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Vibrio parahaemolyticus is a common foodborne pathogenic bacterium and drug-resistant strains are now widespread. Phages led by drug-resistant V. parahaemolyticus strains are promising means to decrease the pressure on public health. We isolated a V. parahaemolyticus-specific bacteriophage F23s1 that was active at wide ranges of temperature (30-60°C) and pH (4-10). Phage F23s1 exhibited a specific host range; in that, only 13 of the 23 V. parahaemolyticus strains were lysed. F23s1 effectively inhibited the growth of V. parahaemolyticus strain F23 in shrimp at 25°C within 12 h at a multiplicity of infection of 1000. We sequenced the genome of phage F23s1 which comprised a 76,648-bp DNA with 105 open reading frames (ORFs) and identified an endolysin gene ORF52 that was then cloned and successfully expressed in Escherichia coli. The recombinant ORF52 protein significantly decreased OD

Multidrug-resistant (MDR) Vibrio parahaemolyticus strains have become a great threat to public health. The purpose of this study was to investigate differences in biological characteristics and antimicrobial resistance gene (ARG) mutations of V. parahaemolyticus that displayed different levels of antimicrobial resistance. The susceptibility of 74 V. parahaemolyticus strains to 9 common antimicrobials was investigated, of which 88% were resistant to 3-4 antimicrobials and 3% to 5-7 antimicrobials. Interestingly, only 9% were resistant to 1-2 antimicrobials. The MDR strains possessed longer growth lag time than the non-MDR strains and displayed weaker swimming abilities. Whole genome sequencing was performed on strains VP41, VP44, 460, and 469 that were resistant to two to three classes of antimicrobials. ARGs were identified and compared with that of reference strain ATCC17802, and some important mutations were deduced. The Val189Ile mutation emerged in qnr gene of a single strain. Besides, the nonsynonymous mutations existed in four ARGs in different strains, including CatB (Pro165Ser, Gly208Asp), VmeA (Ile313Thr), VmeC (Glu329Ala), and VmeD (Asn205Ser). These results linked resistance gene mutations to enhance resistance in V. parahaemolyticus strains and provide a reference for more effective monitoring and prevention of V. parahaemolyticus infections.

Objective: To explore the application of operation room optimization process with multidisciplinary collaborative management in hysteromyoma surgery. Methods: 500 patients who underwent hysteromyoma surgery from March to December 2018 were selected as the control group. 500 patients who underwent hysteromyoma surgery using operation room optimization process with multidisciplinary collaborative management from March to December 2019 were selected as the observation group. The scores of self-care ability (ESCA), psychological status (HAMA, HAMD score), time of postoperative early ambulation activity, comfort of ambulation activity, postoperative hospital stay and total hospital stay, postoperative complications, quality of life score (SF-36), satisfaction with care were compared between the two groups. Results: There was no significant difference in the scores of ESCA, HAMA and HAMD between the two groups before operation (P>0.05). On the 7th day after operation, the score of ESCA of tne two groups was increased (P 0.05). There was significant difference in SF-36 scores between the two groups after operation and after follow up for 3 months (P Conclusion: The application of multidisciplinary collaborative management in hysteromyoma surgery can optimize the operation process, alleviate the patient's operation anxiety, promote the patient's postoperative rehabilitation, improve the patient's quality of lite and improve tne patients satisfaction, and therefore, it is worth popularizing.

The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP+ exosomes. Moreover, uptake of CEMIP+ exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnf and Ccl/Cxcl, known to promote brain vascular remodelling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.

The development of new antibacterial agents to deal with the emergence and spread of antibiotic resistance in Gram-positive bacterial pathogens has become an increasing problem. Here, a new strategy is developed for the effective targeting and killing of Gram-positive bacteria based on vancomycin (Van)-modified gold nanostars (AuNSs). Our work has demonstrated that the Van-modified AuNSs (AuNSs@Van) can not only selectively recognize methicillin-resistant Staphylococcus aureus (MRSA) but also kill MRSA under near-infrared laser irradiation in vitro. Additionally, AuNSs@Van shows satisfactory biocompatibility and antibacterial activity in treating bacterial infection in vivo. The attractive trait of AuNSs@Van is attributed to the physical effect of its antibacterial activity, with less potential for resistance development. The aforementioned advantages indicate the potential of AuNSs@Van as a photothermal antibacterial agent for effectively combating Gram-positive bacteria in the field of health care.

The development of novel antimicrobial agents is a top priority in the fight against drug-resistant bacteria. Here, we synthesized a green nanoantibiotic, nitrogen-doped carbon quantum dots (N-CQDs) from bis-quaternary ammonium salt (BQAS) as carbon and nitrogen sources. The as-obtained N-CQDs possess high antibacterial activity (>99%) against both methicillin-resistant Staphylococcus aureus (MRSA) and Ampicillin-resistant Escherichia coli bacteria in vitro than some known clinical antibiotics (vancomycin and gentamicin). The N-CQDs can kill MRSA pathogens without inducing resistance, prevent biofilm formation and eliminate established biofilm and persister cells. The treatment of N-CQDs can significantly reduce the amount of bacteria on the infected tissue and accelerate wound healing. The N-CQDs are positively charged, thus enabling them to interact with bacterial cell membrane through electrostatic interaction, leading to severe damage and an increased permeability of the cell membrane, which further promotes the penetration of N-CQDs into the membrane and induces the degradation of DNA by N-CQDs generated reactive oxygen species. The N-CQDs also play a role in obstructing the intracellular metabolic pathways of MRSA. The overall data demonstrate the green nanoantibiotic as an excellent eradicator of biofilm and persister cells as well as a promising antibacterial candidate for treating infections induced by drug-resistant bacteria.

Due to their remarkable antibacterial properties, silver nanoparticles (Ag NPs) and curcumin (CCM) have been widely used in the antimicrobial field. In our study, we have fabricated the uniform and stable silver/curcumin composite nanoparticles by a facile ultrasound treatment process and the synergistic antibacterial activity were evaluated. The curcumin not only played a role of reducing agent but also acted as a capping agent. The antibacterial effects of silver/curcumin (cAgNPs) were studied by measuring the growth curve and surface plate assay based on the E. coli and B. subtilis, which showed concentration dependent bacteriostatic and bactericidal effects of cAgNPs. The presence of CCM enhance the binding of Ag to bacterial membrane and Ag+ release in comparison to that without CCM, so that creating a temporary and local high Ag+ concentration near the surface of the bacterium, meanwhile, generation of more reactive oxygen species, lead to membrane damage, bacterial lipases and induce leakage of intracellular contents followed by bacterial death that lead to growth inhibition of the bacteria. The antibacterial effects were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), the effect which were further found to decrease by introducing antioxidant N-acetyl-l-cysteine (NAC) act as a reactive oxygen species (ROS) scavenging agent. These initial data suggest that cAgNPs have a highly antibacterial efficient and might have potential to be developed as an effective antimicrobial nanomaterial.

Multidrug-resistant (MDR)

The development of new antibacterial agents to deal with the emergence and spread of antibiotic resistance in Gram-positive bacterial pathogens has become an increasing problem. Here, a new strategy is developed for the effective targeting and killing of Gram-positive bacteria based on vancomycin (Van)-modified gold nanostars (AuNSs). Our work has demonstrated that the Van-modified AuNSs (AuNSs@Van) can not only selectively recognize methicillin-resistant

Precisely striking the bacterially infected site and avoiding damage to healthy tissues is vital for bacterial infection therapy. Herein, an intelligent antibacterial platform that triggers the aggregation of gold nanoparticles (AuNPs) on bacterial surface based on the acidic environment of bacterial infection was developed. Also, the AuNPs functionalized with an acidity-triggered moiety (Pep-DA) exhibited a charge-convertible properties to target bacterial infection sites. The positively charged acidity-triggered AuNPs endowed the AuNPs aggregate on negatively charged bacterial surface in the infected site rather than in healthy tissues, achieving the threshold to interparticle plasmonic coupling effect among AuNPs, and killing bacteria accurately under NIR irradiation light. This acidity-triggered aggregation strategy provides an excellent therapeutic mode for treating focal bacterial infections with no critical damage to healthy tissues.

Helicobacter pylori (H. pylori) infection has ≈75% probability of causing gastric cancer, so it is considered to be the strongest single risk factor for gastric malignancies. However, the harsh gastric acid environment has created obstacles to medical treatment. This work reports a nanomotor with a bottle-shaped container that can be loaded with small molecules of clarithromycin, nano calcium peroxide (CaO2 ), and Pt nanoparticles (Pt NPs) by ultrasound. Nanomotors can quickly consume gastric acid through the chemical reaction of CaO2 to temporarily neutralize gastric acid. The product hydrogen peroxide (H2 O2 ) is catalytically decomposed into a large amount of oxygen (O2 ) by Pt NPs. The local concentration gradient of O2 bubbles causes it to be expelled from the nanobottles through a narrow opening, and then push the nanobottles forward to provide maximum release and prodrug efficacy. Experiments in animal models show that 15 mg nanomotors can safely and quickly neutralize gastric acid in the stomach and simultaneously release prodrugs to achieve good therapeutic effects without causing acute toxicity. H. pylori burden in mice was 2.6 orders of magnitude lower than that in the control group. The stomach returns to normal pH within 1 d after administration.

Summary There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n = 151) and plasma-derived (n = 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.

The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90–120 nm; small exosome vesicles, Exo-S, 60–80 nm) and discovered an abundant population of non-membranous nanoparticles termed ‘exomeres’ (~35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins as well as specific pathways, such as glycolysis and mTOR signalling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways, and mitotic spindle and IL-2/STAT5 signalling pathways, respectively. Exo-S, Exo-L and exomeres each had unique N-glycosylation, protein, lipid, DNA and RNA profiles and biophysical properties. These three nanoparticle subsets demonstrated diverse organ biodistribution patterns, suggesting distinct biological functions. This study demonstrates that AF4 can serve as an improved analytical tool for isolating extracellular vesicles and addressing the complexities of heterogeneous nanoparticle subpopulations.

The photonic crystals with two-dimensional chirped structure and with apodized structure were analysed, and their transmission characteristics were studied by FDTD method and PML technique. The photonic band gap can be made wider with different chirped coefficient or apodized function. This can provide an effective method for controlling the photonic band gap in the photonic crystal applications.

An effective design of frequency Selective Filter in a two-dimensional (2-D) photonic-crystal (PC) was proposed. At first, a branch-missing-line photonic-crystal waveguide by inserting three different PC materials to the crotch was investigated. By analyzing band gaps of the filter, the characteristics of a frequency selective filter were discussed. Second, by choosing different radii of PC rods in the crotch of a branch waveguide, we could similarly obtain the required frequency of the electromagnetic wave. Finally, by using Thermo-optical effect to change dielectric constant, the operating wavelength of the device could be tuned.

Following a detailed study, a reversed-phase high performance liquid chromatographic method (HPLC) has been developed and validated for analysis of three bioactive alkaloids, matrine, sophoridine and oxymatrine, in Sophora flavescens Ait. HPLC separation of the alkaloids was performed on a Kromasil C(18) column and detected by ultraviolet absorbance at 208 nm. The column temperature was maintained at 40 degrees C. A mobile phase composed of 0.01 mol/L KH(2)PO(4) buffer-methanol-triethylamine in the ratios 94:6:0.01 (v/v) was found to be the most suitable for this separation at a fl ow-rate of 1.0 mL/min and enabled the baseline separation of the three analytes free from interferences with isocratic elution. The analysis time was 24 min per injection. The calibration was linear in the range of 0.2-120.0 micro g/mL for matrine, 0.2-115.2 micro g/mL for sophoridine and 0.2-110.4 micro g/mL for oxymatrine, respectively. For assaying Sophora Flavescens Ait. samples, the relative standard deviations were 2.0% for matrine, 2.8% for sophoridine and 1.8% for oxymatrine analysis. The average recoveries of matrine, sophoridine and oxymatrine were 93.9, 95.3 and 93.5% for the Sophora flavescens Ait. samples, respectively. The method has been successfully applied to the simultaneous determination of matrine, sophoridine and oxymatrine in Sophora Flavescens Ait. samples collected in different habitats.