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The commercialization process of perovskite solar cells (PSCs) is markedly restricted by the power conversion efficiency (PCE) and long-term stability. During fabrication and operation, the bottom interface of the organic-inorganic hybrid perovskite layer frequently exhibits voids and residual PbI 2 , while these defects inevitably act as recombination centers and degradation sites, affecting the efficiency and stability of the devices. Therefore, the degradation and nonradiative recombination originating from the buried interface should be thoroughly resolved. Here, we report a multifunctional passivator by introducing malonic dihydrazide as an interfacial chemical bridge between the electron transport layer and the perovskite (PVK) layer. MADH with hydrazine groups improves the surface affinity of SnO 2 and provides nucleation sites for the growth of PVK, leading to the reduced residual PbI 2 and the voids resulting from the inhomogeneous solvent volatilization at the bottom interface. Meanwhile, the hydrazine group and carbonyl group synergistically coordinate with Pb 2+ to improve the crystal growth environment, reducing the number of Pb-related defects. Eventually, the PCE of the PSCs is significantly enhanced benefiting from the reduced interfacial defects and the increased carrier transport. Moreover, the reductive nature of hydrazide further inhibits I 2 generation during long-term operation, and the device retains 90% of the initial PCE under a 1 sun continuous illumination exposure of 700 h.

Organic-inorganic perovskites face the issues of being vulnerable to oxygen and moisture and the trap sites located at the surface and grain boundaries. Integration of two-dimensional (2D) perovskites as a capping layer is an effective route to enhance both photovoltaic efficiency and environmental stability of the three-dimensional (3D) underlayer. Here, we employ 1,4-butanediammonium diiodide (BDADI), which has a short chain length and diammonium cations, to construct a 3D/2D stacking perovskite solar cells (PSCs). The introduction of BDA 2+ could passivate surface defects in 3D perovskites by forming 2D Dion-Jacobson (DJ) phase perovskites and effectively suppressing nonradiative recombination, thus resulting in a longer carrier lifetime. The DJ 2D capping layer also regulate the energy level arrangement, enabling a better charge extraction and transport process. In addition, the water-resistance ability of 3D perovskite gets improved because of the hydrophobic characteristic of 1,4-butanediammonium cations. Consequently, the 3D/2D stacking PSCs yield an energy conversion efficiency of 20.32% in company with the enhanced long-term stability.

TRPM8 antagonists derived from its cognate ligand, (-)-menthol, are underrepresented. We determine the absolute stereochemistry of a well-known TRPM8 antagonist, (-)-menthyl 1 , using VCD and 2D NMR. We explore 1 for its antagonist effects of the human TRPM8 (hTRPM8) orthologue to uncover species-dependent inhibition versus rat channels. (-)-Menthyl 1 inhibits menthol- and icilin-evoked Ca 2+ responses at hTRPM8 with IC 50 values of 805 ± 200 nM and 1.8 ± 0.6 μM, respectively, while more potently inhibiting agonist responses at the rat orthologue (rTRPM8 IC 50 (menthol) = 117 ± 18 nM, IC 50 (icilin) = 521 ± 20 nM). Whole-cell patch-clamp recordings of hTRPM8 confirm the 1 inhibition of menthol-stimulated currents, with an IC 50 of 700 ± 200 nM. We demonstrate that 1 possesses ≥400-fold selectivity for hTRPM8 versus hTRPA1/hTRPV1. (-)-menthyl 1 can be used as a novel chemical tool to study hTRPM8 pharmacology and differences in species commonly used in drug discovery., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Structure-activity relationship studies of a reported menthol-based transient receptor potential cation channel subfamily M member 8 channel (TRPM8) antagonist, guided by computational simulations and structure-based design, uncovers a novel series of TRPM8 antagonists with >10-fold selectivity versus related TRP subtypes. Spiro[4.5]decan-8-yl analogue 14 inhibits icilin-evoked Ca 2+ entry in HEK-293 cells stably expressing human TRPM8 (hTRPM8) with an IC 50 of 2.4 ± 1.0 nM, while in whole-cell patch-clamp recordings this analogue inhibits menthol-evoked currents with a hTRPM8 IC 50 of 64 ± 2 nM. Molecular dynamics (MD) simulations of compound 14 in our homology model of hTRPM8 suggest that this antagonist forms extensive hydrophobic contacts within the orthosteric site. In the wet dog shakes (WDS) assay, compound 14 dose-dependently blocks icilin-triggered shaking behaviors in mice. Upon local administration, compound 14 dose dependently inhibits cold allodynia evoked by the chemotherapy oxaliplatin in a murine model of peripheral neuropathy at microgram doses. Our findings suggest that 14 and other biphenyl amide analogues within our series can find utility as potent antagonist chemical probes derived from (-)-menthol as well as small molecule therapeutic scaffolds for chemotherapy-induced peripheral neuropathy (CIPN) and other sensory neuropathies.

Epilepsy is a common cause of serious cognitive disorders and is known to have impact on patients' memory and executive functions. Therefore, the development of antiepileptic drugs for the improvement of spatial learning and memory in patients with epileptic cognitive dysfunction is important. In the present work, we systematically predicted and analyzed the potential effects of Ginkgo terpene trilactones (GTTL) on cognition and pathologic changes utilizing in silico and in vivo approaches. Based on our established chemogenomics knowledgebase, we first conducted the network systems pharmacology analysis to predict that ginkgolide A/B/C may target 5-HT 1A, 5-HT 1B, and 5-HT 2B. The detailed interactions were then further validated by molecular docking and molecular dynamics (MD) simulations. In addition, status epilepticus (SE) was induced by lithium-pilocarpine injection in adult Wistar male rats, and the results of enzyme-linked immunosorbent assay (ELISA) demonstrated that administration with GTTL can increase the expression of brain-derived neurotrophic factor (BDNF) when compared to the model group. Interestingly, recent studies suggest that the occurrence of a reciprocal involvement of 5-HT receptor activation along with the hippocampal BDNF-increased expression can significantly ameliorate neurologic changes and reverse behavioral deficits in status epilepticus rats while improving cognitive function and alleviating neuronal injury. Therefore, we evaluated the effects of GTTL (bilobalide, ginkgolide A, ginkgolide B, and ginkgolide C) on synergistic antiepileptic effect. Our experimental data showed that the spatial learning and memory abilities (e.g., electroencephalography analysis and Morris water maze test for behavioral assessment) of rats administrated with GTTL were significantly improved under the middle dose (80 mg/kg, GTTL) and high dose (160 mg/kg, GTTL). Moreover, the number of neurons in the hippocampus of the GTTL group increased when compared to the model group. Our studies showed that GTTL not only protected rat cerebral hippocampal neurons against epilepsy but also improved the learning and memory ability. Therefore, GTTL may be a potential drug candidate for the prevention and/or treatment of epilepsy., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)