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Successful synthesis of glyconanoparticles has attracted much attention due to their various biointeractive capabilities, but it is still a challenge to understand different single-cell responses to exogenous particles among cell populations. Herein, we designed polyaniline-containing galactosylated gold nanoparticles (Au@PGlyco NPs) via in situ polymerization of ortho-nitrophenyl-β-galactoside assisted by Au nucleation. The nanogold-carrying polyaniline block produced electromagnetic enhancement in surface-enhanced Raman scattering (SERS). The underlying polymerization mechanism of ortho-nitrophenyl compounds via the formation of Au nanoparticles was investigated. Depending on how the galactoside moiety reacted with β-galactosidase derived from bacteria, the Au@PGlyco NPs-mediated SERS biosensor could detect low amounts of bacteria (∼1 × 102 CFU/mL). In addition, a high accumulation of Au@PGlyco NPs mediated the immune response of tumor-associated M2 macrophages to the immunogenic M1 macrophage transition, which was elicited by reactive oxygen levels biostimulation using single-cell SERS-combined fluorescence imaging. Our study suggested that Au@PGlyco NPs may serve as a biosensing platform with the labeling capacity on galactose-binding receptors expressed cell and immune regulation.

Design and preparation of layered composite materials alternating between nucleic acids and proteins has been elusive due to limitations in occurrence and geometry of interaction sites in natural biomolecules. We report the design and kinetically controlled stepwise synthesis of a nano-sandwich composite by programmed noncovalent association of protein, DNA and RNA modules. A homo-tetramer protein core was introduced to control the self-assembly and precise positioning of two RNA–DNA hybrid nanotriangles in a co-parallel sandwich arrangement. Kinetically favored self-assembly of the circularly closed nanostructures at the protein was driven by the intrinsic fast folding ability of RNA corner modules which were added to precursor complex of DNA bound to the protein. The 3D architecture of this first synthetic protein–RNA–DNA complex was confirmed by fluorescence labeling and cryo-electron microscopy studies. The synthesis strategy for the nano-sandwich composite provides a general blueprint for controlled noncovalent assembly of complex supramolecular architectures from protein, DNA and RNA components, which expand the design repertoire for bottom-up preparation of layered biomaterials.

Ten compounds (1–10) were obtained from soil-derived Penicillium cremeogriseum W1-1 with the antimicrobial guided isolation procedure. Among them, 4 presented broad-spectrum antimicrobial activities and its preliminary mechanisms were evaluated. Compound 4 showed growth inhibition on drug-resistant pathogenic strains Escherichia coli and Candida albicans with post-contact effect (PCE), changed the morphology and membrane structure, killed cells with leakage, inhibited the growth of C. albicans by eradicating biofilms. Interestingly, the fraction containing 4 presented in vivo anti-pathogenic activities in mice, indicating this indole diterpenoid alkaloid could been used as potential antimicrobial agent.

This study uses the WRF-Chem model combined with the empirical kinetic modeling method (EKMA curve) to study the compound pollution event in Beijing that happened in 13–23 May 2017. Sensitivity tests are conducted to analyze ozone sensitivity to its precursors, and to develop emission reduction measures. The results suggest that the model can accurately simulate the compound pollution process of photochemistry and haze. When VOCs and NOx were reduced by the same proportion, the effect of O3 reduction at peak time was more obvious, and the effect during daytime was more significant than at night. The degree of change in ozone was peak time > daytime average. When reducing or increasing the ratio of precursors by 25% at the same time, the effect of reducing 25% VOCs on the average ozone concentration reduction was most significant. The degree of change in ozone decreased with increasing altitude, the location of the ozone maximum change shifted westward, and its range narrowed. As the altitude increases, the VOCs-limited zone decreases, VOCs sensitivity decreases, NOx sensitivity increases. The controlled area changed from near-surface VOCs-limited to high-altitude NOx-limited. Upon examining the EKMA curve, we have found that suburban and urban are sensitive to VOCs. The sensitivity tests indicate that when VOCs in suburban are reduced about 60%, the O3-1h concentration could reach the standard, and when VOCs of the urban decreased by about 50%, the O3-1h concentration could reach the standard. Thus, these findings could provide references for the control of compound air pollution in Beijing.

Objective Topical sinonasal rinse therapies may alter the local microbiome and improve disease control in chronic rhinosinusitis (CRS). The objective of this study was to examine microbiome changes in post-surgical CRS patients when rinsing with commercially available products containing xylitol or Lactococcus lactis. Methods A crossover-type protocol with a washout period was designed. Swab samples from anterior ethmoid cavities of CRS patients were collected prospectively at baseline. Subjects were provided packets containing either L. lactis W136 or xylitol in non-blinded fashion and instructed to add it to their rinse bottles daily for 28 days, after which another swab was taken. A saline wash-out period was completed and a third swab taken. A final 28-day regimen of the opposite product was followed by a final swab. DNA extraction and sequencing of the 16S rRNA gene allowed for global microbiome analysis. Results We enrolled 25 subjects with CRS and 10 controls resulting in 70 adequate samples. Increased detection of Lactococcus was observed after use of L. lactis. No significant trends in alpha or beta diversity as a result of treatment were observed. SNOT-22 score did not change significantly following treatment with xylitol, L. lactis, or saline. Conclusion We did not detect any major clinical or microbiome-level effect due to treatment with two topical rinse products. Further research is needed to elucidate their clinical utility and possible probiotic effect. Level of evidence 3.

Six new angucycline derivatives, named monacycliones G-K (1-5) and ent-gephyromycin A (6), as well as three known ones (7-9) were discovered from the marine sediment-derived actinomycete Streptomyces sp. HDN15129 guided by Global Natural Products Social (GNPS) molecular networking. Structures including absolute configurations were elucidated by extensive NMR, MS, and ECD analyses. Among them, monacyclione G (1) possesses a unique scaffold featuring a xanthone core linked to the aminodeoxysugar ossamine, and monacycliones H-J (2-4) are rare examples of natural angucyclines with an S-methyl group. Monacycliones I and J (3 and 4) showed cytotoxic activity against multiple human cancer cell lines, with IC50 values ranging from 3.5 to 10 μM.

A porous metal–organic framework (MOF) based on Zn(II) metal nodes was prepared via reaction of rigid V-shaped ligand 2,6-di(2′,5′-dicarboxylphenyl)pyridine (H4L) along with Zn(NO3)2·6H2O in water and DMF mixed solvent, and its chemical formula was [Zn3(L)(OH)2(H2O)4](DMF)5 (1). The results show that the obtained activated 1a has catalytic activity for aromatic aldehydes cyanation under the existence of the trimethylsilyl cyanide, thus providing trimethylsilyl cyanohydrin in the form of shape along with size selection. In addition, a feasible synergistic mechanism of 1a for cyanosilylation of aldehyde also has been put forward. Furthermore, the treatment function of the compound on bladder cancer cells was assessed. The reverse transcription-polymerase chain reaction (PT-PCR) was carried out to determine cyclindromatosis (CYLD) and miR-130 relative expression in bladder cancer cells after the combine therapy. Besides, the mechanism of the compound was explored, by evaluating the level of autophagic programed cell death by western blot.

In this study, potato plants displaying symptoms of blackleg and soft rot were collected in Guangdong Province, China, and the causative bacterial pathogens were isolated from symptomatic tissues. In total, five pathogenic isolates (Po-2, Po-3, Po-4, Po-10, and Po-11) were selected and preliminarily identified as Pectobacterium spp. based on 16S rRNA gene sequencing and detection of the pectate-lyase gene using species-specific primers. Physiological and biochemical tests revealed that the five isolates grew at 37 °C, utilized D-galactose, D-lactose, maltose, melibiose, raffinose, sodium citrate, sucrose and trehalose, but not inosine, inulin, malonate, sorbitol and were sensitive to erythromycin. All isolates were negative for acid production from α-methyl glucoside and production of reducing substances from sucrose. In addition, Po-2, Po-3, and Po-4 utilized Tween 80 and produced indole but did not utilize arabinose, while Po-10 and Po-11 did not use Tween 80 and did not produce indole but utilized arabinose. Pathogenicity assays showed that Po-2, Po-3, and Po-4 infected 32 plant species across 19 families, while Po-10 and Po-11 infected 24 species from 17 families. 16S rDNA and phylogenetic analysis based on eight housekeeping genes (acnA, gapA, icdA, mdh, mtlD, pgi, proA, and rpoS) showed that Po-2, Po-3, and Po-4 clustered with Pectobacterium carotovorum subsp. brasiliensis assignments confirmed using specific primer sets BR1f/L1r, while Po-10 and Po-11 clustered with Pectobacterium parmentieri. This is the first detailed report on P. carotovorum subsp. brasiliensis and P. parmentieri as causative agents of potato blackleg and soft rot in China.

One water-soluble polysaccharide (WDOP) and three alkali-soluble polysaccharides (ADOP1, ADOP2 and ADOP3) were successfully obtained from Dendrobium officinale. Molecular structure of the polysaccharides was analyzed, and in vitro lactic acid fermentation of the polysaccharides by lactic acid bacteria (LAB) and bifidobacteria was performed. All the polysaccharides exerted proliferative effect on the LAB and bifidobacteria. ADOP2 was the most effective one, followed by WDOP. This could be attributed to their molecular structure features, such as a high level of total sugar, uronic acid and reducing sugar, an abundance of glucose and mannose, and a low and middle weight-average molecular weight. ADOP2 and WDOP produced more short-chain fatty acids (SCFAs) than ADOP1 and ADOP3 did during lactic acid fermentation. Propionic and acetic acids were the main SCFAs produced. These findings are useful for understanding the structure-activity relationship of D. officinale polysaccharides in lactic acid fermentation, and for developing new functional foods and beverages from D. officinale.

Dense polycrystalline cubic boron nitride (PcBN) composites were fabricated by high-pressure and high-temperature (HPHT) sintering using polysilazane (PSN) and Al as sintering additive. After high-energy ball milling, the cBN fine particles were uniformly coated with PSN by ultrasonic treatment. After thermocuring and pyrolysis, the cBN–SiCN particles were mixed with Al. The PcBN composites were prepared after sintering at 1450 °C for 10 min with a pressure of 5 GPa. The refining effect of high-energy ball milling on the cBN particles was studied by scanning electron microscopy (SEM) and laser particle size analyzer. The oxidation of the cBN particles after milling was investigated by nitrogen–oxygen analyzer. The phase composition and microstructure of the sintered PcBN composites were investigated by X-ray diffractometer (XRD) and SEM. The main phases of the sintered PcBN composites are cBN, AlN, SiC and Si3N4. The conversion of cBN to hBN was inhibited by the formation of AlN. The mechanical properties of the sintered PcBN composites were improved by the appearance of SiC and Si3N4. The density and mechanical properties of the PcBN composites both increased with the content of the cBN particles increasing. The sintered sample with 60 wt% cBN, 30 wt% PSN and 10 wt% Al showed the best results: density of 99.7%, Vickers’ hardness of (25.2 ± 0.8) GPa and flexural strength of (602 ± 15) MPa.

DNA tetrahedral nanomaterials have been widely used in the fields of biosensing, drug delivery, bioimaging and separation analysis because of their high stability, good biocompatibility and easy modification. Through different designs, specific functional molecules can be modified at DNA tetrahedral vertices, DNA tetrahedral cage structures, DNA double helix structures or DNA tetrahedron arms. The advantages of the materials combine well with the specific functions of the active molecules. This paper reviewed the development of DNA nanotechnology, and introduced four different functional modifications of DNA tetrahedron nanomaterials and their research status.

Objective: To investigate the effects of “Yingwei Fang” on nitric oxide synthase (eNOS), endothelin-converting enzyme (ECE) and homocysteine (Hey) in patients with type 2 diabetes mellitus. Methods: 39 cases of type 2 diabetes mellitus with different syndromes were observed, including 14 cases of Yin deficiency heat, 10 cases of Qi and Yin deficiency and 15 cases of Yin and Yang deficiency. All patients took “Yingwei Fang” capsules orally, 5 capsules per time, 3 times a day. At the same time, they were combined with conventional treatment such as dialectical TCM dialectical theory of treatment and hypoglycemia. The changes of eNOS, ECE and Hcy were measured after 150 days of treatment and compared with those before treatment. RESULTs: After treatment, there were changes in $e$ NOS, ECE and Hcy in patients with Yin deficiency, Qi and Yin deficiency and Yin and Yang deficiency, among which eNOS, ECE and Hcy were significantly improved (P

Single-nucleotide polymorphisms (SNPs) are the abundant forms of genetic variations, which are closely associated with serious genetic and inherited diseases, even cancers. Here, a novel SNP detection assay has been developed for single-nucleotide discrimination by nanopore sensing platform with DNA probed Au nanoparticles as transport carriers. The SNP of p53 gene mutation in gastric cancer has been successfully detected in the femtomolar concentration by nanopore sensing. The robust biosensing strategy offers a way for solid nanopore sensors integrated with varied nanoparticles to achieve single-nucleotide distinction with high sensitivity and spatial resolution, which promises tremendous potential applications of nanopore sensing for early diagnosis and disease prevention in the near future.

Fluorescent derivatives of the β-amyloid peptides (Aβ) are valuable tools for studying the interactions of Aβ with cells. Facile access to labeled expressed Aβ offers the promise of Aβ with greater sequence and stereochemical integrity, without impurities from amino acid deletion and epimerization. Here, we report methods for the expression of Aβ(42) with an N-terminal cysteine residue, Aβ((C1–42)), and its conjugation to generate Aβ(42) bearing fluorophores or biotin. The methods rely on the hitherto unrecognized observation that expression of the Aβ((MC1–42)) gene yields Aβ((C1–42)) peptide, because the N-terminal methionine is endogenously excised by E. coli. Conjugation of the Aβ((C1–42)) with maleimide-functionalized fluorophores or biotin affords the N-terminally labeled Aβ(42). The expression affords ca. 14 mg of N-terminal cysteine Aβ from one liter of bacterial culture. Subsequent conjugation affords ca. 3 mg of labeled Aβ from one liter of bacterial culture with minimal cost for labeling reagents. HPLC analysis indicates the N-terminal cysteine Aβ to be more than 97% pure and labeled Aβ peptides to be 94–97% pure. Biophysical studies show that the labeled Aβ peptides behave similarly to unlabeled Aβ and suggest that labeling of the N-terminus does not substantially alter the properties of the Aβ. We further demonstrate applications of the fluorophore-labeled Aβ peptides, by using fluorescence microscopy to visualize their interactions with mammalian cells and bacteria. We anticipate that these methods will provide researchers convenient access to useful N-terminally labeled Aβ, as well as Aβ with an N-terminal cysteine that enables further functionalization.

Three new phenazine metabolites, strepphenazine A-C (1-3), along with a known compound baraphenazine E 4 were isolated from the culture broth of a Streptomyces strain YIM PH20095. The structures were elucidated based on the spectral data. Compounds 1-4 showed different antifungal activity against Fusarium oxysporum, Plectosphaerella cucumerina, Alternaria panax, and Phoma herbarum, which caused root-rot disease of Panax notoginseng with minimal inhibitory concentrations (MICs) of 16-64 μg/mL; compared with compound 4, compounds 1-3 showed better antifungal activity against some of these pathogenic fungi with MICs of 16-32 μg/mL, while compound 4 showed antifungal activity against F. oxysporum, P. cucumerina, and A. panax with the same MICs of 64 μg/mL. Thus, strain YIM PH20095 provides new sources for the development of biological control agents to prevent the infection of pathogenic fungi of P. notoginseng.

Acyltransferase (AT)-less type I polyketide synthases (PKSs) produce complex natural products due to the presence of many unique tailoring enzymes. The 3-hydroxy-3-methylglutaryl coenzyme A synthases (HCSs) are responsible for β-alkylation of the growing polyketide intermediates in AT-less type I PKSs. In this study, we discovered a large group of HCSs, closely associated with the characterized and orphan AT-less type I PKSs through in silico genome mining, sequence and genome neighbourhood network analyses. Using HCS-based probes, the survey of 1207 in-house strains and 18 soil samples from different geographic locations revealed the vast diversity of HCS-containing AT-less type I PKSs. The presence of HCSs in many AT-less type I PKSs suggests their co-evolutionary relationship. This study provides a new probe to study the abundance and diversity of AT-less type I PKSs in the environment and microbial strain collections. Our study should inspire future efforts to discover new polyketide natural products from AT-less type I PKSs.

Although less common than hematite ores, high-grade magnetite ores represent a distinct type of iron mineralization hosted by banded iron formations (BIFs). The Gongchangling iron deposit hosted in ~2.55 Ga BIFs in the North China craton represents one of the most economically important iron deposits in China. Located in mining area II, it is a high-grade (>50 wt % Fe) magnetite deposit and one of the largest of its type in the world. However, the lack of reliable age constraints on iron mineralization has hindered the testing of competing genetic models for the formation of the Gongchangling deposit. In situ U-Pb geochronology of monazite and zircon intergrown with garnet from the proximal alteration zone of a high-grade iron orebody yielded an age of 1.86 Ga, which represents the timing of formation of high-grade magnetite mineralization. This age is coeval with a tectonic extension event recorded in the northeastern North China craton. Our results preclude the previously suggested genetic link between high-grade magnetite mineralization and ~2.50 Ga regional metamorphism. Growth of authigenic monazite and zircon is likely related to the breakdown of detrital zircon, which has undergone metamictization. In combination with previously published data, we propose that the development of zoned alteration associated with the deposit, which is characterized by the garnet-amphibole-magnetite assemblage in the proximal zone changing to a chlorite-quartz–dominated assemblage in the distal zone, can be attributed to a gradual decrease in temperature from >550° to ~250°C and to alteration minerals forming from leaching of the BIFs instead of by replacement of the wall rocks. Magnetite mineralization was controlled by the well-developed faults that cut the BIFs and provided conduits for silica-undersaturated alkaline meteoric fluids. Fluid flow likely took place in an extensional tectonic regime, similar to that invoked elsewhere for hematite mineralization but at greater depths.

Graphene oxide (GO) coated fiber via deposition of GO sheets on polyvinyl alcohol (PVA) fiber containing silver nanowires (AgNWs) was fabricated, and chemical reduction for GO on the fiber surface was carried out to obtain reduced GO (rGO) coated PVA-AgNWs (rGO/PVA-AgNWs) fiber. The results showed that the rGO sheets were closely adhered on the surface of fiber, the electrical conductivity of the fiber increased with coating times of GO, and the conductivity was high up to 2.05×10-3 S/m when GO was coated 3 times on the fiber and reduced. The synergistic effect of rGO and AgNWs for the conductivity was also clearly indicated.

Functional microspheres with subtle designed molecular recognition sites is much highlighted in recent days. We here study the in situ molecular imprinting in the Stober synthesis of resorcinol-formaldehyde (RF) microspheres, and two different approaches are demonstrated. One approach is named as organic molecular imprinting, during which the target molecules of bisphenol A (BPA) are incorporated as the template in the gelation of RF resin. The other is named as inorganic molecular imprinting, during which the template is introduced together with inorganic precursor of titanate. The sizes of the produced spheric particles are found to rely on the ratio of ethanol/water in the reaction medium. Recognition sites which are BPA specific have been detected on both the RF and RF-carbon/TiO2 spheres, and the latter show slightly higher capacity and selectivity in rebinding tests. Importantly, the integration of the photo active nano TiO2 on the submicron spheric carbon support with BPA imprinted sites is of unique advantages, which exhibits as the specific high photocatalytic efficiency on BPA degradation under UV light. This, together with the high selectivity, substantial efficiency and operable uniform size of the composite spheres would be useful in the engineering for environmental and analysis fields.

In possible accident scenarios of the reactor coolant system, the convection and mixing characteristics of borated water have a great influence on reactivity variations in the reactor, and then impact the reactor safety. The mixing and diffusion characteristics of the boric acid solution in the annular downcomer is studied by laser-induced fluorescence (LIF). An aqueous solution of Rhodamine B (RhB) fluorescence dye, which is used to simulate boron solution, was injected in the coolant inlet to visualize the fluid mixing process in the annular volume. Laser sheet was formed by optical system to emit the fluorescence, a high-speed camera was used to capture the fluorescence information for reconstructing the concentration distribution of dye. In order to guarantee the experimental accuracy, LIF image processing and a calibration technology are applied. The concentration profiles were implemented to illuminate the fluid mixing between dye solution and diluted water in the downcomer. The coefficient of variation (COV) was conducted to quantify the spatial and temporal transport of dye in the annular downcomer. The results indicate that a higher flow improves the transport ability of dye in the transverse direction, and shortens the distance and time to uniform. The mass force can accelerate the dye transport in the vertical direction. The whole-field measurement technique implemented in this study is expected to provide an insight in the research of flow mixing in the complex geometry. The experimental results can provide a better understanding of mixing phenomena in annular downcomer, and it is also useful for the annular downcomer CFD validation.

Staphylococcus aureus (S. aureus) infection leads to a severe inflammatory response and causes acute lung injury (ALI), eventually threatening human life. Therefore, it is of importance to find an agent to inhibit inflammation and reduce ALI. Here, we found that costunolide, a sesquiterpene lactone, displays anti-inflammatory effects and ameliorates heat-killed S. aureus (HKSA)-induced pneumonia. Costunolide treatment attenuated HKSA-induced murine ALI in which pulmonary neutrophil infiltration was inhibited, lung edema was decreased, and the production of pro-inflammatory cytokines was significantly reduced. In addition, costunolide dose-dependently inhibited the generation of IL-6, TNF-α, IL-1β, and keratinocyte-derived cytokine (KC), as well as the expression of iNOS, in HKSA-induced macrophages. Furthermore, costunolide attenuated the phosphorylation of p38 MAPK and cAMP response element-binding protein (CREB). Collectively, our findings suggested that costunolide is a promising agent for alleviating bacterial-induced ALI via the inhibition of the MAPK signaling pathways.

Introduction The structural annotation of target relies on high-resolution mass spectrometry (HRMS) information resulting in dubious identities in most cases. The accurate annotation of isomeric structures is still challenging to be confirmed with significant bottleneck. Objective This study focused on the improvement of structural annotation of candidate structures via four pairs of isomeric flavanone-7-O-diglucosides and their basic flavanone aglycones commonly detected in citrus products. Method An integrated liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) approach merging retention time, accurate mass, tandem mass spectrometry (MS/MS) information (diagnostic ions), ion ratio at selected collision energy was established successfully. Results Feasibility of this approach was validated confidently in biological samples with relative standard deviation (RSD) of ion ratio range from 3.91 to 12.28%. Differences of fragmentation patterns of citrus flavanones were illustrated reasonably. MS/MS fragments of (S)-hesperetin and (S)-isosakuranetin were complicated and showed typical radical ion [1,2 A - H]•- (m/z 164) in negative ESI mode due to the methoxyl group on B-ring, which showed huge difference with (R)-hesperetin and (R)-isosakuranetin. Conclusion This study integrated multiple levels to boost the confidence of structural annotation relied on LC-HRMS, and provided important values in practice for precise identification of citrus flavanones in biological matrices.

The whole plant of Clerodendranthus spicatus (Thunb.) is one of popular functional food in south of China, named as "kidney tea" and used to ameliorate renal inflammation. In order to verify this potential function and explore the accurate compounds responsible for inflammation, the ethanol extract, fractions, and subfractions of this plant were prepared to evaluate anti-inflammation effect on xylene-induced acute inflammatory mice model, and the results indicated that two subfractions from EtOAc fraction show potential activities. Subsequent bioassay-guided isolation of the bioactive subfractions led to isolation of 25 compounds. Among them, compounds 2, 4, 5, 9-11, 13, 16, 17, and 20-22 inhibited the productions of pro-inflammation factors TNF-α, IL-1β, and IL-8 in lipopolysaccharide (LPS) -induced renal epithelia (HK-2) cells, respectively. Further anti-inflammation evaluation in vivo indicated that the major bioactive compounds 1, 2, 5-7, 17, 21, and 22 from C. spicatus were even better than aspirin. PRACTICAL APPLICATIONS: C. spicatus as a healthy tea has been available in the Chinese market and as a medicine for various disorders such as nephritis, rheumatism, inflammation, gout, and diabetes. Previous pharmacological investigation of the plant revealed the potential anti-inflammatory activities, but the material basis of anti-inflammatory activity remains to be elucidated. In our study, the anti-inflammatory fractions and compounds were obtained by the bioassay-guide isolation and the results showed that the highly oxygenated diterpenoids were major anti-inflammatory compounds, in which 1, 2, 5-7, 17, 21, and 22 were even better than aspirin. This information supported kidney tea as a functional food for treatment of renal inflammation reasonably and may add a new dimension to biological activity of this plant in the field of agriculture as a functional food were cultivated.

An iron oxide (Fe3O4)-mediated photothermal treatment has been revealed as the next generation of noninvasive and nontoxic theranostic nanoagents compared with other inorganic nanoparticles. Nevertheless, iron oxide with NIR-mediated activity is limited by its inability to be mass produced and its long-lasting photon-to-thermal conversion. Herein, we develop using a green reagent, tannic acid (TNA), which assisted hydrothermal reaction to generate black Fe3O4 nanoparticles by using commercially available nanoptical γ-Fe2O3 NPs as a starting material. The phase transformation from γ-Fe2O3 to the reduced form of Fe3O4 is assisted by TNA in the solution phase. Based on the formation of the interfacial TNA-Fe chelation and the delicate phase transformation from γ-Fe2O3 to Fe3O4 structures, the colloidal black Fe3O4 nanoparticles exhibit broad absorption that covers the visible and NIR wavelengths. Specific interfacial ligand-to-metal charge transfers between the TNA and iron ions at the surface of iron oxide nanoparticles, improves the absorbance and leads to the highest photon-to-thermal conversion (η = 35.7%) at 808 nm compared with other iron oxide nanomaterials. After modifying d-mannose (MA) onto the surface of the Fe3O4@TNA nanoparticles, the local heat can efficiently transfer from the Fe3O4@TNA nanoparticles to the vicinity of the bacterial FimH adhesion molecule, causing extensive photothermal injury to O157:H7 and ESBL strain bacteria with over 99% cell death at 200 ppm[Fe] with 808 nm light at 2.25 mW/cm2. Based on its robust photostability, Fe3O4@TNA@MA shows photothermal bactericidal recyclability through magnetic collection, adhesion, and photothermal processes.

RNA helicase A (RHA) is a ubiquitously expressed DExH-box helicase enzyme that is involved in a wide range of biological processes including transcription, translation, and RNA processing. A number of RNA viruses recruit RHA to the viral RNA to facilitate virus replication. DNA viruses contain a DNA genome and replicate using a DNA-dependent DNA polymerase. RHA has also been reported to associate with some DNA viruses during replication, in which the enzyme acts on the viral RNA or protein products. As shown for Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, RHA has potential to allow the virus to control a switch in cellular gene expression to modulate the antiviral response. While the study of the interaction of RHA with DNA viruses is still at an early stage, preliminary evidence indicates that the underlying molecular mechanisms are diverse. We now review the current status of this emerging field.

Injectable hydrogels have aroused much attention for the advantages such as minimally invasive surgery, avoidance of surgical trauma, and filling and repairing irregularly shaped tissue defects. Mussel-inspired injectable hydrogels can be immobilized on the surface of tissues, resulting in stable biomaterial-tissue integration. However, the commonly used biomimetic mussel-inspired hydrogels are prepared by the oxidation of catechol groups, which involves the introduction or production of cytotoxic substances. Moreover, mussel-inspired hydrogels generally display weak mechanical strength and poor adhesiveness because of the consumption of catechol groups during oxidation. Herein, we described a strategy to prepare mussel-inspired injectable hydrogels via the Schiff base reaction. We grafted dopamine, an adhesive motif discovered in the holdfast pads of mussels, to aldehyde-modified alginate backbones. A series of injectable mussel-inspired adhesive, self-healing hydrogels were fabricated by in situ crosslinking of hydrazide-modified poly(l-glutamic acid) (PLGA-ADH) and dual-functionalized alginate (catechol- and aldehyde-modified alginate, ALG-CHO-Catechol). Also, oxidized ALG-CHO-Catechol hydrogels and PLGA/ALG-CHO hydrogels were prepared for comparison. The effects of the crosslinking method, catechol grafting ratio and solid content on the mechanical properties, self-healing behavior, adhesive properties, and hemostatic ability were investigated. Compared with the observations for oxidized ALG-CHO-Catechol hydrogels, more reasonable gelation time and notably enhanced mechanical properties and adhesive behavior were detected in the PLGA/ALG-CHO-Catechol hydrogel system. The PLGA/ALG-CHO-Catechol hydrogels also displayed clear self-healing ability and good cytocompatibility. The strong bioadhesion endowed the PLGA/ALG-CHO-Catechol hydrogels with superior hemostatic performance. These results suggested that PLGA/ALG-CHO-Catechol hydrogel might have great potential as an antibleeding and tissue repair material.

In this study, a high-concentration simulated organic wastewater, made by dissolving methyl violet in water, was degraded using dielectric barrier discharge (DBD) plasma generated in air and O2 respectively. The decoloration rate and chemical oxygen demand (COD) of wastewater were evaluated during plasma treatments with the initial concentration of methyl violet of 300 mg L−1. Results showed that the highest decoloration rate of around 100% within 10 min and the highest COD decrease of 33% within 60 min could be achieved with the O2 plasma treatment at the discharge voltage of 10 kV, while air plasma treatment showed lower efficiency in decolorizing the methyl violet solution and lower COD decrease (24%) after 60 min treatment. UV-Vis spectroscopy and chemical analysis of generated by-products during the plasma-enabled degradation process revealed that the methyl violet molecules could be completely decomposed into some refractory organics in the solution. Based on the experimental results and literature review, a pathway of methyl violet degradation attributed to energetic electrons and highly reactive species generated by DBD was proposed.

IgA nephropathy (IgAN) is one of the main causes of primary glomerulonephritis worldwide, and it is also the main primary disease leading to chronic kidney disease. The purpose of this study is to evaluate the epidemiology and risk factors for progression in Chinese patients with IgAN.In this retrospective study, 246 patients with renal biopsy-proven IgAN were enrolled from January 2012 to June 2018. The patients' data were divided into two groups according to eGFR at the end of follow-up: a high-eGFR group (eGFR≥60ml/min) and a low-eGFR group (eGFR60ml/min).At the end of the study, we identified 49 (19.92%) patients with low-eGFR from 246 IgAN patients. Renal function, represented by serum creatinine, urea nitrogen and cystatin-C, was significantly decreased in the low-eGFR group (P0.001 for all) at the time of renal biopsy. Compared with the high-eGFR group, the age, mean arterial blood pressure (MAP), proteinuria, cholesterol, triglycerides and serum uric acid were significantly higher (P0.05 for all). According to the Oxford evaluation, the proportion of S1-2 (59.2%) and T1-2 (65.3%) was significantly increased (P0.001 for both) and the proportion that had a MEST-C score ≥3 was statistically increased in the low-eGFR group (83.7%, P=0.001).Male, MAP, haematuria, Scr, cholesterol, hemoglobin, Lee classification more than 3 and C1-2 are independent risk factors for low-eGFR in Chinese IgAN patients.

Fibroblast-like synoviocytes (FLS) play a pivotal role in Rheumatoid arthritis (RA) pathogenesis through aggressive migration and invasion. Madecassoside (Madec), a triterpenoid saponin present in Centella asiatica herbs, has a potent anti-inflammatory effect. In the present study, Madec exerted an obvious therapeutic effect in reversing the histological lesions in adjuvant-induced arthritis (AIA) rats. To recognize the anti-rheumatoid potentials of Madec, we further investigated whether Madec interfered with FLS invasion and metalloproteinase (MMP) expression. In cultures of primary FLS isolated from the AIA rats, Madec (10 and 30 μmol·L-1) was proven to considerably inhibit migration and invasion of FLS induced by interleukin 1β (IL-1β), but exhibiting no obvious effect on cell proliferation. Madec repressed IL-1β-triggered FLS invasion by prohibiting the expression of MMP-13. Additionally, Madec suppressed MMP-13 transcription via inhibiting the MMP-13 promoter-binding activity of NF-κB. Our results further showed that Madec down-regulated the translocation and phosphorylation of NF-κB as demonstrated by Western blotting and immunofluorescence assays. In conclusion, our results suggest that Madec exerts anti-RA activity via inhibiting the NF-κB/MMP-13 pathway.

A high-content imaging assay was used to screen the fraction collection of the Natural Product Library at The Scripps Research Institute for inhibitors of Cryptosporidium parvum. A chemical investigation of one strain, Streptomyces sp. CB01388, resulted in the isolation of six herbicidins (1-6), one of which is new (herbicidin L, 1). Five of the six herbicidins (1-3, 5, 6) showed moderate inhibitory activity against C. parvum, with 1 and 6 comparable to the FDA-approved drug nitazoxanide, and 2-6 showed no toxicity to the host HCT-8 cells and human HEK293T and HepG2 cells. These findings highlight the herbicidin scaffold for anti- Cryptosporidium drug development.

In this work, a novel strategy is developed to solve the issue of mutually exclusive high mechanical robustness and thermo-stability for thermoplastic polyurethane (PU). A leaf-like and reticulate interfingering superstructure can be seen. The superstructure of polyurethanes can also be tuned by the polarity of chain extender molecular via changing the number for ferrocene redox centres, thus to further enhance the thermal stability and elasticity of PUs. As a result, by incorporating bisferrocene units into the main chain of PU, a high-performance PU elastomer can be synthesized with a highest initial degradation temperature of T5% of 345 °C, a highest tensile strength of 42.3 MPa with an elongation over 1000%, as well as a toughness of 19.6 GJ m−3. These results conclusively suggest that high-performance thermoplastic polyurethane elastomers had great promise for potential application in a wide range of practical fields.

Eleven new compounds with streptazolin- and obscurolide-type skeletons were isolated from soil-derived Streptomyces alboniger obtained from Tibet, China. Two types of unprecedented skeletons of obscurolide dimer and an obscurolide-type compound with an aromatic polyketide of pentanone substituted at the benzene ring were determined by spectral data analysis. Compound 11 was the first evidence of two nitrogens in streptazolin-type structures. Compound 1 indicated an inhibitory effect on nitric oxide production in LPS-activated macrophages with an inhibition ratio of 51.7% at 50 μM, and on anticoagulant activity on platelet activating factor (PAF)-induced platelet aggregation with an inhibition ratio of 26.0 ± 9.1% at 200 μg mL−1. 11 had anti-acetylcholinesterase activity with an inhibition ratio of 27.2% at a concentration of 50 μM. Mechanistic aspects of the non-enzymatic reaction as well as a more detailed picture of the biosynthetic relationships of the streptazolin- and obscurolide-type metabolites are described. Acidic and basic conditions can inhibit the growth of Streptomyces, and γ-butyrolactones were found to be hormones controlling antibiotic production in Streptomyces. In the pH fermentation tests, acylation of γ-butyrolactones was successfully used to explain the mechanism of influence on the growth of Streptomyces.

As promising electrode materials in supercapacitor, metal oxides have attracted significant attention recently. At present, it is highly desirable but remains challenging to prepare three-dimensional (3D) metal oxides hollow materials for further improving the performance of supercapacitors. Herein, 3D chestnut shell-like Li4Ti5O12 hollow sphere is successfully fabricated by using an effective hydrothermal strategy. Owing to the unique structural feature and the desirable chemical composition, Li4Ti5O12 hollow sphere displays a remarkable capacitance of 653.22 F/g at 1 A/g and keeps 88.56% over 4000 cycle. Furthermore, one aqueous asymmetric supercapacitor (ASC) is constructed based on Li4Ti5O12 and N-doped graphene oxide (NGO) which is synthesized by a facile burning method. The Li4Ti5O12//NGO ASC shows an energy density of 26.15 Wh/kg at power density of 799.83 W/kg, and yet keeps 14.45 Wh/kg even at 8.01 kW/kg. This strategy may offer a versatile idea of tailoring new type of 3D metal oxides hollow materials and opens the possibility for using in high energy storage device.

A facile method for the large-scale production of 4MoO3·2NH3·H2O (MAH) nanocrystal with tunable size and morphology is developed through an antisolvent crystallization approach. The introduction of hydroxyl groups during crystallization promotes the formation of oxygen vacancies on the MAH. Due to the high concentration of Mo5+ centres, small nanosheet thickness, and sandwich-like crystal structure, MAH-20 exhibits an outstanding adsorption capability toward cationic dyes, with the maximum adsorption capacities up to 1169.2 mg·g−1 for methylene blue (MB) and 1452.8 mg·g−1 for rhodamine B (RhB), which are almost 10 times as that of MAH-0. An electrostatic adsorption mechanism is proposed to interpret the highly selective adsorption activity toward cationic dyes. Moreover, a fast and recyclable treatment and adsorbent regeneration are realized based on a continuous flow filtration device.

Influenza virus (IAV) infection is a major cause of severe respiratory illness that affects almost every country in the world. IAV infections result in respiratory illness and even acute lung injury and death, but the underlying mechanisms responsible for IAV pathogenesis have not yet been fully elucidated. In this study, the basic fibroblast growth factor 2 (FGF2) level was markedly increased in H1N1 virus-infected humans and mice. FGF2, which is predominately derived from epithelial cells, recruits and activates neutrophils via the FGFR2-PI3K-AKT-NFκB signaling pathway. FGF2 depletion or knockout exacerbated influenza-associated disease by impairing neutrophil recruitment and activation. More importantly, administration of the recombinant FGF2 protein significantly alleviated the severity of IAV-induced lung injury and promoted the survival of IAV-infected mice. Based on the results from experiments in which neutrophils were depleted and adoptively transferred, FGF2 protected mice against IAV infection by recruiting neutrophils. Thus, FGF2 plays a critical role in preventing IAV-induced lung injury, and FGF2 is a promising potential therapeutic target during IAV infection.

A new natural mycotoxin was isolated from the fermentation broth of Trichoderma sp. Jing-8 and the structure was determined as alternariol 1′-hydroxy-9-methyl ether (1), together with twelve known compounds. The structures were elucidated on the basis of their 1D, 2D NMR spectra and mass spectrometric data. Compounds 1, 8 and 9 indicated inhibitions against germination of the seeds of cabbage with MICs 1 showed the antibacterial activity against Bacillus subtilis and Staphylococcus aureus with MICs at 64 μg/mL. Compound 1 and 3 showed significant DPPH radical-scavenging activities with IC50 at 12 μg/mL, respectively. The OH at C-1′ in compound 1 decreased the cytotoxicity of these mycotoxins. A primary structure–activity relationship about the alternariol derivatives was discussed. Compounds 2–7 and 8 were the first time to be isolated from the Trichoderma.

The rare anishidiol and five new isochromans, including three novel dimers with unprecedented skeletons, were isolated from Stachybotrys sp. PH30583. Their structures were determined by spectral analyses. The bioactivities of these compounds were also investigated. The dimers (6–10) inhibited acetylcholinesterase at 50 µM, but the monomers did not. To investigate the biogenesis of the novel dimers, a time-course investigation of metabolite production was undertaken.

Isofuranonaphthoquinones (IFQs) and Isoindolequinones (IIQs) comprise a small family of natural products, with the latter ones are especially uncommon in nature. Here we report the discovery of seven new IFQs, IFQ A-G (1-7), and three new IIQs, IIQ A-C (8-10), along with the known anthraquinone desoxyerythrolaccin (11), from Streptomyces sp. CB01883, expanding the chemical diversity of this family of natural products. The structures of these natural products were established on the basis of their HR-ESI-MS and nuclear magnetic resonance (NMR) spectroscopic data. All compounds were assessed for antibacterial activity, with 11 and 1, 5-7 exhibiting moderate and weak activities, respectively, against several Gram-positive bacteria tested. Bioinformatics analysis of the Streptomyces sp. CB01883 genome revealed the ifq gene cluster that showed identical genetic organization, with high-sequence identity, to the ifn gene cluster recently cloned from Streptomyces sp. RI-77 and confirmed to encode the biosynthesis of two IFQs, JBIR-76 and JBIR-77. Co-isolation of IFQs with IIQs from Streptomyces sp. CB01883 and facile chemical transformation of selected IFQs to IIQs, as exemplified by 1 to 9, together with the finding of the ifq cluster that most likely only encodes IFQ biosynthesis, support the proposal that IIQs may be derived nonenzymatically from IFQs in the presence of an amine.

This study was undertaken to explore the effects of sulfated polysaccharide (SPPM60-D) from masson pine pollen on [Ca(2+)]i and immune function of RAW264.7 macrophages. SPPM60-D was obtained by subjecting Masson pine pollen to boiling water and alcohol precipitation, 60% ethanol grading precipitation, Sephacryl S-400HR purification, and chlorosulfonic acid-pyridine method sulfation. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure the effect of SPPM60-D on relative activity and proliferation of RAW264.7 cells, and a fluorescence spectrophotometer was used to determine [Ca(2+)]i. Phagocytosis of neutral red was used to determine phagocytosis capacity. Adherence, scratch healing, and transwell assays were used to assess migration and adhesion abilities of macrophages. An enzyme-linked immuno sorbent assay (ELISA) assay was used to assess the secretion of cytokines and inflammatory mediators. A dexamethasone (DEX) inhibition method was used to measure the recovery of RAW264.7 immune activity by SPPM60-D. SPPM60-D significantly increased relative activity, proliferation, and [Ca(2+)]i levels of mouse RAW264.7 cells. It also significantly enhanced the immune function of macrophages from normal and immune-suppressed mouse. The results showed that SPPM60-D mainly bound to TLR4 on macrophages. This activated the TLR4-PI3K-PLC-IP3R signaling pathway, leading to the opening of calcium release-activated calcium channels (CRAC), increasing [Ca(2+)]i and activating the macrophages, and thus improving immunity.

To investigate the effect and underlying mechanisms of Tiaoxin Recipe (a Chinese herbal formula) treatment on Alzheimer's disease (AD).Twelve-week-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mice were used as a model of AD-afflicted mice. One group of mice was treated with Tiaoxin Recipe by gastrogavage for 12 weeks, while two other groups were given intraperitoneal injections of nicotinamide adenine dinucleotide or FK866 for 4 weeks. Morris water maze and thioflavin S staining tests were performed to evaluate cognitive impairment and amyloid plaque deposition, respectively. Serum amyloid-β1-42 (Aβ1-42) content was detected using an enzyme-linked immunosorbent assay, and quantitative reverse transcription-polymerase chain reaction was performed to examine the expression levels of microRNA-34a (miR-34a) in cortex and hippocampus samples of the study mice.Compared with the normal control group, the memory and learning abilities of the APP/PS1 model group were found to be impaired (P 0.01), as shown by the increased levels of senile plaque deposition in cortex and hippocampus (P 0.01), miR-34a expression (P 0.01) and serum Aβ1-42 content (P 0.01). Treatment with Tiaoxin Recipe significantly reduced memory impairment (P 0.01) by reducing amyloid plaque accumulation in cortex and hippocampus (P 0.01), miR-34a expression (P 0.01) and serum Aβ1-42 content (P 0.01) in APP/PS1 mice.Tiaoxin Recipe is a viable complementary or alternative therapeutic treatment that is capable of delaying the development of early-stage AD by inhibiting the expression of miR-34a.

A novel paradigm in tumor biology suggests that non-small-cell lung cancer (NSCLC) growth is driven by lung cancer stem cell (LCSC) like cells, but t here are still not any effective strategies to remove LCSCs. The bispecific antibody (BsAb) is a novel antibody, which can target two different antigens and mediate specific killing effects by selectively redirecting effector cells to the target cells. Here, we designed and synthesized a new BsAb, BsAb-5, that can target cellular mesenchymal-to-epithelial transition factor (c-MET) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in CD166+ LCSCs with high affinity and specificity, for the first time. We showed that BsAb-5 could inhibit hepatocyte growth factor (HGF) mediated tumor development, including proliferation, migration, and apoptosis, serving as an inhibitory c-MET antibody. Moreover, we demonstrated that mechanisms responsible for BsAb-5 in CD166+ LCSCs included inducing c-MET degradation and inhibition of HGF-stimulated c-MET-Notch pathway by using AdHGF infection, nuclei location, and Western blot assays. In vivo, xenograft analysis revealed that mice on BsAb-5 group showed significantly reduced tumor volume. At the meantime, the observed antitumor effects of BsAb-5 were dependent on considerably suppressing T-regulatory cells (Tregs) and up-regulating effector T cells. On the basis of these results, we have identified a potential BsAb drug, which can effectively target c-MET and CTLA-4 in CD166+ LCSCs for the treatment of human NSCLC.

Organic aerosol (OA) concentrations are simulated over the Beijing–Tianjin–Hebei (BTH) region from 9 to 26 January 2014 using the Weather Research and Forecasting model coupled with chemistry (WRF-CHEM), with the goal of examining the impact of heterogeneous HONO sources on SOA formation and SOA formation from different pathways during wintertime haze days. The model generally shows good performance with respect to simulating air pollutants and organic aerosols against measurements in BTH. Model results show that heterogeneous HONO sources substantially enhance near-surface SOA formation, increasing the regional average near-surface SOA concentration by about 46.3 % during the episode. Oxidation and partitioning of primary organic aerosols treated as semi-volatile dominate SOA formation, contributing 58.9 % of the near-surface SOA mass in BTH. Irreversible uptake of glyoxal and methylglyoxal on aerosol surfaces constitutes the second most important SOA formation pathway during the episode, with the SOA contribution increasing from 8.5 % under non-haze conditions to 30.2 % under haze conditions. Additionally, direct emissions of glyoxal and methylglyoxal from residential sources contribute about 25.5 % of the total SOA mass on average in BTH. Our study highlights the importance of heterogeneous HONO sources and primary residential emissions of glyoxal and methylglyoxal to SOA formation over the BTH region in winter.

The current study aimed to assess the role and mechanism of astragaloside IV (AS-IV) in myocardial infarction. A myocardial infarction model was established via the ligation of the left anterior descending artery. Rats were randomly divided into sham, DMSO, model, AS-IV, AS-IV-CID755673 and CID755673 inhibitor groups. Rats were then sacrificed following 4 weeks of treatment and segmental heart samples were obtained for hematoxylin and eosin, and masson staining. The expression of PKD1, HDAC5 and VEGF were analyzed using immunohistochemistry, reverse transcription polymerase chain reaction and western blotting. Compared with the sham and DMSO groups, the morphology of myocardium in the model and CID755673 inhibitor groups were disordered and exhibited necrotic myocardial cells and collagen tissues. Following treatment with AS-IV, the morphology of the myocardium was markedly improved and the number of new blood vessels increased. However, following treatment with CID755673, the myocardial tissue of rats became disordered, with an increased number of necrotic cells and the closure of certain vessels. The expression of PKD1, HDAC5 and VEGF mRNA and protein in myocardial tissue of model group and CID755673 inhibitor group were significantly lower than the other four groups (P

Aryl trifluoromethyl ethers (OCF3), aryl difluoromethyl ethers (OCHF2), and aromatic sulfur pentafluorides (SF5) are of particular interest in drug design due to their favorable properties including high chemical and metabolic stability, suitable lipophilicity, unique electronic properties, definitive conformational characteristics, and their roles in molecular recognition in binding sites of biological targets. The deployments of these functional groups are relatively rare, although these compounds are increasingly found in pharmaceutical agents. This chapter describes a number of FDA-approved drugs and drug candidates that contain OCF3, OCHF2, and SF5 groups: Riluzole for amyotrophic lateral sclerosis Delamanid and Pretomanid for tuberculosis, Pantoprazole for erosive esophagitis, Roflumilast for chronic obstructive pulmonary disease ELQ-300 and DSM-265 for malaria, BMS-665053 for depression, and a fluoro-analog of Rimonabant for obesity. The successful case studies substantiate the prominence of their utilities and synthetic enablement in drug discovery research.