Chronic heat stress induces lung injury in broiler chickens by disrupting the pulmonary blood-air barrier and activating TLRs/NF-κB signaling pathway.

As an important respiratory organ, the lung is susceptible to damage during heat stress due to the accelerated breathing frequency caused by an increase in environmental temperature. This can affect the growth performance of animals and endanger their health. This study aimed to explore the mechanism of lung tissue damage caused by heat stress. Broilers were randomly divided into a control group (Control) and a heat stress group (HS). The HS group was exposed to 35°C heat stress for 12 h per d from 21-days old, and samples were taken from selected broilers at 28, 35, and 42-days old. The results showed a significant increase in lactate dehydrogenase (LDH) activity in the serum and myeloperoxidase (MPO) activity in the lungs of broiler chickens across all 3 age groups after heat stress (P < 0.01), while the total antioxidant capacity (T-AOC) was significantly enhanced at 35-days old (P < 0.01). Heat stress also led to significant increases in various proinflammatory factors in serum and expression levels of HSP60 and HSP70 in lung tissue. Histopathological results showed congestion and bleeding in lung blood vessels, shedding of pulmonary epithelial cells, and a large amount of inflammatory infiltration in the lungs after heat stress. The mRNA expression of TLRs/NF-κB-related genes showed an upward trend (P < 0.05) after heat stress, while the mRNA expression of MLCK, a gene related to pulmonary blood-air barrier, significantly increased after heat stress, and the expression levels of MLC, ZO-1, and occludin decreased in contrast. This change was also confirmed by Western blotting, indicating that the pulmonary blood-air barrier is damaged after heat stress. Heat stress can cause damage to the lung tissue of broiler chickens by disrupting the integrity of the blood-air barrier and increasing permeability. This effect is further augmented by the activation of TLRs/NF-κB signaling pathways leading to an intensified inflammatory response. As heat stress duration progresses, broiler chickens develop thermotolerance, which gradually mitigates the damaging effects induced by heat stress.

Epidemiological characteristics and risk factors of multidrug-resistant tuberculosis in Luoyang, China.

Objective: We aimed to examine the prevalence of multidrug-resistant tuberculosis (MDR-TB) in Luoyang, China, identify related risk factors, inform clinical practices, and establish standardized anti-tubercular treatment regimens. Methods: We conducted a retrospective analysis of high-resolution melting curve (HRM) data from 17,773 cases (2,748 of which were positive) between June 2019 and May 2022 to assess the prevalence of MDR-TB and to identify its associated risk factors. Results: Between June 2019 and May 2022, out of the 17,773 HRM results, 2,748 were HRM-positive, and 312 were MDR-TB cases. The detection rates for HRM-positive and MDR-TB were 17.0 and 12.1% for males, and 12.4 and 8.2% for females, respectively. The MDR-TB detection rate was higher in the urban areas (14.6%) than in the rural areas (10.6%) and more common among individuals under 51 years of age (14.1%) than those over 50 years of age (9.3%). Notably, the rate of detecting MDR-TB was 18.3% higher in new male patients than in new female patients, which was at 10.6%, and this difference was statistically significant (p < 0.001). Moreover, the rate of MDR detection in females who had received anti-tuberculosis treatment (21.3%) was higher than that in males (16.9%). In the multivariate model that considered the results of the sputum smear and detection time, MDR-TB was positively correlated with a history of tuberculosis (TB) treatment, being male, being younger than 51 years, and living in urban areas. Conclusion: Local TB infections are complex and diverse; therefore, more comprehensive monitoring methods are needed to curb the spread of MDR-TB.

Immunogenicity and efficacy of serogroup A and D bacterins against Pasteurella multocida in mice.

Introduction: Pasteurella multocida is a widespread respiratory pathogen in pigs, causing swine pneumonia and atrophic rhinitis, and the capsular serogroups A and D are the main epidemic serogroups in infected animals. This study investigated the protective effects of serogroup A and D bacterins against current circulating P. multocida strains, to better understand the immunity generated by bacterins. Method: 13 serogroup A (seven A: L3 and six A: L6 strains) and 13 serogroup D (all D: L6 strains) P. multocida strains were isolated, and used as inactivated whole cell antigen to prepare P. multocida bacterins. Mice were immunized with these bacterins at 21-day interval and intraperitoneally challenged with the homologous and heterologous P. multocida strains, respectively. The antibody titer levels and immunization protective efficacy of vaccines were evaluated. Results: All of the bacterins tested induced high titer levels of immunoglobulin G antibodies against the parental bacterial antigen in mice. Vaccination with the six A: L6 bacterins provided no protection against the parent strain, but some strains did provide heterologous protection against A: L3 strains. Vaccination with the seven A: L3 bacterins provided 50%-100% protection against the parent strain, but none gave heterologous protection against the A:L6 strains. Immunization with the thirteen D: L6 bacterins offered 60%-100% protection against the parent strain, and almost all D: L6 strains gave cross-protection. Discussion: This study found that the cross-protectivity of serogroup A strains was poor, while serogroup D strains was effective, which provided some insights for P. multocida vaccine development.

Disordered Expression of Tight Junction Proteins Is Involved in the Mo-induced Intestinal Microenvironment Dysbiosis in Sheep.

To evaluate the molybdenum (Mo)-induced changes of intestinal morphology and the relationship of intestinal tight junction (TJ) proteins expression and intestinal barrier function, a total of 20 healthy sheep were randomly divided into five groups of four: 0, 5, 10, 20, and 50 mg/kg BW/day Na2MoO4·2H2O were administrated in five groups named control group, Mo 5 group, Mo 10 group, Mo 20 group, and Mo 50 group, respectively. After 28 days of Mo treatment, the duodenum, the jejunum, and the ileum tissue were collected. The histopathology and the developmental parameters were evaluated by hematoxylin-eosin staining. The intestinal epithelial cell DNA damage was detected by TdT-mediated dUTP nick end labeling assay. The intestinal glycoprotein and the goblet cells were analyzed by Alcian Blue-Periodic Acid-Schiff (AB-PAS) staining and PAS staining, respectively. TJ proteins were determined by immunofluorescence technology. Results showed that excessive Mo significantly decreased the small intestinal villus height (VH), crypt depth (CD), VH/CD, and mucosal thickness (P < 0.05 or P < 0.01) while induced the damage of DNA in small intestinal epithelial cells. Moreover, excessive Mo injured intestinal barrier function by decreasing the percent of glycoprotein distribution area (P < 0.05) and the relative density of intestinal goblet cells (P < 0.05). Mo treatment induced decreased (P < 0.01) expression of Zonula Occludens-1, Occludin, and Claudin-1. In conclusion, excessive Mo interfered with the expression of TJ proteins, inhibited intestinal epithelial development, and further aggravated the intestinal barrier function damage, leading to disturbing the small intestinal microenvironment balance.

Regional distribution of Mycobacterium tuberculosis infection and resistance to rifampicin and isoniazid as determined by high-resolution melt analysis.

BACKGROUND: Identifying the transmission mode and resistance mechanism of Mycobacterium tuberculosis (MTB) is key to prevent disease transmission. However, there is a lack of regional data. Therefore, the aim of this study was to identify risk factors associated with the transmission of MTB and regional patterns of resistance to isoniazid (INH) and rifampicin (RFP), as well as the prevalence of multidrug-resistant tuberculosis (MDR-TB). METHODS: High-resolution melt (HRM) analysis was conducted using sputum, alveolar lavage fluid, and pleural fluid samples collected from 17,515 patients with suspected or confirmed MTB infection in the downtown area and nine counties of Luoyang City from 2019 to 2021. RESULTS: Of the 17,515 patients, 82.6% resided in rural areas, and 96.0% appeared for an initial screening. The HRM positivity rate was 16.8%, with a higher rate in males than females (18.0% vs. 14.1%, p < 0.001). As expected, a positive sputum smear was correlated with a positive result for HRM analysis. By age, the highest rates of MTB infection occurred in males (22.9%) aged 26-30 years and females (28.1%) aged 21-25. The rates of resistance to RFP and INH and the incidence of MDR were higher in males than females (20.5% vs. 16.1%, p < 0.001, 15.9% vs. 12.0%, p < 0.001 and 12.9% vs. 10.2%, p < 0.001, respectively). The HRM positivity rate was much higher in previously treated patients than those newly diagnosed for MTB infection. Notably, males at the initial screening had significantly higher rates of HRM positive, INH resistance, RFP resistance, and MDR-TB than females (all, p < 0.05), but not those previously treated for MTB infection. The HRM positivity and drug resistance rates were much higher in the urban vs. rural population. By multivariate analyses, previous treatment, age < 51 years, residing in an urban area, and male sex were significantly and positively associated with drug resistance after adjusting for smear results and year of testing. CONCLUSION: Males were at higher risks for MTB infection and drug resistance, while a younger age was associated with MTB infection, resistance to INH and RFP, and MDR-TB. Further comprehensive monitoring of resistance patterns is needed to control the spread of MTB infection and manage drug resistance locally.

Screening immune adjuvants for an inactivated vaccine against Erysipelothrix rhusiopathiae.

In this study, we screened adjuvants for an inactivated vaccine against Erysipelothrix rhusiopathiae (E. rhusiopathiae). Inactivated cells of E. rhusiopathiae strain HG-1 were prepared as the antigen in five adjuvanted inactivated vaccines, including a mineral-oil-adjuvanted vaccine (Oli vaccine), aluminum-hydroxide-gel-adjuvanted vaccine (Alh vaccine), ISA201-biphasic-oil-emulsion-adjuvanted vaccine (ISA201 vaccine), GEL02-water-soluble-polymer-adjuvanted vaccine (GEL vaccine), and IMS1313-water-soluble-nanoparticle-adjuvanted vaccine (IMS1313 vaccine). The safety test results of subcutaneous inoculation in mice showed that Oli vaccine had the most severe side effects, with a combined score of 35, followed by the ISA201 vaccine (25 points), Alh vaccine (20 points), GEL vaccine (10 points), and IMS1313 vaccine (10 points). A dose of 1.5LD50 of strain HG-1 was used to challenge the mice intraperitoneally, 14 days after their second immunization. The protective efficacy of Oli vaccine and Alh vaccine was 100% (8/8), whereas that of the other three adjuvanted vaccines was 88% (7/8). Challenge with 2.5LD50 of strain HG-1 resulted in a 100% survival rate, demonstrating the 100% protective efficacy of the Oli vaccine, followed by the GEL vaccine (71%, 5/7), IMS1313 vaccine (57%, 4/7), ISA201 vaccine (43%, 3/7), and Alh vaccine (29%, 2/7). Challenge with 4LD50 of strain HG-1 showed 100% (7/7) protective efficacy of the Oli vaccine and 71% (5/7) protective efficacy of the GEL vaccine, whereas the protective efficacy of other three adjuvanted vaccine was 14% (1/7). The Alh and GEL vaccines were selected for comparative tests in piglets, and both caused minor side effects. A second immunization with these two adjuvanted vaccines conferred 60 and 100% protective efficacy, respectively, after the piglets were challenged via an ear vein with 8LD100 of strain HG-1. After challenge with 16LD100 of strain HG-1, the Alh and GEL vaccines showed 40% and 100% protective efficacy, respectively. Our results suggested that GEL is the optimal adjuvant for an inactivated vaccine against E. rhusiopathiae.

Immune Protective Efficacy of China's Traditional Inactivated and Attenuated Vaccines against the Prevalent Strains of Pasteurella multocida in Mice.

Capsular type A and D strains of Pasteurella multocida are the main epidemic serogroups in pigs in China. In this study, we preliminarily evaluated the immune protective efficacy of the two traditional vaccines, an inactivated C44-1 aluminum-hydroxide-gel-adjuvanted (Alh-C44-1) vaccine and a live EO630 vaccine, against currently circulating strains of P. multocida in a mouse model. Mice immunized twice with conventional vaccines generated higher antibody titers, and significantly higher levels of IgG were observed in the mice inoculated with the inactivated Alh-C44-1 vaccine on day 35 (p < 0.05) than those with the live EO630 vaccine. The mice immune protection test showed that the vaccination groups had a 57% or 71% protection effect against the serogroup B strain, but had no protective effect against epidemic strains. In conclusion, our study found that the widely used traditional P. multocida vaccines in China provide good protection against homologous strains, but could not provide cross-protection against heterologous strains in a mouse model.

Comparison of the Glaesserella parasuis Virulence in Mice and Piglets.

In this study, we compared the virulence of the most common serovars of Glaesserella parasuis in China, serovars 4, 5, 12, and 13 (36 strains in total) in BALB/c mice and piglets. In mice, the median lethal doses (LD50s) of the four serovars were roughly 9.80 × 107-4.60 × 109 CFU, 2.10 × 108-8.85 × 109 CFU, 4.81 × 107-7.01 × 109 CFU, and 1.75 × 108-8.45 × 108 CFU, respectively. Serovar 13 showed the strongest virulence, followed by serovar 4, serovar 12, and serovar 5, but a significant difference in virulence was only observed between serovars 5 and 13. The virulence of strains of the same serovars differed significantly in piglets. Virulent and attenuated strains were present in all serovars, but serovar 5 was the most virulent in piglets, followed by serovars 13, 4, and 12. A significant difference in virulence was observed between serovars 5 and 4 and between serovars 5 and 12. However, the virulence of serovars 5 and 13 did not differ significantly. This comprehensive analysis of G. parasuis virulence in mice and piglets demonstrated that: (1) the order of virulence of the four domestic epidemic serovars (from strongest to weakest) in piglets was serovars 5, 13, 4, and 12; (2) both virulent and attenuated strains were present in all serovars, so virulence did not necessarily correlate with serovar; (3) Although G. parasuis was fatal in BALB/c mice, its virulence is inconsistent with that in piglets, indicating that BALB/c mice are inadequate as an alternative model of G. parasuis infection.

[Development of molecular markers of Mycobacterium tuberculosis rifampicin resistance gene rpoB by PARMS technology].

The purpose of this study is to provide a simple and reliable genetic typing approach for molecular drug susceptibility test of Mycobacterium tuberculosis, through the developing of fluorescence molecular marker of rifampicin resistance gene rpoB. Eleven fluorescent molecular markers of the rpoB gene were established by using the sequence difference between the amino acid positions 531, 526, 516, 511 and 513 of rpoB gene of rifampicin-resistant strains and the alleles of rifampicin-sensitive strains, combined with the PARMS technique (Penta-primer amplification refractory mutation system). We used 104 clinical isolates of Mycobacterium tuberculosis to validate this marker and it was verified by sequencing as 100% correct. These samples were also tested with proportional drug sensitivity test. The coincidence rate was 94.23%. The molecular markers had high reliability for genotyping of rpoB gene. It can also detect low-concentration drug-resistant samples (511/533 unit point mutations) whose phenotypic susceptibility cannot be detected. The eleven sets of fluorescent molecular markers could cover 92%-96% of rpoB gene mutation types of rifampicin-resistant strains, and provide new idea for rapid detection of rifampin-resistant Mycobacterium tuberculosis.

Enhancing the antibacterial activity of antimicrobial peptide PMAP-37(F34-R) by cholesterol modification.

BACKGROUND: The problem of increasing resistance against conventional antibiotics has drawn people's attention. Therefore, the development of novel antibacterial agents with effective and safe therapeutic effects is imminent. Antimicrobial peptides (AMPs) are considered a promising class of antibacterial agents due to their broad antibacterial spectrum. RESULTS: In this study, on the basis of our previously studied peptide PMAP-37(F34-R), a novel antimicrobial peptide Chol-37(F34-R) was developed by N-terminal cholesterol modification to increase hydrophobicity. We observed that the N-terminal cholesterol-modified Chol-37(F34-R) showed higher antimicrobial activity than PMAP-37(F34-R) in vitro. Chol-37(F34-R) also exhibited effective anti-biofilm activity and may kill bacteria by improving the permeability of their membranes. Chol-37(F34-R) exerted high stability in different pH, salt, serum, and boiling water environments. Chol-37(F34-R) also showed no hemolytic activity and substantially low toxicity. Furthermore, Chol-37(F34-R) exhibited good potency of bacteria eradication and promoted wound healing and abscess reduction in infected mice. Meanwhile, in S. aureus ATCC25923-infected peritonitis model, Chol-37(F34-R) exhibited an impressive therapeutic effect by reducing the decrease in systemic bacterial burden and alleviating organ damage. CONCLUSIONS: Our findings suggested that the N-terminal cholesterol modification of PMAP-37(F34-R) could improve antibacterial activity. Chol-37(F34-R) displayed excellent bactericidal efficacy and impressive therapeutic effect in vivo. Thus, Chol-37(F34-R) may be a candidate for antimicrobial agents against microbial infection in the clinic.

N-terminal Myristoylation Enhanced the Antimicrobial Activity of Antimicrobial Peptide PMAP-36PW.

Drug-resistant bacteria infections and drug residues have been increasing and causing antibiotic resistance and public health threats worldwide. Antimicrobial peptides (AMPs) are novel antimicrobial drugs with the potential to solve these problems. Here, a peptide based on our previously studied peptide PMAP-36PW was designed via N-terminal myristoylation and referred to as Myr-36PW. The fatty acid modification provided the as-prepared peptide with good stability and higher antimicrobial activity compared with PMAP-36PW in vitro. Moreover, Myr-36PW exhibited effective anti-biofilm activity against Gram-negative bacteria and may kill bacteria by improving the permeability of their membranes. In addition, the designed peptide Myr-36PW could inhibit the bacterial growth of Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa GIM 1.551 to target organs, decrease the inflammatory damage, show an impressive therapeutic effect on mouse pneumonia and peritonitis experiments, and promote abscess reduction and wound healing in infected mice. These results reveal that Myr-36PW is a promising antimicrobial agent against bacterial infections.

Molecular pathogenesis of the hyaluronic acid capsule of Pasteurella multocida.

Pasteurella multocida possesses a viscous capsule polysaccharide on the cell surface, which is a critical structural component and virulence factor. Capsular polysaccharides are structurally similar to vertebrate glycosaminoglycans, providing an immunological mechanism for bacterial molecular mimicry, resistance to phagocytosis, and immune evasion during the infection process. Based on the capsular antigen, P. multocida is divided into A, B, D, E, and F five serogroups. Previously, we systematically reported the biosynthesis and regulation mechanisms of the P. multocida capsule. In this paper, we take serogroup A capsular polysaccharide as the representative, systematically illuminating the P. multocida capsular virulence and epidemiology, molecular camouflage, adhesion and colonization, anti-phagocytosis, anti-complement system, cell invasion and signal transduction mechanism, to provide a theoretical basis for the research of molecular pathogenic mechanism of P. multocida capsule and the development of polysaccharides vaccine.

The prevalence of amphenicol resistance in Escherichia coli isolated from pigs in mainland China from 2000 to 2018: A systematic review and meta-analysis.

BACKGROUND: Amphenicols have been widely used in the pig industry in China, leading to varying degrees of drug resistance. METHODS: The systematic review was performed according to PRISMA (Preferred Reported Items for Systematic Reviews and Meta-Analysis) recommendations on studies investigating the prevalence of amphenicol-resistant Escherichia coli (E. coli) isolated from pig in mainland China from 2000 to 2018, a random-effects model was selected, then followed by meta-analysis. RESULTS: A total of 103 articles were included in the study. The results of the meta-analysis revealed that the pooled summarized prevalence of resistance to chloramphenicol (CAP) was 72.31% (95% confidence interval (95% CI) = 67.12%-77.23%) and to florfenicol (FF) was 58.64% (95% CI = 52.48%-64.67%). During the past 18 years, the resistance rate to CAP remained high initially but then declined rapidly after 2012, whereas the resistance rate to FF plateaued (54.13%-59.60%) from 2000-2018. In different parts of China, the rate of resistance to amphenicols among E. coli isolates was fairly consistent, with the exception of the north and northwest regions. CONCLUSIONS: In 2002, the veterinary use of CAP was prohibited and its resistance levels in E. coli isolated from pigs was initially maintained at a high level but then showed an obvious downward trend in recent years. Resistance to commonly used FF remained at a high but stable level.

Cephalosporin Resistance in Escherichia coli Isolated from Children with Septicemia in Mainland China from 2007 to 2017: A Systematic Review and Meta-Analysis.

Background: Septicemia in children in mainland China has recently become a public health concern. Methods: A meta-analysis was performed on studies investigating the prevalence of cephalosporin-resistant Escherichia coli isolated from children with septicemia in mainland China from 2007 to 2017 following a search of relevant databases. Results: A total of 43 articles reporting 11 cephalosporins were included in the review. The results of the meta-analysis revealed that for the first-generation cephalosporins, the pooled summarized prevalence of resistance to cefazolin was 74.96% (95% confidence interval [CI]: 64.79-83.91) and cephalothin resistance was 62.28% (95% CI: 36.45-100). Regarding the second-generation cephalosporins, cefoxitin-resistant E. coli comprised 23.85% (95% CI: 10.60-40.40) and cefuroxime resistance was 60.32% (95% CI: 51.25-68.73). For the third-generation cephalosporins, the pooled summarized prevalence of resistance was 51.34% for cefotaxime (95% CI: 40.08-62.54), 40.43% for ceftazidime (95% CI: 31.07-50.15), 45.51% for cefoperazone (95% CI: 20.41-70.61), 12.10% for cefoperazone/sulbactam (95% CI: 6.55-18.76), 62.99% for ceftriaxone (95% CI: 55.00-70.98), and 0% for cefotetan. Among the fourth-generation cephalosporins, resistance to cefepime was 34.08% (95% CI: 25.91-43.31). Conclusions: Most third-generation cephalosporins (e.g., cefotaxime and ceftriaxone) retained high resistance rates throughout the 11-year study period without significant changes. The new fourth-generation cephalosporin, cefepime, is rapidly gaining resistance. Interestingly, ceftazidime, cefepime, and cefoperazone/sulbactam showed a recent decreasing trend of drug resistance. These situations may present a risk for treating children with septicemia and should be closely monitored and treated.

Biosynthesis and regulation mechanisms of the Pasteurella multocida capsule.

Pasteurella multocida possesses a polysaccharide capsule composed of a viscous surface layer that acts as a critical structural component and virulence factor. Capsular polysaccharides are structurally similar to vertebrate glycosaminoglycans, providing an immunological mechanism for bacterial molecular mimicry, resistance to phagocytosis, and immune evasion during the infection process. In recent years, a series of important research advances have been made in understanding the biosynthesis and regulatory aspects of the P. multocida capsule. This review systematically examines the serogroups, polysaccharide composition and structures, biosynthetic loci and functions, biosynthesis pathways, and expression regulation mechanisms of the P. multocida capsule, supplying a theoretical basis for the molecular pathogenesis of the P. multocida capsule and the future development of capsular polysaccharide vaccines.

NDM-1-producing Escherichia coli isolated from pigs induces persistent infection with limited pathogenicity.

NDM-1-producing Enterobacteriaceae are multidrug-resistant bacteria, also called superbacteria, that have become important global human health threats in recent years. However, data about NDM-1-producing bacteria in animals are rare. In this study, an NDM-1-producing Escherichia coli isolate (designated E120413) was obtained from pigs in Henan province, China in 2012. The susceptibility of E. coli E120413 to antimicrobial agents was determined using Kirby-Bauer disk diffusion and micro-dilution methods. Susceptibility tests indicated that E. coli E120413 was resistant to almost all common antibiotics with high MIC values obtained for most antibiotics tested. E. coli E120413 was detected in the heart, liver, spleen, lung, kidney, brain, stomach, duodenum, mesenteric lymph nodes, and fecal samples of piglets in both cohabitation and experimental groups and the bacteria persisted for more than 2 weeks. However, no obvious clinical symptoms or serious pathological lesions were observed. This is the first investigation of NDM-1-producing E. coli isolate from pigs in China. Although no significant pathological lesions were observed, NDM-1-producing E. coli was found to be highly transmissible and to cause persistent infection in pigs.

Non-lipopeptide fungi-derived peptide antibiotics developed since 2000.

The 2,5-diketopiperazines (DKPs) are the smallest cyclopeptides and their basic structure includes a six-membered piperazine nucleus. Typical peptides lack a special functional group in the oligopeptide nucleus. Both are produced by at least 35 representative genera of fungi, and possess huge potential as pharmaceutical drugs and biocontrol agents. To date, only cyclosporin A has been developed into a commercial product. This review summarises 186 fungi-derived compounds reported since 2000. Antibiotic (antibacterial, antifungal, synergistic antifungal, antiviral, antimycobacterial, antimalarial, antileishmanial, insecticidal, antitrypanosomal, nematicidal and antimicroalgal) activities are discussed for 107 of them, including 66 DKPs (14 epipolythiodioxopiperazines, 20 polysulphide bridge-free thiodiketopiperazines, and 32 sulphur-free prenylated indole DKPs), 15 highly N-methylated, and 26 non-highly N-methylated typical peptides. Structure-activity relationships, mechanisms of action, and research methods are covered in detail. Additionally, biosynthases of tardioxopiperazines and neoechinulins are highlighted. These compounds have attracted considerable interest within the pharmaceutical and agrochemical industries.

Fungi-derived lipopeptide antibiotics developed since 2000.

Lipopeptide antibiotics have linear or cyclic structures with one or more hydrocarbon tails linked to the N-terminus of a short oligopeptide that may be chemically modified and/or contain unusual amino acid residues in their structures. They possess huge potential as pharmaceutical drugs and biocontrol agents, and ˜30 representative genera of fungi are known to produce them. Some chemically synthesised derivatives have already been developed into commercial products or subjected to clinical trials, including cilofungin, caspofungin, micafungin, anidulafungin, rezafungin, emodepside, fusafungine and destruxins. This review summarizes 200 fungi-derived compounds reported since 2000, including 95 cyclic depsipeptides, 67 peptaibiotics (including 35 peptaibols, eight lipoaminopeptides, and five lipopeptaibols), and 38 non-depsipeptide and non-peptaibiotic lipopeptides. Their sources, structural sequences, antibiotic activities (e.g. antibacterial, antifungal, antiviral, antimycobacterial, antimycoplasmal, antimalarial, antileishmanial, insecticidal, antitrypanosomal and nematicidal), structure-activity relationships, mechanisms of action, and specific relevance are discussed. These compounds have attracted considerable interest within the pharmaceutical and agrochemical industries.

Cyanobacteria-derived peptide antibiotics discovered since 2000.

Members of cyanobacteria, including Moorea spp., Okeania spp., Lyngbya spp., Schizothrix spp., Leptolyngbya spp., Microcystis spp., Symploca spp., Hassallia sp., Anabaena spp., Planktothrix sp., Tychonema spp., Oscillatoria spp., Tolypothrix sp., Nostoc sp., and Hapalosiphon sp. produce an enormously diverse range of peptide antibiotics with huge potential as pharmaceutical drugs and biocontrol agents following screening of structural analogues and analysis of structure-activity relationships (SAR). The need for novel antibiotic lead compounds is urgent, and this review summarizes 78 cyanobacteria-derived compounds reported since 2000, including 32 depsipeptides, 18 cyclic lipopeptides, 13 linear lipopeptides, 14 cyclamides, and one typical cyclic peptide. The current and potential therapeutic applications of these peptides are discussed, including for SAR, antituberculotic, antifungal, antibacterial, antiviral, and antiparasitic (anti-plasmodial, antitrypanosomal and antileishmanial) activities.

Environmental impacts and resource use of milk production on the North China Plain, based on life cycle assessment.

Life cycle assessment methodology was used to quantify the environmental impacts and resource use of milk production on the North China Plain, the largest milk production area in China. Variation in environmental burden caused by cow productivity was evaluated, as well as scenario analysis of the effects of improvement practices. The results indicated that the average environmental impact potential and resource use for producing 1kg of fat and protein corrected milk was 1.34kgCO2eq., 9.27gPO43-eq., 19.5gSO2eq., 4.91MJ, 1.83m2 and 266L for global warming potential (GWP), eutrophication potential (EP), acidification potential (AP), non-renewable energy use (NREU), land use (LU) and blue water use (BWU; i.e. water withdrawal), respectively. Feed production was a significant determinant of GWP, NREU, LU and BWU, while AP and EP were mainly affected by manure management. Scenario analysis showed that reducing use of concentrates and substituting with alfalfa hay decreased GWP, EP, AP, NREU and LU (by 1.0%-5.5%), but caused a significant increase of BWU (by 17.2%). Using imported soybean instead of locally-grown soybean decreased LU by 2.6%, but significantly increased GWP and NREU by 20% and 6.9%, respectively. There was no single perfect manure management system, with variable effects from different management practices. The environmental burden shifting observed in this study illustrates the importance of assessing a wide range of impact categories instead of single or limited indicators for formulating environmental policies, and the necessity of combining multiple measures to decrease the environmental burden. For the North China Plain, improving milking cow productivity and herd structure (i.e. increased proportion of milking cows), combining various manure management systems, and encouraging dairy farmers to return manure to nearby crop lands are promising measures to decrease multiple environmental impacts.