Human amniotic mesenchymal stem cell-islet organoids enhance the efficiency of islet engraftment in a mouse diabetes model.

AIMS: Despite islet transplantation has proved a great potential to become the standard therapy for type 1 diabetes mellitus (T1DM), this approach remains limited by ischemia, hypoxia, and poor revascularization in early post-transplant period as well as inflammation and life-long host immune rejection. Here, we investigate the potential and mechanism of human amniotic mesenchymal stem cells (hAMSCs)-islet organoid to improve the efficiency of islet engraftment in immunocompetent T1DM mice. MAIN METHODS: We generated the hAMSC-islet organoid structure through culturing the mixture of hAMSCs and islets on 3-dimensional-agarose microwells. Flow cytometry, whole-body fluorescent imaging, immunofluorescence, Calcein-AM/PI staining, ELISA, and qPCR were used to assess the potential and mechanism of shielding hAMSCs to improve the efficiency of islet transplantation. KEY FINDINGS: Transplant of hAMSC-islet organoids results in remarkably better glycemic control, an enhanced glucose tolerance, and a higher ß cell mass in vivo compared with control islets. Our results show that hAMSCs shielding provides an immune privileged microenvironment for islets and promotes graft revascularization in vivo. In addition, hAMSC-islet organoids show higher viability and reduced dysfunction after exposure to hypoxia and inflammatory cytokines in vitro. Finally, our results show that shielding with hAMSCs leads to the activation of PKA-CREB-IRS2-PI3K and PKA-PDX1 signaling pathways, up-regulation of SIL1 mRNA levels, and down-regulation of MT1 mRNA levels in ß cells, which ultimately promotes the synthesis, folding and secretion of insulin, respectively. SIGNIFICANCE: hAMSC-islet organoids can evidently increase the efficiency of islet engraftment and might develop into a promising alternative for the clinical treatment of T1DM.

A multichromatic colorimetric detection method for Vibrio parahaemolyticus based on Fe3O4-Zn-Mn nanoenzyme and dual substrates.

IMPORTANCE: The Fe3O4-Zn-Mn nanomimetic enzyme demonstrates significant importance in dual-substrate colorimetric detection for V. parahaemolyticus, owing to its enhanced sensitivity, selectivity, and rapid detection capabilities. Additionally, it offers cost-effectiveness, portability, and the potential for multiplex detection. This innovative approach holds promise for improving the monitoring and control of V. parahaemolyticus infections, thereby contributing to advancements in public health and food safety.

Rapid and sensitive determination of ascorbic acid based on label-free silver triangular nanoplates.

In this study, a new method for the detection of ascorbic acid (AA) was proposed. It was based on the protective effect of AA on silver triangular nanoplates (Ag TNPs) against Cl- induced etching reactions. Cl- can attack the corners of Ag TNPs and etch them, causing a morphological shift from triangular nanoplates to nanodiscs. As a result, the solution changes color from blue to yellow. However, in the presence of AA, the corners of Ag TNPs can be protected from Cl- etching, and the blue color of the solution remains unchanged. Using this effect, a selective sensor was designed to detect AA in the range of 0-40.00 µM with a detection limit of 2.17 µM. As the concentration of AA varies in this range, color changes from yellow to blue can be easily observed, so the designed sensor can be used for colorimetric detection. This method can be used to analyze fruit juice samples.

Experimental Evaluation of Working Fluid Damage to Gas Transport in a High-Rank Coalbed Methane Reservoir in the Qinshui Basin, China.

Formation damage induced by the injected working fluid runs through the whole life cycle of coalbed methane (CBM) extraction and ultimately reduces the production of CBM wells. The conventional method uses permeability as a parameter to evaluate the formation damage severity to coal by working fluids containing solids. However, less attention has been attracted to the formation damage of the pure liquid phase of the working fluid on the multiscale gas transport process of CBM. Therefore, we present a multiscale working fluid filtrate damage evaluation method considering the desorption, diffusion, and seepage and use it to evaluate high-rank coal in the Qinshui Basin of China. The results show that pure liquids with different pH values and salinities significantly damage the desorption-diffusion and seepage ability of CBM. The damage rates of alkaline fluid, hydrochloric acid fluid, and clear water on the methane desorption capacity of coal are 63.64, 17.63, and 24.34%, respectively, while those on the permeability of coal are 29.88, 42.38, and 46.66%, respectively. The formation damage severity in the seepage process is higher than that in the desorption-diffusion process, which proves the necessity of multiscale working fluid damage evaluation on CBM. Effective channel reduction and resistance increase in gas transport are the mechanisms of working fluid filtrate-induced formation damage, which are caused by water blocking, sensitive mineral swelling and clogging, and strengthened stress sensitivity. In addition to controlling the solid damage of the working fluid, reducing the invasion of the working fluid filtrate and maintaining its compatibility with the coal and formation fluids are even more important to protect the coal reservoir.

Multicolor colorimetric visual detection of Staphylococcus aureus based on Fe3O4-Ag-MnO2 composites nano-oxidative mimetic enzyme.

Novel Fe3O4-Ag-MnO2 composites were successfully synthesized. It was noteworthy that the obtained Fe3O4-Ag-MnO2 composites were found to possess three types of enzyme-mimicking activities, including peroxidase-like, catalase-like and oxidase-like activities. Taking advantage of the oxidase properties of Fe3O4-Ag-MnO2, the direct oxidation of TMB could be catalyzed to generate blue oxidation products without H2O2. The oxidase-like activity of Fe3O4-Ag-MnO2 were carefully studied. Based on the Fe3O4-Ag-MnO2-TMB system, a fast, sensitive and intuitive multicolor colorimetric method for Staphylococcus aureus (S. aureus) detection was established under the optimized conditions. The proposed method allows the detection of S. aureus with a detection limit of 3.7 cfu mL-1 and a linear range of 10-106 cfu mL-1. This new colorimetric method has been successfully proved to be applicable to the detection S. aureus of food samples.

Vitamin K3 Suppresses Pyroptosis in THP-1 Cells through Inhibition of NF-κB and JNK Signaling Pathways.

Vitamin K, a necessary nutritional supplement for human, has been found to exhibit anti-inflammatory activity. In the present study, we investigated the effects of vitamin K family on lipopolysaccharide (LPS) plus nigericin induced pyroptosis and explored the underlying mechanism of its action in THP-1 monocytes. Results showed that vitamin K3 treatment significantly suppressed THP-1 pyroptosis, but not vitamin K1 or K2, as evidenced by increased cell viability, reduced cellular lactate dehydrogenase (LDH) release and improved cell morphology. Vitamin K3 inhibited NLRP3 expression, caspase-1 activation, GSDMD cleavage and interleukin (IL)-1ß secretion in pyrophoric THP-1 cells. In addition, vitamin K3 inhibited the pro-inflammatory signaling pathways including nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK). Vitamin K3 treatment also attenuated tissue damage and reduced serum LDH, IL-1ß and IL-6 levels in LPS-induced systemic inflammation of mice. The reduced myeloperoxidase (MPO) activityand F4/80 expression indicated that vitamin K3 effectively reduced the infiltration of neutrophils and macrophages. Moreover, NLRP3 expression in monocytes/macrophages were also decreased in vitamin K3-treatedmice after LPS challenge. These findings suggest that vitamin K3 potently alleviates systemic inflammation and organ injury via inhibition of pyroptosis in monocytes and may serve as a novel therapeutic strategy for patients with inflammatory diseases.

Core-shell-structured magnetic covalent organic frameworks for effective extraction of parabens prior to their determination by HPLC.

Covalent organic framework (COF)-decorated magnetic nanoparticles (Fe3O4@DhaTab) with core-shell structure have been synthesized by one-pot method. The prepared Fe3O4@DhaTab was well characterized, and parameters of magnetic solid-phase extraction (MSPE) for parabens were also investigated in detail. Under optimized conditions, the adsorbent dosage was only 3 mg and extraction time was 10 min. The developed Fe3O4@DhaTab-based MSPE-HPLC analysis method offered good linearity (0.01-20 µg mL-1) with R2 (0.999) and low limits of detection (3.3-6.5 µg L-1) using UV detector at 254 nm. The proposed method was applied to determine four parabens in environmental water samples with recoveries in the range 64.0-105% and relative standard deviations of 0.16-7.8%. The adsorption mechanism was explored and indicated that porous DhaTab shell provided π-π, hydrophobic, and hydrogen bonding interactions in the MSPE process. The results revealed the potential of magnetic-functionalized COFs in determination of environmental contaminants.

Human amniotic mesenchymal stem cells-derived IGFBP-3, DKK-3, and DKK-1 attenuate liver fibrosis through inhibiting hepatic stellate cell activation by blocking Wnt/ß-catenin signaling pathway in mice.

BACKGROUND: Liver fibrosis is an outcome of restoring process in chronic liver injury. Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating liver fibrosis. This study aimed to explore the effect and mechanism of hAMSCs on liver fibrosis. METHODS: hAMSCs were transplanted into carbon tetrachloride (CCl4)-induced liver fibrosis mice via tail vein, and the effects of hAMSCs on hepatic fibrosis were assessed. The effects of hAMSCs and hAMSCs conditional medium (CM) on the activation of hepatic stellate cells (HSCs) were investigated in vivo and in vitro. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may inhibit the activation of HSCs. Finally, the underlying mechanisms were explored by assessing IGF-1R/PI3K/AKT and GSK3ß/ß-catenin signaling pathways in the activated HSCs (LX-2) with hAMSCs and hAMSCs transfected with corresponding siRNAs. RESULTS: Our results showed that hAMSCs possessed the characterizations of mesenchymal stem cells. hAMSCs significantly reduced liver fibrosis and improved liver function in mice by inhibiting HSCs activation in vivo. Both hAMSCs and hAMSC-CM remarkably inhibited the collagen deposition and activation of LX-2 cells in vitro. Antibody array assay showed that insulin-like growth factor binding protein-3 (IGFBP-3), Dickkopf-3 (DKK-3), and Dickkopf-1 (DKK-1) were highly expressed in the co-culture group and hAMSC-CM group compared with LX-2 group. Western blot assay demonstrated that IGFBP-3, DKK-3, and DKK-1 derived from hAMSCs inhibit LX-2 cell activation through blocking canonical Wnt signaling pathway. CONCLUSIONS: Our results demonstrated that IGFBP-3, Dkk3, and DKK-1 secreted by hAMSCs attenuated liver fibrosis in mice through inhibiting HSCs activation via depression of Wnt/ß-catenin signaling pathway, suggesting that hAMSCs or hAMSC-CM provides an alternative therapeutic approach for the treatment of liver fibrosis.

Fabrication of magnetic covalent organic framework for effective and selective solid-phase extraction of propylparaben from food samples.

Efficient magnetic solid phase extraction using crystalline porous polymers can find important applications in food safety. Herein, the core-shell Fe3O4@COFs nanospheres were synthesized by one-pot method and characterized in detail. The porous COF shell with large surface area had fast and selective adsorption for propylparaben via π-π, hydrogen bonding and hydrophobic interactions. The extraction and desorption parameters were evaluated in detail. Under the optimized conditions, the extraction equilibrium was reached only in 5 min, the maximum adsorption capacity for propylparaben was 500 mg g-1 and the proposed Fe3O4@DhaTab-based-MSPE-HPLC-UV method afforded good linearity (4-20000 µg mL-1) with R2 (0.997), low limits of detection (0.55 µg L-1) and limits of quantification (1.5 µg L-1). Furthermore, the developed method was applied to determine propylparaben in soft drinks with the recoveries (97.0-98.3%) and relative standard deviations (0.61 to 3.75%). These results revealed the potential of Fe3O4@DhaTab as efficient adsorbents for parabens in food samples.

Synthesis of polymerizable quaternary thiazole salts and their application as antibacterial agents for dental resin.

For the purpose of endowing dental resin with antibacterial activity without impairing physicochemical properties, polymerizable quaternarized thiazole salts (QAMEMT-x) with different alkyl chain length (12, 14, and 16) were synthesized and characterized by FT-IR and 1H-NMR spectra. After adding 5 wt% of QAMEMT-x into Bis-GMA/TEGDMA (50/50, wt./wt.) dental resin, double bond conversion (DC), volumetric shrinkage (VS), flexural strength (FS) and modulus (FM), water sorption (WS) and solubility (SL), and antibacterial activity against Streptococcus mutans (S. mutans) of obtained resin systems were investigated. The results showed that 5 wt% of QAMEMT-x had no influence on DC, FS, FM, WS, and SL (α > 0.05), while could reduce VS of dental resin (α < 0.05). Cured resins with 5 wt% of QAMEMT-x all showed antibacterial activity against S. mutans, and QAMEMT-16 could endow cured resin with the strongest antibacterial activity which showed an antibacterial efficiency of more than 99%.

A colorimetric sensor for Staphylococcus aureus detection based on controlled click chemical-induced aggregation of gold nanoparticles and immunomagnetic separation.

Staphylococcus aureus (S. aureus) is a pathogen closely associated with foodborne diseases. We prepared a reliable colorimetric sensor to detect S. aureus using click chemical reaction and immunomagnetic separation. Aptamer-functionalized and ALP-labeled Fe3O4 NPs act as separation and signal transduction elements. Under the optimized conditions, the Cu+ generated by signal transduction triggers a click chemistry reaction, which causes the aggregation of azides and alkyne-AuNPs and a color change. The net extinction ratio of Δ(A530/A760) was linearly correlated with the S. aureus concentration from 10 to 106 cfu mL-1, and the limit detection was 2.4 cfu mL-1. The recoveries were 91.15 ~ 106.36% for the analysis of spiked food and water samples without pre-enrichment. Therefore, we believe that the detection platform can be easily and accurately used for S. aureus detection, providing a broad prospect for on-site visual detection.

Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acetaminophen-induced acute liver failure through activating ERK and IGF-1R/PI3K/AKT signaling pathway.

This study aimed to investigate the therapeutic potential of human umbilical cord mesenchymal stem cells derived exosomes (hUCMSC-Exo) in acute liver failure (ALF) in mice as well as its underlying mechanism. We found that a single tail vein administration of hucMSC-Exo effectively enhanced the survival rate, inhibited apoptosis in hepatocytes, and improved liver function in APAP-induced mouse model of ALF. Furthermore, the deletion of glutathione (GSH) and superoxide dismutase (SOD), generation of malondialdehyde (MDA), and the over production of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP were also inhibited by hucMSC-Exo, indicating that hucMSC-Exo inhibited APAP-induced apoptosis of hepatocytes by reducing oxidative stress. Moreover, hucMSC-Exo significantly down-regulated the levels of inflammatory cytokines IL-6, IL-1ß, and TNF-α in APAP-treated livers. Western blot showed that hucMSC-Exo significantly promoted the activation of ERK1/2 and IGF-1R/PI3K/AKT signaling pathways in APAP-injured LO2 cells, resulting in the inhibition of apoptosis of LO2 cells. Importantly, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 could reverse the function of hucMSC-Exo on APAP-injured LO2 cells in some extent. Our results suggest that hucMSC-Exo offer antioxidant hepatoprotection against APAP in vitro and in vivo by inhibitiing oxidative stress-induced apoptosis via upregulation of ERK1/2 and PI3K/AKT signaling pathways.

Bone marrow cells are differentiated into MDSCs by BCC-Ex through down-regulating the expression of CXCR4 and activating STAT3 signalling pathway.

Studies showed that the increase of myeloid-derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour-derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)-secreted exosomes (BCC-Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour-bearing mice and BCC-Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC-Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs-related functional proteins Arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC-Ex significantly down-regulated the expressions of chemokine receptor CXCR4 and markedly up-regulated the levels of inflammatory cytokines IL-6 and IL-10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC-Ex, indicating that BCC-Ex-induced MDSCs might be dependent on the down-regulation of CXCR4. Western blot showed that BCC-Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs.

Carotenoids in Sporidiobolus pararoseus ameliorate diabetic nephropathy in mice through attenuating oxidative stress.

Diabetic nephropathy (DN) is the major life-threatening complication of diabetes, and oxidative stress takes part in its initiation and development. This study was performed to evaluate the effects of carotenoids from Sporidiobolus pararoseus (CSP) on the renal function and oxidative stress status of mice with streptozotocin (STZ)-induced DN. The results indicated that CSP significantly attenuated symptoms of STZ-induced DN shown by decreased fasting blood glucose, reduced urine volume, urine albumin, serum creatinine and serum urea nitrogen, and improved kidney histological morphology. Furthermore, biochemical analysis of serum and kidney revealed a marked increase in oxidative stress of DN mice as evidenced by reduced total antioxidant capacity (T-AOC), decreased activity of antioxidant enzyme -superoxide dismutase (SOD) and increased level of malondialdehyde (MDA). However, treatment with CSP improved oxidative stress status in DN mice as compared with the mice in model group. Exploration of the potential mechanism validated that CSP ameliorated the oxidative stress status in DN mice by activating the expressions of Nrf2, NQO-1, HO-1, GST and CAT in kidney. These data revealed that CSP may retard the progression of DN by ameliorating renal function, improving the oxidative stress status and activating the Nrf2/ARE pathway.

Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells.

Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells (ASCs) are able to repair/replace damaged or degenerative tissues and improve functional recovery in experimental model and clinical trials. However, there are still many limitations and unresolved problems regarding stem cell therapy in terms of ethical barriers, immune rejection, tumorigenicity, and cell sources. By reviewing recent literatures and our related works, human amnion-derived stem cells (hADSCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) have shown considerable advantages over other stem cells. In this review, we first described the biological characteristics and advantages of hADSCs, especially for their high pluripotency and immunomodulatory effects. Then, we summarized the therapeutic applications and recent progresses of hADSCs in treating various diseases for preclinical research and clinical trials. In addition, the possible mechanisms and the challenges of hADSCs applications have been also discussed. Finally, we highlighted the properties of hADSCs as a promising source of stem cells for cell therapy and regenerative medicine and pointed out the perspectives for the directions of hADSCs applications clinically.

Nicaraven inhibits TNFα-induced endothelial activation and inflammation through suppression of NF-κB signaling pathway.

Inflammation-induced activation and dysfunction of endothelial cells play an important role in the pathology of multiple vascular diseases. Nicaraven, a potent hydroxyl radical scavenger, has recently been found to have anti-inflammatory roles; however, the mechanism of its action is not fully understood. Here we investigated the effects of Nicaraven on tumor necrosis factor α (TNFα) - induced inflammatory response in human umbilical vein endothelial cells and we explore the underlying mechanisms related to the nuclear factor-κB (NF-κB) signaling pathway. Our results showed that Nicaraven significantly reduced the reactive oxygen species production after TNFα stimulation. Nicaraven suppressed TNFα-induced mRNA expression of multiple adhesion molecules and pro-inflammatory cytokines, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, MCP-1, TNFα, interleukin-1ß (IL-1ß), IL-6, and IL-8. In addition, Nicaraven inhibited monocyte adhesion and reduced the protein levels of VCAM-1 and ICAM-1. Mechanistically, Nicaraven prevented TNFα-induced activation of NF-κB signaling pathway by suppressing the phosphorylation of NF-κB p65, IκBα, and IκB kinase (IKK)α/ß, stabilizing IκBα, and inhibiting the translocation of p65 from cytosol to nucleus. Finally, we showed that Nicaraven improved the functions of endothelial cells, seen as the upregulation of endothelial nitric oxide synthase and increased nitric oxide levels. Our findings indicated that Nicaraven effectively inhibits TNFα-induced endothelial activation and inflammatory response at least partly through inhibiting NF-κB signaling pathway.

Exploring spatial characteristics of city-level CO2 emissions in China and their influencing factors from global and local perspectives.

In China, cities are the basic units for implementing CO2 abatement policies. However, few studies have comprehensively explored the spatial characteristics of CO2 emissions (CEs) and their influencing factors at the city level from different perspectives. After collecting spatial data from 280 Chinese prefecture-level cities for 2005, 2012, and 2015, this work firstly uncovered the overall and local spatial characteristics of CEs by adopting spatial autocorrelation analysis. Then, five influencing factors, including the total resident population (POP), per capita GDP (PCGDP), energy intensity (EI), the proportion of secondary industry (SI), and climate factor-heating degree days (HDD), were examined using global and local regression models. The analyses revealed that (1) CEs presented spatial agglomeration features from global and local perspectives, indicating spatial association between neighboring cities; and (2) POP, PCGDP, EI, and HDD had statistically significant spatial correlations with CEs, and their effect sizes were as follows: PCGDP > POP > EI > HDD. More importantly, the impacts of these influencing factors on CEs varied across cities, exhibiting obvious spatial heterogeneity. According to these findings, local governments should strengthen coordination and cooperation with their surrounding cities to promote regional synergistic action on emission reduction. In addition, policymakers should also design differentiated abatement policies based on regional characteristics and differences instead of applying similar policies to all cities.

Human amniotic mesenchymal stem cells inhibit hepatocellular carcinoma in tumour-bearing mice.

Hepatocellular carcinoma (HCC) is the third leading cause of the cancer-related death in the world. Human amniotic mesenchymal stem cells (hAMSCs) have been characterized with a pluripotency, low immunogenicity and no tumorigenicity. Especially, the immunosuppressive and anti-inflammatory effects of hAMSCs make them suitable for treating HCC. Here, we reported that hAMSCs administrated by intravenous injection significantly inhibited HCC through suppressing cell proliferation and inducing cell apoptosis in tumour-bearing mice with Hepg2 cells. Cell tracking experiments with GFP-labelled hAMSCs showed that the stem cells possessed the ability of migrating to the tumorigenic sites for suppressing tumour growth. Importantly, both hAMSCs and the conditional media (hAMSC-CM) have the similar antitumour effects in vitro, suggesting that hAMSCs-derived cytokines might be involved in their antitumour effects. Antibody array assay showed that hAMSCs highly expressed dickkopf-3 (DKK-3), dickkopf-1 (DKK-1) and insulin-like growth factor-binding protein 3 (IGFBP-3). Furthermore, the antitumour effects of hAMSCs were further confirmed by applications of the antibodies or the specific siRNAs of DKK-3, DKK-1 and IGFBP-3 in vitro. Mechanically, hAMSCs-derived DKK-3, DKK-1 and IGFBP-3 markedly inhibited cell proliferation and promoted apoptosis of Hepg2 cells through suppressing the Wnt/ß-catenin signalling pathway and IGF-1R-mediated PI3K/AKT signalling pathway, respectively. Taken together, our study demonstrated that hAMSCs possess significant antitumour effects in vivo and in vitro and might provide a novel strategy for HCC treatment clinically.

Effect of red pepper (Zanthoxylum bungeanum Maxim.) leaf extract on volatile flavor compounds of salted silver carp.

Chinese red pepper (Zanthoxylum bungeanum Maxim.) leaf (ZML) extract was added to salted silver carp. The effect of ZML extract on volatile compounds formation of both dorsal and ventral muscle of salted fish was investigated. Lipid oxidation of salted fish with ZML extract was alleviated with lower peroxide value (PV) and thiobarbituric acid reactive substance (TBARS) values than that of the control. Therefore, the contents of some volatile compounds formed mainly by oxidation such as benzene, methylbenzene, 1-octene-3-ol, hexanal, and methyl ketone, which attributed off-odor of salted fish, were reduced. Principal component analysis results showed that the first principal component (PC1) and the second principal component (PC2) explained 62% and 31% of total variance, respectively, and volatile compounds of the dorsal and ventral of control group differentiated from treatment group. These results showed that ZML extract can be a source of natural antioxidants and food additives for improving flavor of salted fish.

The key regulation of miR-124-3p during reprogramming of primary mouse hepatocytes into insulin-producing cells.

Based on the action of small molecule compounds, the efficiency of differentiation of mouse primary hepatocytes into insulin-producing cells (IPCs) was improved by changing the expression of miR-124-2p. Hepatocytes were transfected with microRNA-124-3p (miR-124-3p) mimic or inhibitor, followed by a chemical-defined culture system for maturation of IPCs. Then, detect the expression of insulin-related genes and protein and insulin secretion of each stage during differentiation. The expression of Foxa2, PDX1, NeuroD, insulin1, and insulin2 in IPCs in the miR-124-3p inhibition expression group was significantly upregulated, while the results were opposite in the miR-124-3p overexpression group. The results of cell immunofluorescence and glucose stimulation in vitro of the miR-124-3p inhibition expression group showed that the expression of insulin, PDX1, and C-peptide was increased, and the differentiation efficiency was higher than those of the control group and overexpression group. The primary mouse hepatocytes were successfully reprogrammed into IPCs by small-molecule compounds. We found that miR-124-3p plays a negative regulatory role in the differentiation of hepatocytes into IPCs in vitro. Inhibition of miR-124-3p expression significantly increased the expression of FOXA2 and PDX1, promoted the differentiation of hepatocytes into IPCs, and increased the induction efficiency.