The direct nucleic acid repair dioxygenase FTO is an enzyme that demethylates N(6)-methyladenosine (m(6)A) residues in mRNA in vitro and inside cells. FTO is the first RNA demethylase discovered that also serves a major regulatory function in mammals. Together with structure-based virtual screening and biochemical analyses, we report the first identification of several small-molecule inhibitors of human FTO demethylase. The most potent compound, the natural product rhein, which is neither a structural mimic of 2-oxoglutarate nor a chelator of metal ion, competitively binds to the FTO active site in vitro. Rhein also exhibits good inhibitory activity on m(6)A demethylation inside cells. These studies shed light on the development of powerful probes and new therapies for use in RNA biology and drug discovery.
Summary
Lithium-ion batteries (LIBs) have become one of the main energy storage solutions in modern society. The application fields and market share of LIBs have increased rapidly and continue to show a steady rising trend. The research on LIB materials has scored tremendous achievements. Many innovative materials have been adopted and commercialized by the industry. However, the research on LIB manufacturing falls behind. Many battery researchers may not know exactly how LIBs are being manufactured and how different steps impact the cost, energy consumption, and throughput, which prevents innovations in battery manufacturing. Here in this perspective paper, we introduce state-of-the-art manufacturing technology and analyze the cost, throughput, and energy consumption based on the production processes. We then review the research progress focusing on the high-cost, energy, and time-demand steps of LIB manufacturing. Finally, we share our views of challenges in LIB manufacturing and propose future development directions for manufacturing research in LIBs.
Methicillin-resistant Staphylococcus aureus (MRSA) is the most frequent cause of hospital-acquired infection, which manifests as surgical site infections, bacteremia, and sepsis. Due to drug-resistance, prophylaxis of MRSA infection with antibiotics frequently fails or incites nosocomial diseases such as Clostridium difficile infection. Sortase A is a transpeptidase that anchors surface proteins in the envelope of S. aureus, and sortase mutants are unable to cause bacteremia or sepsis in mice. Here we used virtual screening and optimization of inhibitor structure to identify 3-(4-pyridinyl)-6-(2-sodiumsulfonatephenyl) [1,2,4]
Background: The molecular mechanism of ClpP dynamic switching between different conformations is poorly understood. Results: MD simulations describe the molecular pathway of the transition between three conformations of SaClpP. Conclusion: Helix unfolding/refolding characterizes the functional dynamics and mechanism of ClpP. Significance: This study provides molecular insights into the dynamics and mechanism of ClpP in general.
Composite solid electrolytes (CSEs) are regarded as one of the most promising candidates for all-solid-state lithium metal batteries (ASSLMBs) due to inherited desirable features from both ceramic and polymer materials. However, poor interfacial contact/compatibility between the electrodes and solid electrolytes remains a critical challenge. In this work, we prepare a flexible CSE composed of polyoxyethylene (PEO)−perovskite composite with a layer of PEO on either side. This PEO|PEO− perovskite|PEO structure prevents direct contact between the perovskite and lithium metal at the anode side, avoiding the undesired reaction between the two materials (Ti 4+ + Li → Ti 3+ + Li + ). Moreover, the design incorporating the PEO surface on either side enables superb contact between the electrolyte and the electrodes and buffers the change in electrolyte volume from the cathode and lithium metal during repeated cycling, resulting in low interfacial resistances and excellent cycling stability. Meanwhile, perovskite inorganic electrolyte Li 0.33 La 0.557 TiO 3 (LLTO) 3D nanofiber networks formed by electrospinning enable the CSE to achieve enhanced mechanical strength and high ionic conductivity of 0.16 mS cm −1 at 24 °C. As a result, a Li|PEO− LiTFSI−LLTO|Li symmetric cell remains stable after 400 h of operation without short-circuiting. Most notably, a Li|PEO− LiTFSI−LLTO|LiFePO 4 full battery is capable of delivering a high capacity of 135.0 mAh g −1 even at 2 C with a retention rate of 79.0% after 300 cycles at 60 °C. These results demonstrate that the integrated sandwich structure proposed in this work is effective in developing high-performance composite solid electrolytes for ASSLMBs.
There has been increasing interest in the emerging ionic thermoelectric materials with huge ionic thermopower. However, it’s challenging to selectively tune the thermopower of all-solid-state polymer materials because the transportation of ions in all-solid-state polymers is much more complex than those of liquid-dominated gels. Herein, this work provides all-solid-state polymer materials with a wide tunable thermopower range (+20~−6 mV K−1), which is different from previously reported gels. Moreover, the mechanism of p-n conversion in all-solid-state ionic thermoelectric polymer material at the atomic scale was presented based on the analysis of Eastman entropy changes by molecular dynamics simulation, which provides a general strategy for tuning ionic thermopower and is beneficial to understand the fundamental mechanism of the p-n conversion. Furthermore, a self-powered ionic thermoelectric thermal sensor fabricated by the developed p- and n-type polymers demonstrated high sensitivity and durability, extending the application of ionic thermoelectric materials.
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