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The practical application of high-energy lithium–sulfur battery is plagued with two deadly obstacles. One is the “shuttle effect” originated from the sulfur cathode, and the other is the low Coulombic efficiency and security issues arising from the lithium metal anode. In addressing these issues, we propose a novel silicon-sulfurized poly(acrylonitrile) full battery. In this lithium metal-free system, the Li source is pre-loaded in the cathode, using a nitrogen evolution reaction (NER) to implant Li+ into the silicon/carbon anode. Sulfurized poly(acrylonitrile) based on a solid–solid conversion mechanism can fundamentally circumvent the “shuttle effect”. Meanwhile, the silicon/carbon anode can achieve more efficient utilization and higher security when compared with the Li metal anode. The full cell used in this technology can deliver a capacity of 1169.3 mAh g−1, and it can be stabilized over 100 cycles, implying its excellent electrochemical stability. Furthermore, the practical pouch cell with a high sulfur loading of 4.2 mg cm−2 can achieve a high specific energy of 513.2 Wh kg−1. The mechanism of the NER in cathode has also been investigated and analyzed by in situ methods. Notably, this battery design completely conforms to the current battery production technology because of the degassing of gasbag, resulting in a low manufacturing cost. This work will open the avenue to develop a lithium metal-free battery using the NER.

Coupled with anionic and cationic redox chemistry, Li-rich/excess cathode materials are prospective high-energy-density candidates for the next-generation Li-ion batteries. However, irreversible lattice oxygen loss would exacerbate irreversible transition metal migration, resulting in a drastic voltage decay and capacity degeneration. Herein, a metastable layered Li-excess cathode material, T2-type Li0.72[Li0.12Ni0.36Mn0.52]O2, was developed, in which both oxygen stacking arrangement and Li coordination environment fundamentally differ from that in conventional O3-type layered structures. By means of the reversible Li migration processes and structural evolutions, not only can voltage decay be effectively restrained, but also excellent capacity retention can be achieved upon long-term cycling. Moreover, irreversible/reversible anionic/cationic redox activities have been well assigned and quantified by various in/ex-situ spectroscopic techniques, further clarifying the charge compensation mechanism associated with (de)lithiation. These findings of the novel T2 structure with the enhanced anionic redox stability will provide a new scope for the development of high-energy-density Li-rich cathode materials.

The compulsive lithium dendrite growth and inevitable electrolyte decomposition induced by immediate contact between electrodes and free/weakly coordinated solvent molecules within the solvation sheaths of solvated lithium-ions are long-lasting tricky problems that existed in lithium-metal batteries (LMBs). Salt-concentrated strategy can effectively suppress those detrimental issues, the apparently increased production costs, the increased electrolyte viscosities, or even catastrophic battery explosions caused by adding extra salts, however, greatly restrained their successes. Here, by employing a metal-organic framework (MOF) with narrow channel sizes of 4.2 A (ZIF-71) as a unique electrolyte solvation sheath filter to isolate free or weakly-coordinated solvents from contact with electrodes, we have obtained a special electrolyte composed of merely strongly coordinated solvent molecules. Drawn from the quantitative spectral analysis (FT-IR, Raman), the number of electrolyte solvent molecules in each Li+ solvation sheath was calculated to be 0.54 (the lowest value achieved among carbonate electrolytes), indicated almost completely de-solvation towards the solvated lithium-ions. This ZIF-71 filtered electrolyte displayed remarkably expanded electrochemical stability windows (extended to 5.2 V vs. Li/Li+). When coupled it with two typical high-voltage cathodes (4.4 V-level NCM-811 and 4.9 V-level LNMO), the high-voltage lithium-metal batteries demonstrated remarkably improved electrochemical performances in terms of capacities and lifespans. The cycled high-voltage cathodes and lithium metals demonstrate greatly improved electrode/electrolyte interfaces with negligible cathode electrolyte interface (CEI) and solid electrolyte interface (SEI). This special electrolyte filtering strategy is expected to push the development of high-energy-density LMBs.

Imatinib is a nontoxic tyrosine kinase inhibitor, used in the treatment of advanced renal cell carcinoma. However, some patients with renal cell carcinoma develop resistance to imatinib. Protein disulfide isomerase family 6 (PDIA6) was involved in the chemo-resistance of lung adenocarcinoma. In this study, the effect of PDIA6 on imatinib-resistance of renal cell carcinoma was investigated. First, PDIA6 was found to be up-regulated in the imatinib-resistant renal cell carcinoma tissues and cells. Functional assays showed that knockdown of PDIA6 sensitized imatinib-resistant renal cell carcinoma cells to imatinib through decreasing the half-maximal inhibitory concentration (IC50) of imatinib-resistant renal cell carcinoma cells. Secondly, cell proliferation of imatinib-resistant renal cell carcinoma cells was suppressed by PDIA6 silencing, and the apoptosis was promoted with reduced Bcl-2, enhanced Bax and cleaved caspase-3. Moreover, the interference of PDIA6 increased phosphorylation of H2A histone family member X (γH2AX), while decreased Rad51 and phosphorylated DNA-dependent protein kinase (DNA-PK) (p-DNA-PK) in imatinib-resistant renal cell carcinoma cells. Lastly, protein expression levels of Wnt3a and Frizzled1 (FZD1) in imatinib-resistant renal cell carcinoma cells were down-regulated by silencing of PDIA6. Over-expression of FZD1 attenuated PDIA6 silencing-induced increase in cell apoptosis and decrease in cell proliferation in imatinib-resistant renal cell carcinoma cells. In conclusion, knockdown of PDIA6 sensitized imatinib-resistant renal cell carcinoma cells into imatinib through inactivation of Wnt3a-FZD1 axis.

Microbes are decomposers of crop residues, and climatic factors and residue composition are known to influence microbial growth and community composition, which in turn regulate residue decomposition. However, the succession of the bacterial community during residue decomposition in Northeast China is not well understood. To clarify the property of bacterial community succession and the corresponding factors regulating this succession, bags containing maize residue were buried in soil in Northeast China in October, and then at different intervals over the next 2 years, samples were analyzed for residue mass and bacterial community composition. After residue burial in the soil, the cumulative residue mass loss rates were 18, 69, and 77% after 5, 12, and 24 months, respectively. The release of residue nitrogen, phosphorus, and carbon followed a similar pattern as mass loss, but 79% of residue potassium was released after only 1 month. The abundance, richness, and community diversity of bacteria in the residue increased rapidly and peaked after 9 or 20 months. Residue decomposition was mainly influenced by temperature and chemical composition in the early stage, and was influenced by chemical composition in the later stage. Phyla Actinobacteria, Bacteroidetes, and Firmicutes dominated the bacterial community composition in residue in the early stage, and the abundances of phyla Chloroflexi, Acidobacteria, and Saccharibacteria gradually increased in the later stage of decomposition. In conclusion, maize residue decomposition in soil was greatly influenced by temperature and residue composition in Northeast China, and the bacterial community shifted from dominance of copiotrophic populations in the early stage to an increase in oligotrophic populations in the later stage.

Herein we systematically investigated the coordination assembly behavior of Zr4L6 cages with Eu3+ ions at room temperature. Through adjustment of the concentration of Eu salt and changes of the type and molar ratio of the solvent, a series of Zr4L6-Eu structures with different structure dimensionalities have been synthesized and structurally characterized. In addition, we also studied the optical properties of these materials in detail, including the fluorescent and third-order nonlinear-optical properties. Most notably, a 2D layer structure with a strong aromatic π···π-stacking force exhibits a good optical-limiting effect.

Aprotic lithium–oxygen (Li–O2) batteries have received attention as a result of their high theoretical energy density and potentially low material cost. However, their practical applications are li...

Phosphate, an essential nutrient, is available in organic and inorganic forms. The balance of phosphate is central for cellular homeostasis through the genomic roles of DNA and RNA synthesis and cell signaling processes. Therefore, an imbalance of this nutrient, manifested, either as a deficiency or excess in phosphate levels, can result in pathology, ranging from cytotoxicity to musculoskeletal defects. Inorganic phosphate (Pi) overdosing can result in a wide spectrum of cytotoxicity processes, as noted in both animal models and human studies. These include rewired cell signaling pathways, impaired bone mineralization, infertility, premature aging, vascular calcification, and renal dysfunction. This article briefly reviews the regulation of phosphate homeostasis and elaborates on cytotoxic effects of excessive Pi, as documented in cell-based models.

Quantification of currently attainable yield and fertilizer requirements can provide detailed information for assessing the food supply capacity and offer data support for agricultural decision-making. Datasets from a total of 5 408 field experiments were collected from 2000 to 2015 across the major wheat production regions in China to analyze the spatial distribution of wheat yield, the soil nutrient supply capacity (represented by relative yield, defined as the ratio of the yield under the omission of one of nitrogen (N), phosphorus (P) and potassium (K) to the yield under the full NPK fertilizer application), and N, P and K fertilizer requirements by combining the kriging interpolation method with the Nutrient Expert Decision Support System for Wheat. The results indicated that the average attainable yield was 6.4 t ha–1, with a coefficient of variation (CV) of 24.9% across all sites. The yields in North-central China (NCC) and the northern part of the Middle and Lower reaches of the Yangtze River (MLYR) were generally higher than 7 t ha–1, whereas the yields in Southwest China (SWC), Northeast China (NEC), and the eastern part of Northwest China (NWC) were usually less than 6 t ha–1. The precentage of area having a relative yield above 0.70, 0.85, and 0.85 for N, P, and K fertilizers accounted for 52.3, 74.7, and 95.9%, respectively. Variation existed in N, P, and K fertilizer requirements, with a CV of 24.8, 23.9, and 29.9%, respectively, across all sites. More fertilizer was needed in NCC and the northern part of the MLYR than in other regions. The average fertilizer requirement was 162, 72, and 57 kg ha–1 for N, P2O5, and K2O fertilizers, respectively, across all sites. The incorporation of the spatial variation of attainable yield and fertilizer requirements into wheat production practices would benefit sustainable wheat production and environmental safety.

Two new triucallane triterpenoids, polystanin F (1) and polystanin G (2), along with eight known compounds (3-10) were isolated from the fruits of Aphanamixis polystachya. Their structures were established on the basis of extensive spectroscopic analysis. Moreover, eight compounds were evaluated for their in vitro cytotoxicity against three cancer cell lines (liver cancer RT112, colon cancer HCT-116 and breast cancer M231) using the MTT method. Compound 7 showed significant cytotoxic activity against HCT-116 with IC50 1.27 µM.

The development of hydrogen production via environment-friendly and efficient electrochemical water splitting technology leans heavily on the exploitation of highly active and durable oxygen evolution reaction (OER) electrocatalysts. Herein, nanocoral-like cerium-activated cobalt selenide (Ce-CoSe2) nanocomposites to enhance the OER catalytic activity have been successfully prepared by one-pot hydrothermal route via simply altering the cerium content. Owing to the ingenious introduction of cerium, as-prepared Ce-CoSe2 electrode displays remarkable OER performance in comparison with CoSe2. The nanocoral-like Ce-CoSe2 catalyst prepared under optimal condition just needs low overpotential of 276 and 398 mV at 10 and 50 mA cm−2, respectively. Additionally, it attains the current density of 255 mA cm−2 at the potential of 2.0 V vs. RHE, and shows long-term stability during OER. This work offers a simple and feasible pathway for the design and construct of metal dichalcogenides for green and renewable hydrogen production by electrocatalytic water splitting.

Objectives The new antituberculous drugs delamanid and bedaquiline form the last line of defence against drug-resistant tuberculosis (TB). Understanding the background prevalence of resistance to new drugs can help predict the lifetime of these drugs’ effectiveness and inform regimen design. Methods Mycobacterium tuberculosis without prior exposure to novel anti-TB drugs were analysed retrospectively. Drug susceptibility testing for bedaquiline, delamanid, linezolid, clofazimine and widely used first- and second-line anti-TB drugs was performed. All TB isolates with resistance to new or repurposed drugs were subjected to whole-genome sequencing to explore the molecular characteristics of resistance and to perform phylogenetic analysis. Results Overall, resistance to delamanid, bedaquiline, linezolid and clofazimine was observed in 0.7% (11/1603), 0.4% (6/1603), 0.4% (7/1603) and 0.4% (6/1603) of TB isolates, respectively. Moreover, 1.0% (1/102), 2.9% (3/102), 3.9% (4/102) and 1.0% (1/102) of multidrug-resistant TB (MDR-TB) were resistant to bedaquiline, delamanid, linezolid and clofazimine, respectively. Whereas 22.2% (2/9) of extensively-drug resistant tuberculosis (XDR-TB) isolates were resistant to both delamanid and linezolid, and none was resistant to bedaquiline or clofazimine. Phylogenetic analysis showed that recent transmission occurred in two XDR-TB with additional resistance to delamanid and linezolid. None known gene mutation associated with delamanid resistance was detected. All four isolates with cross-resistance to bedaquiline and clofazimine had a detected gene mutation in Rv0678. Three of five strains with linezolid resistance had a detected gene mutation in rplC. Conclusion Detection of resistance to new anti-TB drugs emphasises the pressing need for intensive surveillance for such resistance before their wide usage.

Nutrient balance is essential for attaining high yield and improving profits in agricultural farming systems, and crop nutrient uptake ratio and stoichiometry can indicate crop nutrient limitations in the field. We collected a large amount of field data to study the variations in yield, nutrient uptake and nutrient stoichiometry of peanut (Arachis hypogaea L.) in Southeast China (SEC), North-central China (NCC), and Northeast China (NEC), during 1993 to 2018. Peanut pod yield gradually increased from 1993 to 2018, with average yields of 4 148, 5 138, and 4 635 kg ha−1 in SEC, NCC, and NEC, respectively. The nitrogen (N) internal efficiency (NIE, yield to N uptake ratio) was similar among the three regions, but phosphorus (P) IE (PIE, yield to P uptake ratio) changed from low to high among regions: NCC

Mineral elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe)) play important biological roles in enzymes, hormones, vitamins, and normal metabolism. The deficiency of mineral elements can lead to abnormal physiological functions. And some elements (such as lead (Pb)) are harmful to the body. We aim to identify genetic loci which can influence the serum levels of mineral elements (Cu, Zn, Ca, Mg, Fe, and Pb). Genotyping was performed using Applied Biosystems Axiom™ PMDA in 587 individuals, and 6,423,076 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study (GWAS) analysis. The association between genotype and phenotype was analyzed using mixed linear regression (additive genetic model) adjusting by age and gender combined with identical by descent (IBD) matrix. Genetic loci in BCHE-LOC105374194, DTX2P1-UPK3BP1-PMS2P11, VAT1L, LINC00908-LINC00683, LINC01310-NONE, and rs6747410 in VWA3B were identified to be associated with serum Cu element concentration (p < 5 × 10-6). ADAMTSL1 rs17229526 (p = 4.96 × 10-6) was significantly associated with serum Zn element levels. Genetic loci in LRP1B, PIGZ-MELTF, LINC01365-LINC02502, and HAPLN3 were related to serum Ca element levels (p < 5 ×1 0-6). Three SNPs in ALPK1, ASAP1-ADCY8 and IER3IP1-SKOR2 also achieved a significant association with Mg element levels (p < 5 × 10-6). TACSTD2-MYSM1, LRP1B, and ASAP1-ADCY8 showed suggestive associations with serum Fe element levels (p < 5 × 10-6). Moreover, the two most significant SNPs associated with Pb were rs304234 in CADPS-LINC00698 (p = 2.47 × 10-6) and rs12666460 in LOC101928211-GPR37 (p = 1.81 × 10-6). In summary, we reported 19 suggestive loci associated with serum mineral elements in the Chinese Han population. These findings provided new insights into the potential mechanisms regulating serum mineral elements levels.

The one-pot synthesis of azide-substituted dihydropyrazoles in isopropanol was performed by using chalcones, hydrazine hydrate, and an acyl chloride at 0 ℃. Subsequent Staudinger–aza-Wittig–dehydroaromatization reactions of the products with methyl(diphenyl)phosphine were also investigated for further application in the construction of pyrazolo[1,5-c]quinazolines.

Hexagonal boron nitride quantum dot (BNQD) has aroused great interest in the optoelectronics field due to their metal-free nature with promising optical properties. However, it has been a great challenge to modulate its photoluminescence to the long-wavelength region so far. Herein, BNQDs with full-color emission (420-610 nm) have been implemented by doping diverse amino ligands in different solvents for the first attempt. This color variation from blue, green, yellow-green, yellow to red is ascribed to the surface states tunable via amination degree. Attractively, the quantum yield of our blue BNQDs has set a record at 32.27%, and rare yellow-green BNQDs have been demonstrated. Combining good thermal dissipation capability and high transparency, our full-color BNQD holds great potential for transparent flexible display and security labels at the elevated temperature.

Triggering oxygen redox activity has been regarded as a promising strategy to boost the output capacity of cathode materials for Li/Na-ion batteries. However, irreversible loss of lattice oxygen aggravates a structural distortion to a spinel phase, which leads to severe voltage decay and capacity degeneration. Herein, via chemical ion exchange procedure, the sodium within the alkali metal layer of a P2-type oxide precursor has been substituted by Li while the transition metal layer can be well preserved, resulting in the formation of a Li-excess O2-type layered oxide cathode, Li0.66[Li0.12Ni0.15Mn0.73]O2. Through systematic in/ex-situ and surface/bulk characterization (hard X-ray absorption spectroscopy, operando Raman/XRD and differential electrochemical mass spectroscopy, etc.), the redox reversibility and structural stability has been comprehensively demonstrated. Moreover, being evolved from the same sodium-based precursor, a similar O2-type compound generated by electrochemical ion exchange procedure presents severely irreversible behavior on both structural and redox processes. These findings elucidated that the chemical ion exchange strategy can be regarded as an efficient way to design high-capacity cathode candidates possessing stable anionic/cationic redox activities and enhanced structural stability.

It is urgent and challenging to exploit highly efficient oxygen evolution reaction (OER) catalysts for water splitting. Bacterial cellulose based carbon nanofiber (BCCNF) is highlighted for its 3D network structure, abundant surface functional groups and good conductivity. Herein, based on the different molar ratio of P/B precursor, a series of nanocotton-like Co–B–P/BCCNF electrocatalysts have been designed and prepared via a simple electroless deposition. When the molar ratio of P/B precursor is 3/7, nanocotton-like Co–B–P/BCCNF catalyst exhibits prominent catalytic performances, delivering the current density of 10 and 50 mA cm−2 at low overpotentials of only 262 and 391 mV, respectively. Besides, it exhibits long-term stability for durative OER in alkaline solution. This result indicates that nanocotton-like Co–B–P/BCCNF catalyst has great potential as OER catalysts for large-scale hydrogen production via water splitting.

The Zygosaccharomyces is notorious for its remarkable spoilage characteristics. In the present study, the visual and rapid identification of the genus Zygosaccharomyces was performed by a loop-mediated isothermal amplification (LAMP) assay using specific primers in Mini Dry Bath within 30 min at 65°C followed by a lateral flow dipstick (LFD) detection. The sensitivity evaluation revealed LAMP-LFD assay with 1.0×101 copies/μL of Zygosaccharomyces DNA as its detection limit, which was the same as the methods of real-time quantitative PCR (qPCR) and conventional polymerase chain reaction (PCR). However, qPCR or PCR methods not only need to be performed in a specialist analytical laboratory with expensive equipment but also with risk of aerosol pollution. The LAMP-LFD assay had no cross-reactivity against 10 other yeast species and its specificity was 100%. A total of 25 Qiangli loquat Dew samples (17 bottles bulged and eight normal-appearing) were detected within 40 min with 100 and 92.0% accurately and specifically, when compared with the qPCR assay and the microbiology culture method, respectively. Therefore, the simple, fast, sensitive and low-cost LAMP-LFD assay is an effective and useful tool for the on-site identification of the genus Zygosaccharomyces. Key words: Zygosaccharomyces, on-site detection, loop-mediated isothermal amplification (LAMP), lateral flow dipstick (LFD).

Plants encode a large number of proteases in activating intracellular signaling through proteolytic cleavages of various protein substrates. One type of the substrates is proligands, including peptide hormones, which are perceived by cell surface-resident receptors. The peptide hormones are usually first synthesized as propeptides, and then cleaved by specific proteases for activation. Accumulating evidence indicates that the protease-mediated cleavage of proligands can be triggered by environmental stresses and subsequently activates plant stress signaling. In this perspective, we highlight several recent publications and provide an update about stress-induced cleavage of propeptides and receptor-associated components by proteases in the activation of cell surface-resident receptor signaling in plants. We also discuss some questions and future challenges in the research of protease functions in plant stress response.

Biosynthesis and replication, from A to Z Four nucleobases. adenine (A), cytosine (C), guanine (G), and thymine (T), are usually thought to be invariable in DNA. In bacterial viruses, however, each of the DNA bases have variations that help them to escape degradation by bacterial restriction enzymes. In the genome of cyanophage S-2L, A is completely replaced by diaminopurine (Z), which forms three hydrogen bonds with T and thus creates non–Watson-Crick base pairing in the DNA of this virus (see the Perspective by Grome and Isaacs). Zhou et al. and Sleiman et al. determined the biochemical pathway that produces Z, which revealed more Z genomes in viruses hosted in bacteria distributed widely in the environment and phylogeny. Pezo et al. identified a DNA polymerase that incorporates Z into DNA while rejecting A. These findings enrich our understanding of biodiversity and expand the genetic palette for synthetic biology. Science , this issue p. 512 , 516 , 520 ; see also p. 460

The utilization of photochemical reaction channel based on radical process is rarely reported, which might be a very efficient and feasible strategy for improving generation of Type I reactive oxygen species (ROS). In this work, a double ionic-type aggregation-induced emission luminogen (AIEgen) of TIdBO was developed as a photosensitizer, of which the potential photocyclization characteristic involving an electron-transfer process had a positive effect on Type I ROS generation in aggregates under continuous light irradiation. Its noticeable photodynamic therapy (PDT) performance and self-monitoring of PDT process by the relationship between cellular morphology change and fluorescence intensity enhancement were achieved. In addition, it showed a good killing ability to microbes and specific interactions with microbes but not cells by regulating the incubation time. These intriguing results reveal a feasible design principle for the implementation of efficient PS preparation in clinical treatment under hypoxic conditions.

Human transcriptional enhanced associate domain (TEAD) family consists of four paralogous transcription factors that function to modulate gene expression by interacting with YAP-like coactivators and have been recognized as potential therapeutic targets of diverse diseases including lung cancer and gastric tumor. Here, we attempt to explore the systematic interaction profile between the 4 TEAD proteins and the peptides derived from the binding sites of 8 known YAP-like coactivators, in order to analyze the binding affinity and recognition specificity of these peptides towards the TEAD family, and to design hydrocarbon-stapled/cyclized peptides that can target the specific interaction profile for each coactivator. Structural, energetic and dynamic investigations of TEAD-coactivator interactions reveal that the coactivators adopt three independent secondary structure regions (β-strand, α-helix and Ω-loop) to surround on the surface of TEAD proteins, in which the α-helical and Ω-loop regions are primarily responsible for the interactions. Five α-helical peptides and four Ω-loop peptides are derived from the 8 YAP-like coactivators, and their systematic binding profile toward the 4 TEAD proteins is created, and hydrocarbon stapling and cyclization strategies are employed to constrain the free α-helical and Ω-loop peptides into their native conformations, respectively, thus effectively promoting peptide binding to TEADs. The all-hydrocarbon and disulfide bridges are designed to point out of the TEAD-peptide complex interface, which would not disrupt the direct intermolecular interaction between the TEAD and peptide. Therefore, the stapling and cyclization only improve peptide binding affinity to these TEADs, but do not alter peptide recognition specificity over different TEADs.

This study proposes two different methods of photocatalytic-controlled and visible light-induced selective oxidation of pyridiniums with air as the terminal oxidant. The key to these transformations is to choose the appropriate light source and photocatalyst. Pyridiniums are successfully converted into pyrroles through oxygen-mediated cycloaddition, proton-coupled electron transfer (PCET), pyridine ring opening, and recyclization. The other route is that pyridiniums selectively form 4-carbonyl pyridines through free radical rearrangement/aerobic oxidation under the catalysis of cobalt (II).

In view of the difficulty of extracting iron from Bayer red mud, a new idea of adding laterite nickel ore into red mud was proposed to prepare a high value-added product. Toward this, the influences of laterite nickel ore on thermodynamic reaction, slagging and smelting reduction of extracting iron from red mud were studied. The results indicated that the product of extracting iron from red mud (R100) was changed with the addition of laterite nickel ore (R70L30). The slag of R100 was strongly basic, while the R70L30 was weakly acidic with composition closer to the ideal blast furnace slag. The metal recovery of R100 was 75.16% and that of R70L30 was 94.05%. At the same temperature, the slag viscosity of R70L30 was significantly lower than that of R100, which proved that laterite nickel ore can adjust the basicity, reduce melting point of slag and improve metal recovery. Because Fe, Ni and Cr in red mud and laterite nickel ore can be reduced sufficiently, a low Ni–Cr alloy cast iron can be directly prepared.

MFI-type zeolitic membranes were prepared on the porous α-A2O3 support to investigate the separation properties of dichlorobenzene isomers. The pervaporation tests were performed with unary and binary isomer mixtures at 333 K. The results indicate that the silicalite membranes, irrespective of being synthesized by the templated or template-free method, are permeable for all dichlorobenzene isomers. The pervaporation fluxes of the pure dichlorobenzene isomers decrease in the order p-DCB > o-DCB > m-DCB. For the binary pervaporation system, the dichlorobenzene fluxes are all less than those with a single component due to the binary interactions between DCB isomers and between the DCB isomer and the zeolite membrane. Comparatively, the template-free MFI-type zeolite exhibits higher selectivity for dichlorobenzene isomers due to less inter-crystalline gaps. The separation factors for p-/o-DCB and p-/m-DCB can reach 16.7 and 22.0, respectively.

Overexpression of AKR1C3, an aldo-keto reductase, was recently discovered in liver cancers. In this study, an inverse correlation between AKR1C3 expression and survival of patients with liver cancer was observed. AKR1C3 inhibitors, however, failed to suppress liver cancer cell growth. The prodrug TH3424, which releases a DNA alkylating reagent upon reduction by AKR1C3, was developed to target tumors with overexpression of AKR1C3. TH3424 showed specific killing of liver cancer cells with AKR1C3 overexpression both in vitro and in vivo. In patient-derived mouse xenograft models, TH3424 at doses as low as 1.5 mg/kg eliminated liver tumors with no apparent toxicity. Therefore, TH3424 is a promising drug candidate for liver cancer and other types of cancers overexpressing AKR1C3.

Vascular calcification (VC) is highly prevailing in cardiovascular disease, diabetes mellitus, and chronic kidney disease and, when present, is associated with cardiovascular events and mortality. The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is regarded as the foundation for mediating VC. Related transcriptional enhancer factor (RTEF-1), also named as transcriptional enhanced associate domain (TEAD) 4 or transcriptional enhancer factor-3 (TEF-3), is a nuclear transcriptional factor with a potent effect on cardiovascular diseases, apart from its oncogenic role in the canonical Hippo pathway. However, the role and mechanism of RTEF-1 in VC, particularly in calcification of VSMCs, are poorly understood. Our results showed that RTEF-1 was reduced in calcified VSMCs. RTEF-1 significantly ameliorated β-glycerophosphate (β-GP)-induced VSMCs calcification, as detected by alizarin red staining and calcium content assay. Also, RTEF-1 reduced alkaline phosphatase (ALP) activity and decreased expressions of osteoblast markers such as Osteocalcin and Runt-related transcription factor-2 (Runx2), but increased expression of contractile protein, including SM α-actin (α-SMA). Additionally, RTEF-1 inhibited β-GP-activated Wnt/β-catenin pathway which plays a critical role in calcification and osteogenic differentiation of VSMCs. Specifically, RTEF-1 reduced the levels of Wnt3a, p-β-catenin (Ser675), glycogen synthase kinase-3β (GSK-3β), and p-GSK-3β (Ser9), but increased the levels of p-β-catenin (Ser33/37). Also, RTEF-1 increased the ratio of p-β-catenin (Ser33/37) to β-catenin proteins and decreased the ratio of p-GSK-3β (Ser9) to GSK-3β protein. LiCl, a Wnt/β-catenin signaling activator, was observed to reverse the protective effect of RTEF-1 overexpression on VSMCs calcification induced by β-GP. Accordingly, Dickkopf-1 (Dkk1), a Wnt antagonist, attenuated the role of RTEF-1 deficiency in β-GP-induced VSMCs calcification. Taken together, we concluded that RTEF-1 ameliorated β-GP-induced calcification and osteoblastic differentiation of VSMCs by inhibiting Wnt/β-catenin signaling pathway.

In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with diverse structures, a series of novel S-DACO analogues of 6-(2-cyclohexyl-1-alkyl)-2-(2-oxo-2-phenyl-ethylsulfanyl)pyrimidin-4(3H)-ones were designed, synthesized and evaluated for their antiviral activities in MT-4 cells. Most of these new compounds showed moderate to good activities against wild type HIV-1 with IC50 values ranging from 7.55 μmol/L to 0.018 μmol/L. Among them, compound 5c was identified as the most promising inhibitor against HIV-1 replication with an IC50 = 0.018 μmol/L, CC50 = 194 μmol/L, and SI = 12791, which was much more potent than the reference drugs NVP and DLV and comparable to AZT and EFV. In addition, 5c also exhibited improved activity against double mutant HIV-1 strain RES056 compared to that of the reference drugs NVP/DLV and DB02. The preliminary structure-activity relationship (SAR) and molecular modeling studies were also discussed, which provides some useful indications for guiding the further rational design of new S-DACO analogues. keywords: NNRTIs, -DABOs, -DACOs, Anti HIV-1 activity, SAR ispartof: Chinese Chemical Letters vol:32 issue:3 pages:1020-1024 status: published

Our previous study has demonstrated that miR-23b enhances oxidized low-density lipoprotein (oxLDL)-induced inflammatory response of macrophages through the A20/NF-κB signaling pathway, thus contributing to atherosclerosis. This study aims to further investigate the upstream regulators of miR-23b in mediating oxLDL-induced inflammatory response. Human monocyte cell line THP1 was induced to differentiate into macrophages followed by the oxLDL stimulation of inflammatory response. The expression of miR-23b, LINC01140, and p53 mRNA was detected by quantitative PCR. The combination of miR-23b and LINC01140 was confirmed by luciferase reporter assay and RNA immunoprecipitation. The binding of p53 and LINC01140 promoter was determined by luciferase reporter assay. The level of inflammatory cytokines, including MCP-1, TNF-α, and IL-1β, was assessed by enzyme-linked immunosorbent assay. LINC01140 was downregulated, while p53 and miR-23b were upregulated in oxLDL-induced inflammatory response of macrophages. Overexpression of LINC01140 reduced NF-κB activity by reducing miR-23b and increasing A20. The transcription of LINC01140 was inhibited by binding of p53 and the LINC01140 promoter region. Knockdown of p53 significantly reduced NF-κB activity and level of inflammatory cytokines by promoting LINC01140 expression. Our findings demonstrated that LINC01140 acts as an anti-inflammatory factor through negatively regulating miR-23/A20 axis. In addition, p53 is identified as a transcriptional repressor of LINC01140.

Domino processes initiated by intramolecular nucleopalladation of alkynes have been developed into powerful synthetic tools for the synthesis of functionalized heterocycles. However, a catalytic enantioselective version of this class of reactions remains scarce. We report herein that reaction of 2-alkynylanilines with prochiral cyclopentenes in the presence of a catalytic amount of Pd(OAc)2 , a chiral bidentate pyrox ligand and O2 as terminal oxidant affords the structurally diverse indole-cyclopentene conjugates bearing two stereocenters in a highly diastereo- and enantio-selective manner. One of the products is converted to a heavily functionalized tetracyclic indolinone derivative.

Phase transition is common during (de)-intercalating layered sodium oxides, which directly affects the structural stability and electrochemical performance. However, the artificial control of phase transition to achieve advanced sodium-ion batteries is lacking, since the remarkably little is known about the influencing factor relative to the sliding process of transition-metal slabs upon sodium release and uptake of layered oxides. Herein, we for the first time demonstrate the manipulation of oxygen vacancy concentrations in multinary metallic oxides has a significant impact on the reversibility of phase transition, thereby determining the sodium storage performance of cathode materials. Results show that abundant oxygen vacancies intrigue the return of the already slide transition-metal slabs between O3 and P3 phase transition, in contrast to the few oxygen vacancies and resulted irreversibility. Additionally, the abundant oxygen vacancies enhance the electronic and ionic conductivity of the Na0.9Ni0.3Co0.15Mn0.05Ti0.5O2 electrode, delivering the high initial Coulombic efficiency of 97.1%, large reversible capacity of 112.7 mAh·g−1, superior rate capability upon 100 C and splendid cycling performance over 1,000 cycles. Our findings open up new horizons for artificially manipulating the structural evolution and electrochemical process of layered cathodes, and pave a way in designing advanced sodium-ion batteries.

Background Sepsis is a complex syndrome characterized by a dysregulated inflammatory response to systemic infection and leads to shock, multiple organ failure and death especially if not recognized early and treated promptly. Previous studies have suggested Maresin 1 (MAR1) can alleviate systemic inflammation in sepsis, but its mechanism has not been clarified. Methods RAW 264.7 cells and human primary peripheral blood mononuclear cells (hPBMCs) were pretreated with LPS and MAR1. The mRNA expression and supernatant levels of pro-inflammatory cytokines, tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-6 were evaluated by RT-qPCR and ELISA, respectively. The expression levels of Sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and Peroxisome proliferator-activated receptor gamma (PPAR-γ) were determined by RT-qPCR and Western blot analysis, respectively. Results Our results show that LPS-induced inflammation increased the expression and secretion of proinflammatory cytokines TNF-α, IL-1β and IL-6 and induced suppression of SIRT1, PGC-1α, and PPAR-γ expression, which could be reversed by MAR1. And the effect of MAR1 was eliminated by repression of SIRT1/PPAR-γ and enhanced by PGC-1α overexpression. Conclusions MAR1 suppressed inflammatory response in LPS-induced RAW 264.7 macrophages and hPBMCs via the SIRT1/PGC-1α/PPAR-γ pathway.

As a kind of electrode materials, zeolite imidazole frameworks have attracted extensive interest for supercapacitor in virtue of its high porosity, large specific surface area and structural diversity. Herein, a novel composite Zn–Ni–Se/Ni(OH)2 hierarchical microflower composed of looser and corrugated nanosheets has been successfully fabricated with coprecipitation and an uncomplicated two-step hydrothermal method utilizing zeolite imidazole frameworks-8 as precursor. The resultant Zn–Ni–Se/Ni(OH)2-based electrode exhibits markedly improved electrochemical properties with a specific capacitance of 1632.8 F g−1 at 2 A g−1 and superior cycling stability (85.4% of the initial retention after 2000 cycles at 6 A g−1), which are superior to those of Zn–Ni–Se and Ni(OH)2 electrodes. The enhanced performance of Zn–Ni–Se/Ni(OH)2 composite is attributed to the synergistic contributions from Zn–Ni–Se and Ni(OH)2 materials together with the superior properties of specific hierarchical microflower structure. This work provides a meaningful guidance for designing and preparing other composites with distinctive morphologies for pseudocapacitor application.

The high charge overpotential of Li–CO2 batteries leads to short calendar life and low energy efficiency. Solid catalysts such as functional carbon materials and noble metals have been studied extensively to facilitate the decomposition of Li2CO3. However, the charge potential is still over 4 V and side reactions of electrolytes are still unavoidable. Unlike progressively developed catalysts, few efforts have been made for the optimization of electrolytes, which is the bottleneck to develop practical Li–CO2 batteries. Here, we demonstrate a binary molten salt Li–CO2 battery operating at elevated temperature. In the presence of an involatile molten salt electrolyte, CO2 evolution during the charging process can be controlled below 3.6 V with a carbon cathode, which is even lower than previously reported values with noble metal catalysts. In addition to this optimized electrolyte solution, Ru nanoparticles with high catalytic activities are also prepared for the solid cathode. Based on this heterogeneous electrocatalysis, the charge potential of this Li–CO2 battery is further reduced to 3.2 V, and the cycling life is extended to 70 cycles. This work provides a promising strategy to extend the working conditions of Li–CO2 batteries to higher temperatures. It also provides a direct insight into the reduction of the high charge overpotential of Li–CO2 batteries, and mitigation of electrolyte decomposition.

Duck egg white (DEW) is considered as an abandoned protein resource. For a higher-value utilization, preparation of immunomodulatory peptides from the extracted ovalbumin in DEW was explored. Among the hydrolysates catalyzed by five proteases, papain hydrolysate (PH) shows the highest degree of hydrolysis and the strongest immunomodulatory activity. PH could significantly enhance the phagocytic capacity and promote the NO, TNF-α, and IL-6 secretion of RAW 264.7 cells, involving toll-like receptor 2 and 4. After purification, nine identified peptides were synthesized to confirm the immunomodulatory effect, and five of them exhibit a strong activity. The peptide, TQIDKVVHFDKLPGF, presents the highest immunomodulatory activity. Moreover, the results of molecular docking indicate that nine peptides interacted with toll-like receptor 2 and 4 and all show good affinity. Furthermore, three peptides with high affinity and strong immune activity were selected for interaction site map analysis. Three peptides could form hydrogen bonds with the receptor and bind stably, which contributes to the immunomodulatory activity of the peptide. Results suggest that DEW can be a promising source of immunomodulatory peptides.

Bone targeting is one of the most potentially valuable therapeutic methods for medically treating bone diseases, such as osteoarthritis, osteoporosis, nonunion bone defects, bone cancer, and myeloma-related bone disease, but its efficacy remains a challenge due to unfavorable bone biodistribution, off-target effects, and the lack of cell specificity. To address these problems, we synthesized a new dual-targeting nanocarrier for delivery to bone by covalently modifying the G4.0 PAMAM dendrimer with the C11 peptide and the CH6 aptamer (CH6-PAMAM-C11). The molecular structure was confirmed using 1H-NMR and FT-IR spectroscopy. CLSM results showed that the novel nanocarrier could successfully accumulate in the targeted cells, mineralized areas and tissues. DLS and TEM demonstrated that CH6-PAMAM-C11 was approximately 40-50 nm in diameter. In vitro targeting experiments confirmed that the C11 ligand had a high affinity for HAP, while the CH6 aptamer had a high affinity for osteoblasts. The in vivo biodistribution analysis showed that CH6-PAMAM-C11 could rapidly accumulate in bone within 4 h and 12 h and then deliver drugs to sites of osteoblast activity. The components of CH6-PAMAM-C11 were well excreted via the kidneys. The accumulation of many more CH6-PAMAM-C11 dual-targeting nanocarriers than single-targeting nanocarriers was observed in the periosteal layer of the rat skull, along with aggregation at sites of osteoblast activity. All of these results indicate that CH6-PAMAM-C11 may be a promising nanocarrier for the delivery of drugs to bone, particularly for the treatment of osteoporosis, and our research strategy may serve as a reference for research in targeted drug, small molecule drug and nucleic acid delivery.

Scaffold proteins play crucial roles in orchestrating synaptic signaling and plasticity in the excitatory synapses by providing a structural link between glutamatergic receptors, signaling molecules, and neuronal cytoskeletons. FRMPD4 is a neural scaffold protein that binds to metabotropic glutamate receptors via its FERM domain. Here, we determine the crystal structure of the FERM domain of FRMPD4 at 2.49 Å resolution. The structure reveals that the canonical target binding groove of FRMPD4 FERM is occupied by a conserved fragment C-terminal to the FERM domain, suggesting that the FRMPD4–mGluR interaction may adopt a distinct binding mode. In addition, FRMPD4 FERM does not contain a typical phosphoinositide binding site at the F1/F3 cleft found in ERM family FERM domains, but it possesses a conserved basic residue cluster on the F2 lobe which could bind to lipid effectively. Finally, analysis of mutations that are associated with X-linked intellectual disability suggests that they may compromise the biological function of FRMPD4 by destabilizing the FERM structure.

Many metal-organic cages (MOCs) and a few hydrogen-bonded organic cages (HOCs) have been investigated, but little is reported about cooperative self-assembly of MOCs and HOCs. Herein, we describe an unprecedented MOC&HOC co-crystal composed of tetrahedral Ti4 L6 (L=embonate) cages and in-situ-generated [(NH3 )4 (TIPA)4 ] (TIPA=tris(4-(1H-1,2,4-triazol-1-yl)phenyl)amine) cages. Chiral transfer is observed from the enantiopure Ti4 L6 cage to enantiopure [(NH3 )4 (TIPA)4 ] cage. Two homochiral supramolecular frameworks with opposite handedness (PTC-235(Δ) and PTC-235(Λ)) are formed. Such MOC&HOC co-crystal features high stability in water and other solvents, affording single-crystal-to-single-crystal transformation to trap CH3 CN molecules and identify disordered NH4 + cations. A tablet pressing method is developed to test the third-order nonlinear optical property of KBr-based PTC-235 thin film. Such a thin film exhibits an excellent optical limiting effect.

Apoptosis is an important programmed cell death process involved in ischemia/reperfusion injury. MicroRNAs are considered to play an important role in the molecular mechanism underlying the regulation of cerebral ischemia and reperfusion injury. However, whether miR-670 can regulate cell growth and death in cerebral ischemia/reperfusion and the underlying mechanism are poorly understood. In this study, we established mouse models of transient middle artery occlusion and Neuro 2a cell models of oxygen-glucose deprivation and reoxygenation to investigate the potential molecular mechanism by which miR-670 exhibits its effects during cerebral ischemia/reperfusion injury both in vitro and in vivo. Our results showed that after ischemia/reperfusion injury, miR-670 expression was obviously increased. After miR-670 expression was inhibited with an miR-670 antagomir, cerebral ischemia/reperfusion injury-induced neuronal death was obviously reduced. When miR-670 overexpression was induced by an miR-670 agomir, neuronal apoptosis was increased. In addition, we also found that miR-670 could promote Yap degradation via phosphorylation and worsen neuronal apoptosis and neurological deficits. Inhibition of miR-670 reduced neurological impairments after cerebral ischemia/reperfusion injury. These results suggest that microRNA-670 aggravates cerebral ischemia/reperfusion injury through the Yap pathway, which may be a potential target for treatment of cerebral ischemia/reperfusion injury. The present study was approved by the Institutional Animal Care and Use Committee of China Medical University on February 27, 2017 (IRB No. 2017PS035K).

Hyperglycemia is the dominant phenotype of diabetes and the main contributor of diabetic complications. Puerarin is widely used in cardiovascular diseases and diabetic vascular complications. However, little is known about its direct effects on diabetes. The aim of our study is to investigate its antidiabetic effect in vivo and in vitro, and explore the underlying mechanism. We used type I diabetic mice induced by streptozotocin to observe the effects of puerarin on glucose metabolism. In addition, oxidative stress and hepatic mitochondrial respiratory activity were evaluated in type I diabetic mice. In vitro, glucose consumption in HepG2 cells was assayed along with the qPCR detection of glucogenesis genes expression. Moreover, ATP production was examined and phosphorylation of AMPK was determined using Western blot. Finally, the molecular docking was performed to predict the potential interaction of puerarin with AMPK utilizing program LibDock of Discovery Studio 2018 software. The results showed that puerarin improved HepG2 glucose consumption and upregulated the glucogenesis related genes expression. Also, puerarin lowered fasting and fed blood glucose with improvement of glucose tolerance in type I diabetic mice. Further mechanism investigation showed that puerarin suppressed oxidative stress and improved hepatic mitochondrial respiratory function with enhancing ATP production and activating phosphorylation of AMPK. Docking study showed that puerarin interacted with AMPK activate site and enhancing phosphorylation. Taken together, these findings indicated that puerarin exhibited the hypoglycemic effect through attenuating oxidative stress and improving mitochondrial function via AMPK regulation, which may serve as a potential therapeutic option for diabetes treatment.