Histoplasty Modification of the Tumor Microenvironment in a Murine Preclinical Model of Breast Cancer.

PURPOSE: To develop a noninvasive therapeutic approach able to alter the biophysical organization and physiology of the extracellular matrix (ECM) in breast cancer. MATERIALS AND METHODS: In a 4T1 murine model of breast cancer, histoplasty treatment with a proprietary 700-kHz multielement therapy transducer using a coaxially aligned ultrasound (US) imaging probe was used to target the center of an ex vivo tumor and deliver subablative acoustic energy. Tumor collagen morphology was qualitatively evaluated before and after histoplasty with second harmonic generation. Separately, mice bearing bilateral 4T1 tumors (n = 4; total tumors = 8) were intravenously injected with liposomal doxorubicin. The right flank tumor was histoplasty-treated, and tumors were fluorescently imaged to detect doxorubicin uptake after histoplasty treatment. Next, 4T1 tumor-bearing mice were randomized into 2 treatment groups (sham vs histoplasty, n = 3 per group). Forty-eight hours after sham/histoplasty treatment, tumors were harvested and analyzed using flow cytometry. RESULTS: Histoplasty significantly increased (P = .002) liposomal doxorubicin diffusion into 4T1 tumors compared with untreated tumors (2.12- vs 1.66-fold increase over control). Flow cytometry on histoplasty-treated tumors (n = 3) demonstrated a significant increase in tumor macrophage frequency (42% of CD45 vs 33%; P = .022) and a significant decrease in myeloid-derived suppressive cell frequency (7.1% of CD45 vs 10.3%; P = .044). Histoplasty-treated tumors demonstrated increased CD8+ (5.1% of CD45 vs 3.1%; P = .117) and CD4+ (14.1% of CD45 vs 11.8%; P = .075) T-cell frequency. CONCLUSIONS: Histoplasty is a nonablative focused US approach to noninvasively modify the tumor ECM, increase chemotherapeutic uptake, and alter the tumor immune microenvironment.

In-silico structural characterization and phylogenetic analysis of Nucleoside diphosphate kinase: A novel antiapoptotic protein of Porphyromonas gingivalis.

The Nucleoside diphosphate kinase (NDK) protein of Porphyromonas gingivalis (P. gingivalis) plays a crucial role in immune evasion and inhibition of apoptosis in host cells and has the potential to cause cancer. However, its structure has not yet been characterized. We used an in-silico approach to determine the 3D structure of the P. gingivalis NDK. Furthermore, structural characterization and functional annotation were performed using computational approaches. The 3D structure of NDK was predicted through homology modeling. The structural domains predicted for the model protein belong to the NDK family. Structural alignment of prokaryotic and eukaryotic NDKs with the model protein revealed the conservation of the domain region. Structure-based phylogenetic analysis depicted a significant evolutionary relationship between the model protein and the prokaryotic NDK. Functional annotation of the model confirmed structural homology, exhibiting similar enzymatic functions as NDK, including ATP binding and nucleoside diphosphate kinase activity. Furthermore, molecular dynamic (MD) simulation technique stabilized the model structure and provides a thermo-stable protein structure that can be used as a therapeutic target for further studies.

Comparative study of ethanol production from sodium hydroxide pretreated rice straw residue using Saccharomyces cerevisiae and Zymomonas mobilis.

Rice straw is a suitable alternative to a cheaper carbohydrate source for the production of ethanol. For pretreatment efficiency, different sodium hydroxide concentrations (0.5-2.5% w/v) were tested. When compared to other concentrations, rice straw processed with 2% NaOH (w/v) yielded more sugar (8.17 ± 0.01 mg/ml). An alkali treatment induces effective delignification and swelling of biomass. The pretreatment of rice straw with 2% sodium hydroxide (w/v) is able to achieve 55.34% delignification with 53.30% cellulose enrichment. The current study shows the effectiveness of crude cellulolytic preparation from Aspergillus niger resulting in 80.51 ± 0.4% cellulose hydrolysis. Rice straw hydrolysate was fermented using ethanologenic Saccharomyces cerevisiae (yeast) and Zymomonas mobilis (bacteria). Overall, superior efficiency of sugar conversion to ethanol 70.34 ± 0.3% was obtained with the yeast compared to bacterial strain 39.18 ± 0.5%. The current study showed that pretreatment with sodium hydroxide is an effective method for producing ethanol from rice straw and yeast strain S. cerevisiae having greater fermentative potential for bioethanol production than bacterial strain Z. mobilis.

Structure based High-Throughput Virtual Screening, Molecular Docking and Molecular Dynamics Study of anticancer natural compounds against fimbriae (FimA) protein of Porphyromonas gingivalis in oral squamous cell carcinoma.

Oral cancer is among the most common cancer in the world. Tobacco, alcohol, and viruses have been regarded as a well- known risk factors of OCC however, 15% of OSCC cases occurred each year without these known risk factors. Recently a myriad of studies has shown that bacterial infections lead to cancer. Accumulated shreds of evidence have demonstrated the role of Porphyromonas gingivalis (P. gingivalis) in OSCC. The virulence factor FimA of P. gingivalis activates the oncogenic pathways in OSCC by upregulating various cytokines. It also led to the inactivation of a tumor suppressor protein p53. The present Insilico study uses High-Throughput Virtual Screening, molecular docking, and molecular dynamics techniques to find the potential compounds against the target protein FimA. The goal of this study is to identify the anti-cancer lead compounds retrieved from natural sources that can be used to develop potent drug molecules to treat P.gingivalis-related OSCC. The anticancer natural compounds library was screened to identify the potential lead compounds. Furthermore, these lead compounds were subjected to precise docking, and based on the docking score potential lead compounds were identified. The top docked receptor-ligand complex was subjected to molecular dynamics simulation. A study of this insilico finding provides potent lead molecules which help in the development of therapeutic drugs against the target protein FimA in OSCC. Workflow of Structure based High-Throughput Virtual Screening, Molecular Docking and Molecular Dynamics Study of anticancer natural compounds against Fimbriae (FimA) protein of P. gingivalis in oral squamous cell carcinoma.

Polymer Translocation and Nanopore Sequencing: A Review of Advances and Challenges.

Various biological processes involve the translocation of macromolecules across nanopores; these pores are basically protein channels embedded in membranes. Understanding the mechanism of translocation is crucial to a range of technological applications, including DNA sequencing, single molecule detection, and controlled drug delivery. In this spirit, numerous efforts have been made to develop polymer translocation-based sequencing devices, these efforts include findings and insights from theoretical modeling, simulations, and experimental studies. As much as the past and ongoing studies have added to the knowledge, the practical realization of low-cost, high-throughput sequencing devices, however, has still not been realized. There are challenges, the foremost of which is controlling the speed of translocation at the single monomer level, which remain to be addressed in order to use polymer translocation-based methods for sensing applications. In this article, we review the recent studies aimed at developing control over the dynamics of polymer translocation through nanopores.

Well-Defined pH-Sensitive Self-Assembled Triblock Copolymer-Based Crosslinked Micelles for Efficient Cancer Chemotherapy.

Delivery of chemotherapeutics to cancer cells using polymeric micelles is a promising strategy for cancer treatment. However, limited stability of micelles, premature drug release and off-target effect are the major obstacles that restrict the utilization of polymeric micelles as effective drug delivery systems. In this work, we addressed these issues through the innovative design of targeted pH-sensitive crosslinked polymeric micelles for chemotherapeutic delivery. A well-defined triblock copolymer, poly(ethylene glycol)-b-poly(2-hydroxyethyl methacrylate)-b-poly(butyl acrylate) (PEG-b-PHEMA-b-PBA), was synthesized by living radical polymerization, and then modified by using 4-pentenoic anhydride to incorporate pendant crosslinkable alkene groups in the middle block. The resulting copolymer underwent self-assembly in aqueous solution to form non-crosslinked micelles (NCMs). Subsequently, intramicellar thiol-ene crosslinking was performed by using 1,4-butanediol bis(3-mercaptopropionate) to give crosslinked micelles (CMs) with pH-sensitive crosslinks. The targeted CM (cRGD-DOX10-CM5) was readily prepared by using tumor-targeting ligand cyclo(Arg-Gly-Asp-D-Phe-Cys) (cRGD) together with the 1,4-butanediol bis(3-mercaptopropionate) during the crosslinking step. The study of cumulative DOX release revealed the pH-sensitive feature of drug release from these CMs. An in vitro MTT assay revealed that NCMs and CMs are biocompatible with MCF 10A cells, and the samples exhibited significant therapeutic efficiency as compared to free DOX. Cellular uptake studies confirmed higher uptake of cRGD-DOX10-CM5 by MCF 10A cancer cells via cRGD-receptor-mediated endocytosis as compared to the corresponding analogues without cRGD. These results indicate that such pH-responsive crosslinked PEG-b-PHEMA-b-PBA-based micelles are therapeutically effective against cancer cells and hold remarkable promise to act as smart drug delivery systems for cancer therapy.

Mesenchymal stem cells from orthodontic premolar teeth.

BACKGROUND: Considering the limitations in isolating Bone Marrow Mesenchymal Stem Cells (BMSCs), alternate sources of Mesenchymal Stem Cells (MSCs) are being intensely investigated. This study evaluated dental pulp MSCs (DP-MSCs) isolated from orthodontically extracted premolar teeth from a bone tissue engineering perspective. METHODS: MSCs isolated from premolar teeth pulp were cultured and studied using BMSCs as the control. Flow cytometry analysis was performed for the positive and negative MSC markers. Multilineage differentiation focusing on bone regeneration was evaluated by specific growth induction culturing media and by alkaline phosphatase (ALP) activity. Data were compared by repeated measurement analysis of variance and Student's t-test at a p value <0.05. RESULTS: Proliferation rate, population doubling time, and colony formation of DP-MSCs were significantly higher (p < 0.001) than BMSCs. More than 85% of DP-MSCs expressed CD44, CD73, CD90, CD105, and CD166. Negative reaction was found for CD11b CD33, CD34, and CD45. Positive reaction was displayed by 7.2% of cells for early MSC marker, Stro-1. Both the cell populations differentiated into adipogenic, osteogenic, and chondrogenic lineages, with adequate ALP expression. CONCLUSION: Because DP-MSCs from orthodontic premolars hold a neural crest/ectomesenchymal ancestry, its prudent growth characteristics and multilineage differentiation open up exciting options in craniofacial tissue engineering.

Cell encapsulation potential of chitosan-alginate electrostatic complex in preventing natural killer and CD8+ cell-mediated cytotoxicity: an in vitro experimental study.

Natural killer and cytotoxic CD8+ T cells are involved in the rapid clearance of cells which express foreign antigens. Hence, these cells are crucial elements of the vertebrate immune system. However, these benefits turn problematic when they cause transplant rejection through their direct cytotoxic effects on donor organs/cells, which is attributed to the human leukocyte antigen disparity. To overcome these limitations, a strategy has been devised wherein the above effects can be minimised by shielding the cells through encapsulation. The layer-by-layer approach was employed for encapsulation using chitosan and alginate. Confocal microscopy, scanning electron microscopy confirmed the complete shielding of cells. Encapsulation did not affect cell viability as no toxicity was discerned. Calcein release assay was applied for assessing cell-mediated cytotoxicity. It was observed that the encapsulated cells underwent lesser lysis, thereby revealing the potential that this approach offers in reducing conditions such as graft failure and hypersensitivity.

Effect of gingival displacement cord and cordless systems on the closure, displacement, and inflammation of the gingival crevice.

STATEMENT OF PROBLEM: The gingival sulcus should remain open long enough for the impression material to flow into it and completely fill the space provided by the gingival displacement. Impressions with less sulcal width have a higher incidence of voids, tearing of impression materials, and reduction in marginal accuracy. PURPOSE: The purpose of this clinical study was to investigate the closure, gingival displacement, and gingival inflammation of the gingival crevice after the use of medicated gingival displacement cord and cordless systems. MATERIAL AND METHODS: Gingival sulcus closure was studied in 40 participants. They were divided into 4 groups: 2 cord (Ultrapack, SilTrax AS) and 2 cordless (Expasyl, Traxodent Hemodent paste) methods. The labial surfaces of the maxillary right and left central incisors were evaluated. Gingival sulcus was photographed every 20 seconds from 0 to 180 seconds after the removal of the cord or cordless system. The bleeding index (BI) and gingival index (GI) were measured at day 0, day 1, and day 7. The width of the sulcal orifice was measured at the mid-buccal (MB) and transitional line angle (TLA) on a digital image, using computer software (Photoshop version 7.0; Adobe). Data were analyzed with ANOVA, Tukey honest significant difference (HSD), Kruskal-Wallis, and Mann-Whitney U tests (α=.05). RESULTS: All groups showed a sulcal width greater than 0.22 mm up to 60 seconds after the removal of the displacement materials at the MB and up to 40 seconds at the TLA. Among all groups, Expasyl showed the fastest closure. Gingival displacement in the MB area for the cord group was greater than for the cordless groups. GI and BI indices were larger for the cord group than for the cordless group at days 0 and 1. CONCLUSIONS: At up to 60 seconds, the cord and cordless techniques were equally effective. The cord group showed a greater amount of displacement than the cordless group. However, the cordless materials showed reduced frequency of changes to the gingival index.

Biophysicochemical perspective of nanoparticle compatibility: a critically ignored parameter in nanomedicine.

Engineered nanomaterials are increasingly used in domestic and commercial products due to the rapid growth and increasing public and industrial interests in nanotechnology. Undoubtedly there will be more exposure of living organisms and the environment to nanomaterials. Therefore, understanding the biophysicochemical interactions of nanoparticles with proteins, membranes, cells, DNA, and organelles at the nano-biointerface will help to control fundamental biological and dynamic colloidal forces to promote biocompatibility of the particles. In this article, we review how bio- and physicochemical surface characteristics at nanoscale govern particle biocompatibility for in vivo and in vitro models. We also revisit the promise and predictions gained from this understanding to design special types of nanoparticles, such as quantum dots (QDs) and superparamagnetic iron oxide nanoparticles (SPIONs), for biomedical applications. This knowledge is essential not only from the perspective of safe use of nanomaterials, but also in paving the way for nontoxic interactions with biological systems. It paves the route for safe implementation of the materials in novel biomedical diagnostics and therapeutics. We also put forward an outlook and future perspective, which are largely "ignored parameters" in nanomedicine. In conclusion, emphasis on the systematic evaluation of nanomaterial toxicity in primary cells derived from vital organs and the need to develop an international consortium for a materialomics database is encouraged.

Treatment Using Functionally Fixed Prosthesis: A Case Report.

Most dental practitioners as well as their patients prefer to have fixed rather than removable prosthesis. However, there are many clinical situations that prohibit the use of the fixed treatment modality. These clinical cases can vary from, simply not having the proper number of healthy teeth and/or implants to, the esthetically challenging cases of high smile lines and severe loss of alveolar support. The approach of using a traditional removable prosthesis in these situations has always been met with severe compromises. The functionally fixed restoration is a third modality of treatment that can solve many of the problems of the removable restoration and at the same time provide the same comfort and success of the fixed prosthesis. This restoration has a pontic assembly that is removed by the patient for periodontal maintenance. This article presents a case report which describes a technique for treatment of partially edentulous maxilla with severe loss of alveolar support using a fixed removable prosthesis/Andrew's bridge.

The specific degree-of-polymerization of A-type proanthocyanidin oligomers impacts Streptococcus mutans glucan-mediated adhesion and transcriptome responses within biofilms.

Cranberry A-type proanthocyanidins (PACs) have been recognized for their inhibitory activity against bacterial adhesion and biofilm-derived infections. However, the precise identification of the specific classes of degree-of-polymerization (DP) conferring PACs bioactivity remains a major challenge owing to the complex chemistry of these flavonoids. In this study, chemically characterized cranberries were used in a multistep separation and structure-determination technique to isolate A-type PAC oligomers of defined DP. The influences of PACs on the 3D architecture of biofilms and Streptococcus mutans-transcriptome responses within biofilms were investigated. Treatment regimens that simulated topical exposures experienced clinically (twice-daily, 60 s each) were used over a saliva-coated hydroxyapatite biofilm model. Biofilm accumulation was impaired, while specific genes involved in the adhesion of bacteria, acid stress tolerance, and glycolysis were affected by the topical treatments (vs the vehicle-control). Genes (rmpC, mepA, sdcBB, and gbpC) associated with sucrose-dependent binding of bacteria were repressed by PACs. PACs of DP 4 and particularly DP 8 to 13 were the most effective in disrupting bacterial adhesion to glucan-coated apatitic surface (>85% inhibition vs vehicle control), and gene expression (eg rmpC). This study identified putative molecular targets of A-type cranberry PACs in S. mutans while demonstrating that PAC oligomers with a specific DP may be effective in disrupting the assembly of cariogenic biofilms.

Coronavirus-mimicking nanoparticles (CorNPs) in artificial saliva droplets and nanoaerosols: Influence of shape and environmental factors on particokinetics/particle aerodynamics.

Severe acute respiratory syndrome coronavirus 2, abbreviated as SARS-CoV-2, has been associated with the transmission of infectious COVID-19 disease through breathing and speech droplets emitted by infected carriers including asymptomatic cases. As part of SARS-CoV-2 global pandemic preparedness, we studied the transmission of aerosolized air mimicking the infected person releasing speech aerosol with droplets containing CorNPs using a vibrating mesh nebulizer as human patient simulator. Generally speech produces nanoaerosols with droplets of <5 µm in diameter that can travel distances longer than 1 m after release. It is assumed that speech aerosol droplets are a main element of the current Corona virus pandemic, unlike droplets larger than 5 m, which settle down within a 1 m radius. There are no systemic studies, which take into account speech-generated aerosol/droplet experimental validation and their aerodynamics/particle kinetics analysis. In this study, we cover these topics and explore role of residual water in aerosol droplet stability by exploring drying dynamics. Furthermore, a candle experiment was designed to determine whether air pollution might influence respiratory virus like nanoparticle transmission and air stability.

Porphyromonas gingivalis in oral squamous cell carcinoma: a review.

Oral cancer contributes significantly to the global cancer burden. Oral bacteria play an important role in the spread of oral cancer, according to mounting evidence. The most proven instance is the carcinogenic implications of Porphyromonas gingivalis, a key pathogen in chronic periodontitis. It is imperative to understand the pathogenesis of P. gingivalis in OSCC. This review aims to gather and assess scientific shreds of evidence on the involvement of P. gingivalis in the molecular mechanism of oral squamous cell carcinoma.

Improvements in SO2 pollution in India: role of technology and environmental regulations.

India relies heavily on coal-based thermal power plants to meet its energy demands. Sulphur dioxide (SO2) emitted from these plants and industries is a major air pollutant. Analysis of spatial and temporal changes in SO2 using accurate and continuous observations is required to formulate mitigation strategies to curb the increasing air pollution in India. Here, we present the temporal changes in SO2 concentrations over India in the past four decades (1980-2020). Our analysis shows that the Central and East India, and Indo-Gangetic Plain (IGP) are the hotspots of SO2, as these regions house a cluster of thermal power plants, petroleum refineries, steel manufacturing units, and cement Industries. Thermal power plants (51%), and manufacturing and construction industries (29%) are the main sources of anthropogenic SO2 in India. Its concentration over India is higher in winter (December-February) and lower in pre-monsoon (March-May) seasons. The temporal analyses reveal that SO2 concentrations in India increased between 1980 and 2010 due to high coal burning and lack of novel technology to contain the emissions during the period. However, SO2 shows a decreasing trend in recent decade (2010-2020) because of the environmental regulations and implementation of effective control technologies such as the flue gas desulphurisation (FGD) and scrubber. Since 2010, India's renewable energy production has also been increased substantially when India adopted a sustainable development policy. Therefore, the shift in energy production from conventional coal to renewable sources, solid environmental regulation, better inventory, and effective technology would help to curb SO2 pollution in India. Both economic growth and air pollution control can be performed hand-in-hand by adopting new technology to reduce SO2 and GHG emissions.

Biofilm inhibition in Candida albicans with biogenic hierarchical zinc-oxide nanoparticles.

The present study demonstrates lignin (L), fragments of lignin (FL), and oxidized fragmented lignin (OFL) as templates for the synthesis of zinc oxide nanoparticles (ZnO NPs) viz., lignin-ZnO (L-ZnO), hierarchical FL-ZnO, and OFL-ZnO NPs. The X-ray diffraction patterns confirmed the formation of phase pure ZnO NPs with a hexagonal wurtzite structure. Electron microscopy confirmed the hierarchical structures with one-dimensional arrays of ZnO NPs with an average particle diameter of 40 nm. The as-synthesized L-ZnO, FL-ZnO, and OFL-ZnO NPs were tested in-vitro for growth and virulence inhibition (morphogenesis and biofilm) in Candida albicans. L-ZnO, FL-ZnO, and OFL-ZnO NPs all inhibited growth and virulence. Growth and virulence inhibitions were highest (more than 90%, respectively at 125, 31.2, and 62.5 µg/mL) in presence of FL-ZnO NPs, indicating that the hierarchical FL-ZnO NPs were potent growth and virulence inhibiting agent than non-hierarchical ZnO NPs. Furthermore, the real-time polymerase chain (RT-PCR) was used to study the virulence inhibition molecular mechanisms of L-ZnO, FL-ZnO, and OFL-ZnO NPs. RT-PCR results showed that the downregulation of phr1, phr2, efg1, hwp1, ras1, als3 and als4, and the upregulation of bcy1, nrg1, and tup1 genes inhibited the virulence in C. albicans. Lastly, we also performed in-vitro test cell cytotoxicity on the cell line, mouse embryo 3T3L1, and in-vivo toxicity on Rats, which showed that FL-ZnO NPs were biocompatible and nontoxic.

Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro.

The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed in vitro enzymatic inhibitory activity of active ingredients in the oral mouth rinse products: aloin A and B, chlorhexidine, eucalyptol, hexetidine, menthol, triclosan, methyl salicylate, sodium fluoride and povidone, against two important proteases of SARS-CoV-2 PLpro and 3CLpro. Our results indicate only aloin A and B effectively inhibited proteolytic activity of PLpro with an IC50 of 13.16 and 16.08 µM. Interestingly, neither of the aloin isoforms inhibited 3CLpro enzymatic activity. Computational structural modelling of aloin A and B interaction with PLpro revealed that, both aloin isoforms form hydrogen bond with Tyr268 of PLpro, which is critical for their proteolytic activity. Furthermore, 100 ns molecular dynamics (MD) simulation studies predicted that both aloin isoforms have strong interaction with Glu167, which is required for PLpro deubiquitination activity. Our results from the in vitro deubiquitinase inhibition assay show that aloin A and B isomers exhibit deubiquitination inhibitory activity with an IC50 value of 15.68 and 17.51 µM, respectively. In conclusion, the isoforms of aloin inhibit both proteolytic and the deubiquitinating activity of SARS-CoV-2 PLpro, suggesting potential in inhibiting the replication of SARS-CoV-2 virus.

Curcumin-Pluronic Nanoparticles: A Theranostic Nanoformulation for Alzheimer's Disease.

There is an increased need of drugs with multifunctional properties for visualization of ß-amyloid (Aß) plaques for early diagnosis and treatment of Alzheimer's disease (AD). Curcumin (Cur) is a potent antiamyloid, antiinflammatory, and antiapoptotic natural product that has been used to treat several neurodegenerative diseases, including AD. Curcumin can reduce amyloid burden, rescue neuronal damage, and restore normal cognitive and sensory motor functions in AD. Curcumin is a promising natural product theranostic because it fluoresces and preferentially binds to misfolded Aß. However, poor water solubility, limited bioavailability, and inability to cross the blood-brain barrier (BBB) limit curcumin use for biological applications. In this work, ultrasmall (~ 11 nm) curcumin encapsulated Pluronic F127 nanoparticles (FCur NPs) were developed and optimized to enhance bioavailability, facilitate circulation in the bloodstream, and improve BBB penetration. We compare BBB crossing ability of FCur NPs and free curcumin using an in vitro BBB model, and we demonstrate brain accumulation following intravenous administration to healthy mice. FCur NPs display 6.5-fold stronger fluorescent intensity in the brain than those from free curcumin. In addition, in vitro comparison with Congo red, a marker for Aß plaques, revealed that encapsulated curcumin maintains its ability to bind to Aß plaques. FCur NPs exhibited antioxidant and antiapoptotic activity when compared to free curcumin. The combination of in vitro and in vivo results suggest potential utility of the inexpensive FCur NPs as a theranostic agent for AD.

3D Printing - Evaluating Particle Emissions of a 3D Printing Pen.

Three-dimensional (3D) printing as a type of additive manufacturing shows continuing increase in application and consumer popularity. The fused filament fabrication (FFF) is an inexpensive method used most frequently by consumers. Studies with 3D printers have shown that during the printing process particulate and volatile substances are released. Handheld 3D printing pens also use the FFF method but the consumer's proximity to the 3D pens gives reason to higher exposure compared to a 3D printer. At the same time, 3D printing pens are often marketed for children who could be more sensitive to the printing emission. The aim of this study was to implement a low cost method to analyze the emissions of 3D printing pens. Polylactide (PLA) and acrylonitrile butadiene styrene (ABS) filaments of different colors were tested. In addition, filaments containing metal and carbon nanotubes (CNTs) were analyzed. An 18.5 L chamber and sampling close to the emission source was used to characterize emissions and concentrations near the breathing zone of the user. Particle emissions and particle size distributions were measured and the potential release of metal particles and CNTs investigated. Particle number concentrations were found in a range of 105 - 106 particles/cm3, which is comparable to previous reports from 3D printers. Transmission electron microscopy (TEM) analysis showed nanoparticles of the different thermoplastic materials as well as of metal particles and CNTs. High contents of metal were observed by inductively coupled plasma mass spectrometry (ICP-MS). These results call for a cautious use of 3D pens due to potential risk to the consumers.

Boron-Nanoparticle-Loaded Folic-Acid-Functionalized Liposomes to Achieve Optimum Boron Concentration for Boron Neutron Capture Therapy of Cancer.

In this study, we have synthesized and characterized a pure boron nanoparticle containing asolectin phospholipid-based liposome construct prepared using a water-in-oil emulsion method, as a novel alternative agent for BNCT, which contain poly(maleic anhydride-alt-1-octadecene) (PMAO) and polyethylene glycol (PEG) on the surface, and Cy5 near infrared (NIR) fluorescent dye and boron nanoparticles in the core (3PCB). A tumor-specific targeting ligand, folic acid (FA), was conjugated to PEG to produce a folate-functionalized liposome (FA-3PCB) for improved targeted delivery and accumulation of boron in cancer cells. The liposomes showed an average diameter of 100-120 nm and zeta potential of -38.0±1.5 mV. Cellular uptake monitored by fluorescence microscopy confirmed the targeting capability of FA-conjugated liposomes. Accumulation of FA-conjugated liposomes in C6-brain tumor cells was much higher than that of non-FA conjugated liposomes under the same conditions. ICP-MS (Inductively Coupled Plasma Mass Spectrometry) quantification confirmed that boron accumulated in cancer cells to sufficient intracellular concentration for therapeutic benefit from BNCT. These liposomes show blood-brain barrier (BBB) crossing ability, low cytotoxicity, and excellent stability under physiological conditions. Thus, these liposomes are a promising new boron carrier for BNCT.