Expansion of CAG repeats is a common feature of various neurodegenerative disorders, including Huntington's disease. Here we show that expanded CAG repeats bind to a translation regulatory protein complex containing MID1, protein phosphatase 2A and 40S ribosomal S6 kinase. Binding of the MID1-protein phosphatase 2A protein complex increases with CAG repeat size and stimulates translation of the CAG repeat expansion containing messenger RNA in a MID1-, protein phosphatase 2A-and mammalian target of rapamycindependent manner. Our data indicate that pathological CAG repeat expansions upregulate protein translation leading to an overproduction of aberrant protein and suggest that the MID1-complex may serve as a therapeutic target for the treatment of CAG repeat expansion disorders.

Mn 3 O 4 , FeMnO x , and FeO x catalysts synthesized via a solvothermal method were employed for catalytic oxidation of methyl−ethyl−ketone (MEK) at low temperature. Mn 3 O 4 with sphere-like morphology exhibited the highest activity for MEK oxidation, over which MEK was completely oxidized to CO 2 at 200°C, and this result can be comparable to typical noble metal loaded catalysts. The activation energy of MEK over Mn 3 O 4 (30.8 kJ/mol) was much lower than that of FeMnO x (41.5 kJ/mol) and FeO x (47.8 kJ/mol). The dominant planes, surface manganese species ratio, surface-absorbed oxygen, and redox capability played important roles in the catalytic activities of catalysts, while no significant correlation was found between specific surface area and MEK removal efficiency. Mn 3 O 4 showed the highest activity, accounting for abundant oxygen vacancies, low content of surface Mn 4+ and strong reducibility. The oxidation of MEK to CO 2 via an intermediate of diacetyl is a reaction pathway on Mn 3 O 4 catalyst. Due to high efficiency and low cost, sphere-shaped Mn 3 O 4 is a promising catalyst for VOCs abatement.

In the present work, a series of MOF-74 (Ni) materials with narrow micropore channels and abundant unsaturated metal sites was respectively prepared via hydrothermal (HT), condensation reflux (CE), and microwave-assisted (MW) methods. The physicochemical properties of synthesized materials were characterized by powder X-ray diffraction, N2-sorption, field-emission scanning electron microscopy, Fourier-transform infrared (FTIR), thermogravimetric (TG)/TG-FTIR, X-ray photoelectron spectroscopy, UV–vis–near infrared, NH3/CO2-temperature programmed desorption, and in situ diffuse reflectance infrared Fourier transform spectroscopy. Their CO2/N2 adsorption performances were evaluated by isotherm adsorption and dynamic adsorption experiments. We found that the MW is a rapid and facile protocol for the synthesis of MOF-74 (Ni) materials with highly efficient CO2 capture capacity. The well-shaped MW-140 adsorbent with superior CO2 adsorption capacity of 5.22 mmol/g at 25 °C can be obtained within 60 min by the MW process, almost 6 times higher than that of the commercial activated carbon (0.89 mmol/g). Results of dynamic adsorption experiments showed that the MW-140 material possesses the highest CO2 adsorption capacity of 3.37 mmol/g under humid conditions (RH = 90%). Importantly, MW-140 has excellent adsorption stability and recyclability, superior CO2 capture selectivity (CO2/N2 = 31), and appropriate isosteric heat in CO2 adsorption (21–38 kJ/mol), making it a promising and potential material for industrial CO2 capture. Characterization results demonstrated that the high capture capability of MOF-74 (Ni) materials can be attributed to the synergistic effect of abundant narrow micropore channels and rich five-coordinated Ni2+ open metal sites which are beneficial for the trapping of CO2 molecules.

Catching primal functional changes in early, ‘very far from disease onset’ (VFDO) stages of Huntington’s disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing in vivo two-photon Ca2+ imaging, we revealed an early pattern of circuit dysregulation in the visual cortex - one of the first regions affected in premanifest Huntington’s disease - characterized by an increase in activity, an enhanced synchronicity and hyperactive neurons. These findings are accompanied by aberrations in animal behavior. We furthermore show that the antidiabetic drug metformin diminishes aberrant Huntingtin protein load and fully restores both early network activity patterns and behavioral aberrations. This network-centered approach reveals a critical window of vulnerability far before clinical manifestation and establishes metformin as a promising candidate for a chronic therapy starting early in premanifest Huntington’s disease pathogenesis long before the onset of clinical symptoms.

The development of highly active single-atom catalysts (SACs) and identifying their intrinsic active sites in oxidizing industrial hazardous hydrocarbons are challenging prospects. Tuning the electronic metal-support interactions (EMSIs) is valid for modulating the catalytic performance of SACs. We propose that the modulation of the EMSIs in a Pt 1 À CuO SAC significantly promotes the activity of the catalyst in acetone oxidation. The EMSIs promote charge redistribution through the unified PtÀ OÀ Cu moieties, which modulates the d-band structure of atomic Pt sites, and strengthens the adsorption and activation of reactants. The positively charged Pt atoms are superior for activating acetone at low temperatures, and the stretched CuÀ O bonds facilitate the activation of lattice oxygen atoms to participate in subsequent oxidation. We believe that this work will guide researchers to engineer efficient SACs for application in hydrocarbon oxidation reactions.