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IntroductionThis study characterized Vibrio alginolyticus isolated from seafood and freshwater products in China (2020).Methods and ResultsIn total, 122 (95.31%) V. alginolyticus isolates were resistant to at least 1 antibiotic category, and 2 (1.56%) isolates were resistant to at least 3 antibiotic categories and belong to multi-drug resistance (MDR) isolates. A high prevalence rate was observed to be blaCARB (98.04%) encoding beta-lactam resistance, followed by tet (97.06%) encoding tetracycline resistance and fos (4.90%) encoding resistance to fosfomycin. Among the 57 V. alginolyticus isolates, the commonest virulence genes were type III secretion system translocated gene vopD, vopB, and vcrH (54.4%, 31/57), type III secretion system regulated gene tyeA (54.39%), followed by vscI and vscF (50.88%) encoded type III secretion system inner rod protein and needle protein, respectively. Multilocus sequence typing (MLST) showed considerable genetic diversity, with 34 distinct sequence types (STs) identified among 55 isolates. ST421 (n = 5), ST166 (n = 4), ST523 (n = 3), ST516 (n = 3), and ST507 (n = 3) were dominant STs among 55 V. alginolyticus isolates.DiscussionThese findings highlight the widespread occurrence of V. alginolyticus in both freshwater and seafood products, underscoring the critical need for vigilant monitoring of these bacteria. Such measures are essential for ensuring effective food safety management and safeguarding public health.

Abstract Sharing of genetic elements among different pathogens and commensals inhabiting same hosts and environments has significant implications for antimicrobial resistance (AMR), especially in settings with high antimicrobial exposure. We analysed 661 Escherichia coli and Salmonella enterica isolates collected within and across hosts and environments, in 10 Chinese chicken farms over 2.5 years using data-mining methods. Most isolates within same hosts possessed the same clinically relevant AMR-carrying mobile genetic elements (plasmids: 70.6%, transposons: 78%), which also showed recent common evolution. Supervised machine learning classifiers revealed known and novel AMR-associated mutations and genes underlying resistance to 28 antimicrobials, primarily associated with resistance in E. coli and susceptibility in S. enterica. Many were essential and affected same metabolic processes in both species, albeit with varying degrees of phylogenetic penetration. Multi-modal strategies are crucial to investigate the interplay of mobilome, resistance and metabolism in cohabiting bacteria, especially in ecological settings where community-driven resistance selection occurs.

Objective Campylobacter species are the main causes of foodborne illness worldwide, posing significant threats to public health. This study aimed to investigate the antibiotic resistance and genomic characterization of C. jejuni/C.coli from retail chickens in Beijing. Methods Antimicrobial susceptibility testing was conducted on 126 C. jejuni/C. coli isolated from retail chickens in Beijing, following CLSI protocols. Whole genomes of all isolates were sequenced using the Illumina platform. Results More C. coli (83.82%) showed multi-drug resistance than C. jejuni (8.62%). Genomic analysis demonstrated 42 sequence types (STs) and 12 clonal complexes (CCs), from which CC828 and CC52 were dominant. cdtA, cdtB and cdtC encoding cytotoxic protein were present spontaneously in most C. jejuni but not found in any C. coli isolates. The abundances of antibiotic resistance genes (ARGs) and virulence genes (VGs) in C. jejuni and C. coli were significantly different, with ARGs numbered in C. coli and VGs in C. jejuni. Conclusions High prevalence of multi-drug resistance C. coli and C. jejuni isolated from Beijing chickens were challenging clinical antibiotic usages in the treatment of Campylobacter infection. The surveillance of particular C. jejuni and C. coli STs correlated with higher resistance and virulence needs to be strengthened in the future.

Salmonella, especially antimicrobial resistant strains, remains one of the leading causes of foodborne bacterial disease. Retail chicken is a major source of human salmonellosis. Here, we investigated the prevalence, antimicrobial resistance (AMR), and genomic characteristics of Salmonella in 88 out of 360 (24.4%) chilled chicken carcasses, together with 86 Salmonella from humans with diarrhea in Qingdao, China in 2020. The most common serotypes were Enteritidis and Typhimurium (including the serotype I 4,[5],12:i:-) among Salmonella from both chicken and humans. The sequence types were consistent with serotypes, with ST11, ST34 and ST19 the most dominantly identified. Resistance to nalidixic acid, ampicillin, tetracycline and chloramphenicol were the top four detected in Salmonella from both chicken and human sources. High multi-drug resistance (MDR) and resistance to third-generation cephalosporins resistance were found in Salmonella from chicken (53.4%) and humans (75.6%). In total, 149 of 174 (85.6%) Salmonella isolates could be categorized into 60 known SNP clusters, with 8 SNP clusters detected in both sources. Furthermore, high prevalence of plasmid replicons and prophages were observed among the studied isolates. A total of 79 antimicrobial resistant genes (ARGs) were found, with aac(6′)-Iaa, blaTEM-1B, tet(A), aph(6)-Id, aph(3″)-Ib, sul2, floR and qnrS1 being the dominant ARGs. Moreover, nine CTX-M-type ESBL genes and the genes blaNMD-1, mcr-1.1, and mcr-9.1 were detected. The high incidence of MDR Salmonella, especially possessing lots of mobile genetic elements (MGEs) in this study posed a severe risk to food safety and public health, highlighting the importance of improving food hygiene measures to reduce the contamination and transmission of this bacterium. Overall, it is essential to continue monitoring the Salmonella serotypes, implement the necessary prevention and strategic control plans, and conduct an epidemiological surveillance system based on whole-genome sequencing.

Abstract Background Gastrointestinal (GI) injury is one of the most common side effects of radiotherapy. However, there is no ideal therapy method except for symptomatic treatment in the clinic. Xuebijing (XBJ) is a traditional Chinese medicine, used to treat sepsis by injection. In this study, the protective effects of XBJ on radiation‐induced intestinal injury (RIII) and its mechanism were explored. Methods The effect of XBJ on survival of irradiated C57BL/6 mice was monitored. Histological changes including the number of crypts and the length of villi were evaluated by H&E. The expression of Lgr5+ intestinal stem cells (ISCs), Ki67+ cells, villin and lysozymes were examined by immunohistochemistry. The expression of cytokines in the intestinal crypt was detected by RT‐PCR. DNA damage and apoptosis rates in the small intestine were also evaluated by immunofluorescence. Results In the present study, XBJ improved the survival rate of the mice after 8.0 and 9.0 Gy total body irradiation (TBI). XBJ attenuated structural damage of the small intestine, maintained regenerative ability and promoted proliferation and differentiation of crypt cells, decreased apoptosis rate and reduced DNA damage in the intestine. Elevation of IL‐6 and TNF‐α was limited, but IL‐1, TNF‐𝛽 and IL‐10 levels were increased in XBJ‐treated group after irradiation. The expression of Bax and p53 were decreased after XBJ treatment. Conclusions Taken together, XBJ provides a protective effect on RIII by inhibiting inflammation and blocking p53‐related apoptosis pathway.

The objective of the present study was to determine the prevalence, antimicrobial resistance, virulence profiles, and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) obtained from ready-to-eat (RTE) foods in China. Two hundred seventy-six RTE food-associated S. aureus isolates were collected from 25 provinces across China in 2018, then characterized by antimicrobial susceptibility testing, virulence factors detecting, multilocus sequence typing (MLST), spa typing, SCC mec typing and pulsed-field gel electrophoresis (PFGE). Two hundred fifty isolates (90.6%) were resistant to at least one antimicrobial agent; 73 (26.4%) isolates were multi-drug resistant (MDR). Thirty MRSA isolates were identified, among which nine toxin genes ( sea, seb, sec, sed, seh, selk, sell, selq , and tsst-1 ) were detected. Sixty percent (18/30) of the MRSA isolates harbored multiple toxin genes. Four virulence gene patterns were identified, with seb-selk-selq (30/30) being the most common pattern. Thirteen sequence types, as well as 13 spa and 4 SCC mec types were found among 30 MRSA isolates. The most prevalent MRSA lineages were CC59-t437-SCC mec IV/V (23.3% [7/30]), CC398-t011-SCC mec V (23.3% [7/30]), and CC1-t114-SCC mec IV (16.7% [5/30]). Our findings highlight the importance for the identification of prevalent clones, assessment of drug-resistance and virulence, and formulation of food safety measures for public health.

Salmonella enterica serotype Indiana (S. Indiana) in Chinese poultry meat has aroused widespread concern because of its high prevalence and strong antimicrobial resistance. In consideration of the relationship in our previous study between S. Indiana and co-resistance to ciprofloxacin and cefotaxime (CIP-CTX), which were the first-line drug which were used in Salmonella infection in clinical, the antimicrobial resistance (AMR) of 224 CIP-CTX co-resistant S. Indiana isolated from retail chicken samples in China were investigated, with the aim of characterizing the AMR profiles and related resistance mechanisms to ciprofloxacin and cefotaxime among these CIP-CTX co-resistant S. Indiana isolates, all of which showed multi-drug-resistant (MDR) phenotypes. GyrA (S83F and D87N/G) with ParC (T57S and S80R) were the dominant amino acid substitution types, with oqxA, oqxB, and aac (6′)-Ib-cr identified as common plasmid-mediated quinolone resistance (PMQR)-encoding genes. Five blaCTX-M gene subtypes were identified with blaCTX-M-65 ranking at the top. Equally important, we obtained one isolate CFSA664 harboring the mcr-1 gene was ESBL producer with co-resistance to nine in ten classes of tested drugs inclduing colistin. A single circular chromosome and 3 circular plasmids were found in its genome. Among the 26 AMR genes identified, 24 were located on plasmid pCFSA664-1, including three ESBL genes, while plasmid pCFSA664-3 owning only the mcr-1 gene and sharing the same backbone structure with plasmids from Enterobacteriaceae. No insertion sequences were found near the mcr-1 gene but a relaxase-encoding gene in the flank, which could transfer into E. coli J53 at a relatively high frequency. S. Indiana in this study exhibited highly drug-resistant phenotypes, contributing to the acceleration of the dissemination and emergence of this pathogen among different sources. Surveillance and a One Health strategy are needed to limit the emergence of S. Indiana along the food chain.

ABSTRACT Sequence type 88 (ST88) methicillin-resistant Staphylococcus aureus (MRSA) has been recognized as an important pathogen that causes infections in humans, especially when it has strong biofilm production and multidrug resistance (MDR). However, knowledge of the determinants of resistance or virulence and genomic characteristics of ST88 MRSA from China is still limited. In this study, we employed the antimicrobial resistance (AMR), biofilm formation, and genomic characteristics of ST88 MRSA collected from various foods in China and estimated the worldwide divergence of ST88 MRSA with publicly available ST88 genomes. All ST88 isolates studied were identified as having resistance genes, while 50% (41/82) harbored MDR genes. All isolates carried core virulence genes related to immune modulation, adherence, secreted enzymes, and hemolysin. In addition, all 20 Chinese ST88 isolates showed biofilm production capacity, three strongly so. Bayesian phylogenetic analysis showed that Chinese ST88 clones formed an independent MRSA lineage, with two subclades associated with acquisition of type IVc staphylococcal cassette chromosome mec (SCCmec) elements. In contrast, all African ST88 strains were subtyped as SCCmecIVa, where the African clades were mixed with a few European and American isolates, suggesting potential transmission from Africa to these regions. In summary, our results revealed the evolution of ST88 MRSA in humans, animals, and foods in Africa and Asia. The food-associated ST88 genomes in this study will remedy the lack of food-associated ST88 isolates, and the study in general will extend the discussion of the potential exchanges of ST88 between humans and foods or food animals. IMPORTANCE ST88 MRSA has frequently been detected in humans, animals, and foods mainly in Africa and Asia. It can colonize and cause mild to severe infections in humans, especially children. Several studies from African countries have described its genotypic characteristics but, limited information is available on the evolution and characterization of ST88 MRSA in Asia, especially China. Meanwhile, the molecular history of its global spread remains largely unclear. In this study, we analyzed the genomic evolution of global ST88 MRSA strains in detail and identified key genetic changes associated with specific hosts or regions. Our results suggested geographical differentiation between ST88 MRSA’s evolution in Africa and its evolution in Asia, with a more recent clonal evolution in China. The introduction of ST88 MRSA in China was aligned with the acquisition of SCCmecIVc elements, specific virulent prophages, and AMR genes.

Abstract Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation in clinic with poor prognosis and limited therapeutic options. Previous results have shown that senescent cells, such as fibroblast and type II airway epithelial cell, are strongly implicated in pathology of RIPF. However, the role of senescent macrophages in the development RIPF is still unknown. In this study, we report that ionizing radiation (IR) increase cellular senescence with higher expression of senescence-associated β-galactosidase (SA-β-Gal) and senescence-specific genes (p16, p21, Bcl-2, and Bcl-xl) in irradiated bone marrow-derived monocytes/macrophages (BMMs). Besides, there’s a significant increase in the expression of pro-fibrogenic factors (TGF-β1 and Arg-1), senescence-associated secretory phenotype (SASP) proinflammatory factors (Il-1α, Il-6, and Tnf-α), SASP chemokines (Ccl2, Cxcl10, and Ccl17), and SASP matrix metalloproteinases (Mmp2, Mmp9 and Mmp12) in BMMs exposed to 10 Gy IR. In addition, the percentages of SA-β-Gal+ senescent macrophages are significantly increased in the macrophages of murine irradiated lung tissue. Moreover, robustly elevated expression of p16, SASP chemokines (Ccl2, Cxcl10, and Ccl17) and SASP matrix metalloproteinases (Mmp2, Mmp9, and Mmp12) is observed in the macrophages of irradiated lung, which might stimulate a fibrotic phenotype in pulmonary fibroblasts. In summary, irradiation can induce macrophage senescence, and increase the secretion of SASP in senescent macrophages. Our findings provide important evidence that senescent macrophages might be the target for prevention and treatment of RIPF.

Abstract ADAMTS9 belongs to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family, and its expression is frequently silenced due to promoter hypermethylation in various human cancers. However, the underlying mechanisms remain largely unknown. In this study, we investigated the inhibitory effects of ADAMTS9 on gastric cancer (GC) cells. We initially examined ADAMTS9 protein level in 135 GC and adjacent normal tissue pairs, showing that ADAMTS9 was strikingly decreased in the malignant specimens and patients with low ADAMTS9 expression exhibited more malignant phenotypes and poorer outcome. ADAMTS9 expression was restored in AGS and BGC-823 cells, which then markedly suppressed cellular viability and motility in vitro and in vivo. As ADAMTS9 was enriched in the nuclei of gastric mucosal cells, RNA-sequencing experiment showed that ADAMTS9 significantly altered gene expression profile in BGC-823 cells. Additionally, DNA methyltransferase 3α (DNMT3A) was identified to be responsible for the hypermethylation of ADAMTS9 promoter, and this methyltransferase was ubiquitinated by ring finger protein 180 (RNF180) and then subject to proteasome-mediated degradation. In conclusion, we uncovered RNF180/DNMT3A/ADAMTS9 axis in GC cells and showed how the signaling pathway affected GC cells.

Non-typhoidal Salmonella (NTS) is a major cause of human salmonellosis globally. Food animals are major NTS reservoirs. An increase in antimicrobial resistance (AMR) in foodborne NTS has led to clinical treatment failures. Here, to examine the prevalence and perform characterization of foodborne NTS with AMR in China, we tested the antimicrobial susceptibility of 1,256 NTS isolates cultured from retail foods in 2020 in China. The antimicrobial susceptibility of 26 antimicrobial agents representing 12 classes was evaluated with the broth-microdilution method; the presence of ten mcr genes was screened with multi-PCR. The complete closed genomes of mcr -gene-carrying isolates were generated by hybrid assembly through whole genome sequencing on both the PacBio and Illumina platforms. Genomic features and genetic environments of the mcr-1 gene were analysed. The overall drug resistance rate was 92.28%, and the multi-drug resistance (MDR) rate was 76.53%. A total of 341 AMR profiles were determined, and resistance was highest to nalidixic acid (63.38%). Among 887 NTS isolates with MDR, 232 showed co-resistance to cefotaxime and ciprofloxacin, and 25 were resistant to ten classes of antimicrobial agents. The resistance of NTS isolated from different regions varied. Isolates from raw chicken sources most frequently showed resistance. Four NTS carried the mcr-1 gene and represented four different serotypes. Four mcr-1 gene-bearing plasmids from the four Salmonella isolates were classified into two replicon types (IncI2 and IncHI2A). Two mcr-1 genes in IncI2 type plasmids were found to be located between a PAP2 family protein-encoding gene and a relaxase-encoding gene, whereas the other two mcr-1 gene structures in IncHI2A type plasmids showed variations in the presence of insertion sequences. Our data demonstrated severe AMR among foodborne NTS isolated from food in China, thus highlighting the importance of antimicrobial susceptibility surveillance to decrease the spread of AMR, particularly to critical drugs in human medicine.

Objective To develop two rapid identification method of Cronobacter use polymerase chain reaction(PCR) and matrix-assisted laser desorption ionization time of flight mass spectrometry(MALDI-TOF-MS), and to achieve high-throughput and low-cost screening of suspicious colonies of Cronobacter on chromogenic medium. Methods A pair of genus specific primers for Cronobacter were designed by internal transcribed spacer(its) gene, and 7 standard strains were set as reference strains to re-identify 214 strains which were preliminarily identified as Cronobacter collected in 2013. 84 isolates were selected randomly and identified by MALDI-TOF-MS and VITEK gram-negative bacteria identification card. Results The molecular weight of 7 reference strains were the same as expected, and PCR result of 214 isolates were positive. All 84 strains were identified as Cronobacter by both MALDI-TOF-MS and VITEK, and the coincidence rate was 100%. Conclusion PCR and MALDI-TOF-MS have the advantages of high-throughput, low-cost and short time consuming, which could achieve the preliminary screening of a large number of suspicious colonies, and could provide technical support for Cronobacter surveillance and control in China.

Screening drugs and compounds to fight against Cronobacter sakazakii (C. sakazakii), one of the most common pathogens that can cause fatal necrotizing enterocolitis, septicema and meningitis, is still needed. We found that p-coumaric acid (pCA) has an inhibitory effect on C. sakazakii in vitro and in vivo. Proteomic changes of C. sakazakii BAA-894 exposed to pCA were studied to reveal the antibacterial mechanisms involved. A total of 1,553 proteins were identified in C. sakazakii BAA-894 by label-free proteomics analysis. Fuzzy cluster analysis showed that 33 were up-regulated, and 110 were down-regulated with pCA treatment. Gene Ontology (GO) analysis concluded that pCA caused the change of metabolic state of bacteria and generally in the state of metabolic inhibition. KEGG Enrichment Analysis (KEGG) analysis showed that pCA inhibited energy metabolism and distorted the balance of amino acid metabolism. Posttranslational modification analysis showed that pCA affected the deamidation of three proteins, including Elongation factor Tu, one of the vital proteins in bacteria. Molecular docking suggested the hydrogen bond between the pCA carboxyl group and Elongation factor Tu Asn-64 might contribute to deamidation. Overall, we found that pCA interfered with cellular energy and amino acid metabolism and promoted elongation factor Tu deamidation, suggesting that pCA can be an effective natural substitute to control C. sakazakii.

Clostridium botulinum is the causative pathogen of botulism. Laboratory detection of C. botulinum is essential for clinical therapy treatment of botulism due to the difficulty in diagnosis, especially in infant botulism. The extreme toxicity of botulinum neurotoxin (BoNT) requires a sensitive detection method. Due to the detection limit of real-time quantitative PCR (q-PCR), a more sensitive detection method, micro-drop digital PCR (ddPCR) was applied in C. botulinum main serotypes A and B. The following performance criteria were evaluated by ddPCR: analytical sensitivity; repeatability; and diagnostic specificity. The limit of detection (LOD) was 0.84 and 0.88 copies/μl for BoNT A and B genes, respectively, by ddPCR with high specificity, compared to 5.04×102 and 6.91×102 copies/μl by q-PCR. It was increased 10 times compared with q-PCR in spiked stool samples. This improvement in sensitivity was especially important in clinical samples as more positive samples were detected by digital PCR compared with q-PCR. Meanwhile, enrichment time for low bacteria content samples was shortened by four hours both in serotypes A and B C. botulinum by ddPCR compared with q-PCR, which are important for laboratory diagnosis and epidemiology work.

Objective Laboratory investigation was performed on a suspected case of infant botulism. Methods Thirty samples of stool, left-over food and environment swabs related to the case were collected, Clostridium spp. isolation, identification and toxicity determination by mouse assay were carried out, and toxin production for isolate was conducted. Results Mice injected with the stool culture supernatant showed the typical signs of botulism including irritable, dyspnea, bellows breathing and quadriplegia followed by death. The toxicity of the stool culture supernatant was enhanced after the treatment by trypsinization but ceased after being heated at 100℃. The polyvalent antibody against botulinum neurotoxins (BoNTs) and the monovalent antibody against BoNT type E could protect mice from death. One gram-positive Clostridium isolate was cultured from infant stool sample. The morphology of the colony on the Columbia blood agar plate showed characteristics of irregular, translucent and flat with rootlike growth. It was positive for type E BoNT-encoding gene and identified as C. butyricum by 16S rRNA sequencing. Toxin production test illustrated that the C. butyricum isolate could produce type E BoNT. Conclusion This was an infant botulism caused by type E BoNT-producing C. butyricum.

Objective A case-control study on Clostridium spp. contamination on infant population and infant formula powdered was carried out, the data on Clostridium spp. exposure in some parts of China was obtained. Methods Epidemiological information and samples were collected from 6 locations in 6 provinces in China. The isolation and identification, of Clostridium spp. were performed. Results Totally 501 infants were investigated. Among them, 247 were exclusive breastfeeding and 254 were mixed feeding. According to the month grouping, 367 were 0-6 months and 134 were 7-12 months. A total of 813 samples were collected. After testing, 246 strains of Clostridium spp. were obtained and the positive rate was 30.3% (246/813). C. sporogenes (8.4%, 68/813), C. bifermentans (6.2%, 50/813) and C. butyricum (4.6%, 37/813) had the highest detection rate.37.3% (187/501) of the stool samples were Clostridium spp. positive, followed by 22.3% (27/121) of the infant formula powder, 19.5% (25/128) of the environmental swab and 11.1% (7/63) of the food samples. The detection rate of Clostridium spp. in mixed feeding group was significantly higher than that of breast-feeding group (χ2=40.833, P

Abstract Purpose This study aimed to assess the effect of nanoparticle albumin‐bound paclitaxel (nab‐PTX) chemotherapy regimens in elderly patients (≥70 years old) with advanced squamous non‐small‐cell lung cancer (NSCLC). Patients and Methods The clinical records of elderly patients aged ≥70 years with advanced squamous NSCLC were reviewed retrospectively. All of these patients received nab‐PTX, with or without combination of chemotherapy in Shandong Cancer Hospital and Institute between 1 July 2012 and 30 June 2017. We analyzed the toxicity profiles, progression‐free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results Totally, 52 elderly patients with squamous NSCLC were included in the analysis. For all patients, the ORR was 34.6%, the DCR was 80.8%, median PFS was 5.9 months (95% confidence interval [CI]: 4.0‐7.8 months), and median OS was 14.3 months (95% CI: 11.0‐17.8 months). Combination with chemotherapy significantly prolonged OS (19.3 vs 11.2 months, P = .016), despite a nonsignificant improvement in PFS (7.1 vs 4.2 months, P = .060) vs monotherapy. For patients who received nab‐PTX as first‐line treatment, the median PFS and OS were 6.7 months and 17.2 months, respectively, and the median OS in combination therapy subgroup was significantly higher than that in monotherapy group (20.3 vs 11.2 months, P = .013). Meanwhile, the median PFS and OS of patients with nab‐PTX as second‐ or later‐line treatment were 4.4 months and 13.3 months, respectively, but no survival benefit was achieved by the combination chemotherapy when compared with single‐agent chemotherapy. Hematologic toxicities were the most common adverse events (AEs), which include grade 3 or 4 neutropenia (13.7%), thrombocytopenia (4.1%), and anemia (6.8%). The main nonhematologic toxicities were peripheral sensory neuropathy (39.7%), followed by anorexia and nausea/vomiting. Conclusion In elderly advanced squamous NSCLC patients, the treatment of nab‐PTX was effective and well tolerated.

The mcr-1 gene mediating mobile colistin resistance in Escherichia coli was first reported in China in 2016 followed by reports among different species worldwide, especially in E. coli and Klebsiella. However, data on its transmission in Salmonella are still lacking. This study analyzed the antimicrobial resistance (AMR) profiles and the mcr-1 gene presence in 755 foodborne Salmonella from 26 provinces of mainland, China in 2016. Genomic features of two mcr-1-carrying isolates, genome sequencing, serotypes and further resistance profiles were studied. Among the 755 Salmonella tested, 72.6% were found to be resistant to at least one antimicrobial agent and 10% were defined as multi-drug resistant (MDR). Salmonella Derby CFSA231 and Salmonella Typhimurium CFSA629 were mcr-1-harboring isolates. Both expressed an MDR phenotype and included a single circular chromosome and one plasmid. Among the 22 AMR genes identified in S. Derby CFSA231, only the mcr-1 gene was localized on the IncX4 type plasmid pCFSA231 while 20 chromosomal AMR genes, including four plasmid-mediated quinolone resistance (PMQR) genes, were mapped within a 64 kb Salmonella genomic island (SGI) like region. S. Typhimurium CFSA629 possessed 11 resistance genes including an mcr-1.19 variant and two ESBL genes. Two IS26-flanked composite-like transposons were identified. Additionally, 153 and 152 virulence factors were separately identified in these two isolates with secretion system and fimbrial adherence determinants as the dominant virulence classes. Our study extends our concern on mcr-1-carrying Salmonella in regards to antimicrobial resistance and virulence factors, and highlight the importance of surveillance to mitigate dissemination of mcr-encoding genes among foodborne Salmonella.

ABSTRACT Staphylococcus aureus is a worldwide leading cause of numerous diseases ranging from food-poisoning to lethal infections. Methicillin-resistant S. aureus (MRSA) has been found capable of acquiring resistance to most antimicrobials. MRSA is ubiquitous and diverse even in terms of antimicrobial resistance (AMR) profiles, posing a challenge for treatment. Here, we present a comprehensive study of S. aureus in China, addressing epidemiology, phylogenetic reconstruction, genomic characterization, and identification of AMR profiles. The study analyzes 673 S. aureus isolates from food as well as from hospitalized and healthy individuals. The isolates have been collected over a 9-year period, between 2010 and 2018, from 27 provinces across China. By whole-genome sequencing, Bayesian divergence analysis, and supervised machine learning, we reconstructed the phylogeny of the isolates and compared them to references from other countries. We identified 72 sequence types (STs), of which, 29 were novel. We found 81 MRSA lineages by multilocus sequence type (MLST), spa, staphylococcal cassette chromosome mec element (SCCmec), and Panton-Valentine leukocidin (PVL) typing. In addition, novel variants of SCCmec type IV hosting extra metal and antimicrobial resistance genes, as well as a new SCCmec type, were found. New Bayesian dating of the split times of major clades showed that ST9, ST59, and ST239 in China and European countries fell in different branches, whereas this pattern was not observed for the ST398 clone. On the contrary, the clonal transmission of ST398 was more intermixed in regard to geographic origin. Finally, we identified genetic determinants of resistance to 10 antimicrobials, discriminating drug-resistant bacteria from susceptible strains in the cohort. Our results reveal the emergence of Chinese MRSA lineages enriched of AMR determinants that share similar genetic traits of antimicrobial resistance across human and food, hinting at a complex scenario of evolving transmission routes. IMPORTANCE Little information is available on the epidemiology and characterization of Staphylococcus aureus in China. The role of food is a cause of major concern: staphylococcal foodborne diseases affect thousands every year, and the presence of resistant Staphylococcus strains on raw retail meat products is well documented. We studied a large heterogeneous data set of S. aureus isolates from many provinces of China, isolated from food as well as from individuals. Our large whole-genome collection represents a unique catalogue that can be easily meta-analyzed and integrated with further studies and adds to the library of S. aureus sequences in the public domain in a currently underrepresented geographical region. The new Bayesian dating of the split times of major drug-resistant enriched clones is relevant in showing that Chinese and European methicillin-resistant S. aureus (MRSA) have evolved differently. Our machine learning approach, across a large number of antibiotics, shows novel determinants underlying resistance and reveals frequent resistant traits in specific clonal complexes, highlighting the importance of particular clonal complexes in China. Our findings substantially expand what is known of the evolution and genetic determinants of resistance in food-associated S. aureus in China and add crucial information for whole-genome sequencing (WGS)-based surveillance of S. aureus.

Subsalt carbonate rocks in Brazil’s deepwater region have broad prospects for oil and gas exploration and development. Due to the low-frequency bandwidth of the seismic data and the poor signal quality for this kind of reservoir target, there is a demand for accurate seismic prediction methods. We employ the facies-controlled inversion using a low-pass filter matrix to ensure the accuracy of the low frequency and to improve the robustness of the inversion results. We integrated the concept of adaptive regularization constraint of the Zoeppritz equation into the generalized linear inversion theory framework, which overcomes the shortcomings of the approximate equation. Making full use of the large angle prestack seismic information, Zoeppritz equation inversion improves the accuracy of the inversion results. The application of this method in carbonate reservoirs under extremely thick salts in the Santos Basin of Brazil indicates the feasibility and practicality of the proposed integrated prediction method.

Abstract Radiotherapy (RT) is used routinely as a standard treatment for more than 50% of patients with malignant tumors. The abscopal effect induced by local RT, which is considered as a systemic anti-tumor immune response, reflects the regression of non-irradiated metastatic lesions at a distance from the primary site of irradiation. Since the application of immunotherapy, especially with immune checkpoint inhibitors, can enhance the systemic anti-tumor response of RT, the combination of RT and immunotherapy has drawn extensive attention by oncologists and cancer researchers. Nevertheless, the exact underlying mechanism of the abscopal effect remains unclear. In general, we speculate that the immune mechanism of RT is responsible for, or at least associated with, this effect. In this review, we discuss the anti-tumor effect of RT and immune checkpoint blockade and discuss some published studies on the abscopal effect for this type of combination therapy. In addition, we also evaluate the most appropriate time window for the combination of RT and immune checkpoint blockade, as well as the optimal dose and fractionation of RT in the context of the combined treatment. Finally, the most significant purpose of this review is to identify the potential predictors of the abscopal effect to help identify the most appropriate patients who would most likely benefit from the combination treatment modality.

Haw pectin pentaglaracturonide (HPPS) significantly lowered the liver weights, hepatic triglycerides (TG) and total lipid levels of high-fat fed mice compared to those of high-fat control (HFC) mice, after 10 weeks administration. Similarly, high fat diets significantly increased plasma TG, non-esterified fatty acids, glucose, insulin and leptin levels compared to normal control diets, but were significantly decreased by HPPS supplementation after 10 weeks administration, these decreases however were not statistically significant at 4-week, compared to HFC diets. While, HPPS administration significantly increased adiponectin levels whatever at 4-week or 10-week. Further analysis found that HPPS administration significantly attenuated high-fat-induced SREBF-1c activation, decreased the levels of mRNA and protein, and enzyme activities of fatty acid synthase, acetyl-CoA carboxylase, and pyruvate kinase in the livers of mice compared to the high-fat control group. Moreover, prolonged administration of HPPS appeared to be more effective to achieve the above changes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

One mcr-1-carrying ST34-type Salmonella Typhimurium WW012 was cultured from 3,200 ready-to-eat (RTE) pork samples in 2014 in China. Broth dilution method was applied to obtain the antimicrobial susceptibility of Salmonella Typhimurium WW012. Broth matting assays were carried out to detect transferability of this phenotype and whole-genome sequencing was performed to analyze its genomic characteristic. Thirty out of 3,200 RTE samples were positive for Salmonella and the three most frequent serotypes were identified as S. Derby (n = 8), S. Typhimurium (n = 6), and S. Enteritidis (n = 6). One S. Typhimurium isolate (S. Typhimurium WW012) cultured from RTE prepared pork was found to contain the mcr-1 gene. S. Typhimurium WW012 expressed a level of high resistance to seven different antimicrobial compounds in addition to colistin (MIC = 8 mg/L). A single plasmid, pWW012 (151,609-bp) was identified and found to be of an IncHI2/HI2A type that encoded a mcr-1 gene along with six additional antimicrobial resistance genes. Plasmid pWW012 contained an IS30-mcr-1-orf-orf-IS30 composite transposon that can be successfully transferred to Escherichia coli J53. When assessed further, the latter demonstrated considerable similarity to three plasmids pHYEC7-mcr-1, pSCC4, and pHNSHP45-2, respectively. Furthermore, plasmid pWW012 also contained a multidrug resistance (MDR) genetic structure IS26-aadA2-cmlA2-aadA1-IS406-sul3-IS26-dfrA12-aadA2-IS26, which showed high similarity to two plasmids, pHNLDF400 and pHNSHP45-2, respectively. Moreover, genes mapping to the chromosome (4,991,167-bp) were found to carry 28 mutations, related to two component regulatory systems (pmrAB, phoPQ) leading to modifications of lipid A component of the lipopolysaccharide structure. Additionally, one mutation (D87N) in the quinolone resistance determining region (QRDR) gene of gyrA was identified in this mcr-1 harboring S. Typhimurium. In addition, various virulence factors and heavy metal resistance-encoding genes were also identified on the genome of S. Typhimurium WW012. This is the first report of the complete nucleotide sequence of mcr-1-carrying MDR S. Typhimurium strain from RTE pork in China.

The elastic and petrophysical parameters of a reservoir can be directly applied to lithology prediction and fluid identification. Existing seismic joint inversion methods for estimating the elastic and petrophysical parameters of a reservoir are primarily based on either the Gassmann equation, with which these parameters are inverted from prestack seismic data through stochastic optimization methods, or Wyllie’s modified equation, with which these parameters are inverted from poststack seismic data using deterministic optimization methods. Regardless of the stochastic or deterministic inversion of reservoir parameters, only the microscopic connection between parameters is considered, without considering the constraints of the macroscopic geological background. The purpose of this work is to develop a strategy for estimating the elastic and petrophysical parameters of a reservoir based on the Gassmann equation and seismic facies using deterministic seismic prestack inversion. We employ the Gassmann equation to construct the relationship between the prestack seismic data and petrophysical parameters and use a low-pass filter matrix to obtain the combination of seismic facies and seismic inversion and improve the robustness of the inversion results. We treat the joint posterior probability of elastic and petrophysical parameters as the objective function under a Bayesian framework by expanding the objective function with the Taylor formula; the joint equations composed of elastic and petrophysical parameters are obtained through differentiation. The conjugate gradient method is subsequently used to find the optimal solutions for the P-wave velocity, S-wave velocity, density, porosity, water saturation, and clay content. Theoretical calculations and actual data inversion results prove the feasibility and applicability of the method.

Objectives: This study aimed to characterize the genomic features of a Salmonella enterica serovar Typhimurium ST34 isolate, CFSA629, which carried a novel mcr-1 variant, designated as mcr-1.19, mapped to an ESBL-encoding IncHI2 plasmid. Methods: Antimicrobial susceptibility assays as well as WGS were carried out on isolate CFSA629. The complete closed genome was obtained and then explored to obtain genomic features. Plasmid sequence comparison was performed for pCFSA629 with similar plasmids and the mcr-1 genetic environment was analysed. Results: S. Typhimurium ST34 CFSA629 expressed an MDR phenotype to six classes of compound and consisted of a single circular chromosome and one plasmid. It possessed 11 resistance genes including 2 ESBL genes that mapped to the chromosome and the plasmid; an IS26-flanked composite-like transposon was identified. A novel mcr-1 variant (mcr-1.19) was identified, which had a unique SNP (G1534A) that gave rise to a novel MCR-1 protein containing a Val512Ile amino acid substitution. Plasmid pCFSA629 possessed a conjugative plasmid transfer gene cluster as well as an antimicrobial resistance-encoding gene cluster-containing region that contained two IS26 composite-like transposonal modules, but was devoid of any plasmid-mediated quinolone resistance genes. The background of mcr-1.19 consisted of an ISApl1-mcr-1-PAP2-ter module. Conclusions: We report on an MDR S. Typhimurium ST34 CFSA629 isolate cultured from egg in China, harbouring an mcr-1.19 variant mapped to an IncHI2 plasmid. This highlights the importance of surveillance to mitigate dissemination of mcr-encoding genes among foodborne Salmonella. Improved surveillance is important for tackling the dissemination of mcr genes among foodborne Salmonella around the world. [ABSTRACT FROM AUTHOR]