Successful post-incomplete resection management of gastrointestinal stromal tumor using imatinib based on adenosine triphosphate-based tumor sensitivity assay in a dog.

Gastrointestinal stromal tumors arising from gastric cardia are uncommon in dogs. A few studies have shown the effectiveness of tyrosine kinase inhibitors in the treatment of canine gastrointestinal stromal tumors, but no standardized protocols are currently available. An 11-year-old spayed female Maltese dog was diagnosed with a gastrointestinal stromal tumor using histopathological and immunohistochemical analyses. An adenosine triphosphate-based tumor chemosensitivity assay revealed that imatinib at lower concentrations had a stronger inhibitory effect than toceranib. Based on the results of the assay, the dog was treated with imatinib after surgery. After 28 mo of therapy, there was no recurrence of the tumor. Key clinical message: Adenosine triphosphate-based tumor chemosensitivity assays may help clinicians to select appropriate postoperative chemotherapeutic drugs for incompletely resected gastrointestinal stromal tumors in dogs.

Gestion réussie à la suite d'une résection incomplète d'une tumeur stromale gastro-intestinale à l'aide de l'imatinib basée sur un test de sensibilité tumorale à base d'adénosine triphosphate chez un chien. Les tumeurs stromales gastro-intestinales résultant du cardia gastrique sont rares chez le chien. Quelques études ont montré l'efficacité des inhibiteurs de la tyrosine kinase dans le traitement des tumeurs stromales gastrointestinales canines, mais aucun protocole standardisé n'est actuellement disponible. Une chienne maltaise stérilisée de 11 ans a reçu un diagnostic de tumeur stromale gastro-intestinale à l'aide d'analyses histopathologiques et immunohistochimiques. Un test de chimiosensibilité tumorale à base d'adénosine triphosphate a révélé que l'imatinib à des concentrations plus faibles avait un effet inhibiteur plus fort que le tocéranib. Sur la base des résultats du test, le chien a été traité avec de l'imatinib après l'opération. Après 28 mois de traitement, il n'y a eu aucune récidive de la tumeur.Message clinique clé :Les tests de chimiosensibilité tumorale à base d'adénosine triphosphate peuvent aider les cliniciens à sélectionner les médicaments chimiothérapeutiques postopératoires appropriés pour les tumeurs stromales gastro-intestinales incomplètement réséquées chez le chien.(Traduit par Dr Serge Messier).

Facile Synthesis of Multifunctional Mesoporous Starch-Based Microparticle for Effective Hemostasis and Wound Healing.

Uncontrolled hemorrhage and infection are the principal causes of mortality associated with trauma in both military and civilian medical settings. Modified starch granules have emerged as a safe hemostatic agent for irregular and noncompressible wounds, but their performance is constrained by limited hemostasis efficiency and modest antibacterial activity. This study reported a directed self-assembly approach for a multifunctional mesoporous starch-based microparticle loaded with chitosan and calcium ions (Ca@MSMP) used for rapid hemostasis and wound healing. Directed self-assembly of uniform Ca@MSMP with a hierarchical hollow structure in the presence of chitosan was confirmed by scanning electron microscopy (SEM) analysis and pore structure analysis. The resulting Ca@MSMP exhibited a well-defined spherical shape and uniform size of 1 µm and demonstrated excellent antibacterial activity (>95%) without hemolytic activity. Importantly, Ca@MSMP enhanced blood coagulation and platelet aggregation via the synergistic effect of rapid calcium release and chitosan-mediated electrostatic interactions, leading to a significant decrease in blood loss and reduction in hemostasis time in rat tail amputation and liver injury models. In comparative analyses, Ca@MSMP significantly outperformed the commercial hemostatic agent Quickclean, notably enhancing the healing of full-thickness skin wounds in vivo by effectively preventing infection. These results underscore the potential of this innovative hemostatic material in diverse clinical scenarios, offering effective solutions for the management of bleeding in wounds that are irregularly shaped and noncompressible.

Hypertrophic Osteopathy Concurrent with an Aberrant Right Subclavian Artery in a Dog.

A 13-year-old spayed female cocker spaniel was presented with a 2-month history of swelling in several digits and intermittent hindlimb lameness. Radiographs revealed marked soft-tissue swelling and periosteal new bone formation without cortical bone destruction, characteristic of hypertrophic osteopathy (HO), in the distal parts of all extremities except for the right forelimb. However, no notable findings were detected in thoracic radiographs. An ultrasonography indicated cranial bladder wall thickening, which resolved following antibiotic therapy. Computed tomographic angiography identified a potential underlying cause as an aberrant right subclavian artery (ARSA) originating from the aortic arch, compressing the esophagus and causing mild esophageal cranial dilation to the aberrant vessel. No other intrathoracic or neoplastic lesions were observed. Gastrointestinal symptoms, such as regurgitation, were absent. Although an ARSA was likely the cause of HO, surgical correction was declined by the owner. To the best of our knowledge, this is the first reported case of HO concurrent with ARSA in dogs.

Enzymatic Synthesis of α-Glucan Microparticles Using Amylosucrases from Bifidobacterium Species and Its Physicochemical Properties.

α-Glucan microparticles (GMPs) have significant potential as high-value biomaterials in various industries. This study proposes a bottom-up approach for producing GMPs using four amylosucrases from Bifidobacterium sp. (BASs). The physicochemical characteristics of these GMPs were analyzed, and the results showed that the properties of the GMPs varied depending on the type of enzymes used in their synthesis. As common properties, all GMPs exhibited typical B-type crystal patterns and poor colloidal dispersion stability. Interestingly, differences in the physicochemical properties of GMPs were generated depending on the synthesis rate of linear α-glucan by the enzymes and the degree of polymerization (DP) distribution. Consequently, we found differences in the properties of GMPs depending on the DP distribution of linear glucans prepared with four BASs. Furthermore, we suggest that precise control of the type and characteristics of the enzymes provides the possibility of producing GMPs with tailored physicochemical properties for various industrial applications.

Ligand-based magnetic extraction and safety assessment of zinc oxide nanoparticles in food products.

Zinc oxide (ZnO) is a zinc supplement widely used in health products and is approved by the FDA as Generally Regarded as Safe (GRAS). However, concerns have arisen regarding the potential health effects of nanoscale ZnO, as its reactivity differs from that of its bulk form. This has led to the need for an efficient method to extract ZnO from food products without altering its physicochemical properties, where conventional methods have proven to be inadequate. This study introduces an innovative approach using starch magnetic particles (SMPs) functionalized with a 12-amino acid peptide modified with five lysines (ZBP), that has specific affinity to ZnO. ZBP@SMPs effectively and rapidly extract intact ZnO from food products, achieving recovery efficiencies ranging from 60% to 90%, all while maintaining its morphology and crystallinity. The diameter of ZnO particles recovered from six commercial food products ranged from 25 to 500 nm, with 33% falling below 100 nm, highlighting the need for a size-dependent toxicity study. However, cytotoxicity assessment on human intestinal Caco-2 cells shows all ZnO samples affects cell proliferation and membrane integrity in a dose-dependent manner due to partial dissolution. This study contributes to understanding the safety of ZnO-containing food products and highlights potential health implications associated with their consumption.

Identification of Micrococcin P2-Derivatives as Antibiotic Candidates against Two Gram-Positive Pathogens.

Thiopeptides exhibit potent antimicrobial activity against Gram-positive pathogens by inhibiting bacterial protein synthesis. Micrococcins are among the structurally simpler thiopeptides, but they have not been exploited in detail. This research involved a computational simulation of micrococcin P2 (MP2) docking in parallel with the structure-activity relationship (SAR) studied. The incorporation of particular nitrogen heterocycles in the side chain of MP2 enhances the antimicrobial activity. Micrococcin analogues 6c and 6d thus proved to be more effective against impetigo and C. difficile infection (CDI), respectively, as compared to current first-line treatments. Compound 6c also showed a shorter treatment period than that of a first-line treatment for impetigo. This may be attributed to its ability to downregulate pro-inflammatory cytokines. Compound 6d had no observed recurrence for C. difficile and exerted a minimal impact on the beneficial gut microbiome. Their pharmacokinetic properties and low toxicity profile make these compounds ideal candidates for the treatment of impetigo and CDI and validate their involvement in preclinical development.

Short-chain glucan self-assembly for green synthesis of functional biomaterials: Mechanism, synthesis, and microstructural control.

Short-chain glucan (SCG) is a linear homopolymer containing 10 to 50 glucose units linked with α(1,4) glycosidic bonds. With its abundant, low-cost, nontoxic, biodegradable/biocompatible nature, self-assembled SCG particles (SSC) have emerged as functional biomaterials, which have recently attracted tremendous attentions in various fields. SCG self-assembly occurs through the spontaneous association of molecules under equilibrium conditions into stable and structurally well-defined nanoscale or micrometer-scale aggregates, which is governed by various intermolecular non-covalent interactions, including hydrogen-bonding, electrostatic, hydrophobic, and van der Waals. With precise and effective control of the self-assembly process of SSC, its structural modulation and function integration can be expected. Thus, we convinced that SCG self-assembly could provide an effective means of developing starch-based functional biomaterials with beneficial health properties and wide application in food industries. In this review, we provide an overview of recent advances in the green approach for the self-assembly of SSC, as well as the influence of thermodynamic and kinetic factors on its morphology and physicochemical properties. We highlight recent contributions to developing strategies for the construction of SSC with increasing complexity and functionality that are suitable for a variety of food applications. Finally, we briefly outline our perspectives and discuss the challenges in the field.

Deep learning-based incoherent holographic camera enabling acquisition of real-world holograms for holographic streaming system.

While recent research has shown that holographic displays can represent photorealistic 3D holograms in real time, the difficulty in acquiring high-quality real-world holograms has limited the realization of holographic streaming systems. Incoherent holographic cameras, which record holograms under daylight conditions, are suitable candidates for real-world acquisition, as they prevent the safety issues associated with the use of lasers; however, these cameras are hindered by severe noise due to the optical imperfections of such systems. In this work, we develop a deep learning-based incoherent holographic camera system that can deliver visually enhanced holograms in real time. A neural network filters the noise in the captured holograms, maintaining a complex-valued hologram format throughout the whole process. Enabled by the computational efficiency of the proposed filtering strategy, we demonstrate a holographic streaming system integrating a holographic camera and holographic display, with the aim of developing the ultimate holographic ecosystem of the future.

High-Shear Granulation of Hygroscopic Probiotic-Encapsulated Skim Milk Powder: Effects of Moisture-Activation and Resistant Maltodextrin.

A fine, hygroscopic, and poorly flowable probiotic powder encapsulating Lactobacillus rhamnosus GG (LGG) was granulated using a high-shear granulation process, wherein a small amount of water (4%, w/w) was used for moisture-activation with or without 10% (w/w) resistant maltodextrin (RM). The process consisted of four steps; premixing, agglomeration, moisture absorption, and drying steps. The moisture content, water activity, and viable cell count were monitored during the granulation. The size, morphology, and flowability of the granules were determined. The powder was successfully converted to about 10-times-larger granules (mass mean diameter = 162-204 µm) by this process, and the granules had a 'snowball' morphology. The LGG cells were well preserved under the high-shear granulation conditions, and the viable cell count of the granules greatly exceeded the minimum therapeutic level recommended for probiotic powders. The addition of RM decreased the moisture content of the granules; improved cell resistance to drying stress; narrowed the particle size distribution, with reductions seen in both very fine and very large particles; and produced more flowable granules. Moisture sorption analysis and differential scanning calorimetry demonstrated that these positive effects of RM on granulation were primarily attributed to its water distribution ability rather than its glass transition-related binding ability.

Metal ion-mediated modulation of morphology, physicochemical properties, and digestibility of type 3 resistant starch microparticle.

Short-chain glucan (SCG) derived from debranched amylopectin has emerged as a promising candidate for the production of resistant starch particle (RSP) due to its controllable self-assembly features. Here, we investigated the effect of metal cations with different valencies and concentrations on the morphology, physicochemical properties, and digestibility of RSP formed by the self-assembly of SCG. The effect of cations on the formation of RSP followed the valency in the following order: Na+, Ka+, Mg2+, Ca2+, Fe3+, and Al3+, of which 10 mM trivalent cations increased the particle size of RSP over 2 µm and considerably decreased the crystallinity by 49.5 % ~ 50.9 %, which were significantly different from that of mono- and divalent ones. Importantly, RSP formed with divalent cations switched the surface charge from -18.6 mV to 12.9 mV, which significantly increased the RS level, indicating that metal cations would be useful for regulating physicochemical properties and digestibility of RSP.

Correction to: Versatile biotechnological applications of amylosucrase, a novel glucosyltransferase.

[This corrects the article DOI: 10.1007/s10068-019-00686-6.].

Modulation of the self-assembly kinetics and digestibility of type 3 resistant starch particles by co-crystallization with amino acid.

The effect of eight different l-amino acids (L-AA) on type-3 resistant starch particles (rSPs) derived from short chain glucan (SCG) was investigated. The L-AA were categorized based on their charge and polarity. The results reveal that positively charged L-AA, such as lysine and arginine, decreased the nucleation and growth rate of rSPs, while non-charged L-AA have negligible effects. Negatively charged L-AA, such as glutamic acid and aspartic acid, had a significant impact on the morphology and crystallinity of the rSPs, resulting in particle size of around 3 µm and crystallinity of around 35%. This implies that charged L-AA influence the arrangement of SCG double helices in the particles. Furthermore, the complexation of SCG with charged L-AA reduced the level of RS in rSPs, indicating that L-AA could be useful in modulating the physical properties and digestibility of rSPs.

Impact of solvent polarity on the morphology, physicochemical properties, and digestibility of A-type resistant starch particles.

Resistant starch particles (RSP) formed by antisolvent precipitation method has attracted much attention as a functional food ingredient having beneficial effects on obesity and diabetes. However, the effect of solvent polarity on the physicochemical properties and digestibility of RSP remains unclear. Here, n-propanol, isopropanol, acetone, and ethanol were employed as antisolvents to prepare RSP. The width and length of the resulting RSP decreased from 0.87 µm to 0.59 µm and from 2.56 µm to 1.31 µm, respectively, upon increasing the solvent polarity, while dramatically decreasing their crystallinity and the gelatinization enthalpy from 80.5% to 62.3% and from 67.9 ± 14.4 J/g to 41.5 ± 8.3 J/g, respectively, suggesting that solvent polarity is critical factor determining morphology, crystallinity, and thermostability of RSP. Furthermore, the level of resistant starch in RSP was found to be inversely proportional to the degree of solvent polarity, which would provide a useful means for modulating the digestibility of RSP.

Antibacterial Activity against Clinical Isolates and In Vivo Efficacy of Coralmycins.

Coralmycins, such as coralmycin A and DH-coralmycin A, have novel molecular skeletons and have been reported to exhibit potent antibacterial activity against standard Gram-positive bacterial strains. Here, the in vitro antibacterial activity against an extensive clinical isolate collection, time-kill kinetics, pharmacokinetics (PK), and in vivo efficacy of coralmycins were studied. Coralmycin A showed potent antibacterial activity with an MIC90 of 1 mg/L against 73 clinical methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci isolates, which was 2-8 times higher than the corresponding activities of DH-coralmycin A, vancomycin, daptomycin, and linezolid, and against 73 vancomycin-resistant Enterococcus and Streptococcus pneumoniae isolates, which was 4-16 times higher than the corresponding activities of DH-coralmycin A, daptomycin, and linezolid. Pharmacokinetic analysis after i.v. injection showed that coralmycins have a moderate volume of distribution and moderate-to-high clearance in mice. The coralmycin A and DH-coralmycin A bioavailability values were 61.3% and 11.7%, respectively, after s.c. administration. In a mouse respiratory tract infection model, coralmycin A showed bacteriostatic and bactericidal in vivo efficacies at an s.c. administration of 4 and 100 mg/kg bid, respectively; these efficacies were similar to those of vancomycin at 4 and 20 mg/kg bid, respectively. The present findings indicate that coralmycin A has great potential as a new class of antibiotic for treating infections caused by multidrug-resistant Gram-positive bacteria.

Facile preparation of highly uniform type 3 resistant starch nanoparticles.

Resistant starch (RS) has emerged as a promising functional food ingredient. To improve the textural and sensory characteristics of RS, there need to be an effective approach to produce RS with well-defined size and shape. Here, we present a facile approach for the synthesis of highly uniform resistant starch nanoparticles (RSNP) based on recrystallization of short-chain glucan (SCG) originated from debranched starch. We found that the ratio of SCG to partially debranched amylopectin was a key parameter in regulating the morphology, size, and crystallinity of the nanoparticles, which enable us to prepare highly uniform RSNP with an average diameter of around 150 nm, while showing a good colloidal stability over a broad range of pH (2-10). Moreover, the in-vitro digestibility and RS content of RSNP was not affected over the ten successive cycles of assembly and disassembly, which would provide useful insights for the development of RS-based functional food ingredients.

Micrococcin P2 Targets Clostridioides difficile.

Clostridioides difficile infection is a global public health threat. Extensive in vitro assays using clinical isolates have identified micrococcin P2 (MP2, 1) as a particularly effective anti-C. difficile agent. MP2 possesses a mode of action that differs from other antibiotics and pharmacokinetic properties that render it especially promising. Its time-kill studies have been investigated using hypervirulent C. difficile ribotype 027. DSS (dextran sulfate sodium)-induced in vivo mouse studies with that strain indicate that 1 is better than vancomycin and fidaxomicin. Thus, micrococcin P2 is a valuable platform to be exploited for the development of new anti-C. difficile antibiotics.

Nitro-Group-Containing Thiopeptide Derivatives as Promising Agents to Target Clostridioides difficile.

The US Centers for Disease Control and Prevention (CDC) lists Clostridioides difficile as an urgent bacterial threat. Yet, only two drugs, vancomycin and fidaxomicin, are approved by the FDA for the treatment of C. difficile infections as of this writing, while the global pipeline of new drugs is sparse at best. Thus, there is a clear and urgent need for new antibiotics against that organism. Herein, we disclose that AJ-024, a nitroimidazole derivative of a 26-membered thiopeptide, is a promising anti-C. difficile lead compound. Despite their unique mode of action, thiopeptides remain largely unexploited as anti-infective agents. AJ-024 combines potent in vitro activity against various strains of C. difficile with a noteworthy safety profile and desirable pharmacokinetic properties. Its time-kill kinetics against a hypervirulent C. difficile ribotype 027 and in vivo (mouse) efficacy compare favorably to vancomycin, and they define AJ-024 as a valuable platform for the development of new anti-C. difficile antibiotics.

Fabrication of starch/zein-based microcapsules for encapsulation and delivery of fucoxanthin.

As a drug carrier, starch-based microparticle (SMP) has attracted widespread attention. However, because SMP is commonly formed in aqueous media, it is facing the challenge of encapsulation of hydrophobic bioactive. Here, we present an effective method for encapsulating fucoxanthin (Fx), a model hydrophobic bioactive, within SMP formed by self-assembly of short-chain glucans (SCG), using zein nanoparticles as intermediate vectors. SMP exhibited higher encapsulation efficiency to chitosan-coated Fx-zein nanoparticles (∼91%) at a given concentration of 50 µg/mL compared to soybean polysaccharide-coated ones. Fx in SMP was found to be more stable against UV radiation-induced degradation and FeCl3-catalyzed oxidative stresses than free Fx. Furthermore, SMP conferred controlled release of Fx in the duodenum (6%), jejunum (13%), ileum (32%), and colon (42%), implying that this approach could be useful in designing an effective drug carrier for delivering several hydrophobic bioactives to different parts of the intestine.

Wide-viewing holographic stereogram based on self-interference incoherent digital holography.

We propose a holographic stereogram synthesis method which uses holograms that are optically captured by self-interference incoherent digital holography (SIDH) based on a geometric phase lens. SIDH is a promising solution for hologram acquisition under low-coherence lighting condition. A mechanical scanning system is constructed to acquire multiple perspective holograms. Numerical simulations and experimental analyses conducted using high-resolution diffractive optical element demonstrate that the proposed method can produce a wide-viewing hologram which can realize realistic 3D scenarios with depth cues such as accommodation and motion parallax. The future objectives include the implementation of a multiple-camera system for holographic videos.

Effect of organic acids on the morphology and particle size of titanium dioxide (E171) in processed food.

TiO2 (E171) is widely used in processed food as a coloring agent. However, growing concerns about the potential health effects of TiO2 nanoparticles (< 100 nm) have necessitated the need for monitoring the size distribution and cytotoxic properties of food additive TiO2 present in commercial food. In this study, we employed magnetic separation method to extract food additive TiO2 from 100 commercial foods. The extracted TiO2 had a mean particle diameter of 121-143 nm along with the fraction in nanoscale (< 100 nm) ranging from 7.5% to 35.7%, where certain types of food, such as candy and jelly, were shown to contain smaller TiO2 with higher fraction of nanoscale particles. Assuming that the low pH of the products with high content of organic acid is responsible for the smaller TiO2, the effect of three organic acids, such as acetic acid, ascorbic acid, and citric acid, on the physicochemical property of TiO2 was investigated. The citric acid was shown to reduce the size of TiO2 along with the generation of fragmented nanoparticles with a size of around 20 nm, whereas the effect of acetic acid and ascorbic acid was negligible. Although TiO2 treated with citric acid did not exhibit short-term cytotoxicity, this study suggests the importance of fully assessing the potential long-term health effect of food additive TiO2 whose physicochemical properties were altered in processed food.