Study on multiscale structures and digestibility of cassava starch and medium-chain fatty acids complexes using molecular simulation techniques.

Effect of complexation of three medium-chain fatty acids (octanoic, decylic and lauric acid, OA, DA and LA, respectively) on structural characteristics, physicochemical properties and digestion behaviors of cassava starch (CS) was investigated. Current study indicated that LA was more easily to combine with CS (complex index 88.9%), followed by DA (80.9%), which was also consistent with their corresponding complexed lipids content. Following the investigation of morphology, short-range ordered structure, helical structure, crystalline/amorphous region and fractal dimension of the various complexes, all cassava starch-fatty acids complexes (CS-FAs) were characterized with a flaked morphology rather than a round morphology in native starch (control CS). X-ray diffraction demonstrated that all CS-FAs had a V-type crystalline structure, and nuclear magnetic resonance spectroscopy confirmed that the complexes made from different fatty acids displayed similar V6 or V7 type polymorphs. Interestingly, small-angle X-ray scattering analysis revealed that α value became greater following increased carbon chain length of fatty acids, indicating the formation of a more ordered fractal structure in the aggregates. Changes in rheological parameters G' and G'' indicated that starch complexed with fatty acids was more likely to form a gel network, but difference among three CS-FAs complexes was significant, which might be contributed to their corresponding hydrophobicity and hydrophilicity raised from individual fatty acids. Importantly, digestion indicated that CS-LA complexes had the lowest hydrolysis degree, followed by the greatest RS content, indicating the importance of chain length of fatty acids for manipulating the fine structure and functionality of the complexes.

Flavor formation of tilapia byproduct hydrolysates in Maillard reaction.

The Maillard reaction (MR) of tilapia byproduct protein hydrolysates was investigated for the use of byproduct protein as a food ingredient and to mask its fishy odor and bitter flavor. The flavor differences in tilapia byproduct hydrolysates before and after the MR were analyzed to explore the key flavor precursor peptides and amino acids involved in MR. The results suggested that eight key volatile substances, including 2,5-dimethylpyrazine, 2-pentylfuran, hexanal, octanal, nonanal, (E)-2-decenal, decanal, and 1-octen-3-ol contributed most to the MR products group (ROAV > 1). Ten volatile compounds, including 1-octen-3-ol, hexanal, 2-pentylfuran, 2,5-dimethylpyrazine, methyl decanoate, and 2-octylfuran, were the flavor markers that distinguished the different samples (VIP > 1). The four most consumed peptides were VAPEEHPTL, GPIGPRGPAG, KSADDIKKAF, and VWEGQNIVK. Umami peptides and bitter free amino acids (FAAs) were the key flavor precursor peptide and FAAs, respectively. Overall, the hydrolysates of tilapia byproducts with flavor improved by MR are a promising strategy for the production of flavorings.

Deep learning-based radiomics model can predict extranodal soft tissue metastasis in gastric cancer.

BACKGROUND: The potential prognostic value of extranodal soft tissue metastasis (ESTM) has been confirmed by increasing studies about gastric cancer (GC). However, the gold standard of ESTM is determined by pathologic examination after surgery, and there are no preoperative methods for assessment of ESTM yet. PURPOSE: This multicenter study aimed to develop a deep learning-based radiomics model to preoperatively identify ESTM and evaluate its prognostic value. METHODS: A total of 959 GC patients were enrolled from two centers and split into a training cohort (N = 551) and a test cohort (N = 236) for ESTM evaluation. Additionally, an external survival cohort (N = 172) was included for prognostic analysis. Four models were established based on clinical characteristics and multiphase computed tomography (CT) images for preoperative identification of ESTM, including a deep learning model, a hand-crafted radiomic model, a clinical model, and a combined model. C-index, decision curve, and calibration curve were utilized to assess the model performances. Survival analysis was conducted to explore the ability of stratifying overall survival (OS). RESULTS: The combined model showed good discrimination of the ESTM [C-indices (95% confidence interval, CI): 0.770 (0.729-0.812) and 0.761 (0.718-0.805) in training and test cohorts respectively], which outperformed deep learning model, radiomics model, and clinical model. The stratified analysis showed this model was not affected by patient's tumor size, the presence of lymphovascular invasion, and Lauren classification (p < 0.05). Moreover, the model score showed strong consistency with the OS [C-indices (95%CI): 0.723 (0.658-0.789, p < 0.0001) in the internal survival cohort and 0.715 (0.650-0.779, p < 0.0001) in the external survival cohort]. More interestingly, univariate analysis showed the model score was significantly associated with occult distant metastasis (p < 0.05) that was missed by preoperative diagnosis. CONCLUSIONS: The model combining CT images and clinical characteristics had an impressive predictive ability of both ESTM and prognosis, which has the potential to serve as an effective complement to the preoperative TNM staging system.

Development of protein-polyphenol particles to stabilize high internal phase Pickering emulsions by polyphenols' structure.

Protein-polyphenol colloidal particles are promising stabilizers for high internal phase Pickering emulsions (HIPPEs). However, the relationship between the structure of the polyphenols and its ability to stabilize HIPPEs has not been studied thus far. In this study, bovine serum albumin (BSA)-polyphenols (B-P) complexes were prepared, and their ability to stabilize HIPPEs was investigated. The polyphenols were bound to BSA via non-covalent interactions. Optically isomeric polyphenols formed similar bonds with BSA, whereas a greater number of trihydroxybenzoyl groups or hydroxyl groups in the dihydroxyphenyl moieties of polyphenols increased the B-P interactions. Polyphenols also reduced the interfacial tension and enhanced the wettability at the oil-water interface. The HIPPE stabilized by BSA-tannic acid complex exhibited the highest stability among the B-P complexes and resisted demixing and aggregation during centrifugation. This study promotes the potential applications of polyphenol-protein colloidal particles-stabilized HIPPEs in the food industry.

Improving the flavor of tilapia fish head soup by adding lipid oxidation products and cysteine.

Deodorization and umami enhancement are important challenges in promoting and consuming fish products. The aim of this study was to establish whether exogenous addition of oxidized lipids and cysteine can improve the fishy, umami and create a characteristic flavor in tilapia fish head soup. The results revealed that adding oxidized lipids and cysteine enhanced the sensory attributes of fish head soup and promoted the production of pleasant-tasting amino acids and fewer bitter amino acids in the Maillard reaction. Additionally, the combination increased the levels of well-flavored aldehydes, esters, heterocyclic compounds and less hydrocarbons in the fish head soup. Among the 13 volatile compounds screened, nine were identified as characteristic aromas of fish head soup, including nonanal, (E,E)-2,4-decadienal, 1-octen-3-ol, (E)-2-decenal, acetic acid, hexanal, heptanal, 2-octenal, and decanal. Exogenous lipid oxidation products, fatty acid oxidation, and Maillard reaction can improve the aroma and umami of tilapia fish head soup.

Ultrasonic-assisted binding of canistel (Lucuma nervosa A.DC) seed starch with quercetin.

In order to provide a reference for improving the physicochemical properties of starch, the study of starch polyphenol complex interaction has aroused considerable interest. As a common method of starch modification, ultrasound can make starch granules have voids and cracks, and make starch and polyphenols combine more closely. In this research, canistel seed starch was modified by ultrasonic treatment alone or combined with quercetin. The molecular structure, particle characteristics and properties of starch were evaluated. With the increase of ultrasonic temperature, the particle size of the dextrinized starch granules increased, but the addition of quercetin could protect the destruction of starch granule size by ultrasonic; X-ray diffraction and infrared spectra indicated that quercetin was bound to the surface of canistel seed starch through hydrogen bonding, and the complex and the original starch had the same crystal structure and increased crystallinity; by molecular simulation, quercetin bound inside the starch molecular helix preserved the crystalline helical configuration of starch to some extent and inhibited the complete unhelicalization of starch molecules. Meanwhile, hydrogen bonding was the main driving force for the binding of starch molecules to quercetin, and van der Waals interactions also promoted the binding of both. In the physicochemical properties, as the temperature increased after the combination of ultrasonic modified starch combined with quercetin, the solubility, swelling force and apparent viscosity of the compound increased significantly, and it has higher stability and shear resistance.

Deep Penetrating and Sensitive Targeted Magnetic Particle Imaging and Photothermal Therapy of Early-Stage Glioblastoma Based on a Biomimetic Nanoplatform.

Early diagnosis can effectively improve the survival of glioblastoma multiforme (GBM). A specific imaging technique that is simultaneously deep penetrating and sensitive to small tissue changes is desired to identify GBM. Due to its excellent features in signal contrast, detection sensitivity, and none or little attenuation in tissue, magnetic particle imaging (MPI) possesses great potential in cancer diagnosis, especially when the imaging modality is equipped with specifically targeted nanoprobes. However, when gliomas are small, the blood-brain barrier (BBB) is complete and prevents nanoprobes from entering the brain, which negates the theranostic effect. This study proposes a biomimetic nanoplatform that assist the MPI tracers in breaking through the BBB and then demonstrate a targeted and sensitive diagnosis of GBM. Afterward, the photothermal therapy and immune regulation show an excellent therapeutic effect on the GBM. It is experimentally confirmed that the MPI signal does not decay with tissue depth and shows excellent sensitivity for thousands-cells. Only small animals are conducted in this study due to the limitations of the current commercial MPI scanner, however, this research theoretically enables large animal and human studies, which encourages a promising pathway toward the noninvasive diagnosis of early-stage GBM in clinics.

Planted Graphene Quantum Dots for Targeted, Enhanced Tumor Imaging and Long-Term Visualization of Local Pharmacokinetics.

While photoluminescent graphene quantum dots (GQDs) have long been considered very suitable for bioimaging owing to their protein-like size, superhigh photostability and in vivo long-term biosafety, their unique and crucial bioimaging applications in vivo remain unreachable. Herein, planted GQDs are presented as an excellent tool for in vivo fluorescent, sustainable and multimodality tumor bioimaging in various scenarios. The GQDs are in situ planted in the poly(ethylene glycol) (PEG) layer of PEGylated nanoparticles via a bottom-up molecular approach to obtain the NPs-GQDs-PEG nanocomposite. The planted GQDs show more than four times prolonged blood circulation and 7-8 times increased tumor accumulation than typical GQDs in vivo. After accessible specificity modification, the multifunctional NPs-GQDs-PEG provides targeted, multimodal molecular imaging for various tumor models in vitro or in vivo. Moreover, the highly photostable GQDs enable long-term, real-time visualization of the local pharmacokinetics of NPs in vivo. Planting GQDs in PEGylated nanomedicine offers a new strategy for broad in vivo biomedical applications of GQDs.

Identification and virtual screening of novel salty peptides from hydrolysate of tilapia by-product by batch molecular docking.

Introduction: Tilapia produces a large number of by-products during processing, which contain potentially flavorful peptides. Methods: The application of PyRx software enabled batch molecular docking andscreening of 16 potential salty peptides from 189 peptides identified in the enzymaticdigestion of tilapia by-products. Results: According to sensory analysis, all 16 peptides werepredominantly salty with a threshold of 0.256 - 0.379 mmol/L with some sournessand astringency, among which HLDDALR had the highest salty intensity, followedby VIEPLDIGDDKVR, FPGIPDHL, and DFKSPDDPSRH. I addition, moleculardocking results showed these four core peptides with high salt intensity bound to thesalt receptor TRPV1 mainly via van der Waals interactions, hydrogen bonds, andhydrophobic forces; Arg491, Tyr487, VAL441, and Asp708 were the key sites for thebinding of salty peptides to TRPV1. Therefore, the application of batch moleculardocking using PyRx is effective and economical for the virtual screening of saltypeptides.

Erratum: Highly sensitive magnetic particle imaging of vulnerable atherosclerotic plaque with active myeloperoxidase-targeted nanoparticles.

[This corrects the article DOI: 10.7150/thno.49812.].

Gut microbiota derived structural changes of phenolic compounds from colored rice and its corresponding fermentation property.

The influence of phenolic compound extracts from three colored rice cultivars on the gut microbiota was investigated. The results revealed that protocatechuic acid, chlorogenic acid, caffeic acid and p-coumaric acid were the major metabolites after gut microbiota fermentation. The presence of phenolic compounds led to a significantly decreased ratio of Firmicutes and Bacteroidetes, while the abundance of Proteobacteria decreased. At the genus level, phenolic compounds promoted an increase of Prevotella, Megamonas and Bifidobacterium, while the abundance of Bacteroides and Escherichia-Shigella was inhibited. The concentration of ferulic acid and syringic acid was positively correlated with Bifidobacterium, while Megamonas was positively correlated with catechin and caffeic acid. The abundance of Escherichia-Shigella and Citrobacter was found to be significantly negatively correlated with chlorogenic acid. More importantly, this study revealed that the presence of phenolic compounds generated more propionate, followed by acetate, but not butyrate after gut microbiota fermentation.

Colourful fluorescence-based carbon dots for tumour imaging-guided nanosurgery.

Fluorescent-intraoperative navigation is a visual technique that allows surgeons to accurately distinguish malignant and normal tissues during surgery. It has the advantages of immediacy, high resolution, and high specificity. However, a single fluorescent source cannot provide sufficient surgical information. Multicolour carbon dots (CDs) are more suitable since they provide outstanding water solubility, photostability, and multicolour-fluorescence imaging. Here, we prepared an optical probe with CD-based multicolour-fluorescence imaging via a hydrothermal method. CDs can be endocytosed by tumour cells, and after intravenous injection, they can effectively accumulate at the tumour site. In a pancreatic cancer mouse model, we demonstrated the multicolour-fluorescence imaging capabilities of CDs, which aided the accurate resection of tumours under fluorescent-intraoperative navigation. Stereoscopic fluorescence microscopy imaging and H&E staining proved that the removed tissue belonged to the pancreatic tumour. This study emphasizes the potential of CDs for fluorescence-guided intraoperative resection and expands the application of CDs in biological fields.

Targeted-detection and sequential-treatment of small hepatocellular carcinoma in the complex liver environment by GPC-3-targeted nanoparticles.

Despite advancements in diagnostic methods and therapeutic strategies, the mortality rate of hepatocellular carcinoma (HCC) remains as high as its incidence rate. Most liver cancers are detected in the advanced stages, when treatment options are limited. Small HCC is difficult to diagnose and is often overlooked by current imaging methods because of the complexity of the liver environment, especially in cirrhotic livers. In the present study, we developed a tumor "cruise missile", mesoporous Fe3O4-containing glucose oxidase-conjugated GPC3 peptide nanoparticles (FGP NPs). It was designed to enhance the accuracy of small HCC visualization to 85.7% using combined ultrasound/photoacoustic imaging in complex liver environment, which facilitated sequential catalytic targeted therapy for small HCC. In a carcinogen-induced mouse HCC model, FGP NPs could be used to accurately diagnose HCC in a liver cirrhosis background as well as distinguish HCC nodules from other abnormal liver nodules, such as cirrhosis nodules and necrotic nodules, by dynamic contrast-enhanced photoacoustic imaging. In a mouse xenograft HCC model, highly reactive oxygen species were formed by sequential catalytic reactions, which promoted HCC cell apoptosis, significantly increasing the survival of the model mice. The present study provides a basis for the precise detection and elimination of small HCCs in the complex liver environment.

A clinical study of a CD44v6-targeted fluorescent agent for the detection of non-muscle invasive bladder cancer.

BACKGROUND: Bladder cancer is the fifth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are difficult to visualize and can be overlooked, resulting in high recurrence rates. We previously developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds specifically to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared fluorescence endoscopic detection of bladder cancer. RESULTS: The purity, efficacy, safety, and nontoxicity of PLSWT7-DMI were confirmed prior to its clinical application. Twenty-two patients diagnosed with suspected non-muscle invasive bladder cancer were enrolled in the present study. Following intravesical administration of the probe, the entire mucosa was imaged under white and near-infrared imaging using an in-house developed endoscope that could switch between these two modes. The illuminated lesions under near-infrared light were biopsied and sent for histopathological examination. We observed a 5.1-fold increase in the fluorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and specificity of 91.2% and 90%, respectively. Common diagnostic challenges, such as small satellite tumors, carcinoma in situ, and benign suspicious mucosa, were visualized and could be distinguished from cancer. Furthermore, no adverse effects were observed in humans. These first-in-human results indicate that PLSWT7-DMI-based near-infrared fluorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence.

Biomimetic manganese-eumelanin nanocomposites for combined hyperthermia-immunotherapy against prostate cancer.

Pro-tumoral and immunosuppressive M2-like tumor-associated macrophages (TAMs) contribute to tumor progression, recurrence and distal metastasis. However, current TAMs-modulating therapeutic strategies often encounter challenges including insufficient immune activation, weak antigen presentation ability and unsatisfactory antitumor immune performance. Herein, cyclic RGD peptide functionalized and manganese doped eumelanin-like nanocomposites (RMnMels) are reported for combined hyperthermia-immunotherapy against PC3 prostate cancer. The RMnMels could promote M2-to-M1 macrophage repolarization via scavenging multiple reactive oxygen species and remodeling the immunosuppressive tumor microenvironment. Following near-infrared light irradiation, RMnMels-mediated thermal ablation not only could destroy tumor cells directly, but also elicit the release of damage associated molecular patterns and tumor-associated antigens, provoking robust tumor immunogenicity and strong antitumor immune responses. The results showed that RMnMels could effectively scavenge reactive oxygen species and promote M2-to-M1 macrophage repolarization both in vitro and in vivo. Synergistically enhanced anti-tumor therapeutic efficacy was achieved following single administration of RMnMels plus single round of laser irradiation, evidenced by decreased primary tumor sizes and decreased number of distant liver metastatic nodules. The as-developed RMnMels may represent a simple and high-performance therapeutic nanoplatform for immunomodulation and enhanced antitumor immune responses.

Physicochemical and volatile characteristics present in different grain layers of various rice cultivars.

Five rice cultivars were applied for investigating effect of milling degree on rice physicochemical properties. The first layer had the lowest peak viscosity, followed by the second and third layers, indicating the effect of non-starchy components on starch gelatinization behaviors. Consistently, more content of non-starch components in the first layer led to an enhanced gelatinization temperature. Rheological study demonstrated the G' and G" were successively increased as the layer moved inward, indicating a stronger gel network due to the increased amylose content and crystallinity in the corresponding layer. This is the first study to reveal the second layer has the highest digestibility, suggesting both non-starch components and starch structure control starch digestion. Furthermore, analysis of volatile compounds found alcohols and ketones concentrated in the first layer, whilst compounds including (E,E)-2,4-decadienal, 3-octanone and 3-nonen-2-one only existed in the second layer, serving as an indicator for managing the rice quality during milling.

Decreasing hyaluronic acid combined with drug-loaded nanoprobes improve the delivery and efficacy of chemotherapeutic drugs for pancreatic cancer.

Pancreatic cancer is one of the common malignant tumors of the digestive system, and its clinical treatment is still very challenging. Most of the pancreatic cancer chemotherapeutic drugs have poor plasma stability, low cell uptake efficiency, and are prone to developing drug resistance and toxic side effects. Besides, pancreatic cancer often has a dense extracellular matrix, which consists of collagens, hyaluronic acid, and other proteoglycans. Among them, hyaluronic acid is a key component of the dense matrix, which results in vascular compression and insufficient perfusion, and hinders the delivery of chemotherapeutic drugs. In this study, we explore using hyaluronidase in tumor-bearing mice to eliminate the hyaluronic acid barrier, to reduce blood vessel compression and reshape the tumor microenvironment. In addition, we evaluate using doxorubicin-loaded nanoprobes to improve the stability and local tumor-killing effect of the drug. The nanoprobes have the characteristics of near-infrared optical imaging, which are used to monitor the tumor size in real-time during the treatment process, and dynamically observe the tumor inhibitory effect. The results show that elimination of the hyaluronic acid barrier combined with the doxorubicin-loaded nanoprobes can greatly increase drug penetration into tumor tissue and improve the effectiveness of chemotherapy drugs. This study provides a novel strategy for the treatment of pancreatic cancer.

Activable Nanoparticle for Tumor Aggressiveness and Drug Resistance Prediction by Glutathione Heterogeneous Imaging.

Studies have shown that a higher GSH level is related to more drug-resistant and invasiveness of a tumor. However, it is a great challenge to accurately imaging the GSH level in vivo, for its imaging intensity will interfered by different accumulation of probes in the tumor. Thus, we hypothesized ratiometric photoacoustic imaging that can be used to predict the drug-resistant and invasiveness of tumors by accurate GSH level imaging. In this study, we synthesized MnO2/Indocyanine Green (MnO2/ICG). It can be used as ratiometric photoacoustic (PA) imaging probe, for its absorption at 780 nm (Ab780) can be decreased and 680 nm (Ab680) remain unchanged upon GSH reduction. And our results confirmed that a lower PA absorption ratio (Ab780/Ab680) corresponded to a higher GSH level of the tumor. Besides, the near-infrared fluorescence (FI) imaging was used as an assistant, for it can be quenched upon GSH. Therefore, MnO2/ICG can predict the tumor invasiveness and drug resistance by imaging the GSH level. This study provides reference to predict the prognosis of tumors by imaging the metabolic biomarker of tumors.

Highly sensitive magnetic particle imaging of vulnerable atherosclerotic plaque with active myeloperoxidase-targeted nanoparticles.

Inflammation is a pivotal driver of atherosclerotic plaque progression and rupture and is a target for identifying vulnerable plaques. However, challenges arise with the current in vivo imaging modalities for differentiating vulnerable atherosclerotic plaques from stable plaques due to their low specificity and sensitivity. Herein, we aimed to develop a novel multimodal imaging platform that specifically targets and identifies high-risk plaques in vivo by detecting active myeloperoxidase (MPO), a potential inflammatory marker of vulnerable atherosclerotic plaque. Methods: A novel multimodal imaging agent, 5-HT-Fe3O4-Cy7 nanoparticles (5HFeC NPs), used for active MPO targeting, was designed by conjugating superparamagnetic iron oxide nanoparticles (SPIONs) with 5-hydroxytryptamine and cyanine 7 N-hydroxysuccinimide ester. The specificity and sensitivity of 5HFeC NPs were evaluated using magnetic particle imaging (MPI), fluorescence imaging (FLI), and computed tomographic angiography (CTA) in an ApoE-/- atherosclerosis mouse model. Treatment with 4-ABAH, an MPO inhibitor, was used to assess the monitoring ability of 5HFeC NPs. Results: 5HFeC NPs can sensitively differentiate and accurately localize vulnerable atherosclerotic plaques in ApoE-/- mice via MPI/FLI/CTA. High MPI and FLI signals were observed in atherosclerotic plaques within the abdominal aorta, which were histologically confirmed by multiple high-risk features of macrophage infiltration, neovascularization, and microcalcification. Inhibition of active MPO reduced accumulation of 5HFeC NPs in the abdominal aorta. Accumulation of 5HFeC NPs in plaques enabled quantitative evaluation of the severity of inflammation and monitoring of MPO activity. Conclusions: This multimodal MPI approach revealed that active MPO-targeted nanoparticles might serve as a method for detecting vulnerable atherosclerotic plaques and monitoring MPO activity.

Effect of drying treatment on the structural characterizations and physicochemical properties of starch from canistel (Lucuma nervosa A.DC).

This work investigated the effects of hot air drying pretreatment (HAD), freeze drying pretreatment (FD) and vacuum drying pretreatment (VD) on the physicochemical properties and structural characterizations of starch isolated from canistels. X-ray diffraction displayed that the starches separated from canistel by different drying pretreatments showed a typical A-type crystal structure. The SEM image showed that cracks and debris appeared on the surface of HVD and VD particles. The molecular structure of starches obtained by different drying pretreatments was studied using Fourier infrared and solid state 13C CP/MAS NMR analysis. The results indicated that vacuum drying pretreatment could promote the formation of the double helix of starch granules, and hot air drying and freeze drying destroyed the ordered structure of starch granules. These structural changed to affect the physicochemical properties of starch granules. The study of different drying pretreatments to separate starches provided practical value for drying pretreatments. Furthermore, the current study affords information for canistel starches cultivated in China that would be convenient for commercial applications.