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Regulating the structural and interfacial properties of transition metal phosphides (TMPs) by coupling carbon-based materials with large surface areas to enhance hydrogen evolution reaction (HER) performance presents significant progress for water splitting technology. Herein, we constructed a composite substrate of a three-dimensional porous graphene oxide matrix (3D-GO) embedded in nickel foam (NF) to grow a Co2P electrocatalyst. Well-defined gladiolus-like Co2P nanowire arrays tightly anchored on the substrate show enhanced electrochemical characteristics for the hydrogen evolution reaction (HER) based on the promoting roles of 3D porous reduced GO (3D-rGO) derived from 3D-GO, which promotes the dispersion of active components, improves the rate of electron transfer, and facilitates the transport of water molecules. As a result, the obtained Co2P@3D-rGO/NF electrode exhibits superior HER activity in 1.0 M KOH media, achieving overpotentials of 36.5 and 264.7 mV at current densities of 10 and 100 mA cm−2, respectively. The electrode also has a low Tafel slope of 55.5 mV dec−1, a large electrochemical surface area, and small charge-transfer resistance, further revealing its mechanism of high intrinsic activity. Moreover, the electrode exhibits excellent HER stability and durability without surface morphology and chemical state changes. [ABSTRACT FROM AUTHOR]

The rational passivation of the defects at the buried interface plays a significant role in reducing energy loss and improving the photovoltaic performance of perovskite solar cells (PSCs). Herein, we have applied a metal–organic framework (MOF)-based host–guest system consisting of zeolitic imidazolate framework-8 (ZIF-8) nanosheets confined with methylammonium chloride (MACl) to modify the SnO2/perovskite interface. The MACl@ZIF-8 not only effectively reduces the oxygen vacancies on SnO2, but also binds with the uncoordinated Pb2+ and halogen ions at the bottom of the perovskite layer. Moreover, the loaded MACl guest plays the role of both crystalline seeds involved in the formation of ZIF-8@perovskite heterojunctions and organic cation vacancy passivators. Thus, the simultaneous passivation of the buried interface and bulk phase of the perovskite is realized, and the photovoltaic performance of devices is enhanced considerably with an optimal efficiency of 22.10%. The introduction of MACl@ZIF-8 also allows the device to achieve excellent moisture stability due to better crystallinity and fewer phase defects. In particular, the UV shielding characteristic of the imidazole ligands in ZIF-8 results in a significant increase in the UV resistance capability. [ABSTRACT FROM AUTHOR]

Myocarditis is classified as an inflammatory disease of the heart muscle and is a leading cause of sudden death. The Keap1-Nrf2-ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1-Nrf2 protein–protein interaction (PPI) is considered as a potential drug target against myocarditis to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes. To gain insights into the relationship between the activity and structure of the compounds and design superior active novel inhibitors, 3D-QSAR, molecular docking and molecular dynamics (MD) simulation were combined to investigate the interaction between Keap1–Nrf2 PPI inhibitors and Keap1. The comparative molecular field analysis (CoMFA) model (q2 = 0.907, n = 7, R2 = 0.997) and the comparative molecular similarity index analysis (CoMSIA) model (q2 = 0.900, n = 7, and R2 = 0.993) showed that the 3D-QSAR models built were credible and predictable. Based on these models, 10 new compounds were discovered and their bioactivity was validated using molecular docking and MD simulation. Furthermore, the plausible ADME/T characteristics of new compounds were evaluated and the key residues (Arg415, Tyr334, Ser602, Ser363, Arg380, etc.) in the active site were also identified by free energy calculation. The binding energy results show that the structurally optimized compounds (N1: −65.409 kcal mol−1, N3: −54.619 kcal mol−1, N4: −62.627 kcal mol−1, N5: −60.903 kcal mol−1, and N8: −66.272 kcal mol−1) have lower binding free energy values than compound 43 (ΔGbind: −49.991 kcal mol−1), indicating that they have a better affinity for the target. These findings provide necessary theoretical guidance for the discovery and design of highly active drugs against myocarditis. [ABSTRACT FROM AUTHOR]

Despite great progress achieved for metal oxide electron transport layers (ETLs), finding alternative inorganic ETLs is necessary and meaningful to further boost the performance and stability of perovskite solar cells (PSCs), and also to expand the inorganic ETL family. Herein, 2D SnS2 nanosheets prepared by a simple hydrothermal route are applied as low-temperature processed ETLs of PSCs. These SnS2 ETLs show a compact and uniform surface, a high transparency, and a fast charge carrier mobility. PSCs based on sole SnS2 ETLs show a high energy conversion efficiency of 18.5%, ranking top among the metal sulfide ETLs. Furthermore, the 2D SnS2 nanosheets are used as an effective interfacial modifier for the traditional SnO2 ETL, which forms an energy level gradient between SnO2 and the perovskite layer. The SnS2 interlayer improves the perovskite crystallization and passivates defects at the interface due to the optimized coupling, enabling a PCE of 21.5% for the SnO2–SnS2 bi-layer PSCs along with enhanced stability. [ABSTRACT FROM AUTHOR]

There is a crucial need for novel antibiotics against multi-drug resistant Gram-negative pathogens. BamA is an outer membrane β-barrel protein that is required for the folding and insertion of β-barrel proteins into the outer membrane. Targeting BamA has been demonstrated as a new avenue for antibiotic discovery. Here, we screened a set of cyclic peptides against BamA from our in-house peptide library by molecular docking with high-precision. All these screened cyclic peptides exhibited activity against Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii and multidrug-resistant Acinetobacter baumannii (MDR A. baumannii). Notably, the lead peptide B2 (cyclo-RRWWRRW) exhibited potent activity against both the standard and clinical MDR A. baumannii strains. Peptide B2 killed A. baumannii by permeabilizing the bacterial membrane and showed little hemolysis. Moreover, peptide B2 showed significant therapeutic effects on lung infections in mice induced by the infection of clinical MDR A. baumannii. Furthermore, we explored the binding mode of peptide B2 complexed with BamA by molecular simulation, and the key residues were identified by their binding energy contributions, which might be used to guide targeted candidate discovery of novel antimicrobial agents. This study provides a new strategy for the development of antimicrobial peptides to address life-threatening infections by Gram-negative pathogens. [ABSTRACT FROM AUTHOR]

Hsp90 is a highly conserved and essential stress protein located in all eukaryotes, involved in the regulation of fungal survival, virulence and resistance, which is an important target for the treatment of fungal infections. Here, we intended to discover a novel inhibitor against Hsp90 guided by theoretical 3-dimensional quantitative structure–activity relationship (3D-QSAR) models for aminopyrazole analogs, which were constructed by the comparative molecular field analysis (CoMFA) and the comparative molecular similarity index analysis (CoMSIA) models. The CoMFA (q2 = 0.708, R2 = 0.962) and CoMSIA (q2 = 0.656, R2 = 0.922) models had good stability and predictability, and their contour maps could provide 3D visual information for structural modification. Subsequently, all the inhibitors used in modeling were docked into the binding site of Hsp90 by the Surflex-Dock method and their interaction was explored, which indicated that inhibitor complexes to Hsp90 mainly relied on hydrogen bonds, Pi–S stacking and hydrophobic interactions. Then, we designed 10 novel candidates guided by contour maps and binding modes, and their potential anti-fungal activity and ADME/T profile were predicted by 3D-QSAR models and online tools, which showed the candidates with better potency and good ADME/T properties. We achieved the stable conformation of candidates (M7 and M9) complexed to Hsp90 by molecular dynamics (MD) simulations and evaluated their binding energy and energy contribution of amino acids by MM/PBSA. Compared to reports in the literature (compound 22: −44.725), the designed candidates (M7: −51.478, M9: −54.964) had better potency represented by binding energy. Based on the energy contribution of amino acids, we identified the key residues that interacted with candidates, such as Asp82, Thr174 and Leu37, which had a crucial role in increasing the binding affinity. Thus, our study could provide theoretical clues to design an inhibitor against Hsp90 which is used as an anti-fungal agent. [ABSTRACT FROM AUTHOR]

The combination of human programmed cell death protein 1 (hPD-1) and its ligand hPD-L1 activates the immune escape of tumors, and the blockage in the PD-1/PD-L1 involved pathway can enhance the endogenous anti-tumor immunity. Therefore, blocking the interaction of PD-1 and its ligand PD-L1 has become a promising cancer immunotherapy technique. Recently, different types of small molecules and peptides have been discovered as PD-1/PD-L1 inhibitors. In the present work, in silico virtual screening and biomolecular interaction analysis (BIAcore) against our internal peptide library are used to discover peptides as probes to inhibit the binding between PD-1 and PD-L1. Particularly, RRQWFW-NH2 and RRWWRR-NH2 are found to have better docking scores of 7.69 and 8.34, respectively. Sequentially, molecular dynamics (MD) simulations and surface plasmon resonance (SPR) are used to further validate our predictions. Interestingly, our results showed that RRQWFW-NH2 and RRWWRR-NH2 show moderate activity to inhibit the protein–protein interaction between PD-1 and PD-L1, in which the experimental data are consistent with the computational data. Our research provides a robust computational method for the development of new PD-1/PD-L1 inhibitors and provides some new candidate peptide drugs for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

A novel strategy to boost the oxygen evolution reaction (OER) activity of NiFe-LDHs has been developed using reduced graphene oxide (rGO) as both the substrate and electronic carrier. Basically, a GO hydrogel is printed on Ni foam by the doctor blade technique, forming a GO matrix embedded in Ni foam, which is then freeze-dried to turn into a 3-dimensional (3D) porous GO (3D-GO) matrix. NiFe-layered double hydroxide (NiFe-LDH) nanoflakes anchored on the 3D-GO matrix embedded in Ni foam are synthesized by a hydrothermal process, together with the in situ reduction of 3D-GO. The obtained electrode has a high degree of reduction of the porous graphene oxide, the mechanical strength of the NiFe-LDH nanoflakes anchored on the matrix, large active surface area and excellent interface conjunction. Based on optimal conditions, the fabricated electrode shows outstanding electrocatalytic oxygen evolution reaction performance in 1 M KOH aqueous solution, achieving a small overpotential of 170 mV, a Tafel slope of 57 mV decade−1 at a current density of 20 mA cm−2 and a relatively stable operating potential after 2000 cycles of the CV test. [ABSTRACT FROM AUTHOR]

Regulating the structural and interfacial properties of transition metal phosphides (TMPs) by coupling carbon-based materials with large surface areas to enhance hydrogen evolution reaction (HER) performance presents significant progress for water splitting technology. Herein, we constructed a composite substrate of a three-dimensional porous graphene oxide matrix (3D-GO) embedded in nickel foam (NF) to grow a Co 2 P electrocatalyst. Well-defined gladiolus-like Co 2 P nanowire arrays tightly anchored on the substrate show enhanced electrochemical characteristics for the hydrogen evolution reaction (HER) based on the promoting roles of 3D porous reduced GO (3D-rGO) derived from 3D-GO, which promotes the dispersion of active components, improves the rate of electron transfer, and facilitates the transport of water molecules. As a result, the obtained Co 2 P@3D-rGO/NF electrode exhibits superior HER activity in 1.0 M KOH media, achieving overpotentials of 36.5 and 264.7 mV at current densities of 10 and 100 mA cm -2 , respectively. The electrode also has a low Tafel slope of 55.5 mV dec -1 , a large electrochemical surface area, and small charge-transfer resistance, further revealing its mechanism of high intrinsic activity. Moreover, the electrode exhibits excellent HER stability and durability without surface morphology and chemical state changes.