INZ-701, a recombinant ENPP1 enzyme, prevents ectopic calcification in an Abcc6-/- mouse model of pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE), a heritable multisystem ectopic calcification disorder, is predominantly caused by inactivating mutations in ABCC6. The encoded protein, ABCC6, is a hepatic efflux transporter and a key regulator of extracellular inorganic pyrophosphate (PPi). Recent studies demonstrated that deficiency of plasma PPi, a potent endogenous calcification inhibitor, is the underlying cause of PXE. This study examined whether restoring plasma PPi levels by INZ-701, a recombinant human ENPP1 protein, the principal PPi-generating enzyme, prevents ectopic calcification in an Abcc6-/- mouse model of PXE. Abcc6-/- mice, at 6 weeks of age, the time of earliest stages of ectopic calcification, were injected subcutaneously with INZ-701 at 2 or 10 mg/kg for 2 or 8 weeks. INZ-701 at both doses increased steady-state plasma ENPP1 activity and PPi levels. In the 8-week treatment study, histopathologic examination and quantification of the calcium content in INZ-701-treated Abcc6-/- mice revealed significantly reduced calcification in the muzzle skin containing vibrissae, a biomarker of the calcification process in these mice. The extent of calcification corresponds to the local expression of two calcification inhibitors, osteopontin and fetuin-A. These results suggest that INZ-701 might provide a therapeutic approach for PXE, a disease with high unmet needs and no approved treatment.

Combined fluorescence-guided surgery and photodynamic therapy for glioblastoma multiforme using cyanine and chlorin nanocluster.

INTRODUCTION: Glioblastoma multiforme (GBM) is the most common primary intracranial malignancy; survival can be improved by maximizing the extent-of-resection. METHODS: A near-infrared fluorophore (Indocyanine-Green, ICG) was combined with a photosensitizer (Chlorin-e6, Ce6) on the surface of superparamagnetic-iron-oxide-nanoparticles (SPIONs), all FDA-approved for clinical use, yielding a nanocluster (ICS) using a microemulsion. The physical-chemical properties of the ICS were systematically evaluated. Efficacy of photodynamic therapy (PDT) was evaluated in vitro with GL261 cells and in vivo in a subtotal resection trial using a syngeneic flank tumor model. NIR imaging properties of ICS were evaluated in both a flank and an intracranial GBM model. RESULTS: ICS demonstrated high ICG and Ce6 encapsulation efficiency, high payload capacity, and chemical stability in physiologic conditions. In vitro cell studies demonstrated significant PDT-induced cytotoxicity using ICS. Preclinical animal studies demonstrated that the nanoclusters can be detected through NIR imaging in both flank and intracranial GBM tumors (ex: 745 nm, em: 800 nm; mean signal-to-background 8.5 ± 0.6). In the flank residual tumor PDT trial, subjects treated with PDT demonstrated significantly enhanced local control of recurrent neoplasm starting on postoperative day 8 (23.1 mm3 vs 150.5 mm3, p = 0.045), and the treatment effect amplified to final mean volumes of 220.4 mm3 vs 806.1 mm3 on day 23 (p = 0.0055). CONCLUSION: A multimodal theragnostic agent comprised solely of FDA-approved components was developed to couple optical imaging and PDT. The findings demonstrated evidence for the potential theragnostic benefit of ICS in surgical oncology that is conducive to clinical integration.

Lattice -Mismatch-Induced Ultrastable 1T-Phase MoS2-Pd/Au for Plasmon-Enhanced Hydrogen Evolution.

Metallic 1T-phase transition metal dichalcogenides (TMDs) are of considerable interest in enhancing catalytic applications due to their abundant active sites and good conductivity. However, the unstable nature of 1T-phase TMDs greatly impedes their practical applications. Herein, we developed a new approach for the synthesis of highly stable 1T-phase Au/Pd-MoS2 nanosheets (NSs) through a metal assembly induced ultrastable phase transition for achieving a very high electrocatalytic activity in the hydrogen evolution reaction. The phase transition was evoked by a novel mechanism of lattice-mismatch-induced strain based on density functional theory (DFT) calculations. Raman spectroscopy and transmission electron microscopy (TEM) were used to confirm the phase transition on experimental grounds. A novel heterostructured 1T MoS2-Au/Pd catalyst was designed and synthesized using this mechanism, and the catalyst exhibited a 0 mV onset potential in the hydrogen evolution reaction under light illumination. Therefore, this method can potentially be used to fabricate 1T-phase TMDs with remarkably enhanced activities for different applications.

Dextran-Benzoporphyrin Derivative (BPD) Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Micelles for T2-Weighted Magnetic Resonance Imaging and Photodynamic Therapy.

Photodynamic therapy (PDT) has attracted extensive attention in recent years as a noninvasive and locally targeted cancer treatment approach. Nanoparticles have been used to improve the solubility and pharmacokinetics of the photosensitizers required for PDT; however, nanoparticles also suffer from many shortcomings including uncontrolled drug release and low tumor accumulation. Herein, we describe a novel biodegradable nanoplatform for the delivery of the clinically used PDT photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA) to tumors. Specifically, the hydrophobic photosensitizer BPD was covalently conjugated to the amine groups of a dextran-b-oligo (amidoamine) (dOA) dendron copolymer, forming amphiphilic dextran-BPD conjugates that can self-assemble into nanometer-sized micelles in water. To impart additional imaging capabilities to these micelles, superparamagnetic iron oxide nanoparticles (SPIONs) were encapsulated within the hydrophobic core to serve as a magnetic resonance imaging (MRI) contrast agent. The use of a photosensitizer as a hydrophobic building block enabled facile and reproducible synthesis and high drug loading capacity (∼30%, w/w). Furthermore, covalent conjugation of BPD to dextran prevents the premature release of drug during systemic circulation. In vivo studies show that the intravenous administration of dextran-BPD coated SPION nanoparticles results in significant MR contrast enhancement within tumors 24 h postinjection and PDT led to a significant reduction in the tumor growth rate.

Ozonation process intensification of p-nitrophenol by in situ separation of hydroxyl radical scavengers and microbubbles.

The ozonation efficiency for removal of recalcitrant organic pollutants in alkaline wastewater is always low because of the presence of some hydroxyl radical scavengers. To solve this problem, the O3/Ca(OH)2 system was put forward, and p-nitrophenol (PNP) was chosen to explore the mechanism of this system. The effects of key operational parameters were studied respectively; the Ca(OH)2 dosage 3 g/L, ozone inlet flow rate 3.5 L/min, ozone concentration 65 mg/L, reactor pressure 0.25 MPa, and temperature 25 °C were obtained as the optimal operating conditions. After 60 min treatment, the organic matter mineralized completely, which was higher than the sum of the ozonation-alone process (55.63%) and the Ca(OH)2 process (3.53%). It suggests that the calcium hydroxide in the O3/Ca(OH)2 process possessed a paramount role in the removal of PNP. The liquid samples and the precipitated substances were analyzed by gas chromatography mass spectrometry, X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy; it was demonstrated that Ca(OH)2 could accelerate the generation of hydroxyl radical and simultaneously in situ separate partial intermediate products and CO3 2- ions through some precipitation reactions.

Site-Specific Labeling of Cyanine and Porphyrin Dye-Stabilized Nanoemulsions with Affibodies for Cellular Targeting.

Recently, it has been shown that amphiphilic dyes such as Indocyanine Green (ICG) and Protoporphyrin IX (PpIX) can solubilize hydrophobic colloids and/or drugs by driving the formation of stable nanoemulsions. These nanoemulsions are unique in that they can be composed entirely of functional and clinically used materials; however, they lack bio-orthogonal chemical handles for the facile attachment of targeting ligands. The ability to target nanoparticles is desirable because it can lead to improved specificity and reduced side effects. Here, we describe variants of ICG and PpIX with azide handles that can be readily incorporated into dye-stabilized nanoemulsions and facilitate the attachment of targeting ligands via click-chemistry in a simple, scalable, and reproducible reaction. As a model system, an anti-Her2 affibody was site-specifically attached to both ICG and PpIX-stabilized nanoemulsions with encapsulated superparamagnetic iron oxide nanoparticles.

Protoporphyrin IX (PpIX)-Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Nanoclusters for Magnetic Resonance Imaging and Photodynamic Therapy.

The ability to produce nanotherapeutics at large-scale with high drug loading efficiency, high drug loading capacity, high stability, and high potency is critical for clinical translation. However, many nanoparticle-based therapeutics under investigation suffer from complicated synthesis, poor reproducibility, low stability, and high cost. In this work, a simple method for preparing multifunctional nanoparticles is utilized that act as both a contrast agent for magnetic resonance imaging and a photosensitizer for photodynamic therapy for the treatment of cancer. In particular, the photosensitizer protoporphyrin IX (PpIX) is used to solubilize small nanoclusters of superparamagnetic iron oxide nanoparticles (SPIONs) without the use of any additional carrier materials. These nanoclusters are characterized with a high PpIX loading efficiency; a high loading capacity, stable behavior; high potency; and a synthetic approach that is amenable to large-scale production. In vivo studies of photodynamic therapy (PDT) efficacy show that the PpIX-coated SPION nanoclusters lead to a significant reduction in the growth rate of tumors in a syngeneic murine tumor model compared to both free PpIX and PpIX-loaded poly(ethylene glycol)-polycaprolactone micelles, even when injected at 1/8th the dose. These results suggest that the nanoclusters developed in this work can be a promising nanotherapeutic for clinical translation.

Radiofrequency-Triggered Drug Release from Nanoliposomes with Millimeter-Scale Resolution Using a Superimposed Static Gating Field.

Drug delivery to a specific site in the body typically relies on the use of targeting agents that recognize a unique biomarker. Unfortunately, it is often difficult to identify unique molecular signatures that exist only at the site of interest. An alternative strategy is to deliver energy (e.g., light) to locally trigger release from a drug carrier; however, the use of this approach is limited because energy delivery to deep tissues is often impractical or invasive. In this work, radiofrequency-responsive superparamagnetic iron oxide nanoparticles (SPIONs) are used to trigger drug release from nanoscale vesicles. Because the body is inherently nonmagnetic, this approach allows for deep tissue targeting. To overcome the unfavorable meter-scale diffraction limit of SPION-compatible radiofrequency (RF) fields, a strong static gating field containing a sharp zero point is superimposed on the RF field. Only drug carriers that are at or near the zero point are susceptible to RF-triggered drug release, thereby localizing drug delivery with millimeter-scale resolution. This approach induces >40% drug release from thermally responsive doxorubicin-loaded liposomes within a 3.2 mm radius of the zero point with <10% release in the surrounding area, leading to a >2.5 therapeutic index in Huh 7 hepatocellular carcinoma cells.

Improved Photodynamic Therapy Efficacy of Protoporphyrin IX-Loaded Polymeric Micelles Using Erlotinib Pretreatment.

Photodynamic therapy (PDT) has attracted widespread attention in recent years as a noninvasive and highly selective approach for cancer treatment. We have previously reported a significant increase in the 90-day complete response rate when tumor-bearing mice are treated with the epidermal growth factor receptor (EGFR) inhibitor erlotinib prior to PDT with the photosensitizer benzoporphyrin-derivative monoacid ring A (BPD-MA) compared to treatment with PDT alone. To further explore this strategy for anticancer therapy and clinical practice, we tested whether pretreatment with erlotinib also exhibited a synergistic therapeutic effect with a nanocarrier containing the clinically relevant photosensitizer protoporphyrin IX (PpIX). The PpIX was encapsulated within biodegradable polymeric micelles formed from the amphiphilic block copolymer poly(ethylene glycol)-polycaprolactone (PEG-PCL). The obtained micelles were characterized systematically in vitro. Further, an in vitro cytotoxicity study showed that PDT with PpIX loaded micelles did exhibit a synergistic effect when combined with erlotinib pretreatment. Considering the distinct advantages of polymeric nanocarriers in vivo, this study offers a promising new approach for the improved treatment of localized tumors. The strategy developed here has the potential to be extended to other photosensitizers currently used in the clinic for photodynamic therapy.

Self-Targeted Polysaccharide Prodrug Suppresses Orthotopic Hepatoma.

Self-targetability is an emerging targeting strategy for polymer nanocarriers with facile preparation and high targeting efficiency. An acid-sensitive dextran-doxorubicin prodrug (Dex-g-DOX) has been synthesized and used as a self-targeted drug delivery system for the treatment of orthotopic hepatoma. The polysaccharide prodrug exhibits ultraselective accumulation in cancerous liver tissue, acid-sensitive DOX release within cells, and high antitumor efficacy in vitro and in vivo. Therefore, Dex-g-DOX demonstrates great potential for chemotherapy of orthotopic hepatoma.

Phosphorylation of Chs2p regulates interaction with COPII.

Trafficking of the chitin synthase Chs2p from the endoplasmic reticulum (ER) to the bud-neck in late mitosis is tightly regulated by the cell cycle via phosphorylation of serine residues in the N-terminus of the protein. Here, we describe the effects of Chs2p phosphorylation on the interaction with coat protein complex II (COPII). Identification of a cdc5(ts) mutant, which fails to transport Chs2p-3xGFP to the bud-neck and instead accumulates the protein in intracellular puncta, led us to discover that Chs2p-3xGFP accumulates at ER exit sites in metaphase-arrested wild-type cells. Using an in vitro ER vesicle formation assay we showed that phosphorylation of Chs2p by the cyclin-dependent kinase CDK1 prevents packaging into COPII vesicles, whereas dephosphorylation of Chs2p by the phosphatase Cdc14p stimulates selection into the vesicles. We found that the cytoplasmic N-terminal domain of Chs2p, which contains the CDK1 phosphorylation sites, interacts with the COPII component Sec24p in a yeast two-hybrid assay and that phosphomimetic substitutions of serines at the CDK1 consensus sites reduces the interaction. Our data suggest that dephosphorylation functions as a molecular switch for regulated ER exit of Chs2p.

A multifunctional nanoplatform for imaging, radiotherapy, and the prediction of therapeutic response.

Gold nanoparticles have garnered interest as both radiosensitzers and computed tomography (CT) contrast agents. However, the extremely high concentrations of gold required to generate CT contrast is far beyond that needed for meaningful radiosensitization, which limits their use as combined therapeutic-diagnostic (theranostic) agents. To establish a theranostic nanoplatform with well-aligned radiotherapeutic and diagnostic properties for better integration into standard radiation therapy practice, a gold- and superparamagnetic iron oxide nanoparticle (SPION)-loaded micelle (GSM) is developed. Intravenous injection of GSMs into tumor-bearing mice led to selective tumoral accumulation, enabling magnetic resonance (MR) imaging of tumor margins. Subsequent irradiation leads to a 90-day survival of 71% in GSM-treated mice, compared with 25% for irradiation-only mice. Furthermore, measurements of the GSM-enhanced MR contrast are highly predictive of tumor response. Therefore, GSMs may not only guide and enhance the efficacy of radiation therapy, but may allow patients to be managed more effectively.

Amyloid precursor protein (APP) traffics from the cell surface via endosomes for amyloid ß (Aß) production in the trans-Golgi network.

Amyloid precursor protein (APP) is processed sequentially by the ß-site APP cleaving enzyme and γ-secretase to generate amyloid ß (Aß) peptides, one of the hallmarks of Alzheimer's disease. The intracellular location of Aß production-endosomes or the trans-Golgi network (TGN)-remains uncertain. We investigated the role of different postendocytic trafficking events in Aß(40) production using an RNAi approach. Depletion of Hrs and Tsg101, acting early in the multivesicular body pathway, retained APP in early endosomes and reduced Aß(40) production. Conversely, depletion of CHMP6 and VPS4, acting late in the pathway, rerouted endosomal APP to the TGN for enhanced APP processing. We found that VPS35 (retromer)-mediated APP recycling to the TGN was required for efficient Aß(40) production. An interruption of the bidirectional trafficking of APP between the TGN and endosomes, particularly retromer-mediated retrieval of APP from early endosomes to the TGN, resulted in the accumulation of endocytosed APP in early endosomes with reduced APP processing. These data suggest that Aß(40) is generated predominantly in the TGN, relying on an endocytosed pool of APP recycled from early endosomes to the TGN.

Facile method for the site-specific, covalent attachment of full-length IgG onto nanoparticles.

Antibodies, most commonly IgGs, have been widely used as targeting ligands in research and therapeutic applications due to their wide array of targets, high specificity and proven efficacy. Many of these applications require antibodies to be conjugated onto surfaces (e.g. nanoparticles and microplates); however, most conventional bioconjugation techniques exhibit low crosslinking efficiencies, reduced functionality due to non-site-specific labeling and random surface orientation, and/or require protein engineering (e.g. cysteine handles), which can be technically challenging. To overcome these limitations, we have recombinantly expressed Protein Z, which binds the Fc region of IgG, with an UV active non-natural amino acid benzoylphenyalanine (BPA) within its binding domain. Upon exposure to long wavelength UV light, the BPA is activated and forms a covalent link between the Protein Z and the bound Fc region of IgG. This technology was combined with expressed protein ligation (EPL), which allowed for the introduction of a fluorophore and click chemistry-compatible azide group onto the C-terminus of Protein Z during the recombinant protein purification step. This enabled the crosslinked-Protein Z-IgG complexes to be efficiently and site-specifically attached to aza-dibenzocyclooctyne-modified nanoparticles, via copper-free click chemistry.

Enhanced photo-Fenton degradation of dyes under visible light with recyclable γ-Fe2O3/CQDs: Catalyst preparation, performance and mechanism insight.

A low band gap and visible light-responsive heterogeneous Photo-Fenton catalyst of γ-Fe2O3/CQDs micron composite was prepared under the one-pot hydrothermal method. The Photo-Fenton degradation of γ-Fe2O3/CQDs towards dye solution of rhodamine B(RhB), methyl blue (MB), and methyl orange (MO) was studied comparatively with α-Fe2O3. The γ-Fe2O3/CQDs exhibited remarkable catalytic performance for various dyes and with a first-order rate (k) of 14 times higher than that of initial α-Fe2O3 with a low concentration of H2O2 of 0.049 mmol. L-1 and a wider pH range of 3.1-7.1. The microstructure of the compounds was observed by XRD, SEM, TEM, FT-IR, and XPS characterization results suggested that the γ-Fe2O3/CQDs nanocomposite was formed through the stable Fe-O-C bonds, thus, the band gap decreased, and it is more favorable for the distance of holes and electrons. The free radical trapping experiment and EPR analysis indicated that •OH and 1O2 were the major active species during the typical photo-Fenton reaction. What's more, the γ-Fe2O3/CQDs also exhibited good stability and magnetic properties. DFT conclusion shows that the mechanism of the potential determination step (PDS) on α-Fe2O3(220) is the cleavage of H2O2 with an energy barrier of only 0.08 eV, which is 0.54 eV lower than that of OH* on γ-Fe2O3(220). Thus it can be deemed that γ-Fe2O3/CQDs perform much higher catalytic activity for the dissociation of H2O2 than α-Fe2O3. This work gives a feasible and economical countermeasure of visible light Photo-Fenton dispose of dye wastewater with a recyclable magnetic γ-Fe2O3/CQDs micron catalyst.

Exploration of a novel electrochemical CN coupling process: Urea synthesis from direct air carbon capture with nitrate wastewater.

Direct air capture (DAC) can be used to decrease the CO2 concentration in the atmosphere, but this requires substantial energy consumption. If residual waste carbon (in the form of bicarbonate solution) from DAC can be directly reused, it might present a novel method for overcoming the aforementioned challenges. Electrochemical CN coupling methods for synthesizing urea have garnered considerable attention for waste carbon utilization, but the carbon source is high-purity CO2. No research has been conducted regarding the application of bicarbonate solution as the carbon source. This study proposes a proof-of-concept electrochemical CN coupling process for synthesizing urea using bicarbonate solution from DAC as the carbon source and nitrate from wastewater as the nitrogen source. These results confirmed the feasibility of synthesizing urea using a three-electrode system employing TF and CuInS2/TF as the working electrodes via potentiostatic electrolysis. Under the optimal conditions (initial pH 5.0 and applied potential of -1.3 V vs. Ag/AgCl), the urea yield after 2 h of electrolysis reached 3017.2 µg h-1 mgcat.-1 and an average Faradaic efficiency of 19.6 %. The in-situ attenuated total reflection surface-enhanced infrared absorption spectroscopy indicated a gradual increase in the intensity of the -CONH bond signal on the surface of the CuInS2/TF electrode as the reaction progressed. This implied that this bond may be a key chemical group in this process. The density functional theory calculations demonstrated that *CONH was a pivotal intermediate during CN coupling, and a two-step CN coupling reaction path was proposed. *NH + *CO primarily transformed into *CONH, followed by the conversion reaction of *CONH + *NO to *NOCONH2. This study offers a groundbreaking approach for waste carbon utilization from DAC and holds the potential to furnish technical underpinnings for advancing electrochemical CN coupling methods.

Eddy Current Identification Methods and Applications in the Chemical Industry: A Mini-Review.

As one of the most common fluid patterns in the fluid flow process of chemical production, a vortex has been successfully demonstrated to be a structure that promotes interphase mixing and enhances heat and mass transfer. Therefore, it is essential to reveal the vortex evolution laws in order to realize more efficient and less energy-consuming chemical production. In this Mini-Review, the vortex identification criteria are introduced in detail and categorized according to their development history. The application of vortex identification technology and its application in the chemical industry are explored with a large number of examples. This review enhances our understanding of vortex structures and provides plenty of innovative ideas for the study of chemical industry production.

Continuous ultrasonic ozone coupling technology-assisted control of ceramic membrane fouling coupled enhanced multiphase mixing to treat dye wastewater and CFD flow field simulation.

In this study, ozone catalysts (hydrogenation-modified red mud, HM-RM) successfully prepared by hydrogenation-modification of industrial hazardous solid waste red mud (RM) as a raw material in accordance with the viewpoint of treating waste with waste and using waste. Meanwhile, as for the common phenomenon of membrane fouling, uneven distribution of multiphase solid catalysts and ozone in liquids, the addition of ultrasound can not only disperse materials, but also play a role in online cleaning of ceramic membranes and catalysts. The optimum treatment conditions for Rhodamine B (RhB) solution with volume of 2 L and concentration of 40 mg/L were catalyst concentration of 0.4 mg/L, reaction temperature of 45 °C, ultrasonic time of 1 h, ultrasonic intensity of 600 W, removal rate of RhB was up to 90 %. In addition, the computational fluid dynamics (CFD) simulation method was used to investigate the fluid flow between the two gas-liquid phases and the effect of the negative pressure of the membrane pump on the fluid by the analysis of flow, pressure and ozone flux of the ceramic membrane(CM) reaction apparatus. The CFD simulation results showed that at the inlet gas-liquid flow rate of 3 m/s and the negative pressure of 20,000 Pa, the maximum flow rates of CM-1 were 3 m/s, 0.752 m/s for CM-2, and 0.228 m/s for CM-3, respectively. Vortices, which are beneficial to solid-liquid mixing and gas-liquid mass transfer, formed between the suction port CM-1 of CM-1 and the inlets of CM-2 and CM-3. This discovery is consistent with relevant experimental research results. Significantly higher concentrations of both •OH and dissolved ozone were observed in the US/HM-RM/O3 system compared to other systems, indicating the significant improvement in ozone utilization rate through the application of ultrasound. The superiority of the US/HM-RM/O3 device was demonstrated. The real dye effluent was tested under optimum operating conditions and the results showed that COD and TOC were reduced by 81.34 % and 60.23 % respectively after 180 min of treatment. The above research can provide technical support for the treatment of dye wastewater using Ultrasound-enhanced ozone oxidation ceramic membranes.

In Vitro Hypoglycemic Activities of Lactobacilli and Bifidobacterium Strains from Healthy Children's Sources and Their Effect on Stimulating GLP-1 Secretion in STC-1 Cells.

A long-term use of chemical drugs cannot cure type II diabetes mellitus (T2DM) and their numerous toxic side effects can be harmful to human health. In recent years, probiotics have emerged as a natural resource to replace chemical drugs in alleviating many human ailments. Healthy children's intestines have a lot of colonized Lactobacilli and Bifidobacterium, and these beneficial bacteria can help promote overall health. The objective of this study was to isolate potential antidiabetic probiotic strains from healthy children and evaluate their application prospects. Firstly, Lactobacillus and Bifidobacterium strains were isolated from healthy children's feces and identified by the pheS or clpC genes with their respective 16S rRNA genes. Then, hydrophobicity, artificial gastrointestinal fluid tolerance, α-Glucosidase and Dipeptidyl peptidase IV (DPP-IV) inhibitory activities of isolated strains were determined, and antioxidant activities and promoting secretion of GLP-1 in STC-1 cells of candidate strains were tested. Results showed that 6 strains of Lactobacillus and Bifidobacterium were obtained from the feces of healthy children aged 3 years, respectively, including Lacticaseibacillus paracasei L-21 and L-25, Levilactobacillus brevis L-16, Lentilactobacillus buchneri L-9, Lactiplantibacillus plantarum L-8 and L-3, Bifidobacterium bifidum 11-1 and B-84, Bifidobacterium longum subsp. longum 6-1, 6-2, B42 and B53. The hydrophobicity and auto-aggregation levels of all these strains were higher than 30% and 50%, respectively, and the decrease in the number of colonies of all strains in the artificial gastrointestinal fluid was less than 2 log CFU/mL. Strains L-3, L-8, L-9, L-21, 6-1, 11-1, B53 and B84 were selected based on their high α-glucosidase inhibitory activity and DPP-IV inhibitory activity, and results of the antioxidant capacity assay showed that the remaining strains all had intense comprehensive antioxidant activity. Additionally, Lacticaseibacillus paracasei L-21 and Bifidobacterium longum subsp. longum B-53 had the most substantial prompting effect on GLP-1 secretion in the STC-1 cell line. These results indicated that Lacticaseibacillus paracasei L-21 and Bifidobacterium longum subsp. longum B-53 could be used as a potential antidiabetic strain; thus, its application as a food supplement and drug ingredient could be recommended after in vivo mitigation of type II diabetes test.

Theranostic Phthalocyanine and Naphthalocyanine Nanoparticles for Photoacoustic Imaging and Photothermal Therapy of Tumors.

Background: Phthalocyanine (PC) and naphthalocyanine (NC) dyes have long garnered interest as theranostic agents for optical imaging and phototherapy due to their near-infrared absorbance, photostability, imaging contrast, and proven safety in clinical trials. Yet, only a small fraction of these dyes has been evaluated as photothermal therapy (PTT) agents for cancer treatment. Methods: Nearly 40 distinct NC and PC dyes were encapsulated within polymeric PEG-PCL micelles via oil-in-water emulsions. The optimal NC/PC-loaded micelle formulations for PTT and photoacoustic (PA) imaging were identified through in vivo and in vitro studies. Results: The most promising candidate, CuNC(Octa)-loaded micelles, demonstrated a strong PA signal with a peak absorbance at ~870 nm, high photothermal efficiency, and photostability. The CuNC(Octa)-loaded micelles exhibited heat generation as good or better than gold nanorods/nanoshells and >10-fold higher photoacoustic signals. Micelle preparation was reproducible/scalable, and the CuNC(Octa)-loaded micelles are highly stable under physiological conditions. The CuNC(Octa)-loaded micelles localize within tumors via enhanced permeability and retention and are readily detectable by PA imaging. In a syngeneic murine tumor model of triple-negative breast cancer, CuNC(Octa)-loaded micelles demonstrate efficient heat generation with PTT, leading to the complete eradication of tumors. Conclusions: CuNC(Octa)-loaded micelles represent a promising theranostic agent for PA imaging and PTT. The ability to utilize conventional ultrasound in combination with PA imaging enables the simultaneous acquisition of information about tumor morphology and micelle accumulation. PTT with CuNC(Octa)-loaded micelles can lead to the complete eradication of highly invasive tumors.