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Neuroinflammation is an important secondary aggravating factor in spinal cord injury (SCI). Inhibition of the inflammatory response is critical for SCI treatment. Glycyrrhizic acid (GA) is an anti-inflammatory drug, but its utility for SCI is unclear. This study aimed to evaluate the effects of GA on inflammation after SCI and the underlying mechanism.Cell counting kit-8 assays were performed to assess the viability of highly aggressively proliferating immortalized cells that had been treated with lipopolysaccharide (LPS) and/or GA. Reverse transcription quantitative polymerase chain reaction and Western blotting were performed to assess expression of high mobility group box-1 protein (HMGB1), ionized calcium binding adaptor molecule 1, and inflammatory factors in vitro and in vivo. GA (100 mg/kg) was intraperitoneally injected into rats. Anti-inflammatory effects of GA were analyzed in SCI tissues. p38/Jun N-terminal kinase signaling pathway proteins were analyzed by Western blotting.Cell counting kit-8 assay results showed that treatment with 100 ng/mL LPS for 12 hours was optimal. After LPS treatment, highly aggressively proliferating immortalized cells were activated; messenger RNA expression levels of HMGB1 and inflammatory factors were increased. GA significantly inhibited LPS-induced HMGB1 expression and inflammatory responses, as determined by reverse transcription quantitative polymerase chain reaction and Western blotting. Transfection with an HMGB1-overexpression plasmid reversed the anti-inflammatory effects of GA. In addition, intraperitoneal injection of GA (100 mg/kg) into rats for 3 days significantly reduced expression levels of HMGB1 and inflammatory factors after SCI in vivo. GA reduced phosphorylation, but not levels, of p38 and Jun N-terminal kinase proteins.GA attenuates the inflammatory response after SCI by inhibiting HMGB1 through the p38/JNK signaling pathway and thus has therapeutic potential for SCI.

The pro-inflammatory cytokine tumor necrosis factor (TNF)-α augments intracellular Ca2+ signaling and contractile responses of airway smooth muscles, leading to airway hyperresponsiveness (AHR). However, the underlying mechanism has not been fully elucidated. This study aims to investigate the cellular mechanism of the potentiated contraction of mouse tracheal smooth muscle induced by TNF-α. The results revealed that TNF-α triggered facilitation of mouse tracheal smooth muscle contraction in an epithelium-independent manner. The TNF-α-induced hypercontractility could be suppressed by the protein kinase C (PKC) inhibitor GF109203X, the tyrosine kinase inhibitor genistein, the Src inhibitor PP2 or the L-type voltage-dependent Ca2+ channel blocker nifedipine. After TNF-α incubation, the α1C L-type Ca2+ channel (CaV1.2) was up-regulated in primary cultured mouse tracheal smooth muscle cells. Pronounced phosphotyrosine level was also observed in mouse tracheas. In conclusion, this study demonstrated that TNF-α enhanced airway smooth muscle contraction via PKC- Src-CaV1.2 pathways, which provides novel insights into the pathological role of pro-inflammatory cytokines in mediating AHR.

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.

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%).

Riboflavin serves as the direct precursor of the FAD/FMN coenzymes and is biosynthesized in most prokaryotes, fungi and plants. Fungal Rib2 possesses a deaminase domain for deamination of pyrimidine in the third step of riboflavin biosynthesis. Here, four high-resolution crystal structures of a Rib2 deaminase from Aspergillus oryzae (AoRib2) are reported which display three distinct occluded, open and complex forms that are involved in substrate binding and catalysis. In addition to the deaminase domain, AoRib2 contains a unique C-terminal segment which is rich in charged residues. Deletion of this unique segment has no effect on either enzyme activity or protein stability. Nevertheless, the C-terminal αF helix preceding the segment plays a role in maintaining protein stability and activity. Unexpectedly, AoRib2 is the first mononucleotide deaminase found to exist as a monomer, perhaps due to the assistance of its unique longer loops (Lβ1–β2, LαB–β3 and LαC–β4). These results form the basis for a molecular understanding of riboflavin biosynthesis in fungi and might assist in the development of antibiotics.

Two novel metal–organic coordination complexes based on L [L = 3,6-bis(imidazol-1-yl)pyridazine], which could also be called as [Ni(L)(1,3,5-H2BTC)2H2O]n 1 (1,3,5-H3BTC = 1,3,5-benzenetricarboxylic acid) and {[Ni2(L)(2,6-PYDC)2(H2O)2]·5H2O}n 2 (2,6-H2PYDC = 2,6-pyridine dicarboxylic acid) have been formed using solvothermal method by reaction of Ni(II) salts with the L ligand in the presence of different carboxylate ligands (1,3,5-H3BTC for 1 and 2,6-H2PYDC for 2). The treatment activity of compounds 1 and 2 on the neonatal hypoxic-ischemic encephalopathy was estimated, then the relevant mechanism was discussed. Firstly, the quantity of the tumor necrosis factor-α (TNF-α) and neuron-specific enolase (NSE) in the cerebrospinal fluid was measured by enzyme linked immunosorbent assay (ELISA) detection kit. In addition to this, the expression levels of the glutamate receptor on the brain nerve cells were estimated by real time reverse transcription-polymerase chain reaction (RT-PCR).

Herein, we have designed and developed a heteromultivalent chitosan base α-Fe2O3/Gadofullerene (GdF) hybrid composite through a simple chemical precipitation method. Unlike other methods, the addition of external stabilizing agents to generate GdF nanoparticles (NPs) was not necessary herein. The prepared chitosan-α-Fe2O3/GdF hybrid nanocomposites were characterized using UV, FT-IR, XRD and morphological microscopic analyses. The results showed that α-Fe2O3 and GdF hybrid nanocomposites were successfully grown on the surface of chitosan. The FT-IR vibration peaks showed the formation of Fe2O3 NPs, and the vibration peak for Fe–O was 568 cm−1. The broad absorption peak observed in the range of 250–350 nm and a sharp absorption peak at 219 nm represents the UV absorption of the synthesized hybrid composites. XRD pattern showed sharp peaks of crystallinity and purity of α-Fe2O3 nanoparticles. Finally, the synthesized chitosan-α-Fe2O3/GdF hybrid composites were screened for their antibacterial resistance against the Escherichia coli, Pseudomonas aeruginosa, Bacilus subtilis, and Staphylococcus aereus. In addition, in vitro biocompatibility results exhibited that developed hybrid samples have provided high cell compatibility with fibroblast (L929) cell line. The in vivo bio inspired nanotherapeutics have the potential action to effective inhibition ability on antibiotic-resistant P. aeruginosa, which has been main factor of inducing pneumonia. In conclusion, we expect biomimicking systems combined with the effective antibacterial agent could be the suitable next generation therapeutic potential factors for prevention and treatment of antibiotic-resistant pneumonia.

Background The aims of this study were to detect the level of histone crotonylation in prostate cancer (PCa) tissues, analyze the correlations between its level and clinical stage and grade, and explore the effects of bromodomain-containing protein 4 (BRD4) inhibitors and sodium crotonate on the histone crotonylation in PCa cell lines and on the functions of PCa cells. Methods PCa tissues from 72 patients and adjacent tissues from 7 patients were collected, and immunohistochemistry was used to measure the level of histone crotonylation. Three human PCa cell lines, PC-3, LNCaP, and C42B, were selected and treated with IC50 value of I-BET762, I-BET726, and CPI-203, respectively. Next, short hairpin RNA (shRNA) transient knockdown was used to inhibit BRD4 expression. Histone crotonylation level and the expression of acetylase were determined by Western blotting. Finally, cell proliferation, migration, and invasion were measured with Cell Counting Kit-8 assay, scratch test, and Transwell test respectively. Results The level of histone crotonylation in PCa tissue was higher than that in adjacent tissues, and histone lysine crotonylation (Kcr) increased with the increasing malignancy of PCa. Treatments with I-BET762, I-BET726, and CPI-203 could inhibit the proliferation, migration, and invasion of PCa cell lines including PC-3, LNCaP, and C42B, and could also regulate the histone crotonylation and androgen receptor signaling pathways via the regulation of BRD4 expression. Conclusions PCa is closely related to histone crotonylation. Inhibition of BRD4 expression can inhibit the proliferation, migration, and invasion of PCa cells.

The application of phosphorene and graphane in different photoelectric devices and energy reserves has attracted wide attention. Here, we investigated the Raman spectra, phonon dispersion and vibration modes of four phosphorene monolayer polymorphs and four graphane allotropes with the corresponding crystal structures to analyze the structure correlation between them. Based on the "three identical, one divergent" pattern found in the sp3 hybrid atomic orbitals of phosphorene and graphane, four new graphane conformers with different hydrogenation modes named γδ-G, αγ-G, βγ-G and αδ-G are successfully predicted. Among these four new graphane conformers, βγ-G has the lowest binding energy, which is only 0.02 eV per atom higher than β-G, the most stable one among all graphane theoretically predicted. This means that βγ-G may co-exist with β-G during the experimental synthesis of graphane, which can be distinguished from the side views with threefold structures for βγ-G and twofold structures for β-G. All the new graphane conformers are direct-band-gap semiconductors with band gaps more than 3 eV, which indicate their great potential in optoelectronic devices. Furthermore, three of them exhibit in-plane negative Poisson's ratios under tensile deformation.

6H-isoindolo[2,1-a]indoles were accessed via a Rh(III)-catalyzed N–H free indole directed C–H activation dialkenylation/annulation cascade in moderate to excellent yields. This protocol also features: reaction procedures that are insensitive to air and moisture, excellent regioselectivity and good functional group tolerance.

Phosphorus anodes offer a high theoretical capacity for lithium-/sodium-ion batteries, but they suffer from serious expansion during charging, even when formed of 2D black phosphorene (α-P), which seriously affects their cycle reversibility. In this work, we systematically investigated a series of phosphorene anodes besides α-P for lithium-/sodium-ion batteries. β-P and γ-P with much lower in-plane atomic density are confirmed to be good substitutes for α-P. Both of them show moderate adsorption energy and low diffusion barriers, which ensure their high capacity and charging/discharging efficiency. Moreover, as β-P has a three-fold symmetrical lattice, the lithium/sodium adsorption and diffusion on it result in not anisotropic but equivalent in-plane expansion during charging, which should be beneficial to its integrity and reversibility. Furthermore, we discussed the conversion pathways from α-P to β-P, and from β-P to γ-P. The final activation barriers are 0.45 eV per atom and 0.52 eV per atom for the conversions from α-P to β-P, and from β-P to γ-P. Under strain induction, the transition barriers will drop significantly, and they are estimated to be 0.06 eV per atom for α-P to β-P, and 0.12 eV per atom for β-P to γ-P. These results can provide theoretical guidance and a reference for the experimental synthesis and application of these novel phosphorenes.

A three-dimensional (3D) metal–organic framework [(CH3)2NH2][Zn2(DMTDC)2(3-mtz)]·4DMF·3H2O (Zn-MOF) has been solvothermally synthesized by using mixed ligands of 3-methyl-1,2,4-triazole (3-Hmtz) and a thiophene-functionalized dicarboxylate ligand, 3,4-dimethylthieno[2,3-b]thiophene-2,5-dicarboxylic acid (H2DMTDC). Zn-MOF exhibits a uninodal 6-connected pcu α-Po topology structure and possesses an anionic framework with large 1D-trapezoidal channels. Gas adsorption studies reveal that the activated Zn-MOF-a displays selective adsorption of CO2 over N2 at 273 K and 298 K as well as a high isosteric heat of CO2 adsorption. Moreover, Zn-MOF shows selective adsorption of the cationic dyes over the anionic and neutral dyes, and can be used as a fast-response and sensitive probe for the detection of Fe3+ by fluorescence quenching after encapsulation of Tb3+ into the pores by postsynthetic cation exchange.

To investigate the reaction mechanism of Ni/SiC system, 0.1 μm-thick pure nickel foil is used to join SiC ceramic at 1245 °C for different times. Interfacial melting is calculated to occur at 964 °C along the interface due to the low eutectic point of θ-Ni2Si and NiSi, a periodical layered structure, consisting alternating layers of silicides/silicides+graphite, is formed along the interface due to periodical detachment of graphite from SiC reaction interface during the reactions between Ni-Si liquid phase and SiC. The reaction products of Ni/SiC are successfully predicted by CALPHAD method, based on a home-made Ni-Si-C ternary database. The reaction processes between Ni and SiC and the morphology changes of the joined seam are discussed in detail in this paper. The average shear strengths of SiC joints held for 15 min, 30 min and 60 min are tested to be 16.53 MPa, 19.32 MPa and 29.43 MPa, respectively.

Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS). Excitatory Amino Acid Transporters (EAATs) regulate extracellular glutamate by transporting it into cells, mostly glia, to terminate neurotransmission and to avoid neurotoxicity. EAATs are also chloride (Cl−) channels, but the physiological role of Cl− conductance through EAATs is poorly understood. Mutations of human EAAT1 (hEAAT1) have been identified in patients with episodic ataxia type 6 (EA6). One mutation showed increased Cl− channel activity and decreased glutamate transport, but the relative contributions of each function of hEAAT1 to mechanisms underlying the pathology of EA6 remain unclear. Here we investigated the effects of five additional EA6-related mutations on hEAAT1 function in Xenopus laevis oocytes, and on CNS function in a Drosophila melanogaster model of locomotor behavior. Our results indicate that mutations with decreased hEAAT1 Cl− channel activity and functional glutamate transport can also contribute to the pathology of EA6, highlighting the importance of Cl− homeostasis in glial cells for proper CNS function. We also identified a novel mechanism involving an ectopic sodium (Na+) leak conductance in glial cells. Together, these results strongly support the idea that EA6 is primarily an ion channelopathy of CNS glia.

Electrolytic water splitting using surplus electricity represents one of the most cost‐effective and promising strategies for hydrogen production. The high overpotential of the oxygen‐evolution reaction (OER) caused by the multi‐electron transfer process with a high chemical energy barrier, however, limits its competitiveness. Here, a highly active and stable OER electrocatalyst was designed through a cobalt‐induced intrastructural enhancement strategy combined with suitable electronic structure modulation. A carved carbon nanobox was embedded with tri‐metal phosphide from a uniform Ni−Co−Fe Prussian blue analogue (PBA) nanocube by sequential NH3 ⋅ H2O etching and thermal phosphorization. The sample exhibited an OER activity in an alkaline medium, reaching a current density of 10 mA cm−2 at an overpotential of 182 mV and displayed a small Tafel slope of 47 mV dec−1, superior to the most recently reported OER electrocatalysts. Moreover, it showed impressive electrocatalytic durability, increasing by approximately 2.7 % of operating voltage after 24 h of continuous testing. The excellent OER activity and stability are ascribed to a favorable transfer of mass and charge provided by the porous carbon shell, synergistic catalysis between the three‐component metal phosphides originating from appropriate electronic structure modulation, more exposed catalytic sites on the hollow structure, and chainmail catalysis resulting from the carbon protective layer. It is foreseen that this successfully demonstrated design concept can be easily extended to other heterogeneous catalyst designs., Make it better: This combined cobalt‐induced intrastructural enhancement and proper electronic structure modulation strategy is developed to fabricate a Ni−Co−Fe−P@CC‐E‐15 carved nanobox as a highly active and stable oxygen evolution electrocatalyst.

The neurohypophyseal hormone oxytocin (OT) plays critical roles in lactation and parturition, while its function in male reproduction system is largely unknown. This study aims to investigate the effect of OT on regulating transepithelial ion transport in rat cauda epididymal epithelium. With the use of RT-PCR, Western blot, and immunohistochemical analysis, we found that OT receptor (OTR) was expressed and localized at the basal membrane of rat cauda epididymal epithelium. The short-circuit current ( Isc) measurement showed that basolateral application of OT to the primary cultured rat cauda epididymal epithelial cells elicited an increase in Isc, which was abrogated by pretreating the epithelial cells with CFTRinh-172, a blocker of cystic fibrosis transmembrane conductance regulator (CFTR). Pretreatment with the prostaglandin H synthase inhibitors indomethacin and piroxicam, or the nonselective antagonists of prostaglandin E2 (PGE2) receptor EP2 or EP4, AH-6809, and AH-23848, significantly attenuated OT-stimulated Iscresponse. Furthermore, the generation of PGE2was measured using enzyme-linked immunosorbent assay, demonstrating that OT induced a substantial increase in PGE2release from primary cultured rat cauda epididymal epithelial cells. In conclusion, activation of OTR by OT triggered PGE2release, resulting in CFTR-dependent Cl−secretion through paracrine/autocrine pathways in rat cauda epididymal epithelium.

Epididymal epithelium possesses active ion transport properties conducive to the maintenance of appropriate epididymal intraluminal microenvironment. The endogenous gasotransmitter carbon monoxide (CO) regulates numerous cellular processes including water and electrolyte transport in various epithelia. However, the functional role of CO in epididymal epithelium is still elusive. This study aims to explore the potential regulatory effect of CO on transepithelial ion transport in rat epididymis. Using qPCR technique, we verified that endogenous CO synthase heme oxygenase 1 was expressed in rat caput, corpus, and cauda epididymis. In addition, endogenous CO was detected in rat cauda epididymis. Ussing chamber experiments showed that CORM-2, a CO donor, induced an increase of the short-circuit current (ISC) in a concentration-dependent manner in rat cauda epididymal epithelium. The ISC response could be abrogated by removing the ambient Cl- or HCO3-. Interfering with the cAMP signaling pathway or blocking cystic fibrosis transmembrane regulator (CFTR) partially suppressed the CO-stimulated ISC response. Moreover, the CO-evoked ISC response was significantly attenuated by blocking Ca2+-activated Cl- channel (CaCC) or chelating intracellular Ca2+. Elevation of intracellular Ca2+ level was also observed after CO stimulation in rat cauda epididymal epithelial cells. Collectively, this study demonstrated that CO stimulated anion secretion via activation of CFTR and CaCC in rat cauda epididymal epithelium, which might contribute to the formation of the appropriate microenvironment essential for sperm storage.

Soybean oligosaccharides have been previously shown to be associated with the production of major odor-causing compounds in broilers, although little is known about the role of stachyose and raffinose, which are key components of soybean oligosaccharide, in broiler cecal microbiota and odor compound production. To this end, soybean oligosaccharide, stachyose, and raffinose were added to the birds' diets to investigate their effects on odor compound production and the microbial community characteristics of the cecum in broilers. A total of 300 one-day-old Arbor Acre broilers with similar initial live weight were randomly allocated into 5 dietary groups with 6 replicates of 10 birds. The diets included soybean meal (positive control), soybean meal-free (negative control), 0.6% soybean oligosaccharide, 0.6% stachyose, or 0.6% raffinose. After a 49-D feeding period, both ceca were aseptically removed postmortem, and the contents were collected and analyzed for skatole, indole, volatile fatty acids, and lactic acid by using high performance liquid chromatography. Bacterial communities were detected by using a high-throughput sequencing platform based on IlluminaMiSeq 2500. Levels of skatole and indole tended to be lower in the dietary supplementation of oligosaccharides. The lowest levels of skatole and indole were observed in the stachyose group (P 0.05). Bacterial genera Alistipes and Parabacteroides were comparably abundant in the stachyose group, while Bacteroides, Lactobacillus, and Akkermansia were more abundant in the negative control, stachyose, and raffinose groups, respectively. Collectively, these findings demonstrated that dietary oligosaccharide supplementation significantly reduced odor compound production by modulating the cecal microbial community. Compared with soybean oligosaccharide and raffinose, the addition of stachyose into diets may help improve gut fermentation and minimize odor compound generation in broilers.

A new triazine charring agent, melamine formaldehyde resin modified with pentaerythritol (named as MF-MPOL), was synthesized through hydroxymethylation, condensation and etherification by using melamine, paraformaldehyde and pentaerythritol as raw materials, and characterized by solid-state 13C NMR and FT-IR. The intumescent flame retardant (IFR) consisting of MF-MPOL with ammonium polyphosphate has good flame retardancy in polypropylene (PP). The analysis of the residues obtained in cone calorimetry test showed that the IFR played a role of flame retardancy mainly in condensed phase. In other words, the porous and dense - continuous intumescent char layer formed during the burning process results in flame retardant effect by insulation of heat, oxygen and preventing the underlying PP from degradation and volatilization of pyrolytic products.

Effects of dietary supplemental stachyose on caecal skatole concentration, hepatic cytochrome P450 (CYP450, CYP) mRNA expressions and enzymatic activities in broilers were evaluated. Arbor Acre commercial mixed male and female chicks were assigned randomly into six treatments. The positive control (PC) diet was based on maize–soyabean meal, and the negative control (NC) diet was based on maize–non-soyabean meal. The NC diet was then supplemented with 4, 5, 6 and 7 g/kg stachyose to create experimental diets, named S-4, S-5, S-6 and S-7, respectively. Each diet was fed to six replicates of ten birds from days 1 to 49. On day 49, the caecal skatole concentrations in the PC, S-4, S-5, S-6 and S-7 groups were lower than those in the NC group by 42·28, 23·68, 46·09, 15·31 and 45·14 % (P < 0·01), respectively. The lowest pH value was observed in the S-5 group (P < 0·05). The stachyose-fed groups of broilers had higher caecal acetate and propionate levels compared with control groups, and propionate levels in the S-6 and S-7 groups were higher than those in the S-4 and S-5 groups (P < 0·001). The highest CYP3A4 expression was found in the S-7 group (P < 0·05), but this was not different from PC, S-4, S-5 and S-6 treatments. There was no significant difference in CYP450 (1A2, 2D6 and 3A4) enzymatic activities among the groups (P > 0·05). In conclusion, caecal skatole levels can be influenced by dietary stachyose levels, and 5 g/kg of stachyose in the diet was suggested.

The purpose of this study is to evaluate in vitro and in vivo antitumor efficacy and subacute toxicity of triptolide (TP) prodrug, a conjugate between TP and carboxymethyl chitosan (CC). The CCTP conjugate contained 4∼ wt % TP and displayed excellent aqueous solubility (5 mg/mL) as compared to the native TP (17 μg/mL). In vitro cytotoxicity of CCTP conjugate was evaluated by CCK8 assay against human pancreatic cancer (PC) cell lines, showing comparable the half maximal inhibitory concentration (IC50) values to the parent TP. In a mouse model of PC (BxPC-3), the CCTP conjugate administered orally (at dose levels as low as 0.2 mg TP equivalent/kg) showed comparable efficacy in reducing or eliminating xenograft tumor to the same dose of TP, but exhibited much lower subacute toxicity as seen in body weight loss and hematological toxicity.

The oxidation behavior of a newly designed Co–Ni-based alloy with varied addition of Ti (1.4 and 2.1 wt.%, hereafter referred as 1.4Ti and 2.1Ti alloys) was explored in air at 900 °C. It is found that an outer oxide layer composed of CoO, an intermediate oxide layer composed of intermittent TiO2 plus continuous Cr, W-rich oxides, and an inner oxidized region composed of Al2O3 were formed on the surface of 1.4Ti alloy, whereas the oxide structure of 2.1Ti alloy was composed of CoO as the outer oxide layer, continuous TiO2, Cr2O3, and WO3 as intermediate oxide layer, and Al2O3 as the inner oxidized region. With increasing Ti content, continuous TiO2 films formed in the intermediate oxide layer, which would lead to the formation of compact Cr2O3 and improved oxidation resistance after 100 h oxidation at 900 °C. These observations indicated that Ti addition can improve the high-temperature oxidation resistance of Co–Ni-based alloys.

Background The relationship between dietary acrylamide intake and renal cell carcinoma risk is inconclusive. In consideration of the recent findings, we conducted an updated meta-analysis to assess the association between acrylamide intake and renal cell carcinoma risk. Results PubMed, EMBASE, and Cochrane databases have been used to identify epidemiological studies on dietary acrylamide intake and renal cell carcinoma risk. This meta-analysis study included eight studies, 2843 cases, and 309 920 controls/participants. We performed meta-analyses to calculate the summary relative risk (RR) for the highest versus lowest intake of dietary acrylamide. No meaningful association was found for renal cell carcinoma; RR was 1.12 (95% confidence interval (CI): 0.97-1.28). Among participants who never smoked, no association was found between dietary acrylamide and renal cell carcinoma; the RR for highest versus lowest intake of dietary acrylamide was 1.11 (95% CI: 0.93-1.32). Conclusion This meta-analysis study indicates that dietary acrylamide is not related to the risk of renal cell carcinoma. © 2020 Society of Chemical Industry.

N-doped carbon armored metal phosphides were anchored in-situ on backbones of nickel foam (NF), by using polydopamine as both carbon source and targeted precursor delivery vehicle. The product served as a highly efficient chainmail bi-functional catalyst toward electrolytic water splitting, requiring small operating cell voltages of only 1.65, 1.73, and 1.79 V at 50, 100, and 250 mA/cm2, respectively for overall water splitting. More importantly, the product catalyst also possessed excellent long-term stability, even tested at 250 mA/cm2. The excellent activity and durability may be ascribed to the positive synergistic effects between well-mixed metal phosphides, advantageous nanostructure of interwoven thin vertical nanosheets, protective and conductive N-doped carbon matrix, hydrophilic and aerophobic characteristics, and well dispersed and utilized active materials on skeleton surfaces of the highly conductive NF. This synergistic effect boosting and protective layer armored design for highly efficient and stable electrocatalysts is unique and scalable, suitable for large-scale applications not only in the field of electrocatalysis, but also in other heterogeneous catalysis.

Electrocatalytic hydrogen production driven by surplus electric energies is considered a promising sustainable process for hydrogen supply. The high overpotential and low energy-conversion efficiency caused by the slow kinetics of the four-electron transfer oxygen-evolution reaction (OER), however, hamper its competitiveness. Herein, a highly stable, efficient OER catalyst was developed, taking the effects of both composition and nanostructure into account for the catalyst design. N-doped carbon-armored mixed metal phosphide nanoparticles confined in N-doped porous carbon nanoboxes, a particle-in-box nanostructure, were synthesized from monodisperse Ni3[Fe(CN)6]2·H2O nanocubes through sequential conformal polydopamine coating, ammonia etching, and thermal phosphorization. The product exhibited outstanding catalytic abilities for the OER in 1.0 M KOH, delivering 10, 100, and 250 mA/cm2 at ultrasmall overpotentials of 203, 242, and 254 mV, respectively, with an ultrasmall Tafel slope of 38 mV/dec, outperforming most recently reported top-notch iron-group-based OER catalysts. The long-term stability was also excellent, showing a small chronopotentiometric decay of 2.5% over a 24 h operation at 50 mA/cm2. The enhanced catalytic efficiency and stability may be attributable to the unique particle-in-box structure as a nanoreactor offering a local, fast reaction environment, the conductive N-doped porous carbon shell for fast charge and mass transport, the synergistic effect between multicomponent metal phosphides for enhanced intrinsic activities, and the carbon protection layer to prevent/delay the catalyst core from being deactivated. This combined particle-in-box and chainmail design concept for electrocatalysts is unique and advantageous and may be readily applied to the general field of heterogeneous reactions.

The quinolactacins are a family of pyrroloquinoline-type natural products from Penicillium sp. From the organic extract of Penicillium sp. ENP701 fermentation broth, a microorganism from the east China sea, one new quinolactacin was isolated and named quinolactacin-H. The structure of quinolactacin-H was determined by spectroscopic analysis and the absolute configurations by X-ray crystallographic analysis. Enantioselective total synthesis of (R)-(+)-quinolactacin-H and (S)-(−)-quinolactacin-H was achieved. When assayed through crystal violet (CV) microtiter plate biofilm, both (R) and (S)-quinolactacin-H showed a strong inhibition and dispersion of Pseudomonas aeruginosa PAO1 biofilms. Thus, quinolactacins could be proposed and developed as natural anti-bioflm agents in order to solve the problem of microbial resistance in future.

While elemene (ELE) can reverse tumor multidrug resistance (MDR), the mechanisms for ELE reversing MDR remain unclear. Numerous studies have suggested that the efflux functionality of ATP-binding cassette (ABC) transporters, not their quantity, is more relevant to tumor MDR. However, no appropriate methods exist for real-time detection of the intracellular drug efflux caused by ABC transporters in vitro, especially in vivo, which hinders the examination of MDR reversal mechanisms. This study directly investigates the correlation between efflux functionality of ABC transporters and MDR reversal via ELE, using D-luciferin potassium salt (D-luc) as the chemotherapeutic substitute to study the intracellular drug efflux. Here, a luciferase reporter assay system combined with bioluminescence imaging confirmed that the efflux of D-luc from MCF-7/DOXFluc cells in vitro and in vivo was significantly reduced by ELE and when combined with Doxorubicin (DOX), ELE showed a synergistically anti-tumor effect in vitro and in vivo. Additionally, the luminescence pharmacokinetics of D-luc in MCF-7/DOXFluc cells and pharmacodynamics of the combined ELE and DOX in vivo showed a great correlation, implying that D-luc might be used as a probe to study ABC transporters-mediated efflux in order to explore mechanisms of traditional Chinese medicines reversing MDR.

The key to develop efficient catalysts is to improve the quantity and activity of catalytic sites of the catalysts through optimal structural and compositional design. Accordingly, open-mouth N-doped carbon nanoboxes embedded with mixed metal phosphide nanoparticles are fabricated from monodisperse Ni3[Fe(CN)6]2·H2O nanocubes through conformal Ni3[Co(CN)6]2·12H2O layer coating, ammonia etching, and thermal phosphorization, sequentially. The product catalyst exhibits highly efficient electrocatalytic performances, achieving low overpotentials of 204 and 129 mV for the oxygen evolution reaction and hydrogen evolution reaction, respectively, and a small working voltage of 1.57 V for the overall water splitting, all at 10 mA cm-2. Its long-term electrocatalytic stability is also outstanding, experiencing only minor chronopotentiometric decay after a 24 h operation at 10 mA cm-2. The enhanced electrocatalytic performance may be attributed to the synergistic effects between the mixed metal phosphides, the protective function offered by the chainmail catalyst design, and the fast mass transport channels for the electrolyte and gaseous products afforded by the large openings on the nanobox shell, as well as the easy access of the inner active sites of the nanobox. The ingenious open-mouth nanobox structure together with embedded mixed metal phosphide nanoparticles is a unique design for improving the quantity and activity of catalytic sites of the catalyst for high efficiency electrolytic water splitting. The present design concept can be readily applied to the fabrication of other heterogeneous catalysts.

Three new alkaline earth metal–organic frameworks (MOFs), namely [Mg2(DMTDC)2(DMF)3(H2O)2]·2DMF·2H2O (1), [Ca(DMTDC)(DMF)] (2) and [Sr(DMTDC)(DMF)] (3), have been synthesized under solvothermal conditions by using a thiophene-functionalized dicarboxylate ligand, 3,4-dimethylthieno[2,3-b]thiophene-2,5-dicarboxylic acid (H2DMTDC). Single-crystal X-ray diffraction analyses demonstrate that the metal ion radii play an important role in coordination numbers and topologies, i.e., hexa-coordinated Mg2+ in 1 gives a two-dimensional layered framework with an sql net, while octa-coordinated Ca2+/Sr2+ in 2/3 exhibit a three-dimensional framework with lvt nets. All frameworks show a one-dimensional rhombus-shaped channel that is occupied by DMF and/or water molecules. Photoluminescence studies reveal that 1–3 can be used as fast-response fluorescence sensors for the sensitive detection of Fe3+ ions with favorable recyclability through fluorescence quenching.

Aconiti kusnezoffii Radix (Caowu), a traditional Chinese medicine and Mongolian medicine, has been commonly used owing to its analgesic and anti-inflammatory effects. Here, we performed a qualitative analysis of aconite alkaloids (AAs) in raw and processed Aconiti kusnezoffii Radix by ultra-high-performance liquid chromatography (HPLC) electrospray ionization-tandem mass spectrometry. Furthermore, we quantified benzoylaconine, benzoylmesaconine, benzoylhypaconine, aconitine, mesaconitine, and hypaconitine in raw and processed Aconiti kusnezoffii Radix using a HPLC system coupled with a diode array detector. The analysis of AA fragmentation patterns in positive electrospray ionization mode revealed 155 AAs, including 6 with unambiguous identities, 109 with putative assignments, and 40 unknown compounds. Additionally, lipopolysaccharide-treated RAW264.7 macrophages were used to evaluate the anti-inflammatory properties of the alkaloid extracts of Aconiti kusnezoffii Radix. Importantly, alkaloid extracts of Aconiti kusnezoffii Radix at three different concentrations exhibited protective effect against lipopolysaccharide-induced inflammation. Thus, the proposed method can be used not only for the qualitative and quantitative analyses of Aconiti kusnezoffii Radix, but also for evaluating other Aconitum spp. Our study lays a foundation for the clinical application of poisonous Aconitum.

Retinal segmentation is a prerequisite for quantifying retinal structural features and diagnosing related ophthalmic diseases. Canny operator is recognized as the best boundary detection operator so far, and is often used to obtain the initial boundary of the retina in retinal segmentation. However, the traditional Canny operator is susceptible to vascular shadows, vitreous artifacts, or noise interference in retinal segmentation, causing serious misdetection or missed detection. This paper proposed an improved Canny operator for automatic segmentation of retinal boundaries. The improved algorithm solves the problems of the traditional Canny operator by adding a multi-point boundary search step on the basis of the original method, and adjusts the convolution kernel. The algorithm was used to segment the retinal images of healthy subjects and age-related macular degeneration (AMD) patients; eleven retinal boundaries were identified and compared with the results of manual segmentation by the ophthalmologists. The average difference between the automatic and manual methods is: 2-6 microns (1~2 pixels) for healthy subjects and 3-10 microns (1~3 pixels) for AMD patients. Qualitative method is also used to verify the accuracy and stability of the algorithm. The percentage of “perfect segmentation” and “good segmentation” is 98% in healthy subjects and 94% in AMD patients. This algorithm can be used alone or in combination with other methods as an initial boundary detection algorithm. It is easy to understand and improve, and may become a useful tool for analyzing and diagnosing eye diseases.

Five pairs of optically pure meroterpenoid enantiomers (1a/1b-5a/5b) and two known compounds (6 and 7) were isolated from Rhododendron fastigiatum. Compounds 1a/1b-5a/5b were resolved from naturally scalemic mixtures by chiral HPLC. Their structures were elucidated by spectroscopic methods, X-ray crystallographic experiments, and ECD analyses. Compounds 1a/1b, 2a/2b, 3b, 4a/4b, and 5a/5b were new meroterpenoids with different polycyclic systems. Two enantiomeric pairs (2a/2b and 3a/3b), 6, and 7 exhibited inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) in vitro.

DNA–protein interaction plays an essential role in the storage, expression, and regulation of genetic information. A 1D/3D facilitated diffusion mechanism has been proposed to explain the extraordinarily rapid rate of DNA‐binding protein (DBP) searching for cognate sequence along DNA and further studied by single‐molecule experiments. However, direct observation of the detailed chronological protein searching image is still a formidable challenge. Here, for the first time, a single‐molecule electrical monitoring technique is utilized to realize label‐free detection of the DBP–DNA interaction process based on high‐gain silicon nanowire field‐effect transistors (SiNW FETs). The whole binding process of WRKY domain and DNA has been visualized with high sensitivity and single‐base resolution. Impressively, the swinging of hydrogen bonds between amino acid residues and bases in DNA induce the dynamic collective motion of DBP–DNA. This in situ, label‐free electrical detection platform provides a practical experimental methodology for dynamic studies of various biomolecules., A single‐molecule electrical detection platform, based on a silicon nanowire field‐effect transistors (SiNW FETs) nanocircuit, is applied to real‐time monitor the complete interaction process of WRKY1N and DNA with single‐base‐pair resolution. A long‐last collective motion correlated to the specific recognition site is observed at the single‐molecule level, providing a novel technique with single‐molecule/single‐event sensitivity to decipher the comprehensive mechanism of biomolecule interactions.

The size and shape of the foveal avascular zone (FAZ) have a strong positive correlation with several vision-threatening retinovascular diseases. The identification, segmentation and analysis of FAZ are of great significance to clinical diagnosis and treatment. We presented an adaptive watershed algorithm to automatically extract FAZ from retinal optical coherence tomography angiography (OCTA) images. For the traditional watershed algorithm, “over-segmentation” is the most common problem. FAZ is often incorrectly divided into multiple regions by redundant “dams”. This paper analyzed the relationship between the “dams” length and the maximum inscribed circle radius of FAZ, and proposed an adaptive watershed algorithm to solve the problem of “over-segmentation”. Here, 132 healthy retinal images and 50 diabetic retinopathy (DR) images were used to verify the accuracy and stability of the algorithm. Three ophthalmologists were invited to make quantitative and qualitative evaluations on the segmentation results of this algorithm. The quantitative evaluation results show that the correlation coefficients between the automatic and manual segmentation results are 0.945 (in healthy subjects) and 0.927 (in DR patients), respectively. For qualitative evaluation, the percentages of “perfect segmentation” (score of 3) and “good segmentation” (score of 2) are 99.4% (in healthy subjects) and 98.7% (in DR patients), respectively. This work promotes the application of watershed algorithm in FAZ segmentation, making it a useful tool for analyzing and diagnosing eye diseases.

Hydrogen is one of the most attractive energy sources at present for its excellent properties, such as high energy density, clean and non-pollution energy. Photocatalytic hydrogen evolution is one of the ideal strategies to obtain hydrogen energy. This work aimed to improve the visible-light absorption ability of the structure similar to g-C3N4 by anchoring azo groups into the structure. By this, the photocatalytic hydrogen production rate of the resulting product was improved apparently. We use melamine as starting material to prepare Melon, which was further reacted with KOH, PCl5 and 4, 4-Diaminoazobenzene to get the target Melon/4, 4-Diaminoazobenzene polymer. The condition influencing on the reaction was investigated, such as reaction temperature, the ratio of reactants and concentration of KOH solution. The structure of the as-synthesized polymer was determined IR, XRD, SEM, TGA and EIS. At the same time, its photocatalytic property was investigated.