Three-dimensional simulation of green soybean infrared-assisted spouted bed drying.

BACKGROUND: The current study introduces a novel infrared-assisted spouted bed drying technique for the dehydration of green soybeans, which aims to enhance the drying quality and efficiency. The investigation involves an examination of the flow pattern in the spouted bed to obtain relevant data, followed by an optimization of the entire drying process. The drying process of green soybeans was simulated using SolidWorks and ANSYS Fluent software, based on the principles of computational fluid dynamics. RESULTS: The simulation test results showed that the simulation outcomes were consistent with the experimental data. The optimal conditions for the process of green soybean infrared-assisted spouted bed drying were found to be an inlet speed of 8 m/s and a temperature of 50 °C with the wavelength and power settings of the infrared board at 10 µm and 500 W, respectively. CONCLUSION: The simulation method selected in this article, based on gas-solid two-phase flow dynamics, is feasible for green soybean infrared-assisted spouted bed drying process. © 2023 Society of Chemical Industry.

Innovative hybrid strategy for quality improvement of Goji tea: ultrasonic-ethyl oleate pretreatment combined with heat pump drying.

BACKGROUND: Goji berries, renowned for their nutritional benefits, are traditionally dried to extend shelf life and preserve quality. However, conventional drying methods often result in uneven drying, color loss and reduced rehydration capacity. This study investigates an innovative hybrid strategy combining ultrasonic-ethyl oleate (US+AEEO) pretreatment with heat pump drying (HPD) to enhance the drying process of Goji berries. RESULTS: Fresh Goji berries underwent US+AEEO pretreatment, which significantly disrupted the waxy layer, enhancing drying efficiency and water infiltration during rehydration. Compared to freeze drying (FD), HPD combined with US+AEEO pretreatment resulted in higher retention of total polyphenol content (TPC) and total flavonoid content (TFC) in the Goji soaking soup. Specifically, the HPD-US+AEEO samples exhibited the highest TPC and TFC levels, significantly outperforming FD samples. Additionally, the DPPH and ABTS antioxidant assays demonstrated higher scavenging activities in HPD-US+AEEO samples. The rehydration kinetics revealed that HPD samples had a superior rehydration rate and final moisture content compared to FD samples. Low-field nuclear magnetic resonance and magnetic resonance imaging analyses confirmed enhanced water distribution and higher mobility in HPD-US+AEEO samples. Scanning electron microscopy indicated a more porous structure in US+AEEO-treated samples, facilitating better water absorption and functional component retention. CONCLUSION: The combination of US+AEEO pretreatment with HPD significantly improves the drying process of Goji berries, enhancing nutrient retention, color preservation and rehydration properties. This innovative drying method offers a promising solution for producing high-quality dried Goji berries, benefiting both the food industry and health-conscious consumers. © 2024 Society of Chemical Industry.

Metabolite Cross-Feeding Promoting NADH Production and Electron Transfer during Efficient SMX Biodegradation by a Denitrifier and S. oneidensis MR-1 in the Presence of Nitrate.

Antibiotics often coexist with other pollutants (e.g., nitrate) in an aquatic environment, and their simultaneous biological removal has attracted widespread interest. We have found that sulfamethoxazole (SMX) and nitrate can be efficiently removed by the coculture of a model denitrifier (Paracoccus denitrificans, Pd) and Shewanella oneidensis MR-1 (So), and SMX degradation is affected by NADH production and electron transfer. In this paper, the mechanism of a coculture promoting NADH production and electron transfer was investigated by proteomic analysis and intermediate experiments. The results showed that glutamine and lactate produced by Pd were captured by So to synthesize thiamine and heme, and the released thiamine was taken up by Pd as a cofactor of pyruvate and ketoglutarate dehydrogenase, which were related to NADH generation. Additionally, Pd acquired heme, which facilitated electron transfer as heme, was the important composition of complex III and cytochrome c and the iron source of iron sulfur clusters, the key component of complex I in the electron transfer chain. Further investigation revealed that lactate and glutamine generated by Pd prompted So chemotactic moving toward Pd, which helped the two bacteria effectively obtain their required substances. Obviously, metabolite cross-feeding promoted NADH production and electron transfer, resulting in efficient SMX biodegradation by Pd and So in the presence of nitrate. Its feasibility was finally verified by the coculture of an activated sludge denitrifier and So.

Constructing C-O bridged CeO2/g-C3N4 S-scheme heterojunction for methyl orange photodegradation：Experimental and theoretical calculation.

Owing to its feasibility, efficiency in light-harvesting and effectiveness in the interfacial charge transfer between two n-type semiconductors, constructing heterojunction photocatalysts have been identified as an effective way for enhancing the photocatalytic properties. In this research, a C-O bridged CeO2/g-C3N4 (cCN) Step-scheme (S-scheme) heterojunction photocatalyst was constructed successfully. Under visible light irradiation, the cCN heterojunction exhibited the photocatalytic degradation efficiency of methyl orange, which was about 4.5 and 1.5 times higher than that of pristine CeO2 and CN, respectively. The DFT calculations, XPS and FTIR analyses demonstrated the formation of C-O linkages. And the calculations of work functions revealed the electrons would flow from g-C3N4 to CeO2 due to the difference in Fermi levels, resulting in the production of internal electric fields. Benefiting from the C-O bond and internal electric field, the photo-induced holes in the valence band of g-C3N4 and the photo-induced electrons from conduction band of CeO2 would be recombined when exposed to visible light irradiation, while leaving the electrons with higher redox potential in the conduction band of g-C3N4. This collaboration accelerated the separation and transfer rate of photo-generated electron-hole pairs, which promoted the generation of superoxide radical (•O2-) and improved the photocatalytic activity.

Effects of Transglutaminase Concentration and Drying Method on Encapsulation of Lactobacillus plantarum in Gelatin-Based Hydrogel.

Lactobacillus plantarum is a kind of probiotic that benefits the host by regulating the gut microbiota, but it is easily damaged when passing through the gastrointestinal tract, hindering its ability to reach the destination and reducing its utilization value. Encapsulation is a promising strategy for solving this problem. In this study, transglutaminase (TGase)-crosslinked gelatin (GE)/sodium hexametaphosphate (SHMP) hydrogels were used to encapsulate L. plantarum. The effects of TGase concentration and drying method on the physiochemical properties of the hydrogels were determined. The results showed that at a TGase concentration of 9 U/gGE, the hardness, chewiness, energy storage modulus, and apparent viscosity of the hydrogel encapsulation system were maximized. This concentration produced more high-energy isopeptide bonds, strengthening the interactions between molecules, forming a more stable three-dimensional network structure. The survival rate under the simulated gastrointestinal conditions and storage stability of L. plantarum were improved at this concentration. The thermal stability of the encapsulation system dried via microwave vacuum freeze drying (MFD) was slightly higher than that when dried via freeze drying (FD). The gel structure was more stable, and the activity of L. plantarum decreased more slowly during the storage period when dried using MFD. This research provides a theoretical basis for the development of encapsulation technology of probiotics.

Infrared-assisted spouted bed drying of Chinese yam cubes: effect of constant and variable temperature drying processes on drying behavior, uniformity, and quality attributes.

BACKGROUND: Infrared-assisted spouted bed drying (IRSBD) is an innovative hybrid drying technology based on infrared drying and spouted bed drying, which has the advantages of higher drying efficiency and better uniformity. Temperature is an important process parameter that affects drying characteristics and product quality. Considering the overall quality of the product, drying at a constant temperature may not be the best solution. However, there is a lack of research on dynamically varying drying schemes. In this study, the effects of constant and variable temperature drying processes on the drying characteristics, uniformity, energy consumption, and quality of Chinese yams were evaluated. RESULTS: The shortest drying time and lowest energy consumption were obtained by IRSBD at 70 °C, followed by staged rising temperature drying (SRTD). However, SRTD achieved the best drying uniformity. The Peleg model could describe the dehydration kinetics of dried yams well (R2 > 0.99). A high drying temperature (70 °C) favored the preservation of bioactive compounds (polyphenols and flavonoids) and gave the best antioxidant activity and equilibrium rehydration ratio of dried yams but resulted in poor color. Samples dried with SRTD showed comparable good antioxidant activity and better color than those dried at 70 °C. CONCLUSION: A reasonable variable temperature drying scheme using IRSBD is considered to be better when considering the drying performance and overall quality of the products. © 2022 Society of Chemical Industry.

Effects of different protectants on the IgY content and physico-chemical properties of spray-dried egg yolk powder.

BACKGROUND: Egg yolk powder (EYP) with high immunoglobulin of yolk (IgY) content and good solubility is in great demand in the market of functional foods. In this article, the properties of spray-dried EYP with the addition of five protectants (maltodextrin, trehalose, mannitol, maltitol and sucrose) were investigated. RESULTS: All the protectants increased IgY activity and solubility of EYP. Among them, EYP with maltodextrin displayed the highest activity of IgY (27.11 mg/g), the highest solubility (66.39%) and the lowest surface hydrophobicity. Moreover, the average particle size of EYP with maltodextrin was the smallest (9.78 µm). The egg yolk particles obtained by adding the protectants are more uniformly distributed and have smaller particle size. Fourier-transform infrared spectroscopy confirmed the structural integrity of the proteins, indicating that the protectants addition enhanced the hydrogen bonding forces between the EYP protein molecules. CONCLUSION: The addition of protectants can significantly improve the IgY content, solubility and structural stability of EYP. © 2023 Society of Chemical Industry.

[Research progress on the role and mechanism of endothelial dysfunction in hyperhomocysteine-induced atherosclerosis].

Hyperhomocysteinemia (HHcy) is considered to be an independent risk factor for cardiovascular diseases, but the molecular mechanisms underlying its pathogenesis are not fully understood. Endothelial dysfunction is a key initiating factor in the pathogenesis of atherosclerosis, which is commonly observed in almost all HHcy-induced vascular diseases. HHcy promotes oxidative stress, inhibits nitric oxide production, suppresses hydrogen sulfide signaling pathway, promotes endothelial mesenchymal transition, activates coagulation pathways, and promotes protein N-homocysteination and cellular hypomethylation, all of which can cause endothelial dysfunction. This article reviews the specific links between HHcy and endothelial dysfunction, and highlights recent evidence that endothelial mesenchymal transition contributes to HHcy-induced vascular damage, with a hope to provide new ideas for the clinical treatment of HHcy-related vascular diseases.

Endothelial cells induce degradation of ECM through enhanced secretion of MMP14 carried on extracellular vesicles in venous malformation.

Venous malformations (VMs), featuring localized dilated veins, are the most common developmental vascular anomalies. Aberrantly organized perivascular extracellular matrix (ECM) is one of the prominent pathological hallmarks of VMs, accounting for vascular dysfunction. Although previous studies have revealed various proteins involved in ECM remodeling, the detailed pattern and molecular mechanisms underlying the endothelium-ECM interplay have not been fully elucidated. Our previous studies revealed drastically elevated extracellular vesicle (EV) secretion in VM lesions. Here, we identified increased EV-carried MMP14 in lesion fluids of VMs and culture medium of TIE2-L914F mutant endothelial cells (ECs), along with stronger ECM degradation. Knockdown of RAB27A, a required regulator for vesicle docking and fusion, led to decreased secretion of EV-carried MMP14 in vitro. Histochemical analysis further demonstrated a highly positive correlation between RAB27A in the endothelium and MMP14 in the perivascular environment. Therefore, our results proved that RAB27A-regulated secretion of EV-MMP14, as a new pattern of endothelium-ECM interplay, contributed to the development of VMs by promoting ECM degradation.

Identification of distinct genomic features reveals frequent somatic AHNAK and PTEN mutations predominantly in primary malignant melanoma presenting in the ureter.

BACKGROUND: Primary malignant melanoma of the ureter is extremely rare. Genetic variants to the increased risk of developing the disease have not yet been investigated. METHODS: Tumour mutation profiling for primary malignant melanoma of the ureter was performed by whole-exome sequencing. Immunohistochemistry was performed to verify histopathological features and the variants of predisposing genes and driver mutation genes. Furthermore, we conducted a literature review and Surveillance, Epidemiology and End Result-based study by searching public databases. RESULTS: We identified 38 somatic single nucleotide variants and 9 somatic insertions and deletions (INDELs) in tumour specimens. After filtering with the Cancer Gene Census database, seven predisposing genes and two driver mutation genes were identified. Moreover, the immunohistochemical profile showed that tumour cells were positive for Melan-A, melanoma gp100 human melanoma black 45 (HMB45), S100 beta and P53. The expression levels of two driver mutation genes (phosphatase and tensin homolog (PTEN) and desmoyokin (AHNAK) and five predisposing genes (AT-rich interaction domain 1B (ARID1B), catalase, eukaryotic translation initiation factor 4 gamma 3 (EIF4G3), ANK3 and collagen type I) were significantly downregulated in tumour tissues compared to paracancerous tissues. In the literature review and Surveillance, Epidemiology and End Results-based study, patients with primary malignant melanoma of the urinary tract had worse clinical outcomes than patients with primary urothelial carcinoma after 1:2 propensity score matching (P = 0.010). Additionally, Cox multivariate analysis for patients with primary malignant melanoma of the urinary tract indicated that distant metastasis (hazard ratio = 1.185; P = 0.044) was an independent predictor for overall survival, and tumour focality (hazard ratio = 0.602; P = 0.017) and non-surgery (hazard ratio = 0.434; P = 0.003) were independent factors for tumour progression. CONCLUSIONS: Our study is the first to provide evidence that the distinct phenotypes of primary malignant melanoma of the ureter may be due to different genetic variations. The prognosis of primary malignant melanoma of the urinary tract was poorer than that of primary urothelial carcinoma of the urinary tract.

Mucilaginibacter Phenanthrenivorans sp. nov., a Novel Phenanthrene Degradation Bacterium Isolated from Wetland Soil.

BJC16-A38T, a Gram-negative, aerobic and non-motile rod-shaped strain was isolated from a permafrost wetland soil sample. BJC16-A38T was oxidase- and catalase-positive, and produced pale yellow colonies on modified R2A agar plates. The 16S rRNA gene sequence of BJC16-A38T shared the highest sequence similarity with those of Mucilaginibacter xinganensis BJC16-A31T (97.44%), Mucilaginibacter gotjawali SA3-7T (96.79%) and Mucilaginibacter frigoritolerans FT22T (96.14%). Phylogenetic analysis revealed that BJC16-A38T formed a separate lineage together with strain M. xinganensis BJC16-A31T in the genus Mucilaginibacter. BJC16-A38T contained menaquinone-7 (MK-7) as the predominant isoprenoid quinine. Major fatty acids in cells were iso-C15:0, summed feature 3 (16:1ω7c/16:1ω6c) and iso-C17:03-OH. BJC16-A38T contained phosphatidylethanolamine, two unknown polar lipids, six unidentified phospholipids and an unidentified aminolipid. The Genome of BJC16-A38T was sequenced using the Genome Analyzer IIx sequence platform and 38 contigs were produced in total with an average G + C percentage of 44.00%. The average nucleotide identity (ANI) of BJC16-A38T with respect to those of M. xinganensis BJC16-A31T, M. gotjawali SA3-7T and M. frigoritolerans FT22T were 79.60%, 77.24% and 77.58%, respectively. Digital DNA-DNA hybridization (DDH) values between BJC16-A38T and the tree reference strains were 21.30%, 19.60% and 19.70%, respectively. BJC16-A38T exhibited phenanthrene biodegradation activity that can degrade 88.02% phenanthrene in the MM medium after 7 days cultivation. Phenotypic, chemotaxonomic, phylogenetic and genomic characteristics concluded that strain BJC16-A38T represents a novel species of the genus Mucilaginibacter. Hence, the name Mucilaginibacter phenanthrenivorans sp. nov. is proposed. The type strain is BJC16-A38T (= CGMCC 1.12693T = NBRC 110383T).

Trends in growth and nutritional status of high school graduates in Hangzhou, China, 2011-2020.

BACKGROUND: During past decades, there was a positive trend in growth and nutrition status of adolescents in China, but there was significant regional disparity. The purpose of this study is to investigate the trends in growth and nutritional status of high school graduates in Hangzhou between 2011 and 2020. METHODS: High school graduates (Grade 12) who finished the physical examination of the national college entrance examination between 2011 and 2020 (n=481,353)were included in this study. Data were obtained from the database of physical examination of the national college entrance exam. Height and weight were measured; body mass index (BMI) was calculated from height and weight. Thinness, overweight and obesity were defined according to the International Obesity Task Force criteria. For the vast majority of the high school graduates were 18 years old or nearly 18 years old, the cutoffs of 18 years were adopted. Those are 18.5, 25 and 30 kg/m2, for thinness, overweight and obesity respectively. RESULTS: There was a significant growth trend in height, weight and BMI in both sexes (P < 0.001). Height increased by 1.80 cm in boys and 1.45 cm in girls. Weight increased by 4.62 kg in boys and 2.51 kg in girls. BMI increased by 1.09 kg/m2 in boys and 0.60 kg/m2 in girls. An increase trend was found in the prevalence of overweight and obesity in both sexes (P < 0.001). Overweight increased by 7.43% (from 9.05 to 16.48%) among boys and 4.05% (from 4.57 to 8.62%) among girls. Obesity increased by 3.85% (from 2.29 to 6.14%) among boys and 1.76% (from 0.64 to 2.40%) among girls. The prevalence of thinness fluctuated in both boys and girls, 12.42-15.59% among boys and 18.97-23.68% among girls. Boys had higher odds of overweight and obesity and lower odds of thinness than girls (P < 0.001). CONCLUSIONS: There is a positive trend in growth and nutritional status of high school graduates in Hangzhou. However, there is still a considerable prevalence of thinness, it indicates a double burden of undernutrition and overnutrition.

Are you a water saver? Discovering people's water-saving intention by extending the theory of planned behavior.

Saving water is a common responsibility of all humanity, which is essential for achieving sustainable use of global water resources. The aim of this study is to discover the determinants of an individual's intention to save water. Based on the theory of planned behavior, a novel comprehensive framework has been developed by extending environmental concern, perceived risk, and information publicity. Partial least squares structural equation modeling was used to perform an empirical analysis with data from questionnaire of 265 residents in Jinan, the famous Chinese "Spring City". The findings indicate that residents have a strong environmental concern and water-saving intention with mean values of 6.78 and 6.67, respectively. Attitude and information publicity are the most important antecedents of water-saving intention, followed by subjective norms and perceived behavioral control. Environmental concern and perceived risk indirectly affect the intention to save water through attitude, subjective norms, and perceived behavioral control. The role of environmental concern is more important than the role of perceived risk. Interestingly, a high level of information publicity may strengthen the impact of attitude on water-saving intention but weaken the impact of perceived behavioral control. This study strongly supplements current knowledge on water-saving behavior. Moreover, these findings provide insights for policymakers to motivate people to save water.

Cookies Fortified with Lonicera japonica Thunb. Extracts: Impact on Phenolic Acid Content, Antioxidant Activity and Physical Properties.

Lonicera japonica Thunb [...].

[A spatial-temporal hybrid feature extraction method for rapid serial visual presentation of electroencephalogram signals].

Rapid serial visual presentation-brain computer interface (RSVP-BCI) is the most popular technology in the early discover task based on human brain. This algorithm can obtain the rapid perception of the environment by human brain. Decoding brain state based on single-trial of multichannel electroencephalogram (EEG) recording remains a challenge due to the low signal-to-noise ratio (SNR) and nonstationary. To solve the problem of low classification accuracy of single-trial in RSVP-BCI, this paper presents a new feature extraction algorithm which uses principal component analysis (PCA) and common spatial pattern (CSP) algorithm separately in spatial domain and time domain, creating a spatial-temporal hybrid CSP-PCA (STHCP) algorithm. By maximizing the discrimination distance between target and non-target, the feature dimensionality was reduced effectively. The area under the curve (AUC) of STHCP algorithm is higher than that of the three benchmark algorithms (SWFP, CSP and PCA) by 17.9%, 22.2% and 29.2%, respectively. STHCP algorithm provides a new method for target detection.

Integrated Metagenomic and Metaproteomic Analyses Unravel Ammonia Toxicity to Active Methanogens and Syntrophs, Enzyme Synthesis, and Key Enzymes in Anaerobic Digestion.

During anaerobic digestion, the active microbiome synthesizes enzymes by transcription and translation, and then enzymes catalyze multistep bioconversions of substrates before methane being produced. However, little information is available on how ammonia affects truly active microbes containing the expressed enzymes, enzyme synthesis, and key enzymes. In this study, an integrated metagenomic and metaproteomic investigation showed that ammonia suppressed not only the obligate acetotrophic methanogens but also the syntrophic propionate and butyrate oxidation taxa and their assistant bacteria (genus Desulfovibrio), which declined the biotransformations of propionate and butyrate → acetate → methane. Although the total population of the hydrolyzing and acidifying bacteria was not affected by ammonia, the bacteria with ammonia resistance increased. Our study also revealed that ammonia restrained the enzyme synthesis process by inhibiting the RNA polymerase (subunits A' and D) during transcription and the ribosome (large (L3, L12, L13, L22, and L25) and small (S3, S3Ae, and S7) ribosomal subunits) and aminoacyl-tRNA synthesis (aspartate-tRNA synthetase) in translation. Further investigation suggested that methylmalonyl-CoA mutase, acetyl-CoA C-acetyltransferase, and CH3-CoM reductase, which regulate propionate and butyrate oxidation and acetoclastic methanation, were significantly downregulated by ammonia. This study provides intrinsic insights into the fundamental mechanisms of how ammonia inhibits anaerobic digestion.

Factors Influencing the Popularity of a Health-Related Answer on a Chinese Question-and-Answer Website: Case Study.

BACKGROUND: Social question-and-answer (Q&A) sites have become an important venue for individuals to obtain and share human papillomavirus (HPV) vaccine knowledge. OBJECTIVE: This study aims to examine how different features of an HPV vaccine-related answer are associated with users' response behaviors on social Q&A websites. METHODS: A total of 2953 answers and 270 corresponding questions regarding the HPV vaccine were collected from a leading Chinese social Q&A platform, Zhihu. Three types of key features, including content, context, and contributor, were extracted and coded. Negative binomial regression models were used to examine their impact on the vote and comment count of an HPV vaccine-related answer. RESULTS: The findings showed that both content length and vividness were positively related to the response behaviors of HPV vaccine-related answers. In addition, compared with answers under the question theme benefits and risks, answers under the question theme vaccination experience received fewer votes and answers under the theme news opinions received more votes but fewer comments. The effects of characteristics of contributors were also supported, suggesting that answers from a male contributor with more followers and no professional identity would attract more votes and comments from community members. The significant interaction effect between content and context features further showed that long and vivid answers about HPV vaccination experience were more likely to receive votes and comments of users than those about benefits and risks. CONCLUSIONS: The study provides a complete picture of the underlying mechanism behind response behaviors of users toward HPV vaccine-related answers on social Q&A websites. The results help health community organizers develop better strategies for building and maintaining a vibrant web-based community for communicating HPV vaccine knowledge.

Soybean glycinin impaired immune function and caused inflammation associated with PKC-ζ/NF-κb and mTORC1 signaling in the intestine of juvenile grass carp (Ctenopharyngodon idella).

Glycinin is a major protein and antinutritional factor of soybean. However, how dietary glycinin affect intestinal immune function of fish were largely unknown. In this study, we used juvenile grass carp as a model to investigate the impacts of glycinin on intestinal immune function of fish and involved mechanisms. We set three treatments including control, glycinin and glycinin + glutamine in this trial. For immune components, results revealed that compared with control group, glycinin group had lower acid phosphatase activities in the foregut, midgut and hindgut, lower C3 and C4 content, and lower mRNA abundances of IgM, IgZ, hepcidin, LEAP-2A, LEAP-2B and ß-defensin-1 in the midgut and hindgut rather than foregut of grass carp. For pro-inflammatory cytokines and relevant signaling, glycinin elevated mRNA abundances of IL-1ß, IL-8, IL-12p35, IL-12p40 and IL-17D in the midgut and IL-1ß, IFN-γ2, IL-6, IL-8, IL-12p35, IL-12p40 and IL-17D in the hindgut, and increased protein abundances of PKC-ζ and nuclear NF-κB p65 in the midgut and hindgut in comparison to control. For anti-inflammatory cytokines and relevant signaling, glycinin reduced mRNA abundances of TGF-ß1, TGF-ß2, IL-4/13B (rather than IL-4/13A), IL-10 and IL-11 in the midgut and hindgut, and reduced p-mTOR (Ser 2448), p-S6K1 (Thr 389) and p-4EBP1 (Thr 37/46) protein abundances in the midgut and hindgut rather than foregut. Co-administration of glutamine with glycinin could partially enhance intestinal function and reduce intestinal inflammation compared with glycinin treatment. Concluded, glycinin decreased intestinal immune components and caused intestinal inflammation associated with PKC-ζ/NF-κB and mTORC1 signaling.

WZ66, a novel acetyl-CoA carboxylase inhibitor, alleviates nonalcoholic steatohepatitis (NASH) in mice.

The global prevalence of nonalcoholic steatohepatitis (NASH) increases incredibly. NASH ends up to advanced liver disease, which is highly threatening to human health. Currently, treatment of NASH is very limited. Acetyl-CoA carboxylases (ACC1/ACC2) are proved as effective drug targets for NASH. We aimed to develop novel ACC inhibitors and evaluate their therapeutic value for NASH prevention. ACC inhibitors were obtained through structure-based drug design, synthesized, screened from ACC enzymatic measurement platform and elucidated in cell culture-based assays and animal models. The lipidome and microbiome analysis were integrated to assess the effects of WZ66 on lipids profiles in liver and plasma as well as gut microbiota in the intestine. WZ66 was identified as a novel ACC1/2 inhibitor. It entered systemic circulation rapidly and could accumulate in liver. WZ66 alleviated NASH-related liver features including steatosis, Kupffer cells and hepatic stellate cells activation in diet-induced obese mice. The triglycerides (TGs) and other lipids including diglycerides (DGs), phosphatidylcholine (PC) and sphingomyelin (SM) were decreased in WZ66-treated mice as evidenced by lipidome analysis in livers. The lipids profiles in plasma were also altered with WZ66 treatment. Plasma TG were moderately increased, while the activation of SREBP1c was not detected. WZ66 also downregulated the abundance of Allobaculum, Mucispirillum and Prevotella genera as well as Mucispirillum schaedleri species in gut microbiota. WZ66 is an ideal lead compound and a potential drug candidate deserving further investigation in the therapeutics of NASH.

The dynamic process of dietary soybean ß-conglycinin in digestion, absorption, and metabolism among different intestinal segments in grass carp (Ctenopharyngodon idella).

The present study aimed to investigate the dynamic process of soybean ß-conglycinin in digestion, absorption, and metabolism in the intestine of grass carp (Ctenopharyngodon idella). Fish fed with 80 g ß-conglycinin/kg diet for 7 weeks, the intestinal digestive enzyme was extracted to hydrolyze ß-conglycinin in vitro, the free amino acid and its metabolism product contents in intestinal segments were analyzed. The present study first found that ß-conglycinin cannot be thoroughly digested by fish intestine digestive enzyme and produces new products (about 60- and 55-kDa polypeptides). The indigestible ß-conglycinin further caused the free amino acid imbalance, especially caused free essential amino acid deficiency in the proximal intestine but excess in the distal intestine. Moreover, these results might be partly associated with the effect of ß-conglycinin in amino acid transporters and tight junction-regulated paracellular pathway. Finally, dietary ß-conglycinin increased the content of amino acid catabolism by-product ammonia while decreased the amino acid anabolism product carnosine content in the proximal intestine and distal intestine. Thus, the current study first and systemically explored the dynamic process of ß-conglycinin in digestion, absorption, and metabolism, which further supported our previous study that dietary ß-conglycinin suppressed fish growth and caused intestine injure.