Temporal gene expression profiling during early-stage traumatic temporomandibular joint bony ankylosis in a sheep model.

BACKGROUND: Investigating the molecular biology underpinning the early-stage of traumatic temporomandibular joint (TMJ) ankylosis is crucial for discovering new ways to prevent the disease. This study aimed to explore the dynamic changes of transcriptome from the intra-articular hematoma or the newly generated ankylosed callus during the onset and early progression of TMJ ankylosis. METHODS: Based on a well-established sheep model of TMJ bony ankylosis, the genome-wide microarray data were obtained from samples at postoperative Days 1, 4, 7, 9, 11, 14 and 28, with intra-articular hematoma at Day 1 serving as controls. Fold changes in gene expression values were measured, and genes were identified via clustering based on time series analysis and further categorised into three major temporal classes: increased, variable and decreased expression groups. The genes in these three temporal groups were further analysed to reveal pathways and establish their biological significance. RESULTS: Osteoblastic and angiogenetic genes were found to be significantly expressed in the increased expression group. Genes linked to inflammation and osteoclasts were found in the decreased expression group. The various biological processes and pathways related to each temporal expression group were identified, and the increased expression group comprised genes exclusively involved in the following pathways: Hippo signaling pathway, Wnt signaling pathway and Rap 1 signaling pathway. The decreased expression group comprised genes exclusively involved in immune-related pathways and osteoclast differentiation. The variable expression group consisted of genes associated with DNA replication, DNA repair and DNA recombination. Significant biological pathways and transcription factors expressed at each time point postoperatively were also identified. CONCLUSIONS: These data, for the first time, presented the temporal gene expression profiling and reveal the important process of molecular biology in the early-stage of traumatic TMJ bony ankylosis. The findings might contributed to identifying potential targets for the treatment of TMJ ankylosis.

Eco-Corona Dictates Mobility of Nanoplastics in Saturated Porous Media: The Critical Role of Preferential Binding of Macromolecules.

Nanoplastics are an increasing environmental concern. In aquatic environments, nanoplastics will acquire an eco-corona by interacting with macromolecules (e.g., humic substances and extracellular polymeric substances (EPS)). Here, we show that the properties of the eco-corona and, consequently, its ability to enhance the transport of nanoplastics vary significantly with the surface functionality of nanoplastics and sources of macromolecules. The eco-corona derived from the EPS of Gram-negative Escherichia coli MG1655 enhances the transport of polystyrene (PS) nanospheres in saturated porous media to a much greater extent than the eco-corona derived from soil humic acid and fulvic acid. In comparison, the eco-corona from all three sources significantly enhance the transport of carboxylated PS (HOOC-PS). We show that the eco-corona inhibits the deposition of the two types of nanoplastics to the porous media mainly via steric repulsion. Accordingly, an eco-corona consisting of a higher mass of larger-sized macromolecules is generally more effective in enhancing transport. Notably, HOOC-PS tends to acquire macromolecules of lower hydrophobicity than PS. The more disordered and flexible structures of such macromolecules may result in greater elastic repulsion between the nanoplastics and sand grains and, consequently, greater transport enhancement. The findings of this study highlight the critical role of eco-corona formation in regulating the mobility of nanoplastics, as well as the complexity of this process.

Biodegradation of polyurethane by the microbial consortia enriched from landfill.

Polyurethanes (PU) are one of the most used categories of plastics and have become a significant source of environmental pollutants. Degrading the refractory PU wastes using environmentally friendly strategies is in high demand. In this study, three microbial consortia from the landfill leachate were enriched using PU powder as the sole carbon source. The consortia efficiently degraded polyester PU film and accumulated high biomass within 1 week. Scanning electron microscopy, Fourier transform infrared spectroscopy, and contact angle analyses showed significant physical and chemical changes to the PU film after incubating with the consortia for 48 h. In addition, the degradation products adipic acid and butanediol were detected by high-performance liquid chromatography in the supernatant of the consortia. Microbial composition and extracellular enzyme analyses revealed that the consortia can secrete esterase and urease, which were potentially involved in the degradation of PU. The dominant microbes in the consortia changed when continuously passaged for 50 generations of growth on the PU films. This work demonstrates the potential use of microbial consortia in the biodegradation of PU wastes. KEY POINTS: • Microbial consortia enriched from landfill leachate degraded polyurethane film. • Consortia reached high biomass within 1 week using polyurethane film as the sole carbon source. • The consortia secreted potential polyurethane-degrading enzymes.

Association between dental visit behavior and mortality: a nationwide longitudinal cohort study from NHANES.

OBJECTIVES: The benefits of professional dental treatment for oral diseases have been widely investigated. However, it is unclear whether professional dental treatment provides additional benefits for improving general health. MATERIALS AND METHODS: Data were obtained from the US National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 and 2011 to 2018 cycles. A total of 36,174 participants were included and followed-up for mortality until December 31, 2019. Dental visit behavior was defined as the time interval of last dental visit (TIDV, < 0.5 year, 0.5-1 year, 1-2 years, 2-5 years, and > 5 years) and the main reasons of the last dental visit (treatment, examination, and other reasons). The Cox proportional risk model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Compared with participants with time interval of less than 0.5 year, the multivariate-adjusted HRs and 95%CI for participants with time interval of more than 5 years were 1.45 (1.31, 1.61) for all-cause mortality (P trend < 0.0001), 1.49 (1.23, 1.80) for cardiovascular diseases mortality (P trend = 0.0009) and 1.53 (1.29, 1.81) for cancer mortality (P trend = 0.013). Compared with dental visit for examination, participants who had their dental visit for treatment had higher risk for mortality. For participants with dental visit for examination, TIDV of less than 1 year showed lower risk for mortality, whereas TIDV of less than 0.5 year is recommend for population with dental visit for treatment. CONCLUSIONS: Poor dental visit behavior is associated with an increased risk of mortality. Further well-designed studies are needed to confirm the association between professional dental visit and mortality. CLINICAL RELEVANCE: This study highlights the potential benefits of regular dental visits in maintaining general health.

Structural Health Monitoring in Long-Span Steel Structures Based on the BeiDou Navigation Satellite System.

The BeiDou navigation satellite system (BDS) provides precise positioning, navigation, and timing (PNT) services in the Asia-Pacific Region, but the BDS-based structural health monitoring (SHM) approach (SHM) is rarely studied, especially in civil engineering. Moreover, how BDS can be applied to complete the tasks of SHM in a real project is also not fully investigated, especially working in conjunction with other techniques. This study aims to propose a BDS-based approach for SHM in civil engineering. The performance of the proposed approach is investigated through a case study-the Tianhan Grand Theater (TGT). A specific Tianhan system corresponding to BDS is proposed to complete the SHM tasks of TGT. Based on the collected data, the trusses with maximum displacement and stress are found by BDS to evaluate structural health in the construction stage. The results show that the maximum displacement and stress have certain safety reserves and meet the requirements of the specifications and regulations. Thus, BDS can satisfactorily complete the tasks of SHM for Long-span steel structures. This study gives a clear view to engineers and researchers that how to apply BDS in structural construction and provides a valuable real case for evaluating the performance of BDS in SHM.

N-Terminal Lysozyme Conjugation to a Cationic Polymer Enhances Antimicrobial Activity and Overcomes Antimicrobial Resistance.

Microbial resistance to antibiotics is one of the greatest global healthcare challenges. There is an urgent need to develop effective strategies to overcome antimicrobial resistance. We, herein, report photoinduced in situ growth of a cationic polymer from the N-terminus of lysozyme. The attachment of the cationic polymer improves the proteolytic and thermal stability of lysozyme. Notably, the conjugate can efficiently overcome lysozyme resistance in Gram-positive bacteria and antibiotics-resistance in Gram-negative bacteria, which may be ascribed to the synergistic interactions of lysozyme and the cationic polymer with the bacteria to disrupt their cell membranes. In a rat periodontitis model, the lysozyme-polymer conjugate not only greatly outperforms lysozyme in therapeutic efficacy but also is superior to minocycline hydrochloride, which is the gold standard for periodontitis therapy. These findings may provide an efficient strategy to dramatically enhance the antimicrobial activities of lysozyme and pave a way to overcome antimicrobial resistance.

Design of an Oxygen-Tolerant Photo-RAFT System for Protein-Polymer Conjugation Achieving High Bioactivity.

Protein-polymer conjugates have significant potential in pharmaceutical and biomedical applications. To enable their widespread use, robust conjugation techniques are crucial. This study introduces a photo-initiated reversible addition-fragmentation chain-transfer (Photo-RAFT) polymerization system that exhibits excellent oxygen tolerance. This system allows for the synthesis of protein-polymer conjugates with high bioactivity under mild and aerobic conditions. Three photocatalytic systems utilizing Eosin Y (EY) as the photocatalyst with two different cocatalysts (ascorbic acid and triethanolamine) were investigated, each generating distinct reactive oxygen species (ROS) such as singlet oxygen, superoxide, hydrogen peroxide, and hydroxyl radicals. The impact of these ROS on three model proteins (lysozyme, albumin, and myoglobin) was evaluated, demonstrating varying bioactivities based on the ROS produced. The EY/TEOA system was identified as the optimal photo-RAFT initiating system, enabling the preparation of protein-polymer conjugates under aerobic conditions while maintaining high protein enzymatic activity. To showcase the potential of this approach, lysozyme-poly(dimethylaminoethyl acrylate) conjugates were successfully prepared and exhibited enhanced antimicrobial property against Gram-positive and Gram-negative bacteria.

Photo-RAFT Polymerization for Hydrogel Synthesis through Barriers and Development of Light-Regulated Healable Hydrogels under NIR Irradiation.

We report an aqueous and near-infrared (NIR) light mediated photoinduced reversible addition-fragmentation chain transfer (photo-RAFT) polymerization system catalyzed by tetrasulfonated zinc phthalocyanine (ZnPcS4 - ) in the presence of peroxides. Taking advantage of its fast polymerization rates and high oxygen tolerance, this system is successfully applied for the preparation of hydrogels. Exploiting the enhanced penetration of NIR light, photoinduced gelation is effectively performed through non-transparent biological barriers. Notably, the RAFT agents embedded in these hydrogel networks can be reactivated on-demand, enabling the hydrogel healing under NIR light irradiation. In contrast to the minimal healing capability (<15 %) of hydrogels prepared by free radical polymerization (FRP), RAFT-mediated networks display more than 80 % recovery of tensile strength. Although healable polymer networks under UV and blue lights have already been established, this work is the first photochemistry system using NIR light, facilitating photoinduced healing of hydrogels through thick non-transparent barriers.

A Dual Sensing Platform for Human Exhaled Breath Enabled by Fe-MIL-101-NH2 Metal-Organic Frameworks and its Derived Co/Ni/Fe Trimetallic Oxides.

Limited by the insufficient active sites and the interference from breath humidity, designing reliable gas sensing materials with high activity and moisture resistance remains a challenge to analyze human exhaled breath for the translational application of medical diagnostics. Herein, the dual sensing and cooperative diagnosis is achieved by utilizing metal-organic frameworks (MOFs) and its derivative. The Fe-MIL-101-NH2 serves as the quartz crystal microbalance humidity sensing layer, which exhibits high selectivity and rapid response time (16 s/15 s) to water vapor. Then, the Co2+ and Ni2+ cations are further co-doped into Fe-MIL-101-NH2 host to obtain the derived Co/Ni/Fe trimetallic  oxides (CoNiFe-MOS-n). The chemiresistive CoNiFe-MOS-n sensor displays the high sensitivity (560) and good selectivity to acetone, together with a lower original resistance compared with Fe2 O3 and NiFe2 O4 . Moreover, as a proof-of-concept application, synergistic integration of Fe-MIL-101-NH2 and derived CoNiFe-MOS-n is carried out. The Fe-MIL-101-NH2 is applied as moisture sorbent materials, which realize a sensitivity compensation of CoNiFe-MOS-n sensors for the detection of acetone (biomarker gas of diabetes). The findings provide an insight for effective utilization of MOFs and the derived materials to achieve a trace gas detection in exhaled breath analysis.

Binding of Proteins to Copolymers of Varying Charges and Hydrophobicity: A Molecular Mechanism and Computational Strategies.

Because of their ability to selectively bind to a target protein, copolymer nanoparticles (NPs) containing a selected combination of hydrophobic and charged groups have been frequently reported as potent antibody-like analogues. However, due to the intrinsic disorder of the copolymer NP in terms of its random monomer sequence and the cross-linked copolymer matrix, the copolymer NP is indeed strikingly different from a well-folded protein antibody and the complexation between the copolymer NP and a target protein is likely not due to a lock-key type of interaction but possibly due to a novel and unexplored molecular mechanism. Here, we study a key biomarker protein, vimentin, interacting with a set of random copolymer chains using implicit-water explicit-ion coarse-grained (CG) molecular dynamics (MD) simulations along with biolayer interferometry (BLI) analysis. Due to the charge and hydrophobicity anisotropy on the vimentin dimer (VD) surface, a set of bound copolymers are found inhomogenously adsorbed on the VD, with energetic heterogeneity for different binding sites and cooperative effect in the adsorption. Increasing the charge or hydrophobicity of the copolymer may have different consequences on the adsorption. In this study, we found that with more copolymer charges, the protein coverage increases for copolymers of low hydrophobicity and decreases of high hydrophobicity, which is explained by the distribution and size of various functional patches on the VD in loading those copolymers. Employing a coverage-dependent Langmuir model, we propose a simulation protocol to address the full profile of the copolymer binding free energy through the fit to the simulated binding isotherm. The obtained results correlate well with those from the BLI experiment, indicating the significance of this method for the rational design of the copolymer NP with engineered protein binding affinity.

Valorization of Polyethylene Terephthalate to Muconic Acid by Engineering Pseudomonas Putida.

Plastic waste is rapidly accumulating in the environment and becoming a huge global challenge. Many studies have highlighted the role of microbial metabolic engineering for the valorization of polyethylene terephthalate (PET) waste. In this study, we proposed a new conceptual scheme for upcycling of PET. We constructed a multifunctional Pseudomonas putida KT2440 to simultaneously secrete PET hydrolase LCC, a leaf-branch compost cutinase, and synthesize muconic acid (MA) using the PET hydrolysate. The final product MA and extracellular LCC can be separated from the supernatant of the culture by ultrafiltration, and the latter was used for the next round of PET hydrolysis. A total of 0.50 g MA was produced from 1 g PET in each cycle of the whole biological processes, reaching 68% of the theoretical conversion. This new conceptual scheme for the valorization of PET waste should have advantages over existing PET upcycling schemes and provides new ideas for the utilization of other macromolecular resources that are difficult to decompose, such as lignin.

A novel liposome-polymer hybrid nanoparticles delivering a multi-epitope self-replication DNA vaccine and its preliminary immune evaluation in experimental animals.

DNA vaccine is an attractive immune platform for the prevention and treatment of infectious diseases, but existing disadvantages limit its use in preclinical and clinical assays, such as weak immunogenicity and short half-life. Here, we reported a novel liposome-polymer hybrid nanoparticles (pSFV-MEG/LNPs) consisting of a biodegradable core (mPEG-PLGA) and a hydrophilic shell (lecithin/PEG-DSPE-Mal 2000) for delivering a multi-epitope self-replication DNA vaccine (pSFV-MEG). The pSFV-MEG/LNPs with optimal particle size (161.61 ±â€¯15.63 nm) and high encapsulation efficiency (87.60 ±â€¯8.73%) induced a strong humoral (3.22-fold) and cellular immune responses (1.60-fold) compared to PBS. Besides, the humoral and cellular immune responses of pSFV-MEG/LNPs were 1.58- and 1.05-fold than that of pSFV-MEG. All results confirmed that LNPs was a very promising tool to enhance the humoral and cellular immune responses of pSFV-MEG. In addition, the rational design and delivery platform can be used for the development of DNA vaccines for other infectious diseases.

Absorbance or organization into ankylosis: a microarray analysis of haemarthrosis in a sheep model of temporomandibular joint trauma.

BACKGROUND: Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles. MATERIAL/METHODS: Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1_0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR. RESULTS: We found 268, 223 and 17 DEGs at least twofold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-ß), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction. CONCLUSIONS: Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. The study will contribute to explaining why few injured TMJs ankylose and most do not from the molecular level.

Comparative Effectiveness of Drug-Coated Balloon vs Balloon Angioplasty for the Treatment of Arteriovenous Fistula Stenosis: A Meta-analysis.

Purpose: To compare the effectiveness and safety outcomes of drug-coated balloon angioplasty (DCBA) vs conventional balloon angioplasty (BA) for arteriovenous fistula (AVF) stenosis. Materials and Methods: A systematic review was conducted of PubMed and Embase databases from 1966 to May 2019 to identify English-language articles evaluating DCBA vs BA for the treatment of AVF stenosis. Data extracted from each study were synthesized to evaluate target lesion revascularization (TLR), technical success, and mortality for the 2 approaches. Meta-analyses were performed on these outcomes using random effects models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Twelve studies [6 randomized controlled trials (RCTs) and 6 cohort studies] comprising 979 patients were included in this meta-analysis. The pooled results showed that AVFs treated with DCBA had significantly fewer TLRs at 6 months (OR 0.31, 95% CI 0.14 to 0.69, p=0.004) and 12 months (OR 0.45, 95% CI 0.21 to 0.97, p=0.04) than BA. The 2 approaches had similar technical success rates (OR 0.22, 95% CI 0.03 to 1.43, p=0.11). Additionally, the pooled OR of 12-month mortality was 0.71 (95% CI 0.20 to 2.51, p=0.60), indicating no significant difference between DCBA and BA. Subgroup analysis based on study design showed the superiority of DCBA to BA in cohort studies but not RCTs, which had high heterogeneity. Significant publication bias was found in the cohort studies. Conclusion: In de novo or recurrent AVF stenosis, DCBA appears to be an effective procedure associated with lower 6- and 12-month TLR compared with BA. However, larger and randomized controlled studies are warranted to draw definitive conclusions.

Gradient Polymerization-Induced Self-Assembly: A One-Step Approach.

In this work, the authors report a novel single-step, one-pot process for the synthesis of self-assembled nanoparticles using a polymerization-induced self-assembly (PISA) mechanism. In contrast to conventional approaches employing a pre-formed macromolecular stabilizer, the disparate reactivities between two monomers, oligo(ethylene glycol) methyl ether methacrylate (OEGMA) and diacetone acrylamide (DAAm), are exploited instead to synthesize a gradient copolymer directly in aqueous solution. Due to the hydrophobicity of poly(DAAm), these gradient copolymers can self-assemble in situ to form spheres and worms stabilized by the OEGMA residues. A surprisingly broad range of parameters are identified in which the worm morphology can be stabilized, which is highlighted by significant gelation of the reaction mixture in situ. This single-step gradient copolymerization approach to PISA is more efficient than conventional two-step syntheses. These results demonstrate improved reproducibility owing to the production of self-assembled nanoparticles directly in a one-pot and single-step synthesis.

Aging Significantly Affects Mobility and Contaminant-Mobilizing Ability of Nanoplastics in Saturated Loamy Sand.

Plastic debris, in particular, microplastics and nanoplastics, is becoming an emerging class of pollutants of global concern. Aging can significantly affect the physicochemical properties of plastics, and therefore, may influence the fate, transport, and effects of these materials. Here, we show that aging by UV or O3 exposure drastically enhanced the mobility and contaminant-mobilizing ability of spherical polystyrene nanoplastics (PSNPs, 487.3 ± 18.3 nm in diameter) in saturated loamy sand. Extended Derjaguin-Landau-Verwey-Overbeek calculations and pH-dependent transport experiments demonstrated that the greater mobility of the aged PSNPs was mainly the result of surface oxidation of the nanoplastics, which increased not only the surface charge negativity, but more importantly, hydrophilicity of the materials. The increased mobility of the aged PSNPs significantly contributed to their elevated contaminant-mobilizing abilities. Moreover, aging of PSNPs enhanced the binding of both nonpolar and polar contaminants, further increasing the contaminant-mobilizing ability of PSNPs. Interestingly, aging enhanced binding of nonpolar versus polar compounds via distinctly different mechanisms: increased binding of nonpolar contaminants (tested using pyrene) was mainly the result of the modification of the polymeric structure of PSNPs that exacerbated slow desorption kinetics; for polar compounds (4-nonylphenol), aging induced changes in surface properties also resulted in irreversible adsorption of contaminants through polar interactions, such as hydrogen bonding. The findings further underline the significant effects of aging on environmental fate and implications of nanoplastics.

Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells.

Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC50 values of CD20-SA-NPs were reduced to 5.7 and 2.6 µg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg-1·d-1, iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.

FcγRIIB receptor-mediated apoptosis in macrophages through interplay of cadmium sulfide nanomaterials and protein corona.

Humans are likely exposed to cadmium sulfide nanomaterials (CdS NMs) due to the increasing environmental release and in vivo application of these materials, which tend to accumulate and cause toxic effects in human lungs, particularly by interrupting the physiological functions of macrophage cells. Here, we showed that protein corona played an essential role in determining cellular uptake and cytotoxicity of CdS NMs in macrophages. Protein-coated CdS NMs enhanced the expression of FcγRIIB receptors on the cell surface, and the interaction between this receptors and proteins inhibited cellular uptake of CdS NMs while triggering cell apoptosis via the AKT/Caspase 3 signaling pathway. Cytotoxicity of CdS NMs was greatly alleviated by coating the nanomaterials with polyethylene glycol (PEG), because PEG decreased the adsorption of proteins that interact with the FcγRIIB receptors on cell surface. Overall, our research demonstrated that surface modification, particularly protein association, significantly affected cellular response to CdS NMs, and cellular uptake may not be an appropriate parameter for predicting the toxic effects of these nanomaterials in human lungs.

Harmonizing the Intracellular Kinetics toward Effective Gene Delivery Using Cancer Cell-Targeted and Light-Degradable Polyplexes.

The success of nonviral gene delivery is often restricted by the multiple cellular barriers that posed inconsistent requirements for vector design. High molecular weight (MW) and cationic charge density are required for polycations to enable effective gene encapsulation, which, however, also lead to high toxicity, restricted intracellular cargo release, and poor serum resistance. We herein developed cross-linked polyethylenimine (PEI) with built-in UV-responsive domains (NP-PEI), which can effectively condense DNA while rapidly de-cross-link upon light triggers to promote intracellular DNA release and reduce material toxicity. HA coating of the polyplexes further enhanced their serum stability by shielding the surface positive charges and enabled cancer cell targeting to potentiate the transfection efficiencies. Thus, the polyplexes afforded high transfection efficiencies in serum upon light irradiation, outperforming PEI 25k by 1-2 orders of magnitude. This study therefore provides a useful strategy to overcome the critical barriers against nonviral gene delivery.

Characterization, Molecular Docking, and In Vitro Dissolution Studies of Solid Dispersions of 20(S)-Protopanaxadiol.

In this study, we prepared solid dispersions (SDs) of 20(S)-protopanaxadiol (PPD) using a melting-solvent method with different polymers, in order to improve the solubility and dissolution performance of drugs with poor water solubility. The SDs were characterized via differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and molecular docking and dynamics study. DSC and PXRD results indicated that PPD crystallinity in SDs was significantly reduced, and that the majority of PPD is amorphous. No interaction was observed between PPD and polymers on FTIR and NMR spectra. Molecular docking and dynamic calculations indicated that the PPD molecule localized to the interpolated charged surface, rather than within the amorphous polymer chain network, which might help prevent PPD crystallization, consequently enhancing the PPD dispersion in polymers. An in vitro dissolution study revealed that the SDs considerably improved the PPD dissolution performance in distilled water containing 0.35% Tween-80 (T-80). Furthermore, among three PPD-SDs formulations, Poloxamer188 (F68) was the most effective in improving the PPD solubility and was even superior to the mixed polymers. Therefore, the SD prepared with F68 as a hydrophilic polymer carrier might be a promising strategy for improving solubility and in vitro dissolution performance. F68-based SD, containing PPD with a melting-solvent preparation method, can be used as a promising, nontoxic, quick-release, and effective intermediate for other pharmaceutical formulations, in order to achieve a more effective drug delivery.