Probing dark particles indirectly at the CEPC

When dark matter candidate and its parent particles are nearly degenerate, it would be difficult to probe them at the Large Hadron Collider directly. We propose to explore their quantum loop effects at the CEPC through the golden channel process $e^+e^-\to \mu^+\mu^-$. We use a renormalizable toy model consisting of a new scalar and a fermion to describe new physics beyond the Standard Model. The new scalar and fermion are general multiplets of the $SU(2)_L\times U(1)_Y$ symmetry, and couple to the muon lepton through Yukawa interaction. We calculate their loop contributions to anomalous $\gamma\mu^+\mu^-$ and $Z\mu^+\mu^-$ couplings which can be applied to many new physics models. The prospects of their effects at the CEPC are also examined assuming a 0.002 accuracy in the cross section measurement

The upper and lower solution method for nonlinear third-order three-point boundary value problem

This paper is concerned with the following nonlinear third-order three-point boundary value problem \left\{ \begin{array}{l} u^{\prime \prime \prime }(t)+f\left( t,u\left( t\right) ,u^{\prime}\left(t\right) \right) =0,\, t\in \left[ 0,1\right], \\ u\left( 0\right) =u^{\prime }\left( 0\right) =0,\, u^{\prime}\left( 1\right) =\alpha u^{\prime }\left( \eta \right),\label{1.1} \end{array} \right. where $0<\eta <1$ and $0\leq \alpha <1.$ A new maximum principle is established and some existence criteria are obtained for the above problem by using the upper and lower solution method

A Label-Free Platform for Identification of Exosomes from Different Sources.

Exosomes contain cell- and cell-state-specific cargos of proteins, lipids, and nucleic acids and play significant roles in cell signaling and cell-cell communication. Current research into exosome-based biomarkers has relied largely on analyzing candidate biomarkers, i.e., specific proteins or nucleic acids. However, this approach may miss important biomarkers that are yet to be identified. Alternative approaches are to analyze the entire exosome system, either by "omics" methods or by techniques that provide "fingerprints" of the system without identifying each individual biomolecule component. Here, we describe a platform of the latter type, which is based on surface-enhanced Raman spectroscopy (SERS) in combination with multivariate analysis, and demonstrate the utility of this platform for analyzing exosomes derived from different biological sources. First, we examined whether this analysis could use exosomes isolated from fetal bovine serum using a simple, commercially available isolation kit or necessitates the higher purity achieved by the "gold standard" ultracentrifugation/filtration procedure. Our data demonstrate that the latter method is required for this type of analysis. Having established this requirement, we rigorously analyzed the Raman spectral signature of individual exosomes using a unique, hybrid SERS substrate made of a graphene-covered Au surface containing a quasi-periodic array of pyramids. To examine the source of the Raman signal, we used Raman mapping of low and high spatial resolution combined with morphological identification of exosomes by scanning electron microscopy. Both approaches suggested that the spectra were collected from single exosomes. Finally, we demonstrate for the first time that our platform can distinguish among exosomes from different biological sources based on their Raman signature, a promising approach for developing exosome-based fingerprinting. Our study serves as a solid technological foundation for future exploration of the roles of exosomes in various biological processes and their use as biomarkers for disease diagnosis and treatment monitoring

Pharmacokinetic/Pharmacodynamic Correlation of Cefquinome Against Experimental Catheter-Associated Biofilm Infection Due to Staphylococcus aureus.

Biofilm formations play an important role in Staphylococcus aureus pathogenesis and contribute to antibiotic treatment failures in biofilm-associated infections. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of cefquinome against an experimental catheter-related biofilm model due to S. aureus, including three clinical isolates and one non-clinical isolate. The minimal inhibitory concentration (MIC), minimal biofilm inhibitory concentration (MBIC), biofilm bactericidal concentration (BBC), minimal biofilm eradication concentration (MBEC) and biofilm prevention concentration (BPC) and in vitro time-kill curves of cefquinome were studied in both planktonic and biofilm cells of study S. aureus strains. The in vivo post-antibiotic effects (PAEs), PK profiles and efficacy of cefquinome were performed in the catheter-related biofilm infection model in murine. A sigmoid E max model was utilized to determine the PK/PD index that best described the dose-response profiles in the model. The MICs and MBICs of cefquinome for the four S. aureus strains were 0.5 and 16 μg/mL, respectively. The BBCs (32-64 μg/mL) and MBECs (64-256 μg/mL) of these study strains were much higher than their corresponding BPC values (1-2 μg/mL). Cefquinome showed time-dependent killing both on planktonic and biofilm cells, but produced much shorter PAEs in biofilm infections. The best-correlated PK/PD parameters of cefquinome for planktonic and biofilm cells were the duration of time that the free drug level exceeded the MIC (fT &gt; MIC, R (2) = 96.2%) and the MBIC (fT &gt; MBIC, R (2) = 94.7%), respectively. In addition, the AUC24h/MBIC of cefquinome also significantly correlated with the anti-biofilm outcome in this model (R (2) = 93.1%). The values of AUC24h/MBIC for biofilm-static and 1-log10-unit biofilm-cidal activity were 22.8 and 35.6 h; respectively. These results indicate that the PK/PD profiles of cefquinome could be used as valuable guidance for effective dosing regimens treating S. aureus biofilm-related infections

Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection.

Linezolid resistance mediated by the cfr gene in MRSA represents a global concern. We investigated relevant phenotype differences between cfr-positive and -negative MRSA that contribute to pathogenesis, and the efficacy of linezolid-based combination therapies in murine models of bacteremia and skin and skin structure infection (SSSI). As a group, cfr-positive MRSA exhibited significantly reduced susceptibilities to the host defense peptides tPMPs, human neutrophil peptide-1 (hNP-1), and cathelicidin LL-37 (P &lt; 0.01). In addition, increased binding to fibronectin (FN) and endothelial cells paralleled robust biofilm formation in cfr-positive vs. -negative MRSA. In vitro phenotypes of cfr-positive MRSA translated into poor outcomes of linezolid monotherapy in vivo in murine bacteremia and SSSI models. Importantly, rifampicin showed synergistic activity as a combinatorial partner with linezolid, and the EC50 of linezolid decreased 6-fold in the presence of rifampicin. Furthermore, this combination therapy displayed efficacy against cfr-positive MRSA at clinically relevant doses. Altogether, these data suggest that the use of linezolid in combination with rifampicin poses a viable therapeutic alternative for bacteremia and SSSI caused by cfr-positive multidrug resistant MRSA

Clinical observation on different nucleus delivery methods in small incision cataract surgery with non-phacoemulsification

AIM: To compare the clinical effect and characteristics of lens loop extracting nucleus method, water irrigation and nucleus fragmentation within anterior chamber in small incision cataract surgery with non-phacoemulsification. <p>METHODS:There were 324 cases(324 eyes)with senile cataract randomly divided into three groups, by the lens loop extracting nucleus method(group A), water irrigation(group B)and nucleus fragmentation within anterior chamber(group C), to complete the process of nucleus division. The time of nuclear removal, complication during operation, the degree of edema of corneal endothelium on the first day after the surgery and visual acuity after surgery were observed and recorded.<p>RESULTS:The average extracting nucleus time was 45s in lens loop(group A); 34s in water irrigation(group B)and 65s in manual fragmentation(group C).The differences of average time are statistically significant(<i>P</i><0.05), and the complications in lens loop and manual fragmentation mainly are iris trauma and posterior capsular rupture; the complication in the water irrigation is hyphema. Regarding corneal edema from 0 to 1degree, the difference between group A and group B, group B and group C were statistically significant(<i>P</i><0.05). The difference between group A and group C had no statistical significance(<i>P</i>>0.05).Regarding the visual acuity on the first day after surgery, the difference between group A and group C, group B and group C were statistically significant(<i>P</i><0.05), The visual acuity on the 7th day after surgery: the difference between group B and group C were statistically significant(<i>P</i><0.05). In terms of the visual acuity on 1 momth after surgery: three groups have no statistically significant difference(<i>P</i>>0.05).<p>CONCLUSION:Manual fragmentation has obvious advantages in removing nuclear above Ⅳ grade; The water irrigation method has fewer complications with low incidence of corner edema, which is more preferable in removing the nuclear below Ⅳ grade

A preliminary study on the immune responses of HPV16-E7 by combined intranasal immunization with lymphotoxin

Objectives: Human papillomavirus (HPV) ranks the first cause of cervical cancer. Cervical cancer has high prevalence ratesin women around the world. The HPV-E7 oncoprotein is expressed in cervical cancer and is a target of developing immunotherapiesagainst HPV-associated tumors. However, the antigenicity of this protein is low. Due to this reason, potentadjuvants are required to enhance its therapeutic efficacy. This preliminary study aims to evaluate whether lymphotoxin(LT) could act as an effective immune adjuvant for HPV infection in mice models.Material and methods: Intranasal immunization was used to explore the effect of HPV-E7 and/or LT immune response.After the third intranasal immunization, the titer for the HPV-E7 antibody was detected in serum and vaginal washing fluid.Also, we assessed the expression of chemokine ligand 13 (CXCL13) and Peripheral Node Addressin (PNAd) in the lymphnodes after intranasal immunization with immunohistochemical analysis.Results: compared to HPV-E7 immunization, intranasal immunization with HPV-E7 plus LT significantly increased HPV-E7-specificserum IgG and vaginal IgA titers. Furthermore, the combined use of HPV-E7 and LT strongly induced E7-specific CTLresponses.Conclusions: LT can be effective for intranasal immunized HPV-E7 to improve E7-specific immune responses to HPV infection.It is new approach to eradicate chronic HPV infection capable of inducing an effective anti-infection method