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Although most patients with acute myeloid leukemia (AML) enter remission after induction chemotherapy, the risk of relapse remains considerable. Therefore, some novel therapeutic strategies are still required. This study found that the overexpression of CD47 on AML cells was at least twofold more than that on normal bone marrow (NBM) cells in 81% (17/21) of the investigated patients; no patients had lower expression level of CD47 compared with healthy donors. The study also demonstrated that blocking the CD47/SIRPα (signal regulatory protein α) signal with the established novel fully human anti‐CD47 monoclonal antibodies increased the phagocytosis of AML cells by macrophages in vitro. Furthermore, in vivo experiments showed that the novel fully human anti‐CD47 monoclonal antibodies could significantly prolong the survival time of mice. Overall, the novel fully human anti‐CD47 antibodies could block CD47/SIRPα interaction, increase macrophage‐mediated phagocytosis, and enhance the elimination of AML cells. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to identify a gene prognostic signature for the head-and-neck squamous cell carcinoma (HNSCC). HNSCC is one of the most common malignancies worldwide; however, the molecular mechanisms underlying the malignancy are unclear.Materials and Methods: We analyzed the gene expression profiles of GSE2379, GSE53819, and GSE59102 derived from the gene expression omnibus, and the cancer genome atlas (TCGA) HNSC databases. The R software was used to identify the differentially expressed genes (DEGs) between HNSCC tissues and normal controls. Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, protein-protein interactions network, and survival analyses of common DEGs were also performed.Results: A total of 52 upregulated and 31 downregulated DEGs were identified. Functional analyses demonstrated that these DEGs were mainly enriched in extracellular matrix-receptor interaction, focal adhesion, tyrosine metabolism, and cytokine-cytokine receptor interaction. According to the survival analyses, PLAU and SERPINE1 could predict the overall survival of HNSCC patients from the TCGA cohort. Multivariable Cox regression analyses showed that the PLAU and SERPINE1 were independent prognostic factors for HNSCC patients. The prediction power of this two-gene signature was evaluated through receiver operating characteristic curve analysis and achieved a better prognostic value than PLAU (area under curve 0.613 [95% confidence interval 0.569-0.656] vs. 0.577 [0.533-0.621]; P = 0.008) or SERPINE1 (0.613 [0.569-0.656] vs. 0.586 [0.541-0.629]; P = 0.043) when considered alone.Conclusions: The study has identified a set of novel genes and pathways that play significant roles in the carcinogenesis and progression of HNSCC. This two-gene signature may prove to be a useful therapeutic target for HNSCC. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the mobile colistin resistance gene mcr-5 in Aeromonas hydrophila from backyard pigs in rural areas of China.Methods: Pig faecal samples from 194 households were directly tested for the presence of mcr-5 by PCR assay and the phenotypic antimicrobial susceptibility profiles of the mcr-5-positive isolates were determined using the broth dilution method. The genomic location and transferability of mcr-5 were analysed by S1-PFGE with Southern blotting and DNA hybridization, and natural transformation, respectively. One strain isolated from an mcr-5-positive sample was subjected to WGS and the stability of the mcr-5-harbouring plasmid over successive generations was examined by subculturing.Results: One mcr-5-positive A. hydrophila isolate showing resistance, with a colistin MIC of 4 mg/L, was isolated from a backyard pig faecal sample. mcr-5 was located on a 7915 bp plasmid designated pI064-2, which could naturally transform into a colistin-susceptible A. hydrophila strain of porcine origin and mediated colistin resistance in both the original isolate and its transformants. The plasmid backbone (3790 bp) of pI064-2 showed 81% nucleotide sequence identity to the corresponding region of the ColE2-type plasmid pAsa1 from Aeromonas salmonicida, while similar replication primases are widely distributed among aeromonads, Enterobacteriaceae and Pseudomonas species.Conclusions: To the best of our knowledge, this is the first identification of the novel colistin resistance gene mcr-5 in an A. hydrophila isolate from the faeces of a backyard pig. mcr-5 is expected to be able to disseminate among different bacterial species and genera. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the presence and molecular characteristics of oxazolidinone resistance genes cfr and optrA in staphylococci from household animals in rural China.Methods: Various samples were collected from household animals in 12 rural villages. Staphylococcal isolates showing florfenicol MICs ≥10 mg/L were identified and screened for the presence of cfr and/or optrA. PCR-positive isolates were characterized by antimicrobial susceptibility testing, S1 nuclease PFGE and Southern blotting. WGS data were analysed to identify the core-genome phylogenetic profile of each isolate as well as the genetic environment of cfr and/or optrA.Results: Nine optrA-positive (seven Staphylococcus sciuri and two Staphylococcus simulans) and 10 cfr-positive staphylococci were identified from eight and five villages, respectively. The gene optrA was chromosomally encoded in all nine isolates, whereas cfr was located on a plasmid in one S. sciuri and three Staphylococcus saprophyticus and in the chromosomal DNA of single Staphylococcus cohnii and Staphylococcus lentus isolates and two S. sciuri isolates. The remaining two cfr-carrying Staphylococcus haemolyticus isolates were indistinguishable by PFGE. Most optrA- or cfr-carrying staphylococci also harboured phenicol, tetracycline and/or macrolide-lincosamide-streptogramin B resistance genes. Genetic environment analysis showed that, for the first time, optrA was associated with transposon Tn6261, while cfr was adjacent to both a tnp (transposase) gene and a Tn558 transposon.Conclusions: The current study reveals for the first time the wide distribution of oxazolidinone resistance genes optrA and cfr in household animals in rural areas of China and is the first identification of optrA in S. simulans isolates. [ABSTRACT FROM AUTHOR]

ABSTRACT Despite no carbapenem use in food animals, carbapenem-resistant Klebsiella pneumoniae (CRKP) perseveres within food animals, rising significant concerns regarding public health risks originating from these non-clinical reservoirs. To investigate the potential link between CRKP in food animals and its infections in humans, we conducted a cross-sectional study encompassing human clinical, meat products, and farm animals, in Qingdao city, Shandong province, China. We observed a relatively higher presence of CRKP among hospital inpatients (7.3%) compared to that in the meat products (2.7%) and farm animals (pig, 4.6%; chicken, 0.63%). Multilocus sequence typing and core-genome phylogenetic analyses confirm there is no evidence of farm animals and meat products in the clinical acquisition of K. pneumoniae isolates and carbapenem-resistant genes. However, potential transmission of K. pneumoniae of ST659 and IncX3 plasmid harbouring bla NDM-5 gene from pigs to pork and farm workers was observed. Our findings suggest a limited role of farm animals and meat products in the human clinical acquisition of K. pneumoniae , and the transmission of K. pneumoniae is more common within settings, than between them.

What Is Already Known on This Topic?: Streptococcus suis ( S. suis ) is a zoonotic pathogen causing disease in humans and animals, and the emergence of its increased resistance to antimicrobial agents has become a significant challenge in many countries., What Is Added by This Report?: Using whole genome sequencing data to accurately predict antimicrobial resistance determinants, it was found that the prevalence of antimicrobial resistance genes was higher in the pig isolates of S. suis than in the human isolates and that the prevalence of these genes varied with serotype., What Are the Implications for Public Health Practice?: The data regarding S. suis antimicrobial resistance will help guide rational drug use in the clinic to better protect the health of humans and animals., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2021.)

Tryptophan decarboxylase (TDC, EC 4.1.1.28) catalyzes tryptophan decarboxylation to form tryptamine through the cofactor pyridoxal-5'-phosphate (PLP), a crucial stage in the production of the terpenoid indole alkaloids like camptothecin (CPT). A new gene encoding TDC was identified from the CPT-producing plant Ophiorrhiza pumila by transcriptome analysis, termed OpTDC2. It contained a 1,536 bp open reading frame that encodes a 511 amino acid protein with a molecular mass of 57.01 kDa and an isoelectric point of 6.39. Multiple sequence alignment and phylogenetic tree analysis showed the closest similarity (85%) with the TDC from Mitragyna speciosa. Moreover, the highest expression of OpTDC2 was observed in the O. pumila root. To achieve high-efficiency expression of OpTDC2 in Escherichia coli, we fused the TF tag onto the N-terminal of the OpTDC2. Optimum enzymatic activity was observed at 45 °C, pH 8 and cofactor concentration of 0.1 mM. The catalytic reaction was strongly inhibited by metal ions of Cu 2+ , Zn 2+ , and Fe 2+ . The l-tryptophan was particularly catalyzed compared with d-tryptophan. Besides, the K m and k cat of the OpTDC2 were 1.08 mM and 0.78 Sec -1 , respectively. The results provided information on new functional OpTDC2 that might be used in synthetic biology for the enhanced biosynthesis of CPT in O. pumila., (© 2020 International Union of Biochemistry and Molecular Biology, Inc.)

The wide dissemination of New Delhi metallo-β-lactamase genes ( bla NDM ) has resulted in the treatment failure of most available β-lactam antibiotics, with IncX3-type bla NDM-5 -carrying plasmids recognised as having spread worldwide. In China, bacteria carrying these plasmids are increasingly being detected from diverse samples, including hospitals, communities, livestock and poultry, and the environment, suggesting that IncX3 plasmids are becoming a vital vehicle for bla NDM dissemination. To elucidate the fitness cost of these plasmids on the bacterial host, we collected bla NDM -negative strains from different sources and tested their ability to acquire the bla NDM-5 -harboring p3R-IncX3 plasmid. We then measured changes in antimicrobial susceptibility, growth kinetics, and biofilm formation following plasmid acquisition. Overall, 70.7% (29/41) of our Enterobacteriaceae recipients successfully acquired the bla NDM-5 -harboring p3R-IncX3 plasmid. Contrary to previous plasmid burden theory, 75.9% (22/29) of the transconjugates showed little fitness cost as a result of plasmid acquisition, with 6.9% (2/29) of strains exhibiting enhanced growth compared with their respective wild-type strains. Following plasmid acquisition, all transconjugates demonstrated resistance to most β-lactams, while several strains showed enhanced biofilm formation, further complicating treatment and prevention measures. Moreover, the highly virulent Escherichia coli sequence type 131 strain that already harbored mcr - 1 also demonstrated the ability to acquire the bla NDM-5 -carrying p3R-IncX3 plasmid, resulting in further limited therapeutic options. This low fitness cost may partly explain the rapid global dissemination of bla NDM-5 -harboring IncX3 plasmids. Our study highlights the growing threat of IncX3 plasmids in spreading bla NDM-5 .

Objective: Currently, the prognosis of standardized uptake value still has no consensus. We evaluated the role of the maximum standardized uptake value (SUV max ) of the MM lesions and the extramedullary disease (EMD) with the highest metabolic activity on PET/CT in predicting survival of newly diagnosed multiple myeloma (MM) patients., Methods: A total of 123 previously untreated, newly diagnosed patients were enrolled in this study, who were diagnosed at the Tianjin Medical University Cancer Institute and Hospital between September 2008 and February 2018. All patients with available PET/CT information at diagnosis were analyzed., Results: We found that no clinical characteristics were significantly different between the pathological fracture groups. However, laboratory findings including elevated creatinine and anemia at diagnosis corresponded to osteolytic lesions at baseline PET/CT (elevated creatinine, P = 0.024; anemia, P = 0.025). Compared to SUV max < 5.7 group, the proportion of patients with EMD was significantly high in the SUV max ≥ 5.7 group (P = 0.046). Multivariate analysis using a Cox proportional hazards model showed that age > 65, poor treatment response and EMD positive were independent poor prognostic factors for newly diagnosed MM patients., Conclusion: We confirm the prognostic value of EMD, as detected by PET/CT, in newly diagnosed multiple myeloma patients. Therefore, the presence of EMD in newly diagnosed MM tends to be more important than the SUV max ., Competing Interests: None., (IJCEP Copyright © 2019.)

The recent emergence of plasmid-mediated tigecycline resistance genes, tet (X3) and tet (X4), in animals and humans in China would pose a foreseeable threat to public health. To illustrate this paradigm shift in tigecycline resistance, here, covering the period 2008-2018, we retrospectively analysed a national strain collection of Escherichia coli (n = 2254), obtained from chickens and pigs, in six representative provinces of China. The gene tet (X4) was identified in five pig isolates collected in 2016 and 2018 from the provinces of Sichuan (3/15, 2018), Henan (1/25, 2018) and Guangdong (1/28, 2016), but not in the isolates prior to 2016. None of the isolates was detected harbouring tet (X3). All tet (X4)-positive E. coli exhibited high levels of tigecycline resistance (MICs, 16-64 mg/L), and two were confirmed as colistin resistant, harbouring chromosome-borne mcr-1 gene. The gene tet (X4) was detected on a plasmid in all five isolates, whereas a co-location of tet (X4) on the chromosome of one isolate was observed. Diverse host strains and novel plasmids related to the tet (X4) gene were observed. Our timely findings of the recent emergence of tet (X4) gene in food animal support the rapid surveillance and eradication of this gene before it is established.

Alveolar soft-part sarcoma (ASPS) is an uncommon soft-tissue neoplasm, which is commonly found in the deep soft tissues of the extremities, with a propensity for recurrence and metastasis. However, the metastasis of ASPS to the heart is exceedingly rare. The present study reports such a rare case with cardiac metastasis. Using computed tomography, a 37-year-old man was diagnosed with brain, lung and spleen metastases from a previously treated ASPS in the left forearm. Cardiac metastasis was then diagnosed 1 month later. Despite chemotherapy and palliative whole-brain radiotherapy, the patient succumbed to the disease shortly after. This case suggests that the widespread metastases and cardiac involvement of ASPS may result in a poor outcome.