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Abstract Aberrant expression of microRNAs (miRNAs) is known to be involved in cancer progression caused by subgroup J avian leukosis virus (ALV-J) in liver tissues. To advance our understanding of the related pathological mechanisms and virus-host interactions, seven previously reported miRNAs were selected for a comparative analysis of miRNA expression between infected and uninfected DF-1 cells, including six miRNAs related to tumorigenesis (let-7b/7i, miR-221/222, miR-125b, miR-375 and miR-2127. The results showed that six of the seven miRNAs except gga-miR-375 were upregulated in cells infected with NX0101 (caused myeloma (ML)) and GD1109 (caused hemangioma (HE)) at 1 h post infection. On day 2 post-infection, all seven miRNAs were upregulated in infected DF-1 cells. On day 6 post-infection, gga-let-7b, gga-miR-125b, and gga-miR-375 were downregulated whereas gga-miR-221 and gga-miR-222 were upregulated in DF-1 cells infected with the two ALV-J strains of different phenotypes. However, expression of gga-let-7i was reduced in DF-1 cells infected with NX0101 and was increased in those infected with GD1109; gga-miR-2127 expression showed no significant difference between infected and uninfected cells. This study is the first to report the changes in the miRNA expression levels in DF-1 cells during the course of ALV-J infection, and suggests a relationship between its pathological mechanisms and miRNAs. Highlights • ALV-J induces abnormal miRNAs expression of DF-1 cells. • ALV-J increases miR-221/222 in DF-1 cells at 1 h post infection. • ALV-J of GD1109 strain increases gga-let-7i in DF-1 cells on day 6 post infection. [ABSTRACT FROM AUTHOR]

Fourth-order boundary value problems with discontinuous boundary conditions are studied. We prove that the eigenvalues depend not only continuously but smoothly on the coefficients and on the boundary conditions and find formulas for the derivatives with respect to each of these parameters. [ABSTRACT FROM AUTHOR]

[Display omitted] • Four unusual sesquilignans compounds were isolated from the resin of Ferula sinkiangensis. • Hypothetic biosynthetic pathways of compound 3 contain a newly formed six-membered C-ring by Diels-Alder cycloaddition. • Biological assay revealed that 2a and 2b could inhibit IL-6 and TNF-α production in LPS induced RAW264.7 cells in a dose-dependent manner. Sinkianlignans A − D (1 – 4), four new sesquilignans with an unusual architectures was characterized with a rarely α-γ′, β-γ′, and γ-γ′ linkage pattern, and sinkianlignans E − F (5 and 6), two lignans, were isolated from the Ferula sinkiangensis. Hypothetic biosynthetic pathway of compound 3 contain a newly formed six-membered C-ring by Diels-Alder cycloaddition. The structures of isolates were established by spectroscopic techniques and computational methods. Biological evaluation of all the isolated compounds revealed that compounds 2a and 2b could inhibit IL-6 and TNF-α production in lipopolysaccharide (LPS) induced RAW264.7 cells in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

The present paper deals with a class of generalized discontinuous Sturm–Liouville problems with boundary conditions rationally dependent on the eigenparameter. Using operator theoretic formulation under the new inner product based on boundary conditions rationally dependent on the eigenparameter and general transmission conditions, the self-adjointness of this operator is proved. We also obtain that the eigenvalues of the problems depend not only continuously but also smoothly on the parameters of the problem: the coefficients, the boundary conditions, the general transmission conditions, as well as the endpoints. Moreover, we find the differential expressions for each parameters, respectively. [ABSTRACT FROM AUTHOR]

Adipose tissue plays a key role in the development of obesity and diabetes. Natural products are one of the main sources for discovering new lead compounds. In the present study, (2 S )-7,4′-dihydroxy-8-prenylflavan (DHPF), a natural prenylated flavan isolated from Morus yunnanensis , was found to significantly promote adipogenesis and increase glucose uptake in 3T3-L1 cells. Real-time PCR results showed that DHPF increased the expression of glucose and lipid metabolism-related genes (C/EBPα, PPARγ, aP2, GLUT4 and adiponectin) and decreased the expression of inflammatory cytokine TNF-α. Western blotting further revealed that DHPF activated p38 MAPK at the initial stage of 3T3-L1 preadipocyte differentiation. DHPF-induced activation of p38, adipogenesis and glucose uptake were effectively blocked by SB203580, a specific p38 inhibitor. These results indicate that DHPF could stimulate adipogenesis and increase glucose uptake through the p38 MAPK pathway, and DHPF may be useful for the prevention and treatment of obesity-associated disorders such as type 2 diabetes (T2D). [ABSTRACT FROM AUTHOR]

Abstract: We consider the following two classes of second order boundary value problems for difference equation: with and with . We establish the existence of positive solutions to both problems. A solver with linear computational complexity for almost tridiagonal linear systems is developed by exploring the special structure of linear system of equations. Based on fast solvers for linear systems, effective algorithms for the computation of positive solutions will be proposed. [Copyright &y& Elsevier]

Abstract: Sildenafil is the first oral PDE5 inhibitor for the treatment of erectile dysfunction and pulmonary arterial hypertension. In the present study, we investigated the effect of sildenafil on adipogenesis in 3T3L1 preadipocytes. Treatment with sildenafil for 8days significantly promoted adipogenesis characterized by increased lipid droplet and triglyceride content in 3T3L1 cells. Meanwhile, sildenafil induced a pronounced up-regulation of the expression of adipocyte-specific genes, such as aP2 and GLUT4. The results by RT-PCR and Western blotting further showed that sildenafil increased the sequential expression of C/EBPβ, PPARγ and C/EBPα. Additionally, we found that the other two PDE5 inhibitors (vardenafil and tadalafil) and the cGMP analog 8-pCPT-cGMP also increased adipogenesis. Likewise, 8-pCPT-cGMP could up-regulate the expression of adipogenic and adipocyte-specific genes. Importantly, the PKG inhibitor Rp-8-pCPT-cGMP was able to inhibit both sildenafil and 8-pCPT-cGMP-induced adipogenesis. Furthermore, sildenafil promoted basal and insulin-mediated glucose uptake in 3T3L1 cells, which was counteracted by Rp-8-pCPT-cGMP. These results indicate that sildenafil could promote adipogenesis accompanied by increased glucose uptake through a PKG pathway at least partly. [Copyright &y& Elsevier]

Abstract: We consider the problem of finding an -optimal solution of a standard linear program with real data, i.e., of finding a feasible point at which the objective function value differs by at most from the optimal value. In the worst-case scenario the best complexity result to date guarantees that such a point is obtained in at most steps of an interior-point method. We show that the expected value of the number of steps required to obtain an -optimal solution for a probabilistic linear programming model is at most . [Copyright &y& Elsevier]

Abstract: If M is a mean on and then we say that M is invariant under f. The problem is to find a class of functions that by invariance determines a mean uniquely. We focus on the geometric mean, which can be transformed to obtain results for other means. [Copyright &y& Elsevier]

Abstract: We consider the eigenvalue problems for boundary value problems of second order difference equations and Comparison results for the eigenvalues of the problem (1) and the problem (2) are established. [Copyright &y& Elsevier]

Two industrial solid wastes, Ti-bearing blast furnace slag (TBFS) and diamond wire saw silicon waste (DWSSW), contain large amounts of Ti and Si, and their accumulation wastes resources and intensifies environmental pollution. In the present study, DWSSW was used as the silicon source to reduce titanium oxide in TBFS by electromagnetic induction smelting, and meanwhile Na 3 AlF 6 was added as a flux to improve the recycling of the wastes. Ti and Si of the two wastes were simultaneously recovered in the form of alloy. The effects of different addition amount of Na 3 AlF 6 flux in the mixture of DWSSW and TBFS on chemical composition, viscosity, basicity and structure of slag were investigated. The dissolution behavior of SiO 2 in Na 3 AlF 6 flux was theoretically deduced and experimentally verification. The optimized recovery rate of Ti and Si were obtained, and the research realizes the efficient recycling of DWSSW and TBFS simultaneously. • Simultaneous utilization of two kinds of solid waste. • The process is clean and pollution-free, simple and easy to operate. • High efficiency recovery of Si and Ti resources. • The effect of Na 3 AlF 6 on alloying is clarified. [ABSTRACT FROM AUTHOR]

• 16 New diarylheptanoid-chalcone hybrids were isolated from A. katsumadai. • Compounds 1 – 3 , 5 – 7 , 11 – 14 , 21 – 25 , and 27 showed PTP1B selective inhibition. • All compounds showed obvious inhibition on α -glucosidase. • Compounds 1 , 3 , and 12 were α -glucosidase and PTP1B mixed-type inhibitors. The EtOH extracts of the dried seeds of Alpinia katsumadai were revealed with hypoglycemic effects on db/db mice at the concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 16 new diarylheptanoid-chalcone hybrids, katsumadainols A 1 −A 16 (1 – 16), together with 13 known analogues (17 – 29), were isolated from A. katsumadai under the guidance of bioassay. Most of the compounds showed α -glucosidase and PTP1B dual inhibition, among which compounds 1 – 3 , 5 – 7 , 11 – 14 , 21 – 25 , and 27 showed PTP1B/TCPTP selective inhibition with IC 50 values ranging from 22.0 to 96.7 μM, which were 2–10 times more active than sodium orthovanadate (IC 50 , 215.7 μM). All compounds exhibited obvious inhibition against α -glucosidase with IC 50 values of 2.9–29.5 μM, indicating 6–59 times more active than acarbose (IC 50 , 170.9 μM). Study of enzyme kinetics indicated compounds 1 , 3 , and 12 were PTP1B and α -glucosidase mixed-type inhibitors with K i values of 13.1, 12.9, 21.6 μM, and 4.9, 7.4, 3.4 μM, respectively. [ABSTRACT FROM AUTHOR]

Herein, a Mott-Schottky heterojunction catalyst was developed by incorporating nickel (Ni) nanometallic particles supported on nitrogen-doped carbon-coated TiO 2 , enabling full-spectrum light absorption and facilitating a robust metal-support interface. This catalyst demonstrated exceptional performance in photo-thermal catalysis. Specifically, the Ni/0.5-TiO 2 @NC catalyst achieved a CO 2 hydrogenation rate of 65.3 mmol/(g cat ·h) with a CH 4 selectivity exceeding 99% under full-spectrum illumination. Remarkably, the catalyst exhibited excellent stability, maintaining its performance over two reaction cycles. The strong metal-support interface of the Mott-Schottky heterojunction catalyst enhanced photo-generated electron-hole separation efficiencies, leading to a substantial rise in catalyst surface temperature. Consequently, this phenomenon accelerated the reaction kinetics and lowered the activation energy, thereby improving overall efficiency. [Display omitted] • Mott-Schottky heterojunctions consisting of TiO 2 @NC-support and highly dispersed Ni NPs catalysts were successfully prepared. • The Mott-Schottky heterojunction catalysts exhibit rapid interface electron transfer, leading to superb carrier separation efficiencies. • The Ni/0.5-TiO 2 @NC catalyst demonstrates exceptional photo-thermal co-catalytic effects, resulting in outstanding performance in the RWGS reaction. • The in-situ DRIFTS analysis revealed that the mechanism governing the photo-thermal co-catalytic RWGS reaction follows the *HCOO pathway. Photo-thermal co-catalytic reduction of CO 2 to synthesize value-added chemicals presents a promising approach to addressing environmental issues. Nevertheless, traditional catalysts exhibit low light utilization efficiency, leading to the generation of a reduced number of electron-hole pairs and rapid recombination, thereby limiting catalytic performance enhancement. Herein, a Mott-Schottky heterojunction catalyst was developed by incorporating nitrogen-doped carbon coated TiO 2 supported nickel (Ni) nanometallic particles (Ni/x-TiO 2 @NC). The optimal Ni/0.5-TiO 2 @NC sample displayed a conversion rate of 71.6 % and a methane (CH 4) production rate of 65.3 mmol/(g cat ·h) during photo-thermal co-catalytic CO 2 methanation under full-spectrum illumination, with a CH 4 selectivity exceeding 99.6 %. The catalyst demonstrates good stability as it shows no decay after two reaction cycles. The Mott-Schottky heterojunction catalysts display excellent efficiency in separating photo-generated electron-hole pairs and elevate the catalysts' temperature, thus accelerating the reaction rate. The in-situ experiments revealed that light-induced electron transfer effectively facilitates H 2 dissociation and enhances surface defects, thereby promoting CO 2 adsorption. This study introduces a novel approach for developing photo-thermal catalysts for CO 2 reduction, aiming to enhance solar energy utilization and facilitate interface electron transfer. [ABSTRACT FROM AUTHOR]

• Eleven new ent -labdane diterpenoids were isolated from C. odontochila. • Their absolute configurations were established by ECD, [ α ] D and X-ray methods. • One ent -labdane and four ent- kauranes showed α -glucosidase inhibitory activity. • Compounds 12 and 16 were mixed-type inhibitors with K i of 334.1 and 589.2 μM. • Docking study disclosed the importance of the carboxyl group at C-4 position. Eleven new ent -labdane diterpenoids, cheodontoins A-K (1 – 11), and thirteen known diterpenoids involving two ent -labdanes (12 – 13) and eleven ent- kauranes (14 – 24), were isolated from the active part of Chelonopsis odontochila (Lamiaceae) under the guidance of bioassay. The structures of cheodontoins A-K (1 – 11) were elucidated by extensive HRESIMS, 1D and 2D NMR, [ α ] D and ECD experiments, X-ray diffraction and quantum calculation. Interestingly, five nor- ent- labdanes (9 – 13) were obtained from this genus for the first time. One ent -labdane diterpenoid (12) and four ent- kaurane diterpenoids (16 , 19 , 23 , and 24) showed α -glucosidase inhibitory activity with IC 50 values of 326.5 ± 3.5, 599.1 ± 13.8, 620.1 ± 16.1, 185.0 ± 4.2, and 190.7 ± 11.6 μM, respectively. Compounds 12 and 16 were α -glucosidase mixed-type inhibitors with K i values of 334.1 and 589.2 μM according to the enzyme kinetics using Lineweaver-Burk and Dixon plots. Docking study manifested that compounds 12 and 23 well located in the catalytic pocket of α -glucosidase by hydrophobic effects with Trp1355, Trp1369, Phe1427, Phe1559, and Phe1560 residues. This study provides new insights for the antidiabetic effects of C. odontochila with ent -labdane and ent -kaurane diterpenoids as the active constituents. [ABSTRACT FROM AUTHOR]

[Display omitted] • 15 new compounds were isolated from the whole bodies of Blaps japanensis. • Compounds 1–3 are novel spiroindole alkaloids with a unique spiro[ chromane -4,3′- indoline ]-2,2′-dione motif. • Biological assay revealed that compounds could inhibit human cancer cells (A549, Huh-7, and K562), JAK3, ROCK1, COX-2, and extracellular matrix in rat renal proximal tubular cells. Blapspirooxindoles A–C (1 – 3), three novel spirooxindole alkaloids with a unique spiro[ chromane -4,3′- indoline ]-2,2′-dione motif, blapcumaranons A and B (4 and 5), two new 2-cumaranon derivatives, blapoxindoles A–J (6 – 15), ten new oxindole alkaloid derivatives, along with one known compound (16), were isolated from the whole bodies of Blaps japanensis. Their structures including absolute configurations were determined by using spectroscopic, X-ray crystallographic, and computational methods. Compounds 1 – 11 and 13 exist as racemic mixtures in nature, and their (–)- and (+)-antipodes were separated by chiral HPLC. Biological evaluations of these compounds were determined with multiple assays including anti-tumor, anti-inflammatory, and renal protection activities in vitro. Several compounds displayed effective activity in one or more assays. [ABSTRACT FROM AUTHOR]

Schematic diagram: Synergetic effect of Au NPs loading over Ni 2 P & CoP for H 2 evolution. [Display omitted] • The catalysts (Au/Ni 2 P, Au/CoP) are synthesized and optimized. • The XPS reveals that the synergetic effect of Au/Ni 2 P is stronger than Au/CoP. • The activation energy of Au/CoP is less than Au/Ni 2 P. • Active sites for ammonia-borane hydrolysis are Auδ+ and (Ni 2 P & CoP) δ-. The hydrogen evolution from ammonia borane is intriguing but challenging due to its sluggish kinetics. In this regard, the gold nanoparticles amalgamation with metal phosphides is speculated to be more efficient catalysts. Here, the catalysts Au/Ni 2 P and Au/CoP with the high synergetic effect of Au nanoparticles and metal phosphides were synthesized for ammonia borane hydrolysis. The activity of Au/Ni 2 P increases 4.8-fold (i.e., 0.08 to 0.40 L∙h−1) compared to pristine Ni 2 P, and the activity of Au/CoP increases 1.7-fold (i.e., 0.74 to 1.27 L∙h−1) compared to pristine CoP. This reveals that the synergetic effect of Auδ+ and (Ni 2 P) δ- is stronger than Auδ+ and (CoP) δ- which is manifested by XPS analysis. The kinetics exposes that the activation energy of Au/Ni 2 P (45.28 kJ∙mole-1) is greater than Au/CoP (31.45 kJ∙mole-1) and the TOF of Au/Ni 2 P is less than Au/CoP. This research work presents an effective approach for producing active sites of Auδ+ and (Ni 2 P & CoP) δ- for ammonia borane hydrolysis to enhance the H 2 evolution rate. [ABSTRACT FROM AUTHOR]

[Display omitted] • A two-step cystine-mediated strategy is developed to alter the symmetry structure of C 3 N 4. • CN-25CYS possesses alkyl groups and nitrogen vacancies. • The distorted arrangements activate n-π* electron transition of carbon nitride. • The spatial separation of oxidation and reduction sites promotes charge separation. • CN-25CYS achieves 9.6-fold and 15.6-fold higher H 2 production rates and RhB degradation rates. The periodical distribution of N and C atoms in the carbon nitride skeleton results in intrinsically insufficient light absorption and serious carrier recombination. Herein, an efficient two-step cystine-mediated strategy was developed to alter the structure symmetry of C 3 N 4 via the introduction of alkyl groups and nitrogen vacancies. The experimental analysis and theoretical calculation confirm that the formation of alkyl groups and nitrogen vacancies can modulate band structure and activate n-π* electron transition. Especially, the charge density in CN-25CYS is redistributed with spatial separation of oxidation and reduction sites, suppressing photogenerated charge recombination effectively. Therefore, the distorted carbon nitride (CN-25CYS) exhibits 9.6-times and 15.6-times higher photoreaction rates in hydrogen production and RhB degradation than the pristine one (CN-0CYS), respectively. [ABSTRACT FROM AUTHOR]

[Display omitted] • Defective TEB-DBT CMPs with alkynyl defects via the molecular design are constructed. • Combination of the DFT calculations and experimental results, the incorporation of alkynyl defect accelerates the separation of photogenerated charge carriers. • The microstructure, band structure, and photocatalytic performance of CMPs can be regulated by varying the content of alkynyl defect. Defect engineering is a versatile approach to modulate band and electronic structures as well as materials performance. Nowadays, more research has been performed for enhancing catalytic performance of organic photocatalysts via the regulation of structure defect. Herein, we constructed the dibenzo[b,d]thiophene-sulfone-based conjugated microporous polymers (CMPs) with alkynyl defects via the molecular design. The effects of the concentration of alkynyl defects on the optical band gap, energy level structure, charge separation and photoactivity of the as-prepared samples were further explored. Combination of the first-principle density functional theory (DFT) calculations and experimental results, the incorporation of alkynyl defects accelerated the separation of photogenerated charge carriers. Furthermore, the concentration of alkynyl defects in CMPs can be adjusted by the dosage of 1,3-diethynylbenzene (MEB), thereby modulating the electronic structure and charge carrier separation properties. At appropriate alkynyl defect concentration, the prepared Defect-TD-2 shows higher visible-light photocatalytic performance for H 2 production and pollutants degradation. The work therefore shows an efficient self-modification strategy for improving the photoactivity of CMPs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Au@Pt decorated Zn-CdS composites are fabricated for promoted charge separation. • Photodeposition leads to formation of Au-S bond and act as charge transfer channel. • The composites show synergetic effect of SPR and charge transfer channel. • Surface Pt serves active sites for rapid surface reaction. • Au@Pt/Zn-CdS exhibits lower charge transfer resistance and higher PEC activity. Photoelectrochemical (PEC) water splitting is a promising approach to solve the current energy and environmental crises. Herein, we developed a "one stone, two birds" strategy to construct Au@Pt decorated ZnO/CdS heterojunctions (ZCAP) with Au-S bond and surface plasmon resonance (SPR) effect for promoted PEC water splitting. The optimized ZCAP structure exhibited the highest photocurrent density of 4.23 mA/cm2 at 1.23 V vs. RHE and hydrogen evolution rate of 72.3 μmol·cm−2·h−1, which is magnitude higher than pure ZnO. In-depth investigations indicate that SPR effect can afford hot electrons, whereas Au-S bonds over interface act as transmission bridge for facilitated electron transfer, the synergy of them achieves efficient charge separation and light utilization. Meanwhile, surface Pt nanoparticles serve as active sites for rapid charge transfer and promoted surface reaction. This article illustrates that the synergy of SPR and electron transfer bridge is an efficient strategy for promoted PEC performance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ten new diarylheptanoid dimers were isolated from A. katsumadai. • Compounds 1 – 5 and 7 – 10 significantly stimulated GLP-1 secretion. • Compounds 1 – 4 showed obvious inhibition on GPa. • Compounds 1 – 5 and 10 were PTP1B selective inhibitors. • Compounds 1 – 4 were GLP-1 secretagogues and multiple-enzyme inhibitors. Ten new diarylheptanoid dimers, katsumadainols C 1 − C 10 (1 – 10), were isolated from the seeds of Alpinia katsumada and elucidated by extensive spectroscopic methods, ECD calculations, and single-crystal X-ray diffraction. Their antidiabetic effects were evaluated by the stimulation of GLP-1 secretion in STC-1 cells and inhibition against four diabetes-related enzymes, GPa, α -glucosidase, PTP1B, and DPP4. Compounds 1 – 5 and 7 – 10 significantly stimulated GLP-1 secretion by 267.5–433.1% (25.0 μM) and 117.8–348.2% (12.5 μM). Compounds 1 – 4 exhibited significant inhibition on GPa with IC 50 values of 18.0–31.3 μM; compounds 1 – 5 showed obvious inhibition on α -glucosidase with IC 50 values of 6.9–18.2 μM; compounds 1 – 5 and 10 possessed PTP1B inhibitory activity with IC 50 values ranging from 35.5 to 80.1 μM. This investigation first disclosed compounds 1 – 4 as intriguing GLP-1 secretagogues and GPa, α -glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants. [ABSTRACT FROM AUTHOR]

[Display omitted] • 1 wt%Pd/NiMoO 4 with different Pd dispersity were synthesized. • Hydrogen spillover process adjusts hydrogenation sites and acidic sites. • 56.3–84.1% yields of cyclopentanones were obtained over Pd/NiMoO 4 -Cl. • 65.4–85.2% yields of cyclopentanols were generated over Pd/NiMoO 4 -AC. • Adsorption configurations of reactants determine the reaction route. Upgrading bioderived furfurals (furfural, 5-hydroxymethylfurfural) to cyclopentanones (cyclopentanone, 3-hydroxymethylcyclopentanone) and cyclopentanols (cyclopentanol, 3-hydroxymethylcyclopentanol) is a representative bifunctional catalytic process in biomass conversion. Here, a class of Pd/NiMoO 4 catalysts (Pd/NiMoO 4 -Cl, Pd/NiMoO 4 -AC) with low Pd loading (1.0 wt%) and different Pd dispersion are synthesized. The hydrogenation active sites and acidic sites of catalysts were adjusted by a water-mediated hydrogen spillover process. 56.3–85.3% yields of cyclopentanones and 65.4–85.2% yields of cyclopentanols were obtained by hydrogenative ring-rearrangement route of furfurals over Pd/NiMoO 4 -Cl and Pd/NiMoO 4 -AC, respectively. Over-hydrogenated byproducts (tetrahydrofurfuryl alcohol, 2,5-bis(hydroxymethyl)tetrahydrofuran) with a yield above 54% were generated by a full hydrogenation route over Pd/C. The difference in catalytic performance is results from alteration of the adsorption configurations of reactants and the transformation of Lewis acid sites to Brønsted acid sites by hydrogen spillover. This work presents an effective strategy for governing reaction routes and enhancing bifunctional catalysis with a hydrogen spillover mechanism. [ABSTRACT FROM AUTHOR]

Abstract: Deregulation of E2F1 activity is characteristic of gastric tumorigenesis, which involves in complex molecular mechanisms. microRNA is one of the post-transcriptional regulators for gene expression. Here, we report a member of miR-331 family, miR-331-3p, which was decreased in some kinds of malignancies. However, the biological function of miR-331-3p on gastric cancer is largely unknown. In this study, we screened the expressing levels of miR-331-3p and E2F1 in gastric cancer cell lines. We transfected precursor or inhibitor of miR-331-3p into gastric cancer cells. As results, miR-331-3p is down-regulated in all gastric cancer cell lines by real-time PCR. Over-expression of miR-331-3p blocked G1/S transition on SGC-7901 and AGS cell lines. Introduction of miR-331-3p dramatically suppressed the ability of colony formation and cell growth in vitro by interfering E2F1 activity. Our data highlight an important role of miR-331-3p in cell cycle control by targeting 3′-UTR of cell cycle-related molecule E2F1. We concluded that miR-331-3p is a potential tumor suppressor in gastric cancer. Restoring miR-331-3p in gastric cancer cells revealed potential application in gastric cancer therapy. [Copyright &y& Elsevier]

Abstract: Scutellarin was purified from the plant Erigeron breviscapus (Vant.) Hand.–Mazz. The activity against 3 strains of human immunodeficiency virus (HIV) was determined in vitro in this study. These were laboratory-derived virus (HIV-1IIIB), drug-resistant virus (HIV-174V), and low-passage clinical isolated virus (HIV-1KM018). From syncytia inhibition study, the EC50 of scutellarin against HIV-1IIIB direct infection in C8166 cells was 26μM with a therapeutic index of 36. When the mode of infection changed from acute infection to cell-to-cell infection, this compound became even more potent and the EC50 reduced to 15μM. This suggested that cell fusion might be affected by this compound. By comparing the inhibitory effects on p24 antigen, scutellarin was also found to be active against HIV-174V (EC50 253μM) and HIV-1KM018 (EC50 136μM) infection with significant difference in potency. The mechanism of its action was also explored in this study. At a concentration of 433μM, scutellarin inhibited 48% of the cell free recombinant HIV-1 RT activity. It also caused 82% inhibition of HIV-1 particle attachment and 45% inhibition of fusion at the concentrations of 54μM. In summary, scutellarin was found to inhibit several strains of HIV-1 replication with different potencies. It appeared to inhibit HIV-1 RT activity, HIV-1 particle attachment and cell fusion. These are essential activities for viral transmission and replication. [Copyright &y& Elsevier]

[Display omitted] In recent years, chemodynamic therapy (CDT) has gained increasing interest in cancer treatment. In contrast to photodynamic therapy and sonodynamic therapy, extrinsic excitations such as laser or ultrasound are not required in CDT. As a result, the CDT performance is not limited by the penetration depth of the external irritation. However, CDT relies heavily on hydrogen peroxide (H 2 O 2) in the tumour microenvironment (TME). Insufficient H 2 O 2 in the TME limits the CDT performance, and the most reported methods to produce H 2 O 2 in the TME are dependent on oxygen supply, which is restricted by the hypoxic TME. In this study, H 2 O 2 self-providing copper nanodots were proposed, and the drug doxorubicin (DOX) was successfully loaded to construct DOX-nanodots. Our results showed that the nanodots produced H 2 O 2 in the weakly acidic TME due to the peroxo group and further generated the most active hydroxyl radical (OH) through the Fenton-like reaction. This process was pH-dependent and did not occur in a neutral environment. In addition to OH, the nanodots also produced singlet oxygen (1O 2) and superoxide anions (O 2 –) in the cancer cells. The copper nanodots performed promising CDT against breast cancer in vitro and in vivo, with enhanced cell apoptosis and decreased cell proliferation. The combination of chemotherapy and CDT using DOX-nanodots further improved the therapeutic effects. The treatments showed good biocompatibility with no obvious toxicity in major tissues, possibly due to the specific OH generation in the weakly acidic TME. In summary, the H 2 O 2 self-providing copper nanodots in combination with DOX showed promising cancer-curing effects due to the oxygen-independent and tumour-specific production of reactive oxygen species and the cooperation of chemotherapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • 51 artemyrianolide H derivatives were synthesized and evaluated for cytotoxicity against human hepatoma cells. • 34 compounds were more active than artemyrianolide H and sorafenib. • Compound 25 induced G2/M phase arrest, apoptosis and bound to PDGFRA and MAP2K2. Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha , and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC 50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure−activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC 50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 μM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25 , and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with K D value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate. [ABSTRACT FROM AUTHOR]

Abstract The complex interplay between genetic and environmental factors, such as diet and lifestyle, defines the initiation and progression of multifactorial diseases, including cancer, cardiovascular and metabolic diseases, and neurological disorders. Given that most of the studies have been performed in controlled experimental settings to ensure the consistency and reproducibility, the impacts of environmental factors, such as dietary perturbation, on the development of animals with different genotypes and the pathogenesis of these diseases remain poorly understood. By analyzing the cdk8 and cyclin C (cycC) mutant larvae in Drosophila , we have previously reported that the CDK8-CycC complex coordinately regulates lipogenesis by repressing dSREBP (sterol regulatory element-binding protein)-activated transcription and developmental timing by activating EcR (ecdysone receptor)-dependent gene expression. Here we report that dietary nutrients, particularly proteins and carbohydrates, modulate the developmental timing through the CDK8/CycC/EcR pathway. We observed that cdk8 and cycC mutants are sensitive to the levels of dietary proteins and seven amino acids (arginine, glutamine, isoleucine, leucine, methionine, threonine, and valine). Those mutants are also sensitive to dietary carbohydrates, and they are more sensitive to monosaccharides than disaccharides. These results suggest that CDK8-CycC mediates the dietary effects on lipid metabolism and developmental timing in Drosophila larvae. Highlights • The cdk8 and cycC mutant Drosophila larvae are hypersensitive to increased levels of dietary proteins. • Of the 20 kinds of amino acids, the cdk8 and cycC mutants are particularly sensitive to the levels of 7 specific amino acids. • Compared to disaccharides, the cdk8 and cycC mutants are more sensitive to increased dietary monosaccharides. • CDK8-CycC may mediate the dietary effects on lipid metabolism and developmental transition in Drosophila larvae. [ABSTRACT FROM AUTHOR]

[Display omitted] • Twenty-one new guaianolide dimers were isolated from Artemisia zhongdianensis. • Nine compounds exhibited cytotoxicity against HSC-LX2. • Compounds 2, 6 and 13 displayed inhibitory activity on the deposition of Col Ⅰ, HA and HL. • This study provides more evidence for understanding of antihepatic fibrosis potency of Artemisia zhongdianensis. In the search for new antihepatic fibrosis candidates, it was observed that the EtOH extract of Artemisia zhongdianensis and EtOAc fraction had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with the inhibitory ratios of 85.7 % and 83.9 % at 400 μg/mL. 21 new guaianolide dimers, artemzhongdianolides A1 − A21 (1 – 21) were isolated from the active fractions under the guidance of bioassay, and elucidated by spectral analyses (HRESIMS, 1D and 2D NMR, IR, ECD). The absolute stereochemistry of compounds 1 , 13 , and 14 was determined by single-crystal X-ray diffraction analyses. Cytotoxicity evaluation suggested that nine compounds exhibited activity against HSC-LX2 with IC 50 values ranging from 14.0 to 95.2 μM. Of them, compounds 2 , 6 , and 13 displayed significant cytotoxicity against HSC-LX2 with IC 50 values of 22.1, 24.3 and 14.0 μM, which were 6 to 10 times more active than the positive drug silybin (IC 50 , 148.6 μM). Preliminary mechanism study revealed that compounds 2 , 6 , and 13 could markedly inhibited the deposition of human collagen type Ⅰ (Col Ⅰ), human hyaluronic acid (HA), and human laminin (HL) with IC 50 values of 37.9, 54.8, and 28.0 μM (Col Ⅰ), 29.5, 25.3, and 42.9 μM (HL), 31.2, 94.6, and 12.4 μM (HA), which were 1.5 to 13-fold more potent than silybin. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fourteen new coumaric acid analogues were isolated from Artemisia capillaris. • Twelve compounds exhibited cytotoxicity against HSC-LX2. • Compound 2 displayed potent inhibitory activity on the deposition of Col Ⅰ, HL and HA. • This study provides more evidence for the traditional use of Artemisia capillaris against hepatic fibrosis. Under the guidance of bioassay against HSC-LX2, the EtOH extract and the EtOAc fraction of Artemisia capillaris (Yin-Chen) exhibited cytotoxic activity against HSC-LX2 with inhibitory ratios of 39.7% and 68.7% at the concentration of 400.0 μg/mL. Bioassay-guided investigation of Fr. D (the active fraction) yielded 14 new coumaric acid analogues, artemicapillasins A–N (1 – 14). The structures of the isolates were elucidated by spectroscopic analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. Cytotoxic activity against HSC-LX2 cells of these isolates was performed to reveal that 12 compounds demonstrated cytotoxicity with inhibitory ratios more than 50% at 400 μM. The most active artemicapillasin B (2) gave an IC 50 value of 24.5 μM, which was about 7 times more toxic than the positive drug silybin (IC 50 , 162.3 μM). Importantly, artemicapillasin B (2) showed significant inhibition on the deposition of human collagen type I (Col I), human laminin (HL) and human hyaluronic acid (HA) with IC 50 values of 11.0, 14.4 and 13.8 μM, which was about 7, 11 and 5 times more active than silybin. Artemicapillasin B (2) as an interesting antihepatic fibrosis candidate is worth in-depth study. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sixteen new guaiane-type sesquiterpenoids were isolated from A. atrovirens. • The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. • Compounds 3 and 5 displayed cytotoxicity with IC 50 values of 8.0 and 16.0 μM (HepG2), 18.2 and 32.2 μM (Huh7). Random screening revealed that the EtOH extract of Artemisia atrovirens showed significant cytotoxicity against two human hepatoma cell lines (HepG2 and Huh7) with the inhibitory ratio of 98.9% and 99.7% at the concentration of 100 μg/mL. Further bioactivity-guided isolation of active fraction led to 16 new guaiane-type sesquiterpenoids, artematrovirenins A–P (1 – 16). Their structures were elucidated by extensive spectroscopic data. The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. Pharmacological evaluation suggested that five compounds (3 , 5 , 8 , 10 , and 15) exhibited cytotoxicity, compounds 3 and 5 displayed cytotoxicity against HepG2 cell line with an IC 50 values of 8.0 and 16.0 μM, as well as against Huh7 cell line with values of 18.2 and 32.2 μM. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the expression of PSD-93 mRNA and NR2B mRNA in the brain tissue from the patients with epilepsy so as to explore the possible mechanisms of the pathogenesis of the epilepsy. Methods: Fifty-six patients with epilepsy were divided into intractable epilepsy (IE) and non-intractable epilepsy (NIE) groups. cDNA microarrays prepared from the brain tissues obtained from these two groups were scanned and comparison to those from the non-epileptogenic control (C) was made. Expression level of PSD-93mRNA and NR2BmRNA were examined by reverse transcription polymerase chain reaction (GAPDH gene, internal control). Expression ratio (target gene/GAPDH) was used to evaluate each gene relative expression level. Results: The cDNA microarray analysis showed that the expression of PSD-93 mRNA related to the function of NMDAR-NO signal transduction pathway was significantly higher in epilepsy patients than those in the controlled group. The results of RT-PCR were consistent with those of the cDNA microarrays. The relative expression ratio of PSD-93 in patients with non-epileptogenic control, NIE, and IE was 0.159, 0.368, and 0.341, respectively. Correspondingly, that of NR2B was 0.198, 0.738, and 0.903, respectively. The expressions of PSD-93 and NR2B in the NIE and IE were significantly higher than those of control, respectively (P <0.05). However, there was no significantly difference the expression of PSD-93 between NIE and IE. (P >0.05), neither do that of NR2B (P >0.05). Conclusions: The upregulated expressions of PSD-93 mRNA and NR2BmRNA may be involved in the pathogenesis of epilepsy. [Copyright &y& Elsevier]

Abstract: Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in the temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures. [Copyright &y& Elsevier]

• Eleven new sesquiterpenoids were isolated from A. lavandulaefolia. • Fourteen compounds exhibited cytotoxicity against HSC-LX2 with IC 50 values ranging from 16.5 to 337.2 μM. • Compounds 14 , 15 and 18 displayed inhibitory activity on the deposition of Col I and HL. The preliminary assay suggested that the EtOH extract of Artemisia lavandulaefolia had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with an inhibitory ratio of 94.1% at 400 μg/mL. Bioassay-guided investigation led to eleven new sesquiterpenoids, artemilavanolides C–F (1 – 4) and artemlavandulolides A–G (5 – 11), as well as thirteen known compounds (12 – 24). Their structures were elucidated by extensive spectroscopic data and X-ray crystallographic analysis. Cytotoxicity evaluation suggested that fourteen compounds exhibited activity against HSC-LX2; compounds 22 , 23 and 24 were comparable to the positive control, silybin (IC 50 , 162.3 μM); compounds 6 , 9 and 16 showed moderate activity with IC 50 values of 109.3, 114.0 and 124.2 μM. Importantly, compounds 14 , 15 and 18 displayed significant cytotoxicity against HSC-LX2 with IC 50 values of 52.1, 16.5 and 21.3 μM, and inhibitory activity on the deposition of human collagen type I (Col I) and human laminin (HL) with IC 50 values ranging from 7.3 to 71.6 μM and from 18.6 to 72.9 μM. [ABSTRACT FROM AUTHOR]

• Thirteen new 2,6-epoxydiarylheptanoids were isolated from A. tsao-ko. • Eight diarylheptanoids showed obvious α -glucosidase inhibitory activity. • Compounds 12 and 13 were noncompetitive inhibitors of α -glucosidase. • The K i values of compounds 12 and 13 on α -glucosidase were 539.6 and 385.2 μM. The dried fruits of Amomum tsao-ko are well-known dietary spices and traditional Chinese medicines. The random screen revealed that 50% ethanol-water extract of A. tsao-ko demonstrated significant α -glucosidase inhibitory activity with an IC 50 value of 38.6 μg/mL. Bioactivity-guided isolation on the active fraction afforded 13 new 2,6-epoxy diarylheptanoids, tsaokopyranols A–M (1 – 13), and four known ones (14–17). Their structures featuring a 2,6-epoxy pyran ring were established by extensively spectroscopic analyses (HRESIMS, IR, UV, 1D and 2D NMR) and ECD calculations. Seven new (4 – 6 , 8 – 11) and one known (16) compounds showed obvious α -glucosidase inhibitory activity with IC 50 values ranging from 59.4 to 116.5 μM, higher than acarbose (IC 50 : 219.0 μM). An enzyme kinetic analysis indicated that compounds 12 and 13 were noncompetitive-type inhibitors of α -glucosidase with K i values of 539.6 and 385.2 μM. This result provided new insights for the usage of A. tsao-ko , and 2,6-epoxydiarylheptanoids as new anti-diabetic candidates. [ABSTRACT FROM AUTHOR]