Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity of PA are largely unknown. Here, we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations, three recapitulating the epithelial states of the normal parotid gland, and two PA-specific epithelial cell (PASE) populations unique to tumours. Then, six subgroups of PASE cells were identified, which varied in epithelium, bone, immune, metabolism, stemness and cell cycle signatures. Moreover, we revealed that CD36⁺ myoepithelial cells were the tumour-initiating cells (TICs) in PA, and were dominated by the PI3K-AKT pathway. Targeting the PI3K-AKT pathway significantly inhibited CD36⁺ myoepithelial cell-derived tumour spheres and the growth of PA organoids. Our results provide new insights into the diversity and origin of PA, offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.
Humans ; Adenoma, Pleomorphic/genetics* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Transcriptome ; Myoepithelioma

Escherichia albertii is an emerging zoonotic enteropathogen which mainly causes infectious diarrhea. Since the discovery and naming of Escherichia albertii, it was found to be responsible for several outbreaks of foodborne gastroenteritis and widely distributed in avian and wild animals. Due to the lack of specific identification system, the global Escherichia albertii infections might be underestimated. Though avian has been considered as the important reservoir of Escherichia albertii, its role in disease transmission remains unclear. This study reviewed the biochemical properties, genomic characteristics, isolation and identification methods of Escherichia albertii, and its prevalence in human, host animals and food. The risk of Escherichia albertii infection and future perspectives in this field were also discussed.

Objective:To understand the molecular characteristics of Escherichia coli producing Shiga toxin 2e subtype isolated from different sources in China. Methods:Three human-derived, 13 animal-derived and eight food-derived stx2e-positive Escherichia coli strains which were isolated during 2012 to 2018 were analyzed by antimicrobial susceptibility testing and whole genome sequencing. The stx subtype, serotype, multi-locus sequence type, virulence genes and antimicrobial resistance genes of each strain were determined by whole genome sequences. The phylogenetic relationship and genetic composition of Shiga-toxin prophage were explored. Results:Twenty-four stx2e-STEC strains were typed into 19 O∶H serotypes and 19 sequence types (STs). Each strain carried at least one kind of antimicrobial resistance gene and 19 out of 24 strains were resistant to at least one kind of antimicrobials. Three human-derived strains were heterogenous in serotypes and STs, but there were several animal and food-derived strains shared the same serotype or ST with human strains and showed close relationship in the phylogenetic analysis. The sequences of stx2e among all strains were highly conserved (similarity >99.7%), but there were significant differences in the size and the gene composition of Shiga toxin prophage genome. Conclusions:This is report about the characteristics of rare human-derived Stx2e-STEC strains in China. Comparing human isolates with animal-and food-derived strains, it indicates that Stx2e-STEC strains are highly genetic diversity and have the potential to infect humans.

Streptomyces are major sources of bioactive natural products. Genome sequencing reveals that Streptomyces have great biosynthetic potential, with an average of 20-40 biosynthetic gene clusters each strain. However, most natural products from Streptomyces are produced in low yields under regular laboratory cultivation conditions, which hamper their further study and drug development. The production of natural products in Streptomyces is controlled by the intricate regulation mechanisms. Manipulation of the regulatory systems that govern secondary metabolite production will strongly facilitate the discovery and development of natural products of Streptomyces origin. In this review, we summarize progresses in pathway-specific regulators from Streptomyces in the last five years and highlight their role in improving the yields of corresponding natural products.
Biological Products ; Multigene Family ; Secondary Metabolism ; Streptomyces/genetics*

Objective:To evaluate the antimicrobial resistance of non-O157 Shiga toxin-producing Escherichia coli (STEC) isolated from human cases. Methods:From 2011 to 2019, 33 non-O157 STEC strains recovered from diarrheal patients from 7 provinces/cities were collected, including Qinghai (1 isolate), Heilongjiang (1 isolate), Guangxi (2 isolates), Shandong (2 isolates), Guangdong (4 isolates), Henan (11 isolates), and Shanghai (12 isolates). Minimum inhibitory concentration (MIC) of 19 antimicrobials were tested by broth microdilution method; O∶H serotypes, Multi-locus sequence typing (MLST) and antimicrobial resistance genes were determined by whole genome sequencing.Results:A total of 33 non-O157 STEC strains were typed into 19 O∶H serotypes and 17 sequence types (STs), respectively. Ten strains were resistant to one or more antibiotics,of which five were multiple drug-resistant (MDR). The resistance rate of tetracycline was 30.3% (10 isolates), and azithromycin resistant strains were detected (12.12%, 4 isolates), but all strains were susceptible to carbapenems. All strains carried the blaEC gene, and the Extended-Spectrum β-Lactamase (ESBL) genotype blaCTX-M-15 were detected (3.0%, 1 isolates). The fosA7 gene was firstly detected in non-O157 STEC strains. Conclusion:MDR, azithromycin resistance, and multiple drug resistance genes were detected in human-derived non-O157 STECs in many regions in China, but they were all susceptible to carbapenems. Our results might guide the clinical treatment of STEC infections.

Objective:To evaluate the antimicrobial resistance of non-O157 Shiga toxin-producing Escherichia coli (STEC) isolated from human cases. Methods:From 2011 to 2019, 33 non-O157 STEC strains recovered from diarrheal patients from 7 provinces/cities were collected, including Qinghai (1 isolate), Heilongjiang (1 isolate), Guangxi (2 isolates), Shandong (2 isolates), Guangdong (4 isolates), Henan (11 isolates), and Shanghai (12 isolates). Minimum inhibitory concentration (MIC) of 19 antimicrobials were tested by broth microdilution method; O∶H serotypes, Multi-locus sequence typing (MLST) and antimicrobial resistance genes were determined by whole genome sequencing.Results:A total of 33 non-O157 STEC strains were typed into 19 O∶H serotypes and 17 sequence types (STs), respectively. Ten strains were resistant to one or more antibiotics,of which five were multiple drug-resistant (MDR). The resistance rate of tetracycline was 30.3% (10 isolates), and azithromycin resistant strains were detected (12.12%, 4 isolates), but all strains were susceptible to carbapenems. All strains carried the blaEC gene, and the Extended-Spectrum β-Lactamase (ESBL) genotype blaCTX-M-15 were detected (3.0%, 1 isolates). The fosA7 gene was firstly detected in non-O157 STEC strains. Conclusion:MDR, azithromycin resistance, and multiple drug resistance genes were detected in human-derived non-O157 STECs in many regions in China, but they were all susceptible to carbapenems. Our results might guide the clinical treatment of STEC infections.

Objective:To investigate the prevalence and molecular characteristics of Escherichia coli ( E. coli) producing a novel Shiga toxin 2k subtype in goat in Lanling county, Shandong province. Methods:In November 2019, 512 goat fecal samples were collected from different households in Lanling county, Shandong province. After enriched with EC broth, stx-positive samples were detected by PCR and inoculated in CHROMagar? ECC agar and CHROMagar? STEC agar. The whole genomes of stx-positive strains were sequenced. Based on the genomic senquences, the stx subtype, serotype, multi-locus sequence type and virulence genes of each strain were analyzed. Results:Eighty-six strains of Shiga toxin-producing E. coli (STEC) were isolated from 512 goat fecal samples. Five stx subtypes were identified and 37 strains were positive for stx2k. The 86 STEC strains belonged to 20 O∶H serotypes and 18 different sequence types (STs). Conclusions:STEC strains circulating in goats in Lanling county, Shandong province were heterogeneous in stx subtypes, serotypes and virulence gene profiles, and a certain proportion of strains producing a novel Shiga toxin 2k subtype were detected.

Shiga toxin (Stx), which can be divided into Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2), is an important virulence factor of Shigella spp. and certain strains of Escherichia coli. Stx, enco-ded by λ-like phage, blocks protein synthesis through removal of an adenine residue from the 28S rRNA. Stx can also induce apoptosis through multiple pathways. Humans may suffer from diarrhea, hemorrhagic colitis ( HC) and hemolytic uremic syndrome ( HUS) and even death when infected with Shiga toxin-producing bac-teria. At present, there is no specific treatment for diseases caused by Stx. In recent years, the application of Stx in cancer therapy and imaging has aroused great interest. This review provided a brief overview of Stx in its nomenclature, typing, structure, genetics, pathogenesis and application perspectives.

For the past several decades, the infectious disease profile in China has been shifting with rapid developments in social and economic aspects, environment, quality of food, water, housing, and public health infrastructure. Notably, 5 notifiable infectious diseases have been almost eradicated, and the incidence of 18 additional notifiable infectious diseases has been significantly reduced. Unexpectedly, the incidence of over 10 notifiable infectious diseases, including HIV, brucellosis, syphilis, and dengue fever, has been increasing. Nevertheless, frequent infectious disease outbreaks/events have been reported almost every year, and imported infectious diseases have increased since 2015. New pathogens and over 100 new genotypes or serotypes of known pathogens have been identified. Some infectious diseases seem to be exacerbated by various factors, including rapid urbanization, large numbers of migrant workers, changes in climate, ecology, and policies, such as returning farmland to forests. This review summarizes the current experiences and lessons from China in managing emerging and re-emerging infectious diseases, especially the effects of ecology, climate, and behavior, which should have merits in helping other countries to control and prevent infectious diseases.
Behavior ; China ; epidemiology ; Climate ; Communicable Diseases ; classification ; epidemiology ; Communicable Diseases, Emerging ; epidemiology ; Disease Outbreaks ; Ecology ; Forecasting ; Humans ; Incidence

Objective To evaluate the efficacy and safety of antibacterial drugs conservative therapy versus appendectomy for treating simple acute appendicitis(AA).Methods Randomized controlled trials (RCT) on antibacterial drugs conservative therapy versus appendectomy for treating simple AA were retrieved from CBM (1978 June 2015),CNKI (1979-June 2015),Medline (1950-June 2015),Pubmed (1950-June 2015),Embase (1970-June 2015) and Cochrane library (issue 2,2015) by computer.The included RCTs were performed the data extraction according to the criteria of the Cochrane handbook by two researchers.Then the included d/literatures were performed the quality assessment and the extracted effective data were performed the meta analysis.Results Six RCTs were included involving 1510 patients with AA,among them,767 cases were treated with antibacterial drugs and 743 cases were treated with appendectomy.Compared with surgical treatment,the effect rate of antibacterial medication conservative therapy was decreased by 25.00％ (RD=-0.25,95％ CI:-0.35--0.14),the recurrence rate was increased by 48.43 times (OR=48.43,95％CI:16.94-138.44),the loss time of labor force was shortened by 1.52 d (MD=-1.52,95％ CI:-3.02 0.02),but the occurrence rate of complications(RD=-0.06,95％CI:-0.15 0.03),pain time(MD=-0.76,95％CI:-3.31 1.79),hospital stay time (MD=4.60,95％CI:-0.89 10.09) and sick leave time(MD=-2.39,95％CI:-5.62-0.84) had no statistical differences between the two kinds of treatment method(P＞0.05).Conclusion Appendectomy may be the gold standard method for treaung simple AA.