Differences in the pathogenicity and molecular characteristics of fowl adenovirus serotype 4 epidemic strains in Guangxi Province, southern China.

Starting in 2015, the widespread prevalence of hydropericardium-hepatitis syndrome (HHS) has led to considerable financial losses within China's poultry farming industry. In this study, pathogenicity assessments, whole-genome sequencing, and analyses were conducted on 10 new isolates of the novel genotype FAdV-4 during a HHS outbreak in Guangxi Province, China, from 2019 to 2020. The results indicated that strains GX2019-010 to GX2019-013 and GX2019-015 to GX2019-018 were highly virulent, while strain GX2020-019 exhibited moderate virulence. Strain GX2019-014 was characterized as a wild-type strain with low virulence, displaying no pathogenic effects when 0.5 mL containing 106 TCID50 virus was inoculated into the muscle of specific pathogen-free (SPF) chickens at 4 weeks of age, while 107 TCID50 and 108 TCID50 resulted in mortality rates of 80 and 100%, respectively. The whole genomes of strains GX2019-010 to GX2019-013, GX2019-015 to GX2019-018, and GX2020-019 showed high homology with other Chinese newly emerging highly pathogenic FAdV-4 strains, whereas GX2019-014 was closer to nonmutant strains and shared the same residues with known nonpathogenic strains (B1-7, KR5, and ON1) at positions 219AA and 380AA of the Fiber-2 protein. Our work enriches the research on prevalent strains of FAdV-4 in China, expands the knowledge on the virulence diversity of the novel genotype FAdV-4, and provides valuable reference material for further investigations into the key virulence-associated genetic loci of FAdV-4.

Intraoperative Computed Tomography in the Surgical Treatment of Zygomatic Complex Fracture: A Retrospective Cohort Study.

This study aimed to assess the effectiveness of intraoperative computed tomography (ICT) in managing zygomatic complex (ZMC) fractures surgically. A total of 143 patients (84 men, 59 women; average age 37.13 y) undergoing surgical treatment for ZMC fractures participated in this retrospective cohort study, with 72 in the ICT group and 71 in the control group. There were no notable differences in gender, age, time from injury to surgery, and surgical duration between the two groups. The ICT group exhibited significantly fewer surgical approaches than the control group (1.39±0.519 vs. 2.07±0.617, P<0.001). Fixation points in the ICT group (1-point: 42, 2-point: 14, 3-point: 16) significantly differed from the control group (1-point: 15, 2-point: 17, 3-point: 39), P<0.001. Symmetry of reduction was assessed through immediate postoperative images, and stability was compared between immediate postoperative images and those taken at least 3 months later. Both assessments revealed no significant differences between the 2 groups. This study indicates that ICT facilitates prompt evaluation of ZMC reduction, minimizing the necessity for incisions and internal fixation, while achieving comparable reduction efficacy and long-term stability to conventional approaches.

CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1.

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.

A sandwich amperometric immunosensor for the detection of fowl adenovirus group I based on bimetallic Pt/Ag nanoparticle-functionalized multiwalled carbon nanotubes.

An enzyme-free sandwich amperometric immunosensor based on bimetallic Pt/Ag nanoparticle (Pt/AgNPs)-functionalized chitosan (Chi)-modified multiwalled carbon nanotubes (MWCNTs) as dual signal amplifiers and Chi-modified MWCNTs (MWCNTs-Chi) as substrate materials was developed for ultrasensitive detection of fowl adenovirus group I (FAdV-I). MWCNTs have a large specific surface area, and many accessible active sites were formed after modification with Chi. Hence, MWCNTs-Chi, as a substrate material for modifying glassy carbon electrodes (GCEs), could immobilize more antibodies (fowl adenovirus group I-monoclonal antibody, FAdV-I/MAb). Multiple Pt/AgNPs were attached to the surface of MWCNTs-Chi to generate MWCNTs-Chi-Pt/AgNPs with high catalytic ability for the reaction of H2O2 and modified active sites for fowl adenovirus group I-polyclonal antibody (FAdV-I/PAb) binding. Amperometric i-t measurements were employed to characterize the recognizability of FAdV-I. Under optimal conditions, and the developed immunosensor exhibited a wide linear range (100.93 EID50 mL-1 to 103.43 EID50 mL-1), a low detection limit (100.67 EID50 mL-1) and good selectivity, reproducibility and stability. This immunosensor can be used in clinical sample detection.

Highly efficient degradation of acetaminophen via nano zero-valent iron biochar with periodate system at low temperature.

The development of more efficient advanced oxidation systems for serving various advanced treatment of wastewater is quite necessary and urgent. In this study, a nano-zero valent iron/periodate (nZVI-BC/PI) advanced oxidation system has been constructed, achieving a rapid degradation of acetaminophen (ACT, 1 mg/L) within 1 min (100 % at pH = 11) at low temperature (5℃). This system shows a great degradation in a wide range of pH (1 âˆ¼ 11), improving the pH limitation of PI oxidation system. During the reaction process, ·OH as the main active species collaborate with 1O2, Fe (IV), ·O2- and electron transfer to degrade ACT. In this system, iron ion leaching is low (0.019 mg/L), ACT was effectively degraded (74.36 %∼97.32 %) under different water, moreover, the material has an expected recyclability. The research provides a significant guidance for the advanced treatment of wastewater especially in cold regions.

Chicken IFI6 inhibits avian reovirus replication and affects related innate immune signaling pathways.

Interferon-alpha inducible protein 6 (IFI6) is an important interferon-stimulated gene. To date, research on IFI6 has mainly focused on human malignant tumors, virus-related diseases and autoimmune diseases. Previous studies have shown that IFI6 plays an important role in antiviral, antiapoptotic and tumor-promoting cellular functions, but few studies have focused on the structure or function of avian IFI6. Avian reovirus (ARV) is an important virus that can exert immunosuppressive effects on poultry. Preliminary studies have shown that IFI6 expression is upregulated in various tissues and organs of specific-pathogen-free chickens infected with ARV, suggesting that IFI6 plays an important role in ARV infection. To analyze the function of avian IFI6, particularly in ARV infection, the chicken IFI6 gene was cloned, a bioinformatics analysis was conducted, and the roles of IFI6 in ARV replication and the innate immune response were investigated after the overexpression or knockdown of IFI6 in vitro. The results indicated that the molecular weight of the chicken IFI6 protein was approximately 11 kDa and that its structure was similar to that of the human IFI27L1 protein. A phylogenetic tree analysis of the IFI6 amino acid sequence revealed that the evolution of mammals and birds was clearly divided into two branches. The evolutionary history and homology of chickens are similar to those of other birds. Avian IFI6 localized to the cytoplasm and was abundantly expressed in the chicken lung, intestine, pancreas, liver, spleen, glandular stomach, thymus, bursa of Fabricius and trachea. Further studies demonstrated that IFI6 overexpression in DF-1 cells inhibited ARV replication and that the inhibition of IFI6 expression promoted ARV replication. After ARV infection, IFI6 modulated the expression of various innate immunity-related factors. Notably, the expression patterns of MAVS and IFI6 were similar, and the expression patterns of IRF1 and IFN-ß were opposite to those of IFI6. The results of this study further advance the research on avian IFI6 and provide a theoretical basis for further research on the role of IFI6 in avian virus infection and innate immunity.

Thallium-mediated NO signaling induced lipid accumulation in microalgae and its role in heavy metal bioremediation.

Thallium (Tl+) is a trace metal with extreme toxicity and is highly soluble in water, posing a great risk to ecological and human safety. This work aimed to investigate the role played by Tl+ in regulating lipid accumulation in microalgae and the removal efficiency of Tl+. The effect of Tl+ on the cell growth, lipid production and Tl+ removal efficiency of Parachlorella kessleri R-3 was studied. Low concentrations of Tl+ had no significant effect on the biomass of microalgae. When the Tl+ concentration exceeded 5 µg L-1, the biomass of microalgae showed significant decrease. The highest lipid content of 63.65% and lipid productivity of 334.55 mg L-1 d-1 were obtained in microalgae treated with 10 and 5 µg L-1 Tl+, respectively. Microalgae can efficiently remove Tl+ and the Tl+ removal efficiency can reach 100% at Tl+ concentrations of 0-25 µg L-1. The maximum nitric oxide (NO) level of 470.48 fluorescence intensity (1 × 106 cells)-1 and glutathione (GSH) content of 343.51 nmol g-1 (fresh alga) were obtained under 5 µg L-1 Tl+ stress conditions. Furthermore, the exogenous donor sodium nitroprusside (SNP) supplemented with NO was induced in microalgae to obtain a high lipid content (59.99%), lipid productivity (397.99 mg L-1 d-1) and GSH content (430.22 nmol g-1 (fresh alga)). The corresponding analysis results indicated that NO could participate in the signal transduction pathway through modulation of reactive oxygen species (ROS) signaling to activate the antioxidant system by increasing the GSH content to eliminate oxidative damage induced by Tl+ stress. In addition, NO regulation of ROS signaling may enhance transcription factors associated with lipid synthesis, which stimulates the expression of genes related to lipid synthesis, leading to increased lipid biosynthesis in microalgae. Moreover, it was found that the change in Tl+ had little effect on the fatty acid components and biodiesel properties. This study showed that Tl+ stress can promote lipid accumulation in microalgae for biodiesel production and simultaneously effectively remove Tl+, which provided evidence that NO was involved in signal transduction and antioxidant defense, and improved the understanding of the interrelation between NO and ROS to regulate lipid accumulation in microalgae.

Legionnaires' Disease in China Caused by Legionella pneumophila Corby.

Legionella pneumophila is an intracellular pathogen causing pneumonia in humans. In February 2022, Legionnaires' disease caused by L. pneumophila strain Corby in a patient with lung adenocarcinoma was identified for the first time in China. This paper includes the case report and phenotypic and genomic analysis of the Corby (ICDC) strain. Its biological characteristics were evaluated by antibiotic sensitivity testing and cytology experiments, and genomic analysis was performed to understand its genetic evolution. The patient's clinical manifestations included cough, fever, pulmonary infiltration, and significantly decreased activity endurance. After empirical antimicrobial therapy, infection indicators decreased. The Corby (ICDC) strain was susceptible to nine antibiotics and exhibited strong intracellular proliferation ability. A phylogenetic tree showed that the Corby (ICDC) strain was closely related to the Corby strain, but under the pressure of a complex environment, its genome had undergone more rearrangement and inversion. The type IF CRISPR-Cas system was identified in its genome, and spacer analysis indicated that it had been invaded by several foreign plasmids, bacteria, and viruses during evolution. Legionnaires' disease caused by L. pneumophila strain Corby may be ignored in China, and it is urgent to improve long-term monitoring and investigation of aquatic environments and patients with respiratory infections to prevent a large-scale outbreak of Legionnaires' disease.

Synergistic effect of hydrogen and nanoscale zero-valent iron on ex-situ biogas upgrading and acetate recovery.

Hydrogen (H2) assisted ex-situ biogas upgrading and liquid chemicals production can augment the fossil fuel-dominated energy market, and alleviate CO2-induced global warming. Recent investigations confirmed that nanoscale zero-valent iron (nZVI) enabled the enhancement of anaerobic digestion for biogas production. However, little is known about the effect of nZVI on the downstream ex-situ biogas upgrading. Herein, different levels (0 mg L-1, 100 mg L-1, 200 mg L-1, 500 mg L-1, 1000 mg L-1, 2000 mg L-1) of nZVI were added for H2-assisted ex-situ biogas upgrading, to study whether nZVI could impact the biomethane purity and acetate yield for the first time. Results showed that all tested nZVI levels were favorable for biogas upgrading in the presence of H2, the highest biomethane content (94.1 %, v/v), the CO2 utilization ratio (95.9 %), and acetate yield (19.4 mmol L-1) were achieved at 500 mg L-1 nZVI, respectively. Further analysis indicated that increased biogas upgrading efficiency was related to an increase in extracellular polymeric substances, which ensures the microbial activity and stability of the ex-situ biogas upgrading. Microbial community characterization showed that the Petrimonas, Romboutsia, Acidaminococcus, and Clostridium predominated the microbiome during biogas upgrading at 500 mg L-1 nZVI with H2 supply. These results suggested that nZVI and H2 contributed jointly to promoting the bioconversion of CO2 in biogas to acetate. The findings could be helpful for paving a new way for efficient simultaneous ex-situ biogas upgrading and liquid chemicals recovery.

Guanidino quinazolines and pyrimidines promote readthrough of premature termination codons in cells with native nonsense mutations.

Using small molecules to induce readthrough of premature termination codons is a promising therapeutic approach to treating genetic diseases and cancers caused by nonsense mutations, as evidenced by the widespread use of ataluren to treat nonsense mutation Duchene muscular dystrophy. Herein we describe a series of novel guanidino quinazoline and pyrimidine scaffolds that induce readthrough in both HDQ-P1 mammary carcinoma cells and mdx myotubes. Linkage of basic, tertiary amines with aliphatic, hydrophobic substituents to the terminal guanidine nitrogen of these scaffolds led to significant potency increases. Further potency gains were achieved by flanking the pyrimidine ring with hydrophobic substituents, inducing readthrough at concentrations as low as 120 nM and demonstrating the potential of these compounds to be used either in combination with ataluren or as stand-alone therapeutics.

Recurrence-Related Factors of Medication-Related Osteonecrosis of the Jaw: A Five-Year Experience.

PURPOSE: The treatment of medication-related osteonecrosis of the jaw (MRONJ) is greatly challenging for surgeons. In this study, we reviewed patients with MRONJ treated in our hospital in the past 5 years and explored the risk factors of recurrence. METHODS: A retrospective cohort study was conducted to review the patients with MRONJ from January 1, 2016 to December 31, 2020. All patients received a monthly intravenous application of zoledronic acid. The primary outcome variable was the treatment outcome during follow-up. The predictor variables were local and systemic factors related to the treatment outcome. Multivariate logistic regression analysis was performed to identify the risk factors of recurrence after MRONJ treatment. RESULTS: A total of 58 patients (62 sites) were included in this study. In multivariate regression analysis, the risk factor associated with recurrence after MRONJ treatment was the duration of medication of more than 18 months (odds ratio = 7.346; 95% confidence interval: 1.461-36.946; P = .016). CONCLUSIONS: Using zoledronic acid over 18 months may increase the risk of recurrence in MRONJ patients.

Role of residue cornstalk derived biochar for the enhanced bio-hydrogen production via simultaneous saccharification and fermentation of cornstalk.

Biochar derived from residue cornstalk left after anaerobic bio-hydrogen production (RCA-biochar) was confirmed to enhance bio-hydrogen production from cornstalk hydrolysate. However, the role of RCA-biochar in simultaneous saccharification and fermentation (SSF) during bio-hydrogen production from cornstalk has not yet been revealed. This study therefore aims to fill this knowledge gap. It was observed that with the increase in RCA-biochar concentration from 0 g/L to 10.0 g/L, the maximal cumulative SSF bio-hydrogen yield varied from 24.3 ± 1.1 mL/g-substrate to 154.3 ± 3.6 mL/g substrate under varying pH values - 5.5, 6.0, 6.5, 7.0. The increasing bio-hydrogen production was observed to correlate with both RCA-biochar level and initial pH. Batch tests confirmed that the initial pH had an obvious effect an saccharification, while RCA-biochar affected anaerobic fermentation a lot. The findings revealed the role of previously unrecognized RCA-biochar in SSF bio-hydrogen production from cornstalk, which can provide an alternative approach for lignocellulosic bio-hydrogen production.

Residue cornstalk derived biochar promotes direct bio-hydrogen production from anaerobic fermentation of cornstalk.

In this study, an innovative approach was proposed based on the implement of biochar derived from residue cornstalk left after anaerobic bio-hydrogen production (RCA-biochar) to improve direct bio-hydrogen production from anaerobic fermentation of cornstalk. The bio-hydrogen production potential and maximum bio-hydrogen production rate increased from 156.2 to 286.1 mL H2/g substrate and 3.5 to 5.7 mL H2/g substrate/h, respectively, following the added RCA-biochar increased from 2.5 to 15.0 g/L. Cornstalk chemical component analysis showed the cellulose and hemicellulose content decreased by 17.9-33.7% and 14.4-25.2%, and lignin content increased by 20.3-42.8%, respectively, after 96 h anaerobic fermentation with RCA-biochar 2.5-15.0 g/L. Further analyses revealed that RCA-biochar not only provided more specific surface area for hydrogen-producing bacteria attachment, but also promoted the cellulolytic enzyme activity, thereby resulted in increased substrate conversion to bio-hydrogen.The findings obtained in this study may provide supports for effective and sustainable lignocellulosic bio-hydrogen production in the future.

Glutaredoxin 1 regulates macrophage polarization through mediating glutathionylation of STAT1.

BACKGROUND: Macrophage polarization affects tumor growth, metabolism, and many other tumor processes. M1 macrophages can promote antitumor immunity response. Signal transducer and activator of transcription 1 (STAT1) is one of the critical transcription factors in this process, which promotes the expression of a series of inflammatory molecules. STAT1 has been reported as a potential target of reactive oxygen species (ROS)-induced glutathionylation, while the glutathionylation of STAT1 in macrophages and its underlying regulatory mechanism remains unclear. Glutaredoxin 1 (Grx1) functions as a deglutathionylation enzyme, which regulates the activities of many proteins through reversing glutathionylation. METHODS: GeneChip and RT-qPCR was first applied to test the mRNA level of Grx1 in M1 macrophages. Western blot was then used to evaluate the variations of the Grx1 protein expression in M1 macrophages. Next, immunoprecipitation was used to investigate the glutathionylated STAT1 in both wild-type and Grx1-/- mouse macrophages. Finally, the induced alterations of STAT1 activity and function by Grx1 in M1 macrophage were examined by western blot and RT-qPCR. RESULTS: In M1-type macrophages, the levels of Grx1 were elevated. Glutathionylation of STAT1 was negatively regulated by Grx1. Furthermore, depletion of Grx1 increased the activity of STAT1, and thereby promoted the mRNA level of C-X-C motif chemokine ligand 9 (CXCL9) during M1-type polarization of macrophages. CONCLUSIONS: Grx1 controlled deglutathionylation of STAT1, which in turn might regulate M1-type polarization of macrophages.

Brd4 inhibition ameliorates Pyocyanin-mediated macrophage dysfunction via transcriptional repression of reactive oxygen and nitrogen free radical pathways.

Macrophages play critical roles in the first-line immune defense against airway infections caused by Pseudomonas aeruginosa (PA). The redox-active phenazine-pyocyanin (PCN), as one of the most essential virulence factors, facilities PA-related infection via a wide spectrum of cellular oxidative damages. However, little is known for PCN cytotoxicity in macrophages. In this study, besides showing PCN-mediated reactive oxygen species (ROS) indeed involved in macrophage viability and function impairment, we at the first time demonstrated a novel role of reactive nitrogen species (RNS) pathway causing cellular damage in PCN-challenged macrophages. Using small molecule inhibitor JQ1 targeting Bromodomain and extra-terminal family proteins, we showed restrained iNOS-dependent nitric oxide (NO) production correlated with abolished Brd4 recruitment to the NOS2 (encoding inducible nitric oxide synthase-iNOS) promoter. Application of JQ1 diminished PCN-mediated peroxynitrite (ONOO-) that followed ROS and NO induction, restored macrophage survival and bacteria clearance as well as repressed local inflammation in PA/PCN-challenged mice lungs. Our results uncover a novel link between PCN-mediated macrophage dysfunction and reactive free radicals that rely on Brd4-dependent transcription modulation of multiple stress-response genes, suggesting Brd4 could be a promising therapeutic target in treating PA-related lung infection.

Anti-Glioma Effect with Targeting Therapy Using Folate Modified Nano-Micelles Delivery Curcumin.

Targeted drug delivery systems have currently demonstrated considerable potential clinical benefits in cancer treatment. Curcumin has become a candidate anti-tumor drug for the therapy of glioblastoma multiforme (GBM) by increasing cell apoptosis and suppressing cell proliferation. In current research, we explored a novel targeted drug delivery system with a self-assembly measure by curcumin, MPEG-PLA and Fa-PEG-PLA. Compared with free curcumin and Cur/MPEG-PLA, Cur/Fa-PEG-PLA can remarkably suppress the growth of GL261 cells and promote apoptotic rate. Moreover, after the procession of tumor-bearing mice with curcumin/Fa-PEG-PLA complex, tumor growth in subcutaneous and intracranial tumor models were repressed via suppressing angiogenesis and facilitating apoptosis in vivo. The Curcumin/Fa-PEG-PLA nanoparticle may be a novel drug for the therapy of GBM.

HMGN2 regulates non-tuberculous mycobacteria survival via modulation of M1 macrophage polarization.

Non-tuberculous mycobacteria (NTM), also known as an environmental and atypical mycobacteria, can cause the chronic pulmonary infectious diseases. Macrophages have been suggested as the main host cell to initiate the innate immune responses to NTM infection. However, the molecular mechanism to regulate the antimicrobial immune responses to NTM is still largely unknown. Current study showed that the NTM clinical groups, Mycobacterium abscessus and Mycobacterium smegmatis, significantly induced the M1 macrophage polarization with the characteristic production of nitric oxide (NO) and marker gene expression of iNOS, IFNγ, TNF-α, IL1-ß and IL-6. Interestingly, a non-histone nuclear protein, HMGN2 (high-mobility group N2), was found to be spontaneously induced during NTM-activated M1 macrophage polarization. Functional studies revealed that HMGN2 deficiency in NTM-infected macrophage promotes the expression of M1 markers and the production of NO via the enhanced activation of NF-κB and MAPK signalling. Further studies exhibited that HMGN2 knock-down also enhanced IFNγ-induced M1 macrophage polarization. Finally, we observed that silencing HMGN2 affected the survival of NTM in macrophage, which might largely relevant to enhanced macrophage polarization into M1 phenotype under the NTM infection. Collectively, current studies thus suggested a novel function of HMGN2 in regulating the anti-non-tuberculous mycobacteria innate immunity of macrophage.

Simultaneous nutrition removal and high-efficiency biomass and lipid accumulation by microalgae using anaerobic digested effluent from cattle manure combined with municipal wastewater.

BACKGROUND: Microalgae as a viable biodiesel feedstock show great potential to approach the challenges of energy shortage and environment pollution, but their economic feasibility was seriously hampered by high production cost. Thus, it is in urgent need to reduce the cost of cultivation and improve the biomass and lipid production of microalgae. In this work, anaerobic digestion effluent from cattle manure combined with municipal wastewater was used as a cost-effective medium for cultivating microalgae and expected to obtain high biomass. The pretreatment of anaerobic digested effluent containing dilution rate, sterilization and nutrient optimization was investigated. Then, initial pH and light intensity for algal growth, lipid production and wastewater purification were optimized in this study. RESULTS: Scenedesmus sp. could grow rapidly in 10% anaerobic digestion effluent from cattle manure combined with secondary sedimentation tank effluent without sterilization. Optimum nutrient additives for higher biomass were as follows: glucose 10 g/L, NaNO3 0.3 g/L, K2HPO4·3H2O 0.01 g/L, MgSO4·7H2O 0.075 g/L and trace element A5 solution 1 mL/L. Biomass of 4.65 g/L and lipid productivity of 81.90 mg/L/day were achieved during 7-day cultivation accompanying over 90% of COD, NO3 --N, NH4 +-N, and 79-88% of PO4 3--P removal with optimized initial pH of 7.0 and light intensity of 5000 l×. The FAME profile in ADEC growth medium consisted in saturated (39.48%) and monounsaturated (60.52%) fatty acids with the 16- to 18-chain-length fatty acids constituting over 98% of total FAME. CONCLUSIONS: This study proves the potential of anaerobic digested effluent combined with municipal wastewater for microalgae culture, and provides an effective avenue for simultaneous microalgal lipid production and treatment of two kinds of wastewater.

Antibiotic Resistance and Azithromycin Resistance Mechanism of Legionella pneumophila Serogroup 1 in China.

Legionnaires' disease, caused by Legionella pneumophila, has been treated primarily with antibiotics. However, few reports have been published on antibiotic-resistant Legionella in China. Our aim was to determine the azithromycin resistance mechanism of L. pneumophila serogroup 1 in China. The sensitivities of 149 L. pneumophila serogroup 1 strains, isolated from clinical cases or environmental water in China from 2002 to 2016, to five antibiotics, including erythromycin, azithromycin, levofloxacin, moxifloxacin, and rifampin, were evaluated. The mechanisms of the resistance of L. pneumophila serogroup 1 to azithromycin were studied. The expression levels of efflux pump gene lpeAB and the MIC of azithromycin-resistant strains in the presence and absence of the efflux pump inhibitor carbonyl cyanide-chlorophenylhydrazone (CCCP) were determined. All 149 strains were sensitive to erythromycin, levofloxacin, moxifloxacin, and rifampin, among which 25 of the strains exhibited azithromycin resistance. These 25 strains, including strains of sequence type 1 (ST1), ST144, ST150, ST154, and ST629, were screened. Expression of lpeAB was responsible for the reduced azithromycin susceptibility in all 25 of these strains. The phenotypes of 25 strains with virulence were linked by evaluating the intracellular growth ability in mouse macrophage J774 cells. Among the 25 strains, 60% were more virulent than the ATCC 33152 reference strain. The results determined in our study represent data supporting the further study of the antibiotic sensitivity of L. pneumophila strains in China.

FoxM1 Induced Paclitaxel Resistance via Activation of the FoxM1/PHB1/RAF-MEK-ERK Pathway and Enhancement of the ABCA2 Transporter.

FoxM1 amplification in human pancreatic cancer predicts poor prognosis and resistance to paclitaxel. Here, a novel role between FoxM1 (FoxM1b and FoxM1c) and Prohibitin1 (PHB1) in paclitaxel resistance has been identified. We adopted a bioinformatics approach to predict the potential effector of FoxM1. It specifically bound to the promoter of PHB1, and it enhanced PHB1 expression at transcriptional and post-transcriptional levels. FoxM1 contributed to the PHB1/C-RAF interaction and phosphorylation of ERK1/2 kinases, thus promoting paclitaxel resistance. Notably, FoxM1 conferred tumor cell resistance to paclitaxel, but knocking down PHB1 could sensitize pancreatic cancer cells to it. Besides, we identified that ABCA2 promoted paclitaxel resistance under the regulation of FoxM1/PHB1/RAF-MEK-ERK. Thiostrepton, an inhibitor of FoxM1, significantly decreased the expression of PHB1, p-ERK1/2, and ABCA2. It increased the influx of paclitaxel into the cell, and it attenuated FoxM1-mediated paclitaxel resistance in vitro and in vivo. Collectively, our findings defined PHB1 as an important downstream effector of FoxM1. It was regulated by FoxM1 to maintain phosphorylation of ERK1/2 in drug-resistant cells, and FoxM1 simultaneously enhanced the function of ABCA2, which collectively contributed to paclitaxel resistance. Targeting FoxM1 and its downstream effector PHB1 increased the sensitivity of pancreatic cells to paclitaxel treatment, providing potential therapeutic strategies for patients with paclitaxel resistance.