Dual-Modal Immunochromatographic Test for Sensitive Detection of Zearalenone in Food Samples Based On Biosynthetic Staphylococcus aureus-Mediated Polymer Dot Nanocomposites.

The rapid detection of toxins is of great significance to food security and human health. In this work, a dual-modality immunochromatographic test (DICT) mediated by Staphylococcus aureus (SA)-biosynthesized polymer dots (SABPDs) was constructed for sensitive monitoring of zearalenone (ZEN) in agro products. The SABPDs as potent microorganism nanoscaffolds with excellent solubility, brightness, and stability were ingeniously fabricated employing hydroquinone and SA as precursors in the Schiff base reaction and a self-assembly technique. Thanks to the fact that they not only preserved an intact microsphere for loading Fc regions of monoclonal antibodies (mAbs) and the affinity of their labeled mAbs to antigen but also generated superb colorimetric-fluorescent dual signals, the versatile SABPDs manifested unique possibilities as the new carriers for dual-readout ICT with remarkable enhancement in sensitivity in ZEN screening (limit of detection = 0.036 ng/mL, which was 31-fold lower than that of traditional gold nanoparticle-based ICT). Ultimately, the proposed immunosensor performed well in millet and corn samples with satisfactory recoveries, demonstrating its potential for point-of-care testing. This work offers a bio-friendly strategy for biosynthesizing cell-based PD vehicles with bimodal signals for food safety analysis.

Polydopamine nanospheres-assisted direct PCR for rapid detection of Escherichia coli O157:H7.

Polymerase chain reaction (PCR) is one of the most common methods for rapid monitoring of foodborne pathogens; however, it requires purified nucleic acid as a template. Conventional nucleic acid purification is a time-consuming and laborious process. To overcome this, we developed polydopamine nanospheres (PDA NPs)-assisted direct PCR for detecting Escherichia coli O157:H7 (E. coli O157:H7). PDA NPs significantly enhanced PCR efficiency because of their strong interaction with PCR reagents, including polymerase and primers, thereby enabling regulation of the PCR performance. The optimal concentration and diameter for PDA NPs were 0.10 µg/µL and 504 nm, respectively. The PDA NPs-assisted direct PCR exhibited high sensitivity in E.coli O157:H7 detection. The detection limit of PDA NPs-assisted direct PCR was 6.7 × 104 CFU/mL, which was 10-fold lower than that of direct PCR (6.7 × 105 CFU/mL). Moreover, the sensor demonstrated excellent selectivity against E. coli O157:H7, with a negative reaction to eight other common pathogens. Most importantly, the PDA NPs-assisted direct PCR detected the order of 104-5 CFU/mL E.coli O157:H7 in milk, beef, and watermelon samples. No cultural enrichment was required, with the whole process taking <3 h. Therefore, PDA NPs-assisted direct PCR has tremendous potential in the rapid and sensitive detection of pathogens.

Is imidafenacin an alternative to current antimuscarinic drugs for patients with overactive bladder syndrome?

PURPOSE: Previous studies have included a limited number of randomized controlled trials (RCTs) and compared limited parameters after treatment with imidafenacin and other anticholinergic drugs (ADs) for overactive bladder syndrome (OAB), and controversy about the superiority of these ADs still remains. We aim to update the evidence and provide better clinical guidance. METHODS: A systematic search of PubMed, Embase, ClinicalTrial.gov and Cochrane Library Central Register of Controlled Trials was conducted from January 2007 to April 2019. Meta-analysis of all published RCTs comparing imidafenacin with other ADs in patients with OAB was performed. The primary outcomes were the changes in OAB symptoms and OAB symptom score (OABSS). Secondary outcomes included adverse events (AEs) and the dropout rate related to AEs. RESULTS: A total of 6 studies including 7 RCTs involving 1430 patients with mean follow-up of 23.43 weeks were included. All ADs improved OAB symptoms. Regarding efficacy, these drugs had similar efficacy in voids, urgency episodes, urgency incontinence episodes, incontinence episodes and OABSS. However, imidafenacin performed better in the reduction of nocturia episodes (MD = -0.24, 95% CI -0.44 to -0.04, P = 0.02). Moreover, imidafenacin was associated with a statistically lower dry mouth rate (RR = 0.87, 95% CI 0.75-1.00, P = 0.04), lower constipation rate (RR = 0.68, 95% CI 0.50-0.93, P = 0.01) and lower AE-related withdrawal rate (RR = 0.51, 95% CI 0.29-0.89, P = 0.02). There was no significant difference in terms of other complications. CONCLUSIONS: In conclusion, imidafenacin was comparable to other ADs in the treatment of OAB. Moreover, imidafenacin presented a lower dry mouth rate, lower constipation rate and higher adherence and persistence.

Oral Delivery of Photopolymerizable Nanogels Loaded with Gemcitabine for Pancreatic Cancer Therapy: Formulation Design, and in vitro and in vivo Evaluations.

Background: Gemcitabine (GEM) faces challenges of poor oral bioavailability and extensive first-pass metabolism. Currently, only injectable formulations are available for clinical use. Hence, there is an urgent demand for the development of advanced, efficacious, and user-friendly dosage forms to maintain its status as the primary treatment for pancreatic ductal adenocarcinoma (PDAC). Nanogels (NGs) offer a novel oral drug delivery system, ideal for hydrophilic compounds like GEM. This study aims to develop NGs tailored for GEM delivery, with the goal of enhancing cellular uptake and gastrointestinal permeability for improved administration in PDAC patients. Methods: We developed cross-linked NGs via photopolymerization of methacryloyl for drug delivery of GEM. We reveal characterization, cytotoxicity, and cellular uptake studies in Caco-2 and MIA PaCa-2 cells. In addition, studies of in vitro permeability and pharmacokinetics were carried out to evaluate the bioavailability of the drug. Results: Our results show NGs, formed via photopolymerization of methacryloyl, had a spherical shape with a size of 233.91±7.75 nm. Gemcitabine-loaded NGs (NGs-GEM) with 5% GelMA exhibited efficient drug loading (particle size: 244.07±19.52 nm). In vitro drug release from NGs-GEM was slower at pH 1.2 than pH 6.8. Cellular uptake studies indicated significantly enhanced uptake in both MIA PaCa-2 and Caco-2 cells. While there was no significant difference in GEM's AUC and Cmax between NGs-GEM and free-GEM groups, NGs-GEM showed markedly lower dFdU content (10.07 hr∙µg/mL) compared to oral free-GEM (19.04 hr∙µg/mL) after oral administration (p<0.01), highlighting NGs' efficacy in impeding rapid drug metabolism and enhancing retention. Conclusion: In summary, NGs enhance cellular uptake, inhibit rapid metabolic degradation of GEM, and prolong retention after oral administration. These findings suggest NGs-GEM as a promising candidate for clinical use in oral pancreatic cancer therapy.

Bimetallic-MOF-derived crystalline-amorphous interfacial sites for highly efficient nitrite sensing.

Considering the importance of rapid and effective detection of nitrite in food samples, herein, we report a multistep heterophase synthetic strategy for constructing crystalline-amorphous zinc/cobalt iron porous nanosheets (C-A Zn/Co-Fe PNSs) on carbon cloth. Notably, the C-A Zn/Co-Fe PNSs@CC electrochemical interface consists of interlaced carbon fibers with many uniformly distributed hybrid nanosheets containing crystalline-amorphous interfacial sites. This particular hybrid structure permits local enrichment of nitrite for enhanced nitrite capture efficiency, laying a solid foundation for the ultrasensitive detection of nitrite. In proof-of-concept experiments, we verified that C-A Zn/Co-Fe PNSs@CC could be used to analyze nitrite with good sensitivity and reproducibility. It is worth mentioning that an ultra-low LOD of 0.44 µM was obtained for the detection of nitrite. The designed electrochemical sensor worked well in complex samples such as sausages and tap water under optimal parameters.

Innovative ratiometric optical strategy: Nonconjugated polymer dots based fluorescence-scattering dual signal output for sensing mercury ions.

A new ratiometric platform was developed for sensing Hg2+, which combined fluorescence and scattering simultaneously. This ratiometric strategy reflected superiorities over conventional methods, since the two independent signals at irrelevant categories meet the requirements of sufficient wavelength separation, stimulation under one excitation, and collection on single instrument. Herein, nonconjugated polymer dots (N-PDs) were served as the recognition unit for Hg2+ with turn-off fluorescence and turn-on scattering. Additionally, two signal collection tactics were proposed to achieve fluorescence and scattering in a window: one was to record down-conversion fluorescence and second-order scattering spectra (FL@SOS), and the other was to gather the fluorescence excited by second-order diffraction light and first-order scattering (SODL-FL@FOS). This ratiometric sensor exhibited outstanding performance toward Hg2+ in the range of 0.1-50 µM with the detection limit of 27 nM. By contrast, the present proposal provided a more ingenious and scalable way to construct ratiometric sensor than traditional approach.

Metal-polydopamine framework based lateral flow assay for high sensitive detection of tetracycline in food samples.

Gold nanoparticles (AuNPs)-based lateral flow assay (LFA) enables a rapid detection of tetracycline (TET) in food samples but suffers from low sensitivity. Herein, metal-polydopamine framework (MPF), as a label, was employed to load monoclonal antibodies (mAbs) directly as the probe in LFA for highly sensitive sensing of TET. Combining zeolitic imidazolate framework (ZIF-67) and polydopamine (PDA), a stable MPF with large size, well water-dispersible, excellent affinity and optical properties was prepared through a versatile layer-by-layer assembly (LLA) strategy. Under optimized conditions, the biosensor (MPF-LFA) exhibited a great linear relationship in the range of 0.09-6 ng/mL and a detection limit of 0.045 ng/mL for TET detection, which was over 66-fold more sensitive than traditional AuNPs based LFA. Furthermore, the MPF-LFA was successfully applied to the screening of TET in fish, chicken, milk and shrimp samples with satisfied recoveries from 91% to 114%.

Novel Mutation of Cleidocranial Dysplasia-related Frameshift Runt-related Transcription Factor 2 in a Sporadic Chinese Case.

BACKGROUND: Cleidocranial dysplasia (CCD) is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of the fontanels, midface hypoplasia, short stature, and delayed eruption of permanent and supernumerary teeth. Previous studies reported a connection between CCD and the haploinsufficiency of runt-related transcription factor 2 (RUNX2). Here, we report a sporadic Chinese case presenting typical symptoms of CCD. METHODS: We made genetic testing on this sporadic Chinese case and identified a novel RUNX2 frameshift mutation: c.1111dupT. In situ immunofluorescence microscopy and osteocalcin promoter luciferase assay were performed to compare the functions of the RUNX2 mutation with those of wild-type RUNX2. RESULTS: RUNX2 mutation was observed in the perinuclear region, cytoplasm, and nuclei. In contrast, wild-type RUNX2 was confined in the nuclei, which indicated that the subcellular compartmentalization of RUNX2 mutation was partially perturbed. The transactivation function on osteocalcin promoter of the RUNX2 mutation was obviously abrogated. CONCLUSIONS: We identified a sporadic CCD patient carrying a novel insertion/frameshift mutation of RUNX2. This finding expanded our understanding of CCD-related phenotypes.

The potential adjuvanticity of quaternized chitosan hydrogel based microparticles for porcine reproductive and respiratory syndrome virus inactivated vaccine.

Infectious diseases possess a big threat to the livestock industry worldwide. Currently, inactivated veterinary vaccines have attracted much attention to prevent infection due to their safer profile compared to live attenuated vaccine. However, its intrinsic poor immunogenicity demands the incorporation of an adjuvant. Mineral oil based adjuvant (Montanide™ ISA206) was usually used to potentiate the efficacy of veterinary vaccines. However, ISA206 could not induce robust cellular immune responses, which was very important in controlling virus replication and clearing the infected cells. Moreover, mineral oil would result in severe side effects. To improve both the humoral and cellular immune responses of porcine reproductive and respiratory syndrome virus (PRRSV) inactivated vaccine, we developed pH-sensitive and size-controllable quaternized chitosan hydrogel microparticles (Gel MPs) without using chemical cross linking agent. Gel MPs, ionic cross-linked with glycerophosphate (GP), were biocompatible and could efficiently adsorb the inactivated PRRSV vaccine with a loading capacity of 579.05µg/mg. After intramuscular immunization in mice, results suggested that Gel MPs elicited significantly higher cell-mediated immune responses and comparable humoral immune responses compared to ISA 206. Regarding the biocompatibility, safety and effectiveness, Gel MPs would be a promising candidate to enhance the efficacy of veterinary vaccine.

[Chin morphology in subjects with different vertical skeletal craniofacial pattern].

OBJECTIVE: To evaluate whether there is difference with regard to chin morphology in subjects with different vertical skeletal craniofacial pattern and the relationship among them. METHODS: The sample was composed of 80 adolescents who denied orthodontic treatment history and presented Class I skeletal pattern, aged (12.69+/-0.70) years. They were divided into three groups according to mandibular plane angle: High angle group (21 cases, FH/MP> or = 32 degrees), average angle group(43 cases, 22 degrees

[Treatment of OSAS with modified twin-block advancement appliances].

OBJECTIVE: To introduce a new modified twin-block advancement appliance and investigate the effects on respiratory variables in patients with OSAS. METHODS: 29 patients with OSAS participated in the study and were fitted with modified twin-block appliances to hold the mandible in an anterior and inferior position. Polysomnography was performed with and without appliance insertion. And questionnaires were used for registration of patients subjective symptoms. Pair-t analysis was used to evaluate the effects of appliances in patients with OSAS. RESULTS: 26 patients responded to the appliance therapy. Apnea-hypopnea index, apnea index and hypopnea index were reduced significantly (P < 0.01). Lowest arterial oxygen saturation improved significantly (P < 0.01). Discomfort with mandibular advancement disappeared within one week. CONCLUSIONS: Modified twin-block advancement appliance is a conservative, successful treatment alternative that could benefit patients suffered from OSAS.