Lacticaseibacillus paracasei JS-3 Isolated from "Jiangshui" Ameliorates Hyperuricemia by Regulating Gut Microbiota and iTS Metabolism.

Background: A diet high in purines can impair the function of the gut microbiota and disrupt purine metabolism, which is closely associated with the onset of hyperuricemia. Dietary regulation and intestinal health maintenance are key approaches for controlling uric acid (UA) levels. Investigating the impacts of fermented foods offers potential dietary interventions for managing hyperuricemia. Methods: In this study, we isolated a strain with potent UA-degrading capabilities from "Jiangshui", a fermented food product from Gansu, China. We performed strain identification and assessed its probiotic potential. Hyperuricemic quails, induced by a high-purine diet, were used to assess the UA degradation capability of strain JS-3 by measuring UA levels in serum and feces. Additionally, the UA degradation pathways were elucidated through analyses of the gut microbiome and fecal metabolomics. Results: JS-3, identified as Lacticaseibacillus paracasei, was capable of eliminating 16.11% of uric acid (UA) within 72 h, rapidly proliferating and producing acid within 12 h, and surviving in the gastrointestinal tract. Using hyperuricemic quail models, we assessed JS-3's UA degradation capacity. Two weeks after the administration of JS-3 (2 × 108 cfu/d per quail), serum uric acid (SUA) levels significantly decreased to normal levels, and renal damage in quails was markedly improved. Concurrently, feces from the JS-3 group demonstrated a significant degradation of UA, achieving up to 49% within 24 h. 16S rRNA sequencing revealed JS-3's role in gut microbiota restoration by augmenting the probiotic community (Bifidobacterium, Bacteroides unclassified_f-Lachnospiraceae, and norank_fynorank_o-Clostridia_UCG-014) and diminishing the pathogenic bacteria (Macrococus and Lactococcus). Corresponding with the rise in short-chain fatty acid (SCFA)-producing bacteria, JS-3 significantly increased SCFA levels (p < 0.05, 0.01). Additionally, JS-3 ameliorated metabolic disturbances in hyperuricemic quails, influencing 26 abnormal metabolites predominantly linked to purine, tryptophan, and bile acid metabolism, thereby enhancing UA degradation and renal protection. Conclusions: For the first time, we isolated and identified an active probiotic strain, JS-3, from the "Jiangshui" in Gansu, used for the treatment of hyperuricemia. It modulates host-microbiome interactions, impacts the metabolome, enhances intestinal UA degradation, reduces levels of SUA and fecal UA, alleviates renal damage, and effectively treats hyperuricemia without causing gastrointestinal damage. In summary, JS-3 can serve as a probiotic with potential therapeutic value for the treatment of hyperuricemia.

Mechanistic Insights into the Excited-State Intramolecular Proton Transfer (ESIPT) Process of 2-(2-Aminophenyl)naphthalene.

The 2-(2-aminophenyl)naphthalene molecule attracted much attention due to excited-state intramolecular proton transfer (ESIPT) from an amino NH2 group to a carbon atom of an adjacent aromatic ring. The ESIPT mechanisms of 2-(2-aminophenyl)naphthalene are still unclear. Herein, the decay pathways of this molecule in vacuum were investigated by combining static electronic structure calculations and nonadiabatic dynamics simulations. The calculations indicated the existence of two stable structures (S0-1 and S0-2) in the S0 and S1 states. For the S0-1 isomer, upon excitation to the Franck-Condon point, the system relaxed to the S1 minimum quickly, and then there exist four decay pathways (two ESIPT ones and two decay channels with C atom pyramidalization). In the ESIPT decay pathways, the system encounters the S1S0-PT-1 or S1S0-PT-2 conical intersection, which funnels the system rapidly to the S0 state. In the other two pathways, the system de-excited from the S1 to the S0 state via the S1S0-1 or S1S0-2 conical intersection. For the S0-2 structure, the decay pathways were similar to those of S0-1. The dynamics simulations showed that 75 and 69% of trajectories experienced the two ESIPT conical intersections for the S0-1 and S0-2 structures, respectively. Our simulations showed that the lifetime of the S1 state of S0-1 (S0-2) is estimated to be 358 (400) fs. Notably, we not only found the detailed reaction mechanism of the system but also found that the different ground-state configurations of this system have little effect on the reaction mechanism in vacuum.

Enhanced Lightweight YOLOX for Small Object Wildfire Detection in UAV Imagery.

Target detection technology based on unmanned aerial vehicle (UAV)-derived aerial imagery has been widely applied in the field of forest fire patrol and rescue. However, due to the specificity of UAV platforms, there are still significant issues to be resolved such as severe omission, low detection accuracy, and poor early warning effectiveness. In light of these issues, this paper proposes an improved YOLOX network for the rapid detection of forest fires in images captured by UAVs. Firstly, to enhance the network's feature-extraction capability in complex fire environments, a multi-level-feature-extraction structure, CSP-ML, is designed to improve the algorithm's detection accuracy for small-target fire areas. Additionally, a CBAM attention mechanism is embedded in the neck network to reduce interference caused by background noise and irrelevant information. Secondly, an adaptive-feature-extraction module is introduced in the YOLOX network's feature fusion part to prevent the loss of important feature information during the fusion process, thus enhancing the network's feature-learning capability. Lastly, the CIoU loss function is used to replace the original loss function, to address issues such as excessive optimization of negative samples and poor gradient-descent direction, thereby strengthening the network's effective recognition of positive samples. Experimental results show that the improved YOLOX network has better detection performance, with mAP@50 and mAP@50_95 increasing by 6.4% and 2.17%, respectively, compared to the traditional YOLOX network. In multi-target flame and small-target flame scenarios, the improved YOLO model achieved a mAP of 96.3%, outperforming deep learning algorithms such as FasterRCNN, SSD, and YOLOv5 by 33.5%, 7.7%, and 7%, respectively. It has a lower omission rate and higher detection accuracy, and it is capable of handling small-target detection tasks in complex fire environments. This can provide support for UAV patrol and rescue applications from a high-altitude perspective.

Evaluation of a miniature mass spectrometer based point-of-care-test method for direct analysis of amlodipine and benazepril in whole blood.

A miniature mass spectrometer (mMS) based point-of-care testing (POCT) method was evaluated for on-site detecting the hypertension drugs, amlodipine and benazepril. The instrument parameters, including voltage, ISO1, ISO2, and CID, were optimized, under which the target compounds could be well detected in MS2. When these two drugs were injected simultaneously, the mutual ionization inhibition and mutual reduction between amlodipine and benazepril were evaluated. This phenomenon was severe on the precursor ions but had a small impact on the product ions, thus making this POCT method suitable for analysis using product ions. Finally, the method was validated and applied. The blood samples from patients were tested one hour after oral administration of the drugs (20 mg), and the benazepril was quantitatively analyzed using a standard curve, with detected concentrations ranging from 190.6 to 210 µg L-1 and a relative standard deviation (RSD) of 8.6 %. In summary, amlodipine has low sensitivity and can only be detected at higher concentrations, while benazepril has high sensitivity, good linearity, and even meets semi-quantitative requirements. The research results of this study are of great clinical significance for monitoring blood drug concentrations during hypertension medication, predicting drug efficacy, and customizing individualized medication plans.

Management after cataract surgery for patients with diabetic retinopathy: a systematic review and meta-analysis.

PURPOSE: To evaluate the safety and effectiveness of various treatment modalities in patients with diabetic retinopathy (DR) who underwent cataract surgery. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted using the PubMed, Embase, Cochrane Library, and CNKI databases up to December 22, 2021. The safety and efficacy of treatment modalities were assessed using the risk ratio (RR) to compare the progression of DR and the mean difference to evaluate the best corrected visual acuity (BCVA) and macular thickness (MT). RESULTS: The meta-analysis of the RCTs revealed that anti-VEGF (anti-vascular endothelial growth factor) drugs significantly reduced the progression of DR [RR: 0.37 (95%CI 0.19, 0.70), P = 0.002] and improved BCVA [mean difference = - 0.06 (- 0.12, - 0.01), P = 0.03] in patients with pre-existing DR who underwent cataract surgery. Steroid drugs also showed a significant reduction in macular thickness [mean difference = - 55.63 (- 90.73, - 20.53), I2 = 56%, P = 0.002] in DR patients two weeks after cataract surgery compared to the control group. The safety profiles of different management options did not differ significantly. CONCLUSION: The present meta-analysis suggests that anti-VEGF drugs can effectively slow down the progression of diabetic retinopathy, improve BCVA, and reduce MT in DR patients who underwent cataract surgery. Steroid drugs also show promise in reducing MT. However, further studies with larger sample sizes are required to compare the efficacy and safety of different management options in a multi-center clinical setting.

Measles Virus-Based Vaccine Expressing Membrane-Anchored Spike of SARS-CoV-2 Inducing Efficacious Systemic and Mucosal Humoral Immunity in Hamsters.

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2).

Schwann cell-derived extracellular vesicles promote memory impairment associated with chronic neuropathic pain.

BACKGROUND: The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP. METHODS: We used an adeno-associated virus harboring the SC-specific promoter Mpz and expressing the CD63-GFP gene to track SC-EVs transport. microRNA (miRNA) expression profiles of EVs and gain-of-function and loss-of-function regulatory experiments revealed that miR-142-5p was the main cargo of SC-EVs. Next, luciferase reporter gene and phenotyping experiments confirmed the direct targets of miR-142-5p. RESULTS: The contents and granule sizes of plasma EVs were significantly greater in rats with chronic sciatic nerve constriction injury (CCI)than in sham rats. Administration of the EV biogenesis inhibitor GW4869 ameliorated memory impairment in CCI rats and reversed CCI-associated dendritic spine damage. Notably, during CCI stress, SC-EVs could be transferred into the brain through the circulation and accumulate in the hippocampal CA1-CA3 regions. miR-142-5p was the main cargo wrapped in SC-EVs and mediated the development of CCI-associated memory impairment. Furthermore, α-actinin-4 (ACTN4), ELAV-like protein 4 (ELAVL4) and ubiquitin-specific peptidase 9 X-linked (USP9X) were demonstrated to be important downstream target genes for miR-142-5p-mediated regulation of dendritic spine damage in hippocampal neurons from CCI rats. CONCLUSION: Together, these findings suggest that SCs-EVs and/or their cargo miR-142-5p may be potential therapeutic targets for memory impairment associated with CNP.

On-site monitoring of nandrolone in cattle farming samples by portable atmospheric pressure chemical ionization mass spectrometry with ambient sampling.

Nandrolone (NT) is a type of androgen anabolic steroid that is often illegally used in cattle farming, leading to unpredictable harm to human health via the food chain. In this study, a rapid detection method for NT in the samples of cattle farming was established using a portable mass spectrometer. The instrument parameters were optimized, including a thermal desorption temperature of 220 °C, a pump speed of 30 %, an APCI ionization voltage of 3900 v, and an injection volume of 6 µL. The samples of bovine urine, feed, sewage, and tissue were selected, and extracted using a solution of methanol:acetonitrile (1:1, v/v), followed by spiking a NT standard solution (1000 ng·mL-1) and ionization through the APCI ion source for detection. The results showed that NT could not be detected in beef and feed due to the complexity of the matrix, while clear signals of NT ions were observed in bovine urine and sewage samples, with LODs of 1000 and 100 ng·mL-1, respectively. Furthermore, quantitative analysis was attempted, and a good linear relationship (R2 = 0.9952) was observed for NT in sewage within the range of 100 to 1000 ng·mL-1. At spiked levels of 100, 500, 1000 and 2000 ng mL-1, the recovery rates ranged from 74.3 % to 92.8 %, with a relative standard deviation (n = 6) of less than 15 %. In conclusion, this detection method offers the advantages of simplicity, rapidity, strong timeliness, and specificity, making it suitable for on-site detection. It can be used for qualitative screening of nandrolone in bovine urine and quantitative analysis of nandrolone in sewage.

Synergistic Effects and Kinetic Analysis in Co-Pyrolysis of Peanut Shells and Polypropylene.

The impact of COVID-19 has boosted growth in the takeaway and medical industries but has also generated a large amount of plastic waste. Peanut shells (PS) are produced in large quantities and are challenging to recycle in China. Co-pyrolysis of peanut shells (PS) and polypropylene (PP) is an effective method for processing plastic waste and energy mitigation. Thermogravimetric analysis was conducted on PS, PP, and their blends (PS-PP) at different heating rates (10, 20, 30 °C·min-1). The results illustrated that the co-pyrolysis process of PS-PP was divided into two distinct decomposition stages. The first stage (170-400 °C) was predominantly linked to PS decomposition. The second stage (400-520 °C) resulted from the combinations of PS and PP's thermal degradations, with the most contribution from PP degradation. With the increase in heating rate, thermogravimetric hysteresis appeared. Kinetic analysis indicated that the co-pyrolysis process reduced the individual pyrolysis activation energy, especially in the second stage, with a correlation coefficient (R2) generally maintained above 0.95. The multi-level reaction mechanism function model can effectively reveal the co-pyrolysis process mechanism. PS proved to be high-quality biomass for co-pyrolysis with PP, and all mixtures exhibited synergistic effects at a mixing ratio of 1:1 (PS1-PP1). This study accomplished effective waste utilization and optimized energy consumption. It holds significance in determining the interaction mechanism of mixed samples in the co-pyrolysis process.

Enhancing bactericidal activities of ciprofloxacin by targeting the trans-translation system that is involved in stress responses in Klebsiella pneumoniae.

Although the trans-translation system is a promising target for antcibiotic development, its antibacterial mechanism in Klebsiella pneumoniae (KP) is unclear. Considering that tmRNA was the core component of trans-translation, this study firstly investigated phenotypic changes caused by various environmental stresses in KP lacking trans-translation activities (tmRNA-deleted), and then aimed to evaluate antibacterial activities of the trans-translation-targeting antibiotic combination (tobramycin/ciprofloxacin) in clinical KP isolates based on inhibition activities of aminoglycosides against trans-translation. We found that the tmRNA-deleted strain P4325/ΔssrA was significantly more susceptible than the wild-type KP strain P4325 under environments with hypertonicity (0.5 and 1 M NaCl), hydrogen peroxide (40 mM), and UV irradiation. No significant differences in biofilm formation and survivals under human serum were observed between P4325/ΔssrA and P4325. tmRNA deletion caused twofold lower MIC values for aminoglycosides. As for the membrane permeability, tmRNA deletion increased ethidium bromide (EtBr) uptake of KP in the presence or absence of verapamil and carbonyl cyanide-m-chlorophenylhydrazone (CCCP), decreased EtBr uptake in presence of reserpine in P4325/ΔssrA, and reduced EtBr efflux in P4325/ΔssrA in the presence of CCCP. The time-kill curve and in vitro experiments revealed significant bactericidal activities of the tmRNA-targeting aminoglycoside-based antibiotic combination (tobramycin/ciprofloxacin). Thus, the corresponding tmRNA-targeting antibiotic combinations (aminoglycoside-based) might be effective and promising treatment options against multi-drug resistant KP.

Structure properties of Canna edulis RS3 (double enzyme hydrolysis) and RS4 (OS-starch and cross-linked starch): Influence on fermentation products and human gut microbiota.

This study investigated the in vitro fermentation characteristics of different structural types of Canna edulis resistant starch (RS). RS3 was prepared through a double enzyme hydrolysis method, and RS4 (OS-starch and cross-linked starch) was prepared using octenyl succinic anhydride and sodium trimetaphosphate/sodium tripolyphosphate, respectively. The RS3 and RS4 samples were structurally analyzed using scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction analysis. This was followed by in vitro fermentation experiments. The results revealed microstructure differences in the two groups of starch samples. Compared to native starch, RS3 and RS4 exhibited a lower degree of order and endothermic energy, with lower crystallinity (RS3: 29.59 ± 1.11 %; RS4 [OS-starch]: 28.01 ± 1.32 %; RS4 [cross-linked starch]: 30.44 ± 1.73 %) than that in native starch (36.29 ± 0.89 %). The RS content was higher in RS3 (63.40 ± 2.85 %) and RS4 (OS-starch: 71.21 ± 1.28 %; cross-linked starch: 74.33 ± 0.643 %) than in native starch (57.71 ± 2.95 %). RS3 and RS4 exhibited slow fermentation rates, promoting the production of short-chain fatty acids. RS3 and cross-linked starch significantly increased the production of acetate and butyrate. Moreover, RS3 significantly promoted the abundance of Lactobacillus, while OS-starch and cross-linked starch significantly enhanced the abundance of Dorea and Coprococcus, respectively. Hence, the morphological structure and RS content of the samples greatly influenced the fermentation rate. Moreover, the different varieties of RS induced specific gut microbial regulation. Hence, they show potential applications in functional foods for tailored gut microbiota management.

Fabrication of multifunctional ethyl cellulose/gelatin-based composite nanofilm for the pork preservation and freshness monitoring.

In this study, an active and intelligent nanofilm for monitoring and maintaining the freshness of pork was developed using ethyl cellulose/gelatin matrix through electrospinning, with the addition of natural purple sweet potato anthocyanin. The nanofilm exhibited discernible color variations in response to pH changes, and it demonstrated a higher sensitivity towards volatile ammonia compared with casting film. Notably, the experimental findings regarding the wettability and pH response performance indicated that the water contact angle between 70° and 85° was more favorable for the smart response of pH sensitivity. Furthermore, the film exhibited desirable antioxidant activities, water vapor barrier properties and also good antimicrobial activities with the incorporation of ε-polylysine, suggesting the potential as a food packaging film. Furthermore, the application preservation outcomes revealed that the pork packed with the nanofilm can prolong shelf life to 6 days, more importantly, a distinct color change aligned closely with the points indicating the deterioration of the pork was observed, changing from light pink (indicating freshness) to light brown (indicating secondary freshness) and then to brownish green (indicating spoilage). Hence, the application of this multifunctional film in intelligent packaging holds great potential for both real-time indication and efficient preservation of the freshness of animal-derived food items.

Imaging S-Adenosyl Methionine Dynamics in Living Cells Using an RNA-Based Fluorescent Sensor.

S-Adenosyl methionine (SAM) is a critical metabolite involved in numerous cellular processes, including DNA methylation and gene expression regulation. Understanding the spatiotemporal dynamics of SAM within living cells is essential for deciphering its roles in maintaining cell homeostasis and in disease development. Here, we describe a protocol based on a recently reported SAM sensor exploiting a fluorogenic RNA and an RNA three-way junction for visualizing SAM dynamics in cultured mammalian cells.

A Colorimetric Nanofiber Film Based on Ethyl Cellulose/Gelatin/Purple Sweet Potato Anthocyanins for Monitoring Pork Freshness.

In this study, colorimetric indicator nanofiber films based on ethyl cellulose (EC)/gelatin (G) incorporating purple sweet potato anthocyanins (PSPAs) were designed via electrospinning technology for monitoring and maintaining the freshness of pork. The film presented good structural integrity and stability in a humid environment with water vapor permeability (WVP) of 6.07 ± 0.14 × 10-11 g·m-1s-1Pa-1 and water contact angle (WCA) of 81.62 ± 1.43°. When PSPAs were added into the nanofiber films, the antioxidant capacity was significantly improved (p < 0.05) with a DPPH radical scavenging rate of 68.61 ± 1.80%. The nanofiber films showed distinguishable color changes as pH changes and was highly sensitive to volatile ammonia than that of casting films. In the application test, the film color changed from light pink (fresh stage) to light brown (secondary freshness stage) and then to brownish green (spoilage stage), indicating that the nanofiber films can be used to detect the real-time freshness of pork during storage. Meanwhile, it could prolong the shelf life of pork by inhibiting the oxidation degree. Hence, these results suggested that the EC/G/PSPA film has promising future for monitoring freshness and extending shelf life of pork.

shRNA Targeting Lentiviral Vector Minus-Strand Product Improves the Viral Titer During Viral Packaging.

Lentiviral vector (LVV) has been used as one of the common carriers for gene therapy in clinical trials. LVV-mediated clinical trials have being reported in successfully treating hundreds of ß-thalassemia cases. These LVVs bear an inversely placed ß-hemoglobin (HBB) gene expression cassette for preserving introns during the viral RNA packaging. Consequently, these LVVs often produce a small amount of negatively orientated transcript driven by its internal gene promoter and would lower the viral titer by the minus-strand complemented with the viral backbone. To overcome this problem, we designed shRNAs specifically target the minus-strand RNA driven by the LVV internal promoter that resulted in a notable increase in the viral titer. This report demonstrates a simple and positive mean for increasing the effectiveness for gene therapy with the LVV system.

Predicting the binding configuration and release potential of heavy metals on iron (oxyhydr)oxides: A machine learning study on EXAFS.

Heavy metals raise a global concern and can be easily retained by ubiquitous iron (oxyhydr)oxides in natural and engineered systems. The complex interaction between iron (oxyhydr)oxides and heavy metals results in various mineral-metal binding configurations, such as outer-sphere complexes and edge-sharing inner-sphere complexes, which determine the accumulation and release of heavy metals in the environment. However, traditional experimental approaches are time-consuming and inadequate to elucidate the complex binding relationships and configurations between iron (oxyhydr)oxides and heavy metals. Herein, a workflow that integrates the binding configuration data of 11 heavy metals on 7 iron (oxyhydr)oxides and then trains machine learning models to predict unknown binding configurations was proposed. The well-trained multi-grained cascade forest models exhibited high accuracy (> 90%) and predictive performance (R2 ∼ 0.75). The underlying effects of mineral properties, metal ion species, and environmental conditions on mineral-metal binding configurations were fully interpreted with data mining. Moreover, the metal release rate was further successfully predicted based on mineral-metal binding configurations. This work provides a method to accurately and quickly predict the binding configuration of heavy metals on iron (oxyhydr)oxides, which would provide guidance for estimating the potential release behavior of heavy metals and remediating heavy metal pollution in natural and engineered environments.

Recent advances in methods for live-cell RNA imaging.

As one of the most fundamental building blocks of life, RNA plays critical roles in diverse biological processes, from X chromosome inactivation, genome stability maintenance, to embryo development. Being able to visualize the localization and dynamics of RNA can provide critical insights into these fundamental processes. In this review, we provide an overview of current methods for live-cell RNA imaging with a focus on methods for visualizing RNA in living mammalian cells with single-molecule resolution.

A nano-platform combats the "attack" and "defense" of cytoskeleton to block cascading tumor metastasis.

The cytoskeleton facilitates tumor cells invasion into the bloodstream via vasculogenic mimicry (VM) for "attack", and protects cells against external threats through cytoskeletal remodeling and tunneling nanotubes (TNTs) for "defense". However, the existing strategies involving cytoskeleton are not sufficient to eliminate tumor metastasis due to mitochondrial energy supply, both within tumor cells and from outside microenvironment. Here, considering the close relationship between cytoskeleton and mitochondria both in location and function, we construct a nano-platform that combats the "attack" and "defense" of cytoskeleton in the cascading metastasis. The nano-platform is composed of KFCsk@LIP and KTMito@LIP for the cytoskeletal collapse and mitochondrial dysfunction. KFCsk@LIP prevents the initiation and circulation of cascading tumor metastasis, but arouses limited suppression in tumor cell proliferation. KTMito@LIP impairs mitochondria to trigger apoptosis and impede energy supply both from inside and outside, leading to an amplified effect for metastasis suppression. Further mechanisms studies reveal that the formation of VM and TNTs are seriously obstructed. Both in situ and circulating tumor cells are disabled. Subsequently, the broken metastasis cascade results in a remarkable anti-metastasis effect. Collectively, based on the nano-platform, the cytoskeletal collapse with synchronous mitochondrial dysfunction provides a potential therapeutic strategy for cascading tumor metastasis suppression.

Study of the self-assembly, drug encapsulating and delivering characteristics of short chain amylose-based type 3 resistant starch nanoparticles from Canna edulis.

In developing type 3 resistant starch (RS3) from Canna edulis for use as functional food ingredients, we investigated the synthesis of C. edulis RS3 nanoparticles. Simultaneously, we explored the potential of C. edulis short-chain amylose (SCA)-based RS3 nanoparticles (RS3N) as a targeted delivery system, with a specific focus on colon targeting, yielding promising insights. Our study revealed that the degree of polymerization (DP) of C. edulis SCA, particularly the chains of DP 36- 100, exhibited a robust correlation with the particle size and physicochemical characteristics of C. edulis SCA-based RS3N. Additionally, recrystallization temperature variation (4, 25, and 45 °C) significantly influenced the self-assembly behavior of C. edulis SCA, with the preparation at 4 °C resulting in more uniform particle size distributions. In further expanding the scope of applications for C. edulis SCA-based RS3N, we harnessed the potential of Fe3O4 and curcumin (CUR) as guest molecules to assess drug encapsulation and colon-targeting capabilities. Incorporating Fe3O4 into the self-assembly system led to the production of magnetic RS3N, confirming the successful encapsulation of Fe3O4 within C. edulis SCA-based RS3N. Furthermore, in vitro experiments have demonstrated that CUR-RS3N was stable in the gastrointestinal tract and gradually released curcumin with fermentation in the colonic environment. Collectively, these findings provide invaluable insights into the intricate self-assembly behavior of C. edulis SCA with varying fine structures and recrystallization temperatures during RS3N formation. Moreover, they underscore the colon-targeted properties of C. edulis SCA-based RS3N, opening promising avenues for its application within the food industry, particularly in advanced controlled drug delivery systems.

Xiao Cheng Qi Decoction, an Ancient Chinese Herbal Mixture, Relieves Loperamide-Induced Slow-Transit Constipation in Mice: An Action Mediated by Gut Microbiota.

Xiao Cheng Qi (XCQ) decoction, an ancient Chinese herbal mixture, has been used in treating slow-transit constipation (STC) for years. The underlying action mechanism in relieving the clinical symptoms is unclear. Several lines of evidence point to a strong link between constipation and gut microbiota. Short-chain fatty acids (SCFAs) and microbial metabolites have been shown to affect 5-HT synthesis by activating the GPR43 receptor localized on intestinal enterochromaffin cells, since 5-HT receptors are known to influence colonic peristalsis. The objective of this study was to evaluate the efficacy of XCQ in alleviating clinical symptoms in a mouse model of STC induced by loperamide. The application of loperamide leads to a decrease in intestinal transport and fecal water, which is used to establish the animal model of STC. In addition, the relationship between constipation and gut microbiota was determined. The herbal materials, composed of Rhei Radix et Rhizoma (Rhizomes of Rheum palmatum L., Polygonaceae) 55.2 g, Magnoliae Officinalis Cortex (Barks of Magnolia officinalis Rehd. et Wils, Magnoliaceae) 27.6 g, and Aurantii Fructus Immaturus (Fruitlet of Citrus aurantium L., Rutaceae) 36.0 g, were extracted with water to prepare the XCQ decoction. The constipated mice were induced with loperamide (10 mg/kg/day), and then treated with an oral dose of XCQ herbal extract (2.0, 4.0, and 8.0 g/kg/day) two times a day. Mosapride was administered as a positive drug. In loperamide-induced STC mice, the therapeutic parameters of XCQ-treated mice were determined, i.e., (i) symptoms of constipation, composition of gut microbiota, and amount of short-chain fatty acids in feces; (ii) plasma level of 5-HT; and (iii) expressions of the GPR43 and 5-HT4 receptor in colon. XCQ ameliorated the constipation symptoms of loperamide-induced STC mice. In gut microbiota, the treatment of XCQ in STC mice increased the relative abundances of Lactobacillus, Prevotellaceae_UCG_001, Prevotellaceae_NK3B31_group, Muribaculaceae, and Roseburia in feces and decreased the relative abundances of Desulfovibrio, Tuzzerella, and Lachnospiraceae_ NK4A136_group. The levels of SCFAs in stools from the STC group were significantly lower than those the control group, and were greatly elevated via treatment with XCQ. Compared with the STC group, XCQ increased the plasma level of 5-HT and the colonic expressions of the GPR43 and 5-HT4 receptor, significantly. The underlying mechanism of XCQ in anti-constipation could be related to the modulation of gut microbiota, the increase in SCFAs, the increase in plasma 5-HT, and the colonic expressions of the GPR43 and 5-HT4 receptor. Our results indicate that XCQ is a potent natural product that could be a therapeutic strategy for constipation.