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Abstract To maintain the growth and development of pepper in saline condition, candidates of plant growth promoting rhizobacteria (PGPR) were isolated, and detected to plant growth promoting (PGP) potential under salt stress was investigated. Thirteen bacterial strains with 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, WU-1–13, were isolated from saline soil in Xinjiang, China. The isolates were shown to belong to the genera Bacillus by partial sequencing analysis of their respective 16 S rRNA genes. Seven isolates had the ability to solubilize phosphate. Moreover, the amount of solubilized phosphate was significantly high (P < 0.05), which ranged from 157.33 μg/mL to 922.41 μg/mL. All tested bacterial strains were shown to produce a large amount of ACC deaminase and NH 3. Furthermore, nine strains were detected for siderophore production. On the aspect of extracellular enzyme, all bacterial isolates produced lipase, amylase and cellulose, whereas only a minority produced chitinase (15.4%) and 10 isolates produced β-glucanase or protease. In growth room experiments, the results showed that the strain WU-5 exhibited better growth promotion of pepper seedlings in terms of fresh weight (75.60%), dry weight (86.68%), shoot length (12.12%) and root length (146.52%) over the control under saline stress followed by WU-13. Furthermore, seedlings accumulated high amounts of proline induced by the different PGPR inoculation treatments to alleviate the negative effects of salt stress. Further growth-promoting assays under different salt stress were set up to confirm that the fresh and dry weight, shoot and root length of pepper plants inoculated by three strains all were significantly higher than non-inoculated control under different saline stress. In summary, the results demonstrated that WU-9, which induced high levels of proline production and antioxidant enzyme activities, and three strains (WU-5, WU-9 and WU-13) can be of great value in maintaining the growth and development of seedlings on saline lands. Highlights • 13 strains with ACC deaminase activity were isolated from saline soil in Xinjiang. • Three strains, WU-5, WU-9 and WU-13, had great potential to promote plant growth. • WU-9 induced high levels of proline content and antioxidant enzyme activities. • Alleviation of salt stress mainly relied on accumulation of proline in seedlings. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the main cause of blindness in elderly individuals. As a metabolic regulator, fibroblast growth factor 21 (FGF-21) has been proven indicated to have an effect on wet AMD, but whether this cytokine has a therapeutic effect on dry AMD is unclear. The current study aimed to evaluate the preventive effects of FGF-21 against retinal degeneration in mice and provide mechanistic insights. FGF-21−/− mice were raised to 10 months of age. Then, the morphological changes in the retinal pigment epithelium (RPE)/choroid of the mice were observed by transmission electron microscopy (TEM), and iTRAQ was used to detect the variations in the protein profile. Next, FGF-21−/− and wild-type mice of the same age were fed hydroquinone to generate a dry AMD mouse model to examine whether exogenous FGF-21 can interfere with the occurrence and development of dry AMD. In vivo studies revealed that following FGF-21 knockout, there was an increase in the expression of complement in the RPE/choroid concomitant with the occurrence of dry AMD-like pathological changes. Furthermore, exogenous FGF-21 administration effectively reversed this phenomenon. FGF-21 also demonstrated strong anti-inflammatory effects in the RPE/choroid by inhibiting the NF-κB pathway. In conclusion, the present study demonstrates that FGF-21 treatment presents a novel therapeutic approach for the prevention and development of dry AMD by reducing complement. • Fibroblast Growth Factor 21 Deficiency Induces Dry AMD in Mice by Elevating Complement in the Eye. • FGF-21 has a novel therapeutic approach for the prevention of dry AMD development via reducing inflammatory process induced by NF-kB pathway. [ABSTRACT FROM AUTHOR]

• IL17A polymorphism (rs8193036) is associated with susceptibility to TB. • rs8193036 is a functional SNP that could regulate IL17A gene expression. • Treatments targeting to the IL17A pathway could be a new therapy strategy to TB. Th17 cells play a key role in immunity against Mycobacterium tuberculosis, our previous research showed that reduced Th17 responses were associated with the severe outcome of Mtb infection. The associations between IL17A polymorphisms and susceptibility of TB has been reported, but the results are inconsistent and the underlying mechanisms is unknown. In this study, we identified a genetic variation (rs8193036) in the promoter region of IL17A is associated with susceptibility to TB. The minor allele T frequency of rs8193036 was significantly different between patients with active TB (29.7%) and healthy controls (32.3%) (OR = 0.81; 95%CI, 0.71–0.93; P = 0.0026). Peripheral blood mononuclear cells from individuals carrying rs8193036CC genotypes produced significantly lower amount of IL17A upon CD3/28 stimulation compared to the individuals carrying rs8193036TT genotypes. Functional assay by reporter luciferase activity and EMSA demonstrated that rs8193036C exhibited significantly lower promotor transcription activities. In conclusion, our study confirmed that IL17A (rs8193036) is a functional SNP that could regulate gene expression though influencing transcription factor binding activity. [ABSTRACT FROM AUTHOR]

A CDR3 mutant library was constructed from a previously isolated anti-HBV neutralizing Homo sapiens scFv-31 template by random mutant primers PCR. Then the library was displayed on the inner membrane surface in Escherichia coli periplasmic space. Seven scFv clones were isolated from the mutant library through three rounds of screening by flow cytometry. Competition ELISA assay indicates that isolated scFv fragments show more efficient binding ability to HBV PreS1 compared with parental scFv-31. HBV neutralization assay indicated that two clones (scFv-3 and 59) show higher neutralizing activity by blocking the HBV infection to Chang liver cells. Our method provides a new strategy for rapid screening of mutant antibody library for affinity-enhanced scFv clones and the neutralizing scFvs obtained from this study provide a potential alternative of Hepatitis B immune globulin. [ABSTRACT FROM AUTHOR]

The pentacyclic triterpenoid quinone methide celastrol (CS) from Tripterygium wilfordii Hook. F. effectively ameliorates inflammation with potential as therapeutics for inflammatory diseases. However, the molecular mechanisms underlying the anti-inflammatory and inflammation-resolving features of CS are incompletely understood. Here we demonstrate that CS potently inhibits the activity of human 5-lipoxygenase (5-LOX), the key enzyme in pro-inflammatory leukotriene (LT) formation, in cell-free assays with IC 50 = 0.19–0.49 µM. Employing metabololipidomics using ultra-performance liquid chromatography coupled to tandem mass spectrometry in activated human polymorphonuclear leukocytes or M1 macrophages we found that CS (1 µM) potently suppresses 5-LOX-derived products without impairing the formation of lipid mediators (LM) formed by 12-/15-LOXs as well as fatty acid substrate release. Intriguingly, CS induced the generation of 12-/15-LOX-derived LM including the specialized pro-resolving mediator (SPM) resolvin D5 in human M2 macrophages. Finally, intraperitoneal pre-treatment of mice with 10 mg/kg CS strongly impaired zymosan-induced LT formation and simultaneously elevated the levels of SPM and related 12-/15-LOX-derived LM in peritoneal exudates, spleen and plasma in vivo. Conclusively, CS promotes a switch from LT biosynthesis to formation of SPM which may underlie the anti-inflammatory and inflammation-resolving effects of CS, representing an interesting pharmacological strategy for intervention with inflammatory disorders. [Display omitted] • 5-LOX is a high affinity target for celastrol (CS) with IC 50 of 0.19–0.49 µM. • CS blocks 5-LOX-derived leukotriene formation in PMNL and M1 macrophages. • in M2 macrophages CS elicits specialized pro-resolving mediator (SPM) formation. • CS impairs the levels of leukotrienes but elevates SPM in murine peritonitis. [ABSTRACT FROM AUTHOR]