The anode oxygen evolution reaction (OER) is known to largely limit the efficiency of electrolyzers owing to its sluggish kinetics. While crystalline metal oxides are promising as OER catalysts, ...their amorphous phases also show high activities. Efforts to produce amorphous metal oxides have progressed slowly, and how an amorphous structure benefits the catalytic performances remains elusive. Now the first scalable synthesis of amorphous NiFeMo oxide (up to 515 g in one batch) is presented with homogeneous elemental distribution via a facile supersaturated co‐precipitation method. In contrast to its crystalline counterpart, amorphous NiFeMo oxide undergoes a faster surface self‐reconstruction process during OER, forming a metal oxy(hydroxide) active layer with rich oxygen vacancies, leading to superior OER activity (280 mV overpotential at 10 mA cm−2 in 0.1 m KOH). This opens up the potential of fast, facile, and scale‐up production of amorphous metal oxides for high‐performance OER catalysts.
Amorphous NiFeMo oxide (up to 515 g one batch) with homogeneous elemental distribution was synthesized through a facile supersaturated co‐precipitation method. The amorphous NiFeMo oxide undergoes rapid surface self‐reconstruction during OER that forms a metal oxy(hydroxide) active layer with oxygen vacancies, enabling efficient OER catalysis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Compared with conventional tumor photothermal therapy (PTT), mild‐temperature PTT brings less damage to normal tissues, but also tumor thermoresistance, introduced by the overexpressed heat shock ...protein (HSP). A high dose of HSP inhibitor during mild‐temperature PTT might lead to toxic side effects. Glucose oxidase (GOx) consumes glucose, leading to adenosine triphosphate supply restriction and consequent HSP inhibition. Therefore, a combinational use of an HSP inhibitor and GOx not only enhances mild‐temperature PTT but also minimizes the toxicity of the inhibitor. However, a GOx and HSP inhibitor‐encapsulating nanostructure, designed for enhancing its mild‐temperature tumor PTT efficiency, has not been reported. Thermosensitive GOx/indocyanine green/gambogic acid (GA) liposomes (GOIGLs) are reported to enhance the efficiency of mild‐temperature PTT of tumors via synergistic inhibition of tumor HSP by the released GA and GOx, together with another enzyme‐enhanced phototherapy effect. In vitro and in vivo results indicate that this strategy of tumor starvation and phototherapy significantly enhances mild‐temperature tumor PTT efficiency. This strategy could inspire people to design more delicate platforms combining mild‐temperature PTT with other therapeutic methods for more efficient cancer treatment.
Thermosensitive liposomes made of DPPC and DSPE‐PEG2000 encapsulating GOx, ICG, and GA are presented. This system is used for synergistic starvation therapy, EEPT, and enhanced mild‐temperature PTT against tumors.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A novel SARS-related coronavirus (SARS-CoV-2) has recently emerged as a serious pathogen that causes high morbidity and substantial mortality. However, the mechanisms by which SARS-CoV-2 evades host ...immunity remain poorly understood. Here, we identified SARS-CoV-2 membrane glycoprotein M as a negative regulator of the innate immune response. We found that the M protein interacted with the central adaptor protein MAVS in the innate immune response pathways. This interaction impaired MAVS aggregation and its recruitment of downstream TRAF3, TBK1, and IRF3, leading to attenuation of the innate antiviral response. Our findings reveal a mechanism by which SARS-CoV-2 evades the innate immune response and suggest that the M protein of SARS-CoV-2 is a potential target for the development of SARS-CoV-2 interventions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Catalytic difunctionalization of alkenes has been an ideal strategy to generate structurally complex molecules with diverse substitution patterns. Although both phosphonyl and carboxyl groups are ...valuable functional groups, the simultaneous incorporation of them via catalytic difunctionalization of alkenes, ideally from abundant, inexpensive and easy-to-handle raw materials, has not been realized. Herein, we report the phosphonocarboxylation of alkenes with CO
via visible-light photoredox catalysis. This strategy is sustainable, general and practical, providing facile access to important β-phosphono carboxylic acids, including structurally complex unnatural α-amino acids. Diverse alkenes, including enamides, styrenes, enolsilanes and acrylates, undergo such reactions efficiently under mild reaction conditions. Moreover, this method represents a rare example of redox-neutral difunctionalization of alkenes with H-P(O) compounds, including diaryl- and dialkyl- phosphine oxides and phosphites. Importantly, these transition-metal-free reactions also feature low catalyst loading, high regio- and chemo-selectivities, good functional group tolerance, easy scalability and potential for product derivatization.
Cyclic GMP-AMP synthase (cGAS) senses double-strand (ds) DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the adaptor MITA/STING to initiate innate ...antiviral response. How cGAS activity is regulated remains enigmatic. Here, we identify ZCCHC3, a CCHC-type zinc-finger protein, as a positive regulator of cytosolic dsDNA- and DNA virus-triggered signaling. We show that ZCCHC3-deficiency inhibits dsDNA- and DNA virus-triggered induction of downstream effector genes, and that ZCCHC3-deficient mice are more susceptible to lethal herpes simplex virus type 1 or vaccinia virus infection. ZCCHC3 directly binds to dsDNA, enhances the binding of cGAS to dsDNA, and is important for cGAS activation following viral infection. Our results suggest that ZCCHC3 is a co-sensor for recognition of dsDNA by cGAS, which is important for efficient innate immune response to cytosolic dsDNA and DNA virus.
Magnesium hydride (MgH
2
), which possesses high hydrogen density of 7.6 wt%, abundant resource and non-toxicity, has captured intense attention as one of the potential hydrogen storage materials. ...However, the practical application of Mg/MgH
2
system is suffering from high thermal stability, sluggish absorption and desorption kinetics. Herein, two-dimensional (2D) vanadium nanosheets (V
NS
) were successfully prepared via a facile wet chemical ball milling method and proved to be highly effective on improving the hydrogen storage performance of MgH
2
. For instance, the MgH
2
+ 7 wt% V
NS
composite began to release hydrogen at 187.2 °C, 152 °C lower than that of additive-free MgH
2
. At 300 °C, 6.3 wt% hydrogen was released from the MgH
2
+ 7 wt% V
NS
composite within 10 min. In addition, the fully dehydrogenated sample could absorb hydrogen even at room temperature under hydrogen pressure of 3.2 MPa. X-ray diffractometer (XRD) and transmission electron microscopy (TEM) results confirmed metallic vanadium served as catalytic unit for facilitating the de/rehydrogenation reaction of MgH
2
. This finding presents an example of facile synthesis of two-dimensional (2D) vanadium with excellent catalysis, which may shed light on future design and preparation of highly effective layered catalysts for hydrogen storage and other energy-related areas.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The newly emerging coronavirus SARS-CoV-2 causes severe lung disease and substantial mortality. How the virus evades host defense for efficient replication is not fully understood. In this report, we ...found that the SARS-CoV-2 nucleocapsid protein (NP) impaired stress granule (SG) formation induced by viral RNA. SARS-CoV-2 NP associated with the protein kinase PKR after dsRNA stimulation. SARS-CoV-2 NP did not affect dsRNA-induced PKR oligomerization, but impaired dsRNA-induced PKR phosphorylation (a hallmark of its activation) as well as SG formation. SARS-CoV-2 NP also targeted the SG-nucleating protein G3BP1 and impaired G3BP1-mediated SG formation. Deficiency of PKR or G3BP1 impaired dsRNA-triggered SG formation and increased SARS-CoV-2 replication. The NP of SARS-CoV also targeted both PKR and G3BP1 to impair dsRNA-induced SG formation, whereas the NP of MERS-CoV targeted PKR, but not G3BP1 for the impairment. Our findings suggest that SARS-CoV-2 NP promotes viral replication by impairing formation of antiviral SGs, and reveal a conserved mechanism on evasion of host antiviral responses by highly pathogenic human betacoronaviruses.
Most structural and evolutionary properties of galaxies strongly rely on the stellar initial mass function (IMF), namely the distribution of the stellar mass formed in each episode of star formation
.... The IMF shapes the stellar population in all stellar systems, and so has become one of the most fundamental concepts of modern astronomy. Both constant and variable IMFs across different environments have been claimed despite a large number of theoretical
and observational efforts
. However, the measurement of the IMF in Galactic stellar populations has been limited by the relatively small number of photometrically observed stars, leading to high uncertainties
. Here we report a star-counting result based on approximately 93,000 spectroscopically observed M-dwarf stars, an order of magnitude more than previous studies, in the 100-300 parsec solar neighbourhood. We find unambiguous evidence of a variable IMF that depends on both metallicity and stellar age. Specifically, the stellar population formed at early times contains fewer low-mass stars compared with the canonical IMF, independent of stellar metallicities. In more recent times, however, the proportion of low-mass stars increases with stellar metallicity. The variable abundance of low-mass stars in our Milky Way establishes a powerful benchmark for models of star formation and can heavily affect results in Galactic chemical-enrichment modelling, mass estimation of galaxies and planet-formation efficiency.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)–Akt–mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N ...(GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K–Akt pathway and regulates the mTOR–ULK1 pathway in liver cancer cells.