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Myricetin, a natural flavonoid found in various foods, was investigated for its antiviral effect against transmissible gastroenteritis virus (TGEV). This α-coronavirus causes significant economic losses in the global swine industry. The study focused on the papain-like protease (PLpro), which plays a crucial role in coronavirus immune evasion by mediating deubiquitination. Targeting PLpro could potentially disrupt viral replication and enhance antiviral responses. The results demonstrated that myricetin effectively inhibited TGEV-induced cytopathic effects in a dose-dependent manner, with an EC50 value of 31.19 μM. Myricetin significantly reduced TGEV viral load within 48 h after an 8-h co-incubation period. Further investigations revealed that myricetin at a concentration of 100 μM directly inactivated TGEV and suppressed its intracellular replication stage. Moreover, pretreatment with 100 μM myricetin conferred a protective effect on PK-15 cells against TGEV infection. Myricetin competitively inhibited PLpro with an IC50 value of 6.563 μM. Molecular docking experiments show that myricetin binds to the Cys102 residue of PLpro through conventional hydrogen bonds, Pi-sulfur, and Pi-alkyl interactions. This binding was confirmed through site-directed mutagenesis experiments, indicating myricetin as a potential candidate for preventing and treating TGEV infection.

ABSTRACT: Currently, developing nonantibiotic growth promoters is a broad consensus in broiler industry, which is one of the effective ways to reduce drug-resistant strains. Chuanminshen violaceum is a traditional Chinese medicinal herb that is commonly used for its roots, while the stems and leaves are often discarded, resulting in a huge amount of waste. This study optimized the preparation process of water extract of Chuanminshen violaceum stems and leaves (CVSLE) by response surface analysis based on the yields of polysaccharide and protein. The CVSLE and herbal powder (CVSL) were then processed into granules before being used as feed additives. The Macleaya cordata powder was used as positive control. The results showed that the addition of CVSLE (0.5% of the feed) showed the highest growth-promoting activity than other CVSLE groups (0.2% and 1%), 1% CVSL group and positive control (0.05%). CVSLE at the dosage of 0.5% could significantly increase the ADG and reduce the FCR from d 21 to 42, d 0 to 42. The HI antibody titers against Newcastle disease virus and avian influenza virus were significantly enhanced at 21, 28 and 42 d. CVSLE did not affect the slaughtering performances, but could significantly elevate the spleen, thymus and bursa of Fabricius indices and the transcriptional levels of IL-2, IL-4, IL-10 and IFN-γ in spleen. The intestinal barrier function of broilers was significantly enhanced by increased levels of immune barrier (sIgA), physical barrier (ZO-1, OCL and Muc-2) and flora barrier (Lactobacillus and Bifidobacterium). These results suggest that CVSLE was a promising herbal additive candidate for broilers.

Pullorum disease (PD) is a bacterial infection caused by Salmonella pullorum (S. pullorum) that affects poultry. It is highly infectious and often fatal. Antibiotics are currently the mainstay of prophylactic and therapeutic treatments for PD, but their use can lead to the development of resistance in pathogenic bacteria and disruption of the host's intestinal flora. We added neomycin sulfate and different doses of tannic acid (TA) to the drinking water of chicks at 3 days of age and infected them with PD by intraperitoneal injection of S. pullorum at 9 days of age. We analyzed intestinal histopathological changes and the expression of immune-related genes and proteins by using the plate smear method, histological staining, real-time fluorescence quantitative PCR, ELISA kits, and 16S rRNA Analysis of intestinal flora. The results demonstrate that S. pullorum induces alterations in the immune status and impairs the functionality of the liver and intestinal barrier. We found that tannic acid significantly ameliorated S. pullorum-induced liver and intestinal damage, protected the intestinal physical and chemical barriers, restored the intestinal immune barrier function, and regulated the intestinal flora. Our results showed that TA has good anti-diarrhoeal, growth-promoting, immune-regulating, intestinal barrier-protecting and intestinal flora-balancing effects, and the best effect was achieved at an additive dose of 0.2%.

Redox balance plays an important role in testicular homeostasis. While lots of antioxidant molecules have been identified as widely expressed, the understanding of the critical mechanisms for redox management in male germ cells is inadequate. This study identified LanCL2 as a major male germ cell-specific antioxidant gene that is important for testicular homeostasis. Highly expressed in the brain and testis, LanCL2 expression correlates with testicular maturation and brain development. LanCL2 is enriched in spermatocytes and round spermatids of the testis. By examining LanCL2 knockout mice, we found that LanCL2 deletion did not affect postnatal brain development but injured the sperm parameters of adult mice. With histopathological analysis, we noticed that LanCL2 KO caused a pre-maturation and accelerated the self-renewal of spermatogonial stem cells in the early stage of spermatogenesis. In contrast, at the adult stage, LanCL2 KO damaged the acrosomal maturation in spermiogenesis, resulting in spermatogenic defects with a reduced number and motility of spermatozoa. Furthermore, we show that this disruption of testicular homeostasis in the LanCL2 KO testis was due to dysbalanced testicular redox homeostasis. This study demonstrates the critical role of LanCL2 in testicular homeostasis and redox balance.

Lead and cadmium are foodborne contaminants that threaten human and animal health. It is well known that lead and cadmium produce hepatotoxicity; however, defense mechanisms against the co-toxic effects of lead and cadmium remain unknown. We investigated the mechanism of autophagy (defense mechanism) against the co-induced toxicity of lead and cadmium in rat hepatocytes (BRL-3A cells). Cultured rat liver BRL-3A cell lines were co-cultured with 10, 20, 40 μM lead and 2.5, 5, 10 μM cadmium alone and in co-culture for 12 h and exposed to 5 mM 3-Methyladenine (3-MA), 10 μM rapamycin (Rapa), and 50 nM Beclin1 siRNA to induce cellular autophagy. Our results show that treatment of BRL-3A cells with lead and cadmium significantly decreased the cell viability, increased intracellular reactive oxygen species levels, decreased mitochondrial membrane potential levels, and induced apoptosis, which are factors leading to liver injury, and cell damage was exacerbated by co-exposure to lead–cadmium. In addition, the results showed that lead and cadmium co-treatment induced autophagy. We further observed that the suppression of autophagy with 3-MA or Beclin1 siRNA promoted lead–cadmium-induced apoptosis, whereas enhancement of autophagy with Rapa suppressed lead–cadmium-induced apoptosis. These results demonstrated that co-treatment with lead and cadmium induces apoptosis in BRL-3A cells. Interestingly, the activation of autophagy provides cells with a self-protective mechanism against induced apoptosis. This study provides insights into the role of autophagy in lead–cadmium-induced apoptosis, which may be beneficial for the treatment of lead–cadmium-induced liver injury.

The antibiotic resistance of Acinetobacter baumannii poses a significant threat to global public health, especially those strains that are resistant to carbapenems. Therefore, novel strategies are desperately needed for the treatment of infections caused by antibiotic-resistant A. baumannii. In this study, we report that brevicidine, a bacterial non-ribosomally produced cyclic lipopeptide, shows synergistic effects with multiple outer membrane-impermeable conventional antibiotics against A. baumannii. In particular, brevicidine, at a concentration of 1 μM, lowered the minimum inhibitory concentration of erythromycin, azithromycin, and rifampicin against A. baumannii strains by 32–128-fold. Furthermore, mechanistic studies were performed by employing erythromycin as an example of an outer membrane-impermeable conventional antibiotic, which showed the best synergistic effects with brevicidine against the tested A. baumannii strains in the present study. The results demonstrate that brevicidine disrupted the outer membrane of A. baumannii at a concentration range of 0.125–4 μM in a dose-dependent manner. This capacity of brevicidine could help the tested outer membrane-impermeable antibiotics enter A. baumannii cells and thereafter exert their antimicrobial activity. In addition, the results show that brevicidine–erythromycin combination exerted strong A. baumannii killing capacity by the enhanced inhibition of adenosine triphosphate biosynthesis and accumulation of reactive oxygen species, which are the main mechanisms causing the death of bacteria. Interestingly, brevicidine and erythromycin combination showed good therapeutic effects on A. baumannii-induced mouse peritonitis–sepsis models. These findings demonstrate that brevicidine is a promising sensitizer candidate of outer membrane-impermeable conventional antibiotics for treating A. baumannii infections in the post-antibiotic age.

Abstract Solid oxide cells (SOCs) are all solid ceramic devices with the dual functionality of solid oxide fuel cells (SOFCs) to convert the chemical energy of fuels like H2, natural gas and other hydrocarbons to electricity and of solid oxide electrolysis cells (SOECs) to store renewable electric energy of sun and wind in hydrogen fuel. Among the electrochemical energy conversion and storage devices, SOCs are the most clean and efficient technology with unique dual functionality. Due to the high operation temperature (typically 600–800°C), SOCs exhibit many advantages over other energy conversion devices, such as low material cost, high efficiency and fuel flexibility. There has been rapid development of SOC technologies over the last decade with significant advantages and progress in key materials and a fundamental understanding of key issues such as an electrode, electrolyte, performance degradation, poisoning, and stack design. The reversible polarization also has a critical effect on the surface segregation and stability of the electrode and electrode/electrolyte interface. This critical review starts with a brief introduction, working principles and thermodynamics of SOC technology to readers with interests in this rapidly developing and emerging field. Then the key materials currently used in SOCs are summarized, followed by the discussion of the most advanced electrode modification methods and critical issues of SOCs, including the surface chemistry, segregation, electrode/electrolyte interface and varying material degradation mechanisms under reversible operations. The challenges and prospects of SOC technology for future developments are discussed.

Abstract Background Organic selenium supplementation during gestation improves the antioxidant status and reproductive performance of sows and increases the antioxidative capacity of the intestines of their offspring. This study was conducted to investigate the effect of maternal basel diet (control) supplemented with an organic Se, 2-hydroxy-4-methylselenobutanoic acid (HMSeBA), or inorganic sodium selenite (Na2SeO3) during gestation on the antioxidant status and development of muscle in newborn and weaned piglets. Newborn piglets before colostrum intake and weaned piglets were selected for longissimus dorsi (LD) muscle collection and analysis. Results The results showed that maternal HMSeBA supplementation increased the muscle area and content of Se in the LD muscle of newborn piglets, improved gene expression of selenoproteins, and decreased oxidative status in the LD muscle of both newborn and weaned piglets compared with the control. The expression of muscle development-related genes of newborn piglets in the HMSeBA group was lower than in the control group, whereas the expression of MRF4 in weaned piglets was higher in the HMSeBA group than in the control and Na2SeO3 groups. In addition, HMSeBA supplementation decreased the mRNA expressions of myosin heavy chains (MyHC) IIx and MyHC IIb and the percentage of MyHC IIb; increased the expression of PGC-1α in the LD muscle of newborn piglets; increased the gene expression of MyHC IIa; and decreased the protein expression of slow MyHC and the activity of malate dehydrogenase in the LD muscle of weaned piglets compared with the control group. Conclusions Maternal HMSeBA supplementation during gestation can improve the antioxidative capacity of the muscle of their offspring and promote the maturity of muscle fibres in weaned offspring.

Major depression disorder is more common among adolescents and is a primary reason for suicide in adolescents. Some antidepressants are ineffective and may possess side effects. Therefore, developing an adolescent antidepressant is the need of the hour. We designed the stress model of adolescent male mice induced by chronic unpredictable stress (CUS). The mice were treated using Tongxieyaofang neutral polysaccharide (TXYF-NP), Tongxieyaofang acidic polysaccharide (TXYF-AP), TXYF-AP + TXYF-NP and fructooligosaccharide + galactooligosaccharides to determine their body weight, behavior, and serum hormone levels. RT-qPCR was used to detect the gene expression of Crhr1, Nr3c1, and Nr3c2 in the hypothalamus and hippocampus and the gene expression of glutamic acid and γ-aminobutyric acid-related receptors in the hippocampus. RT-qPCR, Western blot, and ELISA detected tryptophan metabolism in the colon, serum, and hippocampus. 16s rDNA helped sequence colon microflora, and non-targeted metabolomics enabled the collection of metabolic profiles of colon microflora. In adolescent male mice, CUS induced depression-like behavior, hypothalamic–pituitary–adrenal axis hyperactivity, hippocampal tissue damage, abnormal expression of its related receptors, and dysregulation of tryptophan metabolism. The 16s rDNA and non-targeted metabolomics revealed that CUS led to colon microflora disorder and bile acid metabolism abnormality. Tongxieyaofang polysaccharide could improve the bacterial community and bile acid metabolism disorder by upregulating the relative abundance of Lactobacillus gasseri, Lachnospiraceae bacterium 28–4, Bacteroides and Ruminococcaceae UCG-014 while preventing CUS-induced changes. TXYF-P can inhibit depression-like behavior due to CUS by regulating colonic microflora and restoring bile acid metabolism disorder. Thus, based on the different comparisons, TXYF-NP possessed the best effect.

Background: Pseudorabies virus (PRV) infections in susceptible non-porcine species trigger uncontrolled inflammations and eventually fatal encephalitis. Resveratrol (Res) has broad pharmacological functions including anti-virus, anti-inflammation, and neuroprotective. Purpose: We attempted to investigate the potential of Res in ameliorating PRV infection pathology in mice and decipher the mechanism of Res in treating PRV. Methods: The mice were infected by PRV to investigate the protective effect of Res. Blood-brain barrier (BBB) permeability, H&E/Nissl/TUNEL staining, Real-time PCR and ELISA analyses were performed. Primary microglia and neuron were isolated from mice and cultured. The co-culture model of microglia and neuron was established by transwell. Immunofluorescence assay and flow cytometry were used. Results: In this study, we showed that Res ameliorated brain damage by reducing BBB permeability in PRV-infected mice, and diminished the expressions of MMP-2, MMP-9 and ZO-1 in the cortex. Pathological changes of neurons by H&E/Nissl/TUNEL staining suggested that Res could alleviate neuronal lesions. Moreover, Res inhibited the expressions of pro-inflammatory factors (IL-6, TNF-α) and chemokines (CCL3, CXCL10, MCP-1), but increased the expressions of anti-inflammatory factors (IL-4, IL-10) and neurotrophic factor (TGF-β, NGF and GDNF) in brain. In vitro cultured microglia cells, Res could suppress M1 microglia polarization and activate M2 microglia polarization. Co-culture of PRV-infected microglia with neuron cells by transwell system indicated that Res alleviated inflammatory response and neuronal apoptosis. Conclusion: This study provided evidence that Res could protect mice from PRV-induced encephalitis through regulation of microglia polarization and neuronal apoptosis suggesting the potential for treatment of viral encephalitis.

Eriodictyol occurs naturally in a variety of fruits and vegetables, and has drawn significant attention for its potential health benefits. This study aims to look into the effects of eriodictyol on acute liver injury (ALI) induced by LPS/D-GalN and elucidate its potential molecular biological mechanisms. A total of 47 targets were predicted for the treatment of ALI with eriodictyol, and the PI3K/AKT signaling pathway played a key role in the anti-ALI processing of this drug. The in vivo experiment showed that eriodictyol can effectively reduce liver function-related biochemical indicators such as ALT, AST, and AKP. Eriodictyol can also up-regulate the levels of SOD and GSH, and inhibit the release of IL-1β, IL-6, and TNF-α. Additionally, TUNEL staining, immunohistochemistry, and RT-PCR experiments showed that eriodictyol activated the PI3K/AKT pathway and decreased the expression of Bax, caspase3, and caspase8 while increasing the expression of Bcl-2 m-RNA. Finally, molecular docking experiments and molecular dynamics simulations confirmed the stable binding between eriodictyol and PI3K, AKT molecules. This study showed that eriodictyol can activate the PI3K/AKT signaling pathway to alleviate ALI-related oxidative stress and apoptosis.

Abstract In recent years, with the improvement of people's living standard and the change of diet structure, liver disease and its related complications have become a significant public health problem globally. Pueraria lobata (Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep) belongs to the genus Pueraria, which is widely planted and used as medicine and food in Asia with a long history. A variety of natural active products, including puerarin, daidzein, formononetin, genistein, and soyasaponin, have been isolated and identified from pueraria lobata. A large number of studies have shown that various natural active products of pueraria lobata can play a protective role in different types of liver diseases by regulating oxidative stress, inflammatory response, lipid metabolism, etc. In this review, we focused on the protective effects of isoflavones and triterpenoid saponins from pueraria lobata on the liver through different targeted therapeutic mechanisms. What's more, we summarized their therapeutic potential for different types of liver diseases to provide evidence for their clinical application.

Aging is a biological process that leads to the progressive deterioration and loss of physiological functions in the human body and results in an increase in morbidity and mortality, and aging-related disease is a major global problem that poses a serious threat to public health. Polysaccharides have been shown to delay aging by reducing oxidative damage, suppressing inflammatory responses, and modulating intestinal microbiota. Our previous studies have shown that polysaccharide CPP-1 extracted from the root of Codonopsis pilosula possesses noticeable anti-oxidant activity in vitro. Thus, in our study, we tested the anti-aging effect of CPP-1 in naturally aging mice (in vivo). Eighteen C57/BL mice (48-week-old, male) were divided into a control group, high-dose CPP-1 group (20 mg/mL), and low-dose CPP-1 group (10 mg/mL). We discovered that CPP-1 can exert a reparative effect on aging stress in the intestine and liver, including alleviating inflammation and oxidative damage. We revealed that CPP-1 supplementation improved the intestinal microbiota composition and repaired the intestinal barrier in the gut. Furthermore, CPP-1 was proved to modulate lipid metabolism and repair hepatocyte injury in the liver by influencing the enterohepatic axis associated with the intestinal microbiota. Therefore, we concluded that CPP-1 prevents and alleviates oxidative stress and inflammatory responses in the intestine and liver of aging mice by modulating the intestinal microbiota-related gut–liver axis to delay aging.

Polygonati Rhizoma is a widely used traditional Chinese medicine (TCM) with complex pre-processing steps. Fermentation is a common method for processing TCM to reduce herb toxicity and enhance their properties and/or produce new effects. Here, in this study, using Bacillus subtilis and Saccharomyces cerevisiae, we aimed to evaluate the potential application of solid fermentation in isolating different functional polysaccharides from Polygonatum cyrtonema Hua. With hot water extraction, ethanol precipitation, DEAE anion exchange chromatography and gel filtration, multiple neutral and acidic polysaccharides were obtained, showing different yields, content, compositions and functional groups after fermentation. Combining in vitro experiments and in vivo aging and immunosuppressed mouse models, we further compared the antioxidant and immunomodulating bioactivities of these polysaccharides and found a prominent role of a natural polysaccharide (BNP) from fermented P. cyrtonema via Bacillus subtilis in regulating intestinal antioxidant defense and immune function, which may be a consequence of the ability of BNP to modulate the homeostasis of gut microbiota. Thus, this work provides evidence for the further development and utilization of P. cyrtonema with fermentation, and reveals the potential values of BNP in the treatment of intestinal disorders.

Fungal-infections are mostly due to fungi in an adhering, biofilm-mode of growth and not due to planktonically growing, suspended-fungi. 1, 8-cineole is a natural product, which has been shown to possess antifungal effect. However, the anti-biofilm effect and mechanism of 1,8-cineole against Fusarium solani species complex has not reported previously. In this study, we found that 1,8-cineole has a good antifungal activity against F. solani with an MIC value of 46.1 μg/ml. Notably, 1,8-cineole showed good anti-biofilm formation activity against F. solani via inhibiting cell adhesion, hypha formation and decreasing the secretion of extracellular matrix at the concentration of ≥5.76 μg/ml. In addition, transcriptome sequencing analysis results showed that F. solani species complex genes related to ECM, protein synthesis and energy metabolism were down-expressed in the biofilms formation process treated with 1,8-cineole. In conclusion, these results show that 1,8-cineole has good anti-biofilm formation activity against F. solani species complex, and it exerts its anti-biofilm formation activity by downregulating of ergosterol biosynthetic genes, inhibiting adhesion, hindering the synthesis of ECM and interfering mitochondrial activity. This study suggests that 1,8-cineole is a promising anti-biofilm agent against F. solani species complex.

In recent years, with frequent reports of multi-drug resistant strains, bacteria antibiotic resistance has become an increasingly serious health problem worldwide. One of the most promising ways for combating bacterial infections and antibiotic resistance is development of quorum-sensing (QS) interfering drugs. In this study, the results show that 1,8-cineole inhibited the expression of QS as well as the virulence genes in Escherichia coli O101 (E. coli O101) with a 65% inhibition rate against luxS gene. Therefore, we hypothesized that 1,8-cineole may inhibit the biofilm formation and reduce the pathogenicity of E. coli O101 by inhibiting the expression of luxS gene. To confirm our hypotheses, a luxS gene deleted E. coli O101 was constructed. The results show that the biofilm formation, motility, structure and pathogenicity of E. coli O101 were significantly inhibited following deletion of the luxS gene. In addition, the transcript levels of QS and virulence genes of E. coli O101 were also significantly down-regulated. Interestingly, 1,8-cineole no longer had a significant inhibitory effect on the related phenotype and gene expression of E. coli O101 without luxS gene. In conclusion, the results show that 1,8-cineole can affect bacterial biofilm formation and pathogenicity by suppressing the expression of luxS gene in E. coli O101, which could provide a new perspective for dealing with the biofilm problem of pathogenic bacteria.

Abstract Background Pseudorabies virus (PRV), a member of the Alphaherpesviruses, is one of the most important pathogens that harm the global pig industry. Accumulated evidence indicated that PRV could infect humans under certain circumstances, inducing severe clinical symptoms such as acute human encephalitis. Currently, there are no antiviral drugs to treat PRV infections, and vaccines available only for swine could not provide full protection. Thus, new control measures are urgently needed. Results In the present study, kaempferol exhibited anti-PRV activity in mice through improving survival rate by 22.22 %, which was higher than acyclovir (Positive control) with the survival rate of 16.67 % at 6 days post infection (dpi); meanwhile, the survival rate was 0 % at 6 dpi in the infected-untreated group. Kaempferol could inhibit the virus replication in the brain, lung, kidney, heart and spleen, especially the viral gene copies were reduced by over 700-fold in the brain, which was further confirmed by immunohistochemical examination. The pathogenic changes induced by PRV infection in these organs were also alleviated. The transcription of the only immediate-early gene IE180 in the brain was significantly inhibited by kaempferol, leading to the decreased transcriptional levels of the early genes (EPO and TK). The expression of latency-associated transcript (LAT) was also inhibited in the brain, which suggested that kaempferol could inhibit PRV latency. Kaempferol-treatment could induce higher levels of IL-1β, IL-4, IL-6, TNF-α and IFN-γ in the serum at 3 dpi which were then declined to normal levels at 5 dpi. Conclusions These results suggested that kaempferol was expected to be a new alternative control measure for PRV infection.

Octadecanoic acid-3,4-tetrahydrofuran diester is a compound with acaricidal activity isolated and extracted from neem oil. In this study, a series of derivatives were obtained by structural modification of octadecanoic acid-3,4-tetrahydrofuran diester. The acaricidal activity of these derivatives indicated that introduction of benzyloxy substitution at the 2-position of the furan ring and the formation of a benzoate at the 3,4-position of the furan ring (benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester) could enhance the acaricidal activity. At concentration of 20, 10, and 5 mg/ml, the median lethal time (LT50) values of benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester were 16.138, 47.274, and 108.122 min, respectively. The LC50 value of benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester at 60 min was 5.342 mg/ml. Transmission electron microscopy showed that after treatment with benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester, the body structure of mites was destroyed; dermal organelles were dissolved; nuclear chromatin was ablated. Further, transcriptome sequencing analysis was used to get insight into the acaricidal mechanism of benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester. The results showed that its acaricidal mechanism is related to interfering “energy metabolism” in S. scabiei, including processes such as citric acid cycle, oxidative phosphorylation pathway and fatty acid metabolism. Additionally, through the activity detection of the mitochondrial complexes of S. scabiei, it was further verified that the acaricidal mechanism of benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester was related to the energy metabolism system of S. scabiei.

Dietary oxidized fat contains harmful materials such as hydrogen peroxide and malondialdehyde (MDA). Excessive oxidized fat intake during pregnancy and lactation not only leads to maternal body injury but also damages offspring health. Our previous study demonstrated that vitamin D (VD) had antioxidative capability in sows. This study was conducted to investigate the effect of maternal VD and inulin supplementation in oxidized oil diet on the growth performance and oxidative stress of their offspring. Sixty 5-month-old C57BL/6N female mice were randomly divided into five groups: Control group (basal diet, n = 12), OF group (oxidized-soybean-oil-replaced diet, n = 12), OFV group (oxidized-soybean-oil-replaced diet + 7000 IU/kg VD, n = 12), OFI group (oxidized-soybean-oil-replaced diet + 5% inulin, n = 12) and OFVI group (oxidized-soybean-oil-replaced diet + 7000 IU/kg VD + 5% inulin, n = 12). Mice were fed with the respective diet during pregnancy and lactation. The offspring were then slaughtered on day 21 of age at weaning. Results showed that a maternal oxidized oil diet impaired body weight and liver weight gain of offspring during lactation compared to the control group, while maternal VD, inulin or VD and inulin mixture supplementation reversed this effect. In addition, the activity of T-AOC in the liver of offspring was lower in the OF group than that in the control group, but could be restored by maternal VD and inulin mixture supplementation. Furthermore, the gene expression of both proinflammatory and anti-inflammatory cytokines, such as Il-6, Tnfα and Il-10, in offspring liver were downregulated by a maternal oxidized oil diet compared with the control group, but they were restored by maternal VD or VD and inulin mixture supplementation. The expressions of Vdr and Cyp27a1 were decreased by a maternal oxidized oil diet compared with the control group, while they could be increased by VD or VD and inulin mixture supplementation. Conclusion: maternal oxidized oil diet intake could impair the growth performance by inducing oxidative stress, but this can be relieved by maternal VD and inulin supplementation.

Resveratrol is a natural polyphenolic product in red wine and peanuts and has many pharmacological activities in humans. Our previous studies showed that resveratrol has good antiviral activity against the pseudorabies virus (PRV). However, little is known about the antiviral mechanism of resveratrol against PRV. In this study, we found that resveratrol inhibited the nuclear localization of IE180 protein, which is an important step for activating early/late genes transcription. Interestingly, the results show that resveratrol inhibited the activity of IE180 protein by dual-luciferase assay. Furthermore, molecular docking analysis shows that resveratrol could bind to the Thr601, Ser603, and Pro606 of IE180 protein. Point mutation assay confirmed that resveratrol lost its inhibition activity against the mutant IE180 protein. The results demonstrate that resveratrol exerts its antiviral activity against PRV by targeting the Thr601/Ser603/Pro606 sites of IE180 protein and inhibiting the transcriptional activation activity of IE180 protein. This study provides a novel insight into the antiviral mechanism of resveratrol against herpes viruses.

Endoplasmic reticulum (ER) stress, which can be induced by reactive oxygen species (ROS) and multiple factors, is associated with numerous intestinal diseases. The organic selenium source 2-hydroxy-4-methylselenobutanoic acid (HMSeBA), has been proved to decrease intestinal inflammation and autophagy by improving the expression of selenoproteins. However, it remains unclear whether HMSeBA could alleviate intestinal ER stress by decreasing excessive production of ROS products. This study was conducted to investigate the effect of maternal HMSeBA supplementation on the regulation of intestinal ER stress of their offspring and the regulatory mechanism. Sows were supplemented with HMSeBA during gestation and jejunal epithelial (IPEC-J2) cells were treatment with HMSeBA. Results showed that maternal HMSeBA supplementation significantly upregulated mRNA level of selenoprotein S (SELS) in the jejunum of newborn and weaned piglets compared with the control group, while decreased the gene expression and protein abundance of ER stress markers in the jejunum of LPS challenged weaned piglets. In addition, HMSeBA treatment significantly increased the expression of glutathione peroxidase 4 (GPX4) and SELS, while decreased ROS level and the expression of ER stress markers induced by hydrogen peroxide (H2O2) in IPEC-J2 cells. Furthermore, knockdown of GPX4 did not enhance the ERS signal induced by H2O2, but the lack of GPX4 would cause further deterioration of ER stress signal in the absence of SELS. In conclusion, maternal HMSeBA supplementation might alleviate ROS induced intestinal ER stress by improving the expression of SELS and GPX4 in their offspring. Thus, maternal HMSeBA supplementation might be benefit for the intestinal health of their offspring.

The superbug Pseudomonas aeruginosa is among the most formidable antibiotic-resistant pathogens. With declining options for antibiotic-resistant infections, new medicines are of utmost importance to combat with P. aeruginosa. In our previous study, we demonstrated that Epigallocatechin-3-gallate (EGCG) can inhibit the production of quorum sensing (QS)-regulated virulence factors in vitro. Accordingly, the protective effect and molecular mechanisms of EGCG against P. aeruginosa-induced pneumonia were studied in a mouse model. The results indicated that EGCG significantly lessened histopathological changes and increased the survival rates of mice infected with P. aeruginosa. EGCG effectively alleviated lung injury by reducing the expression of virulence factors and bacterial burden. In addition, EGCG downregulated the production of pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6, and IL-17, and increased the expression of anti-inflammatory cytokines IL-4 and IL-10. Thus, the experimental results supported for the first time that EGCG improved lung damage in P. aeruginosa infection by inhibiting the production of QS-related virulence factors in vivo.

Infectious bronchitis virus (IBV) is the first coronavirus discovered in the world, which is also the prototype of gamma-coronaviruses. Nowadays, IBV is widespread all over the world and has become one of the causative agent causing severe economic losses in poultry industry. Generally, it is believed that the viral replication and immune evasion functions of IBV were modulated by non-structural and accessory proteins, which were also considered as the causes for its pathogenicity. In this study, we summarized the current knowledge about the immune evasion functions of IBV non-structural and accessory proteins. Some non-structural proteins such as nsp2, nsp3, and nsp15 have been shown to antagonize the host innate immune response. Also, nsp7 and nsp16 can block the antigen presentation to inhibit the adapted immune response. In addition, nsp13, nsp14, and nsp16 are participating in the formation of viral mRNA cap to limit the recognition by innate immune system. In conclusion, it is of vital importance to understand the immune evasion functions of IBV non-structural and accessory proteins, which could help us to further explore the pathogenesis of IBV and provide new horizons for the prevention and treatment of IBV in the future.

Abstract Background Enterotoxigenic Escherichia coli (ETEC) is classically associated with acute secretory diarrhea, which induces 2 million people death in developing countries over a year, predominantly children in the first years of life. Previously, tannins (47.75%) were extracted from Galla Chinensis and prepared as Galla Chinensis oral solution (GOS) which showed significant antidiarrheal activity in a castor oil-induced diarrhea in mice. Whether the tannins extract were also effective in treatment of ETEC-induced diarrhea was determined in this study. Methods Mice were randomly divided into 6 groups (n = 22). The mice in the normal and untreated groups were given normal saline. Three GOS-treated groups were received different concentrations of GOS (5, 10 and 15%, respectively) at a dose of 10 mL/kg. Mice in the positive control group were fed with loperamide (10 mg/kg). The treatment with GOS started 3 days before infection with ETEC and continued for 4 consecutive days after infection. On day 3, mice were all infected with one dose of LD50 of ETEC, except those in the normal group. Survival of mice was observed daily and recorded throughout the study. On days 4 and 7, samples were collected from 6 mice in each group. Results GOS could increase the survival rate up to 75%, while in the untreated group it is 43.75%. The body weights of mice treated with 15% GOS were significantly increased on day 7 in comparison with the untreated group and the normal group. GOS-treatment recovered the small intestine coefficient enhanced by ETEC-infection. The diarrhea index of mice treated with GOS was significantly decreased. GOS increased the levels of IgG and sIgA in the terminal ileum and decreased the levels of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, IL-6 and IL-8) in serum. GOS could increase the amount of intestinal probiotics, Lactobacilli and Bifidobacteria. GOS could alleviate colon lesions induced by ETEC-infection. GOS showed higher potency than loperamide. Conclusions GOS could be a promising drug candidate for treating ETEC infections.

Various studies have evaluated the relationship between cholecalciferol (vitamin D3) and reproductive performance. This study aimed at investigating the effects of maternal D3 supplementation during gestation on reproductive performance and antioxidant capacities of gilts and their offsprings. Twenty-three Landrace × Yorkshire gilts were randomly allocated into two groups and fed on one of the following two diets during gestation: control diet or D3 supplemented diet. It was found that D3 supplementation had a tendency to increase the number of total born and born alive piglets. Moreover, it elevated serum 25-hydroxycholecalciferol concentrations in gilts and newborn piglets. Besides, D3 supplementation improved the activities of antioxidant enzymes (GSH-Px, T-AOC and T-SOD) in the blood of gilts, umbilical cord and newborn piglets and piglets’ liver, while serum malondialdehyde concentrations of gilts and umbilical cord were reduced in the D3 group. In addition, D3 supplementation upregulated the expression of antioxidant related genes in the placenta and piglets’ liver. In conclusion, D3 supplementation during gestation might improve antioxidant capacities in gilts, placenta and in newborn piglets. Therefore, D3 supplementation has the potential to enhance the reproductive performance of gilts.HIGHLIGHTS D3 supplementation has a significant role in the nutrition of gilts. Maternal D3 supplementation during gestation increased the number of born and born alive piglets. Maternal D3 supplementation during gestation improved the antioxidant capacities of gilts, placenta and newborn piglets.

ABSTRACT: Infectious bronchitis virus (IBV) is a causative agent that causes severe economic losses in the poultry industry worldwide. Papain-like protease (PLpro) is a nonstructural protein encoded by IBV. It has deubiquitinating enzyme activity, which can remove the ubiqutin modification from the protein in nuclear factor kappa-B (NF-κB) and interferon regulatory factor 7 (IRF7) signaling pathway, so as to negatively regulate the host's innate immune response to promote viral replication. In this study, PLpro was selected as the target to screen antiviral agents against IBV. Through protein prokaryotic expression technology, we successfully expressed the active IBV PLpro. Among the 16 natural products, myricetin showed the strongest inhibitory effect on IBV PLpro. Next, we tested the antiviral activity of myricetin against IBV and verified whether it can exert antiviral activity by inhibiting the deubiquitinating activity of PLpro. The results showed that myricetin can significantly inhibit IBV replication in primary chicken embryo kidney (CEK) cells and it can significantly upregulate the transcription levels in the NF-κB and IRF7 signaling pathways. Moreover, we verified that myricetin can increase the ubiquitin modification level on tumor necrosis factor receptor-associated factor 3 and 6 (TRAF3 and TRAF6) reduced by IBV PLpro. In conclusion, these results indicated that myricetin exerts antiviral activity against IBV by inhibiting the deubiquitinating activity of PLpro, which can provide new perspective for the prevention and treatment of IBV.

Resveratrol is a naturally occurring stilbene phytoalexin phenolic compound, which has been extensively studied on its biological activity. It has been widely accepted that resveratrol possesses anti-inflammatory and antiviral activities. In this review, we summarize the anti-inflammatory dosages and mechanism and antiviral mechanism of resveratrol. Since viral infections are often accompanied by inflammation, we propose that the NF-κB signaling pathway is a key and common molecular mechanism of resveratrol to exert anti-inflammatory and antiviral effects. For future studies, we believe that resveratrol’s anti-inflammatory and antiviral mechanisms can consider the upstream signaling molecules of the NF-κB signaling pathway. For resveratrol antivirus, future studies can be conducted on the interaction of resveratrol with key proteins or important enzymes of the virus. In addition, we also think that the clinical application of resveratrol is very important. In short, resveratrol is a promising anti-inflammatory and antiviral drug, and research on it needs to be expanded.

Abstract In this study, the optimal naphthoquinones‐enriched ethanol extract from the roots of Onosma hookeri Clarke. var. longiforum Duthie (OHC‐LD) was obtained under an optimal condition (69% ethanol, material to solution ratio of 27:1 at 60℃ for 59 min) by the ultrasound‐assisted extraction, according to four‐variable three‐level Box–Behnken design‐response surface methodology. The experimental yield of ethanol extract was 42.08 ± 0.65%, and the contents of naphthoquinones reached to 1.07 ± 0.004%. The optimal extract exhibited similar scavenging activity against ABTS (2,2'‐azino‐bis‐3‐ethylbenzthiazoline‐6‐sulfonic acid) radical as BHT(butylated hydroxytoluene) at 1,250 µg/ml, and better DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) scavenging activity than BHT at 250 µg/ml. However, the optimal ethanol extract was not sensitive to MCF‐7 cell line ( IC50 of 321.849 µg/ml). The results revealed the naphthoquinones‐enriched ethanol extract from the roots of OHC‐LD had could be used as a potential natural antioxidant.

Context Resveratrol is a natural polyphenol compound. It exhibits antitumor, immunostimulatory, and antiviral activities. However, poor water solubility and structural instability limit its administration and storage. Objective A resveratrol dry suspension (RDS) was prepared and immunomodulatory effect in immunosuppressive mice induced by cyclophosphamide and anti-inflammatory activities in mice were evaluated. Materials and methods The preparation of RDS was optimized by the orthogonal design method. To evaluate the immunomodulatory effects, SPF Kunming mice were divided into seven groups comprising of nine males and nine females for each group. The RDS supplemented group was administrated doses of 3.33, 1.67, and 0.83 g/kg/d. Then visceral index, lymphocyte proliferation, the ratio of CD3+ CD4+/CD3+ CD8+, and the contents of cytokines in serum were tested. To ameliorate effects of acetic acid induced capillary permeability, xylene-based ear oedema, and cotton pellet granuloma, RDS as anti-inflammatory agent was administered at doses of 1, 0.33, and 0.1 g/kg/d as compared to indomethacin (IM) provided as a positive control at 10 mg/kg. Results RDS inhibited the degradation of resveratrol and enhanced the CD3+ CD4+/CD3+ CD8+ ratio, spleen index, IL-2 level, and splenic lymphocytes in immunosuppressive mice. RDS (0.1 g/kg/d) significantly inhibited the acetic acid-induced capillary permeability, and at doses of 0.33 and 1 g/kg/d repressed the ear swelling and granuloma formation in immunocompromised mice. Discussion and Conclusion RDS is a stable, cheaper, and suitable preparation with potent immunoregulatory and anti-inflammatory activities. Keeping in view these remarkable properties, RDS could be an appropriate preparation for clinic use of resveratrol.

Context Fructus Meliae toosendan extracts (FMTE) have a good therapeutic effect on coccidiosis, but there is no relevant research on its prophylactic effect on coccidiosis. Objective This study comprehensively evaluates the anticoccidial effect of FMTE. Materials and methods In vitro, the unsporulated oocysts were treated with serial dilutions of FMTE and incubated for 7 d, and the sporulated oocysts were counted for calculating the median lethal concentration (LC50) of FMTE. In vivo, 180 10-day-old broiler chickens free of coccidiosis were weighted and randomly distributed into six groups: normal group, untreated group, 4 protective groups (positive group and three FMTE groups). From day 10 to day 21, chickens in the three FMTE groups were pre-treated with FMTE at the dosage of 2.5, 5 and 10 g/kg/d, respectively, and chickens in the positive group were pre-treated with qiuliling (10 g/kg/d). On day 14, chickens in all groups except the normal group were orally infected with 1.5 × 104 sporulated oocysts. The clinical symptoms were observed from day 10 to day 21, the anticoccidial index (ACI), tissue lesions, and intestinal microflora were determined on day 21. Results FMTE showed anti-sporulation effect against E. tenella and the LC50 value was 245.83 µg/mL in vitro. In vivo, FMTE at the dosage of 10 g/kg/d was effective against E. tenella infection, and its ACI value was 162.56, which was higher than the value of positive drug qiuliling (128.81). Discussion and conclusions: FMTE have potent anticoccidial effects, and it presents an alternative anticoccidial agent for avian coccidiosis control.

Adipose tissue inflammation plays an important role in the regulation of glucose and lipids metabolism. It is unknown whether Ursolic acid (UA) could regulate adipose tissue inflammation, though it can regulate inflammation in many other tissues. In this study, 3T3-L1 adipocytes, DIO mice and lean mice were treated with UA or vehicle. Gene expression of inflammatory factors, chemokines and immune markers in adipocytes and adipose tissue, cytokines in cell culture medium and serum, and inflammation regulatory pathways in adipocytes were detected. Results showed that UA increased the expression of interleukins and chemokines, but not TNFα, in both adipocytes and adipose tissue. IL6 and MCP1 levels in the cell culture medium and mouse serum were induced by UA treatment. Cd14 expression level and number of CD14+ monocytes were higher in UA treated adipose tissue than those in the control group. Glucose tolerance test was impaired by UA treatment in DIO mice. Mechanistically, UA induced the expression of Tlr4 and the phosphorylation levels of ERK and NFκB in adipocytes. In conclusion, our study indicated that short-term UA administration could induce CD14+ monocytes infiltration by increasing the production of interleukins and chemokines in mouse adipose tissue, which might further impair glucose tolerance test.

ABSTRACT: The antiviral mechanism of sulfated polysaccharides is supposed to prevent virus entry, which is mediated by the interactions of anionic charges on sulfated polysaccharides with positively charged domains of viral envelope glycoproteins, leading to shielding of the functional domain involved in virus attachment to cell surface receptors. But, few direct evidences were reported. In the previous study, we found that sulfated Chuanmingshen violaceum polysaccharides (sCVPS) possessed remarkable inhibitory effect against Newcastle disease virus (NDV) through inhibition of NDV attachment to host cells. Whether sCVPS bound to hemagglutinin-neuraminidase (HN) leading to inhibition of NDV attachment needs to be further clarified. The present study conducted site-directed mutagenesis of possible positively charged residues of HN, and found that mutants R197G, H199G, R363G, and R523G could significantly decrease the inhibitory effects of sCVPS on receptor binding ability through hemadsorption assay, especially R363G which suggested that binding to R363 is more effective to shield the sialic acid binding sites. Dual mutants (R363G/R197G, R363G/H199G and R363G/R523G) induced more decreased inhibitory effect of sCVPS than single mutants. The immunofluorescence study using FITC-labeled sCVPS found that the fluorescence intensity of mutants R363G and R363G/H199G were significantly decreased. The binding kinetics of sCVPS to HN measured by surface plasmon resonance indicated that sCVPS had a higher binding affinity for wild-type HN than mutants R363G and R363G/H199G. Plaque reduction study was performed using recombinant NDV with mutant HNR363G and HNR363G/H199G, which showed significantly decreased inhibitory effects of sCVPS against mutant NDV adsorption to BHK-21 cells. These results suggested that the residues R197, H199, R363, and R523 were the binding sites for sCVPS, especially R363 act as the main interaction site. The present study provided direct evidence for the theory that antiviral mechanism of sulfated polysaccharides attributed to anionic groups binding to the positively charged residues of viral proteins which led to the shielding of receptor binding sites.

With the prevalence of multidrug-resistant bacteria and clinical -acquired pathogenic infections, the development of quorum-sensing (QS) interfering agents is one of the most potential strategies to combat bacterial infections and antibiotic resistance. Chinese herbal medicines constitute a valuable bank of resources for the identification of QS inhibitors. Accordingly, in this research, some compounds were tested for QS inhibition using indicator strains. Paeonol is a phenolic compound, which can effectively reduce the production of violacein without affecting its growth in Chromobacterium violaceum ATCC 12472, indicating its excellent anti-QS activity. This study assessed the anti-biofilm activity of paeonol against Gram-negative pathogens and investigated the effect of paeonol on QS-regulated virulence factors in Pseudomonas aeruginosa. A Caenorhabditis elegans infection model was used to explore the anti-infection ability of paeonol in vivo. Paeonol exhibited an effective anti-biofilm activity against Gram-negative bacteria. The ability of paeonol to interfere with the AHL-mediated quorum sensing systems of P. aeruginosa was determined, found that it could attenuate biofilm formation, and synthesis of pyocyanin, protease, elastase, motility, and AHL signaling molecule in a concentration- and time-dependent manner. Moreover, paeonol could significantly downregulate the transcription level of the QS-related genes of P. aeruginosa including lasI/R, rhlI/R, pqs/mvfR, as well as mediated its virulence factors, lasA, lasB, rhlA, rhlC, phzA, phzM, phzH, and phzS. In vivo studies revealed that paeonol could reduce the pathogenicity of P. aeruginosa and enhance the survival rate of C. elegans, showing a moderate protective effect on C. elegans. Collectively, these findings suggest that paeonol attenuates bacterial virulence and infection of P. aeruginosa and that further research elucidating the anti-QS mechanism of this compound in vivo is warranted.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide, thus treatments for it have attracted lots of interest. In this study, the Salviae miltiorrhizae Radix et Rhizoma (SMRR) polysaccharide was isolated by hot water extraction and ethanol precipitation, and then purified by DEAE anion exchange chromatography and gel filtration. With a high-fat-diet-induced obesity/NAFLD mouse model, we found that consumption of the SMRR polysaccharide could remarkably reverse obesity and its related progress of NAFLD, including attenuated hepatocellular steatosis, hepatic fibrosis and inflammation. In addition, we also reveal the potential mechanism behind these is that the SMRR polysaccharide could regulate the gut–liver axis by modulating the homeostasis of gut microbiota and thereby improving intestinal function.

A. hydrophila is an important pathogen that mainly harms aquatic animals and has exhibited resistance to a variety of antibiotics. Here, to seek an effective alternative for antibiotics, the effects of umbelliferone (UM) at sub-MICs on A. hydrophila virulence factors and the quorum-sensing system were studied. Subsequently, RNA sequencing was employed to explore the potential mechanisms for the antivirulence activity of umbelliferone. Meanwhile, the protective effect of umbelliferone on grass carp infected with A. hydrophila was studied in vivo. Our results indicated that umbelliferone could significantly inhibit A. hydrophila virulence such as hemolysis, biofilm formation, swimming and swarming motility, and their quorum-sensing signals AHL and AI-2. Transcriptomic analysis showed that umbelliferone downregulated expression levels of genes related to exotoxin, the secretory system (T2SS and T6SS), iron uptake, etc. Animal studies demonstrated that umbelliferone could significantly improve the survival of grass carps infected with A. hydrophila, reduce the bacterial load in the various tissues, and ameliorate cardiac, splenic, and hepatopancreas injury. Collectively, umbelliferone can reduce the pathogenicity of A. hydrophila and is a potential drug for treating A. hydrophila infection.

A maternal low-protein (LP) diet during gestation and/or lactation results in metabolic syndrome in their offspring. Here, we investigated the effect of maternal LP diet during puberty and adulthood on the metabolic homeostasis of glucose and lipids in offspring. Female mice were fed with normal-protein (NP) diet or a LP diet for 11 weeks. Male offspring were then fed with a high-fat diet (NP-HFD and LP-HFD groups) or standard chow diet (NP-Chow and LP-Chow groups) for 4 months. Results showed that maternal LP diet during puberty and adulthood did not alter the insulin sensitivity and hepatic lipid homeostasis of their offspring under chow diet, but aggravated insulin resistance, hepatic steatosis, and hypercholesterolemia of offspring in response to a post-weaning HFD. Accordingly, transcriptomics study with offspring’s liver indicated that several genes related to glucose and lipid metabolism, including lipoprotein lipase (Lpl), long-chain acyl-CoA synthetase 1 (Acsl1), Apoprotein A1 (Apoa1), major urinary protein 19 (Mup19), cholesterol 7α hydroxylase (Cyp7a1) and fibroblast growth factor 1 (Fgf1), were changed by maternal LP diet. Taken together, maternal LP diet during puberty and adulthood could disarrange the expression of metabolic genes in the liver of offspring and aggravate insulin resistance and hepatic steatosis in offspring fed a HFD.

Obesity is considered as a major cause for the development and progress of non-alcoholic fatty liver disease (NAFLD), which is one of the most prevalent chronic liver diseases worldwide. However, molecular mechanisms that implicate in obesity-driven pathophysiology of NAFLD are not well defined. Here, we report a tripartite motif (TRIM) protein family member—TRIM67—that is hardly expressed in liver but is inducible on obese conditions. Enhanced expression of TRIM67 activates hepatic inflammation to disturb lipid metabolic homeostasis and promote the progress of NAFLD induced by obesity, while the deficiency in TRIM67 is protective against these pathophysiological processes. Finally, we show that the important transcription coactivator PGC-1α implicates in the response of hepatic TRIM67 to obesity.

Reversible solid oxide cells (SOCs) are very efficient and clean for storage and regeneration of renewable electrical energy by switching between electrolysis and fuel cell modes. One of the most critical factors governing the efficiency and durability of SOCs technology is the stability of the interface between oxygen electrode and electrolyte, which is conventionally formed by sintering at a high temperature of ~1000–1250 ​°C, and which suffers from delamination problem, particularly for reversibly operated SOCs. On the other hand, our recent studies have shown that the electrode/electrolyte interface can be in situ formed by a direct assembly approach under the electrochemical polarization conditions at 800 ​°C and lower. The direct assembly approach provides opportunities for significantly simplifying the cell fabrication procedures without the doped ceria barrier layer, enabling the utilization of a variety of high-performance oxygen electrode materials on barrier layer–free yttria-stabilized zirconia (YSZ) electrolyte. Most importantly, the in situ polarization induced interface shows a promising potential as highly active and durable interface for reversible SOCs. The objective of this progress report is to take an overview of the origin and research progress of in situ fabrication of oxygen electrodes based on the direct assembly approach. The prospect of direct assembly approach in the development of effective SOCs and in the fundamental studies of electrode/electrolyte interface reactions is discussed.

Context: Methicillin-resistant Staphylococcus aureus (MRSA) is a very harmful bacterium. Oridonin, a component in Rabdosia rubescens (Hemsl.) Hara (Lamiaceae), is widely used against bacterial infections in China. Objective: We evaluated oridonin effects on MRSA cell membrane and wall, protein metabolism, lactate dehydrogenase (LDH), DNA and microscopic structure. Materials and methods: Broth microdilution and flat colony counting methods were used to measure oridonin minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against USA300 strain. Electrical conductivity and DNA exosmosis were analysed to study oridonin effects (128 μg/mL) on cell membrane and wall for 0, 1, 2, 4 and 6 h. Sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to detect effects on soluble protein synthesis after 6, 10 and 16 h. LDH activity was examined with an enzyme-linked immunosorbent assay. Effects of oridonin on USA300 DNA were investigated with DAPI staining. Morphological changes in MRSA following oridonin treatment were determined with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: Oridonin MIC and MBC values against USA300 were 64 and 512 μg/mL, respectively. The conductivity and DNA exosmosis level of oridonin-treated USA300 improved by 3.20±0.84% and increased by 58.63 ± 1.78 μg/mL, respectively. LDH and soluble protein levels decreased by 30.85±7.69% and 27.51 ± 1.39%, respectively. A decrease in fluorescence intensity was reported with time. Oridonin affected the morphology of USA300. Conclusions: Oridonin antibacterial mechanism was related to changes in cell membrane and cell wall permeability, disturbance in protein and DNA metabolism, and influence on bacterial morphology. Thus, oridonin may help in treating MRSA infection.

Maturing male germ cells undergo a unique developmental process in spermiogenesis that replaces nucleosomal histones with protamines, the process of which is critical for testicular development and male fertility. The progress of this exchange is regulated by complex mechanisms that are not well understood. Now, with mouse genetic models, we show that barrier-to-autointegration factor-like protein (BAF-L) plays an important role in spermiogenesis and spermatozoal function. BAF-L is a male germ cell marker, whose expression is highly associated with the maturation of male germ cells. The genetic deletion of BAF-L in mice impairs the progress of spermiogenesis and thus male fertility. This effect on male fertility is a consequence of the disturbed homeostasis of histones and protamines in maturing male germ cells, in which the interactions between BAF-L and histones/protamines are implicated. Finally, we show that reduced testicular expression of BAF-L represents a risk factor of human male infertility.

(−)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic compound present in green tea and has been shown to possess bio-activities. In this study, we investigated the protective effects of EGCG against restraint stress (RS)-induced liver injury and immunosuppression. EGCG (10, 20 and 40 mg/kg) was orally administered to mice daily for 7 days before modeling the restraint stress. lood, liver and broncho-alveolar lavage fluid (BALF) samples were collected and tested. We found that EGCG significantly reduced the release of stress hormones to weak restraint stress response. EGCG effectively improved hepatic damage by decreas the serum levels of alanine aminotransaminase (ALT) and aspartate transaminase (AST) in restraint-challenged mice. Furthermore, EGCG also significantly prevented the release of H2O2, NOS and 8-isoprostane, and reduced the levels of interleukin (IL)-1β, IL-2,and IL-6 restrained mice. EGCG can normal the level of cytochrome P450 (CYP450) 1A2, 2D22, 2E1 and 3A11 that induced by restraint stress., the inhibition status of T cells subsets in serum and gA in BALF were significantly relieved EGCG pretreatment. Taken together, our data suggest that EGCG possesse hepatic- and immune-protective properties against restraint stress through its anti-oxidant, anti-inflammatory and immunomodulatory activities.

The morbidity and mortality of primary liver cancer is one of the highest amongst all cancers. Deficiency of effective treatment and characteristics of cancer metastasis are believed to be responsible for this situation, thus a great demand is required for new agent development. Polyphyllin II (PP2), an important steroidal saponin extracted from Rhizoma Paris, has emerged as a potential anti-cancer agent, but the effects of PP2 in liver cancers and its underlying mechanisms remain unexplored. In our study, we found that PP2 could remarkably suppress the proliferation of two liver cancer cell lines, HepG2 and BEL7402, resulting in significant cell death. Besides, low doses of PP2 have displayed properties that inhibit cellular motility and invasion of liver cancer cells. In addition, we have found that PP2-mediated cofilin activity suppression was implicated in the inhibition of liver cancer cell motility. Decreased expression of two major hydrolytic enzymes (MMP2/MMP9), through the AKT/NF-κB signaling pathway may also be also responsible for this process. Rescue experiments done with either non-phosphorylatable mutant cofilin-1 (S3A) transfection or an activator of the AKT pathway significantly reversed the inhibition effects of PP2 on liver cancer cells. Taken together, we report a potential agent for liver cancer treatment and reveal its underlying mechanisms.

Abstract Pseudorabies virus (PRV) is a pathogen of swine resulting in devastating disease and economic losses worldwide. Resveratrol (Res) exhibits inhibitory activity against a wide range of viruses. Despite these important advances, the molecular mechanism(s) by which Res exerts its broad biological effects have not yet been elucidated. In this paper, the antiviral activity of Res against PRV and its mechanism of action were investigated. The results showed that Res potently inhibited PRV replication in a dose-dependent manner, with a 50% inhibition concentration of 17.17 μM. The inhibition of virus multiplication in the presence of Res was not attributed to direct inactivation or inhibition of viral entry into the host cells but to the inhibition of viral multiplication in host cells. Further studies demonstrated that Res is a potent inhibitor of both NF-κB activation and NF-κB-dependent gene expression through its ability to inhibit IκB kinase activity, which is the key regulator in NF-κB activation. Thus, the inhibitory effect of Res on PRV-induced cell death and gene expression may be due to its ability to inhibit the degradation of IκB kinase. These results provided a new alternative control measure for PRV infection and new insights into the antiviral mechanism of Res.

Neuroglobin (NGB), distributed mainly in central and peripheral nervous systems, is a nerve globin with neuroprotective effects against oxidative stress resulting from hypoxia and ischemia. Recent studies have indicated that the expression of NGB is related to neurodegenerative disorders and cancers, but the molecular mechanisms for its transcriptional regulation and protection are not well defined. Here, we report that the expression of NGB in glioma is grade related and is negatively regulated by PPARγ. Specific PPARγ agonist reduces the expression of NGB, while its inhibitor enhances the expression. Moreover, NGB participates in regulating the phosphorylation of AKT in glioma cells, which may contribute to the glioma progression where accumulating oxidative pressure presents. Overexpression of NGB could protect glioma cells against 4-HNE induced cell death, and partially reverse PPARγ’s pro-apoptotic and anti-proliferative abilities. These results display an important role of NGB in glioma progression and a mechanism for its transcriptional regulation, and suggest that the treatment on glioma through PPARγ agonist appears to be triggered by the modulation of NGB.

Truffles are world-renowned premium commodities. Due to their unique aroma and rarity, the price of truffles has always been very high. In this study, Diethylaminoethyl anion exchange chromatography and gel filtration were employed for polysaccharide purification from two different species of Chinese truffles. Three polysaccharide fractions were obtained from Tuber panzhihuanense and referred to as TPZ-NP, TPZ-I, and TPZ-II. Additionally, two polysaccharide fractions were purified from T. pseudoexcavatum (TPD-NP and TPD-I). The results of structural elucidation indicated that the polysaccharide from different species showed different monosaccharide composition and linkage units, as well as molecular weight. Two of the polysaccharide fractions with the highest yield, TPZ-I and TPD-I, were chosen for biological testing. The results indicated that both fractions displayed antioxidant properties through mediation of the intestinal cellular antioxidant defense system, which could protect cultured intestinal cells from oxidative stress-induced damage and cell viability suppression. The TPD-I fraction showed stronger antioxidant effects, which may be due to the difference in structure. Further study on the structure-activity relationship is needed to be done.

Coccidiosis is one of the most economically important diseases affecting the poultry industry. Currently, anticoccidial drugs used in veterinary clinics show many deficiencies, and new control measures are urgently needed. This study presents an anticoccidial herbal powder “Shi Yin Zi”, which consists of Cnidium monnieri (L.) Cuss, Taraxacum mongolicum Hand.-Mazz., and sodium chloride. In chickens infected with Eimeria tenella, supplementation with “Shi Yin Zi” powder for 3 d prior to infection or treatment with “Shi Yin Zi” powder after infection could improve the survival rate and relative growth rate and alleviate the pathological changes in the cecum, liver, and kidney. “Shi Yin Zi” powder could recover the levels of alanine aminotransferase, creatinine, albumin, and triglycerides in serum. The hemorrhage occurrence and total number of oocysts in feces were reduced. The anti-coccidial indexes reached 165 for the prophylactic effect and 144 for the therapeutic effect. The anti-coccidial effects were equal to positive controls (monensin and sulfamlopyrazine). These results suggest that “Shi Ying Zi” powder possesses a potent anticoccidial effect and exhibits the potential to control E. tenella infection.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common human pathogen that causes several difficult-to-treat infections, including biofilm-associated infections. The biofilm-forming ability of S. aureus plays a pivotal role in its resistance to most currently available antibiotics, including vancomycin, which is the first-choice drug for treating MRSA infections. In this study, the ability of thymol (a monoterpenoid phenol isolated from plants) to inhibit biofilm formation and to eliminate mature biofilms, was assessed. We found that thymol could inhibit biofilm formation and remove mature biofilms by inhibiting the production of polysaccharide intracellular adhesin (PIA) and the release of extracellular DNA (eDNA). However, cotreatment with thymol and vancomycin was more effective at eliminating MRSA biofilms, in a mouse infection model, than monotherapy with vancomycin. Comparative histopathological analyses revealed that thymol reduced the pathological changes and inflammatory responses in the wounds. Assessments of white blood cell counts and serum TNF-α and IL-6 levels showed reduced inflammation and an increased immune response following treatment with thymol and vancomycin. These results indicate that combinatorial treatment with thymol and vancomycin has the potential to serve as a more effective therapy for MRSA biofilm-associated infections than vancomycin monotherapy.

Goji (fruits of Lycium barbarum L. and L. chinense Mill.) has been used in China as food and medicine for millennia, and globally has been consumed increasingly as a healthy food. Ningxia, with a semi-arid climate, always had the reputation of producing best goji quality (daodi area). Recently, the increasing market demand pushed the cultivation into new regions with different climates. We therefore ask: How does goji quality differ among production areas of various climatic regions? Historical records are used to trace the spread of goji production in China over time. Quality measurements of 51 samples were correlated with the four main production areas in China: monsoon (Hebei), semi-arid (Ningxia, Gansu, and Inner Mongolia), plateau (Qinghai) and arid regions (Xinjiang). We include morphological characteristics, sugar and polysaccharide content, antioxidant activity, and metabolomic profiling to compare goji among climatic regions. Goji cultivation probably began in the East (Hebei) of China around 100 CE and later shifted westward to the semi-arid regions. Goji from monsoon, plateau and arid regions differ according to its fruit morphology, whereas semi-arid goji cannot be separated from the other regions. L. chinense fruits, which are exclusively cultivated in Hebei (monsoon), are significantly lighter, smaller and brighter in color, while the heaviest and largest fruits (L. barbarum) stem from the plateau. The metabolomic profiling separates the two species but not the regions of cultivation. Lycium chinense and samples from the semi-arid regions have significantly (p < 0.01) lower sugar contents and L. chinense shows the highest antioxidant activity. Our results do not justify superiority of a specific production area over other areas. Instead it will be essential to distinguish goji from different regions based on the specific morphological and chemical traits with the aim to understand what its intended uses are.

Rotavirus (RV), belonging to Reoviridae family, is the leading cause of acute severe viral diarrhea in children (under 5 years old) and infant animals worldwide. Although vaccines are commonly used to prevent infection, episodes of diarrhea caused by RV frequently occur. Thus, this study was conducted to determine whether resveratrol had protective effects against RV infection in piglets. Following pretreatment with resveratrol dry suspension through adding into the basal diet for 3 weeks, the piglets were orally challenged with RV. We found that resveratrol could alleviate diarrhea induced by RV infection. Resveratrol-treatment inhibited the TNF-α production, indicating that the anti-RV activity of resveratrol may be achieved by reducing the inflammatory response. The IFN-γ level was elevated in 10mg/kg/d resveratrol-treated group and 30mg/kg/d resveratrol-treated group after RV infection. The ratios of CD4+/CD8+ in resveratrol-treated groups were the same as that in mock infected group, suggesting that resveratrol could maintain the immune function in RV-infected piglets. It was found that resveratrol could alleviate diarrhea induced by RV infection. These results revealed that resveratrol dry suspension could be a new control measure for RV infection.