RESUMO
Personalizing treatments to account for genetically mediated differences in drug responses is an exciting opportunity to improve patient outcomes. In this issue, Soccio et al. reveal new mechanisms by which non-coding variants alter the activity of the anti-diabetic drug rosiglitazone.
Assuntos
Hipoglicemiantes/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Polimorfismo de Nucleotídeo Único , Animais , HumanosRESUMO
Rechargeable battery devices with high energy density are highly demanded by the modern society. The use of lithium (Li) anodes is extremely attractive for future rechargeable battery devices. However, the notorious Li dendritic and instability of solid electrolyte interface (SEI) issues pose series of challenge for metal anodes. Here, based on the inspiration of in situ photoelectrochemical engineering, it is showed that a tailor-made composite photoanodes with good photoelectrochemical properties (Li affinity property and photocatalytic property) can significantly improve the electrochemical deposition behavior of Li anodes. The light-assisted Li anode is accommodated in the tailor-made current collector without uncontrollable Li dendrites. The as-prepared light-assisted Li metal anode can achieve the in situ stabilization of SEI layer under illumination. The corresponding in situ formation mechanism and photocatalytic mechanism of composite photoanodes are systematically investigated via DFT theoretical calculation, ex situ UV-vis and ex situ XPS characterization. It is worth mentioning that the as-prepared composite photoanodes can adapt to the ultra-high current density of 15 mA cm-2 and the cycle capacity of 15 mAh cm-2 under light, showing no dendritic morphology and low hysteresis voltage. This work is of great significance for the commercialization of new generation Li metal batteries.
RESUMO
Phase change material (PCM) can provide a battery system with a buffer platform to respond to thermal failure problems. However, current PCMs through compositing inorganics still suffer from insufficient thermal-transport behavior and safety reliability against external force. Herein, a best-of-both-worlds method is reported to allow the PCM out of this predicament. It is conducted by combining a traditional PCM (i.e., paraffin wax/boron nitride) with a spirally weaved polyethylene fiber fabric, just like the traditional PCM is wearing functional underwear. On the one hand, the spirally continuous thermal pathways of polyethylene fibers in the fabric collaborate with the boron nitride network in the PCM, enhancing the through-plane and in-plane thermal conductivity to 10.05 and 7.92 W m-1 K, respectively. On the other, strong polyethylene fibers allow the PCM to withstand a high puncture strength of 47.13 N and tensile strength of 18.45 MPa although above the phase transition temperature. After this typical PCM packs a triple Li-ion battery system, the battery can be promised reliable safety management against both thermal and mechanical abuse. An obvious temperature drop of >10 °C is observed in the battery electrode during the cycling charging and discharging process.
RESUMO
The crystalline/amorphous heterophase nanostructures are promising functional materials for biomedicals, catalysis, energy conversion, and storage. Despite great progress is achieved, facile synthesis of crystalline metal/amorphous multinary metal oxides nanohybrids remains challenging, and their electrocatalytic oxygen evolution reaction (OER) performance along with the catalytic mechanism are not systematically investigated. Herein, two kinds of ultrafine crystalline metal domains coupled with amorphous Ni-Fe-Mo oxides heterophase nanohybrids, including Ni/Ni0.5-a Fe0.5 Mo1.5 Ox and Ni-FeNi3 /Ni0.5-b Fe0.5-y Mo1.5 Ox , are fabricated through controllable reduction of amorphous Ni0.5 Fe0.5 Mo1.5 Ox precursors by simply tuning the amount of used reductant. Due to the suited component in metal domains, the special structure with dense crystalline/amorphous interfaces, and strong electronic coupling of their components, the resultant Ni-FeNi3 /Ni0.5-b Fe0.5-y Mo1.5 Ox nanohybrids show greatly enhanced OER activity with a low overpotential (278 mV) to reach 10 mA cm-2 current density and ultrahigh turnover frequency (38160 h-1 ), outperforming Ni/Ni0.5-a Fe0.5 Mo1.5 Ox , Ni0.5 Fe0.5 Mo1.5 Ox precursors, commercial IrO2 , and most of recently reported OER catalysts. Also, such Ni-FeNi3 /Ni0.5-b Fe0.5-y Mo1.5 Ox nanohybrids manifest good catalytic stability. As revealed by a series of spectroscopy and electrochemical analyses, their OER mechanism follows the lattice-oxygen-mediated (LOM) pathway. This work may shed light on the design of advanced heterophase nanohybrids, and promote their applications in water splitting, metal-air batteries, or other clean energy fields.
RESUMO
Anodes with high capacity and long lifespan play an important role in the advanced batteries. However, none of the existing anodes can meet these two requirements simultaneously. Lithium (Li)-graphite composite anode presents great potential in balancing these two requirements. Herein, the working mechanism of Li-graphite composite anode is comprehensively investigated. The capacity decay features of the composite anode are different from those of Li ion intercalation in Li ion batteries and Li metal deposition in Li metal batteries. An intercalation and conversion hybrid storage mechanism are proposed by analyzing the capacity decay ratios in the composite anode with different initial specific capacities. The capacity decay models can be divided into four stages including Capacity Retention Stage, Relatively Independent Operation Stage, Intercalation & Conversion Coupling Stage, Pure Li Intercalation Stage. When the specific capacity is between 340 and 450 mAh g-1, its capacity decay ratio is between that of pure intercalation and conversion model. These results intensify the comprehensive understandings on the working principles in Li-graphite composite anode and present novel insights in the design of high-capacity and long-lifespan anode materials for the next-generation batteries.
RESUMO
The typical chalcopyrite AgGaQ2 (Q = S, Se) are commercial infrared (IR) second-order nonlinear optical (NLO) materials; however, they suffer from unexpected laser-induced damage thresholds (LIDTs) primairy due to their narrow band gaps. Herein, what sets this apart from previously reported chemical substitutions is the utilization of an unusual cationic substitution strategy, represented by [[SZn4 ]S12 + [S4 Zn13 ]S24 + 11ZnS4 â MS12 + [M4 Cl]S24 + 11GaS4 ], in which the covalent Sx Zny units in the diamond-like sphalerite ZnS are synergistically replaced by cationic Mx Cly units, resulting in two novel salt-inclusion sulfides, M[M4 Cl][Ga11 S20 ] (M = A/Ba, A = K, 1; Rb, 2). As expected, the introduction of mixed cations in the GaS4 anionic frameworks of 1 and 2 leads to wide band gaps (3.04 and 3.01 eV), which exceeds the value of AgGaS2 , facilitating the improvement of high LIDTs (9.4 and 10.3 × AgGaS2 @1.06 µm, respectively). Furthermore, compounds 1 and 2 exhibit moderate second-harmonic generation intensities (0.84 and 0.78 × AgGaS2 @2.9 µm, respectively), mainly originating from the orderly packing tetrahedral GaS4 units. Importantly, this study demonstrates the successful application of the cationic substitution strategy based on diamond-like structures to provide a feasible chemical design insight for constructing high-performance NLO materials.
RESUMO
Reducing the dark current of photodetectors is an important strategy for enhancing the detection sensitivity, but hampered by the manufacturing cost due to the need for controlling the complex material composition and processing intricate interface. This study reports a new single-component photochromic semiconductor, [(HDMA)4(Pb3Br10)(PhSQ)2]n (1, HDMA = dimethylamine cation, PhSQ = 1-(4-sulfophenyl)-4,4'-bipyridinium), by introducing a redox-active monosubstituted viologen zwitterion into inorganic semiconducting skeleton. It features yellow to green coloration after UV irradiation with the sharply dropping intrinsic conductivity of 14.6-fold, and the photodetection detection sensitivity gain successfully doubles. The reason of decreasing conductivity originates from the increasing the band gap of the inorganic semiconducting component and formation of Frenkel excitons with strong Coulomb interactions, thereby decreasing the concentration of thermally excited intrinsic carriers.
RESUMO
Inubritantrimer A (1), a trace trimerized sesquiterpenoid [4 + 2] adduct featuring an unusual exo-exo type spiro-polycyclic scaffold, together with three new endo-exo [4 + 2] adducts, inubritantrimers B-D (2-4), were discovered from the flowers of Inula britannica. Their structures were elucidated using 1D/2D NMR, X-ray diffraction, and ECD approaches. 1 is characterized as a novel exo-exo trimer, synthesized biogenetically from three sesquiterpenoid monomers, featuring a unique linkage of C-11/C-1', C-13/C-3' and C-13'/C-3â³, C-11'/C-1â³ through a two-step exo [4 + 2] cycloaddition process. Compounds 1-4 exhibited modest cytotoxicity against breast cancer cells with IC50 values in the range of 5.84-12.01 µM.
Assuntos
Inula , Sesquiterpenos , Inula/química , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Sesquiterpenos/farmacologia , Sesquiterpenos/químicaRESUMO
Protein kinase A (PKA) is a ubiquitous cAMP-dependent enzyme in mammalian tissues. The inactive PKA holoenzyme disassociates into a homodimer of regulatory (R) subunits and two active catalytic (C) subunits upon cAMP binding to two tandem domains (termed CBD-A and CBD-B) in R subunits. The release of cAMP facilitates reassociation of R and C subunits, resetting PKA to its basal state. The cAMP-mediated structural changes in the activation-termination cycle remain partially understood. The multimeric states of PKA complicate the issue and are particularly less studied. Therefore, we computationally investigated the conformational dynamics of the PKA RIα homodimer in different cAMP-bound states. The absence of cAMP in two CBDs differently affects the conformational dynamics of protomers. Moreover, such disparate responses are extended to the dimer interface constituted by the N-terminal helical sub-domains termed N3A motifs. The removal of cAMP from CBD-A induces large-scale structural changes of individual R subunits towards the holoenzyme state, consistent with previous simulations of a single R subunit. Meanwhile it keeps the structural heterogeneity of the N3A-N3A' dimer interface observed in the fully bound state. By contrast, the removal of cAMP from CBD-B does not affect individual R subunits but alters the conformational space of the N3A-N3A' dimer interface. The cAMP-coupled structural changes of each protomer and conserved conformational space of the N3A-N3A' dimer interface are essential for the transition between the fully cAMP-bound R2 homodimer and the R2C2 holoenzyme as suggested by their crystal structures. Our work provides structural insights into the regulatory mechanism of cAMP in PKA signaling.
Assuntos
Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico , AMP Cíclico , Multimerização Proteica , AMP Cíclico/metabolismo , AMP Cíclico/química , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/química , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Simulação de Dinâmica Molecular , Conformação ProteicaRESUMO
Z-discs are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-disc-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-disc proteome in vivo. We found palmdelphin (PALMD) as a novel Z-disc-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific Palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed the transverse tubule (T-tubule)-sarcoplasmic reticulum (SR) ultrastructures, which formed the Z-disc-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with the reduction of nexilin (NEXN), a crucial Z-disc-associated protein that is essential for both Z-disc and JMC structures and functions. PALMD interacted with NEXN and enhanced its protein stability while the Nexn mRNA level was not affected. AAV-based NEXN addback rescued the exacerbated cardiac injury in isoproterenol-treated PALMD-depleted mice. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis.
RESUMO
Luminescent metal halides have been exploited as a new class of X-ray scintillators for security checks, nondestructive inspection, and medical imaging. However, the charge traps and hydrolysis vulnerability are always detrimental to the three-dimensional ionic structural scintillators. Here, the two zero-dimensional organic-manganese(II) halide coordination complexes 1-Cl and 2-Br were synthesized for improvements in X-ray scintillation. The introduction of a polarized phosphine oxide can help to increase the stabilities, especially the self-absorption-free merits of these Mn-based hybrids. The X-ray dosage rate detection limits reached up to 3.90 and 0.81 µGyair/s for 1-Cl and 2-Br, respectively, superior to the medical diagnostic standard of 5.50 µGyair/s. The fabricated scintillation films were applied to radioactive imaging with high spatial resolutions of 8.0 and 10.0 lp/mm, respectively, holding promise for use in diagnostic X-ray medical imaging.
RESUMO
Tumor treatment fields (TTFields) can effectively inhibit the proliferation of tumor cells, but its mechanism remains exclusive. The destruction of cellular microtubule structure caused by TTFields through electric field force is considered to be the main reason for inhibiting tumor cell proliferation. However, the validity of this hypothesis still lacks exploration at the mesoscopic level. Therefore, in this study, we built force models for tubulins subjected to TTFields, based on the physical and electrical properties of tubulin molecules. We theoretically analyzed and simulated the dynamic effects of electric field force and torque on tubulin monomer polymerization, as well as the alignment and orientation of α/ß tubulin heterodimer, respectively. Research results indicate that the interference of electric field force induced by TTFields on tubulin monomer is notably weaker than the inherent electrostatic binding force among tubulin monomers. Additionally, the electric field torque generated by the TTFileds on α/ß tubulin dimers is also difficult to affect their random alignment. Therefore, at the mesoscale, our study affirms that TTFields are improbable to destabilize cellular microtubule structures via electric field dynamics effects. These results challenge the traditional view that TTFields destroy the microtubule structure of cells through TTFields electric field force, and proposes a new approach that should pay more attention to the "non-mechanical" effects of TTFields in the study of TTFields mechanism. This study can provide reliable theoretical basis and inspire new research directions for revealing the mesoscopic bioelectrical mechanism of TTFields.
Assuntos
Microtúbulos , Neoplasias , Tubulina (Proteína) , Tubulina (Proteína)/metabolismo , Microtúbulos/metabolismo , Humanos , Neoplasias/terapia , Proliferação de Células , Eletricidade Estática , Polimerização , Campos EletromagnéticosRESUMO
The study of facile-synthesis and low-cost X-ray scintillators with high light yield, low detection limit and high X-ray imaging resolution plays a vital role in medical and industrial imaging fields. However, the optimal balance between X-ray absorption, decay lifetime and excitonic utilization efficiency of scintillators to achieve high-resolution imaging is extremely difficult due to the inherent contradiction. Here two thermally activated delayed fluorescence (TADF)-actived coinage-metal clusters M6 S6 L6 (M=Ag or Cu) were synthesized by simple solvothermal reaction, where the cooperation of heavy atom-rich character and TADF mechanism supports strong X-ray absorption and rapid luminescent collection of excitons. Excitingly, Ag6 S6 L6 (SC-Ag) displays a high photoluminescence quantum yield of 91.6 % and scintillating light yield of 17420â photons MeV-1 , as well as a low detection limit of 208.65â nGy s-1 that is 26â times lower than the medical standard (5.5â µGy s-1 ). More importantly, a high X-ray imaging resolution of 16â lp/mm based on SC-Ag screen is demonstrated. Besides, rigid core skeleton reinforced by metallophilicity endows clusters M6 S6 L6 strong resistance to humidity and radiation. This work provides a new view for the design of efficient scintillators and opens the research door for silver clusters in scintillation application.
RESUMO
Rechargeable battery devices with high energy density are highly demanded by our modern society. The use of metal anodes is extremely attractive for future rechargeable battery devices. However, the notorious metal dendritic and instability of solid electrolyte interface issues pose a series of challenges for metal anodes. Recently, considering the indigestible dynamical behavior of metal anodes, photoelectrochemical engineering of light-assisted metal anodes have been rapidly developed since they efficiently utilize the integration and synergy of oriented crystal engineering and photocatalysis engineering, which provided a potential way to unlock the interface electrochemical mechanism and deposition reaction kinetics of metal anodes. This review starts with the fundamentals of photoelectrochemical engineering and follows with the state-of-art advance of photoelectrochemical engineering for light-assisted rechargeable metal batteries where photoelectrode materials, working principles, types, and practical applications are explained. The last section summarizes the major challenges and some invigorating perspectives for future research on light-assisted rechargeable metal batteries.
RESUMO
Great changes have occurred in the energy storage area in recent years as a result of rapid economic expansion. People have conducted substantial research on sustainable energy conversion and storage systems in order to mitigate the looming energy crisis. As a result, developing energy storage materials is critical. Materials with an open frame structure are known as Prussian blue analogs (PBAs). Anode materials for oxides, sulfides, selenides, phosphides, borides, and carbides have been extensively explored as anode materials in the field of energy conversion and storage in recent years. The advantages and disadvantages of oxides, sulfides, selenides, phosphides, borides, carbides, and other elements, as well as experimental methodologies and electrochemical properties, are discussed in this work. The findings reveal that employing oxides, sulfides, selenides, phosphides, borides, and other electrode materials to overcome the problems of low conductivity, excessive material loss, and low specific volume is ineffective. Therefore, this review intends to address the issues of diverse energy storage materials by combining multiple technologies to manufacture battery materials with low cost, large capacity, and extended service life.
RESUMO
The design of a novel photoelectric integrated system is considered to be an efficient way to utilize and store inexhaustible solar energy. However, the mechanism of photoelectrode under illuminate conditions is still unclear. Density functional theory (DFT) provides standardized analysis and becomes a powerful way to explain the photoelectrochemical mechanism. Herein, the feasibility of four metal oxide configurations as photoelectrode materials by using a high throughput calculation method based on DFT are investigated. According to the photoelectrochemical properties, band structure and density of states are calculated, and the intercalate/deintercalate simulation is performed with adsorption configuration. The calculation indicates that the band gap of Fe2 CoO4 (2.404 eV) is narrower than that of Co3 O4 (2.553 eV), as well as stronger adsorption energy (-3.293 eV). The relationship between the electronic structure and the photoelectrochemical performance is analyzed and verified according to the predicted DFT results by subsequent experiments. Results show that the Fe2 CoO4 photoelectrode samples exhibit higher coulombic efficiency (97.4%) than that under dark conditions (94.9%), which is consistent with the DFT results. This work provides a general method for the design of integrated photoelectrode materials and is expected to be enlightening for the adjustment of light-assisted properties of multifunctional materials.
RESUMO
Cations that can regulate the configuration of anion group are greatly important but regularly unheeded. Herein, the structural transformation from 2D CS to 3D noncentrosymmetric (NCS, which is the prerequisite for second-order NLO effect) is rationally designed to newly afford two sulfides LiMGa8 S14 (M = Rb/Ba, 1; Cs/Ba, 2) by introducing the smallest alkali metal Li+ cation into the interlamination of 2D centrosymmetric (CS) RbGaS2 . The unusual frameworks of 1 and 2 are constructed from C2 -type [Ga4 S11 ] supertetrahedrons in a highly parallel arrangement. 1 and 2 display distinguished NLO performances, including strong phase-matchable second-harmonic generation (SHG) intensities (0.8 and 0.9 × AgGaS2 at 1910 nm), wide optical band gaps (3.24 and 3.32 eV), and low coefficient of thermal expansion for favorable laser-induced damage thresholds (LIDTs, 4.7, and 7.6 × AgGaS2 at 1064 nm), which fulfill the criteria of superior NLO candidates (SHG intensity >0.5 × AGS and band gap >3.0 eV). Remarkably, 1 and 2 melt congruently at 873.8 and 870.5 °C, respectively, which endows them with the potential of growing bulk crystals by the Bridgeman-Stockbarge method. This investigated system provides a new avenue for the structural evolution from layered CS to 3D NCS of NLO materials.
RESUMO
Chalcohalides not only keep the balance between the nonlinear optical (NLO) coefficient and wide band gap, but also provide a promising solution to achieve sufficient birefringence for phase-matching ability in NLO crystals. In this study, a novel chalcohalide, Cs4 Zn5 P6 S18 I2 (1) is successfully synthesized, by incorporating the highly electropositive Cs and the large electronegative I element into the zinc thiophosphate. Its 3D open framework features an edge-shared by distorted [ZnS4 ], ethanol-like [P2 S6 ], and unusual [ZnS2 I2 ] polyhedrons, which is inconsistent with the soft-hard-acids-bases theory. Remarkably, compound 1 simultaneously exhibits the large second-harmonic generation (SHG, 1.1×AgGaS2 , @1.3 µm) and a wide band gap (3.75 eV) toward a high laser-induced damage threshold (16.7×AgGaS2 , @1.06 µm), satisfying the rigorous requirements for a prominent infrared NLO material with concurrent SHG intensity (≥0.5×AGS) and band gap (≥3.5 eV). Moreover, to the best of the knowledge, the experimental result shows that phase 1 has the largest birefringence (0.108, @546 nm) in chalcohalide and meets phase-matching behavior demand originating from the polarizable anisotropy of NLO-functional motifs. This finding may provide great opportunities for designing birefringent chalcohalides.
RESUMO
Anisotropic charge transport plays a pivotal role in clarifying the conductivity mechanism in direct X-ray detection to improve the detection sensitivity. However, the anisotropic photoelectric effect of semiconductive single crystal responsive to X-ray is still lacking of theoretical and experimental proof. The semiconductive coordination polymers (CPs) with designable structures, adjustable functions, and high crystallinity provide a suitable platform for exploring the anisotropic conductive mechanism. Here,the study first reveals a 1D conductive transmission path for direct X-ray detection from the perspective of structural chemistry. The semiconductive copper(II)-based CP 1 single crystal detector exhibits unique anisotropic X-ray detection performance. Along the 1D π-π stacking direction, the single crystal device (1-SC-a) shows a superior sensitivity of 2697.15 µCGyair -1 cm-2 and a low detection limit of 1.02 µGyair s-1 among CPs-based X-ray detectors. This study provides beneficial guidance and deep insight for designing high-performance CP-based X-ray detectors.
RESUMO
Conversion-type cathodes for aqueous zinc ion batteries (ZIBs) can provide flat plateau slop and stable output potential, compared to general intercalation-type cathodes. The high volumetric capacity and stable output potential of Te make it a promising cathode for ZIBs, but sluggish kinetics and large volume change hinder its further application. To address these issues, we revisit fully zinced ZnTe and construct ZnTe/rGO composites as the new conversion-type cathode. The electrode undergoes a solid-to-solid conversion reaction and shows a stable output potential with ultra-flat discharge plateau slop of 0.09â V (Ah g-1 )-1 . When ZnTe is de-zinced and transformed to Te during charge process, it has a volume shrinkage which generates empty space in graphene matrix for latter volume expansion of Te. The graphene matrix also improves conductivity and reaction kinetics of the cathode. Due to the combination of pre-zincation of ZnTe, graphene matrix and the elimination of "shuttle effects" process, ZnTe/rGO electrode exhibits a high and stable capacity of 186â mAh g-1 at 500â mA g-1 after 300 cycling, with almost no decay after initial 10 cycles.