Efficient extraction of lignin from moso bamboo by microwave-assisted ternary deep eutectic solvent pretreatment for enhanced enzymatic hydrolysis.

Applications of deep eutectic solvent (DES) systems to separate lignocellulosic components are of interest to develop environmentally friendly processes and achieve efficient utilization of biomass. To enhance the performance of a binary neutral DES (glycerol:guanidine hydrochloride), various Lewis acids (e.g., AlCl3·6H2O, FeCl3·6H2O, etc.) were introduced to synthesize a series of ternary DES systems; these were coupled with microwave heating and applied to moso bamboo. Among the ternary DES systems evaluated, the FeCl3-based DES effectively removed lignin (81.17%) and xylan (85.42%), significantly improving enzymatic digestibility of the residual glucan and xylan (90.15% and 99.51%, respectively). Furthermore, 50.74% of the lignin, with high purity and a well-preserved structure, was recovered. A recyclability experiment showed that the pretreatment performance of the FeCl3-based DES was still basically maintained after five cycles. Overall, the microwave-assisted ternary DES pretreatment approach proposed in this study appears to be a promising option for sustainable biorefinery operations.

Downregulation of lncRNA EPB41L4A-AS1 promotes gastric cancer cell proliferation, migration and invasion.

BACKGROUND: The incidence of gastric cancer ranks the first among digestive tract tumors in China. However, there are no specific symptoms in the early stage of the tumor and the diagnosis process is complex, so more effective detection methods are very needed. In this study, a novel long noncoding RNA (lncRNA) was introduced as a diagnostic biomarker for gastric cancer, which brought new thinking to the exploration of its pathological mechanism and clinical prediction. METHODS: The level of lncRNA EPB41L4A-AS1 (EPB41L4A-AS1) in gastric cancer serum and cells was verified via real-time quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curve was performed based on the EPB41L4A-AS1 level, and the diagnostic possibility of EPB41L4A-AS was analyzed. The chi-square test evaluated the correlation between EPB41L4A-AS expression and clinical information. The cells were cultured and transfected in vitro, and the mediations of abnormal EPB41L4A-AS level on the viability and motility of gastric cancer cells were verified through cell counting kit-8 (CCK-8) and Transwell assay. Furthermore, luciferase activity assay was performed to confirm the sponge molecule microRNA-17-5p (miR-17-5p) of EPB41L4A-AS1. RESULTS: EPB41L4A-AS1 was decreased in gastric cancer, and low EPB41L4A-AS1 level indicated resultful diagnostic value. Overexpression of EPB41L4A-AS1 inhibited the activity of gastric cancer cells, while knockdown of EPB41L4A-AS1 promoted tumor deterioration. EPB41L4A-AS1 directly targeted and regulated the expression ofmiR-17-5p. CONCLUSION: This study elaborated that EPB41L4A-AS1 is lowly expressed in gastric cancer. Silencing EPB41L4A-AS1 was beneficial to cell proliferation, migration, and invasion. EPB41L4A-AS1 provides a new possibility for the diagnosis of gastric cancer patients by targeting miR-17-5p.

Genome-Wide Association Analysis of Effective Tillers in Rice under Different Nitrogen Gradients.

Nitrogen is a crucial element that impacts rice yields, and effective tillering is a significant agronomic characteristic that can influence rice yields. The way that reduced nitrogen affects effective tillering is a complex quantitative trait that is controlled by multiple genes, and its genetic basis requires further exploration. In this study, 469 germplasm varieties were used for a genome-wide association analysis aiming to detect quantitative trait loci (QTL) associated with effective tillering at low (60 kg/hm2) and high (180 kg/hm2) nitrogen levels. QTLs detected over multiple years or under different treatments were scrutinized in this study, and candidate genes were identified through haplotype analysis and spatio-temporal expression patterns. A total of seven genes (NAL1, OsCKX9, Os01g0690800, Os02g0550300, Os02g0550700, Os04g0615700, and Os04g06163000) were pinpointed in these QTL regions, and were considered the most likely candidate genes. These results provide favorable information for the use of auxiliary marker selection in controlling effective tillering in rice for improved yields.

Mdpg: a novel multi-disease diagnosis prediction method based on patient knowledge graphs.

Diagnosis prediction, a key factor in enhancing healthcare efficiency, remains a focal point in clinical decision support research. However, the time-series, sparse and multi-noise characteristics of electronic health record (EHR) data make it a great challenge. Existing methods commonly address these issues using RNNs and incorporating medical prior knowledge from medical knowledge bases, but they neglect the local spatial characteristics and spatial-temporal correlation of the data. Consequently, we propose MDPG, a diagnosis prediction model based on patient knowledge graphs. Initially, we represent the electronic visit records of patients as a patient-centered temporal knowledge graph, capturing the local spatial structure and temporal characteristics of the visit information. Subsequently, we design the spatial graph convolution block, temporal self-attention block, and spatial-temporal synchronous graph convolution block to capture the spatial, temporal, and spatial-temporal correlations embedded in them, respectively. Ultimately, we accomplish the prediction of patients' future states through multi-label classification. We conduct comprehensive experiments on two real-world datasets independently and evaluate the results using visit-level precision@k and code-level accuracy@k metrics. The experimental results demonstrate that MDPG outperforms all baseline models, yielding the best performance.

Drp1-mediated mitochondrial fission promotes pulmonary fibrosis progression through the regulation of lipid metabolic reprogramming by ROS/HIF-1α.

OBJECTIVE: To confirm the mechanism of dynamic-related protein 1 (Drp1)-mediated mitochondrial fission through ROS/HIF-1α-mediated regulation of lipid metabolic reprogramming in the progression of pulmonary fibrosis (PF). METHODS: A mouse model of PF was established by intratracheal instillation of bleomycin (BLM) (2.5 mg/kg). A PF cell model was constructed by stimulating MRC-5 cells with TGF-ß (10 ng/mL). Pathological changes in the lung tissue and related protein levels were observed via tissue staining. The indicators related to lipid oxidation were detected by a kit, and lipid production was confirmed through oil red O staining. Inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). RT-qPCR, Western blotting and immunofluorescence staining were used to detect the expression of genes and proteins related to the disease. We used CCK-8 and EdU staining to confirm cell proliferation, flow cytometry was used to confirm apoptosis and ROS levels, α-SMA expression was detected by immunofluorescence staining, and mitochondria were observed by MitoTracker staining. RESULTS: The BLM induced lung tissue structure and alveolar wall thickening in mice. Mitochondrial fission was observed in MRC-5 cells induced by TGF-ß, which led to increased cell proliferation; decreased apoptosis; increased expression of collagen, α-SMA and Drp1; and increased lipid oxidation and inflammation. Treatment with the Drp1 inhibitor mdivi-1 or transfection with si-Drp1 attenuated the induction of BLM and TGF-ß. For lipid metabolism, lipid droplets were formed in BLM-induced lung tissue and in TGF-ß-induced cells, fatty acid oxidation genes and lipogenesis-related genes were upregulated, ROS levels in cells were increased, and the expression of HIF-1α was upregulated. Mdivi-1 treatment reversed TGF-ß induction, while H2O2 treatment or OE-HIF-1α transfection reversed the effect of mdivi-1. CONCLUSION: In PF, inhibition of Drp1 can prevent mitochondrial fission in fibroblasts and regulate lipid metabolism reprogramming through ROS/HIF-1α; thus, fibroblast activation was inhibited, alleviating the progression of PF.

2,4-Dihydroxybenzoic Acid, a Novel SA Derivative, Controls Plant Immunity via UGT95B17-Mediated Glucosylation: A Case Study in Camellia Sinensis.

The plant hormone salicylic acid (SA) plays critical roles in plant innate immunity. Several SA derivatives and associated modification are identified, whereas the range and modes of action of SA-related metabolites remain elusive. Here, the study discovered 2,4-dihydroxybenzoic acid (2,4-DHBA) and its glycosylated form as native SA derivatives in plants whose accumulation is largely induced by SA application and Ps. camelliae-sinensis (Pcs) infection. CsSH1, a 4/5-hydroxylase, catalyzes the hydroxylation of SA to 2,4-DHBA, and UDP-glucosyltransferase UGT95B17 catalyzes the formation of 2,4-DHBA glucoside. Down-regulation reduced the accumulation of 2,4-DHBA glucosides and enhanced the sensitivity of tea plants to Pcs. Conversely, overexpression of UGT95B17 increased plant disease resistance. The exogenous application of 2,4-DHBA and 2,5-DHBA, as well as the accumulation of DHBA and plant resistance comparison, indicate that 2,4-DHBA functions as a potentially bioactive molecule and is stored mainly as a glucose conjugate in tea plants, differs from the mechanism described in Arabidopsis. When 2,4-DHBA is applied exogenously, UGT95B17-silenced tea plants accumulated more 2,4-DHBA than SA and showed induced resistance to Pcs infection. These results indicate that 2,4-DHBA glucosylation positively regulates disease resistance and highlight the role of 2,4-DHBA as potentially bioactive molecule in the establishment of basal resistance in tea plants.

Fructose overconsumption impairs hepatic manganese homeostasis and ammonia disposal.

Arginase, a manganese (Mn)-dependent enzyme, is indispensable for urea generation and ammonia disposal in the liver. The potential role of fructose in Mn and ammonia metabolism is undefined. Here we demonstrate that fructose overconsumption impairs hepatic Mn homeostasis and ammonia disposal in male mice. Fructose overexposure reduces liver Mn content as well as its activity of arginase and Mn-SOD, and impairs the clearance of blood ammonia under liver dysfunction. Mechanistically, fructose activates the Mn exporter Slc30a10 gene transcription in the liver in a ChREBP-dependent manner. Hepatic overexpression of Slc30a10 can mimic the effect of fructose on liver Mn content and ammonia disposal. Hepatocyte-specific deletion of Slc30a10 or ChREBP increases liver Mn contents and arginase activity, and abolishes their responsiveness to fructose. Collectively, our data establish a role of fructose in hepatic Mn and ammonia metabolism through ChREBP/Slc30a10 pathway, and postulate fructose dietary restriction for the prevention and treatment of hyperammonemia.

Conductive and antibacterial dual-network hydrogel for soft bioelectronics.

Conductive hydrogels have shown significant potential for use in soft bioelectronics due to their unique similarities to biological tissue, including high water content, low modulus, and conductivity. However, their high water content makes them susceptible to absorbing microorganisms and promoting bacterial growth, which can trigger an immune response. Besides, the adhesion and biocompatibility of the hydrogel are not satisfactory, seriously limiting the conductive hydrogel's high-performance applications in human healthcare monitoring. Herein, the problem is addressed by introducing borax through a swelling and a semi-dehydration method into the interpenetrated network of a polyvinyl alcohol and poly(acrylic acid) hydrogel. The hydrogel exhibits both outstanding antibacterial (>99.99% toward E. coli and S. aureus) activity and high ionic conductivity, in addition to tissue-like softness, strong wet-tissue adhesion (600 J m-2 for skin), environmental stability, and excellent biocompatibility. Furthermore, the as-prepared hydrogel can serve as a biosensing conductor, showing high-quality recording and monitoring of real-time tiny yet complex muscle movements during speaking and realizing neuromodulation through low-current electronic stimulation (40 µA) of a rat's nerve. Simultaneously, the hydrogel also exhibits the capacity to accelerate wound healing. Therefore, the proposed antibacterial conductive hydrogel is a safer option for next-generation bioelectronic materials in human healthcare.

Structural characterization and anti-inflammatory effects of Enteromorpha prolifera polysaccharide-Fe/Zn complexes.

The structure of polysaccharide has a great influence on its biological functions, and the chelation with metal ions is an effective way to change polysaccharide structural configuration. Herein, the structure of Enteromorpha prolifera polysaccharide (EP)-Fe/Zn complexes were characterized and the results showed that the iron (III) existed in form of ß-FeOOH in EP-Fe (III) complex and the zinc (II) existed in form of C-O-Zn in EP-Zn (II) complex. Besides, the chelation with iron (III) or zinc (II) completely changed the apparent forms, and improved the thermal stability of EP. Furthermore, the anti-inflammatory activities of EP, EP-Fe and EP-Zn were proved by a lipopolysaccharide (LPS)-induced RAW264.7 macrophages model. The results showed that EP, EP-Fe (III) and EP-Zn (II) could decrease the mitochondrial membrane potential and the secretion of NO and cytokines induced by LPS. One of the anti-inflammatory mechanisms of EP, EP-Fe (III) and EP-Zn (II) was that they could inhibit mitogen-activated protein kinase (MAPK) signaling pathway via increasing its inhibitor content in cells. Collectively, the research suggested that the chelation with iron (III) or zinc (II) could change the structure and improve the anti-inflammatory activities of EP.

Dietary lysozyme improves growth performance and intestinal barrier function of weaned piglets.

Lysozyme (LZ) is a purely natural, nonpolluting and nonspecific immune factor, which has beneficial effects on the healthy development of animals. In this study, the influences of LZ on the growth performance and intestinal barrier of weaned piglets were studied. A total of 48 weaned piglets (Landrace × Yorkshire, 22 d old) were randomly divided into a control group (basal diet) and a LZ group (0.1% LZ diet) for 19 d. The results showed that LZ could significantly improve the average daily gain (ADG, P < 0.05) and average daily feed intake (ADFI, P < 0.05). LZ also improved the intestinal morphology and significantly increased the expression of occludin in the jejunum (P < 0.05). In addition, LZ down-regulated the expression of interleukin-1ß (IL-1ß, P < 0.05) and tumor necrosis factor-α (TNF-α, P < 0.05), and inhibited the expression of the genes in the nuclear factor-k-gene binding (NF-κB, P < 0.05) signaling pathway. More importantly, the analysis of intestinal flora showed LZ increased the abundance of Firmicutes (P < 0.05) and the ratio of Firmicutes to Bacteroidota (P = 0.09) at the phylum level, and increased the abundance of Clostridium_sensu_stricto_1 (P < 0.05) and reduced the abundance of Olsenella and Prevotella (P < 0.05) at the genus level. In short, this study proved that LZ could effectively improve the growth performance, relieve inflammation and improve the intestinal barrier function of weaned piglets. These findings provided an important theoretical basis for the application of LZ in pig production.

Formation and isomerization of (Z)-methyl epijasmonate, the key contributor of the orchid-like aroma, during tea processing.

The elegant orchid-like fragrance of tea has always been tea processors and consumers' top priority. Controlling the production process is very important for tea aroma formation. This study aims to investigate the synthesis of (Z)-methyl epijasmonate (epi-MeJA), a key contributor to orchid-like aroma properties in tea, during tea processing. The changes in content of epi-MeJA were analysed during the processing of two tea varieties (Anxi Tieguanyin and Taiping Houkui) with typical orchid-like fragrance. It was found to be mainly synthesized and accumulated during tea processing, as fresh tea leaves contained little or even no epi-MeJA. Its content was positively correlated with the processing time in the enzyme active stages (before fixation). During the fixation stages, isomerization occurred due to high temperatures, with a degree of epimerization to the much less odor active isomer (Z)-methyl jasmonate. Isomerization could also occurred during the drying process, which is dominated by the drying temperature.

Extracorporeal membrane oxygenation in immunocompromised patients with acute respiratory failure: A retrospective cohort study.

BACKGROUND: The clinical indications of extracorporeal membrane oxygenation (ECMO) in immunosuppressed patients are not clear. This study aimed to analyse the effectiveness of ECMO and to identify the risk factors for the mortality of ECMO in immunocompromised patients with acute respiratory failure. METHODS: This retrospective, cohort study included 46 confirmed immunocompromised patients with acute hypoxemic respiratory failure treated with ECMO between July 2014 and August 2020. The clinical features and outcomes of the survival group and the non-survival group were statistically analysed. RESULTS: The mean age of the enrolled patients was 60.0 (50.0, 66.0) years; male patients accounted for 60.9% of patients, and the mean CD4 level was 213 cells/µL (150.3, 325.3). The hospital mortality rate of the cohort was 67.4% (31/46 patients). Patients in the survival group showed a higher rate of receiving awake ECMO (11/15 vs. 4/31; p = 0.006), a lower rate of acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT) (1/15 vs. 12/31; p = 0.035), fewer platelet transfusion units (0/15 vs. 2/31 units; p = 0.039) and a lower rate of ventilator-associated pneumonia (2/15 vs. 19/31; p = 0.006). In a multivariate Cox regression analysis model, intubated ECMO (hazard ratio = 1.77, 95% confidence interval: 1.34-2.32, p < 0.001) and AKI requiring CRRT (1.37, 95% confidence interval: 1.14-1.61, p = 0.003) were identified as independent risk factors for mortality. CONCLUSIONS: In-hospital mortality has remained high in ECMO-treated immunocompromised patients with acute respiratory failure. Intubated ECMO and AKI receiving CRRT during ECMO treatment may predict ECMO failure in immunocompromised patients with ARF. A primarily awake ECMO strategy seems feasible in some selected immunocompromised patients.

Bacterial Diversity Analysis and Screening for ACC Deaminase-Producing Strains in Moss-Covered Soil at Different Altitudes in Tianshan Mountains-A Case Study of Glacier No. 1.

The elevation of the snowline of the No. 1 Glacier in the Tianshan Mountains is increasing due to global warming, which has created favorable conditions for moss invasion and offers an opportunity to investigate the synergistic effects of incipient succession by mosses, plants, and soils. In this study, the concept of altitude distance was used instead of succession time. To investigate the changes of bacterial-community diversity in moss-covered soils during glacial degeneration, the relationship between bacterial community structure and environmental factors was analyzed and valuable microorganisms in moss-covered soils were explored. To do so, the determination of soil physicochemical properties, high-throughput sequencing, the screening of ACC-deaminase-producing bacteria, and the determination of ACC-deaminase activity of strains were performed on five moss-covered soils at different elevations. The results showed that the soil total potassium content, soil available phosphorus content, soil available potassium content, and soil organic-matter content of the AY3550 sample belt were significantly different compared with those of other sample belts (p < 0.05). Secondly, there was a significant difference (p < 0.05) in the ACE index or Chao1 index between the moss-covered-soil AY3550 sample-belt and the AY3750 sample-belt bacterial communities as the succession progressed. The results of PCA analysis, RDA analysis, and cluster analysis at the genus level showed that the community structure of the AY3550 sample belt and the other four sample belts differed greatly and could be divided into two successional stages. The enzyme activities of the 33 ACC-deaminase-producing bacteria isolated and purified from moss-covered soil at different altitudes ranged from 0.067 to 4.7375 U/mg, with strains DY1-3, DY1-4, and EY2-5 having the highest enzyme activities. All three strains were identified as Pseudomonas by morphology, physiology, biochemistry, and molecular biology. This study provides a basis for the changes in moss-covered soil microhabitats during glacial degradation under the synergistic effects of moss, soil, and microbial communities, as well as a theoretical basis for the excavation of valuable microorganisms under glacial moss-covered soils.

Advances on novel iron saccharide-iron (III) complexes as nutritional supplements.

Iron deficiency is prevalent worldwide, and iron supplementation is a promising strategy to address iron needs of the body. However, traditional oral supplements such as ferrous sulfate, ferrous succinate, and ferrous gluconate are absorbed in the form of ferrous ions, leading to lipid peroxidation and side effects due to other reasons. In recent years, saccharide-iron (III) complexes (SICs) as novel iron supplements have aroused attention for the high iron absorption rate and no gastrointestinal irritation at oral doses. In addition, research on the biological activities of SICs revealed that they also exhibited good abilities in treating anemia, eliminating free radicals, and regulating the immune response. This review focused on the preparation, structural characterization, and bioactivities of these new iron supplements, as promising candidates for the prevention and treatment of iron deficiency.

Physicochemical characterization, rheological properties, and hypolipidemic and antioxidant activities of compound polysaccharides in Chinese herbal medicines by fractional precipitation.

This study aimed to investigate the effects of different compound polysaccharides (CPs) extracted from Folium nelumbinis, Fructus crataegi, Fagopyrum tataricum, Lycium barbarum, Semen cassiae, and Poria cocos (w/w, 2:4:2:1:1.5:1) by gradient ethanol precipitation on the physicochemical properties and biological activities. Three CPs (CP50, CP70, and CP80) were obtained and comprised rhamnose, arabinose, xylose, mannose, glucose, and galactose in different proportions. The CPs contained different amounts of total sugar, uronic acid, and proteins. These also exhibited different physical properties, including particle size, molecular weight, microstructure, and apparent viscosity. Scavenging abilities of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), 1,1'-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and superoxide radicals of CP80 were more potent compared to those of the other two CPs. Furthermore, CP80 significantly increased serum levels of high-density lipoprotein cholesterol (HDL-C) and lipoprotein lipase (LPL), and hepatic lipase (HL) activity in the liver, while decreasing the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), along with LPS activity. Therefore, CP80 may serve as a natural novel lipid regulator in the field of medicinal and functional food.

Magnesium lithospermate B ameliorates diabetic nephropathy by suppressing the uremic toxin formation mediated by gut microbiota.

Diabetic nephropathy (DN) is a major cause of renal failure and urgently necessitates new therapeutic strategies. Magnesium lithospermate B (MLB) showed a good protective effect on kidney injure by oral administration, despite its extremely low bioavailability. The current study aimed to investigate its gut microbiota-targeted mechanism to explain the paradoxical properties of pharmacodynamics and pharmacokinetics. Here we show that MLB alleviated DN by recovering the dysfunction of gut microbiota and their associated metabolites in colon content, such as short-chain fatty acids and amino acids. Moreover, MLB significantly decreased uremic toxin levels in plasma, especially the p-cresyl sulfate. We further discovered that MLB could affect the metabolism of p-cresyl sulfate by suppressing the formation of its intestinal precursors, i.e. the microbiota-mediated conversion from 4-hydroxyphenylacetate to p-cresol. In addition, the inhibition effects of MLB were confirmed. MLB and its metabolite danshensu exhibited inhibitory effects on p-cresol formation mediated by three strains belonging to the genus Clostridium, Bifidobacterium, and Fusobacterium, respectively. Meanwhile, MLB decreased the levels of p-cresyl sulfate in plasma and p-cresol in feces caused by rectal administration of tyrosine in mice. To summarize, the results indicated that MLB ameliorated DN through modulating gut microbiota-associated p-cresyl sulfate metabolism. Together, this study provides new insights on the microbiota-targeted mechanism of MLB in intervening DN and a new strategy in lowering plasma uremic toxins by blocking the formation of their precursors in intestine.

Can neurological soft signs and neurocognitive deficits serve as a combined endophenotype for Han Chinese with bipolar disorder?

BACKGROUND: Bipolar disorder's (BD) potential endophenotypes include neurological soft signs (NSS) and neurocognitive disorders (ND). Few research, meanwhile, has coupled NSS and ND as combined endophenotypes of BD. OBJECT: This study intends to investigate NSS and ND and compare their differences in euthymic patients with bipolar disorder (EBP), their unaffected first-degree relatives (FDR), and healthy controls (HC). Additionally, search for potential endophenotypic subprojects of NSS and ND and construct and verify a composite endophenotypic. METHODS: The subjects were all Han Chinese and consisted of 86 EBP, 81 FDR, and 81HC. Cambridge Neurological Inventory and MATRICSTM Consensus Cognitive Battery tested NSS and ND independently. RESULTS: All three groups displayed a trapezoidal distribution of NSS levels and cognitive abnormalities, with EBP having the most severe NSS levels and cognitive deficits, followed by FDR and HC. Among them, motor coordination in NSS and Information processing speed (IPS), Verbal learning (VL), and Working memory (WM) in neurocognitive function are consistent with the traits of the endophenotype of BD. The accuracy in differentiating EBP and HC or FDRs and HC was higher when these items were combined as predictor factors than in differentiating EBP and FDR. CONCLUSION: These results provide more evidence that motor coordination, IPS, VL, and WM may be internal characteristics of bipolar disease. When these characteristics are combined into a complex endophenotype, it may be possible to distinguish BD patients and high-risk groups from normal populations.

Hepatic but not Intestinal FBP1 Is Required for Fructose Metabolism and Tolerance.

Fructose intolerance in mammals is caused by defects in fructose absorption and metabolism. Fructose-1,6-bisphosphatase 1 (FBP1) is a key enzyme in gluconeogenesis, and its deficiency results in hypoglycemia as well as intolerance to fructose. However, the mechanism about fructose intolerance caused by FBP1 deficiency has not been fully elucidated. Here, we demonstrate that hepatic but not intestinal FBP1 is required for fructose metabolism and tolerance. We generated inducible knockout mouse models specifically lacking FBP1 in adult intestine or liver. Intestine-specific deletion of Fbp1 in adult mice does not compromise fructose tolerance, as evidenced by no significant body weight loss, food intake reduction, or morphological changes of the small intestine during 4 weeks of exposure to a high-fructose diet. By contrast, liver-specific deletion of Fbp1 in adult mice leads to fructose intolerance, as manifested by substantial weight loss, hepatomegaly, and liver injury after exposure to a high-fructose diet. Notably, the fructose metabolite fructose-1-phosphate is accumulated in FBP1-deficient liver after fructose challenge, which indicates a defect of fructolysis, probably due to competitive inhibition by fructose-1,6-bisphosphate and may account for the fructose intolerance. In conclusion, these data have clarified the essential role of hepatic but not intestinal FBP1 in fructose metabolism and tolerance.

IL-27 induces autophagy through regulation of the DNMT1/lncRNA MEG3/ERK/p38 axis to reduce pulmonary fibrosis.

PURPOSE: Previous studies have shown that interleukin-27 (IL-27) can reduce bleomycin (BLM)-induced pulmonary fibrosis (PF). However, the underlying mechanism by which IL-27 attenuates PF is not fully clear. METHODS: In this research, we used BLM to construct a PF mouse model, and MRC-5 cells stimulated by transforming growth factor-ß1 (TGF-ß1) were used to construct a PF model in vitro. The lung tissue status was observed by Masson and hematoxylin and eosin (HE) staining. To detect gene expression, RT‒qPCR was used. The protein levels were detected by western blotting and immunofluorescence staining. EdU and ELISA were used to detect cell proliferation viability and hydroxyproline (HYP) content, respectively. RESULTS: Aberrant IL-27 expression was observed in BLM-induced mouse lung tissues, and the use of IL-27 attenuated mouse lung tissue fibrosis. TGF-ß1 induced autophagy inhibition in MRC-5 cells, and IL-27 alleviated MRC-5 cell fibrosis by activating autophagy. The mechanism is inhibition of DNA methyltransferase 1 (DNMT1)-mediated lncRNA MEG3 methylation and ERK/p38 signaling pathway activation. Overexpression of DNMT1, knockdown of lncRNA MEG3, autophagy inhibitor or ERK/p38 signaling pathway inhibitors reversed the positive effect of IL-27 in a lung fibrosis model in vitro. CONCLUSION: In conclusion, our study shows that IL-27 upregulates MEG3 expression through inhibition of DNMT1-mediated lncRNA MEG3 promoter methylation, which in turn inhibits ERK/p38 signaling pathway-induced autophagy and attenuates BLM-induced PF, providing a contribution to the elucidation of the potential mechanisms by which IL-27 attenuates PF.