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Background: Low-molecular citrus pectin (LCP) is a pectin polysaccharide with low molec-ular weight, low degree of crux, and no branching. It is obtained by degrading natural citrus pectin (CP) through physical, chemical and enzymatic methods. LCP has received considerable attention in recent years due to its potential applications in the medical and biological fields. Methods: In our previous study, LCP was prepared from CP by using recombinant Bacillus subtilis pectate lyase B. Monosaccharide comparative analysis revealed that the galacturonic acid content of LCP was higher than that of CP. The cell viability effect of LCP was elucidated by using HepG2 cells and the Cell Counting Kit-8 (CCK-8) assay. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, Annexin V-FITC/PI staining, and flow cytometer propidium iodide stain-ing were performed to detect the effects of LCP on apoptosis and cell cycle arrest in HepG2 cells. Mi-tochondrial membrane potential (MMP) was observed through 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine assay. Results & discussion: The Mw of the prepared LCP was 7.6 kDa, which was significantly lower than that of CP (140 kDa). Cell viability decreased with the increase in the concentration of LCP. The half-inhibitory concentration of 1.46 ± 0.02 mg/mL was determined. Treatment with 1.6 mg/mL LCP in-duced the apoptosis of HepG2 cells with the inhibition rate of 83.10% ± 4.72%, and the cell cycle was arrested in the S phase. Furthermore, the MMP of HepG2 cells decreased with the increase in LCP concentration. Conclusion: The enzymatically prepared LCP could inhibit the proliferation of HepG2 cells. This study provided a partial experimental basis and reference for LCP to become a potential functional food for anti-liver cancer.

Background Docetaxel (DTX) exhibits antitumor effects against breast cancer by stabilizing microtubules and increasing the accumulation of reactive oxygen species (ROS). DTX extravasation during infusion often causes skin injury. The present study aimed to investigate the effects and mechanisms of icaritin (ICT) on DTX‐induced skin injury. Methods The effects of ICT on the viability and apoptosis of HaCaT cells were measured by SRB assay and flow cytometry, respectively. Endogenous LC3 puncta and microtubules were determined by immunofluorescence. The number of mitochondria was measured by MitoTracker orange staining. ROS were determined by dihydroethidium staining. The expression of markers of ROS and autophagy were measured by western blotting. Chloroquine, compound D, and tamoxifen were employed as the inhibitor for autophagy and AMPK, estrogen receptors (ERs) modulator, respectively. Results DTX inhibited the viability and decreased apoptosis of HaCaT cells, which can be rescued by ICT. ICT decreased microtubule bundles, increased the number of mitochondria, and attenuated ROS of HaCaT cells induced by DTX. ICT blocks autophagy and the autophagic flux. Compound C or tamoxifen diminished the protection effects of ICT on DTX‐treated HaCaT cells. Conclusion ICT alleviates DTX‐induced skin injury by suppressing ROS, reducing microtubule bundles, and blocking autophagy via ERs. Our study indicated that ICT may be a potential candidate for DTX‐induced skin injury., ICT alleviates DTX‐induced skin injury by alleviating the microtubule bundles, while the specific mechanism is unknown. At the same time, ICT, as an ER modulator, promotes the phosphorylation of the α subunit of AMPK to activate AMPK, thereby regulating the level of autophagy. ICT also reduces the level of ROS by acting as an ER modulator to reduce cell apoptosis.

As the high-power density and environmentally friendly energy resources, proton exchange membrane fuel cells (PEMFCs) have a promising future in portable power generation. Herein, the hybrid Nafion membranes of ionic hydrogen-bonded organic frameworks (iHOFs) for PEMFC applications are demonstrated. By adjusting the position of sulfonic groups on naphthalene disulfonic acid compounds, four iHOFs with different types of hydrogen bonds were synthesized successfully based on 1,1'-diamino-4,4'-bipyridylium and naphthalene disulfonic acid. The formation of hydrogen bond interactions between amino and sulfonate groups provides a rich hydrogen bond network, which makes such iHOFs have high conductivity, and the maximum value is 2.76 × 10-3 S·cm-1 at 100 °C and 98% RH. Besides, composite membrane materials were obtained by mixing Nafion and iHOFs, and the maximum proton conductivity values can achieve 1.13 × 10-2 S·cm-1 for 6%-iHOF-3/Nafion and 2.87 × 10-3 S·cm-1 for 6%-iHOF-4/Nafion membranes at 100 °C under 98% RH. Through the H2/O2 fuel cell performance test by using iHOF/Nafion as the solid electrolyte, the maximum power and current density values of hybrid membranes are 0.36 W·cm-2 and 1.10 A·cm-2 for 6%-iHOF-3/Nafion and 0.42 W·cm-2 and 1.20 A·cm-2 for 6%-iHOF-4/Nafion at 80 °C and 100% RH. This work provides a practicable approach for establishing high-performance proton exchange hybrid membranes by doping high proton-conducting iHOFs into the Nafion matrix.

A series of acid-activated montmorillonites (Acid-MMTs) were prepared via Na-montmorillonite treated with nitric acid solution at different treatment temperature and time. And the Acid-MMTs used as solid acid were physically mixed with commercial Cu/ZnO/Al2O3 to obtain bifunctional catalysts for steam reforming of dimethyl ether (SRD) reaction. The results showed that the structure, texture and acidity of Acid-MMTs were significantly changed compared with Na-MMT, which was dependent on the acid treatment conditions. The structure and acidity of Acid-MMTs obviously affected the SRD performance over bifunctional catalyst. The bifunctional catalyst composed of the Na-MMT activated in 20% nitric acid solution at 80°C for 12 h (Acid-MMT-80/12) and Cu/ZnO/Al2O3 exhibited the best SRD performance, with the dimethyl ether conversion and H2 yield reaching 97% and 94% under the conditions of p=0.1 MPa, t=350°C, GHSV=3000 h−1, respectively, and DME conversion and H2 yield remained basically constant in 10 h, indicating that the catalyst had better stability.

Although chirality is an ever-present characteristic in biology and some artificial molecules, controlling the chirality and demystifying the chirality origin of complex assemblies remain challenging. Herein, we report two homochiral Ag14 nanoclusters with inherent chirality originated from identical rotation of six square faces on a Ag8 cube driven by intra-cluster π···π stacking interaction between pntp− (Hpntp = p-nitrothiophenol) ligands. The spontaneous resolution of the racemic (SD/rac-Ag14a) to homochiral nanoclusters (SD/L-Ag14 and SD/R-Ag14) can be realized by re-crystallizing SD/rac-Ag14a in acetonitrile, which promotes the homochiral crystallization in solid state by forming C–H···O/N hydrogen bonds with nitro oxygen atoms in pntp− or aromatic hydrogen atoms in dpph (dpph = 1,6-bis(diphenylphosphino)hexane) on Ag14 nanocluster. This work not only provides strategic guidance for the syntheses of chiral silver nanoclusters in an all-achiral environment, but also deciphers the origin of chirality at molecular level by identifying the special effects of intra- and inter-cluster supramolecular interactions., The preparation of chiral monolayer-protected metal clusters is interesting for their potential applications in a variety of fields, including catalysis. Here, the authors synthesize chiral Ag14 nanoclusters in an all-achiral environment, and decipher the origin of chirality at the molecular level; the solvent choice is key to achieve homochiral crystallization.

When treated with an alkoxide base like t-BuOK in aprotic solvent, N-diphenylmethyl imino oxindoles, made conveniently through condensation of corresponding isatins with N-diphenylmethyl amine, are deprotonated to form azaallyl anions. Allylation and alkylation of this type of intermediates proceed smoothly with diverse C-electrophiles. Acidic work up finishes 3-amino-3-allyl/alkyl oxindoles. The overall transformation equals to an umpolung process at the C3 of isatins.

Background The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma (HCC) used placebo or sorafenib as comparators, and there are limited data providing a cross comparison of treatments in this setting, especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination treatments. Aim To systematically review and compare response rates, survival outcomes, and safety of first-line systemic therapies for advanced hepatocellular carcinoma. Methods We searched PubMed, Science Direct, the Cochrane Database, Excerpta Medica Database, and abstracts from the American Society of Clinical Oncology 2020 annual congress. Eligible studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable HCC. Risk of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials. A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments. P value, a frequentist analog to the surface under the cumulative ranking curve, was used to rank treatments. Results In total, 1398 articles were screened and 27 included. Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and three other combination therapies. For overall response rate, lenvatinib ranked 1/19, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival (PFS), atezolizumab + bevacizumab was ranked 1/15, followed by lenvatinib. With the exception of atezolizumab + bevacizumab [hazard ratios (HR)PFS = 0.90; 95% confidence interval (CI): 0.64-1.25], the estimated HRs for PFS for all included treatments vs lenvatinib were > 1; however, the associated 95%CI passed through unity for bevacizumab plus erlotinib, linifanib, and FOLFOX4. For overall survival, atezolizumab plus bevacizumab was ranked 1/25, followed by vandetanib 100 mg/d and donafinib, with lenvatinib ranked 6/25. Atezolizumab + bevacizumab was associated with a lower risk of death vs lenvatinib (HRos = 0.63; 95%CI: 0.44-0.89), while the HR for overall survival for most other treatments vs lenvatinib had associated 95%CIs that passed through unity. Vandetanib 300 mg/d and 100 mg/d were ranked 1/13 and 2/13, respectively, for the lowest incidence of treatment terminations due to adverse events, followed by sorafenib (5/13), lenvatinib (10/13), and atezolizumab + bevacizumab (13/13). Conclusion There is not one single first-line treatment for advanced HCC associated with superior outcomes across all outcome measurements. Therefore, first-line systemic treatment should be selected based on individualized treatment goals.

Electronic and mechanic properties of single-walled carbon nanotubes (SWNTs) are uniquely dependent on the tube’s chiralities and diameters. Isolation of different type SWNTs remains one of the fundamental and challenging issues in nanotube science. Herein, we demonstrate that SWNTs can be effectively enriched to a narrow diameter range by sequential treatment of the HiPco sample with nitric acid and a π-conjugated copolymer poly(phenyleneethynylene) (PPE)–co-poly(phenylenevinylene) (PPV). On the basis of Raman, fluorescence, and microscopic evidence, the nitric acid is found to selectively remove the SWNTs of small diameter. The polymer not only effectively dispersed carbon nanotubes but also exhibited a good selectivity toward a few SWNTs. The reported approach thus offers a new methodology to isolate SWNTs, which has the potential to operate in a relatively large scale.

Cyclopropenes carrying an alkene moiety undergo a stereoselective Alder-ene cycloisomerization under thermal conditions. Diverse functionalized (hetero)spiro[2.4]heptanes are obtained with excellent trans diastereoselectivity. According to computational studies, this thermal process takes place via transition state TS(E-exo) or TS(Z-endo) if the former is not available.

This paper mainly investigated the synthesis of a high purity PbS crystal directly from lead ash which was collected from Tin ash removal process (LATR). The LATR was firstly disposed by nitric acid leaching system to generate the lead nitrate solution. The PbS crystal was prepared by mixing the lead nitrate solution with the sodium sulfide at the room temperature (25?C). The effects of molar ratio of HNO3 to Pbin the LATR on Pb leaching efficiency was investigated, demonstrating that the Pb leaching efficiency could attain to 82.9 % at molar ratio of 3. The leaching ratio of As, Cu, Fe, and Al generally increased with increasing molar ratio of HNO3 to Pbin the LATR, while 99.99 wt% of Sn was still left in the residue. In the process of generating PbS crystal from the leaching solution, the yield of PbS crystal increased with increasing molar ratio of Na2S to Pbin the filtrate. The yield of PbS crystal could up to 93.1% at a molar ratio of 1.5. Overall, this method proved to be an efficient and environmental friendly route for synthesis of high quality PbS crystal directly from the common lead containing waste from the lead ore or secondary smelting factory.

Hydrogenation reactions are an important process in today's chemical industry. Typically, hydrogenation reactions involve the removal of an unsaturated bond in olefins or other polyenes via thermal catalysis using hydrogen. As hydrogenation reactions are often carried out at temperatures up to several hundred degrees, they require significant energy input which typically comes from burning fossil fuels. In order to conserve fossil fuels and reduce CO2 emissions, researchers are now developing photothermal catalysts for hydrogenation reactions, which harness concentrated sunlight to achieve the required reaction temperatures or introduce sunlight into thermal-driven reaction systems to reduce the reaction temperatures. Photothermal catalysts thus need to be able to efficiently absorb sunlight, whilst also being able to drive the desired hydrogenation reaction with high activity and selectivity. In this review, we summarize recent research aimed at the development of photothermal catalysts for CO2/CO hydrogenation and alkene/alkyne/aromatic hydrogenation. Particular emphasis is placed on uncovering the reaction mechanisms at the molecular level, which in turn guides the rational design of photothermal catalysts with better performance.

Two new quassinoids (1 and 2) were isolated from the twigs of Harrisonia perforata (Blanco) Merr. Perforalactone E (2) possesses an uncommon hexacyclic 1α,12α:5α,13α-dicyclo-9βH-picrasane skeleton. Its structure was determined based on spectroscopic data and X-ray crystallography. Compounds 1 and 2 could significantly induce lysosomal biogenesis through transcriptional activation of lysosomal genes.

Introduction Perampanel is a highly selective and noncompetitive α‐amino‐3 ‐hydroxy‐5‐methyl‐4‐isoxazole propionate receptor (AMPAR) antagonist, which has been used as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was shown to exert neuroprotective effects in hemorrhagic and ischemic stroke models via regulating blood–brain barrier (BBB) function. Aim Here, the protective effects of perampanel were investigated in an in vitro neurovascular unit (NVU) system established using a triple cell co‐culture model (neurons, astrocytes, and brain microvascular endothelial cells) and in an in vivo traumatic brain injury (TBI) model. Results Neurons in the NVU system exhibit a more mature morphological phenotype compared with neurons cultured alone, and the co‐culture system mimicked an impermeable barrier in vitro. Perampanel protects the NVU system against traumatic and excitotoxic injury, as evidenced by reduced lactate dehydrogenase (LDH) release and apoptotic rate. Treatment with perampanel attenuated lipid peroxidation and expression of inflammatory cytokines. In addition, perampanel increased Sirt3 protein expression, enhanced the activities of mitochondrial enzyme IDH2 and SOD2, and preserved BBB function in vitro. Knockdown of Sirt3 using specific siRNA (Si‐Sirt3) partially reserved the effects of perampanel on neuronal injury and BBB function. Treatment with perampanel in vivo attenuated brain edema, preserved neurological function, inhibited apoptosis and microglia activation after TBI. Furthermore, perampanel increased the expression of Sirt3 and preserved BBB function after TBI. The effect of perampanel on BBB function and brain edema was abolished by knockdown of Sirt3 in vivo. Conclusion Our results indicate that the noncompetitive AMPAR antagonist perampanel protects the NVU system and reduces brain damage after TBI via activating the Sirt3 cascades.

Harpertrioate A (1), an A,B,D-seco-limonoid with a rearranged ring B incorporating exocyclic C-30, was isolated from the EtOAc extract of Harrisonia perforata twigs. Its structure, including absolute configurations, was determined on the basis of spectroscopic data and X-ray crystallography. This compound exhibited biological activities against Alzheimer's disease by reducing Aβ42 and Aβ40 production and shifting APP processing toward nonamyloidogenic pathway. The effect of 1 on the Aβ production was comparable to that of gemfibrozil.

The effect of sodium chloride (NaCl) curing salt content on protein oxidation, lipid oxidation and lipolysis of Chinese dry sausage was investigated. Two groups Chinese dry sausages with 2% and 4% (m/m) salt content were studied. The degree of protein oxidation increased during the processes in two groups sausages, while the content of phospholipids decreased, neutral lipids and free fatty acids increased. The degree of protein oxidation, lipid oxidation and lipolysis in 4% NaCl content group was higher than those in 2% NaCl content group, while 4% NaCl content group has higher lipase activity. In conclusion, 4% NaCl may facilitate the protein oxidation, lipid hydrolysis and oxidation in Chinese dry sausage, and the protein oxidation had strong correlation with lipid oxidation and lipolysis. The results could provide a basis for improving the technology of industrial production.

C30H46O3·1/6H2O, monoclinic, C2 (no. 5), a = 29.4307(4) Å, b = 15.42797(17) Å, c = 18.4667(2) Å, β = 104.4652(12)°, V = 8119.11(17) Å3, Z = 12, R gt(F) = 0.0432, wR ref(F 2) = 0.1197, T = 293(2) K. CCDC no.: 2016692

Recent evidence suggests that hypoxia preconditioning can alter the microRNA (miRNA) profile of extracellular vesicles (EVs) and has better neuroprotective effects when enriched miRs are delivered to recipients. However, the roles of exosomal miRNAs in regulating ischaemia-reperfusion (IR)-induced pain hypersensitivity are largely unknown. Thus, we isolated EVs from normoxia-conditioned neurons (Nor-VSC EVs) and Hypo-VSC EVs by ultracentrifugation. After the initial screening by a microarray analysis and quantitative RT-PCR (qRT-PCR), miR-126-3p, which was detected as the most altered miR in the Hypo-VSC EVs, was further confirmed by applying GW4869 to inhibit exosomal secretion. Moreover, transfection with a miR-126 mimic obviously increased miR-126-3p expression in Nor-VSC EVs, whereas a miR-126 inhibitor prevented the increase in miR-126-3p in Hypo-VSC EVs. A rat model of pain was established by performing 8-min occlusion of the aorta. Following IR, compared with the Nor-VSC EVs- or antagomir-126-injected rats, the Hypo-VSC EVs-injected rats displayed improved pain hypersensitivity demonstrated as higher PWT and PWL values. Mechanistically, PIK3R2 is a target of miR-126-3p and might be a modulator of the phosphoinositide 3-kinase (PI3K)/Akt pathway as the PIK3R2 and PI3K immunoreactivities in each group were changed in opposite directions. Compared with the controls, higher protein levels of PI3K and phosphorylated Akt but lower levels of phosphorylated nuclear factor-κ B (NF-κB), tumour necrosis factor (TNF)-α and interleukin (IL)-1β were detected in the spinal cords of the Hypo-VSC EVs-injected rats, and these effects were impaired by an injection of Hypo-VSC EVs combined with antagomir-126. Collectively, the miR-126-3p-enriched Hypo-VSC EVs attenuated IR-induced pain hypersensitivity by restoring miR-126-3p expression in the injured spinal cord and subsequently modulating PIK3R2-mediated PI3K/Akt and NF-κB signalling pathways.

To investigate the effects of emodin on inflammation and autophagy in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and reveal its underlying mechanism. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was conducted to find the appropriate dose for emodin. RAW264.7 cells pretreated with different concentrations (0–50 μmol/L) of emodin or vehicle for 2 h prior to exposure to LPS for 16 h. Cell morphology was examined and propidium iodide staining was used to examine cell cycle. Expressions of inflammation-related proteins [nuclear factor-kappaB (NF-κ B) and I-kappaB (I κ B)α] and autophagy-related proteins [light chain (LC)3, P62/sequestosome 1, mammalian target of rapamycin (mTOR), and p-mTOR] were examined using Western blot analysis. Expression of inflammation-related cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were detected by enzyme-linked immunosorbent assay. Autophagy was examined with LC3B fluorescence intensity and aggregation. The effect of emodin on autophagy was conducted with an autophagy inhibitor, 3-methyladenine (3-MA). The expression of NF-κ B in LPS-induced cells was significantly increased (P

Background/objective Coagulation factor V (FV), a multidomain glycoprotein, is an essential cofactor in the blood clotting cascade. FV deficiency is a rare bleeding disorder that results in poor clotting after an injury or surgery. The only treatment for the disease is infusions of fresh frozen plasma and blood platelets. Glycosylation affects the biological activity, pharmacokinetics, immunogenicity, and in vivo clearance rate of proteins in the plasma. The glycan profile of FV, as well as how it affects the activity, stability, and immunogenicity, remains unknown. Methods In this study, we comprehensively mapped the glycosylation patterns of human plasma-derived FV by combining multienzyme digestion, hydrophilic interaction chromatography enrichment of glycopeptides, and alternated fragmentation mass spectrometry analysis. Results/conclusion A total of 57 unique N-glycopeptides and 51 O-glycopeptides were identified, which were categorized into 40 N-glycan and 17 O-glycan compositions. Such glycosylation details are fundamental for future functional studies and therapeutics development. In addition, the established methodology can be readily applied to analyze glycosylation patterns of proteins with more than 2000 amino acids.

More and more research had focused on the osteogenesis of demineralized dentin in clinic, especially when the first application of deminerized dentin in 2008. The study tried to compare the osteogenetic ability of the demineralized dentin block, which were processed two different regents by VacuaSonic system. The extracted human permanent teeth were demineralized by two different methods. Then the MC3T3-E1 cells were invited to culture on the surface of these demineralized dentin blocks (DDB). The cell attachment, proliferation and differentiation were tested. Adhesion of MC3T3-E1 on DDM was observed using scanning electron microscopy and confocal test, the Alizarin Red S, ALP activity, and the protein of BMP-2/-7 and OCN were employed to confirm the level of cell differentiation. The P value was set at 0.05. The microfilaments established a good contact and formed a network in Group A. The Group A had more full cytoskeleton and actin stretched more obviously than Group C, the number of cells on three scaffolds were difference (p < 0 05). The MTT results showed no cytotoxicity in all experiment groups, and Group C had a significant difference in cell proliferation than other groups (p < 0 05) except for day 1. While when related to the cell differentiation, Group A showed a similar result with Group C, but in Alizarin Red S, Group A had a superior result (p < 0 05). The tooth dentin scaffold processed with composite acids in Group A presents the superiority in osteoconduction and preferable osteogenesis ability, which could be an alternative method to process the tooth scaffold.

Vascular endothelial growth factor (VEGF) had neuroprotective effects on dopaminergic (DA) neurons. In order to overcome the gastrointestinal digestion and bioaccessibility, VEGF was encapsulated with poly-lactic-co-glycolic acid nanospheres (NS) in order to prevent the VEGF degradation until its release. The caudal administration of VEGF and NS encapsulated VEGF at different doses (1.0, 10.0, and 100.0 ng/ml) on the rats with Parkinson's disease lesion was evaluated. Intravenous injected VEGF at the dose of 1 ng/ml displayed the strongest neuroprotective effect than other groups as well as the stereotaxic group. The NS encapsulated with VEGF can pass through blood-brain barrier and protect the DA neurons. There was no significant difference between intravenous injection method and stereotaxic method, while the first method is simpler and convenient. Injection of NS encapsulated with VEGF may become a valuable neurorescuing therapeutic approach for Parkinson's disease.

Bladder cancer (BCa) is the fourth most common urological malignancy in the world, it has become the costliest cancer to manage due to its high rate of recurrence and lack of effective treatment modalities. As a natural byproduct of cellular metabolism, reactive oxygen species (ROS) have an important role in cell signaling and homeostasis. Although up-regulation of ROS is known to induce tumorigenesis, growing evidence suggests a number of agents that can selectively kill cancer cells through ROS induction. In particular, accumulation of ROS results in oxidative stress-induced apoptosis in cancer cells. So, ROS is a double-edged sword. A modest level of ROS is required for cancer cells to survive, whereas excessive levels kill them. This review summarizes the up-to-date findings of oxidative stress-regulated signaling pathways and transcription factors involved in the etiology and progression of BCa and explores the possible therapeutic implications of ROS regulators as therapeutic agents for BCa.

Catalytic transesterification reaction between a cyclic carbonate and a low alcohol is the most important and practical strategy for the manufacture of dimethyl carbonate and other alkyl carbonates. However, most developed heterogeneous catalysts have potential metal and halide contamination. Herein, a graphitic carbon nitride (g-C3N4) material has been synthesized, thermally exfoliated, and treated with an alkaline solution. The physicochemical properties of eg-C3N4 materials have been analyzed by XRD, TG, N2 adsorption–desorption, FT-IR, UV-vis, and XPS spectroscopy. The characterization results reveal that the exfoliation has effectively enhanced the surface area of g-C3N4, and alkaline treatment could lead to the deprotonation of eg-C3N4, depending on the treatment temperature and alkaline solution. In the transesterification reaction between ethylene carbonate and CH3OH, the eg-C3N4-NH3 catalyst demonstrates superior catalytic activity to the pure g-C3N4, eg-C3N4 and eg-C3N4-HCl, affording a maximum DMC yield of 60% at 393 K. Furthermore, the eg-C3N4-NH3 shows good catalytic reproducibility and versatility for other substrates.

An efficient asymmetric multicatalytic system involving iminium catalysis and anion-binding catalysis has been developed, which exhibited high catalytic activity in a one-pot, two-step reaction sequence of 2-hydroxycinnamaldehydes and enolic 1,3-dicarbonyl nucleophiles to construct an enantioenriched 2,8-dioxabicyclo[3.3.1]nonane scaffold. The inherent phenolic hydroxyl group of 2-hydroxycinnamaldehyde played an important role in the catalytic process, which potentially provided a phenoxide anion to combine with the thiourea moiety of a bifunctional tertiary amine-thiourea catalyst via anion binding, thus making the developed multicatalytic system more economic and different from the previously reported catalytic mode.

Objective: To explore the underlying molecular mechanisms of cellular response to the challenge by 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis of PC12 cells, an in vitro cell model for Parkinson’s disease, and the effect of NF-κB activation on the protection of Parkinson’s disease by Isoflavone (I). Methods: PC12 cells were used to establish the cell model of Parkinson’s disease, and are divided into five groups: control group; MPP+ group; I (Isoflavone) + MPP+ group; I group; SN-50 + MPP+ group. The content of NF-κB in PC12 cells was determined by immunocytochemistry; The viability of PC12 cells after treated with cell-permeable NF-κB inhibitor SN-50 and cell viability were measured by MTT assay; the expression levels of NF-κB p65 in cytoplasm and nuclear fractions were evaluated by western blot analysis; the mRNA expression of NF-κB p65 was analyzed by in situ hybridization (ISH). Results: Compared with the control group, the protein of NF-κB p65 both in cytoplasm and in nuclei was significantly higher than in I + MPP+ and MPP+ groups; similarly, the mRNA expression level of NF-κB p65 gene was also significantly higher; moreover, the protein expression of NF-κB p65 was much lower in I group (P + group, the protein of NF-κB p65 was significantly lower in I + MPP+ group, the mRNA expression level of NF-κB p65 gene was also significantly lower, and the protein expression level of NF-κB p65 was much lower in I + MPP+ group (P + group (P > 0.05). Conclusion: NF-κB activation is essential to MPP+-induced apoptosis in PC12 cells; but Isoflavone can inhibit the cell damage to some extent to execute its protective function, which may be involved in nigral neurodegeneration in patients with Parkinson’s disease.

Ethylene insensitive 3 (EIN3), a key transcription factor in ethylene signal transduction, play important roles in plant stress signaling pathways. In this study, we isolated and characterized an EIN3-like gene from cotton (Gossypium hirsutum), designated as GhEIN3. GhEIN3 is highly expressed in vegetative tissues, and its expression is induced by 1-aminocyclopropane-1-carboxylic acid (ACC) and NaCl. Ectopic expression of GhEIN3 in Arabidopsis elevated plants' response to ethylene, which exhibit smaller leaves, more root hairs, shorter roots and hypocotyls. The germination rate, survival rate and root length of GhEIN3 transgenic plants were significantly improved compared to wild type under salt stress. GhEIN3 transgenic plants accumulated less H2O2 and malondialdehyde (MDA), while higher superoxide dismutase (SOD) and peroxidase (POD) activities were detected under salt stress. In addition, expression of several genes related to reactive oxygen species (ROS) pathway and ABA signaling pathway was increased in the GhEIN3 transgenic plants under salt stress. In contrast, virus-induced gene silencing (VIGS) of GhEIN3 in cotton enhanced the sensitivity of transgenic plants to salt stress, accumulating higher H2O2 and MDA and lower SOD and POD activities compared to control plants. Collectively, our results revealed that GhEIN3 might be involved in the regulation of plant response to salt stress by regulating ABA and ROS pathway during plant growth and development.

Sodium-glucose cotransporter 2(SGLT2) inhibitors show prominent renal protective effect in diabetic kidney disease (DKD), anti-inflammatory effect being one of its key mechanisms. Over-activation of the complement system, a crucial part of innate immunity, plays an important role in DKD. We aimed to investigate the effect of SGLT2 inhibitors on alleviating complement over-activation in DKD. Db/db mice were randomly divided into two groups, with 7 mice in each group treated with dapagliflozin and vehicle respectively, and 7 mice in m/m mice group. Laboratory and renal pathological parameters were evaluated. Mouse proximal tubular epithelial cells (MPTECs) were cultured and treated with high glucose. Dapagliflozin and dimethyloxallyl glycine (DMOG) were added as conditional treatment. Dapagliflozin-treated db/db mice showed significantly lower urinary albumin than vehicle-treated ones. Besides typical glomerular and tubulointerstitial injury, both C3b and membrane attack complex (MAC) depositions were significantly attenuated in dapagliflozin-treated db/db mice. The expression of complement receptor type 1-related protein y (Crry), a key complement regulator which inhibits complement over-activation, was significantly upregulated by dapagliflozin. Dapagliflozin-mediated Crry upregulation was associated with inhibition of HIF-1α accumulation under high glucose. When HIF-1α expression was stabilized by DMOG, the protective effect of dapagliflozin via upregulating Crry was blocked. In conclusion, dapagliflozin could attenuate complement over-activation in diabetic mice via upregulating Crry, which is associated with the suppression of HIF-1α accumulation in MPTECs.

Ethnopharmacological relevance Eucommia ulmoides (E. ulmoides) leaves are included in the Chinese Pharmacopoeia, and are traditionally used to treat hypertension, obesity, diabetes, and other diseases. Numerous pharmacological studies have shown that E. ulmoides has a good effect on lowering blood lipids and can improve obesity and nonalcoholic fatty liver. Aim To study the mechanism of E. ulmoides leaves in regulating nonalcoholic fatty liver disease by combining prediction and validation. Methods Using network pharmacology, and molecular docking to predict E. ulmoides in regulating the action mechanism and potential active ingredients of nonalcoholic fatty liver, large hole adsorption resin enrichment active sites, in vitro experiments were performed to verify its fat-lowering effect and mechanism. Results The major components of E. ulmoides leaves exhibited good combination with lipid metabolism-regulating core proteins, particularly flavonoids. EUL 50 significantly reduced lipid accumulation, and increased PPARγ. Compared with the control group, the autophagy level increased after the administration of EUL 50. PPARγ decreased significantly after the addition of chloroquine (CQ, autophagy inhibitor). Conclusion The active ingredients in E. ulmoides leaves regulating nonalcoholic fatty liver disease are mainly flavonoids and phenolics. EUL 50 may play a role in lowering lipids by regulating PPARγ expression through inducing autophagy.

C32H52O5, monoclinic, P21 (no. 4), a = 11.816(2) Å, b = 7.4064(15) Å, c = 17.101(3) Å, β = 97.01(3)°, V = 1485.5(5) Å3, Z = 2, R gt(F) = 0.0543, wR ref(F 2) = 0.1501, T = 293(2) K.

Characterization of aqueous extract in traditional Chinese medicine (TCM) is challenging due to the poor retention of the analytes on conventional C18 columns. This study presents a systematic characterization method based on a rapid chromatographic separation (8 min) on a polar-modified C18 (Waters Cortecs T3) column of aqueous extract of Cordyceps sinensis. UHPLC-HRMS method was used to profile components in both untargeted and targeted manners by full MS/PIL/dd-MS2 acquisition approach. The components were identified or tentatively identified by reference standards comparison, fragmentation rules elucidation and available databases search. A total of 91 components, including 10 nucleobases, 20 nucleosides, 39 dipeptides, 18 amino acids and derivatives and 4 other components, were characterized from the aqueous extract of C. sinensis. And this was the first time to systematically report the presence of nucleosides and dipeptides in C. sinensis, especially for modified nucleosides. The chemical basis inquiry of this work would be beneficial to mechanism exploration and quality control of C. sinensis and related products. Meanwhile, this work also provided an effective solution for characterization of aqueous extract in TCM.

Oxidative stress and effector memory CD8+ T cells have been greatly implicated in vitiligo pathogenesis. However, the crosstalk between these two crucial pathogenic factors has been merely investigated. IL-15 has been regarded as an important cytokine exerting its facilitative effect on memory CD8+ T cells function in various autoimmune diseases. In the present study, we initially discovered that the IL-15 expression was significantly increased in vitiligo epidermis and highly associated with epidermal H2O2 content. In addition, epidermal IL-15 expression was mainly derived from keratinocytes. Then, we showed that oxidative stress promoted IL-15 and IL-15Rα expression as well as IL-15 trans-presentation by activating NF-κB signaling in keratinocytes. What's more, the trans-presented IL-15, rather than the secreted one, was accounted for the potentiation of CD8+ TEMs activation. We further investigated the mechanism underlying trans-presented IL-15 in potentiating CD8+ TEMs activation and found that the blockage of IL-15-JAK-STAT signaling could be a potent therapeutic approach. Taken together, our results demonstrate that oxidative stress-induced IL-15 trans-presentation in keratinocytes contributes to the activation of CD8+ TEMs, providing a novel mechanism by which oxidative stress initiates autoimmunity in vitiligo.

Background Ischemia-reperfusion (IR)-induced pain hypersensitivity shares features of neuroinflammation and neuropathic pain, accompanied by overproduction of interleukin (IL)-1β. Multiple microRNAs (miRs) are dysregulated during IR; among these miRs, miR-187-3p was recently reported to drive IL-1β release in retinal disease by activating members of the purinergic receptor family. However, the roles of miR-187-3p in the spinal cord are unclear. Thus, we investigated whether miR-187-3p is involved in the pathogenesis of IR-induced pain hypersensitivity by regulating the P2X7R signal and subsequent IL-1β release. Methods A mouse model was established by 5-min occlusion of the aortic arch. Pain hypersensitivity was assessed by the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). MiR-187-3p, P2X7R, cleaved caspase-1 and mature IL-1β expression levels were measured by RT-PCR and Western blotting. The in vivo roles of miR-187-3p, P2X7R and IL-1β were explored by intrathecal treatment with synthetic miRs, selective agonists and antagonists in separate experiments. Double immunofluorescence staining was performed to delineate the cellular distribution of P2X7R and IL-1β. Results IR-induced progressively decreased PWT and PWL values were closely related to decreases in miR-187-3p and increases in P2X7R expression levels over time. The functional miR-187-3p/P2X7R pair was preliminarily predicted by a bioinformatic database and confirmed in vivo by quantitative analysis, as mimic-187 greatly increased miR-187-3p but decreased P2X7R expression levels, whereas inhibitor-187 reversed these changes. In contrast, downregulating P2X7R by mimic-187 or A-438079 treatment comparably increased PWT and PWL values in IR-injured mice, while upregulating P2X7R by inhibitor-187 or BzATP treatment decreased PWT and PWL values in sham-operated mice. Moreover, P2X7R and IL-1β immunoreactivities in each group were changed in the same patterns. This finding was further supported by results showing that downregulating IL-1β by A-438079 and IL-1β-neutralizing antibody similarly decreased P2X7R, cleaved caspase-1 and mature IL-1β expression levels, whereas BzATP treatment increased these levels. Expectedly, mimic-187 treatment preserved PWT and PWL values, with decreased cleaved caspase-1 and mature IL-1β expression levels, whereas inhibitor-187 reversed these effects. Conclusions The spinal miR-187-3p/P2X7R pair functioned in a mouse IR model. Increasing miR-187-3p protected against pain hypersensitivity and mature IL-1β overproduction, partially through inhibiting P2X7R activation.

The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic N-alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral N-aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis., NOBINs and other axially chiral entities have received a great deal of interest in recent years. Here, the authors report the kinetic resolution of racemic amino phenols and the enantioselective preparation of axially chiral N-aryl sulfonamides with excellent level of enantiopurity and broad substrate scope.

Vitiligo is a common skin depigmenting disorder characterized by the loss of functional melanocytes. Its pathogenesis is complicated and oxidative stress plays a critical role in the development of vitiligo. Thus, antioxidant therapy is a promising therapeutic strategy to prevent or even reverse the progression of depigmentation. Ginkgo biloba extract EGb761 has been confirmed to have protective effects on neurons against oxidative stress. Notably, several clinical trials have shown that patients with stable vitiligo achieved repigmentation after taking EGb761. However, the exact mechanism underlying the protective effects of EGb761 on melanocytes against oxidative stress has not been fully elucidated. In the present study, we found that EGb761 effectively protected melanocytes against oxidative stress‐induced apoptosis and alleviated the excessive accumulation of reactive oxygen species (ROS) and lipid peroxidation by enhancing the activity of antioxidative enzymes. Furthermore, the antioxidative effect of EGb761 was achieved by activating Nrf2 and its downstream antioxidative genes. In addition, interfering Nrf2 with siRNA abolished the protective effects of EGb761 on melanocytes against oxidative damage. In conclusion, our study proves that EGb761 could protect melanocytes from H2O2‐induced oxidative stress by activating Nrf2. Therefore, EGb761 is supposed to be a potential therapeutic agent for vitiligo.

Herein, a facile poly- l -lysine (PLL)-mediated one-pot hydrothermal approach was developed for large-scaled synthesis of Pd nanocones enclosed by the {1 1 1} facets, followed by uniformly dispersing them on graphitic carbon nitride (g-C3N4). The Pd nanocones/g-C3N4 demonstrated dramatic enhancement for photocatalytic transformation of Cr(VI) to Cr(III) via the dehydrogenation pathway under visible-light irradiation, which outperforms the {1 0 0} facets enclosed Pd nanocubes/g-C3N4, Pd black/g-C3N4, and bare g-C3N4 catalysts. Meanwhile, the as-prepared nanocomposite showed dramatically enhanced conversion up to 99.9% and improved reusable ability via the recycling test. It would advance the development of largely efficient g-C3N4 supported Pd nanocatalysts via morphology- and composition-engineering.

Accumulating evidences indicates that chronic neuropathic pain is a kind of neuro-immune disorder with enhanced activation of the immune system. Although the prevalence is very high, neuropathic pain remains extremely difficult to cure. miRNAs are a group of short nonprotein coding RNAs, regulating target genes expression via targeting 3'-untranslated region. More and more research indicates that altered miRNAs expression profile relates to the pathogenesis of neuropathic pain. In this study, we firstly detected the expression of six candidate miRNAs in the plasma samples from 23 patients with neuropathic pain and 10 healthy controls. Subsequently, the level of miR-132 and miR-101 was detected in the sural nerve biopsies. We found miR-101 level was significantly repressed in both the plasma samples and sural nerve biopsies from neuropathic pain patients. Predicted by bioinformatics tools and confirmed by dual luciferase assay and immunoblotting, we identified that KPNB1 is a direct target of miR-101. The negative correlation between miR-101 and KPNB1 was also confirmed in the sural nerve biopsies, and miR-101 reduction relates to the activation of NF-κB signaling in vivo and in vitro which contributes to the pathogenesis of neuropathic pain.

Lack of blood or glucose supply is the most common pathological factor in the brain. To cope with such an energy stress, initiating programmed autophagic processes in neurons is required. However, the mechanisms controlling neuronal autophagy during starvation remain far from clear. Here, we report an essential role of 14-3-3γ in starvation-activated neuronal autophagic influx signaling and elucidate the underlying mechanism. Double-fluorescent immunostaining demonstrates that 14-3-3γ protein elevation is well co-localized with Beclin-1 and LC3 elevation in cortical neurons in ischemic brains. Starvation treatment activates autophagic influx and upregulates Beclin-1 and only the γ isoform of 14-3-3 in N2a cells and cultured cortical neurons. Suppressing overall 14-3-3 function by difopein overexpression or knocking-out the γ isoform of 14-3-3 is sufficient to abolish starvation-induced Beclin-1 induction and LC3 activation while overexpressing 14-3-3γ but no other 14-3-3 isoform significantly upregulate Beclin-1-LC3 signaling. Upon starvation, 14-3-3γ binds more p-β-catenin but less Beclin-1. Finally, overexpressing 14-3-3γ reactivates β-catenin-suppressed Beclin-1-LC3 signaling in neuronal cells. Taken together, our data reveal that starvation-induced 14-3-3γ is required for β-catenin-Beclin-1-LC3-autophagy in starved neurons in vitro and in vivo, which may provide insights in the treatment of neurologic diseases such as stoke.

Mitochondrial dysregulation has been implicated in oxidative stress-induced melanocyte destruction in vitiligo. However, the molecular mechanism underlying this process is merely investigated. Given the prominent role of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase Sirtuin3 (SIRT3) in sustaining mitochondrial dynamics and homeostasis and that SIRT3 expression and activity can be influenced by oxidative stress-related signaling, we wondered whether SIRT3 could play an important role in vitiligo melanocyte degeneration by regulating mitochondrial dynamics. Methods: We initially testified SIRT3 expression and activity in normal and vitiligo melanocytes via PCR, immunoblotting and immunofluorescence assays. Then, cell apoptosis, mitochondrial function and mitochondrial dynamics after SIRT3 intervention were analyzed by flow cytometry, immunoblotting, confocal laser microscopy, transmission electron microscopy and oxphos activity assays. Chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP), immunoblotting and immunofluorescence assays were performed to clarify the upstream regulatory mechanism of SIRT3. Finally, the effect of honokiol on protecting melanocytes and the underlying mechanism were investigated via flow cytometry and immunoblotting analysis. Results: We first found that the expression and the activity of SIRT3 were significantly impaired in vitiligo melanocytes both in vitro and in vivo. Then, SIRT3 deficiency led to more melanocyte apoptosis by inducing severe mitochondrial dysfunction and cytochrome c release to cytoplasm, with Optic atrophy 1 (OPA1)-mediated mitochondrial dynamics remodeling involved in. Moreover, potentiated carbonylation and dampened peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) activation accounted for SIRT3 dysregulation in vitiligo melanocytes. Finally, we proved that honokiol could prevent melanocyte apoptosis under oxidative stress by activating SIRT3-OPA1 axis. Conclusions: Overall, we demonstrate that SIRT3-dependent mitochondrial dynamics remodeling contributes to oxidative stress-induced melanocyte degeneration in vitiligo, and honokiol is promising in preventing oxidative stress-induced vitiligo melanocyte apoptosis.

Peptide nucleic acid (PNA) is a nucleic acid analog which consists of purines, pyrimidines bases, and a neutrally charged peptide backbone. The PNA has the potential as a very useful biological probe for protein analysis since it has more in vivo biological stability as compared to DNA- or RNA-based aptamers. Usually, the addition of amino acids or peptide to the PNA backbone is used to improve its water-solubility and cell-permeability, but these modifications may affect the interaction between PNA and proteins. To date, the investigation of the interaction between PNA and proteins is rare, and there is no reported study about the effects of modifications. In this work, we designed two types of amino acid modified PNAs, (Lys)2-PNA and (Glu)2-PNA, which kept the same base sequence with 15-mer thrombin aptamer and had two basic lysine and two acidic glutamic acid residues on N-terminal of the peptide backbone, respectively. To rapidly assess the binding affinity and specificity of modified PNA and proteins, the online CE reaction method was developed to analyze the interactions of (Lys)2-PNA/(Glu)2-PNA and three proteins: thrombin (THB), single-strand DNA-binding protein (SSB) and human serum albumin (HSA). Meanwhile, the interactions of (Lys)2-PNA/(Glu)2-PNA and thrombin were compared with that of the corresponding complementary base sequence (Lys)2-cPNA/(Glu)2-cPNA and thrombin. The online CE reaction results showed that the interaction of (Lys)2-PNA and (Glu)2-PNA with three proteins was in the order of THB > SSB > HSA. However, (Lys)2-PNA and (Lys)2-cPNA showed similar binding affinity with thrombin; while the binding affinity of (Glu)2-PNA with thrombin was stronger than that of (Glu)2-cPNA with thrombin. Moreover, the binding constant Kb of (Glu)2-PNA and three proteins was determined by affinity capillary electrophoresis (ACE). The online CE reaction eliminates the requirement of incubation, and thus it is fast in detection, and easy to operate with minimum cost. The method is particularly suitable for the interaction studies of expensive modified PNAs and proteins, and can assist the design of PNA probe that binds to proteins.