Response surface optimization of sludge dewatering process: synergistic enhancement by ultrasonic, chitosan and sludge-based biochar.

Due to the colloidal stability, the high compressibility and the high hydration of extracellular polymeric substances (EPS), it is difficult to efficiently dehydrate sludge. In order to enhance sludge dewatering, the process of ultrasonic (US) cracking, chitosan (CTS) re-flocculation and sludge-based biochar (SBB) skeleton adsorption of water-holding substances to regulate sludge dewaterability was proposed. Based on the response surface method, the prediction model of the specific resistance to filtration (SRF) and sludge cake moisture content (MC) was established. The US cracking time and the dosage of CTS and SBB were optimized. The results showed that the optimal parameters of the three were 5.08 s, 10.1 mg/g dry solids (DS) and 0.477 g/g DS, respectively. Meantime, the SRF and MC were 5.4125 × 1011 m/kg and 76.8123%, which significantly improved the sludge dewaterability. According to the variance analysis, it is found that the fitting degree of SRF and MC model is good, which also confirms that there is significant interaction and synergy between US, CTS and SBB, and the contribution of CTS and SBB is greater. Moreover, the process significantly improves the sludge's calorific value and makes its combustion more durable.

Xanthohumol alleviates oxidative stress and impaired autophagy in experimental severe acute pancreatitis through inhibition of AKT/mTOR.

Severe acute pancreatitis (SAP) is a lethal gastrointestinal disorder, yet no specific and effective treatment is available. Its pathogenesis involves inflammatory cascade, oxidative stress, and autophagy dysfunction. Xanthohumol (Xn) displays various medicinal properties, including anti-inflammation, antioxidative, and enhancing autophagic flux. However, it is unclear whether Xn inhibits SAP. This study investigated the efficacy of Xn on sodium taurocholate (NaT)-induced SAP (NaT-SAP) in vitro and in vivo. First, Xn attenuated biochemical and histopathological responses in NaT-SAP mice. And Xn reduced NaT-induced necrosis, inflammation, oxidative stress, and autophagy impairment. The mTOR activator MHY1485 and the AKT activator SC79 partly reversed the treatment effect of Xn. Overall, this is an innovative study to identify that Xn improved pancreatic injury by enhancing autophagic flux via inhibition of AKT/mTOR. Xn is expected to become a novel SAP therapeutic agent.

Drug D, a Diosgenin Derive, Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway.

Acute pancreatitis (AP) is one of the most common causes of hospitalization for gastrointestinal diseases, with high morbidity and mortality. Endoplasmic reticulum stress (ERS) and Gasdermin D (GSDMD) mediate AP, but little is known about their mutual influence on AP. Diosgenin has excellent anti-inflammatory and antioxidant effects. This study investigated whether Diosgenin derivative D (Drug D) inhibits L-arginine-induced acute pancreatitis through meditating GSDMD in the endoplasmic reticulum (ER). Our studies were conducted in a mouse model of L-arginine-induced AP as well as in an in vitro model on mouse pancreatic acinar cells. The GSDMD accumulation in ER was found in this study, which caused ERS of acinar cells. GSDMD inhibitor Disulfiram (DSF) notably decreased the expression of GSDMD in ER and TXNIP/HIF-1α signaling. The molecular docking study indicated that there was a potential interaction between Drug D and GSDMD. Our results showed that Drug D significantly inhibited necrosis of acinar cells dose-dependently, and we also found that Drug D alleviated pancreatic necrosis and systemic inflammation by inhibiting the GSDMD accumulation in the ER of acinar cells via the TXNIP/HIF-1α pathway. Furthermore, the level of p-IRE1α (a marker of ERS) was also down-regulated by Drug D in a dose-dependent manner in AP. We also found that Drug D alleviated TXNIP up-regulation and oxidative stress in AP. Moreover, our results revealed that GSDMD-/- mitigated AP by inhibiting TXNIP/HIF-1α. Therefore, Drug D, which is extracted from Dioscorea zingiberensis, may inhibit L-arginine-induced AP by meditating GSDMD in the ER by the TXNIP /HIF-1α pathway.

Deoxyarbutin attenuates severe acute pancreatitis via the HtrA2/PGC-1α pathway.

Severe acute pancreatitis (SAP) is an inflammatory disorder of the exocrine pancreas associated with high morbidity and mortality. SAP has been proven to trigger mitochondria dysfunction in the pancreas. We found that Deoxyarbutin (dA) recovered impaired mitochondrial function. High-temperature requirement protein A2 (HtrA2), a mitochondrial serine protease upstream of PGC-1α, is charge of quality control in mitochondrial homeostasis. The molecular docking study indicated that there was a potential interaction between dA and HtrA2. However, whether the protective effect of dA against SAP is regulated by HtrA2/PGC-1α remains unknown. Our study in vitro showed that dA significantly reduced the necrosis of primary acinar cells and reactive oxygen species (ROS) accumulation, recovered mitochondrial membrane potential (ΔΨm) and ATP exhaustion, while UCF-101 (HtrA2 inhibitor), and SR-18292 (PGC-1α inhibitor) eliminated the protective effect of dA. Moreover, HtrA2 siRNA transfection efficiently blocked the protective of dA on HtrA2/PGC-1α pathway in 266-6 acinar cells. Meanwhile, dA also decreased LC3II/I ration, as well as p62, and increased Parkin expression, while UCF-101 and Bafilomycin A1 (autophagy inhibitor) reversed the protective effect of dA. Our study in vivo confirmed that dA effectively alleviated severity of SAP by reducing pancreatic edema, plasma amylase, and lipase levels and improved the HtrA2/PGC-1α pathway. Therefore, this is the first study to identify that dA inhibits pancreatic injury caused by oxidative stress, mitochondrial dysfunction, and impaired autophagy in a HtrA2/PGC-1α dependent manner.

Dispersible MoS2 micro-sheets induced a proinflammatory response and apoptosis in the gills and liver of adult zebrafish.

Molybdenum disulfide (MoS2), one of the next-generation two-dimensional materials (2DMs), has attracted increasing attention due to its unique physicochemical properties. However, the aquatic toxicity of dispersible MoS2 is still unknown. Herein, we synthesized chitosan functionalized MoS2 (CS-MoS2) micro-sheets with a satisfying water-dispersible performance. The average length and width of the as-prepared CS-MoS2 micro-sheets were 5.04 µm and 3.12 µm, respectively, and they had a pristine 2H polymorph. The toxicity of CS-MoS2 micro-sheets was assessed by investigating the organs, gills and liver of adult zebrafish. We found that exposure to high concentrations of CS-MoS2 micro-sheets (10 mg L-1 and 20 mg L-1) led to lamellar fusions in the gills, and significant localized lesions, such as peripheral nuclei and vacuole formation, in the liver. In addition, treatment with 20 mg L-1 CS-MoS2 micro-sheets suppressed gene expression of antioxidant enzymes (e.g., CAT and GPx1a gene) and induced the expression levels of the proinflammatory response and apoptosis (e.g., IL-1ß, IL-6, and AIF gene) in gill and liver tissues. Further, reactive oxygen species (ROS) were generated upon treatment with 20 mg L-1 CS-MoS2 micro-sheets in both organs. To the best of our knowledge, this is the first investigation of the aquatic toxicity of dispersible MoS2 in zebrafish, and further highlights the potential environmental risk of MoS2.

Dispersible MoS2 Nanosheets Activated TGF-ß/Smad Pathway and Perturbed the Metabolome of Human Dermal Fibroblasts.

In postgraphene two-dimensional materials (2DMs), MoS2 has attracted increasing attention in the biomedical field due to its excellent physicochemical properties. However, the toxicity and biocompatibility evaluation of MoS2 is not fully addressed. Herein, chitosan functionalized MoS2 (CS-MoS2) nanosheets, which showed perfect dispersibility and stability performances, were synthesized and characterized. We found that CS-MoS2 nanosheets inhibited the viability of human dermal fibroblasts (HDFs) moderately while causing cell membrane instability, ROS generation, and DNA damage in a dosage-dependent manner. CS-MoS2 nanosheets did not induce significant changes in the cell morphologies, but they seemed to impair the cell division of HDFs. CS-MoS2 nanosheets (100 µg/mL) activated EGFR and induced reactive oxygen species, Smad, and IL-1, which in turn led to cell inflammation and apoptosis. Furthermore, HDFs showed cellular stress responses when they were exposed to low concentrations of CS-MoS2 nanosheets (25 and 100 µg/mL) because most of the intracellular metabolites such as amino acids were induced at 25 µg/mL but were inhibited at 100 µg/mL. Pyroglutamic acid, phosphoric acid, and inositol might be used as biomarkers for evaluating the toxicity of CS-MoS2 nanosheets. Additionally, 100 µg/mL CS-MoS2 nanosheets inhibited glutathione metabolism and induced the imbalance of cellular redox homeostasis. It further suppressed the tricarboxylic acid cycle and other metabolic pathways, causing insufficient supply of substrates and energy for HDFs. These findings will fuel the risk assessment of MoS2 and other 2DMs and guide the safe material design and 2DM applications.