Near-Infrared Imaging of Steroid Hormone Activities Using Bright BRET Templates

Bioluminescence (BL) is an excellent optical readout for bioassays and molecular imaging. Herein, we accomplished new near infrared bioluminescence resonance energy transfer (NIR-BRET) templates for monitoring molecular events in cells with higher sensitivity. We first identified the best resonance energy donor for the NIR-BRET templates through the characterization of many coelenterazine (CTZ)–marine luciferase combinations. As a result, we found that NLuc–DBlueC and ALuc47–nCTZ combinations showed luminescence in the blue emission wavelength with excellent BL intensity and stability, for example, the NLuc–DBlueC and ALuc47–nCTZ combinations were 17-fold and 22-fold brighter than their second highest combinations, respectively, and were stably bright in living mammalian cells for at least 10 min. To harness the excellent BL properties to the NIR-BRET systems, NLuc and ALuc47 were genetically fused to fluorescent proteins (FPs), allowing large “blue-to-red” shifts, such as LSSmChe, LSSmKate2, and LSSmNep (where LSS means Large Stokes Shift). The excellent LSSmNep–NLuc combination showed approximately 170 nm large resonance energy shift from blue to red. The established templates were further utilized in the development of new NIR-BRET systems for imaging steroid hormone activities by sandwiching the ligand-binding domain of a nuclear receptor (NR-LBD) between the luciferase and the FP of the template. The NIR-BRET systems showed a specific luminescence signal upon exposure to steroid hormones, such as androgen, estrogen, and cortisol. The present NIR-BRET templates are important additions for utilizing their advantageous imaging of various molecular events with high efficiency and brightness in physiological samples.     

Pinostrobin Suppresses the α-Melanocyte-Stimulating Hormone-Induced Melanogenic Signaling Pathway

Pinostrobin is a dietary flavonoid found in several plants that possesses pharmacological properties, such as anti-cancer, anti-virus, antioxidant, anti-ulcer, and anti-aromatase effects. However, it is unclear if pinostrobin exerts anti-melanogenic properties and, if so, what the underlying molecular mechanisms comprise. Therefore, we, in this study, investigated whether pinostrobin inhibits melanin biosynthesis in vitro and in vivo, as well as the potential associated mechanism. Pinostrobin reduced mushroom tyrosinase activity in vitro in a concentration-dependent manner, with an IC₅₀ of 700 μM. Molecular docking simulations further revealed that pinostrobin forms a hydrogen bond, as well as other non-covalent interactions, between the C-type lectin-like fold and polyphenol oxidase chain, rather than the previously known copper-containing catalytic center. Additionally, pinostrobin significantly decreased α-melanocyte-stimulating hormone (α-MSH)-induced extracellular and intracellular melanin production, as well as tyrosinase activity, in B16F10 melanoma cells. More specifically, pinostrobin inhibited the α-MSH-induced melanin biosynthesis signaling pathway by suppressing the cAMP–CREB–MITF axis. In fact, pinostrobin also attenuated pigmentation in α-MSH-stimulated zebrafish larvae without causing cardiotoxicity. The findings suggest that pinostrobin effectively inhibits melanogenesis in vitro and in vivo via regulation of the cAMP–CREB–MITF axis.     

Atractylodin Ameliorates Colitis via PPARα Agonism

Atractylodin is a major compound in the rhizome of Atractylodes lancea, an oriental herbal medicine used for the treatment of gastrointestinal diseases, including dyspepsia, nausea, and diarrhea. Recent studies have shown that atractylodin exerts anti-inflammatory effects in various inflammatory diseases. Herein, we investigated the anti-colitis effects of atractylodin and its molecular targets. We determined the non-cytotoxic concentration of atractylodin (50 μM) using a cell proliferation assay in colonic epithelial cells. We found that pretreatment with atractylodin significantly inhibits tumor necrosis factor-α-induced phosphorylation of nuclear factor-κ-light-chain-enhancer of activated B in HCT116 cells. Through docking simulation analysis, luciferase assays, and in vitro binding assays, we found that atractylodin has an affinity for peroxisome proliferator-activated receptor alpha (PPARα). Daily administration of atractylodin (40 mg/kg) increased the survival rate of mice in a dextran sodium sulfate-induced colitis mouse model. Thus, atractylodin can be a good strategy for colitis therapy through inducing PPARα-dependent pathways.     

Enhanced Tumor Uptake and Retention of Cyanine Dye–Albumin Complex for Tumor-Targeted Imaging and Phototherapy

Heptamethine cyanine dyes are widely used for in vivo near-infrared (NIR) fluorescence imaging and NIR laser-induced cancer phototherapy due to their good optical properties. Since most of heptamethine cyanine dyes available commercially are highly hydrophobic, they can usually be used for in vivo applications after formation of complexes with blood plasma proteins, especially serum albumin, to increase aqueous solubility. The complex formation between cyanine dyes and albumin improves the chemical stability and optical property of the hydrophobic cyanine dyes, which is the bottom of their practical use. In this study, the complexes between three different heptamethine cyanine dyes, namely clinically available indocyanine green (ICG), commercially available IR-786 and zwitterionic ZW800-Cl, and bovine serum albumin (BSA), were prepared to explore the effect of cyanine dyes on their tumor uptake and retention. Among the three complexes, IR-786©BSA exhibited increased tumor accumulation with prolonged tumor retention, compared to other complexes. Moreover, IR-786 bound to BSA played an important role in tumor growth suppression due to its cytotoxicity. To achieve complete tumor ablation, the tumor targeted by IR-786©BSA was further exposed to 808 nm laser irradiation for effective photothermal cancer treatment.     

设置垫板的形件螺栓连接滞回性能试验研究

该文综述了对称和非对称型摩擦耗能连接40多年以来的发展历史和研究现状。摩擦耗能连接可用于结构的减震耗能,通过合理设计可实现地震作用下带摩擦耗能连接结构的低损伤,提高结构的韧性。研发滞回性能稳定、重复性好的摩擦耗能连接是相关研究的主要目标之一。该文从微观和宏观两个方面介绍了金属滑移面之间的摩擦磨损机理,从摩擦磨损的角度讨论了不同摩擦片材料对摩擦连接减震性能的影响。描述了螺栓预紧力大小对摩擦连接减震性能的影响,也总结了摩擦连接的抗腐蚀和抗火性能。阐述了摩擦耗能连接在钢结构支撑、梁柱节点和柱脚节点的应用,并介绍了相关节点的设计方法。对此类连接的关键技术进行了总结,并对该技术的后续研究进行了展望。     

Correction to: A note on the three methods of item analysis

Behaviormetrika - In the original publication of the article, Appendix A was published incorrectly.     

Toward a Nanoscale-Defect-Free Ni-Rich Layered Oxide Cathode Through Regulated Pore Evolution for Long-Lifespan Li Rechargeable Batteries

Ni-rich layered oxides are envisioned as the most promising cathode materials for next-generation lithium-ion batteries; however, their practical adoption is plagued by fast capacity decay originating from chemo-mechanical degradation. The intrinsic chemical–mechanical instability, inherited from atomic- and nanoscale defects generated during synthesis, is not yet resolved. Here, atomic- and nanoscale structural evolution during solid-state synthesis of Ni-rich layered cathode, Li[Ni_0.92Co_0.03Mn_0.05]O₂, is investigated using combined X-ray/neutron scattering and electron/X-ray microscopy. The multiscale analyses demonstrate the intertwined correlation between phase transition and microstructural evolution, with atomic-scale defects derived from the decomposition of precursors leading to the creation of intra/inter-granular pores. The nucleation and coalescence mechanism of pore defects during the synthesis of Ni-rich layered cathodes are quantitatively revealed. Furthermore, a modified synthetic route is proposed to effectively circumvent the formation of nanoscale defects in Ni-rich layered cathodes by facilitating uniform synthetic reactions, resulting in superior electrochemical and microstructural stability.     

Weakly Binding Molecules-Based Fast Charging Li-Ion Batteries

Fast charging of Li-ion batteries (LIBs) beyond standard 0.3 C (charged in 3.3 h) are desperately pursued but hindered by sluggish desolvation kinetics of ethylene carbonate-based traditional electrolyte, and Li-plating and dendrites growth at graphite anode and fire hazard. Herein, a new class of weakly binding all linear molecules-based nonflammable electrolyte (WNLE) is reported, comprising 1 m LiPF₆ in ethyl methyl carbonate and 2,2,2-trifluoroethyl acetate with additives for 10–20 times faster charging LIBs than traditional ones. The critical benefits of WNLE are 44% lower viscosity, 62% higher Li⁺ diffusion coefficient, 20% higher Li⁺ transference number, and 17% lower desolvation energy, which promotes diffusion kinetics and desolvation kinetics of Li⁺ in the vicinity of graphite anode enabling dendrites-free LIB, along with nonflammability. Under 3 C (charged in 20 min), WNLE-based industrial 800 mAh graphite//LiNi_0.8Mn_0.1Co_0.1O₂ (high active mass 13 mg cm⁻²) Li-ion pouch battery achieves outstanding 700 cycles, delivering 82% capacity retention and high Coulombic efficiencies ≈100%. Robust solid electrolyte interphase layers formed at the anode and cathode mitigate interfacial failures, making fast charge to 7 C and longer cycle-life. This new class of electrolyte formulation is a promising solution and a new opportunity to realize safe and long operation of fast-charging LIBs for practical applications.