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The mechanism of sphingosine-1-phosphate (S1P)-mediated phagocytosis remains unknown. Here, we found that S1P or FTY720 (an analog of S1P) promoted microglial phagocytosis in stroke independent of S1PRs. First, we used computer simulation of molecular docking to predict that S1P might be a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). Next, microscale thermophoresis (MST), surface plasmon resonance (SPR) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) were performed to reveal that S1P was a novel TREM2 ligand. Then, we confirmed the pro-phagocytosis of S1P targeting in Trem2-Dap12 transfected CHO cells and TREM2 knockdown microglia. Point mutation analysis showed that D104 was the critical binding residue. Trem2–/– mice were used to demonstrate the role of S1P-induced phagocytosis targeting on TREM2 in protecting against ischemic brain injury. Finally, further studies revealed that apolipoprotein E (APOE) loaded with S1P was released by microglia and bound to apoptotic neurons via LDL receptor related protein 1B (LRP1B) and thereby induced microglia to phagocytose apoptotic neurons. Overall, the present work reveals for the first time that S1P acts as a novel endogenous ligand of TREM2 to effectively promote microglial phagocytosis. Our findings provide a new lead compound for developing immunomodulator targeting on TREM2.

An electrochemically promoted decarboxylative borylation reaction is reported. The reaction proceeds under mild conditions in an undivided cell without use of transition metal- or photo-catalysts. The key feature of the reaction is the compatibility of diboron reagents with the electrochemical conditions. This reaction exhibits broad substrate scope, good functional group tolerability, and easy scalability.

Aureobasidium melanogenum P16, the high pullulan producer, had only one GATA type transcriptional activator AreA and one GATA type transcriptional repressor AreB. It was found that 2.4 g/L of (NH4)2SO4 had obvious nitrogen repression on pullulan biosynthesis by A. melanogenum P16. Removal of the AreB gene could make the disruptant DA6 produce 34.8 g/L pullulan while the P16 strain only produced 28.8 g/L pullulan at the efficient nitrogen condition. Further both removal of the native AreA gene and overexpression of the mutated AreAS628-S678 gene with non-phosphorylatable residues could render the transformant DEA12 to produce 39.8 g/L pullulan. The transcriptional levels of most of the genes related to pullulan biosynthesis in the transformant DEA12 were greatly enhanced. The mutated AreAS628-S678 was localized in the nuclei of the transformant DEA12 while the native AreA was distributed in the cytoplasm in A. melanogenum P16. This meant that nitrogen repression on pullulan biosynthesis in the transformant DEA12 was indeed significantly relieved. This was the first time to report that the GATA type transcriptional factors of nitrogen catabolite repression system could regulate pullulan biosynthesis in Aureobasidium spp.

Although ether-based electrolytes have been extensively applied in anode evaluation of batteries, anodic instability arising from solvent oxidability is always a tremendous obstacle to matching with high-voltage cathodes. Herein, by rational design for solvation configuration, the fully coordinated ether-based electrolyte with strong resistance against oxidation is reported, which remains anodically stable with high-voltage Na3 V2 (PO4 )2 O2 F (NVPF) cathode under 4.5 V (versus Na+ /Na) protected by an effective interphase. The assembled graphite//NVPF full cells display superior rate performance and unprecedented cycling stability. Beyond that, the constructed full cells coupling the high-voltage NVPF cathode with hard carbon anode exhibit outstanding electrochemical performances in terms of high average output voltage up to 3.72 V, long-term cycle life (such as 95 % capacity retention after 700 cycles) and high energy density (247 Wh kg-1 ). In short, the optimized ether-based electrolyte enriches systematic options, the ability to maintain oxidative stability and compatibility with various anodes, exhibiting attractive prospects for application.

A pair of new oxindole alkaloids, named macrophyllines C (1) and D (2), together with two known oxindole alkaloids isorhynchophylline (3) and corynoxine (4) were isolated from Uncaria macrophylla. Their structures were elucidated based on detailed spectroscopic analysis and by comparison with literature data. In addition, all the isolates were tested for their anti-HIV activities and cytotoxicities in C8166 cells and compounds 2-4 showed weak anti-HIV activities with EC50 values of 11.31 ± 3.29 μM, 18.77 ± 6.14 μM and 30.02 ± 3.73 μM, respectively.

We recently reported that intraperitoneal injection of 7,8-dihydroxyflavone (7,8-DHF), a brain-derived neurotrophic factor-mimicking small compound, could attenuate alcohol-related behaviors in a two-bottle choice ethanol consumption procedure (IA2BC) in rats via tropomyosin receptor kinase B in the ventral tegmental area (VTA), which is closely related to alcohol use disorder. However, the detailed mechanisms underlying the regulation of 7,8-DHF on alcohol drinking behavior remain elusive. In this study, we determined the role of nitric oxide (NO), a pleiotropic signaling molecule, in the VTA in the action of 7,8-DHF upon alcohol drinking behavior. Intermittent alcohol exposure led to the overexpression of NO in the VTA, especially 72 h after withdrawal from four weeks of ethanol exposure in IA2BC rats. A higher amount of alcohol intake was also found at the same time point, consistent with the overexpression of NO in the VTA. Microinjection of NG-Nitro-l-Arginine Methyl Ester, (NO synthase inhibitor) or 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (NO scavenger) into the VTA inhibited alcohol intake, whereas application of S-Nitroso-N-acetyl-DL-penicillamine (SNAP, the NO donor) in the VTA further enhanced alcohol consumption in IA2BC rats. Interestingly, either 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (a sGC inhibitor) or KT5823 [a selective protein kinase G (PKG) inhibitor] blocked NO's enhancing effect on ethanol intake. Intraperitoneal injection of 7,8-DHF reduced the overexpression of NO; SNAP microinjected into the VTA reversed the inhibitory effects of 7,8-DHF on alcohol consumption. Our findings suggest that NO-cGMP-PKG might be involved in regulation of 7,8-DHF on alcohol consumption in IA2BC rats.

One new ionone glycoside, named centrantheroside F (1), together with 9 known compounds (2-10), were isolated from the roots of Centranthera grandiflora. Their structures were determined by spectroscopic data analyses and comparing with the literature data. The absolute configuration of 1 was confirmed via 2 D NMR and electronic circular dichroism (ECD). All isolated compounds were evaluated for their inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production.

Peroxisome proliferator-activated receptor α (PPARα), a ligand-activated nuclear receptor critical for systemic lipid homeostasis, has been shown closely related to cardiac remodeling. However, the roles of cardiomyocyte PPARα in pressure overload-induced cardiac remodeling remains unclear because of lacking a cardiomyocyte-specific Ppara-deficient (Ppara(ΔCM)) mouse model. This study aimed to determine the specific role of cardiomyocyte PPARα in transverse aortic constriction (TAC)-induced cardiac remodeling using an inducible Ppara(ΔCM) mouse model. Ppara(ΔCM) and Ppara(fl/fl) mice were randomly subjected to sham or TAC for 2 weeks. Cardiomyocyte PPARα deficiency accelerated TAC-induced cardiac hypertrophy and fibrosis. Transcriptome analysis showed that genes related to fatty acid metabolism were dramatically downregulated, but genes critical for glycolysis were markedly upregulated in Ppara(ΔCM) hearts. Moreover, the hypertrophy-related genes, including genes involved in extracellular matrix (ECM) remodeling, cell adhesion, and cell migration, were upregulated in hypertrophic Ppara(ΔCM) hearts. Western blot analyses demonstrated an increased HIF1α protein level in hypertrophic Ppara(ΔCM) hearts. PET/CT analyses showed an enhanced glucose uptake in hypertrophic Ppara(ΔCM) hearts. Bioenergetic analyses further revealed that both basal and maximal oxygen consumption rates and ATP production were significantly increased in hypertrophic Ppara(fl/fl) hearts; however, these increases were markedly blunted in Ppara(ΔCM) hearts. In contrast, hypertrophic Ppara(ΔCM) hearts exhibited enhanced extracellular acidification rate (ECAR) capacity, as reflected by increased basal ECAR and glycolysis but decreased glycolytic reserve. These results suggest that cardiomyocyte PPARα is crucial for the homeostasis of both energy metabolism and ECM during TAC-induced cardiac remodeling, thus providing new insights into potential therapeutics of cardiac remodeling-related diseases.

Electrospun polyimide (PI) ultrafine non-woven fibrous mats (UFMs) with good heat-fusibility via hot press procedure were successfully fabricated. For this purpose, two organo-soluble PI resins were prepared via a two-step chemical imidization procedure from two isomeric oxydiphthalic dianhydrides, including the asymmetrical ODPA (2,3,3′,4′-oxydiphthalic dianhydride, or aODPA) and symmetrical ODPA (4,4′-oxydiphthalic dianhydride, or ODPA) with an aromatic diamine containing phenolphthalein unit in the main chain, 3,3-bis[4-(4-aminophenoxy)phenyl]phthalide (BAPPT), respectively. The derived PI-1 (aODPA-BAPPT) and PI-2 (ODPA-BAPPT) resins showed high numerical average molecular weights (Mn) over 105 g/mol and were easily soluble in polar aprotic solvents, such as N-methyl-2-pyrrolidinone (NMP) and N, N-dimethylacetamide (DMAc). PI-1 and PI-2 UFMs were successfully prepared from the PI solutions in DMAc via the one-step electrospinning procedure. Different rotating speeds of 500–2500 round per minute (rpm) for the cylindrical collector were set to investigate the effects of the fiber morphologies on the properties of the PI UFMs. The derived PI UFMs showed good thermal stability with the glass transition temperatures (Tg) over 280 °C and 5 % weight loss temperatures (T5%) higher than 510 °C in nitrogen. The PI UFMs could be successfully heat-sealed via the hot-press temperature at 320 °C (about 40 °C higher than Tg) for 60s with the pressure of 0.5 MPa.

Two organo-soluble polyimide resins containing phenyl-substituted quinoxaline units (PIPQ) were successfully prepared via the two-step chemical imidization procedure from an aromatic diamine, 6(7)-amino-2-(4-aminophenyl)-3-phenylquinoxaline (PQDA) and aromatic dianhydrides with flexible molecular structures. The derived PIPQ-1 resin from PQDA and 4,4′-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) and the PIPQ-2 resin from PQDA and 2,2-bis[4-(3,4-dicarboxyphenoxy)phenyl]propane dianhydride (BPADA) were all soluble in polar aprotic solvents, such as N-methyl-2-pyrrolidone (NMP) and N,N-dimethylacetamide (DMAc). The PIPQ/DMAc solutions with the solid contents of 25–35 wt% were used as the starting mediums and the PIPQ ultrafine non-woven fibrous membranes (UFMs) were successfully prepared by the one-step electrospinning (ES) procedure. For comparison, the standard polyimide reference electrospun UFM (PI-ref) was also fabricated via the two-step ES procedure from the soluble poly(amic acid) (PAA) precursor based on pyromellitic anhydride (PMDA) and 4,4′-oxydianiline (ODA), followed by thermal imidization at elevated temperatures from 80–300 °C. The fabricated PIPQ UFMs exhibited good thermal stability with the 5 % weight loss temperatures (T5%) of 537 °C for PIPQ-1 (6FDA-PQDA) and 517 °C for PIPQ-2 (BPADA-PQDA) in nitrogen, respectively. In addition, the PIPQ UFMs exhibited glass transition temperatures (Tg) higher than 252 °C. Meanwhile, the PIPQ UFMs exhibited improved optical properties with the reflectance values over 75 % at the wavelength of 457 nm and high whiteness. At last, the PIPQ UFMs showed greatly enhanced hydrolysis stability in highly alkaline aqueous solution (sodium hydroxide in water, 20 wt%) either at room temperature or at elevated temperature. The PIPQ UFMs survived even during the aging in boiling aqueous sodium hydroxide solution (concentration: 20 wt%) for 3 h while the PI-ref UFM totally hydrolyzed during the test.

Background Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood–brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration. Methods Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly. Results The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and −15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect. Conclusion Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic., Graphical Abstract

Background Caudate lobe hemangioma of the liver is relatively rare. Due to the unique anatomical location of the caudate lobe, the caudate lobectomy accounts for only 0.5% to 4% of hepatic resection, which is difficult to operate and takes a long time, and even has many postoperative complications. Case summary A 34-year-old female presented with a 1 year history of intermittent pain in the right side of the waist without obvious inducement. All laboratory blood tests were within normal limits. Indocyanine green 15 min retention was rated 2.9%, and Child-Pugh was rated A. Computed tomography and magnetic resonance imaging diagnosed giant hemangioma of the caudate lobe with hemangioma of left lobe of liver. After discussion, surgical treatment was performed, which lasted 410 min, with intraoperative bleeding of about 600 mL and postoperative pathological findings of cavernous hemangioma. There were no obvious postoperative complications, and the patient was discharged 10 d after surgery. Conclusion Caudate lobectomy is difficult due to its special anatomical location. Under the condition of fully exposing the anatomy of the first porta hepatis, the second porta hepatis, the third porta hepatis, the fourth porta hepatis and middle hepatic vein and combining with the Pringle maneuver, caudate lobectomy can be performed in a precise and safe process.

We have developed an efficient formylation of pyrroloisoquinolines using bromoisobutyrate and dimethyl sulfoxide as carbonyl reagent. Various formylated pyrroloisoquinolines could be prepared in good yields (up to 94%). This formylation process can be easily scaled up to gram scale with good yield. In most cases of pyrroloisoquinolines without methoxy groups, the combination of bromoisobutyrate and dimethyl sulfoxide could act as a bromination reagent, delivering brominated pyrroloisoquinolines in acceptable to good yields (up to 82%).

Two new lignan glucosides, tinsinlignans A and B ( 1 and 2 ), two new oxyneolignans, tinsinlignans C and D ( 3 and 4 ), along with one known analogue ( 5 ), were isolated from the stems of Tinospora sinensis. The structures of the new compounds were elucidated based on analysis of spectroscopic data, and the absolute configuration of 1 was determined through electronic circular dichroism (ECD) calculation based on the time-dependent density functional theory (TD-DFT). Compounds 1 − 4 were evaluated for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells and compounds 1 and 2 exhibited moderate inhibitory activities with IC50 values of 18.5 ± 2.0 and 28.8 ± 1.2 μmol·L−1, respectively.

AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus (ICP and DCP) in patients with retinal deep vascular complex ischemia (RDVCI), using 3D projection artifacts removal (3D PAR) optical coherence tomography angiography (OCTA). METHODS: RDVCI patients and gender- and age-matched healthy controls were assessed and underwent OCTA examinations. The parafoveal vessel density (PFVD) of retinal deep vascular complex (DVC), ICP, and DCP were analyzed, and the percentage of reduction (PR) of PFVD was calculated. RESULTS: Twenty-four eyes in 22 RDVCI patients (20 in acute phase and 4 in chronic phase) and 24 eyes of 22 healthy subjects were enrolled as the control group. Significant reduction of PFVD in DVC, ICP, and DCP was observed in comparison with the controls (DVC: acute: 43.59%±6.58% vs 49.92%±5.49%, PR=12.69%; chronic: 43.50%±3.33% vs 51.20%±3.80%, PR=15.04%. ICP: acute: 40.28%±7.91% vs 46.97%±7.14%, PR=14.23%; chronic: 41.48%±2.87% vs 46.43%±3.29%, PR=10.66%. DCP: acute: 45.44%±8.27% vs 51.51%±9.97%, PR=11.79%; chronic: 37.78%±3.48% vs 51.73%±5.17%, PR=26.97%; all P

Background Tissue-engineered bone grafts (TEBGs) that undergo vascularization and neurotization evolve into functioning bone tissue. Previously, we verified that implanting sensory nerve tracts into TEBGs promoted osteogenesis. However, the precise mechanisms and interaction between seed cells were not explored. In this study, we hypothesized that neurotization may influence the osteogenesis of TEBGs through vascularization. Methods We cultured rat Schwann cells (SCs), aortic endothelial cells (AECs), and bone marrow-derived mesenchymal stem cells (BM-MSCs) and then obtained BM-MSC-derived induced endothelial cells (IECs) and induced osteoblasts (IOBs). IECs and AECs were cultured in an SC-conditioned medium (SC-CM) to assess proliferation, migration, capillary-like tube formation, and angiogenesis, and the vascular endothelial growth factor (VEGF) levels in the supernatants were detected. We established an indirect coculture model to detect the expression of nestin and VEGF receptors in IECs and tissue inhibitor of metalloproteinase (TIMP)-2 in SCs. Then, SCs, IECs, and IOBs were labeled and loaded into a β-tricalcium phosphate scaffold to induce prevascularization, and the scaffold was implanted into a 6-mm-long defect of rat femurs. Three groups were set up according to the loaded cells: I, SCs, and IECs (coculture for 3 days) plus IOBs; II, IECs (culture for 3 days) plus IOBs; III, IOBs. Nestin and TIMP-2 expression and osteogenesis of TEBGs were evaluated at 12 weeks post-implantation through histological and radiological assessments. Results We found that SC-CM promoted IEC proliferation, migration, capillary-like tube formation, and angiogenesis, but no similar effects were observed for AECs. IECs expressed nestin extensively, while AECs barely expressed nestin, and SC-CM promoted the VEGF secretion of IECs. In the coculture model, SCs promoted nestin and VEGF receptor expression in IECs, and IECs inhibited TIMP-2 expression in SCs. The promotion of prevascularized TEBGs by SCs and IECs in group I augmented new bone formation at 6 and 12 weeks. Nestin expression was higher in group I than in the other groups, while TIMP-2 expression was lower at 12 weeks. Conclusions This study demonstrated that SCs can promote TEBG osteogenesis via IECs and further revealed the related specific characteristics of IECs, providing preliminary cytological evidence for neurotization of TEBGs.

Liamocins synthesized by Aureobasidium spp. are glycolipids composed of a single mannitol or arabitol headgroup linked to either three, four or even six 3,5-dihydroxydecanoic ester tail-groups. The...

The incidence of nonalcoholic steatohepatitis (NASH) is increasing worldwide. Activation of Kupffer cells (KCs) is central to the development of diet-induced NASH. We investigated whether a combination of two active chemical components, geniposide and chlorogenic acid (GC), at a specific ratio (67 : 1), ameliorates diet-induced NASH and the underlying mechanisms involved. C57BL/6J mice exposed to a high-fat and high-cholesterol (HFHC) diet containing cholesterol, choline, and high-sugar drinking water, as well as RAW264.7 cells stimulated with lipopolysaccharide (LPS) were studied. The combination exerted a therapeutic effect on HFHC-induced NASH in mice. Simultaneously, GC was found to reduce the expression of cytokines secreted by hepatic macrophages, including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6, monocyte chemotactic protein 1 (MCP-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, GC reduced the number of KCs expressing F4/80. Furthermore, TNF-α, inducible nitric oxide synthase (INOS), IL-1β, and IL-6 mRNA and TNF-α protein expression levels were suppressed upon GC treatment in RAW264.7 cells. Our findings suggest that GC has a strong anti-inflammatory effect in NASH, and this effect can be attributed to the suppression of KC activity in the liver.

Luminescent copper(I) halide complexes with bi- and tridentate rigid ligands have gained wide research interests. In this paper, six tetracoordinate dinuclear copper(I) halide complexes, Cu2X2(ppda)2 [ppda = 2-[2-(dimethylamino)phenyl(phenyl)phosphino]-N,N-dimethylaniline, X = I (1), Br (2), Cl (3)] and Cu2X2(pfda)2 [pfda = 2-[2-(dimethylamino)-4-(trifluoromethyl)phenyl(phenyl)phosphino]-N,N-dimethyl-5-trifluoromethylaniline, X = I (4), Br (5), Cl (6)], were successfully prepared and systematically characterized on their structures and photophysical properties. Complexes 1-5 have a centrosymmetric form with a planar Cu2X2 unit, and complex 6 has a mirror symmetry form with a butterfly-shaped Cu2X2. Solid complexes 1, 4, and 5 emit delayed fluorescence at room temperature, intense blue to greenish yellow (λmax = 443-570 nm) light, and their peak wavelengths are located at 443-570 nm with microsecond lifetimes (τ = 0.4-19.2 μs, ΦPL = 0.05-0.48). Complexes 2, 3, and 6 show prompt fluorescence, very weak yellowish green to yellow (λmax = 534-595 nm) emission with peak wavelengths at 534-595 nm, and lifetimes in nanoseconds (τ = 4.4-9.3 ns, ΦPL < 0.0001). (Metal + halide) to ligand and intraligand charge transitions are the main origin of the emission of the complexes. Solution-processed, complex-4-based nondoped and doped devices emit yellow green light with CIE coordinated at (0.41, 0.51), a maximum EQE up to 0.17%, and luminance reaching 75.52 cd/m2.

Compared with traditional polymers, biopolymers are more environmentally friendly due to their sustainable sources, easy decomposition and naturally recycled by biological processes. Among all biopolymers, chitosan (CS) proves attractive for several adsorption-related applications such as in gas capture and removal of dyes or heavy metal ions. However, there are considerable drawbacks such as unstable yield, non-uniform sizes, lack of process repeatability, low mechanical strength and chemical resistance. Thus, physical and chemical modifications have been proposed to obtain stable size and improved mechanical property of CS beads, microspheres, film or fiber. This paper introduces the research background of CS and modified CS as an adsorbent and analyzes the modification, application and adsorption mechanism of CS and CS composite materials. The research progress of the adsorption of metal ions, dyes and anions by CS and CS composite materials is reviewed, and the main factors affecting their adsorption performance are summarized. Finally, the development trend of CS as adsorbents is prospected.

The enhancement of electron-and-hole separation efficiency and facile generation of reactive oxygen species are significant factors for performance improvement of photocatalysts in selective toluen...

The synthesis and characterization of new pyran derivatives (1–3) were realized by means of infrared spectroscopy (IR), 1H nuclearmagnetic resonance spectroscopy (1H NMR), high resolution mass spectrum (HRMS) and single crystal X-ray crystallography. The anti-proliferation activity of compounds 1–3 was investigated against human ovarian cancer cells CAOV3 by Cell Counting Kit-8 (CCK-8) assay. The RT-PCR assay was performed to detect the relative expression level of the Foxm1b in the CAOV3 cell line after treated with compounds 1–3. Furthermore, molecular docking studies supported the biological assay data and suggested that compared with compounds 1 and 3, compound 2 has stronger interaction with protein.

Methane hydrate (MH) has attracted increasing interest as one potential alternative clean energy. However, creating efficient MH field tests is a great challenge faced by the industry. It requires ...

It is challenging to develop highly stable lanthanide luminescent sensors for detecting heavy metal ions and nitroaromatics in view of the human health and environmental security. To this end, two water stable Ln-MOFs with the chemical constitution of {[Ln(HL)]·3DMF·3H2O}n (Ln = Eu, LZG-Eu and Ln = Tb, LZG-Tb) have been developed solvothermally using a multidentate ligand (H4L) with the central phenyl backbone bisubstituted by 2,6-pyridine-dicarboxylic acid at the para-position, H4L = 1,4-bis(2',2'',6',6''-tetracarboxy-1,4':4,4''-pyridyl)benzene. Single crystal analysis demonstrates that two novel Ln-MOFs feature 4,4,4-connected nets with an unprecedented topology symbol of {42·6·83}2{42·62·82}{42·84} and contain two kinds of one-dimensional channels. Powder X-ray diffraction as well as the luminescence determination results indicate that they retain their crystallinity and structural integrity in harsh acidic and basic conditions with pH in the range of 4-11. Moreover, they are highly luminescent, which makes them excellent chemical sensors for detecting Cu2+ and 4-NP (4-nitrophenol) with high selectivity and sensitivity in aqueous media such as deionized water, tap water, and river water based on distinct quenching effects. To the best of our knowledge, their detection limits are lower than those documented so far. In addition, the quenching efficiency of 4-NP was retained in the presence of interfering ions even after the compounds were used for five cycles, which makes them attractive, reliable, visual, and recyclable luminescent Ln-MOF sensor materials for 4-NP. The recognition mechanism for Cu2+ could be attributed to the dissociation of the main framework induced by Cu2+ and the subsequent formation of a Cu2+ coordination species and that for 4-NP is considered to be multi-quenching mechanisms dominated by competition absorption.

Designing a structurally stable anode with a high reversible capacity for sodium ion batteries (SIBs) is particularly crucial so that batteries are able to meet the requirements for large-scale applications in grid electrical energy storage. Polyaromatic hydrocarbons (PAHs) are organic molecules with well-defined structures that demonstrate excellent performance in lithium storage. Based on our well-established correlation between battery property and molecular structure, for the first time, we applied a recently synthesized hexabenzocoronene (HBC) and corresponding derivate HBC–OMe to engage in sodium storage. The HBC molecule forms self-assemblies with a long-range ordered face-center cubed (fcc) structure due to the interaction between two HBC moieties. Such a unique 3D structure is expected to generate a strong π–π interaction between flakes and thus yield amazing durability during the long-term cycling process. In addition, the surface-dominated Na+ storage mechanism can facilitate the Na+ transport kinetics and simultaneously alleviate the structural strain during charging–discharging cycles. Benefiting from the coupling effect of the surface-driven capacitive process and the robust 3D self-assembled hierarchical nature, an oxygen-containing sample, HBC–OMe, exhibited an extraordinary sodium storage capability, attaining a high capacity of 506 mA h g−1 at 0.1 A g−1 with excellent rate capability (217 mA h g−1 at 5 A g−1) and superior long-term cycling performance (290 mA h g−1 at 2 A g−1 with negligible capacity fade after 1000 cycles).

In the past years, sodium-ion batteries (SIBs) have attracted much attention due to their potential application in large-scale energy storage. However, for now, it is difficult for anode materials to achieve further practical application. In this work, we designed a sandwich structure in which SnO nanoparticles were entrapped between the layers of reduced graphene oxide (SnO/rGO) via freeze drying. The unique structure can not only offer a 3D carbon network but also relieve volume expansion during discharge/charge processes. When used as an anode material for SIBs, the material exhibits excellent rate capability and stable cycling performance. It can be found that a reversible capacity of 132.3 mA h g−1 can be obtained even at a current density of 5 A g−1. In addition, SnO/rGO shows a charge capacity of 109.5 mA h g−1 with a capacity retention of 70.62% after 1200 cycles at 4 A g−1. When assembled with Na3V2(PO4)2O2F (NVPOF) as the cathode, the sodium-ion full cells also display high rate performance, suggesting a reversible capacity of 65.7 mA h g−1 at 20C and an energy density of 138.95 W h kg−1 at −0.1C. The unique structure provides a simple and facile method to achieve high electrochemical performance which is beneficial for developing commercial anode materials for SIBs.

The biological valorization of lignin to aromatic compounds has attracted extensive attention as this route actively contributes to the bioeconomy. However, the diversity of lignin-derived monomers causes difficulties in the biological upgrading of lignin. Protocatechuic acid is an important potential precursor in polymer synthesis and the pharmaceutical industry. This study aims to effectively funnel lignin derived monomers to a compound platform, protocatechuic acid, by designing a cell factory of engineered Saccharomyces cerevisiae. A biological funnel pathway was successfully constructed in S. cerevisiae to produce protocatechuic acid from p-coumaric acid and ferulic acid. A S. cerevisiae chassis was optimized to reduce the further metabolism of intermediates and the generation of byproducts with the deletion of ADH6, ADH7, BDH2, and FDC1 genes. The key genes fcs, ech, and vdh in the CoA-dependent non-β-oxidation pathway were screened to produce the precursor of protocatechuic acid, including p-hydroxybenzoic acid and vanillic acid from p-coumaric acid and ferulic acid, respectively. Following that, the regulatory module of tetrahydrofolic acid metabolism was introduced into the biological funnel pathway with the overexpression of MET6 and metf1 genes and knockout of MHT1 and SAM4 genes, by which 120 mg L−1 protocatechuic acid was produced from ferulic acid. Excitingly, by integrating the multi-copy heterologous pobA gene in the yPCA12 strain, the titer of protocatechuic acid was improved to 720 mg L−1 from p-coumaric acid. Interestingly, the yPCA12 strain also exhibited a good ligninolytic capacity of the actual lignin streams. Together with fermentation optimization, the highest titer of 810 mg L−1 protocatechuic acid was obtained from alkaline pretreatment liquor. Overall, a biological funnel pathway of lignin-derived monomers was constructed in S. cerevisiae to produce a compound platform, protocatechuic acid, for valuable product synthesis. The design of the S. cerevisiae cell factory could be a promising potential route to make lignin valorization sustainable.

Inexpensive and readily available calcium carbide (CaC2) has been developed as a promoter for the transition metal-free, solvent-free and one-pot conversion of acid chlorides and dimethyl sulfoxide (DMSO) to the corresponding β-keto sulfoxide. Four drug molecules were successfully converted to their β-keto sulfoxides using this method, emphasising its potential utility in medicinal chemistry.

The first-row transition metal compounds, [MII(L1)2](ClO4)2 (M = Ni (1); Co (2)), have been prepared by treatment of a neutral tetradentate ligand (L1 = N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide) with metal perchlorate salts in MeOH. Both compounds have been structurally characterized by X-ray crystallography and it was found that the coordination numbers are 6 and 7, respectively. The reaction of 6,6′-bis(2-tbutyl-tetrazol-5-yl)-2,2′-bipyridine (L2) with hydrated FeII(ClO4)2 afforded a 8-coordinate Fe(II) compound, [FeII(L2)2](ClO4)2 (3); however its reaction with hydrated CoII(ClO4)2 resulted in 6-coordinate [CoII(L2)2](ClO4)2. It is interesting to observe field-induced slow magnetic relaxation in the 7-coordinate Co(II) compound 2 and 8-coordinate Fe(II) compound 3, which further supports the validity of designing high coordination number compounds as single-molecule magnets. Direct current magnetic studies demonstrate that 2 has a very large positive D value (56.2 cm−1) and a small E value (0.66 cm−1), indicating easy plane magnetic anisotropy. Consistent with the larger D value, an effective spin-reversal barrier of Ueff = 100 K (71.4 cm−1) is obtained, which is the highest value reported for 7-coordinate Co(II) complexes with a pentagonal bipyramidal geometry. In contrast, 8-coordinate Fe(II) compound 3 exhibits uniaxial magnetic anisotropy.

Background Gastric cancer (GC) is one of the most common and deadliest types of cancer worldwide due to its delayed diagnosis and high metastatic frequency, but its exact pathogenesis has not been fully elucidated. ETS homologous factor (EHF) is an important member of the ETS family and contributes to the pathogenesis of multiple malignant tumors. To date, whether EHF participates in the development of GC via the c-Met signaling pathway remains unclear. Aim To investigate the role and mechanism of EHF in the occurrence and development of GC. Methods The expression of EHF mRNA in GC tissues and cell lines was measured by quantitative PCR. Western blotting was performed to determine the protein expression of EHF, c-Met, and its downstream signal molecules. The EHF expression in GC tissues was further detected by immunohistochemical staining. To investigate the role of EHF in GC oncogenesis, small interfering RNA (siRNA) against EHF was transfected into GC cells. The cell proliferation of GC cells was determined by Cell Counting Kit-8 and colony formation assays. Flow cytometry was performed following Annexin V/propidium iodide (PI) to identify apoptotic cells and PI staining to analyze the cell cycle. Cell migration and invasion were assessed by transwell assays. Results The data showed that EHF was upregulated in GC tissues and cell lines in which increased expression of c-Met was also observed. Silencing of EHF by siRNA reduced the proliferation of GC cells. Inhibition of EHF induced significant apoptosis and cell cycle arrest in GC cells. Cell migration and invasion were significantly inhibited. EHF silencing led to c-Met downregulation and further blocked the Ras/c-Raf/extracellular signal-related kinase 1/2 (Erk1/2) pathway. Additionally, phosphatase and tensin homolog was upregulated and glycogen synthase kinase 3 beta was deactivated. Moreover, inactivation of signal transducer and activator of transcription 3 was detected following EHF inhibition, leading to inhibition of the epithelial-to-mesenchymal transition (EMT). Conclusion These results suggest that EHF plays a key role in cell proliferation, invasion, apoptosis, the cell cycle and EMT via the c-Met pathway. Therefore, EHF may serve as an antineoplastic target for the diagnosis and treatment of GC.

One novel two-dimensional (2D) terbium-based framework [Tb (L2−) (Ac) (DMA)]n (1) (H2L = 4'-(3,5-dicarboxyphenyl)-4,2':6′,4″-terpyridine) was successfully isolated and structurally characterized. The structural analysis reveals that two Tb3+ ions in 1 are bridged by two η1:η1:μ2 carboxylates from L2− to form a binuclear unit, which is further linked by L2− to generate a 2D layer with kgd topology. Moreover, 1 displays excellent thermostability and extensive solvent stability. Luminescent measurements reveal that 1 can be used as a recyclable luminescent probe for detecting pyridine with the lowest detection limit of 0.12 vol%, and the luminescent mechanism is also discussed.

The photocatalyst is a crucial factor in determining solar-to-H2 efficiency for solar-driven water splitting. Here, the FeP/CdS well-defined heterostructure was elaborately designed and successfully constructed in-situ to achieve efficient water splitting by using a simple and green solvothermal approach. In the synthetic process, the ethylenediamine plays an important role in the construction of intimate contact interface between FeP and CdS. This good quality FeP/CdS heterostructure can efficiently promote charge separation and transportation, and therefore the charge recombination of CdS was significantly suppressed. As a result, the as-synthesized FeP/CdS heterostructure showed excellent photocatalytic performance under visible-light irradiation with an optimal hydrogen evolution rate of 37.92 mmol g−1 h−1 and an apparent quantum yield of 31.50% at 420 nm far exceeding that of pristine CdS by more than 122 folds. This rate, to the best of our knowledge, outperforms other similar catalytic systems.

Cyclic dimeric adenosine 3'-5'-monophosphate (c-di-AMP) is a recently discovered nucleotide messenger in bacteria. It plays an important role in signaling, transcription, and cell physiology, such as in bacterial growth, potassium transport, fatty acid synthesis, the metabolic balance of cell wall components, and biofilm formation. Exopolysaccharides (EPSs) have distinct physico-chemical properties and diverse bioactivities including antibacterial, hypolipidemic, and antioxidative activities, and they are widely used in the food, pharmaceutical, and cosmetic industries. Although c-di-AMP has been demonstrated to regulate the biosynthesis of bacterial EPSs, only a single c-di-AMP receptor, CabpA, has been identified in EPS synthesis. With the aim of describing current understanding of the regulation of microbial EPSs, this review summarizes c-di-AMP biosynthesis and degradation as well as the mechanism through which c-di-AMP regulates bacterial EPSs.

Schisandra chinensis (Turcz.) Baill., Schisandraceae, is a common Chinese traditional medicine for the treatment of nervous system disorders and cardiovascular diseases. However, little is known about its efficacy in treating gastrointestinal diseases. In the present study, the protective effect of the ethanol extract of S. chinensis against ethanol-induced acute gastric lesions was investigated in mice. Furthermore, we developed a method based on high-performance liquid chromatography for the quantification of bioactive lignans with a dibenzocyclooctadiene skeleton. The ethanol extract of S. chinensis significantly decreased the ulcer index, sheltered mucosa from lesions, increased levels of superoxide dismutase, decreased malondialdehyde levels, and downregulated plasma levels of tumor necrosis factor-α and interleukin-1β. Our findings demonstrated the gastroprotective properties of the ethanol extract of S. chinensis.

The high efficiency, convenience and diversity of clustered regular interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems are driving a technological revolution in the gene editing of lactic acid bacteria (LAB). Cas-RNA cassettes have been adopted as tools to perform gene deletion, insertion and point mutation in several species of LAB. In this article, we describe the basic mechanisms of the CRISPR-Cas system, and the current gene editing methods available, focusing on the CRISPR-Cas models developed for LAB. We also compare the different types of CRISPR-Cas-based genomic manipulations classified according to the different Cas proteins and the type of recombineering, and discuss the rapidly evolving landscape of CRISPR-Cas application in LAB.

BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis (UC). Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice. Resveratrol exerts anti-inflammatory functions by regulating autophagy. AIM To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium (DSS)-induced ulcerative colitis mice. METHODS Male C57BL/6 mice were divided into four groups: negative control group, DSS model group, DSS + resveratrol group, and DSS + 5-aminosalicylic acid group. The severity of colitis was assessed by the disease activity index, serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay. Colon tissues were stained with haematoxylin and eosin, and mucosal damage was evaluated by mean histological score. The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis. In addition, the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot, and morphology of autophagy was observed by transmission electron microscopy. RESULTS The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42, 3.81, and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α, interleukin-6 and interleukin-1β, respectively, in DSS-induced colitis mice compared with DSS group (P < 0.05). The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased, and were increased in resveratrol-treated colitis group. Resveratrol also increased the levels of LC3B (by 1.39-fold compared with DSS group) and Beclin-1 (by 1.49-fold compared with DSS group) (P < 0.05), as well as the number of autophagosomes, which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy. CONCLUSION Resveratrol treatment decreased the expression of inflammatory factors, increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction; this effect may be achieved by enhancing autophagy in intestinal epithelial cells.

Oxidative stress-mediated neuron damage is considered an important contributor to the pathogenesis and development of neurodegenerative diseases. Although β-asarone is widely known for its neuroprotective pharmacological properties, the exact mechanism of β-asarone against oxidative stress has not been fully elucidated. The aim of the present study was to investigate underlying mechanisms of β-asarone against oxidative damage in PC12 cells. Our results demonstrated that the treatment of β-asarone significantly alleviated the reduction in cell viability and the excessive accumulation of lactate dehydrogenase (LDH), malondialdehyde (MDA) and reactive oxygen species (ROS) by increasing the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH). Moreover, β-asarone pretreatment also activated nuclear factor 2 erythroid-related factor 2 (Nrf2) and its downstream target heme oxygenase-1 (HO-1), which was involved in quenching reactive oxygen to inhibit oxidative stress. Furthermore, when silenced by Nrf2 siRNA, the protective effect of β-asarone was reduced and the oxidative stress induced by H2O2 was enhanced. In conclusion, our findings revealed that β-asarone could reduce oxidative stress via activating Nrf2/HO-1 pathway in PC12 cells, highlighting the potential therapeutic role of β-asarone in neurodegenerative diseases.

Selective photooxidation of toluene to benzaldehyde using O2 as an oxidant has the advantages of mild reaction conditions and excellent atomic economy, but it often suffers from low conversion effi...

Exosome-associated liquid biopsies are hampered by challenges in the exosomal quantification and phenotyping. Here, we present a bioinspired exosome-activated DNA molecular machine (ExoADM) with multivalent cyclic amplification that enables highly sensitive detection and phenotyping of circulating exosomes. ExoADM harbors two (an exposed and a hidden) DNA toehold domains that actuate sequential branch migration and multivalent recycling in response to exosomal surface markers. Importantly, this self-powered ExoADM achieves a high sensitivity (33 particles/μL) and is compatible with another DNA nanomachine targeting different exosomal surface markers for dual-color phenotyping. Using this strategy, we can simultaneously track the dynamic changes of ExoPD-L1 and ExoCD63 expression induced by signaling molecules. Further, we found that their expression levels on circulating exosomes could well differentiate cancer patients from the normal individuals. More importantly, ExoPD-L1 levels could reflect the efficacy of different treatments and guide anti-PD-1 immunotherapy, suggesting the potential of ExoPD-L1 in clinical diagnosis and targeted therapy monitoring.

Vesicular stomatitis (VS), characterized by vesicular lesions, produces significant economic losses in livestock industry. Infection by its causative agent, VS virus (VSV), has been previously shown to be mediated by the glycoprotein (G) during attachment, endocytosis and membrane fusion. In the current study, we revealed a novel role of VSV G protein in negative regulation of host cell pro-inflammatory responses. We determined that VSV G protein inhibited lipopolysaccharide (LPS)-induced pro-inflammatory responses as naïve VSV virions in murine peritoneal macrophage-like cell line RAW 264.7. Furthermore, we identified that VSV G protein suppressed nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK)-mediated pro-inflammatory pathways in a dose-dependent manner. Moreover, we demonstrated that α2-3-linked sialic acids on VSV G protein were involved in antagonizing NF-κB- and MAPK-mediated pro-inflammatory responses. All these results expand the knowledge of VSV pathogenesis and strengthen the importance of VSV G protein in host innate immunity, which support implications for the development of VSV-based vaccination and oncolysis.

Biobutanol, as an advanced biofuel substitute, is reviving via microbial acetone-butanol-ethanol (ABE) fermentation. However, this biochemical process compromises low butanol production and product...

Development of degradable polyester elastomers plays an important role in the applications of soft mateirals. Noncrystalline polymenthides (PMs) from menthol derived lactone monomers are excellent soft segments for preparing degradable polyester elastomers. By using cyclic trimeric phosphazene base (CTPB) as an organocatalyst, we successfully synthesized PMs with different molecular weights (8.2 kDa to 100.7 kDa) in high yields via ring-opening polymerization (ROP) of menthide. When a CTPB/urea binary catalytic system was adopted, the polymerizations proceeded in a more controlled manner. Using glycerol as initiator, star shaped PMs with well-defined structure were synthesized and subsequently end-capped by acrylate. UV irradiation of the terminal acrylate groups in the star-shaped PMs resulted in formation of chemically cross-linked polyester elastomers without heat or other stimuli. The obtained polyester elastomers exhibit matched modulus (3.8–5.5 MPa), tensile strength (0.56–0.68 MPa), and strain at break (280%–320%) with soft body tissues, displaying great potential in biomedical applications.

One main challenge for phosphate cathodes in sodium-ion batteries (SIBs) is to increase the working voltage and energy density to promote its practicability. Herein, an advanced Na3V2(PO4)2F3@C cathode is prepared successfully for sodium-ion full cells. It is revealed that, carbon coating can not only enhance the electronic conductivity and electrode kinetics of Na3V2(PO4)2F3@C and inhibit the growth of particles (i.e., shorten the Na+-migration path), but also unexpectedly for the first time adjust the dis-/charging plateaux at different voltage ranges to increase the mean voltage (from 3.59 to 3.71 V) and energy density (from 336.0 to 428.5 Wh kg−1) of phosphate cathode material. As a result, when used as cathode for SIBs, the prepared Na3V2(PO4)2F3@C delivers much improved electrochemical properties in terms of larger specifc capacity (115.9 vs. 93.5 mAh g−1), more outstanding high-rate capability (e.g., 87.3 vs. 60.5 mAh g−1 at 10 C), higher energy density, and better cycling performance, compared to pristine Na3V2(PO4)2F3. Reasons for the enhanced electrochemical properties include ionicity enhancement of lattice induced by carbon coating, improved electrode kinetics and electronic conductivity, and high stability of lattice, which is elucidated clearly through the contrastive characterization and electrochemical studies. Moreover, excellent energy-storage performance in sodium-ion full cells further demonstrate the extremely high possibility of Na3V2(PO4)2F3@C cathode for practical applications.

Low angle dependence single green polystyrene colloidal crystal films were prepared by vertical deposition method using polystyrene microspheres with size of 380 ± 10 nm as raw material and further modified by adding nano-carbon. Without nano-carbon addition, the film showed various colors with changing the angle of incident light under natural light. With nano-carbon addition, saturation and angle dependence of the polystyrene colloidal crystal film were remarkably improved. With 0.01 wt % nano-carbon addition, since the stray light of other wavelengths other than the band gap light was absorbed by the added nano-carbon, the film showed only green color under different angles of incident light, suggesting that the film had low angle dependence. It is significant in the research of color behavior and is helpful to obtain single color polystyrene colloidal crystal film.