Fermented dietary fiber from soy sauce residue exerts antidiabetic effects through regulating the PI3K/AKT signaling pathway and gut microbiota-SCFAs-GPRs axis in type 2 diabetic mellitus mice.

The gut plays a crucial role in the development and progression of metabolic disorders, particularly in relation to type 2 diabetes mellitus (T2DM). While a high intake of dietary fiber is inversely associated with the risk of T2DM, the specific effects of various dietary fibers on T2DM are not fully understood. This study investigated the anti-diabetic properties of fermented dietary fiber (FDF) derived from soy sauce residue in T2DM mice, demonstrating its ability to lower blood glucose levels and ameliorate insulin resistance. Our findings revealed that FDF could enhance hepatic glucose metabolism via the IRS-1/PI3K/AKT/mTOR pathway. Additionally, the anti-diabetic effect of FDF was correlated with alterations in gut microbiota composition in T2DM mice, promoting a healthier gut environment. Specifically, FDF increased the abundance of beneficial flora such as Dubosiella, Butyricimonas, Lachnospiraceae_NK4A136_group, Lactobacillus and Osillibacter, while reducing harmful bacteria including Bilophila, Parabacteroides and Enterorhabdus. Further analysis of microbial metabolites, including short-chain fatty acids (SCFAs) and bile acids (BAs), provided evidence of FDF's regulatory effects on cecal contents in T2DM mice. Importantly, FDF treatment significantly restored the G-protein-coupled receptors (GPRs) expression in the colon of T2DM mice. In conclusion, our study suggests that the anti-diabetic effects of FDF are associated with the regulation of both the liver-gut axis and the gut microbiota-SCFAs-GPRs axis.

Clear cell hepatocellular carcinoma: Gd-EOB-DTPA-enhanced MR imaging features and prognosis.

PURPOSE: To investigate imaging findings on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and prognosis of clear cell hepatocellular carcinoma (CCHCC) comparing with non-otherwise specified hepatocellular carcinoma (NOS-HCC). METHODS: The clinical, pathological and MR imaging features of 42 patients with CCHCC and 84 age-matched patients with NOS-HCC were retrospectively analyzed from January 2015 to October 2021. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors for CCHCC. Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan-Meier analysis. RESULTS: CCHCC showed fat content more frequently (P < 0.001) and relatively higher Edmondson tumor grade (P = 0.001) compared with NOS-HCC. The lesion-to-muscle ratio (LMR) and lesion-to-liver ratio (LLR) of CCHCC on pre-enhancement T1-weighted imaging (pre-T1WI) (P = 0.001, P = 0.003) and hepatobiliary phase (HBP) (P = 0.007, P = 0.048) were significantly higher than those of NOS-HCC. The area under the curve (AUC) for fat content, LLR on pre-T1WI and their combination with better diagnostic performance in predicting CCHCC were 0.678, 0.666, and 0.750, respectively. There was no statistically significant difference in clinical outcomes between CCHCC and NOS-HCC. Multivariate Cox analysis confirmed that tumor size > 2 cm and enhancing capsule were independent prognostic factors for DFS and OS among CCHCC patients. CONCLUSION: Fat content and adjusted lesion signal intensity on pre-T1WI and HBP could be used to differentiate CCHCC from NOS-HCC. CCHCC had similar prognosis with NOS-HCC.

Dietary nobiletin regulated cefuroxime- and levofloxacin-associated "gut microbiota-metabolism" imbalance and intestinal barrier dysfunction in mice.

Nobiletin (NOB) exhibits significant biological activities and may be a potential dietary treatment for antibiotic-associated gut dysbiosis. In this study, mice were gavaged with 0.2 mL day-1 of 12.5 g L-1 cefuroxime (LFX) and 10 g L-1 levofloxacin (LVX) for a duration of 10 days, accompanied by 0.05% NOB to investigate the regulatory effect and potential mechanisms of NOB on antibiotic-induced intestinal microbiota disorder and intestinal barrier dysfunction. Our results indicated that dietary NOB improved the pathology of intestinal epithelial cells and the intestinal permeability by upregulating the expression of intestinal tight junction proteins (TJs) and the number of goblet cells. Furthermore, dietary NOB reduced the levels of serum lipopolysaccharide (LPS) and pro-inflammatory factors (TNF-α and IL-1ß), thereby facilitating the restoration of the intestinal mucosal barrier. Additionally, dietary NOB increased the abundance of beneficial bacteria f_Lachnospiraceae and regulated the metabolic disorders of short-chain fatty acids (SCFAs) and bile acids (BAs). Notably, NOB supplementation resulted in elevated levels of butyric acid and lithocholic acid (LCA), which contributed to the repair of the intestinal mucosal barrier function and the maintenance of intestinal homeostasis. Collectively, our results propose a healthy dietary strategy for the prevention or mitigation of antibiotic-associated gut dysbiosis by dietary NOB.

Dietary tangeretin improved antibiotic-associated diarrhea in mice by enhancing the intestinal barrier function, regulating the gut microbiota, and metabolic homeostasis.

Antibiotic-associated diarrhea is mediated by antibiotic treatment and is usually caused by the disruption of the intestinal barrier, gut microbiota, and metabolic balance. To identify a dietary strategy that can mitigate the side effects of antibiotics, this study investigated the effect of tangeretin on antibiotic-associated diarrhea in C57BL/6 mice. The results revealed that dietary tangeretin significantly ameliorated symptoms of antibiotic-associated diarrhea, as evidenced by the decreased diarrhea status scores, the reduced fecal water content, the decreased caecum/body weight ratio, and the alleviated colonic tissue damage. Dietary tangeretin also exhibited a protective effect on the intestinal barrier function by upregulating the mRNA and protein expression of claudin-1 and ZO-1. Furthermore, analysis of the gut microbiota using 16S rRNA gene sequencing indicated that dietary tangeretin modulated the gut microbiota of mice with antibiotic-associated diarrhea via increasing the gut microbiota diversity and the abundance of beneficial bacteria, e.g., Lactobacillaceae and Ruminococcaceae, and decreasing the abundance of harmful bacteria, e.g., Enterococcus and Terrisporobacter. Additionally, dietary tangeretin restored the levels of short-chain fatty acids and modulated metabolic pathways by enriching purine metabolism, bile acid metabolism, ABC transporters, and choline metabolism in cancer. Collectively, these findings provide a solid scientific basis for the rational use of tangeretin as a preventive and therapeutic agent for antibiotic-associated diarrhea.

Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling.

Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transporter SLC15A4, and then activates IRF5, which in turn triggers the transcription of type I interferons and cytokines. Here, we report three cryo-electron microscopy (cryo-EM) structures of human SLC15A4 in the apo monomeric and dimeric state and as a TASL-bound complex. The apo forms are in an outward-facing conformation, with the dimeric form showing an extensive interface involving four cholesterol molecules. The structure of the TASL-bound complex reveals an unprecedented interaction mode with solute carriers. During the recruitment of TASL, SLC15A4 undergoes a conformational change from an outward-facing, lysosomal lumen-exposed state to an inward-facing state to form a binding pocket, allowing the N-terminal helix of TASL to be inserted into. Our findings provide insights into the molecular basis of regulatory switch involving a human solute carrier and offers an important framework for structure-guided drug discovery targeting SLC15A4-TASL-related human autoimmune diseases.

Can financial technology development reduce household energy consumption? Evidence from China.

This paper examines whether financial technology (FinTech) development affect household energy consumption. The proposed point that FinTech can reduce household energy consumption is theoretically discussed and empirically tested using data from the 2017 Digital Financial Inclusion Index, the 2018 China Family Panel Studies (CFPS), the 2018 China Environmental Statistical Yearbook and the 2018 China Science and Technology Statistical Yearbook. The results show that FinTech contributes to reducing household energy consumption. Several retests, including the instrumental variable, replacement sample and propensity score matching methods, prove its robustness. Mechanism tests show that investment in environmental governance and technological innovation promotion are the two main transmission channels. We also find that the reducing effect is more significant in the following groups: the low-middle income level classes, the eastern regional residents, those with bachelor's degrees and above, the those aged over 60 and rural residents. The outcomes of this paper call for government departments to positively guide FinTech development to reduce household energy consumption. From another perspective, the conclusions drawn from our analysis make a great reference value for countries and provide new ideas for Chinese carbon peaking and carbon neutralisation goals.

Review of recent advances on health benefits, microbial transformations, and authenticity identification of Citri reticulatae Pericarpium bioactive compounds.

The extensive health-promoting effects of Citri Reticulatae Pericarpium (CRP) have attracted researchers' interest. The difference in storage time, varieties and origin of CRP are closely related to the content of bioactive compounds they contain. The consitituent transformation mediated by environmental microorganisms (bacteria and fungi) and the production of new bioactive components during the storage process may be the main reason for 'the older, the better' of CRP. In addition, the gap in price between different varieties can be as large as 8 times, while the difference due to age can even reach 20 times, making the 'marketing young-CRP as old-CRP and counterfeiting origin' flood the entire market, seriously harming consumers' interests. However, so far, the research on CRP is relatively decentralized. In particular, a summary of the microbial transformation and authenticity identification of CRP has not been reported. Therefore, this review systematically summarized the recent advances on the main bioactive compounds, the major biological activities, the microbial transformation process, the structure, and content changes of the active substances during the transformation process, and authenticity identification of CRP. Furthermore, challenges and perspectives concerning the future research on CRP were proposed.

Dietary 5-demethylnobiletin attenuated dextran sulfate sodium-induced colitis in mice by inhibiting immune response and regulating gut microbiota.

This study investigated the preventive effect of 5-demethylnobiletin (5DN), a natural polymethoxyflavone found mainly in citrus fruits, on dextran sulfate sodium (DSS)-induced colitis in mice and explored its potential mechanisms. Our results indicated that dietary 5DN (0.05% w/w in diet) could alleviate colitis symptoms in DSS-treated mice by preventing body weight loss, reducing the disease activity index, decreasing the colon weight to colon length ratio, and lessening colon tissue damage. Additionally, 5DN inhibited the inflammatory response in colitis mice through decreasing the production of inflammatory cytokines. Immunohistochemical analysis revealed that 5DN could reverse the DSS-induced decrease in the expression of claudin-1 and ZO-1 to improve the intestinal barrier function. Furthermore, 5DN altered gut microbiota dysbiosis in DSS-treated mice via up-regulating the level of probiotics (Roseburia) and down-regulating the level of pathogenic bacteria (Clostridium, Parabacteroides, and Sutterella). Taken together, these data provided a solid scientific basis for utilizing 5DN as a therapeutic candidate in colitis and related diseases.

Single-pixel imaging with high spectral and spatial resolution.

It has long been a challenge to obtain high spectral and spatial resolution simultaneously for the field of measurement and detection. Here we present a measurement system based on single-pixel imaging with compressive sensing that can realize excellent spectral and spatial resolution at the same time, as well as data compression. Our method can achieve high spectral and spatial resolution, which is different from the mutually restrictive relationship between the two in traditional imaging. In our experiments, 301 spectral channels are obtained in the band of 420-780 nm with a spectral resolution of 1.2 nm and a spatial resolution of 1.11 mrad. A sampling rate of 12.5% for a 64×64p i x e l image is obtained by using compressive sensing, which also reduces the measurement time; thus, high spectral and spatial resolution are realized simultaneously, even at a low sampling rate.

Dietary 5-demethylnobiletin prevents antibiotic-associated dysbiosis of gut microbiota and damage to the colonic barrier.

5-Demethylnobiletin (5DN) is an important ingredient of citrus extract that is rich in polymethoxyflavones (PMFs). In this study, we systemically investigated the preventive effects of 5DN on antibiotic-associated intestinal disturbances. Experimental mice were gavaged 0.2 mL per day of the antibiotic cocktail (12.5 g L-1 cefuroxime and 10 g L-1 levofloxacin) for 10 days, accompanied by dietary 0.05% 5DN for 10 and 20 days. The results showed that the combination of cefuroxime and levofloxacin caused swelling of the cecum and injury to the colon tissue. Meanwhile, the balance of intestinal oxidative stress and the barrier function of mice was also damaged by the antibiotics through upregulation of the relative mRNA levels of superoxide dismutase 3 (SOD3), quinine oxidoreductase 1 (NQO1) and glutathione peroxidase 1 (GPX1), and downregulation of the relative protein levels of tight junction proteins (TJs). Moreover, antibiotic exposure led to disorder of the gut microbiota, particularly increased harmful bacteria (Proteobacteria) and decreased beneficial bacteria (Bacteroideta). However, dietary 5DN could reduce antibiotic-associated intestinal damage, evidenced by the results that 5DN alleviated gut oxidative damage and attenuated intestinal barrier injury via increasing the expression of TJs including occludin and zonula occluden1 (ZO1). Additionally, dietary 5DN modulated the composition of the gut microbiota in antibiotic-treated mice by increasing the relative levels of beneficial bacteria, such as Dubosiella and Lactobacillus. Moreover, PMFs increased the contents of isobutyric acid and butyric acid, which were almost eliminated by antibiotic exposure. In conclusion, 5DN could alleviate antibiotic-related imbalance of intestinal oxidative stress, barrier function damage, intestinal flora disorders and the reduction of short-chain fatty acids (SCFAs), which lays a foundation for exploring safer and more effective ways to prevent or mitigate antibiotic-associated intestinal damage.

Modulating effects of capsaicin on glucose homeostasis and the underlying mechanism.

Abnormal glucose homeostasis is linked to a variety of metabolic syndromes, such as insulin resistance, obesity, type-2 diabetes mellitus, hypertension and cardiovascular diseases. Maintenance of normal glucose homeostasis is important for the body to keep normal biological functions. As the major bioactive ingredient in chili peppers responsible for the pungent flavor, capsaicin has been reported to effectively improve glucose homeostasis with low cytotoxicity. In this review, the modulating effects of capsaicin on glucose homeostasis in cell models, animal models and human trials are summarized through both TRPV1 dependent and TRPV1 independent pathways. The relevant molecular mechanisms underlying its regulatory effects are also evaluated. Understanding the effects and mechanisms of capsaicin on glucose metabolism could provide theoretical evidence for its application in the food and pharmaceutical industries.

Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3', 4'-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells.

Hydroxylated polymethoxyflavones (PMFs) are a unique class of flavonoid compounds mainly found in citrus plants. We investigated the anti-inflammatory effects of one major 5-hydroxy PMF, namely 5-demethylnobiletin (5DN) and its metabolites 5, 3'-didemethylnobiletin (M1), 5, 4'-didemethylnobiletin (M2), and 5, 3', 4'-tridemethylnobiletin (M3) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that M2 and M3 produced stronger inhibitory effects on the production of nitric oxide (NO) than their parent compound at non-cytotoxic concentrations. Western blotting and real-time PCR analyses demonstrated that M2 and M3 significantly decreased iNOS and COX-2 gene expression. The results also showed that M1 and M3 induced heme oxygenase-1(HO-1) gene expression. Overall, our results demonstrated that metabolites of 5DN significantly inhibited LPS-induced inflammation in RAW 264.7 macrophage cells and generally possessed more potent anti-inflammatory activity than the parent compound, 5DN.

Reconstruction algorithm of haze image based on blind separation model of polarized orthogonal airlight.

Polarization-based dehazing methods can enhance the quality of haze images. However, existing methods tend to a manual selection of sky area and bias coefficient to estimate the degree of polarization (DoP) of the airlight, which leads to inaccurate estimation of the airlight. Aiming at the problem, a reconstruction algorithm based on the blind separation model of polarized orthogonal airlight is proposed. Importantly, the depth-dependent DoP of the airlight is automatically estimated without manual selection of sky area and bias coefficient. To reduce the interference of white objects on the estimation of airlight at infinity, an adaptive estimation method using the deviation between the DoP of the airlight and incident light is proposed. In order to accurate estimate the airlight from the airlight at infinity, a blind separation model of the airlight with multi-regularization constraints is established based on the decomposition of the airlight at infinity into a pair of polarized components with orthogonal angles. The experimental results show that the method effectively improves the visibility of scenes under different haze concentrations, especially in dense or heavy haze weather.

Updated design strategies for oral delivery systems: maximized bioefficacy of dietary bioactive compounds achieved by inducing proper digestive fate and sensory attributes.

Interest in the application of dietary bioactive compounds (DBC) in healthcare and pharmaceutical industries has motivated researchers to develop functional delivery systems (FDS) aiming to maximize their bioefficacy. As the direct and indirect health benefiting effects of DBC are acknowledged, traditional design principle of FDS aiming at improving the bioavailability of intact DBC is challenged by the updated one, where the maximized bioefficacy of DBC delivered by FDS will be achieved via rationally absorbed at target sites with proper metabolism pathways. This article briefly summarized the absorption and metabolic fates of orally digested DBC along with their direct and indirect mechanisms to perform health benefiting effects. Current strategies in designing the next generation FDS with an emphasis on their modulation effects on the distribution portion between the upper and lower digestive tract, portal vein and lymphatic absorption, human digestive and gut microbiota enzymatic mediated metabolism were highlighted. Updated research progresses of FDS in adjusting sensory attributes of food end products and inducing synergistic effects rooting from matrix materials and co-delivered cargos were also discussed. Challenges as well as future perspectives concerning the precise nutrition and the critical role of delivery systems in dietary intervention were proposed.

iRGD-modified exosomes-delivered BCL6 siRNA inhibit the progression of diffuse large B-cell lymphoma.

Clinical applications of siRNA therapeutics have been limited by the immunogenicity of the siRNA and low efficiency of siRNA delivery to target cells. Recently, evidence have shown that exosomes, endogenous nano-vesicles, can deliver siRNA to the tumor tissues in mice. Here, to reduce immunogenicity, we selected immature dendritic cells (DCs) to produce exosomes. In addition, tumor targeting was achieved by engineering the DCs to express exosomal membrane protein (Lamp2b), fused to av integrin-specific iRGD peptide (CRGDKGPDC). Next, iRGD targeted exosomes (iRGD-Exo) were isolated from the transfected DCs, and then the isolated exosomes were loaded with BCL6 siRNA by electroporation. Our results found that integrin (αvß3) receptors were highly expressed on OCI-Ly8 cells. In addition, iRGD-Exo showed high targeting ability with avß3 integrins positive OCI-Ly8 cells. Significantly, iRGD-Exo loaded with BCL6 siRNA suppressed DLBCL cell proliferation in vitro. Furthermore, intravenously injected iRGD-Exo delivered BCL6 siRNA to tumor tissues, resulting in inhibition of tumor growth in DLBCL. Meanwhile, exosomes mediated BCL6 siRNA delivery did not exhibit appreciable toxicity in mice. Collectively, our study demonstrates a therapeutic potential of exosomes as a promising vehicle for RNAi delivery to treat DLBCL.

Intervention effects of delivery vehicles on the therapeutic efficacy of 6-gingerol on colitis.

The emerging concept that "the maximized therapeutic efficacy of encapsulates would be achieved by inducing appropriate absorption site and pharmacological signal pathways through smart intervention of targeted delivery systems" is quite intriguing in the field of drug delivery. Herein, we developed 6-gingerol (6G) loaded delivery system in the form of nanostructured lipid carriers (6G-NLC) or NLC imbedded microcapsule (6G-MC). The modulation effects of the constructed formulations on the digestive fate and functioning mechanisms of 6-gingerol on colitis were investigated. The small intestine dominant absorption of 6G-NLC differed significantly with the colorectal dominated accumulation of 6G-MC in terms of the site-specific release behavior, biodistribution and transit time. Moreover, 6G-NLC alleviated DSS-induced colitis primarily through interfering with the antioxidant/anti-inflammatory pathways and Firmicutes/Bacteroidetes ratio. Whereas, better therapeutic efficacy was achieved in 6G-MC via sustained release at site close to the colonic lesion, and triggering multiple mitigation mechanisms including enhancing the mucus barrier and immune homeostasis, maintaining the structure and diversity of gut microbiota and promoting the intestinal barrier function. This work confirmed that rational design of oral delivery system can flexibly interfere with the pharmacological function pathways of encapsulated cargos, guided by which the maximized and precise therapeutic efficacy could be achieved.

Enzymatic Synthesis of Diacylglycerol-Enriched Oil by Two-Step Vacuum-Mediated Conversion of Fatty Acid Ethyl Ester and Fatty Acid From Soy Sauce By-Product Oil as Lipid-Lowering Functional Oil.

Soy sauce by-product oil (SSBO), a by-product of the soy sauce production process, is the lack of utilization due to an abundance of free fatty acid (FFA) and fatty acid ethyl ester (EE). The utilization of low-cost SSBO to produce value-added diacylglycerol (DAG)-enriched oil and its applications are promising for the sustainability of the oil industry. The objective of this study was to utilize SSBO containing a high content of EE and FFA as raw material to synthesize DAG-enriched oil and to evaluate its nutritional properties in fish. Based on different behaviors between the glycerolysis of EE and the esterification of FFA in one-pot enzymatic catalysis, a two-step vacuum-mediated conversion was developed for the maximum conversions of EE and FFA to DAG. After optimization, the maximum DAG yield (66.76%) and EE and FFA conversions (96 and 93%, respectively) were obtained under the following optimized conditions: lipase loading 3%, temperature 38°C, substrate molar ratio (glycerol/FFA and EE) 21:40, a vacuum combination of 566 mmHg within the initial 10 h and 47 mmHg from the 10th to 14th hour. Further nutritional study in fish suggested that the consumption of DAG-enriched oil was safe and served as a functional oil to lower lipid levels in serum and liver, decrease lipid accumulation and increase protein content in body and muscle tissues, and change fatty acid composition in muscle tissues. Overall, these findings were vital for the effective utilization of SSBO resources and the development of future applications for DAG-enriched oil as lipid-lowering functional oil in food.

Limonin Isolated From Pomelo Seed Antagonizes Aß25-35-Mediated Neuron Injury via PI3K/AKT Signaling Pathway by Regulating Cell Apoptosis.

Pomelo seed as a by-product from pomelo consumption is rich in bioactive compounds, however, a huge volume of pomelo seed was disposed as wastes, the comprehensive utilization of pomelo seed could not only generate valued-added products/ingredients, but also decrease the environmental pollution. In this study, the main active substance limonin in pomelo seed was considered as a high-value bioactive compound. The purification of limonin from pomelo seed was investigated, and the neuroprotective and mechanism were characterized. The UPLC-MS/MS results indicated that 29 compounds in pomelo seed were identified, including 14 flavonoids, 3 limonids, 9 phenols and 3 coumarins. Moreover, high purity of limonin was obtained by crystallization and preparative-HPLC. Furthermore, limonin pretreatment can antagonize the cell damage mediated by Aß25-35 in a concentration-dependent relationship. The regulation of Bax/Bcl-2, expression of caspase-3 protein and the activation of PI3K/Akt signaling pathway were observed in the cells pretreated with limonin. Treatment of PC12 cells with PI3K inhibitor LY294002 weakened the protective effect of limonin. These results indicated that limonin prevented Aß25-35-induced neurotoxicity by activating PI3K/Akt, and further inhibiting caspase-3 and up-regulating Bcl-2. This study enables comprehensive utilization of pomelo seed as by-product and offers a theoretical principle for a waste-to-wealth solution, such as potential health benefits of food ingredient and drug.