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Bonded interactions are fundamental ingredients of molecular mechanics force fields because they directly determine the local structure of a molecule. In this work, we parametrize the advanced bonded energy functionals that consider the vibrational anharmonicity, the coupling effects, and the out-of-plane bending for sp2-hybridized atoms. It is expected that these models can describe the spectroscopic properties and overall structures of a molecule more accurately when they are used with polarizable AMOEBA-based force fields. 

Fluorescent light-up aptamers (FLAPs) are well-performed biosensors for cellular imaging and the detection of different targets of interest, including RNA, non-nucleic acid molecules, metal ions, and so on. They could be easily designed and emit a strong fluorescence signal once bound to specified fluorogens. Recently, one unique aptamer called Mango-II has been discovered to possess a strong affinity and excellent fluorescent properties with fluorogens TO1-Biotin and TO3-Biotin. To explore the binding mechanisms, computational simulations have been performed to obtain structural and thermodynamic information about FLAPs at atomic resolution. AMOEBA polarizable force field, with the capability of handling the highly charged and flexible RNA system, was utilized for the simulation of Mango-II with TO1-Biotin and TO3-Biotin in this work. The calculated binding free energy using published crystal structures is in excellent agreement with the experimental values. Given the challenges in modeling complex RNA dynamics, our work demonstrates that MD simulation with a polarizable force field is valuable for understanding aptamer-fluorogen binding and potentially designing new aptamers or fluorogens with better performance. 

The catalytic function of Lysyl hydroxylase-2 (LH2), a member of the Fe(II)/αKG-dependent oxygenase superfamily, is to catalyze the hydroxylation of lysine to hydroxylysine in collagen, resulting in stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs). Reports show that high amounts of LH2 lead to the accumulation of HLCCs, causing fibrosis and specific types of cancer metastasis. Some members of the Fe(II)/αKG-dependent family have also been reported to have intramolecular O2 tunnels, which aid in transporting one of the required co-substrates into the active site. While LH2 can be a promising target to combat these diseases, efficacious inhibitors are still lacking. We have used computational simulations to investigate a series of forty-four small molecules as lead compounds for LH2 inhibition. Tunneling analyses indicate the existence of several intra-molecular tunnels. The lengths of the calculated O2-transporting tunnels in holoenzymes are relatively longer than the apoenzyme suggesting that the ligands may affect the enzyme's structure and possibly block (at least partially) the tunnels. The sequence alignment analysis between LH enzymes from different organisms shows that all the amino acid residues with the highest occurrence rate in the oxygen tunnels are conserved. Our results suggest that the enolate form of diketone compounds establishes stronger interactions with the Fe(II) in the active site. Branching the enolate compounds with functional groups such as phenyl and pyridinyl enhances the interaction with various residues around the active site. Our results provide information about possible leads for further LH2 inhibition design and development. 

The skyrocketing popularity of health monitoring has spurred increasing interest in wearable electrochemical biosensors. Compared with the traditionally rigid and bulky electrochemical biosensors, flexible and stretchable devices render a unique capability to conform to the complex, hierarchically textured surfaces of the human body. With a recognition element (e.g., enzymes, antibodies, nucleic acids, ions) to selectively react with the target analyte, wearable electrochemical biosensors can convert the types and concentrations of chemical changes in the body into electrical signals for easy readout. Initial exploration of wearable electrochemical biosensors integrates electrodes on textile and flexible thin-film substrate materials. A stretchable property is needed for the thin-film device to form an intimate contact with the textured skin surface and to deform with various natural skin motions. Thus, stretchable materials and structures have been exploited to ensure the effective function of a wearable electrochemical biosensor. In this mini-review, we summarize the recent development of flexible and stretchable electrochemical biosensors, including their principles, representative application scenarios (e.g., saliva, tear, sweat, and interstitial fluid), and materials and structures. While great strides have been made in the wearable electrochemical biosensors, challenges still exist, which represents a small fraction of opportunities for the future development of this burgeoning field. 

To tackle the severe fine particle (PM_2.5) pollution in China, the government has implemented stringent control policies mainly on power plants, industry, and transportation since 2005, but estimates of the effectiveness of the policy and the temporal trends in health impacts are subject to large uncertainties. By adopting an integrated approach that combines chemical transport simulation, ambient/household exposure evaluation, and health-impact assessment, we find that the integrated population-weighted exposure to PM_2.5(IPWE) decreased by 47% (95% confidence interval, 37–55%) from 2005 [180 (146–219) μg/m³] to 2015 [96 (83–111) μg/m³]. Unexpectedly, 90% (86–93%) of such reduction is attributed to reduced household solid-fuel use, primarily resulting from rapid urbanization and improved incomes rather than specific control policies. The IPWE due to household fuels for both cooking and heating decreased, but the impact of cooking is significantly larger. The reduced household-related IPWE is estimated to avoid 0.40 (0.25–0.57) million premature deaths annually, accounting for 33% of the PM_2.5-induced mortality in 2015. The IPWE would be further reduced by 63% (57–68%) if the remaining household solid fuels were replaced by clean fuels, which would avoid an additional 0.51 (0.40–0.64) million premature deaths. Such a transition to clean fuels, especially for heating, requires technology innovation and policy support to overcome the barriers of high cost of distribution systems, as is recently being attempted in the Beijing–Tianjin–Hebei area. We suggest that household-fuel use be more highly prioritized in national control policies, considering its effects on PM_2.5exposures.