Chiral MoS2@BC fibrous membranes selectively promote peripheral nerve regeneration.

BACKGROUND: Molybdenum disulfide (MoS2) has excellent physical and chemical properties. Further, chiral MoS2 (CMS) exhibits excellent chiroptical and enantioselective effects, and the enantioselective properties of CMS have been studied for the treatment of neurodegenerative diseases. Intriguingly, left- and right-handed materials have different effects on promoting the differentiation of neural stem cells into neurons. However, the effect of the enantioselectivity of chiral materials on peripheral nerve regeneration remains unclear. METHODS: In this study, CMS@bacterial cellulose (BC) scaffolds were fabricated using a hydrothermal approach. The CMS@BC films synthesized with L-2-amino-3-phenyl-1-propanol was defined as L-CMS. The CMS@BC films synthesized with D-2-amino-3-phenyl-1-propanol was defined as D-CMS. The biocompatibility of CMS@BC scaffolds and their effect on Schwann cells (SCs) were validated by cellular experiments. In addition, these scaffolds were implanted in rat sciatic nerve defect sites for three months. RESULTS: These chiral scaffolds displayed high hydrophilicity, good mechanical properties, and low cytotoxicity. Further, we found that the L-CMS scaffolds were superior to the D-CMS scaffolds in promoting SCs proliferation. After three months, the scaffolds showed good biocompatibility in vivo, and the nerve conducting velocities of the L-CMS and D-CMS scaffolds were 51.2 m/s and 26.8 m/s, respectively. The L-CMS scaffolds showed a better regenerative effect than the D-CMS scaffolds. Similarly, the sciatic nerve function index and effects on the motor and electrophysiological functions were higher for the L-CMS scaffolds than the D-CMS scaffolds. Finally, the axon diameter and myelin sheath thickness of the regenerated nerves were improved in the L-CMS group. CONCLUSION: We found that the CMS@BC can promote peripheral nerve regeneration, and in general, the L-CMS group exhibited superior repair performance. Overall, the findings of this study reveal that CMS@BC can be used as a chiral nanomaterial nerve scaffold for peripheral nerve repair.

Effects of Microplastics on Soil Carbon Mineralization: The Crucial Role of Oxygen Dynamics and Electron Transfer.

Although our understanding of the effects of microplastics on the dynamics of soil organic matter (SOM) has considerably advanced in recent years, the fundamental mechanisms remain unclear. In this study, we examine the effects of polyethylene and poly(lactic acid) microplastics on SOM processes via mineralization incubation. Accordingly, we evaluated the changes in carbon dioxide (CO2) and methane (CH4) production. An O2 planar optical sensor was used to detect the temporal behavior of dissolved O2 during incubation to determine the microscale oxygen heterogeneity caused by microplastics. Additionally, the changes in soil dissolved organic matter (DOM) were evaluated using a combination of spectroscopic approaches and ultrahigh-resolution mass spectrometry. Microplastics increased cumulative CO2 emissions by 160-613%, whereas CH4 emissions dropped by 45-503%, which may be attributed to the oxygenated porous habitats surrounding microplastics. Conventional and biodegradable microplastics changed the quantities of soil dissolved organic carbon. In the microplastic treatments, DOM with more polar groups was detected, suggesting a higher level of electron transport. In addition, there was a positive correlation between the carbon concentration, electron-donating ability, and CO2 emission. These findings suggest that microplastics may facilitate the mineralization of SOM by modifying O2 microenvironments, DOM concentration, and DOM electron transport capability. Accordingly, this study provides new insights into the impact of microplastics on soil carbon dynamics.

NDGA enhances the physicochemical and anti-biodegradation performance of dentin collagen.

OBJECTIVES: Collagen fibrils from carious dentin matrix are prone to enzymatic degradation. This study investigates the feasibility and mechanism of nordihydroguaiaretic acid (NDGA), as a collagen crosslinker, to bio-modify the demineralized dentin matrix. METHODS: The physicochemical properties of the crosslinked dentin matrix were characterized by swelling ratio, ninhydrin assay, Fourier Transform Infrared spectroscopy, and atomic force microscopy. The collagenase degradation resistance was evaluated by measuring loss of dry mass, hydroproline release, loss of elasticity, and micro-nano structure integrity. The cytotoxicity of NDGA-crosslinked dentin collagen was evaluated by flow cytometry. RESULTS: NDGA crosslinked dentin matrix without destroying the integrity of collagen. Mechanistically, NDGA formed bisquinone bond between two adjacent o-quinone groups, resulting in NDGA polymeric matrix in which collagen fibrils were embedded. NDGA modification could significantly enhance the stiffness of dentin matrix at macro-nano scale. The NDGA-crosslinked dentin matrix exhibited remarkably low collagen degradation and sustained bulk elasticity after collagenase challenge, which were attributed to decreased water content, physical masking of collagenase bind sites on collagen, and improved stiffness of collagen fibrils. Notably, NDGA-crosslinked dentin matrix exhibited excellent biocompatibility. CONCLUSION: NDGA, as a biocompatible collagen crosslinker, improves the mechanical properties and biodegradation resistance of demineralized dentin matrix.

Oral squamous cell carcinoma diagnosed from saliva metabolic profiling.

Saliva is a noninvasive biofluid that can contain metabolite signatures of oral squamous cell carcinoma (OSCC). Conductive polymer spray ionization mass spectrometry (CPSI-MS) is employed to record a wide range of metabolite species within a few seconds, making this technique appealing as a point-of-care method for the early detection of OSCC. Saliva samples from 373 volunteers, 124 who are healthy, 124 who have premalignant lesions, and 125 who are OSCC patients, were collected for discovering and validating dysregulated metabolites and determining altered metabolic pathways. Metabolite markers were reconfirmed at the primary tissue level by desorption electrospray ionization MS imaging (DESI-MSI), demonstrating the reliability of diagnoses based on saliva metabolomics. With the aid of machine learning (ML), OSCC and premalignant lesions can be distinguished from the normal physical condition in real time with an accuracy of 86.7%, on a person by person basis. These results suggest that the combination of CPSI-MS and ML is a feasible tool for accurate, automated diagnosis of OSCC in clinical practice.

The significance of the best puncture side bone cement/vertebral volume ratio to prevent paravertebral vein leakage of bone cement during vertebroplasty: a retrospective study.

OBJECTIVES: To verify the clinical significance of the best puncture-side bone cement/vertebral volume ratio (PSBCV/VV%) and bone cement leakage in paravertebral veins during vertebroplasty. METHODS: This was a retrospective analysis of a total of 210 patients from September 2021 to December 2022, who were divided into an observation group (110 patients) and a control group (100 patients). In the observation group, patients' preoperative computed tomography (CT) data were imported into Mimics software, and the VV was calculated using the three-dimensional (3D) reconstruction function. Then, based on the best PSBCV/VV% of 13.68% determined in a previous study, the optimal PSBCV to be injected during vertebroplasty was calculated. In the control group, vertebroplasty was performed directly using the conventional method. The incidence of cement leakage into paravertebral veins was observed postoperatively in both groups. RESULTS: There were no statistically significant differences (P > 0.05) in the evaluated indicators between the two groups pre- or postoperatively, including the anterior vertebral margin height, mid-vertebral height, injured vertebral Cobb angle, visual analogue scale (VAS) score, and Oswestry Disability Index (ODI). Intragroup comparisons showed improvements in the anterior vertebral height, mid-vertebral height, injured vertebral Cobb angle, VAS score, and ODI after surgery compared with before surgery (P < 0.05). In the observation group, there were 3 cases of cement leakage into the paravertebral veins, for a leakage rate of 2.7%. In the control group, there were 11 cases of cement leakage into the paravertebral veins, for a leakage rate of 11%. The difference in the leakage rate between the two groups was statistically significant (P = 0.016). CONCLUSION: In vertebroplasty, preoperative VV calculations using Mimics software, combined with calculation of the PSBCV according to the best PSBCV/VV% (13.68%), can effectively prevent leakage of bone cement into paravertebral veins and further prevent serious life-threatening complications such as pulmonary embolism.

Endoscopic resection of a descending duodenal polyp with the string-clip traction.

There is few studies about modified endoscopic treatment of duodenal lesions. The string-clip method is an effective option for large pedunculated duodenal polyp. On the one hand, it could increase the tension of the lesion and make endoscopic resection easy. What is more, with the help of clip and dental floss, we do not have to worry about specimen losing. We could deal with the wound first and then retrieve the resected specimen, resulting in an increased safety and efficiency of the endoscopic treatment.

Microplastics reduce soil microbial network complexity and ecological deterministic selection.

Microplastics have been proposed as emerging threats for terrestrial systems as they may potentially alter the physicochemical/biophysical soil environments. Due to the variety of properties of microplastics and soils, the microplastic-induced effects in soil ecosystems are greatly manifold. Here, we studied effects of three polymer microplastics (polyamide-6, polyethylene, and polyethylene terephthalate) on soil properties with four different soil types. The success patterns, interaction relationships, and assembly processes of soil bacterial communities were also studied. Microplastics have the potential to promote CO2 emissions and enhance the soil humification. Even though microplastics did not significantly alter the diversity and composition of the soil microbial community, the application of microplastics decreased the network complexity and stability, including network size, connectivity, and the number of module and keystone species. The bacterial community assembly was governed by deterministic selection (77.3%-90.9%) in all treatments, while microplastics increased the contribution of stochastic processes from 9.1% in control to 13.6%-22.7%. The neutral model results also indicated most of the bacterial taxa were present in the predicted neutral region (approximately 98%), suggesting the importance of stochastic processes. These findings provided a fundamental insight in understanding the effects of microplastics on soil ecosystems.

Directional Water Transport Janus Composite Nanofiber Membranes for Comfortable Bioprotection.

The Janus membrane has a huge prospect for personal comfortable protection. However, there still is a huge imbalance between the comfort and protection of the existing Janus membrane. There is an urgent need to further improve the comprehensive performance of the protective membrane to realize both protection and comfort. Herein, we report the Janus membrane with directional water transport capacity and dust rejection performance by compounding the polyvinyl chloride hydrophobic nanofiber membrane and polyamide-6 blended polyvinyl pyrrolidone hydrophilic nanofiber membrane. This Janus composite nanofiber membrane exhibited an excellent dust rejection efficiency of 99.99%, air permeability of 42.15 mm/s, which was 76 times that of the commercial waterproof and breathable PTFE membrane, water vapor transmission rate of 4.89 kg/(m2 × 24 h), and accumulative one-way transport capacity of 888.7%. In addition, the breakthrough pressure of the Janus membrane in the reverse direction (i.e., hydrophilic layer to hydrophobic layer) was four times that in the positive direction (i.e., hydrophobic layer to hydrophilic layer), suggesting it to be a potential substrate for comfortable bioprotection with a comprehensive protection capability.

Microplastic presence significantly alters soil nitrogen transformation and decreases nitrogen bioavailability under contrasting temperatures.

Plastic mulch is frequently used to increase crop yield, resulting in large quantities of residues accumulating in soil due to low recovery rates. However, the effects of microplastic residues from traditional and biodegradable plastic films on soil nitrogen (N) transformation and bioavailability are not well understood. Here, the main objectives were to examine the effects of micro-sized residues (diameter <5 mm) of polyethylene (PE) and biodegradable plastic mulch films (PLA) on the soil N in two contrasting soils (clay soil and sandy loam soil) in different temperatures (15 °C vs. 25 °C). Results showed that the microplastic presence showed a little effect on soil N transformation and bioavailability at 15 °C, but both microplastics significantly decreased NO3-, mineral N (MN), total dissolved N (TDN), the net cumulative N nitrification (Nn), and the net cumulative N mineralization (Nm) at 25 °C, indicating that microplastics decreased soil N bioavailability at elevated temperature. Meanwhile, the microplastics significantly reduced the temperature sensitivity (Q10) of N mineralization. The presence of microplastics changed the composition of soil mineral N with lower relative NO3- and higher NH4+ compared to the control in clay soil. The sandy loam soil was more susceptible to microplastic pollution compared to clay soil in N transformation, due to different textures and biochemistry properties in the two soils, which showed that microplastics have a significant soil heterogeneity-dependent effect on soil N processes. Therefore, the results underline that the effects of microplastic residues on soil N cycling can be partly linked to soil properties, suggesting the urgent need for further studies examining their impacts on soil nutrient cycling in different soil systems.

A Two-Dimensional Metallacycle Cross-Linked Switchable Polymer for Fast and Highly Efficient Phosphorylated Peptide Enrichment.

The selective and efficient capture of phosphopeptides is critical for comprehensive and in-depth phosphoproteome analysis. Here we report a new switchable two-dimensional (2D) supramolecular polymer that serves as an ideal platform for the enrichment of phosphopeptides. A well-defined, positively charged metallacycle incorporated into the polymer endows the resultant polymer with a high affinity for phosphopeptides. Importantly, the stimuli-responsive nature of the polymer facilitates switchable binding affinity of phosphopeptides, thus resulting in an excellent performance in phosphopeptide enrichment and separation from model proteins. The polymer has a high enrichment capacity (165 mg/g) and detection sensitivity (2 fmol), high enrichment recovery (88%), excellent specificity, and rapid enrichment and separation properties. Additionally, we have demonstrated the capture of phosphopeptides from the tryptic digest of real biosamples, thus illustrating the potential of this polymeric material in phosphoproteomic studies.

Novel biallelic loss-of-function variants in CEP290 cause Joubert syndrome in two siblings.

BACKGROUND: Joubert syndrome (JS) is a rare genetic disorder, which can be defined by brain stem malformation, cerebellar vermis hypoplasia, and consequent "molar tooth sign" (MTS). JS always shares variety of phenotypes in development defects. With the development of next-generation sequencing, dozens of causative genes have been identified to JS so far. Here, we investigated two male siblings with JS and uncovered a novel pathogenesis through combined methods. RESULTS: The siblings shared similar features of nystagmus, disorders of intellectual development, typical MTS, and abnormal morphology in fourth ventricle. Whole-exome sequencing (WES) and chromosome comparative genomic hybridization (CGH) were then performed on the proband. Strikingly, a maternal inherited nonsense variant (NM_025114.3: c.5953G>T [p.E1985*]) in CEP290 gene and a paternal inherited deletion in 12q21.32 including exons 1 to 10 of CEP290 gene were identified in the two affected siblings. We further confirmed the two variants by in vitro experiments: quantitative PCR and PCR sequencing. CONCLUSIONS: In this study, we first reported a novel causative mechanism of Joubert syndrome: a copy number variation (CNV) combined with a single-nucleotide variant in CEP290 gene, which can be helpful in the genetic diagnosis of this disease.

Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor.

BACKGROUND: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. RESULTS: The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. CONCLUSIONS: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment.

iTRAQ-based quantitative analysis reveals the mechanism underlying the changes in physiological activity in a glutamate racemase mutant strain of Streptococcus mutans UA159.

Streptococcus mutans UA159 is responsible for human dental caries with robust cariogenic potential. Our previous study noted that a glutamate racemase (MurI) mutant strain (designated S. mutans FW1718), with the hereditary background of UA159, displayed alterations of morphogenesis, attenuated stress tolerance, and weakened biofilm-forming capabilities, accompanying with unclear mechanisms. In this study, we applied isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics to characterize the proteome profiles of the murI mutant strain vs. the wild-type strain in chemically defined media to elucidate the mechanisms by which S. mutans copes with MurI deficiency. Whole-cell proteins of S. mutans FW1718 and UA159 were assessed by iTRAQ-coupled LC-ESI-MS/MS. Furthermore, differentially expressed proteins (DEPs) were identified by Mascot, Gene Ontology (GO) annotation, Cluster of Orthologous Groups of proteins (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, a protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Among 1173 total bacterial proteins identified, 112 DEPs exhibited altered expression patterns in S. mutans UA159 with or without the murI mutation. The ΔmurI cells displayed an increase in the relative expression of 93 proteins (fold change ≥ 1.2, p < 0.05) and a decrease in 29 proteins (fold change ≤ 0.833, p < 0.05) compared with the wild-type cells. PPI analysis revealed a complex network of DEPs containing 191 edges and 122 nodes. The DEPs significantly upregulated after murI knockout had roles in diverse functional processes spanning cell-wall biosynthesis, energy production, and DNA replication and repair. We identified distinct variations and diverse modulators caused by murI mutation in the proteome of S. mutans, indicating that the modification of cell membrane structure, redistribution of energy metabolism and enhanced nucleic acid machinery contributed to the S. mutans response to specific environmental contexts.

Identification and characterization of a novel bacterial carbohydrate esterase from the bacterium Pantoea ananatis Sd-1 with potential for degradation of lignocellulose and pesticides.

OBJECTIVE: Identification and characterization of a novel bacterial carbohydrate esterase (PaCes7) with application potential for lignocellulose and pesticide degradation. RESULTS: PaCes7 was identified from the lignocellulolytic bacterium, Pantoea ananatis Sd-1 as a new carbohydrate esterase. Recombinant PaCes7 heterologously expressed in Escherichia coli showed a clear preference for esters with short-chain fatty acids and exhibited maximum activity towards α-naphthol acetate at 37 °C and pH 7.5. Purified PaCes7 exhibited its catalytic activity under mesophilic conditions and retained more than 40% activity below 30 °C. It displayed a relatively wide pH stability from pH 6-11. Furthermore, the enzyme was strongly resistant to Mg2+, Pb2+, and Co2+ and activated by K+ and Ca2+. Both P. ananatis Sd-1 and PaCes7 could degrade the pesticide carbaryl. Additionally, PaCes7 was shown to work in combination with cellulase and/or xylanase in rice straw degradation. CONCLUSIONS: The data suggest that PaCes7 possesses promising biotechnological potential.

The Crystallinity and Aspect Ratio of Cellulose Nanomaterials Determine Their Pro-Inflammatory and Immune Adjuvant Effects In Vitro and In Vivo.

Nanocellulose is increasingly considered for applications; however, the fibrillar nature, crystalline phase, and surface reactivity of these high aspect ratio nanomaterials need to be considered for safe biomedical use. Here a comprehensive analysis of the impact of cellulose nanofibrils (CNF) and nanocrystals (CNC) is performed using materials provided by the Nanomaterial Health Implications Research Consortium of the National Institute of Environmental Health Sciences. An intermediary length of nanocrystals is also derived by acid hydrolysis. While all CNFs and CNCs are devoid of cytotoxicity, 210 and 280 nm fluorescein isothiocyanate (FITC)-labeled CNCs show higher cellular uptake than longer and shorter CNCs or CNFs. Moreover, CNCs in the 200-300 nm length scale are more likely to induce lysosomal damage, NLRP3 inflammasome activation, and IL-1ß production than CNFs. The pro-inflammatory effects of CNCs are correlated with higher crystallinity index, surface hydroxyl density, and reactive oxygen species generation. In addition, CNFs and CNCs can induce maturation of bone marrow-derived dendritic cells and CNCs (and to a lesser extent CNFs) are found to exert adjuvant effects in ovalbumin (OVA)-injected mice, particularly for 210 and 280 nm CNCs. All considered, the data demonstrate the importance of length scale, crystallinity, and surface reactivity in shaping the innate immune response to nanocellulose.

Fenofibrate-Loaded Biodegradable Nanoparticles for the Treatment of Experimental Diabetic Retinopathy and Neovascular Age-Related Macular Degeneration.

Fenofibrate is a peroxisome proliferator-activated receptor α (PPARα) agonist and has been shown to have therapeutic effects on diabetic retinopathy (DR). However, the effects of fenofibrate through systemic administration are not as potent as desired due to inefficient drug delivery to the retina. The present study aimed to explore the sustained therapeutic effects of fenofibrate-loaded biodegradable nanoparticles (NP) on both DR and neovascular age-related macular degeneration (AMD). Fenofibrate was successfully encapsulated into poly(lactic- co-glycolic acid) (PLGA) NP (Feno-NP), and Feno-NP were optimized by varying polymer composition to achieve high drug loading and prolonged drug release. The Feno-NP made of PLGA 34 kDa demonstrated a drug content of 6% w/w and a sustained drug release up to 60 days in vitro. Feno-NP (PLGA 34 kDa) was selected for following in vivo studies, and one single intravitreal (IVT) injection of Feno-NP into rat eyes with a 30G fine needle maintained sustained fenofibric acid drug level in the eye for more than 60 days. The efficacy of Feno-NP in DR and neovascular AMD was investigated using streptozotocin (STZ)-induced diabetic rats, laser-induced choroidal neovascularization (CNV) rats, and very low-density lipoprotein receptor knockout ( Vldlr -/-) mice. Therapeutic effects of Feno-NP were evaluated by measuring electroretinogram (ERG), retinal vascular leakage, leukostasis, CNV size, and retinal levels of vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1). In diabetic rats, Feno-NP ameliorated retinal dysfunctions, reduced retinal vascular leakage, inhibited retinal leukostasis, and downregulated the overexpression of VEGF and ICAM-1 at 8 weeks after one IVT injection. In addition, Feno-NP reduced retinal vascular leakage and CNV formation in both CNV rats and Vldlr -/- mice. Moreover, no toxicity of Feno-NP or Blank-NP to retinal structure and function was detected. Feno-NP exhibited good physiochemical characteristics and controlled drug release profile, conferring prolonged beneficial effects on DR and neovascular AMD.

Evaluation of six white-rot fungal pretreatments on corn stover for the production of cellulolytic and ligninolytic enzymes, reducing sugars, and ethanol.

Fungal pretreatment on lignocellulosic biomass has the advantages of being eco-friendly, having low operating cost, and producing no inhibitor. In this study, six white-rot fungi (Trametes versicolor, Pleurotus ostreatus, Phanerochaete chrysosporium, Coriolopsis gallica, Pleurotus sajor-caju, Lentinula edodes) were applied to corn stover pretreatment. Biomass degradation, production of enzymes, reducing sugar via hydrolysis, and ethanol yield via yeast fermentation were quantified during 30 days cultivation, and samples were taken every 5 days. Among six fungi, the highest lignin degradation was 38.29% at 30 days for P. sajor-caju pretreatment, the highest sugar yield was 71.24%, and the highest ethanol yield was 0.124 g g-1 corn stover under P. sajor-caju pretreatment for 25 days. The highest activities of laccase and manganese peroxidase were 29.22 and 10.22 U g-1 dry biomass, respectively, under T. versicolor pretreatment at 25 days. The highest levels of enzyme, sugar, and ethanol production are comparable or higher than what has been reported in previous literature. P. sajor-caju is one of the most widely worldwide cultivated mushrooms. The findings in this study show the potential to incorporate P. sajor-caju mushroom cultivation into corn stover pretreatment to enhance the production of a suite of products such as enzymes, sugars, and ethanol.

Effects of active and passive smoking on salivary cytokines levels in rats: A pilot study.

Cigarette smoking is an established risk factor for some oral diseases. As an essential fluid in the oral cavity, saliva is crucial to maintain oral health. Relative to active smoking, there are very few studies assessing the effect of passive smoking on salivary cytokines levels. In the present study, we established the rat models by the means of the intraoral cigarette smoking or whole body cigarette smoke exposure to simulate human active or passive smoking, respectively. The effects of active or passive smoking on salivary cytokines levels were assessed by using ProcartaPlex multiplex immunoassays. The results of the current study indicated that both active and passive smoking diminished the body weights of rats and increased the levels of some blood counts. Intriguingly, active smoking enhanced the salivary levels of IL-6 and IL-12 p70 and passive smoking elevated the salivary IL-6 level. Moreover, active smoking appeared to have a more prominent activation effect on the salivary IL-6 level. It was noted that active or passive smoking had no significant effect on the salivary IFN-γ level. Active or passive smoking could have potential effects on the salivary levels of some pro-inflammatory cytokines.

Leutusome: A Biomimetic Nanoplatform Integrating Plasma Membrane Components of Leukocytes and Tumor Cells for Remarkably Enhanced Solid Tumor Homing.

Cell membrane-camouflaged nanoparticles have appeared as a promising platform to develop active tumor targeting nanomedicines. To evade the immune surveillance, we designed a composite cell membrane-camouflaged biomimetic nanoplatform, namely, leutusome, which is made of liposomal nanoparticles incorporating plasma membrane components derived from both leukocytes (murine J774A.1 cells) and tumor cells (head and neck tumor cells HN12). Exogenous phospholipids were used as building blocks to fuse with two cell membranes to form liposomal nanoparticles. Liposomal nanoparticles made of exogenous phospholipids only or in combination with one type of cell membrane were fabricated and compared. The anticancer drug paclitaxel (PTX) was used to make drug-encapsulating liposomal nanoparticles. Leutusome resembling characteristic plasma membrane components of the two cell membranes were examined and confirmed in vitro. A xenograft mouse model of head and neck cancer was used to profile the blood clearance kinetics, biodistribution, and antitumor efficacy of the different liposomal nanoparticles. The results demonstrated that leutusome obtained prolonged blood circulation and was most efficient accumulating at the tumor site (79.1 ± 6.6% ID per gram of tumor). Similarly, leutusome composed of membrane fractions of B16 melanoma cells and leukocytes (J774A.1) showed prominent accumulation within the B16 tumor, suggesting the generalization of the approach. Furthermore, PTX-encapsulating leutusome was found to most potently inhibit tumor growth while not causing systemic adverse effects.

Toxicological Profiling of Highly Purified Single-Walled Carbon Nanotubes with Different Lengths in the Rodent Lung and Escherichia Coli.

Carbon nanotubes (CNTs) exhibit a number of physicochemical properties that contribute to adverse biological outcomes. However, it is difficult to define the independent contribution of individual properties without purified materials. A library of highly purified single-walled carbon nanotubes (SWCNTs) of different lengths is prepared from the same base material by density gradient ultracentrifugation, designated as short (318 nm), medium (789 nm), and long (1215 nm) SWCNTs. In vitro screening shows length-dependent interleukin-1ß (IL-1ß) production, in order of long > medium > short. However, there are no differences in transforming growth factor-ß1 production in BEAS-2B cells. Oropharyngeal aspiration shows that all the SWCNTs induce profibrogenic effects in mouse lung at 21 d postexposure, but there are no differences between tube lengths. In contrast, these SWCNTs demonstrate length-dependent antibacterial effects on Escherichia coli, with the long SWCNT exerting stronger effects than the medium or short tubes. These effects are reduced by Pluronic F108 coating or supplementing with glucose. The data show length-dependent effects on proinflammatory response in macrophage cell line and antibacterial effects, but not on collagen deposition in the lung. These data demonstrate that over the length scale tested, the biological response to highly purified SWCNTs is dependent on the complexity of the nano/bio interface.