2-associated genes, leading to the polarization of HD11 macrophage to M1-type. In term of mechanism, transcriptomics was performed to analyze the M1-type polarization triggered by DTMUV, it was found that most differential genes were implicated in biological processes, and DTMUV infection significantly activated innate immune signaling pathways, including cytokine-cytokine receptor interaction, MAPK signaling pathway. Moreover, transcription factors NF-κB and AP1 also be activated after viral infection. However, further validation analysis by inhibitors and siRNAs of NF-κB and AP1 showed that NF-κB molecule was essential for DTMUV-induced M1 polarization in HD11 cell, but not AP1. Additionally, the inhibiting assays targeting MyD88 and TRIF molecules were conducted to determine their effect on NF-κB and M1-associated genes upregulated by DTMUV. The results showed that although the inhibition of both MyD88 and TRIF significantly downregulated the mRNA level of NF-κB, but the expression of M1-associated genes such as CD86 was lower in MyD88 inhibition group than in the other group, indicating that the role of MyD88 in mediating M1 polarization induced by DTMUV was more important. Overall, these results demonstrated that DTMUV infection induces M1-type polarization in chicken macrophage HD11 through MyD88-NF-κB signaling pathways. This finding will lay the foundation for further study the pathogenesis of DTMUV, and provide new insights into the prevention and control of this disease.

Novel insight into RNA modifications in tumor immunity: Promising targets to prevent tumor immune escape.

An immunosuppressive state is a typical feature of the tumor microenvironment. Despite the dramatic success of immune checkpoint inhibitor (ICI) therapy in preventing tumor cell escape from immune surveillance, primary and acquired resistance have limited its clinical use. Notably, recent clinical trials have shown that epigenetic drugs can significantly improve the outcome of ICI therapy in various cancers, indicating the importance of epigenetic modifications in immune regulation of tumors. Recently, RNA modifications (N6-methyladenosine [m6A], N1-methyladenosine [m1A], 5-methylcytosine [m5C], etc.), novel hotspot areas of epigenetic research, have been shown to play crucial roles in protumor and antitumor immunity. In this review, we provide a comprehensive understanding of how m6A, m1A, and m5C function in tumor immunity by directly regulating different immune cells as well as indirectly regulating tumor cells through different mechanisms, including modulating the expression of immune checkpoints, inducing metabolic reprogramming, and affecting the secretion of immune-related factors. Finally, we discuss the current status of strategies targeting RNA modifications to prevent tumor immune escape, highlighting their potential.

Dietary aflatoxin B1 caused the growth inhibition, and activated oxidative stress and endoplasmic reticulum stress pathway, inducing apoptosis and inflammation in the liver of northern snakehead (Channa argus).

The purpose of this study was to investigate the effects of dietary aflatoxin B1 (AFB1) on growth performance and AFB1 biotransformation, and hepatic oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and inflammation in northern snakehead (Channa argus). A total of 600 northern snakeheads (7.52 ± 0.02 g) were divided into five groups (three replicates/group) and fed the diets with AFB1 at concentrations of 0, 50, 100, 200, and 400 ppb for 8 weeks. The results demonstrated that dietary AFB1 (≥ 200 ppb) reduced FBW, WG, and SGR. 100, 200, and 400 ppb AFB1 treatment groups significantly decreased the PER, CRP, C3, C4, IgM, and LYS levels in northern snakehead, while FCR was significant increased. Moreover, dietary AFB1 (100, 200, and 400 ppb) increased cyp1a, cyp1b (except 400 ppb), and cyp3a mRNA expression levels, while reducing the GST enzymatic activity and mRNA expression levels in northern snakehead. Furthermore, AFB1 (≥ 100 ppb) increased ROS, MDA, and 8-OHdG levels, and grp78, ire1, perk, jnk, chop, and traf2 mRNA expression levels, and decreased SOD, CAT, GSH-Px, and GSH (except 100 ppb) levels and the gene expression levels of cat, gsh-px (except 100 ppb), and Cu/Zn sod. In addition, AFB1 (100, 200, and 400 ppb) up-regulated the cyt-c, bax, cas-3, and cas-9 mRNA levels in the liver, while down-regulating the bcl-2 expression levels. Meanwhile, the expression levels of nf-κb, tnf-α (except 100 ppb), il-1ß, and il-8 in the liver were up-regulated in AFB1 treatment groups (≥ 100 ppb), while the iκbα mRNA levels were down-regulated. In summary, dietary AFB1 reduced growth performance and humoral immunity in northern snakehead. Meanwhile, the cyclic occurrence of oxidative stress and ER stress, and induced apoptosis and inflammation, is one of the main reasons for AFB1-induced liver injury in the northern snakehead, which will provide valuable information and a fresh perspective for further research into AFB1-induced liver injury in fish.

Oral Administration of Lactobacillus Casei Expressing Flagellin A Protein Confers Effective Protection against Aeromonas Veronii in Common Carp, Cyprinus Carpio.

Aeromonas veronii is a pathogen capable of infecting humans, livestock and aquatic animals, resulting in serious economic losses. In this study, two recombinant Lactobacillus casei expressing flagellin A (FlaA) of A. veronii, Lc-pPG-1-FlaA (surface-displayed) and Lc-pPG-2-FlaA (secretory) were constructed. The immune responses in fish administered with recombinant L. casei were evaluated. The two recombinant L. casei were orally administered to common carp, which stimulated high serum IgM and induced higher ACP, AKP, SOD and LYZ activity. Using qRT-PCR, the expression of IL-10, IL-8, IL-1ß, TNF-α and IFN-γ in the tissue of fish immunized with recombinant L. casei was significantly (p < 0.05) upregulated, which indicated that recombinant L. casei could activate the innate immune system to trigger the cell immune response and inflammatory response. Furthermore, recombinant L. casei was able to survive the intestinal environment and colonize in intestine mucosal. The study showed that after being challenged by A. veronii, fish administered with Lc-pPG-1-FlaA (70%) and Lc-pPG-2-FlaA (50%) had higher survival rates compared to Lc-pPG and PBS, indicating that recombinant L. casei might prevent A. veronii infection by activating the immune system to trigger immune responses. We demonstrated that flagellin as an antigen of vaccine, is acceptable for preventing A. veronii infection in fish. The recombinant L. casei expressing FlaA may be a novel mucosal vaccine for treating and controlling A. veronii.