Development and evaluation of guar gum-coated nano-nutriosomes for cyanidin-3-O-glucoside encapsulation.

Cyanidin-3-O-glucoside (C3G) is a type of water-soluble flavonoid compound that is abundantly found in fruits and vegetables. C3G possesses numerous biological activities, however, it is prone to breakdown under environmental conditions. To overcome these issues, we developed nano-nutriosome (NS) carriers created by vortex-mixing and probe-sonication techniques for C3G encapsulation in which the phospholipid and Nutriose® FB06 were chosen as carrier material, and guar gum (GG) as a coating material to formulate a unilamellar and multicompartment structure. This study aimed to develop and evaluate C3G-loaded nano-nutriosomes coated by GG (GG-C3G-NS) for improving physicochemical stability, antioxidant activity, cellular uptake, and controlled release properties. The C3G-NS and GG-C3G-NS are nanosized (143.47 to 154.13 nm), with high encapsulation efficiency (>93.31 %). The NS carriers successfully encapsulated C3G which was confirmed by transmission electron microscopy, differential scanning calorimetry, and Fourier transform infrared spectroscopy. C3G showed more stability in storage, thermal, pH, ionic, and oxidative conditions. Furthermore, the NS exhibited a better-controlled release of C3G in different food stimulant conditions and in vitro release study. Additionally, NS systems enhanced cellular uptake and showed no cytotoxicity. Overall, GG-NS could be a promising nanocarrier for improving the stability, controlled release, and antioxidant activity of bioactive compounds.

Genipin Activates Autophagy and Promotes Myoblast Differentiation by Activating AMPK Pathway.

Cultured meat technology is expected to solve problems such as resource shortages and environmental pollution, but the muscle fiber differentiation efficiency of cultured meat is low. Genipin is the active compound derived from Gardenia jasminoides Ellis, which has a variety of activities. Additionally, genipin serves as a noncytotoxic agent for cross-linking, which is suitable as a foundational scaffold for in vitro tissue regeneration. However, the impact of genipin on myoblast differentiation remains to be studied. The research revealed that genipin was found to improve the differentiation efficiency of myoblasts. Genipin improved mitochondrial membrane potential by activating the AMPK signaling pathway of myoblasts, promoting mitochondrial biogenesis, and mitochondrial network remodeling. Genipin activated autophagy in myoblasts and maintained cellular homeostasis. Autophagy inhibitors blocked the pro-differentiation effect of genipin. These results showed that genipin improved the differentiation efficiency of myoblasts, which provided a theoretical basis for the development of cultured meat technology.

Acetylated pelargonidin-3-O-glucoside alleviates hepatocyte lipid deposition through activating the AMPK-mediated lysosome-autophagy pathway and redox state.

Nonalcoholic fatty liver disease (NAFLD) is a worldwide public health issue, but a widely accepted therapy is still lacking until now. Anthocyanins are natural flavonoid compounds that possess various bioactivities, but their applications are limited due to their low bioavailability and stability. Acylated anthocyanins are reported to show higher stability, whereas their effects on NAFLD are still unclear. Herein, pelargonidin-3-O-(6''-acetyl)-glucoside (Ace Pg3G) was found to dose-dependently reduce intracellular lipid droplets and triglycerides, and improve cellular oxidative stress that accompanied lipid deposition. Besides, Ace Pg3G was proved to activate AMPK phosphorylation, thus stimulating AMPK-mediated lysosome-autophagy pathway to eliminate overloaded lipid. Further study unveiled that Ace Pg3G regulated genes related to lipid metabolism downstream of AMPK to inhibit lipid synthesis and accelerate lipid oxidation. Overall, this study provided the first evidence, to our best knowledge, that Ace Pg3G ameliorated free fatty acid-induced lipid deposition in hepatocytes through regulating AMPK-mediated autophagy pathways and redox state.

Recombinant bovine FGF1 promotes muscle satellite cells mitochondrial fission and proliferation in serum-free conditions.

Cell cultured meat is a novel and promising technology, but developing specific culture medium for muscle cells remains one of the main technical obstacles. FGF1 signaling is reported to promote proliferation and maintain proliferative capacity of satellite cells. However, the effect of FGF1 as a supplement to serum-free medium on satellite cells in vitro culture is still unclear. In this study, an efficient method for the production of soluble and biologically active recombinant bovine FGF1 (rbFGF1) protein in Escherichia coli was established. The soluble expression level of TrxA-rbFGF1 fusion protein was 562 mg/L in shake flasks, resulting in 5.5 mg of pure rbFGF1 from 0.1 L of starting culture. In serum-free culture conditions, rbFGF1 effectively promoted the proliferation and regulated the mitochondrial morphology and function of C2C12 myoblasts.rbFGF1 activated extracellular signal-regulated kinases1/2 (ERK1/2) signaling in C2C12 myoblasts, which further stimulated dynamin related protein 1 (DRP1) Ser616 phosphorylation. These findings highlighted the potential application of rbFGF1 in developing effective serum-free medium for cultured meat production.

Outcomes of different parenchymal-sparing hepatectomies in patients with colorectal liver metastases and prognostic impact of peritumoral imaging features.

OBJECTIVES: Parenchymal-sparing hepatectomy (PSH) is recommended in patients with colorectal liver metastases (CRLM). Based on the principle of PSH, to investigate the impact of anatomical resection (AR) and non-anatomic resection (NAR) on the outcome of CRLM and to evaluate the potential prognostic impact of three peritumoral imaging features. METHODS: Fifty-six patients who had abdominal gadoxetic acid-enhanced magnetic resonance imaging (MRI) before CRLM surgery were included in this retrospective research. Peritumoral early enhancement, peritumoral hypointensity on hepatobiliary phase (HBP), and biliary dilatation to the CRLM at MRI were evaluated. Survival estimates were calculated using the Kaplan-Meier method, and multivariate analysis was conducted to identify independent predictors of liver recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS). RESULTS: NAR had a lower 3-year LRFS compared with AR (36.6% vs. 78.6%, p = 0.012). No significant differences were found in 3-year RFS (34.1% vs. 41.7%) and OS (61.7% vs. 81.3%) (p > 0.05). In NAR group, peritumoral early enhancement was associated with poor LRFS (p = < 0.001, hazard ratio [HR] = 6.260; 95% confidence interval [CI], 2.322,16.876]) and poor RFS (p = 0.035, HR =2.516; 95% CI, 1.069,5.919). No independent predictors of CRLM were identified in the AR group. CONCLUSIONS: In patients with CRLM, peritumoral early enhancement was a predictor of LRFS and RFS after NAR according to the principle of PSH.

Functional Analysis of a Methyltransferase Involved in Anthocyanin Biosynthesis from Blueberries (Vaccinium corymbosum).

Anthocyanins are natural water-soluble pigments that widely exist in plants, with various biological activities, including antioxidant, anti-obesity, and anti-diabetic activities. Currently, monomeric anthocyanins are mainly obtained through natural sources, which limits their availability. In the biosynthesis of anthocyanins, anthocyanin methyltransferases are recognized to play important roles in the water solubility and structural stability of anthocyanins. Blueberries are a rich source of anthocyanins with more than 30 chemical structures. However, the enzymes that were responsible for the methylation of anthocyanidin cores in blueberries had not been reported. Here, blueberries (Vaccinium corymbosum) have been selected as the candidate for characterization of the key enzyme. Phylogenic analysis, enzymatic activity assay, homology modeling, molecular simulation, protein expression and purification assay, site-directed mutation, isothermal titration calorimetry assay, and enzyme kinetic assay were used to identify the enzymatic function and molecular mechanism of VcOMT, which was responsible for the methylation of anthocyanidin cores. VcOMT could use delphinidin as a substrate but not cyanidin, petunidin, anthocyanins, flavonols, and flavonol glycosides. Ile191 and Glu198 were both identified as important amino acid residues for the binding interactions of anthocyanidins with VcOMT.

Renal fat fraction is significantly associated with the risk of chronic kidney disease in patients with type 2 diabetes.

Backgrounds: Ectopic fat deposition is closely related to chronic kidney disease (CKD). Currently, there are few population studies that have been conducted to determine the relationship between renal parenchyma fat deposition and the risk of CKD among patients with type 2 diabetes mellitus (T2DM). Therefore, we employed magnetic resonance imaging (MRI) to detect renal parenchyma fat content in individuals with T2DM, expressed as renal fat fraction (FF), to explore whether renal FF is an important risk factor for CKD in patients with T2DM. Methods: In this cross-sectional study, 189 subjects with T2DM were enrolled. CKD was defined as the estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2. Measurement of the renal FF was performed on a 3.0-T MRI (MAGNETOM Skyra, Siemens, Erlangen, Germany). Binary logistic regression was used to determine the association between tertiles of renal FF and risk of CKD. Receiver-operator characteristic (ROC) curves were constructed to evaluate the sensitivity and specificity of renal FF in detecting CKD in T2DM patients. Results: The patients were divided into three groups according to tertiles of the renal FF level (2.498 - 7.434). As renal FF increases, patients tend to be older, and more abdominally obese, with a decreased eGFR (p<0.05). After adjustment for potential confounders, patients in the highest tertile of renal FF had a significantly increased risk of CKD than those in the lowest tertile (odds ratio (OR) = 3.98, 95% confidence interval (CI) = 1.12 - 14.09, p = 0.032), and the area under the ROC curve for this model was 0.836 (0.765-0.907). Conclusions: The renal FF is significantly independently associated with CKD in patients with T2DM.

High-power cylindrical vector beams generated from an all-fiber linearly polarized laser by metasurface extracavity conversion.

Five-hundred-watt cylindrical vector beams (CVBs) at 1030 nm with the 3 dB linewidth being less than 0.25 nm have been generated from a narrow linewidth all-fiber linearly polarized laser by metasurface extracavity conversion. At maximum output power, the transmission efficiency and polarization extinction ratio of radially polarized cylindrical vector beams (RP-CVBs) are beyond 98% and 95%, respectively. The average power is approximately an order higher than previously reported high-power narrow-linewidth CVBs generated from fiber lasers. The temperature rise of the metasurface is less than 10°C at 500 W output power, which means that the system can be further power-scaled in the near future. The high-power, high-purity, and high-efficiency RP-CVBs generated by the metasurface demonstrate potential application of a metasurface in high-power CVBs lasers.

Bioavailability, Absorption, and Metabolism of Pelargonidin-Based Anthocyanins Using Sprague-Dawley Rats and Caco-2 Cell Monolayers.

The present study is aimed to clarify the absorption and metabolism properties of pelargonidin-based anthocyanins. Results showed that pelargonidin-3-O-rutinoside (Pg3R) was absorbed in its intact form after oral administration and reached a maximum plasma concentration of 175.38 ± 55.95 nM at 60 min. Three main metabolites were identified in plasma, including Pg3R-monoglucuronide (m/z 755.2046), Pg3R-hydroxylated (m/z 595.1644), and Pg3R-demethylated (m/z 565.1569) metabolites. The plasma concentration of the Pg3R-demethylated metabolite (57.04 ± 23.15 nM) was much higher than that of other two metabolites, indicating that demethylation was the main metabolic pathway for Pg3R, while the glucuronide conjugate was detected as the dominant metabolic form of pelargonidin-3-O-glucoside (Pg3G). The bioavailability of Pg3R (1.13%) was fourfold higher than that of Pg3G (0.28%), demonstrating that anthocyanins linked to the rutinoside may exhibit higher bioavailability than that of glucoside. In vitro transport study unveiled that passive diffusion and active efflux were involved in the absorption of Pg3R and Pg3G.

Experimental investigation of quasi-static mode degradation in a high power large mode area fiber amplifier.

In this work, quasi-static mode degradation in high power fiber amplifiers has been investigated experimentally. An increase of M2 from 1.3 to 2.6 with distortion of the beam profile is observed, which results in the signal spectra and backward light characterization departing from the traditional phenomena. The amplifier has been operated at the same input pump power of 705 W for nearly 2.2 hours to investigate the relationship between quasi-static mode degradation and photodarkening. The evolution of M2 factor/beam profile, mode correlation coefficient and output laser power at different working times indicate that the quasi-static mode degradation in the high power fiber amplifiers is dependent on photodarkening and evolves on the scale of tens of minutes. A visible green light has been injected to photobleach the gain fiber for 19 hours, which reveals that the quasi-static mode degradation has been suppressed simultaneously. To the best of our knowledge, this is the first detail report of photodarkening-induced quasi-static degradation in high power fiber amplifiers.

Malvidin-3-O-Glucoside from Blueberry Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Transcription Factor EB-Mediated Lysosomal Function and Activating the Nrf2/ARE Signaling Pathway.

Nonalcoholic fatty liver disease (NAFLD) has become a universal health issue, whereas there is still a lack of widely accepted therapy until now. Clinical research studies have shown that blueberry could effectively regulate the lipid metabolism, thereby improving obesity-related metabolic syndromes; however, the specific active substances and mechanisms remain unclear. Herein, the effects of the major 10 kinds of anthocyanins from blueberry against NAFLD were investigated using an free fatty acid (FFA)-induced cell model. Among these anthocyanins, malvidin-3-O-glucoside (M3G) and malvidin-3-O-galactoside (M3Ga) could remarkably ameliorate FFA-induced lipid accumulation. Besides, M3G and M3Ga also inhibited oxidative stress via suppressing reactive oxygen species and superoxide anion overproduction, increasing glutathione levels, and enhancing activities of antioxidant enzymes. Further studies unveiled that the representative anthocyanin M3G-upregulated transcription factor EB (TFEB)-mediated lysosomal function possibly interacted with TFEB and activated the Nrf2/ARE (antioxidant responsive element) signaling pathway. Overall, this study enriched the knowledge about the health-promoting effects of blueberry anthocyanins against NAFLD and provided ideas for the development of functional foods of blueberry anthocyanins.

Discovery of anthocyanins from cranberry extract as pancreatic lipase inhibitors using a combined approach of ultrafiltration, molecular simulation and spectroscopy.

Obesity is a chronic disease that has been causing serious problems all over the world. However, there is a lack of available therapeutic approaches to treat obesity. The FDA-approved drug orlistat has severe side effects, such as abdominal pain, flatulence and oily stool. As the therapeutic target of orlistat is pancreatic lipase, there is an urgent need for discovery of new pancreatic lipase inhibitors from natural sources that have reduced side effects compared with orlistat. In this study, ultrafiltration in combination with molecular simulation and spectroscopy was reported as an effective approach for identifying new pancreatic lipase inhibitors from anthocyanin-rich berry sources. Using this approach, four monomeric anthocyanins cyanidin-3-O-arabinoside (C3A), cyanidin-3-O-galactoside (C3Ga), peonidin-3-O-arabinoside (Pn3A) and peonidin-3-O-galactoside (Pn3Ga) from cranberries were discovered as potent pancreatic lipase inhibitors. These four cranberry anthocyanins were shown to form hydrophobic interactions and hydrogen bonds with pocket amino acid residues in molecular docking and molecular dynamics simulations. C3A showed greater impact on secondary structures of the enzyme and showed higher binding capacity with the enzyme compared with C3Ga, Pn3A and Pn3Ga as observed by CD and fluorescence spectroscopy. The structure-activity relationships were then investigated and summarized as both the structures of the B ring and glycosyl group were related to the inhibitory activities of anthocyanins. In short, our results suggested that cranberry anthocyanins could be developed as food supplements to facilitate the prevention and treatment of obesity.

Andrographolide Exerts Antihyperglycemic Effect through Strengthening Intestinal Barrier Function and Increasing Microbial Composition of Akkermansia muciniphila.

Accumulating evidence indicates that type 2 diabetes (T2D) is associated with intestinal barrier dysfunction and dysbiosis, implying the potential targets for T2D therapeutics. Andrographolide was reported to have several beneficial effects on diabetes and its associated complications. However, the protective role of andrographolide, as well as its underlying mechanism against T2D, remains elusive. Herein, we reported that andrographolide enhanced intestinal barrier integrity in LPS-induced Caco-2 cells as indicated by the improvement of cell monolayer barrier permeability and upregulation of tight junction protein expression. In addition, andrographolide alleviated LPS-induced oxidative stress by preventing ROS and superoxide anion radical overproduction and reversing glutathione depletion. In line with the in vitro results, andrographolide reduced metabolic endotoxemia and strengthened gut barrier integrity in db/db diabetic mice. We also found that andrographolide appeared to ameliorate glucose intolerance and insulin resistance and attenuated diabetes-associated redox disturbance and inflammation. Furthermore, our results indicated that andrographolide modified gut microbiota composition as indicated by elevated Bacteroidetes/Firmicutes ratio, enriched microbial species of Akkermansia muciniphila, and increased SCFAs level. Taken together, this study demonstrated that andrographolide exerted a glucose-lowering effect through strengthening intestinal barrier function and increasing the microbial species of A. muciniphila, which illuminates a plausible approach to prevent T2D by regulating gut barrier integrity and shaping intestinal microbiota composition.

In vitro study of bioaccessibility, antioxidant, and α-glucosidase inhibitory effect of pelargonidin-3-O-glucoside after interacting with beta-lactoglobulin and chitosan/pectin.

Polysaccharides and fruit extracts are applied in dairy products to enhance their nutritional property, but the effects of such formulations on the functions and biological activities are yet to be explored. Therefore, this study was aimed at evaluating the effect of interactions among milk protein (beta-lactoglobulin; BLG), polysaccharides (pectin, P; chitosan, CH), and anthocyanin (pelargonidin-3-O-glucoside; P3G) in improving the bioavailability and biological activity of P3G. After gastrointestinal digestion (GID), the content of free P3G in different model solutions were as follows: P3G-alone (73.59 µg/mL), P3G-P (66.59 µg/mL), P3G-CH (36.72 µg/mL), P3G-BLG (64.92 µg/mL), P3G-P-BLG (64.92 µg/mL), and P3G-CH-BLG (39.61 µg/mL). Less amount of free P3G in model solutions indicated increased complex formation of P3G with protein and/or polysaccharides during GID. These complexes resulted in protection and progressive release of P3G in the gastrointestinal tract. Chitosan exhibited more protection to P3G compared with P and BLG. In addition, α-glucosidase inhibitory activity and ROS scavenging activities of conjugated-P3G samples were potentially augmented after GID. However, the presence of polysaccharides and protein in the model solutions did not show any negative effect on the biological activity of P3G. Thus, pure P3G can be used as a nutritional ingredient in dairy industries.

Structure-based design of human pancreatic amylase inhibitors from the natural anthocyanin database for type 2 diabetes.

Human Pancreatic Amylase (HPA) is an important target for prevention and treatment of type 2 diabetes. Acarbose is a currently available drug acting as a HPA inhibitor, but its gastrointestinal side-effects cannot be neglected. Thus, developing novel HPA inhibitors with no side-effects is of great importance. Herein, we adopted a structure-based design approach and discovered a potent HPA inhibitor, malvidin 3-O-arabinoside (M3A), from the natural anthocyanin database. We identified M3A as an effective HPA inhibitor through virtual screening, enzyme activity and enzyme kinetic assays. We reported the structure and activity relationships as both the anthocyanidin core and glucosyl group affected the HPA inhibitory effect of anthocyanins. Molecular dynamics studies indicated that the HPA inhibition of M3A occurred via its binding to the HPA key catalytic residues Arg195 and Asp197 through stable hydrogen bonding. In addition, M3A was found to reduce α-helix fractions and increase ß-sheet fractions in CD spectrometry. Further in vivo studies showed that M3A significantly ameliorated the postprandial blood glucose level. Taken together, our results provide new insights into the development of novel HPA inhibitors from natural sources as food supplements for type 2 diabetes.

Pelargonidin-3-O-glucoside Derived from Wild Raspberry Exerts Antihyperglycemic Effect by Inducing Autophagy and Modulating Gut Microbiota.

Increasing evidence indicates that anthocyanins exert beneficial effects on type 2 diabetes (T2D), but the underlying mechanism remains unclear. Herein, the hyperglycemia-lowering effect of Pg3G derived from wild raspberry was investigated on high-glucose/high-fat (HG+HF)-induced hepatocytes and db/db diabetic mice. Our results indicated that Pg3G promoted glucose uptake in HG+HF-induced hepatocytes. Moreover, Pg3G induced autophagy, whereas autophagy inhibitors blocked the hypoglycemic effect of Pg3G. Transcriptional factor EB (TFEB) was found to be linked to Pg3G-induced autophagy. In vivo study showed that Pg3G treatment contributed to the improvement of glucose tolerance, insulin sensitivity, and induction of autophagy. Furthermore, Pg3G not only modified the gut microbiota composition, as indicated by an increased abundance of Prevotella, and elevated Bacteroidetes/Firmicutes ratio, but also strengthened the intestinal barrier integrity. This study unveils a novel mechanism that Pg3G attenuates hyperglycemia through inducing autophagy and modulating gut microbiota, which implicates a potential nutritional intervention strategy for T2D.

Dietary fibers as emerging nutritional factors against diabetes: focus on the involvement of gut microbiota.

Diabetes mellitus (DM) increases the risk of cardiovascular diseases and other secondary complications, such as nephropathy, neuropathy, retinopathy, etc. The important risk factors for the pathogenesis of DM are aging, family history, sedentary lifestyle, unhealthy dietary habits, and obesity. Evidence from epidemiological studies also indicates that DM is characterized by specific alterations in the human gut microbiota (GM). GM transplantation in rodents and humans revealed that a specific GM constituent can be the cause and not just the consequence of the DM condition and complications. These findings suggest a potential role of GM in human health, disease prevention, and treatment. Dietary intervention studies using dietary fibers (DFs) suggested that modulation of the GM can suppress the metabolic risk markers in humans. However, a causal role of GM in such studies remains unexplored. Long-term follow-up studies disclosed that the diet rich in insoluble and non-viscous fibers are responsible for DF-mediated antidiabetic activities, while soluble and viscous fibers have little influence on DM despite having a profound impact on glycemia. However, general conclusions cannot be drawn simply based on these findings. Long-term follow-up studies are urgently required in this area to explore the therapeutic potential of different DFs in treating DM and to delineate the exact role of GM involvement. Here we review and discuss the signature of GM during DM, antidiabetic activity of metformin via GM modulation, DFs from different sources and their antidiabetic activity, and the possible role of GM involvement.

Pelargonidin-3-O-rutinoside as a novel α-glucosidase inhibitor for improving postprandial hyperglycemia.

A novel strategy for the isolation of anthocyanins was developed by a combination of high-speed countercurrent chromatography (HSCCC) and HPLC techniques. Using this strategy, a novel α-glucosidase inhibitor (pelargonidin-3-O-rutinoside, a natural anthocyanin) was isolated from strawberries. Structural determinants for inhibition of α-glucosidase by Pg3R and the SAR of natural anthocyanins were revealed in detail by enzymatic kinetics and molecular docking analysis.

Procyanidin B2 ameliorates free fatty acids-induced hepatic steatosis through regulating TFEB-mediated lysosomal pathway and redox state.

Procyanidin B2, a naturally occurring phenolic compound, has been reported to exert multiple beneficial functions. However, the effect of procyanidin B2 on free fatty acids (FFAs)-induced hepatic steatosis remains obscure. The present study is therefore aimed to elucidate the protective effect of procyanidin B2 against hepatic steatosis and its underlying mechanism. Herein, we reported that procyanidin B2 attenuated FFAs-induced lipid accumulation and its associated oxidative stress by scavenging excessive ROS and superoxide anion radicals, blocking loss of mitochondrial membrane potential, restoring glutathione content, and increasing activity of antioxidant enzymes (GPx, SOD and CAT) in hepatocytes. Procyanidin B2 mechanistically promoted lipid degradation via modulation of transcription factor EB (TFEB), a master regulator of lysosomal pathway. Molecular docking analysis indicated a possible ligand-binding position of procyanidin B2 with TFEB. In addition, administration of procyanidin B2 resulted in a significant reduction of hepatic fat accumulation in high-fat diet (HFD)-induced obese mice, and also ameliorated HFD-induced metabolic abnormalities, including hyperlipidemia and hyperglycemia. It was confirmed that procyanidin B2 prevented HFD-induced hepatic fat accumulation through down-regulating lipogenesis-related gene expressions (PPARγ, C/EBPα and SREBP-1c), inhibiting pro-inflammatory cytokines production (IL-6 and TNF-α) and increasing antioxidant enzymes activity (GPx, SOD and CAT). Moreover, hepatic fatty acids analysis indicated that procyanidin B2 caused a significant increase in the levels of palmitic acid, oleic acid and linoleic acid. Intriguingly, procyanidin B2 restored the decreased nuclear TFEB expression in HFD-induced liver steatosis and up-regulated its target genes involved in lysosomal pathway (Lamp1, Mcoln, Uvrag), which suggested a previously unrecognized mechanism of procyanidin B2 on ameliorating HFD-induced hepatic steatosis. Taken together, our results demonstrated that procyanidin B2 attenuated FFAs-induced hepatic steatosis through regulating TFEB-mediated lysosomal pathway and redox state, which had important implications that modulation of TFEB might be a potential therapeutic strategy for hepatic steatosis and procyanidin B2 could represent a promising novel agent in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD).

Temporal pulse precisely sculpted millijoule-level fiber laser injection system for high-power laser driver.

A fiber laser injection system used as a seeder for a high-power laser facility of inertial confinement fusion was designed to meet stringent requirements. Herein, we demonstrate the fiber laser injection system, whose output single-pulse energy reaches the millijoule class. With two-stage amplitude modulators, the system produces a pulse with a higher pulse shaping capability. In addition, amplifying the pulse with large-mode-area fiber and single polarization, large-mode-area photonic crystal fiber (PCF) ensures a good beam quality output. In this proof-of-principle experiment, the long-term stability of FM-to-AM modulation and pulse energy is demonstrated. The successful demonstration of this laser injection system holds great significance for future high-power laser drivers.