Enhanced Gene Transfection Efficacy and Safety Through Granular Hydrogel Mediated Gene Delivery Process

Although gene therapy has made great achievements in both laboratory research and clinical translation, there are still challenges such as limited control of drug pharmacokinetics, acute toxicity, poor tissue retention, insufficient efficacy, and inconsistent clinical translation. Herein, a gene therapy gel is formulated by directly redispersing polyplex nanoparticles into granular hydrogels without any gelation pre-treatment, which provides great convenience for storage, dosing and administration. In vitro studies have shown that use of granular hydrogels can regulate the gene drug release, reduce dose dependent toxicity and help improve transfection efficacy. Moreover, the developed gene therapy gel is easy to operate and can be directly used in vitro to evaluate its synergistic efficacy with various gene delivery systems. As such, it represents a major advance over many conventional excipient-based formulations, and new regulatory strategies for gene therapy may be inspired by it

Immune features that afford protection from clinical disease versus sterilizing immunity to Bordetella pertussis infection in a nonhuman primate model of whooping cough

The respiratory bacterial infection caused by Bordetella pertussis (whooping cough) is the only vaccine-preventable disease whose incidence has been increasing over the last 3 decades. To better understand the resurgence of this infection, a baboon animal model of pertussis infection has been developed. Naïve baboons that recover from experimental pertussis infection are resistant both to clinical disease and to airway colonization when re-challenged. In contrast, animals vaccinated with acellular pertussis vaccine and experimentally challenged do not develop disease, but airways remain colonized for 4-6 weeks. We explored the possibility that the IgG antibody response to pertussis infection is qualitatively different from antibodies induced by acellular pertussis vaccination. IgG was purified from pertussis-convalescent baboons shown to be resistant to pertussis disease and airway colonization. Purified IgG contained high titers to pertussis toxin, pertactin, and filamentous hemagglutinin. This pertussis-immune IgG or control IgG was passively transferred to naïve, juvenile baboons before experimental airway pertussis inoculation. The control animal that received normal IgG developed a typical symptomatic infection including leukocytosis, cough and airway colonization for 4 weeks. In contrast, baboons that received convalescent IgG maintained normal WBC counts and were asymptomatic. However, despite remaining asymptomatic, their airways were colonized for 4-6 weeks with B. pertussis. All animals developed IgG and IgA anti-pertussis antibody responses. Interestingly, the clearance of B. pertussis from airways coincided with the emergence of a serum anti-pertussis IgA response. These studies demonstrate that passive administration of pertussis-specific IgG from previously infected animals can prevent clinical disease but does not affect prolonged airway colonization with B. pertussis. This outcome is similar to that observed following acellular pertussis vaccination. Understanding immune mechanisms—other than IgG—that are capable of preventing airway colonization with B. pertussis will be critical for developing more effective vaccines to prevent whooping cough

A Blow-Up Criterion for 3D Compressible Isentropic Magnetohydrodynamic Equations with Vacuum

In this paper, we investigate a blow-up criterion for compressible magnetohydrodynamic equations. It is shown that if density and velocity satisfy (∥ρ∥L∞(0,T;L∞)+∥u∥C([0,T];L3)∞), then the strong solutions to isentropic magnetohydrodynamic equations can exist globally over [0,T]. Notably, our analysis accommodates the presence of an initial vacuum

Detection of Aflatoxin B1 Based on a Porous Anodized Aluminum Membrane Combined with Surface-Enhanced Raman Scattering Spectroscopy

An Aflatoxin B1 (AFB1) biosensor was fabricated via an Ag nanoparticles assembly on the surface of a porous anodized aluminum (PAA) membrane. First, the Raman reporter 4-Aminothiophenol (4-ATP) and DNA (partially complementary to AFB1 aptamer) were attached to the surface of Ag nanoparticles (AgNPs) by chemical bonding to form a 4-ATP-AgNPs-DNA complex. Similarly, the surface of a PAA membrane was functionalized with an AFB1 aptamer. Then, the PAA surface was functionalized with 4-ATP-AgNPs-DNA through base complementary pairing to form AgNPs-PAA sensor with a strong Raman signal. When AFB1 was added, AgNPs would be detached from the PAA surface because of the specific binding between AFB1 and the aptamer, resulting in a reduction in Raman signals. The detection limit of the proposed biosensor is 0.009 ng/mL in actual walnut and the linear range is 0.01–10 ng/mL. The sensor has good selectivity and repeatability; it can be applied to the rapid qualitative and quantitative detection of AFB1

Surface Enhanced Raman Spectroscopy Detection of Sodium Thiocyanate in Milk Based on the Aggregation of Ag Nanoparticles

A method is developed for detecting the concentration of sodium thiocyanate (NaSCN) in milk based on surface-enhanced Raman scattering (SERS) technology. A trichloroacetic acid solution can be used to enhance the SERS signal because of its function in promoting the aggregation of Ag nanoparticles (Ag NPs). Meanwhile, the protein in milk would be precipitated as trichloroacetic acid added and the interference from protein could be reduced during the detection. In this work, the enhancement factor (EF) is 7. 56 × 105 for sodium thiocyanate in water and the limit of detection (LOD) is 0.002 mg/L. Meanwhile, this method can be used to detect the concentration of sodium thiocyanate in milk. Results show that SERS intensity increased as the concentration of sodium thiocyanate increase from 10 to 100 mg/L. The linear correlation coefficient is R2 = 0.998 and the detection limit is 0.04 mg/L. It is observed that the concentration of sodium thiocyanate does not exceed the standard in the three kinds of milk. The confirmed credibility of SERS detection is compared with conventional methods

Use of an anti-CD16 antibody for in vivo depletion of natural killer cells in rhesus macaques

Non-human primates serve as key animal models for a variety of viral infections. To evaluate the contribution of natural killer (NK) cells to the immune-mediated control of these viruses in macaque monkeys, we have described a method for depleting NK cells in vivo by administration of anti-human CD16 mouse monoclonal antibody. Using a fluorometric NK-cell cytotoxicity assay, we show that most NK-cell cytotoxicity in rhesus monkey peripheral blood mononuclear cells resides in the CD16+ and/or CD159A+ subset of lymphocytes. The anti-human CD16 antibody, 3G8, binds to subsets of rhesus monkey lymphocytes and monocytes but not to neutrophils. Intravenous administration of 10–50 mg/kg of 3G8 to normal rhesus monkeys resulted in anti-CD16 antibody persistence in the plasma for 1–3 weeks. This treatment also depleted 80–90% of CD3– CD159A+ lymphocytes, putative NK cells, from blood for at least 1 week and was associated with the loss of NK-cell cytotoxicity when evaluated by in vitro assays. Using this method, transient depletion of NK cells from two rhesus monkeys chronically infected with simian immunodeficiency virus failed to cause changes in virus replication. These studies describe a non-human primate model for in vivo NK-cell depletion and suggest a limited role for cytotoxic CD16+ NK cells in controlling AIDS virus replication during chronic infection

Modified Inguinal Microscope-Assisted Varicocelectomy under Local Anesthesia: A Non-randomised Controlled Study of 3565 Cases

Abstract Varicocele is a common abnormality, but the conventional microsurgical subinguinal varicocelectomy (CMSV) has some disadvantages. We invented Modified Inguinal Microscope-Assisted Varicocelectomy (MIMV) under local anesthesia. This study aims to evaluate MIMV by comparing it to CMSV in operating duration, time to return to normal activity, postoperative complications, achievement of natural pregnancy and improvement of semen quality for patients with infertility, pain score for those with scrotal pain, and so on. We enrolled 3089 patients who underwent MIMV and 476 who underwent CMSV in our hospital. Both the operating duration and the time to return to normal activity of MIMV was shorter than that of CMSV (P < 0.001). The recurrence rate (P < 0.001) and injury rate of vas deferens (P = 0.011) after MIMV were lower than that after CMSV. Moreover, patients with MIMV showed higher degree of satisfaction with the surgery experience and outcome than those with CMSV (P < 0.001). However, no statistical difference was found between the two groups in scores of pain due to surgery, postoperative varicose veins diameters, reflux duration, and the postoperative complications of wound infection, hydrocele, atrophy of testis, epididymitis, and scrotal hematoma. In summary, MIMV is a promising varicocelectomy and could be applied more in clinical practice

The Experimental Conditions for Quantitative Determination of Trace Elements Si, Ta and W in Rare Polymetallic Ore by Electron Probe Microanalyzer

BACKGROUND: In recent years, the study of rare polymetallic ore tends to be increasingly detailed. As one of the important research methods, electron probe quantitative analysis has made great progress in trace element measurement. During analysis, in addition to increasing the beam size and time to reduce the detection limit, more attention should be paid to removing the interference from other elements, especially the main elements. During the routine testing of rare polymetallic samples, Si, Ta, W interfere with each other. Such interference affects the analytical results of trace elements, and is not easily detected due to its low content, thus affecting the accuracy of the final conclusion.OBJECTIVES: To determine the interference relationship among Si, Ta and W under different analytical conditions.METHODS: Taking SiO2, metal Ta and W of SPI as the research object, each element was analyzed under different conditions by electron probe microanalyzer.RESULTS: In the analysis of silicate, TAP-Kα is used for Si, and LIF-Lα is recommended for Ta and W. In the analysis of niobium tantalum ore, it is suggested to use PET-Kα, PET-Mα and TAP-Mβ for Si, Ta and W, respectively; since 100% Ta will produce about 0.1% Si, therefore, the results are more accurate with the interference correction of Ta on Si.CONCLUSIONS: It is important to understand the spectral peak stripping method and the principle of element interference and spectral peak overlap, adjusting the parameters according to the actual situation to ensure the accuracy of data