A Recyclable Magnetic Aminated Lignin Supported Zr-La Dual-Metal Hydroxide for Rapid Separation and Highly Efficient Sequestration of Phosphate.

The application of lignin-based adsorbents in the efficient removal of phosphate from wastewater has attracted much attention and been intensively studied in recent years. However, most currently reported lignin-based adsorbents are difficult to recover and recycle. Herein, we have developed a recyclable, nanostructured bio-adsorbent, poly(ethyleneimine) (PEI)-modified lignin (LG) integrated with Fe3O4 and Zr-La dual-metal hydroxide (LG-NH2@Fe3O4@Zr-La), by the Mannich reaction followed by the chemical coprecipitation method. Multilayer adsorption existed on the surface of LG-NH2@Fe3O4@Zr-La based on the isotherm fitting curve, and its adsorption capacity reached 57.8 mg P g-1, exhibiting a higher phosphate uptake than most reported metallic oxide-based composites. The adsorption process was dominated by inner-sphere complexation of ligand-exchange and electrostatic interactions. Moreover, LG-NH2@Fe3O4@Zr-La exhibited excellent selectivity against coexisting anions, and the adsorption was more efficient under acidic conditions. When the phosphate concentration was 2.0 mg P L-1, the removal efficiency of phosphate reached 99.5% and the residual concentration was only 10 µg P L-1, which meets the United States Environmental Protection Agency (USEPA) standard for eutrophication prevention. In addition, the LG-NH2@Fe3O4@Zr-La displayed excellent reusability, maintaining 91.8% of removal efficiency after five cycles. Importantly, owing to the magnetic properties of the loaded Fe3O4, the resulting composite could be separated within 30 s under an external magnetic field. Thus, the separable and recyclable biobased magnetic adsorbent developed in this work exhibited promising application in phosphate capture from real sewage. This research study provides a new perspective for lignin valorization in lignocellulose biorefineries and establishes an approach for developing an economical and efficient bio-adsorbent for phosphate removal from wastewater.

Improved Stability and Catalytic Efficiency of ω-Transaminase in Aqueous Mixture of Deep Eutectic Solvents.

The efficient biosynthesis of chiral amines at an industrial scale to meet the high demand from industries that require chiral amines as precursors is challenging due to the poor stability and low catalytic efficiency of ω-transaminases (ω-TAs). Herein, this study adopted a green and efficient solvent engineering method to explore the effects of various aqueous solutions of deep eutectic solvents (DESs) as cosolvents on the catalytic efficiency and stability of ω-TA. Binary- and ternary-based DESs were used as cosolvents in enhancing the catalytic activity and stability of a ω-TA variant from Aspergillus terreus (E133A). The enzyme exhibited a higher catalytic activity in a ternary-based DES that was 2.4-fold higher than in conventional buffer. Moreover, the thermal stability was enhanced by a magnitude of 2.7, with an improvement in storage stability. Molecular docking studies illustrated that the most potent DES established strong hydrogen bond interactions with the enzyme's amino acid, which enhanced the catalytic efficiency and improved the stability of the ω-TA. Molecular docking is essential in designing DESs for a specific enzyme.

m6 A transferase KIAA1429-stabilized LINC00958 accelerates gastric cancer aerobic glycolysis through targeting GLUT1.

Emerging evidence has demonstrated that N6 -methyladenosine (m6 A) and long noncoding RNAs (lncRNAs) are both crucial regulators in gastric cancer (GC) tumorigenesis. However, the interaction of m6 A and lncRNAs in GC progression are still unclear. Here, our team discovered that lncRNA LINC00958 expression up-regulated in GC tissue and cells. Clinically, high-expression of LINC00958 was clinically correlated to lower survival of GC patients. Functionally, in vitro assays demonstrated that LINC00958 promoted the GC cells' aerobic glycolysis. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) found that there were m6 A-modificated sites in LINC00958, and moreover m6 A methyltransferase KIAA1429 catalyzed the m6 A modification on LINC00958 loci. Moreover, LINC00958 interacted with GLUT1 mRNA via the m6 A-dependent manner to enhance GLUT1 mRNA transcript stability, thereby positively regulating the aerobic glycolysis of GC. In conclusion, our findings reveal the function and mechanism of KIAA1429-induced LINC00958 in GC, delineating novel understanding of m6 A-lncRNA in cancer biology.

Protective Effect of Fuzi Lizhong Decoction against Non-alcoholic Fatty Liver Disease via Anti-inflammatory Response through Regulating p53 and PPARG Signaling.

Fuzi Lizhong decoction (FLD) is derived from an ancient Chinese Pharmacopoeia and has been used in clinical treatment for years. The present study aimed to investigate the activities and underlying mechanisms of FLD against non-alcoholic fatty liver disease (NAFLD). Network pharmacology analysis demonstrated that FLD might affect NAFLD through regulating p53 and peroxisome proliferator activated receptor gamma (PPARG), which has been confirmed in vitro and in vivo. In vivo NAFLD was induced in rats by a high-fat diet, and in vitro studies were performed on HL-7702 cells treated with oleic acid and linoleic acid. We showed that FLD significantly improved NAFLD by regulating the immune system to induce the release of interleukin-10 (IL-10), interferon-α (IFN-α), and IFN-ß through activating p53 signaling and inhibiting PPARG signaling in vivo and in vitro. P53 inhibition induced by NAFLD was recused by FLD, while PPARG overexpression induced by NAFLD was inhibited by FLD. In addition, NAFLD resulted in increased levels of total cholesterol, triglyceride, and blood glucose in the serum and free fatty acid in the liver, which were reduced by FLD treatment. Evidently, FLD exhibited potent protective effects against NAFLD via p53 and PPARG signaling. Our study could provide novel insights into the mechanisms of FLD as an anti-inflammatory candidate for the treatment of NAFLD in the future.

[Analysis of medication regularity and pharmacodynamic characteristics of traditional Chinese medicine treatment in 444 severe cases of COVID-19].

The coronavirus disease 2019(COVID-19) is developing rapidly and posing great threat to public health. There is no effective intervention for the severe patients, and their prognosis is poor. It is worth noting that in the fight against COVID-19, China has always put equal emphasis on both Chinese and Western medicine. Traditional Chinese medicine has played an important role in the whole process. It is of great significance to discuss the rules and characteristics of the prescription of traditional Chinese medicine in the treatment of COVID-19. In this study, information was collected from 444 severe COVID-19 patients who were admitted to a hospital designated to treat patients with severe COVID-19 in Wuhan before March 20, 2020. We collected traditional Chinese medicine prescriptions for patients with severe COVID-19, referred to Chinese Pharmacopoeia to standardize the names of traditional Chinese medicine, and extract the property, flavor and channel tropism of traditional Chinese medicines to analyze the rules of the prescriptions. IBM SPSS Modeler 18.0 software was used to conduct correlation analysis of traditional Chinese medicine. Effective traditional Chinese medicines against COVID-19 was identified by the TCMATCOV platform. In the end, 1 532 effective prescriptions were included. Among them, the high-frequency drugs are Poria, Astragali Radix, Pogostemonis Herba, Armeniacae Semen Amarum, Atractylodis Macrocephalae Rhizoma, Pinelliae Rhizoma, Glycyrrhizae Radix et Rhizoma, Magnoliae Officinalis Cortex, Ephedrae Herba, Cinna-momi Ramulus. Most of the drugs have the following functions: resolving dampness, replenishing deficiency, resolving phlegm, cough, and asthma. The core combinations are Pogostemonis Herba-Poria, Astragali Radix-Pogostemonis Herba-Poria, Amomi Fructus-Poria, Amomi Fructus-Pogostemonis Herba, Amomi Fructus-Astragali Radix. The majority of the medicines are with cold and warm properties, and the proportions are 41.03% and 38.46%, respectively. The medicinal flavors are mainly concentrated in sweet and bitter, and the proportions are 34.71% and 30.58%, respectively. The meridian of the drug is more into the lung, stomach and spleen, with lung accounting for 22.87%. From the analysis of high-frequency drugs to the core combinations, one can see that the main treatment principle for severe COVID-19 is to remove internal and external dampness, protect the spleen and stomach, remove evil energy, and support righteousness. TCMATCOV platform was used to calculate the network disturbances of the high-frequency drugs. It was found that the traditional Chinese medicine with a high disturbance score accounted for a high proportion of the classic anti-COVID-19 prescriptions used by clinicians. Among them, the drugs with top scores are Ephedrae Herba, Citri Reticulatae Pericarpium, Eupatorii Herba, Platycodonis Radix, Cinnamomi Ramulus, Astragali Radix, Magnoliae Officinalis Cortex, Atractylodis Macrocephalae Rhizoma, Pogostemonis Herba, Scutellariae Radix. After a further exploration of the action targets, it was showed that disease-specific factor TNF was the target of the above ten drugs, and traditional Chinese medicine can exert anti-inflammatory and immune-modulating effects.

[Effect of Fuzi Lizhong decoction in reducing liver injury of rats with non-alcoholic fatty liver via activating AMPK and suppressing NF-κBp65 pathway].

To investigate the protective effect and relevant mechanism of Fuzi Lizhong decoction (FZLZD) on liver of rats with non-alcoholic fatty liver disease (NAFLD), totally 32 male SPF Wistar rats were randomly divided into 4 groups: control group, model group, Yishanfu (YSF) group (200 mg·kg⁻¹·d⁻¹) and FZLZD group (10 g·kg⁻¹·d⁻¹), with 8 rats in each group. Rat model of NAFLD was prepared through the intragastric administration with fat emulsion for 4 weeks. After the successful modeling, rats in each administration group were continuously administered for 4 weeks. After 8 weeks, the rats in each group were put to death, and the pathological changes in liver tissue were detected by HE staining. Automatic biochemical analyzer was used to detect fasting serum lipid levels (T-Chol, TG, LDL-C, HDL-C) and liver functions (ALT, TP, ALB) of rats in each group. The rat liver index was calculated by weighing method. Enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of inflammatory cytokines TNF-α and IL-6 in liver tissue. Real-time quantitative PCR (qRT-PCR) was used to detect the mRNA expressions of fat metabolism-related factors SREBP-1c and FASN in liver tissue. Western blot was used to detect the p-AMPK and p-NF-κBp65 protein expressions in liver tissue. The results of HE staining showed that compared with the control group, the pathological changes in liver tissue in the model group rats were obvious; specifically, the outline of hepatic lobule was unclear, the hepatic cells showed diffuse steatosis of adipose tissue, and were accompanied by inflammatory infiltration, nuclear condensation, coloring deep; compared with the model group, liver lesions of all of the treatment groups were significantly alleviated; especially, the FZLZD group showed the most significant degree of remission. The results of serum test showed that the levels of serum lipids (T-Chol, TG, LDL-C, HDL-C), liver functions (ALT, TP, ALB) and liver index in model group were significantly higher than those in control group (P<0.01); compared with the model group, the indexes of serum lipid and liver function of rats in each treatment group were significantly decreased (P<0.01), and those in FZLZD group were significantly decreased (P<0.05), while those in YSF group were not significantly changed. The results of ELISA and qRT-PCR showed that compared with the control group, the secretion levels of TNF-α, IL-6 and the mRNA levels of SREBP-1c and FASN in the liver tissue of model group rats were significantly increased (P<0.01); compared with model group, the secretion levels of TNF-α, IL-6 and the mRNA levels of SREBP-1c, FASN in liver tissue of rats in each treatment group were significantly decreased (P<0.01); compared with YSF group, the secretion levels of TNF-α and IL-6 and the mRNA levels of SREBP-1c and FASN in FZLZD group were significantly different (P<0.01). Western blotting showed that compared with the model group, the protein expression of p-AMPK in liver tissue of rats in FZLZD group was significantly increased (P<0.01), while the protein expression of p-NF-κBp65 was significantly decreased (P<0.01). FZLZD can significantly improve hepatic pathological changes, reduce serum lipid levels, promote liver function and liver index in NAFLD rats, which may be associated with the activation of the AMPK pathway and thereby the inhibition of the expressions of SREBP-1c and FASN, and the inhibition of the NF-κBp65 pathway and thereby the reduction of the release of inflammatory factors.

[Effects of three Wenyang Jianpi Tang on cell proliferation and apoptosis of nonalcoholic fatty liver cells].

To investigate the effects of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang on the cell proliferation and apoptosis of nonalcoholic fatty liver cells through the nonalcoholic fatty liver cell model established by inducing L02 cells with oleic acid. Different concentrations of oleic acid were added into L02 cells to induce the nonalcoholic fatty liver cell model. Oil red O staining was used to observe fatty droplets of fatty liver cells. Automatic biochemical analyzer was used to detect the levels of aspartic transaminase(AST), alanine aminotransferase(ALT), total cholesterol(TC), and triglyceride(TG) in the cell supernatants. There were five groups, namely normal group, model group, model and Sijunzi Tang group, model and Lizhong Tang group, and model and Fuzi Lizhong Tang group. The cell proliferation and apoptosis of the five groups were detected by MTT colorimetry test and flow cytometer. The expressions of PCNA, cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax and Bcl-2 proteins of the five groups were detected by Western blot. The oil red O staining results showed that the optimum concentration of oleic acid that was used to induce nonalcoholic fatty liver cell models was 80 mg•L-1. The levels of AST, ALT, TC and TG in the nonalcoholic fatty liver cell supernatants were higher than that in normal liver cell supernatants(P<0.01). MTT colorimetry test and flow cytometer results showed that all of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell proliferation, and inhibit the cellular apoptosis of nonalcoholic fatty liver cells(P<0.01). And Fuzi Lizhong Tang showed the best effect. Western blot results showed that Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could down-regulate the expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and Bax proteins, and up-regulate the expressions of PCNA and Bcl-2 proteins of nonalcoholic fatty liver cells. And Fuzi Lizhong Tang showed the best effect. In conclusion, all of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell proliferation, and inhibit the cellular apoptosis of nonalcoholic fatty liver cells. And Fuzi Lizhong Tang showed the best effect. The pharmacodynamic mechanism may be related to the expressions of key factors in pathways related with proliferation and apoptosis mediated by the three decoctions.

[Efficacy of tongfu mixture for treating post-ERCP pancreatitis: a clinical study].

OBJECTIVE: To observe the clinical efficacy of Tongfu Mixture (TM) for post-ERCP pancreatitis (PEP). METHODS: Totally 54 PEP patients were randomly assigned to the control group (treated by routine therapy, 26 cases) and the TM treatment group (treated by TM, 28 cases). Clinical indices including the alleviation time of abdominal pain/distention, gastrointestinal function recovery time, and the post-surgical length of stay were observed. Blood amylase (AMY), C-reactive protein (CRP), plasma endotoxin (PLS), TNF-alpha, and IL-6 were detected before surgery, 12 h, 48 h, and 96 h after surgery. RESULTS: The alleviation time of abdominal pain/distention, the gastrointestinal function recovery time, and the post-surgical length of stay were obviously shorter in the TM treatment group than those in the control group (P < 0.05). The recovery of AMY and CRP were better in the TM treatment group than in the control group at post-operative 48 h and 96 h (P < 0.05). The levels of LPS, TNF-alpha, and IL-6 were lower in the TM group than in the control group at post-operative 96 h (P < 0.05). CONCLUSION: TM showed better clinical efficacy and could significantly decrease the post-surgical length of stay. post-ERCP pancreatitis; integrative medicine; Tongfu Mixture

Exploration of genetic characterization in hyperprogressive disease after immunotherapy retreatment in a patient with LCNEC: A case report.

Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic option for large cell neuroendocrine carcinoma (LCNEC). However, various studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving ICI, which might be associated with gene alterations. Here, this is the first report on an unknown primary LCNEC patient who had achieved a long-term response from ICI treatment (atezolizumab), but developed HPD after tumor progression due to receiving another ICI agent (serplulimab). The mutation region of FAT4, SMARCA4, CYLD, CTNNB1, and KIT was altered prior to serplulimab treatment compared to before atezolizumab treatment. This case suggested a potential association between these mutated genes and HPD. Patients with the aforementioned genes should caution when selecting ICI treatment. These findings required further confirmation in a larger study cohort.

Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling.

Cancer stem cells (CSCs) play a crucial role in tumor initiation, recurrence, metastasis, and drug resistance. However, the current understanding of CSCs in hepatocellular carcinoma (HCC) remains incomplete. Through a comprehensive analysis of the database, it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a critical enzyme involved in cholesterol synthesis, is up-regulated in HCC tissues and liver CSCs. Moreover, high expression of HMGCR is associated with a poor prognosis in patients with HCC. Functionally, HMGCR promotes the stemness and metastasis of HCC both in vitro and in vivo. By screening various signaling pathway inhibitors, we have determined that HMGCR regulates stemness and metastasis by activating the Hedgehog signaling in HCC. Mechanistically, HMGCR positively correlates with the expression of the Smoothened receptor and facilitates the nuclear translocation of the transcriptional activator GLI family zinc finger 1. Inhibition of the Hedgehog pathway can reverse the stimulatory effects of HMGCR on stemness and metastasis in HCC. Notably, simvastatin, an FDA-approved cholesterol-lowering drug, has been shown to inhibit stemness and metastasis of HCC by targeting HMGCR. Taken together, our findings suggest that HMGCR promotes the regeneration and metastasis of HCC through the activation of Hedgehog signaling, and simvastatin holds the potential for clinical suppression of HCC metastasis.

SPOP promotes CREB5 ubiquitination to inhibit MET signaling in liver cancer.

Liver cancer is ranked as the sixth most prevalent from of malignancy globally and stands as the third primary contributor to cancer-related mortality. Metastasis is the main reason for liver cancer treatment failure and patient deaths. Speckle-type POZ protein (SPOP) serves as a crucial substrate junction protein within the cullin-RING E3 ligase complex, acting as a significant tumor suppressor in liver cancer. Nevertheless, the precise molecular mechanism underlying the role of SPOP in liver cancer metastasis remain elusive. In the current study, we identified cAMP response element binding 5 (CREB5) as a novel SPOP substrate in liver cancer. SPOP facilitates non-degradative K63-polyubiquitination of CREB5 on K432 site, consequently hindering its capacity to activate receptor tyrosine kinase MET. Moreover, liver cancer-associated SPOP mutant S119N disrupts the SPOP-CREB5 interactions and impairs the ubiquitination of CREB5.This disruption ultimately leads to the activation of the MET signaling pathway and enhances metastatic properties of hepatoma cells both in vitro and in vivo. In conclusion, our findings highlight the functional significance of the SPOP-CREB5-MET axis in liver cancer metastasis.

Clinical Experience of External Application of Clearing Heat and Removing Dampness in Relieving Grade 2 to 3 Rash Caused by Programed Cell Death Protein 1 (PD-1)/Programed Cell Death Ligand 1 (PD-L1) Inhibitors: A Single-Center Retrospective Study.

OBJECTIVE: In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash. METHODS: A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed. RESULTS: Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn't increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P < .0001), emotions (58.33 vs 15.48, P < .0001), functioning (46.67 vs 13.33, P < .0001) and composite (52.60 vs 14.06, P < .0001). CONCLUSION: External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs.

RBBP6 maintains glioblastoma stem cells through CPSF3-dependent alternative polyadenylation.

Glioblastoma is one of the most lethal malignant cancers, displaying striking intratumor heterogeneity, with glioblastoma stem cells (GSCs) contributing to tumorigenesis and therapeutic resistance. Pharmacologic modulators of ubiquitin ligases and deubiquitinases are under development for cancer and other diseases. Here, we performed parallel in vitro and in vivo CRISPR/Cas9 knockout screens targeting human ubiquitin E3 ligases and deubiquitinases, revealing the E3 ligase RBBP6 as an essential factor for GSC maintenance. Targeting RBBP6 inhibited GSC proliferation and tumor initiation. Mechanistically, RBBP6 mediated K63-linked ubiquitination of Cleavage and Polyadenylation Specific Factor 3 (CPSF3), which stabilized CPSF3 to regulate alternative polyadenylation events. RBBP6 depletion induced shortening of the 3'UTRs of MYC competing-endogenous RNAs to release miR-590-3p from shortened UTRs, thereby decreasing MYC expression. Targeting CPSF3 with a small molecular inhibitor (JTE-607) reduces GSC viability and inhibits in vivo tumor growth. Collectively, RBBP6 maintains high MYC expression in GSCs through regulation of CPSF3-dependent alternative polyadenylation, providing a potential therapeutic paradigm for glioblastoma.

Preparation and Characterization of an Invasive Plant-Derived Biochar-Supported Nano-Sized Lanthanum Composite and Its Application in Phosphate Capture from Aqueous Media.

Invasive plants pose a great threat to natural ecosystems owing to their rapid propagation and spreading ability in nature. Herein, a typical invasive plant, Solidago canadensis, was chosen as a novel feedstock for the preparation of nano-sized lanthanum-loaded S. canadensis-derived biochar (SCBC-La), and its adsorption performance for phosphate removal was evaluated by batch adsorption experiment. The composite was characterized by multiple techniques. Effects of parameters, such as the initial concentration of phosphate, time, pH, coexisting ions, and ionic strength, were studied on the phosphate removal. Adsorption kinetics and isotherms showed that SCBC-La shows a faster adsorption rate at a low concentration and SCBC-La exhibits good La utilization efficiency than some of the reported La-modified adsorbents. Phosphate can be effectively removed over a relatively wide pH of 3-9 because of the high pH pzc of SCBC-La. Furthermore, the SCBC-La shows a strong anti-interference capability in terms of pH value, coexisting ions, and ionic strength, exhibiting a highly selective capacity for phosphate removal. Additionally, Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) measurements reveal that hydroxyl groups on the surface of SCBC-La were replaced by phosphate and manifest the reversible transformation between La(OH)3 and LaPO4. Considering its high adsorption capacity and excellent selectivity, SCBC-La is a promising material for preventing eutrophication. This work gives a new method of pollution control with waste treatment since the invasive plant (S. canadensis) is converted into biochar-based nanocomposite for effective removal of phosphate to mitigate eutrophication.

A magnetically recyclable lignin-based bio-adsorbent for efficient removal of Congo red from aqueous solution.

It has been always attractive to design a sustainable bio-derived adsorbent based on industrial waste lignin for removing organic dyes from water. However, existing adsorbent strategies often lead to the difficulties in adsorbent separation and recycling. Herein, we report a novel magnetically recyclable bio-adsorbent of Mg(OH)2/Fe3O4/PEI functionalized enzymatic lignin (EL) composite (EL-PEI@Fe3O4-Mg) for removing Congo red (CR) by Mannish reaction and hydrolysis-precipitation. The Mg(OH)2 and PEI functionalized EL on the surface act as active sites for the removal of CR, while the Fe3O4 allows for the easy separation under the help of a magnet. As-obtained EL-PEI@Fe3O4-Mg forms flower-like spheres and has a relatively lager surface area of 24.8 m2 g-1 which is 6 times that of EL. The EL-PEI@Fe3O4-Mg exhibits a relatively high CR adsorption capacity of 74.7 mg g-1 which is 15 times that of EL when initial concentration is around 100 mg L-1. And it can be easily separated from water by applying an external magnetic field. Moreover, EL-PEI@Fe3O4-Mg shows an excellent anti-interference capability according to the results of pH values and salt ions influences. Importantly, EL-PEI@Fe3O4-Mg possesses a good reusability and a removal efficiency of 92 % for CR remains after five consecutive cycles. It is illustrated that electrostatic attraction, π-π interaction and hydrogen binding are primary mechanisms for the removal of CR onto EL-PEI@Fe3O4-Mg. This work provides a novel sustainable strategy for the development of highly efficient, easy separable, recyclability bio-derived adsorbents for removing organic dyes, boosting the efficient utilization of industrial waste lignin.

Rhein Exhibits Anti-Inflammatory Effects in Chronic Atrophic Gastritis via Nrf2 and MAPK Signaling.

BACKGROUND: Chronic atrophic gastritis is a premalignant lesion with a high risk of developing into gastric cancer. Rhein is a key active ingredient of several traditional Chinese medicines with multiple pharmacological effects. Nevertheless, the role of rhein in chronic atrophic gastritis is unclear. METHODS: Helicobacter pylori infection was used to establish chronic atrophic gastritis in a mouse model. Murine gastric mucosa treated with saline or rhein was used in experiments. Hematoxylin and eosin staining and Alcian blue-periodic acid-Schiff staining were utilized for histopathological observation of murine gastric mucosa. The levels of proinflammatory factors were detected by enzyme-linked immunosorbent assay, and oxidative stress-associated markers were detected by commercially available assay kits. Western blotting was used for measuring the levels of nuclear factor, erythroid 2-like bZIP transcription factor 2, and mitogen-activated protein kinase signaling-related proteins. RESULTS: Rhein mitigated the gastric mucosal injury and suppressed inflammation and oxidative stress in H. pylori-infected chronic atrophic gastritis mouse models. Rhein inactivated mitogen-activated protein kinase and activated erythroid 2-like bZIP transcription factor 2 signaling in gastric mucosa of mice with chronic atrophic gastritis. CONCLUSION: Rhein exhibits anti-inflammatory and antioxidant effects in chronic atrophic gastritis via erythroid 2-like bZIP transcription factor 2 and mitogen-activated protein kinase signaling.

Titanium dioxide nanoparticles functionalized chitosan toward bio-based antibacterial adsorbent for enhanced phosphate capture.

Developing an eco-friendly, sustainable and antibacterial adsorbent is significant for actual water treatment. Herein, a bio-based antibacterial adsorbent based on titanium dioxide (TiO2) nanoparticles functionalized chitosan (CS) was prepared through an in-situ hydrolysis strategy using titanium oxysulfate as the source of TiO2. The as-obtained CS/TiO2 nanocomposite was characterized by a variety of analytical techniques. According to the Langmuir mode, the adsorption capacity of CS/TiO2 reached 23.64 mg P g-1, almost 8 times higher than that of CS. In addition, the normalized adsorption capacity (adsorption value per Ti) of CS/TiO2 was calculated to be 102.68 mg P g-1 Ti-1, much higher than pure TiO2 (60.11 mg P g-1 Ti-1). Moreover, CS/TiO2 exhibited a highly selective capacity for phosphate removal in the presence of competing anions, and showed high stability in a wide pH range of 3.0-8.0. When the phosphate concentration was 2.0 mg P L-1, the removal efficiency of phosphate reached 99.5 % and the residual concentration was only 10 µg P L-1, which meets the USEPA standards for eutrophication prevention and control. In addition, after treatment by CS/TiO2, the phosphate concentration of two sewage water samples decreased from 1.50 and 1.0 mg P L-1 to <0.10 mg P L-1, meeting the standard of level II water based on the Environmental Quality Standard of China (GB3838-2002). Ligand exchange and electrostatic interactions are mainly responsible for phosphate adsorption by CS/TiO2. Furthermore, the CS/TiO2 nanocomposites exhibited excellent antibacterial activity, which could avoid biofouling contamination caused by microorganisms. Benefiting from the above advantages, the as-designed CS/TiO2 nanocomposite has great potential as a bio-based antibacterial adsorbent for phosphate capture or removal from wastewater.

Analysis of clinical features and identification of risk factors in patients with non-alcoholic fatty liver disease based on FibroTouch.

Our aim was to explore the correlation between ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) based on FibroTouch (China) and clinical features in patients with non-alcoholic fatty liver disease (NAFLD), so as to provide a certain basis for the clinical application of FibroTouch in NAFLD. Hepatic steatosis and fibrosis in patients with NAFLD were graded according to FibroTouch, and the relationship between steatosis and fibrosis levels and clinical characteristics was retrospectively analyzed. Hepatic steatosis was positively related with weight, BMI, waist, hyperlipidemia, hyperuricemia, FBG, UA, TG, ALT, AST, GGT, LSM and hepatic fibrosis grading, and was negatively related with gender (male), age and AST/ALT ratio. Hepatic fibrosis was positively related with age, BMI, waist, hypertension, FBG, ALT, AST, GGT, NFS, APRI, FIB-4, UAP and hepatic steatosis grading, and was negatively related with blood platelet (PLT) counts. Moreover, BMI, waist, TG, ALT and LSM were independent risk factors of hepatic steatosis, while decreased PLT counts, AST and UAP were independent risk factors of hepatic fibrosis. Body mass parameters, metabolic risk factors and liver function indicators increase the risk of hepatic steatosis and fibrosis in patients with NAFLD, and UAP and LSM can interact with each other.

ATX/LPA axis regulates FAK activation, cell proliferation, apoptosis, and motility in human pancreatic cancer cells.

Previous studies implicated ATX/LPA axis as a potential driver of tumorigenesis and progression in pancreatic cancer. This study aimed to determine the existence of the autocrine pathway of ATX/LPA action in pancreatic cancer cells, and to elucidate its influence on focal adhesion kinase (FAK) activation, cellular proliferation, apoptosis, and migration. Firstly, we identified the lysophosphatidic acid (LPA) concentrations in cultured cell supernatant by ELISA and observed the effect of the autotaxin (ATX)-specific inhibitor S32826 on LPA concentrations. We found the existence of a certain concentration of LPA in cellular supernatant, which was significantly decreased by S32826 in a dose- and time-dependent manner. A maximum response was observed at 50 µM for 72 h. Secondly, the effect of S32826 on the protein expression and intracellular sublocalization of total FAK and phosphorylated FAK (pY397 FAK) was determined by Western blot and immunofluorescence staining. It was found that the expression of total FAK and pY397 FAK and their distribution along the cell membrane where adhesion structures are located were significantly decreased by S32826. Finally, we observed the influence of S32826 on cell proliferation, apoptosis, and migration by CCK-8 assay, flow cytometric analysis, and transwell migration assay. Results showed that cell viability and migration were significantly declined, and the proportions of apoptotic cells were significantly increased by S32826. This study verified the existence of autocrine regulation of LPA secretion via producing ATX by pancreatic cancer cells in vitro and the important role of LPA/ATX axis on FAK activation, cell proliferation, apoptosis, and motility.

A lignin-based epoxy/TiO2 hybrid nanoparticle for multifunctional bio-based epoxy with improved mechanical, UV absorption and antibacterial properties.

Lignin, as a natural polymer material, has the advantages of green safety, renewable, and pollution-free. It has a wide application prospect in the field of thermosetting. However, it has been attractive but a huge challenge to design high performance and high added-value lignin-based epoxy resin. Herein, lignin-based epoxy (LEP) was synthesized from moso bamboo-derived lignin, and then lignin-based epoxy/titanium dioxide (LEP/TiO2) hybrid nanoparticle was synthesized via liquid deposition method for modifying lignin-based epoxy resin to prepare multifunctional bio-based epoxy. The results show that the LEP/TiO2 hybrid nanoparticle exhibits a stable topological surface shape and good dispersion and uniformity. By adding 10 wt% LEP/TiO2 hybrid nanoparticles, the multifunctional bio-based epoxy exhibits good mechanical strength and toughness, and the tensile strength and fracture toughness reach 36 MPa and 1.26 MPa·m1/2, respectively. In addition, the thermal stability, UV absorption and antibacterial properties of the multifunctional bio-based epoxy are further improved. This study provides a facile and efficient method for the preparation of high-performance multifunctional bio-based epoxy composite and a novel solution for the utilization of lignin.