Genomic context as well as sequence of both psr and penicillin-binding protein 5 contributes to ß-lactam resistance in Enterococcus faecium.

Penicillin-binding protein 5 (PBP5) of Enterococcus faecium (Efm) is vital for ampicillin resistance (AMP-R). We previously designated three forms of PBP5, namely, PBP5-S in Efm clade B strains [ampicillin susceptible (AMP-S)], PBP5-S/R (AMP-S or R), and PBP5-R (AMP-R) in clade A strains. Here, pbp5 deletion resulted in a marked reduction in AMP minimum inhibitory concentrations (MICs) to 0.01-0.09 µg/mL for clade B and 0.12-0.19 µg/mL for clade A strains; in situ complementation restored parental AMP MICs. Using D344SRF (lacking ftsW/psr/pbp5), constructs with ftsWA/psrA (from a clade A1 strain) cloned upstream of pbp5-S and pbp5-S/R alleles resulted in modest increases in MICs to 3-8 µg/mL, while high MICs (>64 µg/mL) were seen using pbp5 from A1 strains. Next, using ftsW ± psr from clade B and clade A/B and B/A hybrid constructs, the presence of psrB, even alone or in trans, resulted in much lower AMP MICs (3-8 µg/mL) than when psrA was present (MICs >64 µg/mL). qRT PCR showed relatively greater pbp5 expression (P = 0.007) with pbp5 cloned downstream of clade A1 ftsW/psr (MIC >128 µg/mL) vs when cloned downstream of clade B ftsW/psr (MIC 4-16 µg/mL), consistent with results in western blots. In conclusion, we report the effect of clade A vs B psr on AMP MICs as well as the impact of pbp5 alleles from different clades. While previously, Psr was not thought to contribute to AMP MICs in Efm, our results showed that the presence of psrB resulted in a major decrease in Efm AMP MICs. IMPORTANCE: The findings of this study shed light on ampicillin resistance in Enterococcus faecium clade A strains. They underscore the significance of alterations in the amino acid sequence of penicillin-binding protein 5 (PBP5) and the pivotal role of the psr region in PBP5 expression and ampicillin resistance. Notably, the presence of a full-length psrB leads to reduced PBP5 expression and lower minimum inhibitory concentrations (MICs) of ampicillin compared to the presence of a shorter psrA, regardless of the pbp5 allele involved. Additionally, clade B E. faecium strains exhibit lower AMP MICs when both psr alleles from clades A and B are present, although it is important to consider other distinctions between clade A and B strains that may contribute to this effect. It is intriguing to note that the divergence between clade A and clade B E. faecium and the subsequent evolution of heightened AMP MICs in hospital-associated strains appear to coincide with changes in Pbp5 and psr. These changes in psr may have resulted in an inactive Psr, facilitating increased PBP5 expression and greater ampicillin resistance. These results raise the possibility that a mimicker of PsrB, if one could be designed, might be able to lower MICs of ampicillin-resistant E. faecium, thus potentially resorting ampicillin to our therapeutic armamentarium for this species.

Metabolic Regulation of Two pksCT Gene Transcripts in Monascus ruber Impacts Citrinin Biosynthesis.

Citrinin (CIT), a secondary metabolite produced by the filamentous fungi Monascus species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of Monascus-derived products. CIT synthesis is mediated through the pksCT gene and modified by multiple genetic factors. Here, the regulatory effects of two pksCT transcripts, pksCTα, and pksCTß, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + ß) transformants decreased from 7.2 µg/mL in the wild-type strain to 3.8 µg/mL and 0.08 µg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically mrl3, mrl5, mrr1, and mrr5 in the ihpRNA-pksCT (α + ß) transformant, were downregulated. Transcriptome results revealed that silencing pksCT has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in Monascus, thus providing a foundation for future research.

Integrated bioinformatics analysis of microarray data from non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), with its high mortality rate, lack of early diagnostic markers and prevention of distant metastases are the main challenges in treatment. To identify potential miRNAs and key genes in NSCLC to find new biomarkers and target gene therapies. The GSE102286, GSE56036, GSE25508, GSE53882, GSE29248 and GSE101929 datasets were obtained from the Gene Expression Omnibus (GEO) database and screened for differentially co-expressed miRNAs (DE-miRNAs) and lncRNAs (DElncRs) by GEO2R and R software package. Pathway enrichment analysis of DE-miRNAs-target genes was performed by String and Funrich database to construct protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) network and visualized with Cytoscape software. Nineteen co-expressed DE-miRNAs were screened from five datasets. The 7683 predicted up- and down-regulated DE-miRNAs-target genes were significantly concentrated in cancer-related pathways. The top 10 hub nodes in the PPI were identified as hub genes, such as MYC, EGFR, HSP90AA1 and TP53, MYC, and ACTB. By constructing miRNA-hub gene networks, hsa-miR-21, hsa-miR-141, hsa-miR-200b and hsa-miR-30a, hsa-miR-30d, hsa-miR-145 may regulate most hub genes and hsa-miR-141, hsa-miR-200, hsa-miR-145 had higher levels in the miRNA and ceRNA regulatory networks, respectively. In conclusion, the identification of hsa-miR-21, hsa-miR-141, hsa-miR-200b hsa-miR-30a, hsa-miR-30d and hsa-miR-145 provides a new theoretical basis for understanding the development of NSCLC.

Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancer.

Background: Breast cancer (BRCA) has become the most diagnosed cancer worldwide for female and seriously endanger female health. The epithelial-mesenchymal transition (EMT) process is associated with metastasis and drug resistance in BRCA patients. However, the prognostic value of EMT-related lncRNA in BRCA still needs to be revealed. The aim of this study is to construct an EMT-related lncRNA (ERL) signature with accuracy predictive ability for the prognosis of BRCA patients. Methods: RNA-seq expression data and Clinical characteristics obtained from the TCGA (The Cancer Genome Atlas) were used in the study. First, we identified the EMT-related lncRNA by the Pearson correlation analysis. An EMT-related lncRNAs prognostic risk signature was constructed using univariate Cox regression and Lasso-penalized Cox regression analyses. The model's performance was validated using Kaplan-Meier (KM) survival analysis, ROC curve and C-index. Finally, a nomogram was constructed for clinical practice in evaluating the patients with BRCA and validated by calibration curve and decision curve analysis (DCA). We also evaluated the drug sensitivity of signature lncRNA and the tumor immune cell infiltration in breast cancer. Results: We constructed a 10-lncRNA risk score signature based on the lncRNAs associated with the EMT process. We could assign BRCA patients to the high- and low-risk group according to the median risk score. The prognostic risk signature showed excellent accuracy and demonstrated sufficient independence from other clinical characteristics. The immune cell infiltration analysis showed that the prognostic risk signature was related to the infiltration of the immune cell subtype. Drug sensitivity analysis proved ERLs signature could effectively predict the sensitivity of patients to common chemotherapy drugs in BRCA and provide guidance for chemotherapy drugs for high-risk and low-risk patients. Conclusion: Our ERL signature and nomogram have excellent prognostic value and could become reliable tools for clinical guidance.

Prophylactic Central Neck Dissection Based on Preoperative Imaging and Intraoperative Surgeon's Palpation Versus Total Thyroidectomy Alone for Papillary Thyroid Cancer.

INTRODUCTION: To compare the overall morbidity and recurrence of papillary thyroid cancer (PTC) after total thyroidectomy (TT) with or without prophylactic central compartment neck dissection (CCND) in cases of both preoperative and intraoperative nonsuspicious central lymph nodes (CLNs). METHODS: A total of 570 PTC patients who harbored no preoperative and intraoperative suspicious CLNs at two institutions were enrolled. They were randomly assigned to TT alone or TT with prophylactic CCND (pCCND) after intraoperative assessment of CLNs during the surgery. Lymph nodes that were hard or large enough to be palpated were regarded as suspicious metastatic lymph nodes during the surgery. The characteristics, postoperative complications, and locoregional recurrence of the two groups were recorded and compared. RESULTS: With a median follow-up of 5 y, the rates of lymph node recurrence in the TT alone and TT with pCCND groups were similar (7.3% versus 4.6%, P = 0.247), but there were significantly higher rates of overall morbidity (6.6% versus 19.1%, P < 0.001) when pCCND was performed. CONCLUSIONS: pCCND is not recommended for patients with clinically node-negative PTC preoperatively and intraoperatively because of the high complication rate and lack of benefit of reducing recurrence.

Molecular crowding promotes the aggregation of parallel structured G-quadruplexes.

G-quadruplexes are widely distributed in cells and are usually essential in mediating biological processes. The intracellular environment is often in a state of molecular crowding, and the current research considerably focuses on the effect of molecular crowding on the conformation of telomeric G-quadruplexes. However, G-quadruplex-forming oligonucleotides are primarily located in the promoter region of the proto-oncogene and on mRNA inside the cell and are reported to fold into parallel structures. Thus, studying the interaction mechanism between ligands and parallel structured G-quadruplexes under crowding conditions is crucial for the design of drugs targeting G-quadruplexes. In our study, molecular crowding was simulated through polyethylene glycol with an average molecular weight of 200 (PEG200) to investigate the parallel structure of the canonical G-quadruplexes c-KIT1, c-MYC, and 32KRAS and their interactions with ligands. Circular dichroism (CD) spectral scanning, fluorescence resonance energy transfer (FRET), and native polyacrylamide gel electrophoresis (PAGE) analysis revealed that molecular crowding failed to induce oligonucleotides to form parallel G-quadruplex structures in the explored model sequences while induced telomeric G-rich sequences to form antiparallel G-quadruplexes in solution without K+. Molecular crowding did not induce changes in their parallel structures but promoted the formation of G-quadruplex aggregates. Moreover, to some extent, molecular crowding also induced a looser structure of the monomer G-quadruplexes. Further studies showed that molecular crowding did not alter the binding stoichiometry of the ligand 3,11-difluoro-6,8,13-trimethyl-8H-quino [4,3,2-kl] acridinium methosulfate (RHPS4) to c-KIT1, while it inhibited its interaction with parallel structured G-quadruplexes. This work provides new insights into developing anticancer drugs targeting parallel structured G-quadruplexes.

Monascus Red Pigment Liposomes: Microstructural Characteristics, Stability, and Anticancer Activity.

Monascus red pigments (MRPs), which are a kind of natural colorant produced by Monascus spp., are widely used in the food and health supplements industry but are not very stable during processing and storage. Thus, MRPs were embedded into liposome membranes using a thin-film ultrasonic method to improve stability in this study. Monascus red pigments liposomes (MRPL) exhibited spherical unilamellar vesicles (UV) with particle size, polydispersity indexes (PDI), and zeta potential of 20-200 nm, 0.362 ± 0.023, and -42.37 ± 0.21 mV, respectively. pH, thermal, light, metal ion, storage, and in vitro simulated gastrointestinal digestion stability revealed that, compared with free MRPs, liposomes embedding significantly enhanced the stability of MRPs when exposed to adverse environmental conditions. Furthermore, anticancer assay suggested that MRPL exhibited a stronger inhibitory effect on MKN-28 cells by damaging the integrity of cells, with the IC50 value at 0.57 mg/mL. Overall, MRPLs possess stronger stability in external environment and in vitro simulated digestion with greater anticancer activity, indicating that MRPLs have the potential for promising application in the functional foods and pharmaceutical industries.

Development of the expression and prognostic significance of m5 C-related LncRNAs in breast cancer.

BACKGROUND: 5-Methylcytosine (m5C) methylation is a major epigenetic RNA modification and is closely related to tumorigenesis in various cancers. This study aimed to explore the prognostic value of m5C-related lncRNAs in breast cancer. METHODS: Clinical characteristics and RNA-seq expression data from TCGA (The Cancer Genome Atlas) were used in the study. First, we performed differentially expressed gene (DEG) analysis and constructed a PPI network for the 12 m5C regulators. Then, we identified the m5C-related LncRNAs by the "cor. test." An m5C-related lncRNA prognostic risk signature was developed using univariate Cox regression and Lasso-penalized Cox regression analyses. The model's performance was determined using Kaplan-Meier (KM) survival analysis and ROC curves. Finally, a nomogram was constructed for clinical application in evaluating patients with BRCA. We also researched the drug sensitivity of signature lncRNAs and immune cell infiltration. Finally, we validated the expression of the signature lncRNAs through qRT-PCR in a breast cancer cell line and a breast epithelial cell line. RESULTS: Overall, we constructed an 11-lncRNA risk score signature based on the lncRNAs associated with m5C regulators. According to the median risk score, we divided BRCA patients into high- and low-risk groups. The prognostic risk signature displayed excellent accuracy and demonstrated sufficient independence from other clinical characteristics. The immune cell infiltration analysis showed that the prognostic risk signature was related to the infiltration of immune cell subtypes. Drug sensitivity proved that our prognostic risk signature potentially has therapeutic value. CONCLUSIONS: The m5C-related lncRNA signature reliably predicted the prognosis of breast cancer patients and may provide new insight into the breast cancer tumor immune microenvironment.

Highly Efficient Biotransformation and Production of Selenium Nanoparticles and Polysaccharides Using Potential Probiotic Bacillus subtilis T5

Selenium is an essential microelement required for human health. The biotransformation of selenium nanoparticles has attracted increasing attention in recent years. However, little of the literature has investigated the comprehensive evaluation of the strains for practical application and the effect on the functional properties in the existence of Se. The present study showed the selenite reduction strain Bacillus subtilis T5 (up to 200 mM), which could produce high yields of selenium polysaccharides and selenium nanoparticles in an economical and feasible manner. Biosynthesized selenium nanoparticles by B. subtilis T5 were characterized systematically using UV-vis spectroscopy, FTIR, Zeta Potential, DLS, and SEM techniques. The biosynthesized SeNPs exhibited high stability with small particle sizes. B. subtilis T5 also possessed a tolerance to acidic pH and bile salts, high aggregation, negative hemolytic, and superior antioxidant activity, which showed excellent probiotic potential and can be recommended as a potential candidate for the selenium biopharmaceuticals industry. Remarkably, B. subtilis T5 showed that the activity of α-amylase was enhanced with selenite treatment to 8.12 U/mL, 2.72-fold more than the control. The genus Bacillus was first reported to produce both selenium polysaccharides with extremely high Se-content (2.302 g/kg) and significantly enhance the activity to promote α-amylase with selenium treatment. Overall, B. subtilis T5 showed potential as a bio-factory for the biosynthesized SeNPs and organ selenium (selenium polysaccharide), providing an appealing perspective for the biopharmaceutical industry.

Weighted gene co-expression network reveals driver genes contributing to phenotypes of anaplastic thyroid carcinoma and immune checkpoint identification for therapeutic targets.

Background: Anaplastic thyroid carcinoma (ATC) is a rare but extremely malignant tumor, with a rapid growth rate and early metastasis thus leading to poor survival of patients. The molecular mechanisms underlying these aggressive traits of ATC remain unknown, which impedes the substantial progress in treatment to prolong ATC patient survival. Methods: We applied weighted gene co-expression network analysis (WGCNA) to identify ATC-specific modules. The Metascape web and R package clusterProfiler were employed to perform enrichment analysis. Combined with differentially expressed gene analysis, we screened out the most potential driver genes and validated them using receiver operator characteristic (ROC) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry (IHC), and triple immunofluorescence staining. Results: A gene expression matrix covering 75 normal samples, 83 papillary thyroid carcinoma (PTC), 26 follicular thyroid carcinoma (FTC), 19 poor-differentiated thyroid carcinoma (PDTC), and 41 ATC tissue samples were integrated, based on which we detected three most potential ATC-specific modules and found that hub genes of these modules were enriched in distinct biological signals. Hub genes in the turquoise module were mainly enriched in mitotic cell cycle, tube morphogenesis, and cell differentiation, hub genes in the magenta module were mainly clustered in the extracellular matrix organization, positive regulation of cell motility, and regulation of Wnt signaling pathway, while hub genes in the blue module primarily participated in the inflammatory response, innate immune response, and adaptive immune response. We showed that 9 top genes, 8 transcription factors (TFs), and 4 immune checkpoint genes (ICGs) were differentially expressed in ATC compared to other thyroid samples and had high diagnostic values for ATC, among which, 9 novel ATC-specific genes (ADAM12, RNASE2, CASP5, KIAA1524, E2F7, MYBL1, SRPX2, HAVCR2, and TDO2) were validated with our clinical samples. Furthermore, we illustrated that ADAM12, RNASE2, and HAVCR2 were predominantly present in the cytoplasm. Conclusion: Our study identified a set of novel ATC-specific genes that were mainly related to cell proliferation, invasion, metastasis, and immunosuppression, which might throw light on molecular mechanisms underlying aggressive phenotypes of ATC and provide promisingly diagnostic biomarkers and therapeutic targets.

Phage controlling method against novel freshwater-derived Vibrio parahaemolyticus in ready-to-eat crayfish (Procambarus clarkii).

Vibrio parahaemolyticus is a halophilic foodborne pathogen majorly isolated from seafood, threatening public health worldwide. However, our recent study reported the presence of this bacterium in freshwater crayfish, which were rarely identified and investigated. Its pathogenicity and genomic features remain unclear, and the controlling method to inhibit this bacterium in ready-to-eat (RTE) crayfish is not developed. Compared with a clinical strain (ATCC17802), the representative strain (LVP1) from freshwater crayfish showed higher pathogenicity in a zebrafish model, indicating its hypervirulence and foodborne infection risk. Unlike most clinical V. parahaemolyticus isolates that carried tdh and (or) trh, two classic virulence factor genes associated with clinical infections, the hypervirulent LVP1 lacked these two genes, indicating it is a novel strain and other unknown virulence factors play key roles in its pathogenicity. Genomic and phylogenetic analyses demonstrated this strain is V. parahaemolyticus, while it is phylogenetically distant from other global isolates. Therefore, LVP1 is considered a novel V. parahaemolyticus strain from freshwater crayfish, being hypervirulent, and lacking virulence marker genes. The antimicrobial resistant genes drfA6 and qnrV1 were unique in LVP1 and absent in other reference V. parahaemolyticus strains. Antimicrobial susceptibility testing confirms it as multidrug resistance, with resistance to ampicillin, amoxicillin/clavulanate, trimethoprim, and colistin. To control this novel and multidrug-resistant V. parahaemolyticus strain in food production chains, we developed a phage cocktail and applied it to the surface of RTE crayfish meat, resulting in a significant decrease in the bacterial load by 2.36 log10 CFU/mL. These data highlight freshwater food products pose threats to public health through 'farm-to-fork' transmission of hypervirulent V. parahaemolyticus and reveal the phage cocktail as a promising method to attenuate this bacterium in RTE food, emphasizing the necessity to prevent food contamination caused by this bacterium from freshwater products.

RHPS4 shifted the conformation ensemble equilibrium of Tel24 by preferentially stabilizing the (3 + 1) hybrid-2 conformation.

Telomeric G-quadruplexes have been a promising target for developing antitumor drugs with fewer side effects. The intracellular environment is usually in a state of molecular crowding. Studying the interaction mechanism among ligands and telomeric G-quadruplexes under crowded conditions is important for designing drugs that target telomeric G-quadruplexes. In the present study, the telomeric G-quadruplex Tel24 (TTAGGG)4 was found to fold into a conformational ensemble of parallel and (3 + 1) hybrid-2 conformations in solution with molecular crowding conditions created by PEG200. G-quadruplex-ligand 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl] acridinium methosulfate (RHPS4) preferentially stabilized the (3 + 1) hybrid-2 conformation and shifted the conformational ensemble equilibrium of Tel24 towards the hybrid conformation. We also found that the (3 + 1) hybrid-2 conformation of Tel24 was more likely to form as compared to the parallel conformation in the conformational ensemble of Tel24. Overall, this study provides new insights into the conformation of telomere G-quadruplexes and their interactions with ligands in a physiological environment.

The initial expression alterations occurring to transcription factors during the formation of breast cancer: Evidence from bioinformatics.

BACKGROUND: Breast cancer (BC) is the leading malignancy among women worldwide. AIM: This work aimed to present a comprehensively bioinformatic analysis of gene expression profiles and to identify the hub genes during BC tumorigenesis, providing potential biomarkers and targets for the diagnosis and therapy of BC. MATERIALS & METHODS: In this study, multiple public databases, bioinformatics approaches, and online analytical tools were employed and the real-time reverse transcription polymerase chain reaction was implemented. RESULTS: First, we identified 10, 107, and 3869 differentially expressed genes (DEGs) from three gene expression datasets (GSE9574, GSE15852, and GSE42568, covering normal, para-cancerous, and BC samples, respectively), and investigated different biological functions and pathways involved. Then, we screened out 8, 16, and 29 module genes from these DEGs, respectively. Next, 10 candidate genes were determined through expression and survival analyses. We noted that seven candidate genes JUN, FOS, FOSB, EGR1, ZFP36, CFD, and PPARG were downregulated in BC compared to normal tissues and lower expressed in aggressive types of BC (basal, HER2+ , and luminal B), TP53 mutation group, younger patients, higher stage BC, and lymph node metastasis BC, while CD27, PSMB9, and SELL were upregulated. The present study discovered that the expression levels of these candidate genes were correlated with the infiltration of immune cells (CD8+ T cell, macrophage, natural killer [NK] cell, and cancer-associated fibroblast) in BC, as well as biomarkers of immune cells and immune checkpoints. We also revealed that promoter methylation, amplification, and deep deletion might contribute to the abnormal expressions of candidate genes. Moreover, we illustrated downstream-targeted genes of JUN, FOS, FOSB, EGR1, and ZFP36 and demonstrated that these targeted genes were involved in "positive regulation of cell death", "pathways in cancer", "PI3K-Akt signaling pathway", and so on. DISCUSSION & CONCLUSION: We presented differential gene expression profiles among normal, para-cancerous, and BC tissues and further identified candidate genes that might contribute to tumorigenesis and progression of BC, as potential diagnostic and prognostic targets for BC patients.

Genome analysis provides insight into hyper-virulence of Streptococcus suis LSM178, a human strain with a novel sequence type 1005.

Streptococcus suis has been well-recognized as a zoonotic pathogen worldwide, and the diversity and unpredictable adaptive potential of sporadic human strains represent a great risk to the public health. In this study, S. suis LSM178, isolated from a patient in contact with pigs and raw pork, was assessed as a hyper-virulent strain and interpreted for the virulence based on its genetic information. The strain was more invasive for Caco-2 cells than two other S. suis strains, SC19 and P1/7. Sequence analysis designated LSM178 with serotype 2 and a novel sequence type 1005. Phylogenetic analysis showed that LSM178 clustered with highly virulent strains including all human strains and epidemic strains. Compared with other strains, these S. suis have the most and the same virulent factors and a type I-89 K pathogenicity island. Further, groups of genes were identified to distinguish these highly virulent strains from other generally virulent strains, emphasizing the key roles of genes modeling transcription, cell barrier, replication, recombination and repair on virulence regulation. Additionally, LSM178 contains a novel prophage conducive potentially to pathogenicity.

High Expression of CEMIP Correlates Poor Prognosis and the Tumur Microenvironment in Breast Cancer as a Promisingly Prognostic Biomarker.

Cell migration-inducing hyaluronidase 1 (CEMIP), a Wnt-related protein and also known as KIAA1199, is implicated in the process of metastatic colonization in a variety of malignant tumors, including breast cancer (BC), which is one of the most frequently diagnosed tumors in women worldwide. In this study, multiple public databases, online analytical tools, and bioinformatics approaches were applied to explore the expression levels, regulatory mechanisms, and biological functions of CEMIP in BC. We illustrated that CEMIP was highly expressed in various kinds of carcinomas, including BC, especially advanced subtypes, and predicted less favorable prognosis (negatively associated with overall survival) in BC patients, which might be an independent prognostic factor. Then, we revealed that the mutation and high expression of CEMIP might lead to it as an oncogene. We also demonstrated that TP53 mutation, DNA hypo-methylation, and the expression changes of three potential upstream transcription factors (EZH2, EGR1, and JUN) of CEMIP were likely to cause the hyperexpression of CEMIP in BC. Moreover, our findings suggested that CEMIP might exert its carcinogenic roles in the tumor microenvironment via participation in the extracellular matrix formation, increasing cancer-associated fibroblast (CAF), M2 macrophage, and neutrophil infiltration and decreasing CD8+ T cell infiltration. In summary, our study provided more solid evidence for CEMIP as a prognostic and metastatic biomarker and a potential therapeutic target in BC. Of course, these findings also need more confirmations of basic experiments and further clinical trials in the future.

The global emergence of a novel Streptococcus suis clade associated with human infections.

Streptococcus suis, a ubiquitous bacterial colonizer in pigs, has recently extended host range to humans, leading to a global surge of deadly human infections and three large outbreaks since 1998. To better understand the mechanisms for the emergence of cross-species transmission and virulence in human, we have sequenced 366 S. suis human and pig isolates from 2005 to 2016 and performed a large-scale phylogenomic analysis on 1,634 isolates from 14 countries over 36 years. We show the formation of a novel human-associated clade (HAC) diversified from swine S. suis isolates. Phylogeographic analysis identified Europe as the origin of HAC, coinciding with the exportation of European swine breeds between 1960s and 1970s. HAC is composed of three sub-lineages and contains several healthy-pig isolates that display high virulence in experimental infections, suggesting healthy-pig carriers as a potential source for human infection. New HAC-specific genes are identified as promising markers for pathogen detection and surveillance. Our discovery of a human-associated S. suis clade provides insights into the evolution of this emerging human pathogen and extend our understanding of S. suis epidemics worldwide.

A tetravalent single-chain variable fragment antibody for the detection of staphylococcal enterotoxin A.

Staphylococcal enterotoxin A (SEA) synthesized by Staphylococcus aureus is a foodborne and heat-stable toxin, which is a great threat to human health (Pexaraet al., 2010). Highly sensitive antibodies are a key factor in the immunological detection of SEA, which is one of the most effective ways to detect SEA because of its accuracy, agility, and efficiency (Nouri et al., 2018). In this study, we constructed a tetravalent anti-SEA antibody gene by linking the tetramerization domain of human p53 to the C-terminus of the anti-SEA single-chain variable fragment (scFv), which was then transformed into Escherichia coli BL21 (DE3) for the production of a SEA-specific tetravalent antibody. Successful expression of the tetravalent antibody was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot. An indirect non-competitive enzyme-linked immunosorbent assay (ELISA) revealed that the tetravalent antibody exhibited SEA-specific binding activity. A sandwich ELISA demonstrated that compared to the scFv monomer, the tetravalent antibody was more sensitive in detecting SEA. Molecular docking analysis revealed that the SEA interacted with the scFv mainly on the opposite side of the residue linked to p53. Thus, this study indicated that genetically engineered tetramerization is a potential way to improve the sensitivity of SEA-specific scFv.

Application of a Novel Phage LPSEYT for Biological Control of Salmonella in Foods.

Salmonella is a leading cause of foodborne diseases, and in recent years, many isolates have exhibited a high level of antibiotic resistance, which has led to huge pressures on public health. Phages are a promising strategy to control food-borne pathogens. In this study, one of our environmental phage isolates, LPSEYT, was to be able to restrict the growth of zoonotic Salmonella enterica in vitro over a range of multiplicity of infections. Phage LPSEYT exhibited wide-ranging pH and thermal stability and rapid reproductive activity with a short latent period and a large burst size. Phage LPSEYT demonstrated potential efficiency as a biological control agent against Salmonella in a variety of food matrices, including milk and lettuce. Morphological observation, comparative genomic, and phylogenetic analysis revealed that LPSEYT does not belong to any of the currently identified genera within the Myoviridae family, and we suggest that LPSEYT represents a new genus, the LPSEYTvirus. This study contributes a phage database, develops beneficial phage resources, and sheds light on the potential application value of phages LPSEYT on food safety.

Functionalized metal-organic frameworks for photocatalytic degradation of organic pollutants in environment.

Currently, many kinds of organic pollutants in air and water have a negative impact on humans and the environment. Notably, as a type of new functional materials, metal-organic frameworks (MOFs) with well-ordered porous structures and numerous active sites have been proven to be ideal photocatalysts for the degradation of organic pollutants. In the past few years, many encouraging achievements have been made in the research field of MOFs for photocatalysis. And a large number of functionalized MOFs have been constructed to improve photocatalytic activity. In this review, recent progress in the photocatalytic degradation of organic pollutants in both air and water using functionalized MOFs are summarized in detail. The focus is on photocatalytic mechanisms and some strategies employed to achieve higher degradation efficiency. Furthermore, the challenges and outlooks in this promising filed are also discussed. We hope this review would be useful for designing more functionalized MOFs with greater photocatalytic performance for the degradation of organic pollutants in the environment.

New principle for busbar protection based on the Euclidean distance algorithm.

A new fast busbar protection algorithm based on the comparison of the similarity of back-wave waveforms is proposed in this paper. The S-transform is performed on the back-wave from each defected transmission line connected to the busbar, and the protection criterion is thus constructed by using the Euclidean distance to analyze the similarity of the back-waves, with the implementation of the S-transform between the transmission lines. When a fault occurs internally on the busbar, the Euclidean distance of the S-transformed back-wave between each associated transmission line is small, and there is a remarkable similarity between the waveform. When a fault occurs externally on the busbar, the Euclidean distance of the S-transformed backward traveling wave between the faulty line and the nonfaulty line is larger than that between the nonfaulty lines. The wave-forms of the faulty line and the nonfaulty line bear little similarity, while there is a striking similarity between the nonfaulty lines. Therefore, a protection criterion is established according to the ratio between the maximal similarity and the minimal similarity to discriminate the internal and external faults of the busbar zones. The simulation results show that the proposed busbar protection method can discriminate the internal and external faults of busbar zones in a sensitive and reliable way.