Heart failure (HF) is the end-stage of cardiovascular diseases, which is associated with a high mortality rate and high readmission rate. Household early diagnosis and real-time prognosis of HF at bedside are of significant importance. Here, we developed a highly sensitive and quantitative household prognosis platform (termed as UC-LFS platform), integrating a smartphone-based reader with multiplexed upconversion fluorescent lateral flow strip (LFS). Dual-color core-shell upconversion nanoparticles (UCNPs) were synthesized as probes for simultaneously quantifying two target antigens associated with HF, i.e., brain natriuretic peptide (BNP) and suppression of tumorigenicity 2 (ST2). With the fluorescent LFS, we achieved the specific detection of BNP and ST2 antigens in spiked samples with detection limits of 5 pg/mL and 1 ng/mL, respectively, both of which are of one order lower than their clinical cutoff. Subsequently, a smartphone-based portable reader and an analysis app were developed, which could rapidly quantify the result and share prognosis results with doctors. To confirm the usage of UC-LFS platform for clinical samples, we detected 38 clinical serum samples using the platform and successfully detected the minimal concentration of 29.92 ng/mL for ST2 and 17.46 pg/mL for BNP in these clinical samples. Comparing the detection results from FDA approved clinical methods, we obtained a good linear correlation, indicating the practical reliability and stability of our developed UC-LFS platform. Therefore, the developed UC-LFS platform is demonstrated to be highly sensitive and specific for sample-to-answer prognosis of HF, which holds great potential for risk assessment and health monitoring of post-treatment patients at home.
Periodontitis is an inflammatory disease negatively affecting up to 15% of adults worldwide. Periodontal ligament stem cells (PDLSCs) hold great promises for periodontal tissue regeneration, where it is necessary to find proper extracellular matrix (ECM) materials (e.g., composition, concentration). In this study, we proposed a bioprinting-based approach to generate nano-liter sized three-dimensional (3D) cell-laden hydrogel array with gradient of ECM components, through controlling the volume ratio of two hydrogels, such as gelatin methacrylate (GelMA) and poly(ethylene glycol) (PEG) dimethacrylate. The resulting cell-laden array with a gradient of GelMA/PEG composition was used to screen human PDLSC response to ECM. The behavior (e.g., cell viability, spreading) of human PDLSCs in GelMA/PEG array were found to be depended on the volume ratios of GelMA/PEG, with cell viability and spreading area decreased along with increasing the ratio of PEG. The developed approach would be useful for screening cell-biomaterial interaction in 3D and promoting regeneration of functional tissue.
Background
Schistosoma mansoni tetraspanin 2 (Sm-TSP-2) has been shown to be strongly recognized by IgG1 and IgG3 antibodies from individuals putatively resistant to schistosome infection, but not chronically infected people, and to induce high levels of protection against challenge infection in the murine model of schistosomiasis. Amplification by PCR of homologous sequences from male and female S. japonicum worms showed the presence of 7 different clusters or subclasses of S. japonicum TSP-2. We determined the protective efficacy of one subclass – Sj-TSP-2e.Methodology/Principal FindingsFollowing the alignment of 211 cDNAs, we identified 7 clusters encoding S. japonicum TSP-2 (Sj-TSP-2) based on sequence variation in the large extracellular loop (LEL) region with differing frequency of transcription in male and female worms. Quantitative PCR analysis revealed elevated expression of Sj-TSP-2 in adult worms compared with other life cycle stages. We expressed in E. coli the LEL region of one of the clusters which exhibited a high frequency of transcription in female worms, and showed the purified recombinant protein (Sj-TSP-2e) was recognised by 43.1% of sera obtained from confirmed schistosomiasis japonica patients. Vaccination of mice with the recombinant protein induced high levels of IgG1 and IgG2 antibodies, but no consistent protective efficacy against challenge infection was elicited in three independent trials.Conclusions/SignificanceThe highly polymorphic nature of the Sj-TSP-2 gene at the transcriptional level may limit the value of Sj-TSP-2 as a target for future S. japonicum vaccine development.
In situ photopolymerized hydrogel dressings create minimally invasive methods that offer advantages over the use of preformed dressings such as conformability in any wound bed, convenience of application, and improved patient compliance and comfort. Here, we report an in situ-formed hydrogel membrane through ultraviolet cross-linking of a photocross-linkable azidobenzoic hydroxypropyl chitosan aqueous solution. The hydrogel membrane is stable, flexible, and transparent, with a bulk network structure of smoothness, integrity, and density. Fluid uptake ability, water vapor transmission rate, water retention, and bioadhesion of the thus resulted hydrogel membranes (0.1 mm thick) were determined to range from 97.0-96.3%, 2,934-2,561 g/m(2)/day, 36.69-22.94% (after 6 days), and 4.8-12.3 N/cm(2), respectively. These data indicate that the hydrogel membrane can maintain a long period of moist environment over the wound bed for enhancing reepithelialization. Specifically, these properties of the hydrogel membrane were controllable to some extent, by adjusting the substitution degree of the photoreactive azide groups. The hydrogel membrane also exhibited barrier function, as it was impermeable to bacteria but permeable to oxygen. In vitro experiments using two major skin cell types (dermal fibroblast and epidermal keratinocyte) revealed the hydrogel membrane have neither cytotoxicity nor an effect on cell proliferation. Taken together, the in situ photocross-linked azidobenzoic hydroxypropyl chitosan hydrogel membrane has a great potential in the management of wound healing and skin burn.
We prepared two types of cholesterol hydrophobically modified pullulan nanoparticles (CHP) and carboxyethyl hydrophobically modified pullulan nanoparticles (CHCP) substituted with various degrees of cholesterol, including 3.11, 6.03, 6.91 and 3.46 per polymer, and named CHP−3.11, CHP−6.03, CHP−6.91 and CHCP−3.46. Dynamic laser light scattering (DLS) showed that the pullulan nanoparticles were 80–120 nm depending on the degree of cholesterol substitution. The mean size of CHCP nanoparticles was about 160 nm, with zeta potential −19.9 mV, larger than CHP because of the carboxyethyl group. A greater degree of cholesterol substitution conferred greater nanoparticle hydrophobicity. Drug-loading efficiency depended on nanoparticle hydrophobicity, that is, nanoparticles with the greatest degree of cholesterol substitution (6.91) showed the most drug encapsulation efficiency (90.2%). The amount of drug loading increased and that of drug release decreased with enhanced nanoparticle hydrophobicity. Nanoparticle surface-negative charge disturbed the amount of drug loading and drug release, for an opposite effect relative to nanoparticle hydrophobicity. The drug release in pullulan nanoparticles was higher pH 4.0 than pH 6.8 media. However, the changed drug release amount was not larger for negative-surface nanoparticles than CHP nanoparticles in the acid release media. Drug release of pullulan nanoparticles was further slowed with human serum albumin complexation and was little affected by nanoparticle hydrophobicity and surface negative charge.
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