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Microtubules are composed of αβ‐tubulin heterodimers, and drugs that interfere with microtubule dynamics are used widely in cancer chemotherapy. Small synthetic molecules with an indole nucleus as a core structure have been identified as microtubule inhibitors and recognized as anticancer agents. However, structural information for the interactions between indole derivatives and tubulin is sparse. Here, we present the 2.55 Å crystal structure of tubulin in complex with the indole derivative D64131. We compare the binding modes of D64131, colchicine, and five other indole derivatives to tubulin. These results reveal the interactions between the indole derivatives and tubulin, explain previous results of structure‐activity‐relationship (SAR) studies and, thus, provide insights into the development of new indole derivatives targeting the colchicine binding site. [ABSTRACT FROM AUTHOR]

Peptidyl‐prolyl cis‐trans isomerase Pin1 plays a crucial role in the development of human cancers. Recently, we have disclosed that Pin1 regulates the biogenesis of miRNA, which is aberrantly expressed in HCC and promotes HCC progression, indicating the therapeutic role of Pin1 in HCC therapy. Here, 7‐(benzyloxy)‐3,5‐dihydroxy‐2‐(4‐methoxyphenyl)‐8‐(3‐methylbut‐2‐en‐1‐yl)‐4H‐chromen‐4‐one (AF‐39) was identified as a novel Pin1 inhibitor. Biochemical tests indicate that AF‐39 potently inhibits Pin1 activity with an IC50 values of 1.008 μm, and also displays high selectivity for Pin1 among peptidyl prolyl isomerases. Furthermore, AF‐39 significantly suppresses cell proliferation of HCC cells in a dose‐ and time‐dependent manner. Mechanistically, AF‐39 regulates the subcellular distribution of XPO5 and increases miRNAs biogenesis in HCC cells. This work provides a promising lead compound for HCC treatment, highlighting the therapeutic potential of miRNA‐based therapy against human cancer. Neat as a pin: Prenylated flavonol AF‐39 was discovered as a novel and selective Pin1 inhibitor with an IC50 value of 1.008 μm. In hepatocellular carcinoma (HCC) cells, AF‐39 significantly suppresses HCC proliferation via restoring ERK‐phosphorylated exportin‐5 (XPO5) nucleus–cytoplasm distribution and upregulating microRNA biogenesis. [ABSTRACT FROM AUTHOR]

In practical applications, part of solar rays incidence on reflectors of compound parabolic concentrators (CPC, in short) undergoes diffuse reflections instead of specular reflections due to imperfect reflector profile, rough surface and dust deposition, leading a considerable fraction of solar rays escape from the cavity of CPCs and making their optical performance decrease. In this article, a detailed mathematical procedure to estimate the optical efficiency factor of CPCs with semi-diffuse reflectors and one-sided flat absorber is developed based on the knowledge of two-dimensional radiation transfer, and the effect of diffuse reflections within the CPC on its energy collection is theoretically investigated. Ray-tracing analysis shows that the use of semi-diffuse reflectors in CPCs can not make solar flux on the absorber more uniform except using perfect diffuse reflectors, in turn leads the optical efficiency decrease. Comparisons of the optical efficiency factors between theoretically expected and those obtained by ray-tracing simulation indicate that the mathematical model proposed in this work can accurately estimate the optical performance of such CPC. Theoretical calculations show that the contribution of diffuse reflections within CPCs to the radiation collection of CPCs is limited as a result of the fact that the diffuse radiation transfer shape factor from the reflectors to the absorber is very small, and the annual average optical concentration decreases with the increase of diffuse reflectivity of reflectors for CPCs with a given total reflectivity. [ABSTRACT FROM AUTHOR]

To perform this comparison, the compound parabolic concentrator with a restricted exit angle of 65° (CPC-65) and the one without exit angle restriction (CPC-90) were fabricated and tested for concentrating radiation on multi-crystalline solar cells. Both CPC-65 and CPC-90 are identical in the acceptance half-angle (20°) and geometrical concentration factor (2×). Theoretical calculations showed that CPC-90 based PV system (CPV-90) annually concentrated about 3–5% more radiation on solar cells as compared to CPC-65 based PV system (CPV-65). For CPV-65, all radiation would arrive on the solar cells at the incidence angle less than 65°, but for CPV-90, about 8–10% of annual collectible radiation would arrive on solar cells at the incidence angle larger than 65°. Measurements at outdoor conditions showed that the CPV-65 performed slightly better than CPV-90 in terms of short-circuit current and power output as the projection incidence angle of solar rays on the cross-section of CPC-troughs ( θ p ) less than the acceptance half-angle, otherwise the CPV-90 did better. Compared to CPV-90, the power output at maximum power points from CPV-65 were slightly higher, and increases of 2.1%, 5.4% and 8.17% were measured for θ p = 0°, 10° and 16°, respectively. Analysis indicated that effect of solar flux distribution over solar cells on power output of both CPVs was almost identical and insignificant, and the CPV-65 performed slightly but insignificantly better than the CPV-90 in terms of annual power output except in areas with poor solar resources where the annual power output from both systems was almost identical. [ABSTRACT FROM AUTHOR]

Natalizumab antibody to α4-integrins is used in therapy of multiple sclerosis and Crohn's disease. A crystal structure of the Fab bound to an α4 integrin β-propeller and thigh domain fragment shows that natalizumab recognizes human-mouse differences on the circumference of the β-propeller domain. The epitope is adjacent to but outside of a ligand-binding groove formed at the interface with the β-subunit β1 domain and shows no difference in structure when bound to Fab. Competition between Fab and the ligand vascular cell adhesion molecule (VCAM) for binding to cell surface α4β1 shows noncompetitive antagonism. In agreement, VCAM docking models suggest that binding of domain 1 of VCAM to α4-integrins is unimpeded by the Fab, and that bound Fab requires a change in orientation between domains 1 and 2 of VCAM for binding to α4β1. Mapping of species-specific differences onto α4β1 and α4β7 shows that their ligand-binding sites are highly conserved. Skewing away from these conserved regions of the epitopes recognized by current therapeutic function-blocking antibodies has resulted in previously unanticipated mechanisms of action. [ABSTRACT FROM AUTHOR]

Biochar has been reported as an effective additive to improve methane production during anaerobic digestion (AD). However, the mechanism for such a stimulatory impact remains unclear. Here we investigated the capability of three pyrolytic biochars with distinctive electrochemical properties (BC300, BC500, BC700) to promote methanogenic performance of anaerobic digesters treating waste activated sludge (WAS). The cumulative methane production and the maximum methane production rate were increased by 46.9% and 181.6%, respectively, with BC300 amendment. By characterizing the electrochemical properties of biochar, we found out that methane production in AD of sludge was positively correlated to biochar's electron-donating capacity (EDC) rather than its bulk electrical conductivity. These results indicate that the electron transfer mediated by the redox-active functional groups may prevail over the direct electron migration as the predominant mechanism to facilitate interspecies electron transfer in syntrophic communities for enhanced methanogenesis. Microbial community analysis suggests that biochar enriched Methanosarcina and Methanobacterium. Overall, this study shows that functional groups-mediated electron transfer contributes greatly to the improved methane production in WAS digester with biochar amendment. Image 1 • Redox-active biochar greatly promoted methane production from sludge digestion. • BC300 increased methane production and maximal methanogenic rate by 47% and 181%. • The stimulatory effect greatly attributed to biochar's electron donating capacity. • Biochar improved anaerobic digestion independently of its electric conductivity. • Biochar as electron donor promote metabolism of syntrophic methanogenic consortia. [ABSTRACT FROM AUTHOR]

The lymphocyte homing receptor integrin \(\alpha_4 \beta_7\) is unusual for its ability to mediate both rolling and firm adhesion. \(\alpha_4 \beta_1\) and \(\alpha_4 \beta_7\) are targeted by therapeutics approved for multiple sclerosis and Crohn’s disease. Here, we show by electron microscopy and crystallography how two therapeutic Fabs, a small molecule (RO0505376), and mucosal adhesion molecule-1 (MAdCAM-1) bind α4β7. A long binding groove at the \(\alpha_4 -\beta_7\)interface for immunoglobulin superfamily domains differs in shape from integrin pockets that bind Arg-Gly-Asp motifs. RO0505376 mimics an Ile/Leu-Asp motif in \(\alpha_4\) ligands, and orients differently from Arg-Gly-Asp mimics. A novel auxiliary residue at the metal ion–dependent adhesion site in \(\alpha_4 \beta_7\) is essential for binding to MAdCAM-1 in \(Mg^{2+}\) yet swings away when RO0505376 binds. A novel intermediate conformation of the \(\alpha_4 \beta_7\) headpiece binds MAdCAM-1 and supports rolling adhesion. Lack of induction of the open headpiece conformation by ligand binding enables rolling adhesion to persist until integrin activation is signaled.

This document is a correction notice for an article titled "Carbon quantum dots of ginsenoside Rb1 for application in a mouse model of intracerebral hemorrhage" published in the Journal of Nanobiotechnology. The correction addresses an error in the affiliations of the authors. The correct affiliations are provided in the correction notice. The original article has been corrected. Springer Nature, the publisher, remains neutral regarding jurisdictional claims and institutional affiliations. [Extracted from the article]