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Conjugated polymers (CPs) attract a lot of attention in sensing, imaging, and biomedical applications by taking advantage of their extraordinary characteristics. However, most of them inevitably aggregate at higher concentrations, leading to attenuated fluorescence efficiency. Herein, we report a fluorescence enhancement strategy for conjugated polymers by using cellulose as a mediator. The composite nanoparticles CMC@PFE-1-NPs are prepared based on carboxymethyl cellulose (CMC) and poly(fluorene-co-phenylene ethynylene) derivative (PFE-1) via self-assembly through electrostatic and hydrophobic interactions. This spatial confinement effectively restricts π-π stacking effects and other nonradiative channels, leading to high luminescent efficiency of isolated PFE-1. A 5-folds enhancement in fluorescence quantum yield for CMC@PFE-1-NPs is obtained compared with conjugated polymers themselves. Furthermore, the nanoparticles realized more sensitive cell imaging. Therefore, this simple and effective method provides a new way for reducing the aggregation between rigid fluorescent molecules and improving their photophysical properties and biological application.

This investigation assessed the responses of soil fertility, enzyme activity, and microbial community diversity to soil texture and land use type. The tested soils included five soil textures (sandy loam, medium loam, heavy loam, light clay, and medium clay soils) with two land use types (uncultivated and paddy soils) in the coastal zone of Zhejiang Province, China. Soil texture had a significant effect on soil pH, electrical conductivity (EC), organic carbon (OC), total nitrogen (TN), available nitrogen (AN), phosphorus (AP) and potassium (AK), catalase and protease activities, total phospholipid fatty acids (PLFAs), bacterial and actinomycetes PLFAs, and microbial diversity (MD). The clay content was significantly positively correlated to soil EC, OC, TN, AN, AP, AK, catalase activity, total PLFAs, bacterial and actinomycetes PLFAs, and MD but significantly negatively associated with soil pH and protease activity. Land use type also had significantly influenced soil pH, EC, OC, TN, AN, AP, AK, catalase, protease and urease activities, total PLFAs, bacterial, actinomycetes, and fungal PLFAs, and MD. The paddy soil had higher OC, TN, AN, AP, catalase, protease and urease activities, total PLFAs, bacterial and actinomycetes PLFAs, and MD but lower soil pH, EC, and AK than the uncultivated soil. The interaction with soil texture and land use type had significantly affected soil pH, EC, OC, TN, AN, AP, AK, catalase and protease activities, total PLFAs, bacterial and actinomycetes PLFAs, and MD. Soil texture and land use type could be considered important factors in improving soil fertility, enzyme activity, and microbial diversity in coastal saline soils.

The oxygen reduction reaction (ORR) has been regarded as a bottleneck in air-cathode microbial fuel cells (MFC). Herein, transition metal oxides and silver were used in combination with a conductive and hydrophilic MXene (Ti3C2) for ORR. The transition metal oxides could facilitate oxygen adsorption and OO bond dissociation to improve the ORR catalytic performance of catalysts, and silver was capable of increasing the ORR kinetics and decreasing the activation overpotential significantly. Ti3C2–MxOy–Ag exhibited high ORR activity with a direct four-electron and indirect four-electron pathway in a neutral medium. In MFCs, the maximum power density was achieved by Ti3C2–MnO2–Ag (418.09 mW m−2), which was 41% higher than that of Ag–Ti3C2 (295.78 mW m−2) and 10.8 times that of Ti3C2 (38.89 mW m−2). This could be attributed to the synergistic effect between transition metal oxides and silver to promote ORR.

Inspired by sanguinarine and chelerythrine, a novel antifungal 2-phenylphthalazin-2-ium scaffold as a simple analogue was designed. Most of the 30 compounds showed excellent inhibition activity against almost all eight phytopathogenic fungi, far superior to sanguinarine and chelerythrine. A third of the compounds were more active than azoxystrobin in most cases. Compounds 26 and 27 showed the highest total activity against all the fungi with EC50 means of ca. 4.6 μg/mL. Fusarium solani showed the highest susceptibility with an EC50 mean of 3.62 μg/mL to 19 compounds. A concentration of 25.0 μg/mL 27 can fully control the Colletotrichum gloeosporioides infection in apples over 9 days. Electron microscopic observations showed that 27 was able to damage the structures of the hypha and cell membrane. The structure-activity relationship showed that the presence of electron-withdrawing groups on the C-ring increases the activity against most of the fungi. Thus, 2-phenylphthalazin-2-ium compounds represent promising leads for the development of novel fungicides.

Titanomagnetite concentrate is difficult to agglomerate by the traditional sintering process (TSP). In this study, the agglomeration properties of titanomagnetite concentrate were studied using the composite agglomeration process (CAP). It was shown that, by adding 40 wt.% pelletized feed, an excellent sinter with yield of 74.33%, a tumbler index of 58.93%, and productivity of 1.65 t (m2 h)−1 were achieved, which were increased by 11.72%, 12.03%, and 37.16% compared with TSP, respectively. Meanwhile, for CAP, the solid fuel consumption was only 43.87 kgcoke/tproduct and the reduction disintegration index of RDI+3.15 was 73.53%. They were decreased by 6.34 kgcoke/tproduct and increased by 24.31%, respectively. The better product quality was mainly attributed to a larger proportion of calcium ferrite and silicoferrite of calcium and aluminum group minerals formed in CAP, which restrained the negative effect of perovskite on agglomeration in association with the matrix feed with ultra-high basicity. The results showed that CAP is an efficient method for agglomeration of titanomagnetite concentrate.

Cancer is a common disease that poses a serious threat to human health. Angiogenesis is essential for the growth and metabolism of tumors, providing oxygen and nutrition for the growth of cells and tissues. However, angiogenesis of tumors depends on the stimulation of growth factors. Vascular Endothelial Growth Factor (VEGFR) is the most unique factor. Therefore, VEGF/VEGFR targeting anticancer drugs are playing an increasingly significant role in clinical trials. In addition, it has been proved that chalcone, the precursor of natural flavonoids, has potential anti-tumor activity, especially anti-angiogenesis activity. This review summarizes the reports about the anti-angiogenesis of chalcone derivatives. Based on the chalcone skeleton, it is divided into substituted chalcones and modified chalcones. The anti-angiogenesis activities of natural or synthetic chalcones, benzene ring modified or connecting bridge modified chalcones are described in this review.

Nalfurafine, a moderately selective kappa opioid receptor (KOR) agonist, is used in Japan for treatment of itch without causing dysphoria or psychotomimesis. Here we characterized the pharmacology of compound 42B, a 3-dehydroxy analogue of nalfurafine and compared with that of nalfurafine. Nalfurafine and 42B acted as full KOR agonists and partial μ opioid receptor (MOR) agonists, but 42B showed much lower potency for both receptors and lower KOR/MOR selectivity, different from previous reports. Molecular modeling revealed that water-mediated hydrogen-bond formation between 3-OH of nalfurafine and KOR accounted for its higher KOR potency than 42B. The higher potency of both at KOR over MOR may be due to hydrogen-bond formation between nonconserved Y7.35 of KOR and their carbonyl groups. Both showed modest G protein signaling biases. In mice, like nalfurafine, 42B produced antinociceptive and antiscratch effects and did not cause conditioned place aversion (CPA) in the effective dose ranges. Unlike nalfurafine, 42B caused motor incoordination and hypolocomotion. As both agonists showed G protein biases, yet produced different effects on locomotor activity and motor incoordination, the findings and those in the literature suggest caution in correlating in vitro biochemical data with in vivo behavior effects. The factors contributing to the disconnect, including pharmacodynamic and pharmacokinetic issues, are discussed. In addition, our results suggest that among the KOR-induced adverse behaviors, CPA can be separated from motor incoordination and hypolocomotion.

Nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) has been widely proposed to reduce nitrogen (N) loss and improve N availability in paddy soil. However, little knowledge exists regarding the optimum dose of DMPP required for inhibiting nitrification in different soil types. In undisturbed soil columns under greenhouse conditions, dynamics of ammonium (NH4+–N) and nitrate (NO3−–N) in floodwater and leachate, and ammonia (NH3) volatilization were studied in two paddy soils (hydragic and gleyed), amended with urea-N at 180 N kg/ha with DMPP applied at 0, 0.45, 0.675, and 0.90 kg/ha (0.25%, 0.375%, and 0.5% of urea-N, respectively). The source of DMPP was Entec® 46 (46% urea-N and DMPP at 0.5% of urea-N) that was mixed with pure urea (fertilizer mixture). DMPP application rates and soil types significantly influenced NH4+–N and NO3−–N concentrations in floodwater and leachate; however, DMPP application rates did not significantly impact NH4+–N concentrations in floodwater. Results indicate that concentrations of both NH4+– N and NO3−–N in leachate and floodwater were peaked between 10 and 20 days after fertilizer application. Increased DMPP application rates increased floodwater and leachate NH4+–N concentrations, while significantly decreasing NO3−–N concentrations in floodwater and leachate, with largest decrease seen in the 0.90-kg/ha DMPP treatment. NH3 emissions were observed after fertilizer was applied and decreased gradually, with no significant differences in response to the DMPP amount. The total N losses via leaching and NH3 emission were significantly decreased at treatments of 0.675 kg/ha and 0.90 kg/ha DMPP, and positively correlated with sand fraction in soil. Compared with the gleyed paddy soil, higher total N loss was observed in the hydragic paddy soil, which was related to the higher sand fraction of the hydragic paddy soil and the better behavior of DMPP in this soil type. Considering economic factors, mineral N concentrations in floodwater and leachate, together with N losses via leaching and volatilization, application of 0.675 kg/ha DMPP could significantly inhibit nitrification in the hydragic paddy soil while application of 0.90 kg/ha DMPP was shown to be the best choice to inhibit nitrification in the gleyed paddy soil.

A new one-dimensional (1-D) copper(II) coordination polymer, namely, {[Cu(L)(2,2’-bipy)]·0.5DMF}n (1) (H2L= 2,2’-[benzene-1,4-diylbis(methanediylsulfanediyl)]dibenzoic acid, 2,2’-bipy= 2,2’-bipyrid...

By means of first-principles calculations, we have proposed an ab initio modeling to establish a formula between the hydrogen evolution rate and its overpotential of hydrogen evolution reaction (HER), relating with three different rate determining mechanisms, when Volmer reaction, Tafel reaction and Heyrowsky reaction are the rate determining steps of the entire reaction, respectively. Within this modeling, the free energy ( Δ G H * ) of the adsorbed hydrogen atom and the concentration of hydrogen ions in the solution have been correlated to the exchange current density. The hydrogen evolution modeling has been validated by available experimental results. Furthermore, by combining the previously proposed first-principles modeling of the anodic dissolution and this modeling of the HER in the electrochemical corrosion, the polarization curves of the 18 crystallographic surfaces of pure Mg have been theoretically derived. It has been found that in a neutral solution ( p H = 7 ) the corrosion current densities (icorr) of the 18 crystallographic surfaces range from 10 − 3.477 to 10 − 0.455 A/cm2 and their corresponding corrosion potentials (Ecorr) range from −1.36 to −0.892 VSHE, respectively. The base (0001) surface exhibits a lower corrosion rate of 10 − 3.345 A/cm2, whereas the crystal (21 3 ¯ 0) surface has a fast corrosion rate of 10 − 0.455 A/cm2. The calculations even reveal that except for Ag, all the other alloying elements considered here accelerate the rates of the cathodic HER. In agreement with theoretical results, the experimentally measured polarization curves of the Mg-1Zn and Mg-2Sn alloys verify that both Zn and Sn additions accelerate the rate of the HER of Mg.

Histone chaperones regulate all aspects of histone metabolism. NASP is a major histone chaperone for H3–H4 dimers critical for preventing histone degradation. Here, we identify two distinct histone binding modes of NASP and reveal how they cooperate to ensure histone H3–H4 supply. We determine the structures of a sNASP dimer, a complex of a sNASP dimer with two H3 α3 peptides, and the sNASP–H3–H4–ASF1b co-chaperone complex. This captures distinct functionalities of NASP and identifies two distinct binding modes involving the H3 α3 helix and the H3 αN region, respectively. Functional studies demonstrate the H3 αN-interaction represents the major binding mode of NASP in cells and shielding of the H3 αN region by NASP is essential in maintaining the H3–H4 histone soluble pool. In conclusion, our studies uncover the molecular basis of NASP as a major H3–H4 chaperone in guarding histone homeostasis.

We present details of on-wafer-level 16-term error model calibration kits used for the characterization of W-band circuits based on a grounded coplanar waveguide (GCPW). These circuits were fabricated on a thin gallium arsenide (GaAs) substrate, and via holes, were utilized to ensure single mode propagation (i.e., eliminating the parallel-plate mode or surface mode). To ensure the accuracy of the definition for the calibration kits, multi-line thru-reflect-line (MTRL) assistant standards were also fabricated on the same wafer and measured. The same wafer also contained passive and active devices, which were measured subject to both 16-term and conventional line-reflect-reflect-match calibrations. Measurement results show that 16-term calibration kits are capable of determining the cross-talk more accurately. Other typical calibration techniques were also implemented using the standards on the GCPW calibration kits, and were compared with the MTRL calibration using a passive device under test. This revealed that the proposed GCPW GaAs calibration substrate could be a feasible alternative to conventional CPW impedance standard substrates, for on-wafer measurements at W-band and above.

Opioid and opioid-like receptors are activated by a variety of endogenous peptides including [Met]enkephalin (met), [Leu]enkephalin (leu), β-endorphin (β-end), α-neodynorphin, dynorphin A (dynA), dynorphin B (dynB), big dynorphin (Big dyn), nociceptin/orphanin FQ (N/OFQ); endomorphin-1 and endomorphin-2 are also potential endogenous peptides. The Greek letter nomenclature for the opioid receptors, μ, δ and κ, is well established, and NC-IUPHAR considers this nomenclature appropriate, along with the symbols spelled out (mu, delta, and kappa), and the acronyms, MOP, DOP, and KOP. [121, 100, 91]. The human N/OFQ receptor, NOP, is considered 'opioid-related' rather than opioid because, while it exhibits a high degree of structural homology with the conventional opioid receptors [294], it displays a distinct pharmacology. Currently there are numerous clinically used drugs, such as morphine and many other opioid analgesics, as well as antagonists such as naloxone, however only for the μ receptor.

The MYB transcription factors (TFs) are evolving as critical role in the regulation of the phenylpropanoid and tanshinones biosynthetic pathway. MYB TFs relate to a very important gene family, which are involved in the regulation of primary and secondary metabolisms, terpenoids, bioactive compounds, plant defense against various stresses and cell morphology. R2R3 MYB TFs contained a conserved N-terminal domain, but the domain at C-terminal sorts them different regarding their structures and functions. MYB TFs suppressors generally possess particular repressive motifs, such as pdLNLD/ELxiG/S and TLLLFR, which contribute to their suppression role through a diversity of complex regulatory mechanisms. A novel flower specific “NF/YWSV/MEDF/LW” conserved motif has a great potential to understand the mechanisms of flower development. In the current review, we summarize recent advanced progress of MYB TFs on transcription regulation, posttranscriptional, microRNA, conserved motif and propose directions to future prospective research. We further suggest there should be more focus on the investigation for the role of MYB TFs in microalgae, which has great potential for heterologous protein expression system for future perspectives.

HMCES and yedK were recently identified as sensors of abasic sites in ssDNA. In this study, we present multiple crystal structures captured in the apo-, nonspecific-substrate-binding, specific-substrate-binding, and product-binding states of yedK. In combination with biochemical data, we unveil the molecular basis of AP site sensing in ssDNA by yedK. Our results indicate that yedK has a strong preference for AP site-containing ssDNA over native ssDNA and that the conserved Glu105 residue is important for identifying AP sites in ssDNA. Moreover, our results reveal that a thiazolidine linkage is formed between yedK and AP sites in ssDNA, with the residues that stabilize the thiazolidine linkage important for the formation of DNA-protein crosslinks between yedK and the AP sites. We propose that our findings offer a unique platform to develop yedK and other SRAP domain-containing proteins as tools for detecting abasic sites in vitro and in vivo.

Magnesium salt is a known cellulose protector during the oxygen delignification process and it has been widely used in commercial practice, in particular, for feedstocks with a low magnesium presence. Minimizing the negative impact of transition metals by magnesium is one of the main mechanisms. A key parameter affecting the magnesium salt performance for this purpose is its particle size. In this study, different particle sizes of magnesium hydroxide were used as additives to the oxygen delignification system, and various transition metal ions (Cu2+, Mn2+ and Fe3+) were added to the radiata pine Kraft pulp. The results show that the magnesium hydroxide particle sizes had negligible effects on the pulp yield, Kappa number and brightness; however, when large size magnesium hydroxide was used, handsheet physical properties suffered a great loss, which was accompanied with much lowered viscosity and degree of polymerization in the resultant pulp. The explanation is that small sized magnesium hydroxide particles have large specific surface area and can adsorb more transition metal ions than the magnesium hydroxide with larger particle size, consequently, the transition metal contents of resultant pulp in the former are significantly lowered, which then decreases the negative impact of transition metals on the cellulose degradation in the process. It is thus concluded that smaller particle size of magnesium hydroxide is favorable as a cellulose protector during the oxygen delignification process.

Agonist-induced internalization of G protein-coupled receptors (GPCRs) is a significant step in receptor kinetics and is known to be involved in receptor down-regulation. However, the dopamine D3 receptor (D3R) has been an exception wherein agonist induces D3Rs to undergo desensitization followed by pharmacological sequestration - which is defined as the sequestration of cell surface receptors into a more hydrophobic fraction within the plasma membrane without undergoing the process of receptor internalization. Pharmacological sequestration renders the receptor in an inactive state on the membrane. In our previous study we demonstrated that a novel class of D3R agonists exemplified by SK608 have biased signaling properties via the G-protein dependent pathway and do not induce D3R desensitization. In this study, using radioligand binding assay, immunoblot or immunocytochemistry methods, we observed that SK608 induced internalization of human D3R stably expressed in CHO, HEK and SH-SY5Y cells which are derived from neuroblastoma cells, suggesting that it is not a cell-type specific event. Further, we have evaluated the potential mechanism of D3R internalization induced by these biased signaling agonists. SK608-induced D3R internalization was time- and concentration-dependent. In comparison, dopamine induced D3R upregulation and pharmacological sequestration in the same assays. GRK2 and clathrin/dynamin I/II are the key molecular players in the SK608-induced D3R internalization process, while β-arrestin 1/2 and GRK-interacting protein 1(GIT1) are not involved. These results suggest that SK608-promoted D3R internalization is similar to the type II internalization observed among peptide binding GPCRs.

BACKGROUND A20 inhibits intestinal epithelial cell apoptosis in Crohn's disease, and herbs-partitioned moxibustion (HPM) has been demonstrated to be an effective treatment for Crohn's disease. However, the mechanism by which HPM reduces intestinal epithelial cell apoptosis in Crohn's disease has not been thoroughly elucidated to date. AIM To elucidate whether HPM exerts its effects by upregulating A20 to affect intestinal epithelial cell apoptosis in a Crohn's disease mouse model. METHODS In this study, mice with A20 deletion in intestinal epithelial cells (A20IEC-KO) were utilized to establish a Crohn's disease mouse model with 2,4,6-trinitrobenzene sulfonic acid (TNBS) administration, as well as wild-type mice. Mice were randomly divided into normal control (NC), model control (MC), mesalazine (MESA), and HPM groups. The morphology of the colonic mucosa was observed by hematoxylin-eosin staining, and serum endotoxin and apoptosis of epithelial cells were evaluated by enzyme-linked immunosorbent assay and terminal dUTP nick-end labeling assay accordingly. The protein expression levels of A20 and tumor necrosis factor receptor 1 (TNFR1)-related signaling molecules were evaluated by Western blot, and co-expression of A20 and TNFR1-associated death domain (TRADD) and co-expression of A20 and receptor-interacting protein 1 (RIP1) were observed by double immunofluorescence staining. RESULTS The intestinal epithelial barrier was noted to have an improvement in the HPM group of wild-type (WT) mice compared with that in A20IEC-KO mice. Compared with A20 IEC-KO HPM mice, serum endotoxin levels and apoptosis percentages were decreased (P < 0.01), A20 expression levels were increased (P < 0.01), and expression of TNFR1, TRADDD, and RIP1 was decreased in the HPM group of WT mice (PTNFR1 < 0.05, PTRADD < 0.01, PRIP1 < 0.01). Both of the co-expression of A20/TRADD and A20/RIP1 showed a predominantly yellow fluorescence in the HPM group of WT mice, while a predominantly red fluorescence was noted in the HPM group of A20IEC-KO mice. CONCLUSION Our findings suggest that HPM in treating Crohn's disease functions possibly via upregulation of the A20 expression level, resulting in downregulation of TNFR1, TRADD, and RIP1 to alleviate increased cell apoptosis in the intestinal epithelial barrier in Crohn's disease.

Furfural (FAL) is one of the most important biomass-derived platform compounds. The catalytic transformation of FAL was investigated with three porous Zr–thiophenedicarboxylate hybrids for the production of furfuryl alcohol (FOL). Three Zr-based catalysts, including DUT-67(Zr), DUT-68(Zr) and DUT-69(Zr) were synthesized through a facile assembly of 2,5-thiophenedicarboxylate acid with ZrCl4 using the acetic acid as a modulator under hydrothermal conditions. These catalysts were also characterized using FT-IR, XRD, SEM, TEM, N2 adsorption–desorption, XPS and TG. The specific surface area of the DUT-69(Zr) is smaller than that of the DUT-68(Zr) and slightly larger than that of the DUT-67(Zr), but it has a relatively large pore volume and pore diameter. Although all three catalysts showed excellent catalytic activity towards the catalytic transfer hydrogenation of FAL into FOL, the DUT-69(Zr) material has slightly higher catalytic activity than the other two catalysts. Besides, considering the cost of catalyst preparation, the DUT-69(Zr) material was used as the optimal catalyst and studied in detail. A high FOL yield of 92.2% at 95.9% FAL conversion was achieved at 120 °C for 4 h over DUT-69(Zr). Meanwhile, the DUT-69(Zr) could be reused more than six times with a minor decrease in catalytic activity. Finally, a plausible mechanism for catalytic transfer hydrogenation of carbonyl compounds to produce corresponding alcohols was presented based on the results of the experiments and previous reports.

This paper analyzes the spatial and temporal distribution of CO2 emissions intensity and energy intensity in China by using spatial measuring method from 2000 to 2013 and estimates the potential for CO2 emissions reduction. The results obtained in this study include: (1) Both CO2 emissions intensity and energy intensity are declining; (2) the spatial distribution of carbon emission intensity and energy intensity in China shows the characteristics of lower from north to south; (3) China’s total growth of energy consumption and carbon emissions is clearly slowing, which will peak before 2030; the carbon emission reduction potential in China is great with 167,316.91 million tons, and Shanxi, Inner Mongolia and Hebei have the greatest potential to reduce CO2 emissions with 29,885.8 Mt, 32,704.49 Mt and 34,222.1 Mt, respectively; (4) the differences of CO2 emissions intensity and energy intensity among provinces are distinctive. This study can provide a reference for the sustainable development of China’s energy and environment.

As a small molecule gas, formaldehyde (FA) is the simplest carbonyl active material and plays an important role in the carbon cycle of metabolism. However, due to the volatile nature of the gas, it is difficult to accurately quantify its content, which limits the study of the mechanism of action in life activities. Thus, an efficient approach to quantitative detection of FA in cells especially in single cell is urgent needed. Nevertheless, no method for quantifying FA in single cell has been reported to date. In this work, a fluorescent probe N-propyl-4-hydrazino-naphthalimide (NPHNA), which has highly desirable attributes and has been applied to living biological samples, was chosen as labeling reagent to detect endogenous FA at single cell level. After optimization of separation conditions, fast baseline separation of the FA derivative N-propyl-4-hydrazone-naphthalimide product (NPHNA-FA) and NPHNA was achieved in about 5 min by CE with LIF detection. The detection limit for FA was 5 amol (S/N ratio of 3). The developed method was validated by the measurements of intracellular levels of FA in single cell.

Aim: This study aimed to investigate the oncogenic activity of microRNA-10b by targeting CUB and sushi multiple domains protein 1 (CSMD1) in human gastric cancer (GC) and the underlying mechanisms. Methods: The expression of CSMD1 in human GC tissues was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemical analysis. The expressive abundance of microRNA-10b was detected by stem-loop RT-PCR. Molecular and cellular techniques, including lentiviral vector-mediated knockdown or overexpression, were used to elucidate the effect of microRNA-10b on the expression of CSMD1. Results: CSMD1 was targeted and downregulated by microRNA-10b in human GC tissues and cells, and the down-regulated expression of CSMD1 contributed to poor survival. The knockdown of microRNA-10b expression inhibited cell proliferation in GC cells in vitro and tumor growth in vivo. The inhibition of microRNA-10b expression repressed invasion and migration of HGC27 cells and retarded GC cells metastasis to the liver in Balb/c nude mice. The up-regulated expression of microRNA-10b promoted the proliferation and metastasis of MKN74 cell in vitro. Intratumoral injection of microRNA-10b mimic also promoted the growth and metastasis of tumor xenografts in Balb/c nude mice. Mechanistically, microRNA-10b promoted the invasion and metastasis of human GC cells through inhibiting the expression of CSMD1, leading to the activation of the nuclear factor-κB (NF-κB) pathway that links inflammation to carcinogenesis, subsequently resulting in the upregulation of c-Myc, cyclin D1 (CCND1), and epithelial-mesenchymal transition (EMT) markers. Conclusions: The findings established that microRNA-10b is an oncomiR that drives metastasis. Moreover, a set of critical tumor suppressor mechanisms was defined that microRNA-10b overcame to drive human GC progression.

A key challenge for phytoextraction is the identification of high efficiency, growth-supporting, and low cost chelating agents. To date, no substance has satisfied all above criteria. This study investigated nine traditional Chinese herbs and found that Phyllanthus emblica fruit (FPE) extract could be utilised as an optimal chelate for the phytoextraction of cadmium (Cd)-contaminated soils. FPE application into soil at a ratio of 0.1% (w/w) significantly increased extractable Cd (by 43%) compared to the control. The success of FPE as a chelating agent was attributed to high quantities of polyphenol compounds (0.76%) and organic acids (9.6%), in particular, gallic acid (7.6%). Furthermore, antioxidative properties (1.4%) and free amino acids in FPE alleviated Cd-induced oxidant toxicity and enhanced plant biomass. FPE promoted 78% higher phytoextraction efficiency in Platycladus orientalis compared to traditional chelating agents (EDTA). Furthermore, 76% of FPE was degraded 90 days after the initial application, and there was no difference in extractable Cd between the treatment and control. FPE has been commercially produced at a lower market price than other biodegradable chelates. As a commercially available and cost-effective chelator, FPE could be utilised to treat Cd-contaminated soils without adverse environmental impacts.

We reported previously that GEC1 (glandular epithelial cell 1), a member of microtubule-associated proteins (MAPs), interacted directly with the C-tail of KOR (KCT) and tubulin, and enhanced cell surface expression of KOR in CHO cells by facilitating its trafficking along the export pathway. Two GEC1 analogs (GABARAP and GATE16) were also shown to increase KOR expression. In addition, to understand the underlying mechanism, we demonstrated that N-ethylmaleimide-sensitive factor (NSF), an essential component for membrane fusion, co-immunoprecipitated with GEC1 from brain extracts. In this study, using pull-down techniques, we have found that (1) GEC1 interacts with NSF directly, and prefers the ADP-bound NSF to the ATP-bound NSF; (2) D1 and/or D2 domain(s) of NSF interact with GEC1, but the N domain of NSF does not; (3) NSF does not interact with KCT directly, but forms a protein complex with KCT via GEC1; (4) NSF and/or α-SNAP do not affect KCT-GEC1 interaction. Thus, GEC1 (vs the α-SNAP/SNAREs complex) binds to NSF in distinctive ways in terms of the ADP- or ATP-bound form and domains of NSF involved. In conclusion, GEC1 may, via its direct interactions with KOR, NSF and tubulin, enhance trafficking and fusion of KOR-containing vesicles selectively along the export pathway, which leads to increase in surface expression of KOR. GABARAP and GATE16 may enhance KOR expression in a similar way.

Background As a pattern recognition receptor, Toll‐like receptor 7 (TLR7) widely presented in the endosomal membrane of various cells. However, the precise role and mechanism of TLR7 in septic cardiomyopathy remain unknown. This study aims to determine the role of TLR7 in cardiac dysfunction during sepsis and explore the mechanism of TLR7 in septic cardiomyopathy. Methods We generated a mouse model of septic cardiomyopathy by challenging with lipopolysaccharide (LPS). TLR7‐knockout (TLR7−/−), wild‐type (WT) mice, cardiac‐specific TLR7‐transgenic (cTG‐TLR7) overexpression, and littermates WT (LWT) mice were subjected to septic model. Additionally, to verify the role and mechanism of TLR7 in vitro, we transfected neonatal rat ventricular myocytes (NRVMs) with Ad‐TLR7 and TLR7 siRNA before LPS administration. The effects of TLR7 were assessed by Ca2+ imaging, western blotting, immunostaining, and quantitative real‐time polymerase chain reaction (qPCR). Results We found that TLR7 knockout markedly exacerbated sepsis‐induced systolic dysfunction. Moreover, cardiomyocytes isolated from TLR7−/− mice displayed weaker Ca2+ handling than that in WT mice in response to LPS. Conversely, TLR7 overexpression alleviated LPS‐induced systolic dysfunction, and loxoribine (TLR7‐specific agonist) improved LPS‐induced cardiac dysfunction. Mechanistically, these optimized effects were associated with enhanced the adenosine (cAMP)‐protein kinase A (PKA) pathway, which upregulated phosphorylate‐phospholamban (p‐PLN) (Ser16) and promoted sarco/endoplasmic reticulum Ca2+ ATPase (Serca) and Ryanodine Receptor 2 (RyR2) expression in the sarcoplasmic reticulum (SR), and ultimately restored Ca2+ handling in response to sepsis. While improved Ca2+ handling was abrogated after H89 (a specific PKA inhibitor) pretreatment in cardiomyocytes isolated from cTG‐TLR7 mice. Consistently, TLR7 overexpression improved LPS‐induced Ca2+‐handling decrement in NRVMs. Nevertheless, TLR7 knockdown showed a deteriorative phenotype. Conclusions Our data demonstrated that activation of TLR7 protected against sepsis‐induced cardiac dysfunction through promoting cAMP‐PKA‐PLN pathway, and we revealed that TLR7 might be a novel therapeutic target to block the septic cardiomyopathy and support systolic function during sepsis., Our study explored the effect of TLR7 activation, by which TLR7 modulated Ca2+ handling in septic cardiomyopathy. TLR7 protected against sepsis‐induced cardiac dysfunction through activation of cAMP‐PKA‐PLN pathway. Targeting this newly identified TLR7 may yield novel interventional solutions against septic cardiomyopathy.

Antibodies are important tools for protein and peptide research, including for the kappa opioid receptor (KOR) and dynorphins (Dyns). Well-characterized antibodies are essential for rigorous and reproducible research. However, lack of validation of antibody specificity has been thought to contribute significantly to the reproducibility crisis in biomedical research. Since 2003, many scientific journals have required documentation of validation of antibody specificity and use of knockout mouse tissues as a negative control is strongly recommended. Lack of specificity of antibodies against many G protein-coupled receptors (GPCRs) after extensive testing has been well-documented, but antibodies generated against partial sequences of the KOR have not been similarly investigated. For the dynorphins, differential processing has been described in distinct brain areas, resulting in controversial findings in immunohistochemistry (IHC) when different antibodies were used. In this chapter, we summarized accepted approaches for validation of antibody specificity. We discussed two KOR antibodies most commonly used in IHC and described generation and characterization of KOR antibodies and phospho-KOR specific antibodies in western blotting or immunoblotting (IB). In addition, applying antibodies targeting prodynorphin or mature dynorphin A illustrates the diversity of results obtained regarding the distribution of dynorphins in distinct brain areas.

In the present study, the role of 3-hydroxy group of a series of epoxymorphinan derivatives in their binding affinity and selectivity profiles toward the opioid receptors (ORs) has been investigated. It was found that the 3-hydroxy group was crucial for the binding affinity of these derivatives for all three ORs due to the fact that all the analogues 1a-e exhibited significantly higher binding affinities compared to their counterpart 3-dehydroxy ones 6a-e. Meanwhile most compounds carrying the 3-hydroxy group possessed similar selectivity profiles for the kappa opioid receptor over the mu opioid receptor as their corresponding 3-dehydroxy derivatives. [(35)S]-GTPγS functional assay results indicated that the 3-hydroxy group of these epoxymorphinan derivatives was important for maintaining their potency on the ORs with various effects. Further molecular modeling studies helped comprehend the remarkably different binding affinity and functional profiles between compound 1c (NCP) and its 3-dehydroxy analogue 6c.

Activation of κ opioid receptor (KOR) produces analgesia, antipruritic effect, sedation and dysphoria. To characterize neuroanatomy of KOR at high resolutions and circumvent issues of specificity of KOR antibodies, we generated a knock-in mouse line expressing KOR fused at the C terminus with the fluorescent protein tdTomato (KtdT). The selective KOR agonist U50,488H caused anti-scratch effect and hypolocomotion, indicating intact KOR neuronal circuitries. Clearing of brains with CLARITY revealed three-dimensional (3-D) images of distribution of KOR, and any G-protein-coupled receptors, for the first time. 3-D brain images of KtdT and immunohistochemistry (IHC) on brain sections with antibodies against tdTomato show similar distribution to that of autoradiography of [3H]U69,593 binding to KOR in wild-type mice. KtdT was observed in regions involved in reward and aversion, pain modulation, and neuroendocrine regulation. KOR is present in several areas with unknown roles, including the claustrum (CLA), dorsal endopiriform nucleus, paraventricular nucleus of the thalamus (PVT), lateral habenula (LHb), and substantia nigra pars reticulata (SNr), which are discussed. Prominent KtdT-containing fibers were observed to project from caudate putamen (CP) and nucleus accumbens (ACB) to substantia innominata (SI) and SNr. Double IHC revealed co-localization of KtdT with tyrosine hydroxylase (TH) in brain regions, including CP, ACB, and ventral tegmental area (VTA). KOR was visualized at the cellular level, such as co-localization with TH and agonist-induced KOR translocation into intracellular space in some VTA neurons. These mice thus represent a powerful and heretofore unparalleled tool for neuroanatomy of KOR at both the 3-D and cellular levels.

Kappa opioid receptor (KOR) agonists possess adverse dysphoric and psychotomimetic effects, thus limiting their applications as non-addictive anti-pruritic and analgesic agents. Here, we showed that protein kinase C (PKC) inhibition preserved the beneficial antinociceptive and antipruritic effects of KOR agonists, but attenuated the adverse condition placed aversion (CPA), sedation, and motor incoordination in mice. Using a large-scale mass spectrometry-based phosphoproteomics of KOR-mediated signaling in the mouse brain, we observed PKC-dependent modulation of G protein-coupled receptor kinases and Wnt pathways at 5 min; stress signaling, cytoskeleton, mTOR signaling and receptor phosphorylation, including cannabinoid receptor CB1 at 30 min. We further demonstrated that inhibition of CB1 attenuated KOR-mediated CPA. Our results demonstrated the feasibility of in vivo biochemical dissection of signaling pathways that lead to side effects.

An MTH1 inhibitor is integrated with nanoparticles to enhance therapy effect of reactive oxygen species in cancer treatment., Although photodynamic therapy (PDT) has been clinically applied tumor hypoxia still greatly restricts the performance of this oxygen-dependent oncological treatment. The delivery of oxygen donors to tumor may produce excessive reactive oxygen species (ROS) and damage the peripheral tissues. Herein, we developed a strategy to solve the hypoxia issue by enhancing the lethality of ROS. Before PDT, the ROS-defensing system of the cancer cells was obstructed by an inhibitor to MTH1, which is a key for the remediation of ROS-caused DNA damage. As a result, both nuclei and mitochondrial DNA damages were increased, remarkably promoting cellular apoptosis. The therapeutic results demonstrated that the performance of PDT can be improved by the MTH1 inhibitor, leading to efficient cancer cell killing effect in the hypoxic tumor. This strategy makes better use of the limited oxygen, holding the promise to achieve satisfactory therapeutic effect by PDT without generating redundant cytotoxic ROS.

As the main active ingredient in Chinese medicine safflower, hydroxysafflor yellow A (HSYA) has multiple pharmacological effects. In the work, the absorption and fluorescence spectra of HSYA under different environmental conditions (such as acidity, temperature, ions, viscosity, and surfactant) were investigated. The fluorescence intensity of HSYA varied greatly with acidity, temperature, viscosity, and surfactant, but was less affected by common cations and anions. Among various surfactants, we found that borax can significantly enhance the HSYA fluorescence intensity, and thus, a borax-HSYA sensitization system for HSYA fluorescence was established. In the optimized sensitization system, the fluorescence intensity of HSYA increased by 20 times and showed a good linearity with HSYA concentrations in the range of 0∼10 μM with a detection limit of 8 nM. The borax-HSYA sensitization system is nontoxic to T24 cells and mice and can be used for the fluorescence imaging of HSYA in cells, thereby providing an effective method for analyzing HSYA in vitro and monitoring its metabolism in cells.

Peroxymonosulfate (PMS) based advanced oxidation process has been proved to be an efficient method for Antibiotic treatment. B, N co-doped carbon porous material was derived from metal-organic frameworks. B-NC catalysts showed excellent efficiency for removal of tetracycline hydrochloride. Nitrogen doping essentially changed the degradation pathway of tetracycline hydrochloride, while boron doping provided more active sites. through more defect sites, which is closely related to the adsorption and catalytic performance of the catalyst. The major active species of B-NC/PMS system was singlet oxygen (1O2) through quenching experiments and electron paramagnetic resonance (EPR) studies. Electron transfer was another non-radical oxidation pathway of B-NC/PMS system. This provides a new idea for the selective oxidation of antibiotics by metal-free activated PMS.

We reported previously that the selective agonist U50,488H promoted phosphorylation of the mouse kappa opioid receptor (mKOR) in vitro at four residues in the C-terminal domain. In this study, we generated a mutant mouse line in which all the four residues were mutated to Ala (K4A) to examine the in vivo functional significance of agonist-induced KOR phosphorylation. U50,488H promoted KOR phosphorylation in brains of the wildtype (WT), but not K4A, male and female mice. Autoradiography of [3H] 69,593 binding to KOR in brain sections showed that WT and K4A mice had similar KOR distribution and expression levels in brain regions without sex differences. In K4A mice, U50,488H inhibited compound 48/80-induced scratching and attenuated novelty-induced hyperlocomotion to similar extents as in WT mice without sex differences. Interestingly, repeated pretreatment with U50,488H (80 mg/kg, s.c.) resulted in profound tolerance to the anti-scratch effects of U50,488H (5 mg/kg, s.c.) in WT mice of both sexes and female K4A mice, while in male K4A mice tolerance was attenuated. Moreover, U50,488H (2 mg/kg) induced conditioned place aversion (CPA) in WT mice of both sexes and male K4A mice, but not in female K4A mice. In contrast, U50,488H (5 mg/kg) caused CPA in male, but not female, mice, regardless of genotype. Thus, agonist-promoted KOR phosphorylation plays important roles in U50,488H-induced tolerance and CPA in a sex-dependent manner, without affecting acute U50,488H-induced anti-pruritic and hypo-locomotor effects. These results are the first to demonstrate sex differences in the effects of GPCR phosphorylation on the GPCR-mediated behaviors.

Carbonyl compounds are widely distributed in organisms, and the commonly used methods for determination of them like UV/fluorescence/mass spectrometry always require derivatization reagents. However, the reported derivatization reagents have significant difference in reactivity, which is very unfavorable for developing highly reactive reagent. In this study, we theoretically investigated the factors affecting the reactivity of hydrazine-based derivatization reagents, and proposed a strategy for filtering highly reactive reagents by quantum chemical calculation. With this strategy, N-propyl-4-hydrazino-1,8-naphthalimide (NPHNA) was filtered out as a fluorescent derivatization reagent. Taking aliphatic aldehydes as representatives, we evaluated the reactivity of NPHNA for carbonyl compounds. The derivatization of NPHNA with aliphatic aldehydes could be finished at room temperature within 60 min or 35 °C within 35 min, which showed higher reactivity than the most popular UV/MS reagent, 2,4-dinitrophenylhydrazine (DNPH). We believe that the strategy we proposed in this work is of great potential to design highly reactive UV/fluorescent/MS labeling reagents for carbonyl compounds and even other analytes.

The orchid Dendrobium catenatum Lindl. has both ornamental and medicinal value. Studies on genetic transformation of other Dendrobium species have been reported; however, due to the heterogeneity among the Dendrobium species, an independent transformation system is required for optimum D. catenatum transformation. Agrobacterium tumefaciens-mediated transformation system for D. catenatum is reported herein. Three A. tumefaciens strains, GV3101, LBA4404, and EHA105, were tested for their ability to transform D. catenatum protocorms. It was found that infection with strain GV3101 at an OD600 of 0.6 yielded the highest transformation frequency of 56.5%. Addition of 0.001% (v/v) Triton™ X-100 or pretreatment with ultrasound (300 W, 40 kHz, 3 min) increased the transformation frequency by up to 2-fold. After 1 year, both green fluorescent protein (GFP) imaging and glucuronidase (GUS) histochemical analysis of transgenic plants demonstrated that DcObg-GFP and pDcObg-GUS construct DNA was transferred into the D. catenatum and expressed successfully. Functional and gene expression level analyses of transgenic plants containing a D. catenatum chloroplast-targeted homolog of Spo0B-associated GTP-binding protein (DcObgC) RNA interference construct (DcObgC-RNAi) further demonstrated that this transformation system was reliable and efficient for D. catenatum. The A. tumefaciens-based transformation protocol established and optimized in this current report could provide a powerful and efficient tool for academic research and genetic engineering-based breeding of D. catenatum.

Herein, a highly reactive long-wavelength fluorescent labeling reagent, 1,7-dimethyl-3,5-distyryl-8-phenyl-(4-oxy-acetic acid N-hydroxysuccinimidyl ester) difluoroboradiaza-s-indacene (DMDSPAB-OSu), was designed and synthesized for amino compounds. Using DMDSPAB-OSu as a pre-column derivatization reagent, an HPLC-fluorescence detection method was developed for the determination of trace amounts of aliphatic amines in samples. Prior to analysis, amines were derivatized with DMDSPAB-OSu at room temperature in 0.2 mol L−1 pH 8.8 borate buffer for only 5 min, and the baseline separation of 11 aliphatic amines was achieved within 25 min. Limits of detection between 0.8 to 1.2 nM were obtained at 630 nm with an excitation wavelength of 610 nm. Furthermore, the proposed DMDSPAB-OSu-based HPLC method was applied to the analysis of lake water and human urine with satisfying recoveries ranging from 93.0–109.7%.