Susceptibility and cecal microbiota alteration to Eimeria-infection in Yellow-feathered broilers, Arbor Acres broilers and Lohmann pink layers.

Coccidiosis, which is caused by Eimeria species, results in huge economic losses to the poultry industry. Arbor Acres (AA) broilers and yellow-feathered broilers are the dominant broilers in northern and southern China, respectively. However, their susceptibility to coccidiosis has not been fully compared. In this study, the susceptibility of yellow-feathered broilers, AA broilers and Lohmann pink layers to E. tenella was evaluated based on mortality rate, relative body weight gain rate, intestinal lesion score, oocyst output, anticoccidial index (ACI), and cecum weight and length. The yellow-feathered broilers were shown to produce significantly fewer oocysts with higher intestinal lesion score compared to AA broilers, which had the highest growth rates and ACI scores. Subsequently, changes in the cecal microbiota of the 3 chicken lines before and after high-dose infection (1 × 104 oocysts) with E. tenella were determined by 16S rRNA sequencing. The results showed that composition of the microbiota changed dramatically after infection. The abundance of Firmicutes and Bacteroidetes in the infected chickens decreased, and Proteobacteria increased significantly among the different chicken lines. At the genus level, Escherichia increased significantly in all 3 groups of infected chickens, but Lactobacillus decreased to 0% in the infected yellow-feathered broilers. The results of the study indicate that the susceptibility to E. tenella varies among the 3 chicken lines, and that changes in intestinal microbiota by E. tenella-infection among the different chicken lines had a similar trend, but to different degrees. This study provides basic knowledge of the susceptibility in the 3 chicken lines, which can be helpful for the control and prevention of coccidiosis.

Mulberry leaf polysaccharide improves cyclophosphamide-induced growth inhibition and intestinal damage in chicks by modulating intestinal flora, enhancing immune regulation and antioxidant capacity.

Polysaccharides are generally considered to have immune enhancing functions, and mulberry leaf polysaccharide is the main active substance in mulberry leaves, while there are few studies on whether mulberry leaf polysaccharide (MLP) has an effect on immunosuppression and intestinal damage caused by cyclophosphamide (CTX), we investigated whether MLP has an ameliorative effect on intestinal damage caused by CTX. A total of 210 1-day-old Mahuang cocks were selected for this experiment. Were equally divided into six groups and used to evaluate the immune effect of MLP. Our results showed that MLP significantly enhanced the growth performance of chicks and significantly elevated the secretion of cytokines (IL-1ß, IL-10, IL-6, TNF-α, and IFN-γ), immunoglobulins and antioxidant enzymes in the serum of immunosuppressed chicks. It attenuated jejunal damage and elevated the expression of jejunal tight junction proteins Claudin1, Zo-1 and MUC2, which protected intestinal health. MLP activated TLR4-MyD88-NF-κB pathway and enhanced the expression of TLR4, MyD88 and NF-κB, which served to protect the intestine. 16S rDNA gene high-throughput sequencing showed that MLP increased species richness, restored CTX-induced gut microbiome imbalance, and enhanced the abundance of probiotic bacteria in the gut. MLP improves cyclophosphamide-induced growth inhibition and intestinal damage in chicks by modulating intestinal flora and enhancing immune regulation and antioxidant capacity. In conclusion, this study provides a scientific basis for MLP as an immune enhancer to regulate chick intestinal flora and protect chick intestinal mucosal damage.

Effects of Six Natural Compounds and Their Derivatives on the Control of Coccidiosis in Chickens.

Chicken coccidiosis costs the poultry industry over GBP 10 billion per year. The main method of preventing and controlling coccidiosis in chickens continues to be the use of drugs. Unfortunately, the prevalence of drug resistance in the field reduces or even eliminates the effectiveness of drugs, and drug residues in the food supply chain can also can be harmful to humans. Therefore, safe and effective anticoccidial drugs are urgently needed. Natural products have many advantages such as being safe, effective and inexpensive and are a sustainable way to control coccidiosis. In this study, the anticoccidial effects of six natural compounds were tested by Eimeria tenella infection. Oocyst production, cecum lesion, body weight gain, feed conversion ratio, and intestinal microbiota were measured. The results showed that nerolidol had a moderate effect on maintaining both body weight gain and feed conversion ratio. Silymarin and dihydroartemisinin showed significant anticoccidial effects by reducing total oocyst output. Dihydroartemisinin also significantly reduced the cecum lesion caused by Eimeria infection, but this compound may be toxic to the host at such informed doses because it decreases growth and survival rates. In addition, both silymarin and dihydroartemisinin partly restored the microbiota after challenge. This indicates that silymarin, dihydroartemisinin, and nerolidol are effective in the control of chicken coccidiosis. Our data provide basic knowledge about the anticoccidial effects of such natural compounds/derivates.

Inhibition of inflammation by berberine: Molecular mechanism and network pharmacology analysis.

BACKGROUND: Traditional Chinese Medicine (TCM), renowned for its holistic approach with a 2000-year history of utilizing natural remedies, offers unique advantages in disease prevention and treatment. Berberine, found in various Chinese herbs, has been employed for many years, primarily for addressing conditions such as diarrhea and dysentery. Berberine has recently become a research focus owing to its pharmacological activities and benefits to human bodies. However, little is known about the anti-inflammatory mechanism of berberine. PURPOSE: To summarize recent findings regarding the pharmacological effects and mechanisms of berberine anti-inflammation and highlight and predict the potential therapeutic effects and systematic mechanism of berberine. METHODS: Recent studies (2013-2023) on the pharmacological effects and mechanisms of berberine anti-inflammation were retrieved from Web of Science, PubMed, Google Scholar, and Scopus up to July 2023 using relevant keywords. Network pharmacology and bioinformatics analysis were employed to predict the therapeutic effects and mechanisms of berberine against potential diseases. RESULTS: The related pharmacological mechanisms of berberine anti-inflammation include the inhibition of inflammatory cytokine production (e.g., IL-1ß, IL-6, TNF-α), thereby attenuating the inflammatory response; Inhibiting the activation of NF-κB signaling pathway and IκBα degradation; Inhibiting the activation of MAPK signaling pathway; Enhancing the activation of the STAT1 signaling pathway; Berberine interacts directly with cell membranes through a variety of pathways, thereby influencing cellular physiological activities. Berberine enhances human immunity and modulates immune system function, which is integral to addressing certain autoimmune and tumour-related health concerns. CONCLUSION: This study expounds on the correlation between berberine and inflammatory diseases, encapsulating the mechanisms through which berberine treats select typical inflammatory ailments. Furthermore, it delves into a deeper understanding of berberine's effectiveness by integrating network pharmacology and molecular docking techniques in the context of treating inflammatory diseases. It provides guidance and reference for berberine's subsequent revelation of the modern scientific connotation of Chinese medicine.

Carboxymethylated Abrus cantoniensis polysaccharide prevents CTX-induced immunosuppression and intestinal damage by regulating intestinal flora and butyric acid content.

As a Chinese folk health product, Abrus cantoniensis exhibits good immunomodulatory activity because of its polysaccharide components (ACP), and carboxymethylation of polysaccharides can often further improve the biological activity of polysaccharides. In this study, we explored the impact of prophylactic administration of carboxymethylated Abrus cantoniensis polysaccharide (CM-ACP) on immunosuppression and intestinal damage induced by cyclophosphamide (CTX) in mice. Our findings demonstrated that CM-ACP exhibited a more potent immunomodulatory activity compared to ACP. Additionally, CM-ACP effectively enhanced the abundance of short-chain fatty acid (SCFA)-producing bacteria in immunosuppressed mice and regulated the gene expression of STAT6 and STAT3 mediated pathway signals. In order to further explore the relationship among polysaccharides, intestinal immunity and intestinal flora, we performed a pseudo-sterile mouse validation experiment and fecal microbiota transplantation (FMT) experiment. The findings suggest that CM-FMT and butyrate attenuate CTX-induced immunosuppression and intestinal injury. CM-FMT and butyrate show superior immunomodulatory ability, and may effectively regulate intestinal cell metabolism and repair the damaged intestine by activating STAT6 and STAT3-mediated pathways. These findings offer new insights into the mechanisms by which CM-ACP functions as functional food or drug, facilitating immune response regulation and maintaining intestinal health.

Gut microbiota-mediated IL-22 alleviates metabolic inflammation.

Low-grade chronic inflammation, also known as metabolic inflammation, promotes the development of metabolic diseases. Increasing evidence suggests that changes in gut microbes and metabolites disrupt the integrity of the gut barrier and exert significant effects on the metabolism of various tissues, including the liver and adipose tissue, thereby contributing to metabolic inflammation. We observed that IL-22 is a key signaling molecule that serves as a bridge between intestinal microbes and the host, effectively alleviating metabolic inflammation by modulating the host immunomodulatory network. Here, we focused on elucidating the underlying mechanisms by which the gut microbiota and their metabolites reduce inflammation via IL-22, highlighting the favorable impact of IL-22 on metabolic inflammation. Furthermore, we discuss the potential of IL-22 as a therapeutic target for the management of metabolic inflammation and related diseases.

Natural Magnolol ameliorates coccidiosis infected with Eimeria tenella by affecting antioxidant, anti-inflammatory, and gut microbiota of chicks.

Magnolol, a natural extract from magnolia officinalis, has received growing interest in its bioactive properties such as antioxidant, anti-inflammatory, and antibacterial activities. Nevertheless, there is little research on Magnolol in the treatment of parasitic infections currently. Eimeria tenella (E. tenella) infection causes damage to epithelial cells and cecal mucosa, resulting in increased intestinal permeability, which is pretty detrimental to the balance of the intestinal microenvironment. However, at present, in the treatment of chicken coccidiosis, the abuse of antibiotics is quite serious, which has brought losses and harms to the chicken farming industry that cannot be ignored. In this study, based on the excellent antioxidant and anti-inflammatory properties of Magnolol, we proved that it does have a desirable therapeutic potential on chicks infected with E. tenella. Actually, the results showed that the clinical symptoms of the chicks infected with E. tenella were relieved and their growth performance was restored by Magnolol treatment. Furthermore, Magnolol improved the antioxidant and anti-inflammatory properties of chicks. Meanwhile, the Magnolol reversed the imbalance of the intestinal microbiota of sick chicks, which recovered the diversity, promoted the potential beneficial bacteria, and inhabited the potential pathogenic bacteria. Overall, Magnolol may be an alternative to chemical drugs that are effective in treating E. tenella infections.

Inflammasome activation by viral infection: mechanisms of activation and regulation.

Viral diseases are the most common problems threatening human health, livestock, and poultry industries worldwide. Viral infection is a complex and competitive dynamic biological process between a virus and a host/target cell. During viral infection, inflammasomes play important roles in the host and confer defense mechanisms against the virus. Inflammasomes are polymeric protein complexes and are considered important components of the innate immune system. These immune factors recognize the signals of cell damage or pathogenic microbial infection after activation by the canonical pathway or non-canonical pathway and transmit signals to the immune system to initiate the inflammatory responses. However, some viruses inhibit the activation of the inflammasomes in order to replicate and proliferate in the host. In recent years, the role of inflammasome activation and/or inhibition during viral infection has been increasingly recognized. Therefore, in this review, we describe the biological properties of the inflammasome associated with viral infection, discuss the potential mechanisms that activate and/or inhibit NLRP1, NLRP3, and AIM2 inflammasomes by different viruses, and summarize the reciprocal regulatory effects of viral infection on the NLRP3 inflammasome in order to explore the relationship between viral infection and inflammasomes. This review will pave the way for future studies on the activation mechanisms of inflammasomes and provide novel insights for the development of antiviral therapies.

Emergence of novel tigecycline resistance gene tet(X5) variant in multidrug-resistant Acinetobacter indicus of swine farming environments.

Antibiotic-resistant bacteria are emerging all the time, but the continued emergence of novel resistance genes and genetic structures is even more alarming. Tigecycline is currently the important last barrier in the treatment of multidrug-resistant (MDR) infections. tet(X), a resistance gene to tigecycline, is the most prevalent and constantly emerging novel variants. In this research, we characterized two MDR Acinetobacter indicus strains to tigecycline that were identified and analyzed by antimicrobial susceptibility testing, conjugation transfer, whole genome sequencing (WGS) and bioinformatics analysis, and gene function analysis. The results showed that three tet(X) variants were carried in BDT201, including tet(X6) on the chromosome, tet(X3) on the plasmid pBDT201-2, and a novel tet(X5) variant adjacent to the ISAba1 elements on the plasmid pBDT201-3. The novel Tet(X5) variant showed 98.7% amino acid identity with Tet(X5) and was named Tet(X5.4). By expressing tet(X5.4) gene, the tigecycline minimum inhibitory concentration (MIC) values for Escherichia coli JM109 increased 32- fold (from 0.13 to 4 mg/L). BDT2076 contained tigecycline and carbapenems resistance genes, such as tet(X3), blaOXA-58, blaNDM-3, and blaCARB-2. The continuous emergence of MDR bacteria and resistance genes is a global environmental health issue that can not be ignored and therefore needs to pay more urgent attention to it.

Forward genetic analysis of monensin and diclazuril resistance in Eimeria tenella.

Worldwide distributed coccidiosis is caused by infection of both Eimeria species and Cystoisospora in the host intestine and causes huge economic losses to the livestock industry, especially the poultry industry. The control of such diseases relies mainly on chemoprophylaxis with anticoccidials, which has led to a very common drug resistance in this field. However, the genetic mechanisms underlying resistance to many anticoccidial drugs remain unknown. In this study, strains of E. tenella resistant to 250 mg/kg monensin were generated and characterized. Forward genetic approaches based on pooled genome sequencing, including experimental evolution and linkage group selection, were used to locate candidate targets responsible for resistance to monensin and diclazuril in E. tenella. A total of 16 nonsynonymous mutants in protein-coding genes were identified in monensin-resistant strains, and two genomic regions with strong selection signals were also detected in diclazuril-resistant strains. Our study reveals the genetic characterization of the experimental evolution and linkage group selection in Eimeria species, and also provides important information that contributes to the understanding of the molecular mechanism of drug resistance in coccidia.

Development of a Crystal Digital RT-PCR for the Detection of Atypical Porcine Pestivirus.

Atypical porcine pestivirus (APPV), a newly discovered virus, is associated with the type A-II congenital tremor (CT) in neonatal piglets. APPV distributes throughout the world and causes certain economic losses to the swine industry. The specific primers and probe were designed targeting the 5' untranslated region (UTR) of APPV to amplify a 90 bp fragment, and the recombinant standard plasmid was constructed. After optimizing the concentrations of primers and probe, annealing temperature, and reaction cycles, a crystal digital RT-PCR (cdRT-PCR) and real-time quantitative RT-PCR (qRT-PCR) were successfully established. The results showed that the standard curves of the qRT-PCR and the cdRT-PCR had R2 values of 0.999 and 0.9998, respectively. Both methods could specifically detect APPV, and no amplification signal was obtained from other swine viruses. The limit of detection (LOD) of the cdRT-PCR was 0.1 copies/µL, and that of the qRT-PCR was 10 copies/µL. The intra-assay and inter-assay coefficients of variation of repeatability and reproducibility were less than 0.90% for the qRT-PCR and less than 5.27% for the cdRT-PCR. The 60 clinical tissue samples were analyzed using both methods, and the positivity rates of APPV were 23.33% by the qRT-PCR and 25% by the cdRT-PCR, with a coincidence rate of 98.33%. The results indicated that the cdRT-PCR and the qRT-PCR developed here are highly specific, sensitive methods for the rapid and accurate detection of APPV.

Which strain of the avian coronavirus vaccine will become the prevalent one in China next?

Infectious bronchitis virus (IBV) is a vital pathogen in poultry farms, which can induce respiratory, nephropathogenic, oviduct, proventriculus, and intestinal diseases. Based on the phylogenetic classification of the full-length S1 gene, IBV isolates have been categorized into nine genotypes comprising 38 lineages. GI (GI-1, GI-2, GI-3, GI-4, GI-5, GI-6, GI-7, GI-13, GI-16, GI-18, GI-19, GI-22, GI-28, and GI-29), GVI-1 and GVII-1 have been reported in China in the past 60 years. In this review, a brief history of IBV in China is described, and the current epidemic strains and licensed IBV vaccine strains, as well as IBV prevention and control strategies, are highlighted. In addition, this article presents unique viewpoints and recommendations for a more effective management of IBV. The recombinant Newcastle Disease virus (NDV) vector vaccine expressed S gene of IBV QX-like and 4/91 strains may be the dominant vaccine strains against NDV and IBV.

Silver nanoparticles combat Salmonella Typhimurium: Suppressing intracellular infection and activating dendritic cells.

Salmonella Typhimurium (ST) can hide inside cells, avoid antibiotic therapy and being killed by host's immune system to cause persistent infection in humans and animals. Metal nanoparticles are regarded as an alternative to overcome the above limitations, silver nanoparticles especially have been applied in combating drug-resistant bacteria. However, the therapeutic effects of silver nanoparticles against intracellular infection and their impacts on host immunity remain an area of further investigation. In this work, we synthesized Ganoderma extract-capped silver nanoparticles (Ag@Ge) and explored the therapeutic potential and immune adjuvant effects of Ag@Ge against intracellular ST. Firstly, Ag@Ge had a small particle size of 35.52±7.46 nm, good stability, and biocompatibility. Then, Ag@Ge effectively entered RAW 264.7 cells, suppressed intracellular ST infection. Furthermore, Ag@Ge activated mouse dendritic cells (DCs) in vitro, evidenced by increased phenotypic markers (CD80/CD86/CD40/major compatibility complex II (MHCII)) expression and cytokine and chemokine (interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL-2), and chemokine (C-C motif) receptor-7 (CCR-7)) transcription. More notably, the combination of Ag@Ge with inactivated ST recruited intestinal DCs to mitigate ST infection in mice, evidenced by decreased body weight loss and bacterial loads in the tissues (liver, jejunum, and colon), and improved platelets count. The above findings indicate that Ag@Ge has the potential as an alternative nano-antibiotic against intracellular ST infection.

Citric Acid and Magnolol Ameliorate Clostridium perfringens Challenge in Broiler Chickens.

Clostridium perfringens (C. perfringens) is a common pathogenic bacterium implicated in the enteric diseases of animals. Each year, the disease is responsible for billions of dollars of losses worldwide. The development of new phytomedicines as alternatives to antibiotics is becoming a new hotspot for treating such diseases. Citric acid (CA) and magnolol (MA) have been shown to have antibacterial, antioxidant, and growth-promoting properties. Here, the bacteriostatic effects of combinations of CA and MA against C. perfringens were investigated, together with their effects on yellow-hair chickens challenged with C. perfringens. It was found that the optimal CA:MA ratio was 50:3, with a dose of 265 µg/mL significantly inhibiting C. perfringens growth, and 530 µg/mL causing significant damage to the bacterial cell morphology. In animal experiments, C. perfringens challenge reduced the growth, damaged the intestinal structure, activated inflammatory signaling, impaired antioxidant capacity, and perturbed the intestinal flora. These effects were alleviated by combined CA-MA treatment. The CA-MA combination was found to inhibit the TLR/Myd88/NF-κB and Nrf-2/HO-1 signaling pathways. In conclusion, the results suggest the potential of combined CA-MA treatment in alleviating C. perfringens challenge by inhibiting the growth of C. perfringens and affecting the TLR/MyD88/NF-κB and Nrf-2/HO-1 signaling pathways.

Development of a Multiplex Crystal Digital RT-PCR for Differential Detection of Classical, Highly Pathogenic, and NADC30-like Porcine Reproductive and Respiratory Syndrome Virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) type 1 (European genotype) and PRRSV type 2 (North American genotype) are prevalent all over the world. Nowadays, the North American genotype PRRSV (NA-PRRSV) has been widely circulating in China and has caused huge economic losses to the pig industry. In recent years, classical PRRSV (C-PRRSV), highly pathogenic PRRSV (HP-PRRSV), and NADC30-like PRRSV (NL-PRRSV) have been the most common circulating strains in China. In order to accurately differentiate the circulating strains of NA-PRRSV, three pairs of specific primers and corresponding probes were designed for the Nsp2 region of C-PRRSV, HP-PRRSV, and NL-PRRSV. After optimizing the annealing temperature, primer concentration, and probe concentration, a multiplex real-time quantitative RT-PCR (qRT-PCR) and a multiplex Crystal digital RT-PCR (cdRT-PCR) for the differential detection of C-PRRSV, HP-PRRSV, and NL-PRRSV were developed. The results showed that the two assays illustrated high sensitivity, with a limit of detection (LOD) of 3.20 × 100 copies/µL for the multiplex qRT-PCR and 3.20 × 10-1 copies/µL for the multiplex cdRT-PCR. Both assays specifically detected the targeted viruses, without cross-reaction with other swine viruses, and indicated excellent repeatability, with coefficients of variation (CVs) of less than 1.26% for the multiplex qRT-PCR and 2.68% for the multiplex cdRT-PCR. Then, a total of 320 clinical samples were used to evaluate the application of these assays, and the positive rates of C-PRRSV, HP-PRRSV, and NL-PRRSV by the multiplex qRT-PCR were 1.88%, 21.56%, and 9.69%, respectively, while the positive rates by the multiplex cdRT-PCR were 2.19%, 25.31%, and 11.56%, respectively. The high sensitivity, strong specificity, excellent repeatability, and reliability of these assays indicate that they could provide useful tools for the simultaneous and differential detection of the circulating strains of C-PRRSV, HP-PRRSV, and NL-PRRSV in the field.

Comparison of the Effects between Tannins Extracted from Different Natural Plants on Growth Performance, Antioxidant Capacity, Immunity, and Intestinal Flora of Broiler Chickens.

In this study, four plant tannins, including AT (Acacia mearnsii tannin, 68%), CT (Castanea sativa tannin, 60%), QT (Schinopsis lorenzii tannin, 73%) and TT (Caesalpinia spinosa tannin, 50%) were added to broiler diets for 42 days to evaluate and compare their effects on growth performance, antioxidant capacity, immune performance and gut microbiota in broilers. The results showed that the supplementation of five tannins could increase the production of T-AOC, GSH-Px, SOD and CAT and reduce the production of MDA in the serum of broilers (p < 0.01), but the antioxidant effect of the AT group was lower than that of the other three groups (p < 0.01). All four tannins decreased the level of the pro-inflammatory factor IL-1ß and increased the level of the anti-inflammatory factor IL-10 (p < 0.01). CT, QT and TT decreased the levels of pro-inflammatory factors IL-6 and TNF-α (p < 0.01), while AT and CT increased the level of IL-2 in serum (p < 0.01). Supplementation with four tannins also increased the levels of IgG, IgM, IgA and sIgA in serum (p < 0.01) and the levels of ZO-1, claudin-1 and occludin in the jejunum (p < 0.01). The detection results of ALT and AST showed that CT, QT and TT decreased the concentrations of ALT and AST in serum (p < 0.01). The results of the gut microbiota showed that the abundance of Clostridia and Subdoligranulum increased, and the abundance of Oscillospiraceae decreased, compared to the control group after adding the four tannins to the diets (p > 0.05). In addition, CT, QT and TT decreased the abundance of Lactobacillus and increased the abundance of Bacteroides compared to the control group, while AT showed the opposite result (p > 0.05). Overall, our study shows that tannins derived from different plants have their own unique effects on broilers. AT and CT can promote broilers' growth better than other tannins, CT has the best ability to improve immune and antioxidant properties, and QT and TT have the best effect on broilers' liver protection.

Protective Effects of Sophorae tonkinensis Gagnep. (Fabaceae) Radix et Rhizoma Water Extract on Carbon Tetrachloride-Induced Acute Liver Injury.

Sophorae tonkinensis Radix et Rhizoma (STR) is a traditional Chinese herbal medicine. STR can reduce aminotransferase activity; however, the specific mechanism remains unclear. Here, we explored the potential therapeutic effects and hepatoprotective mechanism of STR on liver damage in mice. The chemical characteristics of the extract were characterized using ultra-high-performance liquid chromatography-tandem mass spectrometry fingerprinting, and its antioxidant capacity was verified using free radical scavenging tests. Forty-eight Kunming mice were randomly assigned into six groups. The model was made after the corresponding drug was given. The results showed that the STR water extract pretreatment significantly reduced serum aminotransferase and related liver function indicators compared with that in the model group. Furthermore, the STR water extract pretreatment significantly inhibited the apoptosis of liver cells, the level of liver high-mobility group box 1 (HMGB1), and inflammatory factors in hepatic tissue compared with that in the model group, and significantly downregulated the levels of toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B (NF-κB) compared with those in the model group. Overall, the STR water extract exerted a significant protective effect on CCL4-induced acute liver injury in this study, and the accurate active ingredients of the STR water extract will be explored in the near future.

Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter Species.

The emergence of the tet(X) gene is a severe challenge to global public health security, as clinical tigecycline resistance shows a rapidly rising trend. In this research, we identified two tigecycline-resistant Acinetobacter sp. strains containing seven novel tet(X3) variants recovered from fecal samples from Chinese farms. The seven Tet(X3) variants showed 15.4% to 99.7% amino acid identity with Tet(X3). By expressing tet(X3.7) and tet(X3.9), the tigecycline MIC values for Escherichia coli JM109 increased 64-fold (from 0.13 to 8 mg/L). However, the other tet(X3) variants did not have a significant change in the MIC of tigecycline. We found that the 26th amino acid site of Tet(X3.7) changed from proline to serine, and the 25th amino acid site of Tet(X3.9) changed from glycine to alanine, which reduced the MIC of tigecycline by 2-fold [the MIC of tet(X3) to tigecycline was 16 mg/L] but did not affect its expression to tigecycline. The tet(X3) variants surrounded by mobile genetic elements appeared in the structure of gene clusters with tandem repeat sequences and were adjacent to the site-specific recombinase-encoding gene xerD. Therefore, there is a risk of horizontal transfer of resistant genes. Our study reports seven novel tet(X3) variants; the continuing emergence of tigecycline variants makes continuous monitoring of resistance to tigecycline even more critical. IMPORTANCE Although it is illegal to use tigecycline and carbapenems to treat bacterial infections in animals, we can still isolate bacteria containing both mobile resistance genes from animals, and tet(X) is currently an essential factor in degrading tigecycline. Here, we characterized two multidrug-resistant Acinetobacter sp. strains that contained vital resistance genes, such as sul2, a blaOXA-164-like gene, floR, tetM, and multiple novel tet(X3) variants with different tandem structures. It is of paramount significance that their mechanism may transfer to other Gram-negative pathogens, even if their tandem structures have no cumulative effect on tigecycline resistance.

Green synthesis of silver nanoparticles through oil: Promoting full-thickness cutaneous wound healing in methicillin-resistant Staphylococcus aureus infections.

Due to the emergence of multi-drug resistant microorganisms, the development and discovery of alternative eco-friendly antimicrobial agents have become a top priority. In this study, a simple, novel, and valid green method was developed to synthesize Litsea cubeba essential oil-silver nanoparticles (Lceo-AgNPs) using Lceo as a reducing and capping agent. The maximum UV absorbance of Lceo-AgNPs appeared at 423 nm and the size was 5-15 nm through transmission electron microscopy result. The results of Fourier transform infrared and DLS showed that Lceo provided sufficient chemical bonds for Lceo-AgNPs to reinforce its stability and dispersion. The in vitro antibacterial effects of Lceo-AgNPs against microbial susceptible multidrug-resistant Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) were determined. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Lceo-AgNPs against E. coli were 25 and 50 µg/ml. The MIC and MBC of Lceo-AgNPs against MRSA were 50 and 100 µg/ml, respectively. The results of scanning electron microscopy showed that the amount of bacteria obviously decreased and the bacteria cells were destroyed by Lceo-AgNPs. In vivo research disclosed significant wound healing and re-epithelialization effects in the Lceo-AgNPs group compared with the self-healing group and the healing activity was better than in the sulfadiazine silver group. In this experiment, Lceo-AgNPs has been shown to have effects on killing multidrug-resistant bacteria and promoting wound healing. This study suggested Lceo-AgNPs as an excellent new-type drug for wound treatment infected with multidrug-resistant bacteria, and now expects to proceed with clinical research.

Characterization and macrophages immunomodulatory activity of two water-soluble polysaccharides from Abrus cantoniensis.

The study aims to elucidate the physicochemical properties and immunomodulatory activity of two polysaccharides (ACP t0 and ACP t2) from Abrus cantoniensis. Results revealed that ACP t0 with a molecular weight of 26.0 kDa, was mainly composed of glucose (83.1%) and galactose (6.1%), and that ACP t2 with a molecular weight of 145.6/8.9 kDa, consisted of galactose (25.6%), galacturonic acid (22.2%), arabinos (16.6%) and galactose (11.0%) respectively. AFM and Congo red experiments suggested that ACP t0 and ACP t2 might be spherical particles with triple-helix conformation in aqueous solution. ACP t0 and ACP t2 exhibited immunomodulatory activity by promoting the proliferation, augmenting pinocytic and phagocytic capacities, releasing immunoactive molecules such as ROS, NO, iNOS, TNF-α, IL-6 and IL-1ß, upregulation of the mRNA levels of corresponding cytokines in macrophages. Moreover, ACP t0 and ACP t2 were recognized by toll-like receptor 4 (TLR4) and exerted immunomodulatory effects via activating Myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinases (MAPKs) and serine/threonine kinase (Akt) signaling pathways in macrophages. Notably, ACP t2 had higher immunomodulatory activity than ACP t0. Based on the present findings, ACP t0 and ACP t2 could be explored as an active component of immunomodulators in the food and pharmaceutical fields.