Model-Based Simulation and Prediction of an Antiviral Strategy against Influenza A Infection

There is a strong need to develop novel strategies in using antiviral agents to efficiently treat influenza infections. Thus, we constructed a rule-based mathematical model that reflects the complicated interactions of the host immunity and viral life cycle and analyzed the key controlling steps of influenza infections. The main characteristics of the pandemic and seasonal influenza strains were estimated using parameter values derived from cells infected with Influenza A/California/04/2009 and Influenza A/NewCaledonia/20/99, respectively. The quantitative dynamics of the infected host cells revealed a more aggressive progression of the pandemic strain than the seasonal strain. The perturbation of each parameter in the model was then tested for its effects on viral production. In both the seasonal and pandemic strains, the inhibition of the viral release (k_C), the reinforcement of viral attachment (k_V), and an increased transition rate of infected cells into activated cells (k_I) exhibited significant suppression effects on the viral production; however, these inhibitory effects were only observed when the numerical perturbations were performed at the early stages of the infection. In contrast, combinatorial perturbations of both the inhibition of viral release and either the reinforcement of the activation of infected cells or the viral attachment exhibited a significant reduction in the viral production even at a later stage of infection. These results suggest that, in addition to blocking the viral release, a combination therapy that also enhances either the viral attachment or the transition of the infected cells might provide an alternative for effectively controlling progressed influenza infection.     

A simple process for the isolation of epithelial cells from bacteria-contaminated samples using anchoring molecules

A simple and efficient tool to isolate epithelial cells from bacteria-contaminated samples has been developed using two different microparticles functionalized with chemical molecules. The epithelial cells could be captured simply by biocompatible anchors for membranes (BAM), consisting of poly(ethylene glycol) functionalized with oleyl-chain-conjugated NHS (N-hydroxysuccinimide) on glass microparticles, whereas bacteria were adsorbed on 3-aminopropyltrimethoxysilane (ATPS)-functionalized magnetic microparticles. In the case of samples highly contaminated with bacteria, epithelial cells were not isolated successfully by both of the single BAM- and antibody-functionalized microparticles. Therefore, serial isolation steps of these two different chemical functionalized microparticles were introduced. The concentration of bacteria was decreased dramatically by using APTS-functionalized magnetic particles prior to the isolation of epithelial cells by BAM microparticles. With these serial processes, successful isolation of epithelial cells was achieved from bacteria-contaminated epithelial samples. The applicability of this method was verified with bacteria-contaminated intestinal samples biopsied from a BALB/C mouse for primary cell cultivation.     

Ablation of Gadd45β ameliorates the inflammation and renal fibrosis caused by unilateral ureteral obstruction

The growth arrest and DNA damage‐inducible beta (Gadd45β) protein have been associated with various cellular functions, but its role in progressive renal disease is currently unknown. Here, we examined the effect of Gadd45β deletion on cell proliferation and apoptosis, inflammation, and renal fibrosis in an early chronic kidney disease (CKD) mouse model following unilateral ureteral obstruction (UUO). Wild‐type (WT) and Gadd45β‐knockout (KO) mice underwent either a sham operation or UUO and the kidneys were sampled eight days later. A histological assay revealed that ablation of Gadd45β ameliorated UUO‐induced renal injury. Cell proliferation was higher in Gadd45β KO mouse kidneys, but apoptosis was similar in both genotypes after UUO. Expression of pro‐inflammatory cytokines after UUO was down‐regulated in the kidneys from Gadd45β KO mice, whereas UUO‐mediated immune cell infiltration remained unchanged. The expression of pro‐inflammatory cytokines in response to LPS stimulation decreased in bone marrow‐derived macrophages from Gadd45β KO mice compared with that in WT mice. Importantly, UUO‐induced renal fibrosis was ameliorated in Gadd45β KO mice unlike in WT mice. Gadd45β was involved in TGF‐β signalling pathway regulation in kidney fibroblasts. Our findings demonstrate that Gadd45β plays a crucial role in renal injury and may be a therapeutic target for the treatment of CKD.     

An Antiaging Electrolyte Additive for High‐Energy‐Density Lithium‐Ion Batteries

High‐capacity Li‐rich layered oxide cathodes along with Si‐incorporated graphite anodes have high reversible capacity, outperforming the electrode materials used in existing commercial products. Hence, they are potential candidates for the development of high‐energy‐density lithium‐ion batteries (LIBs). However, structural degradation induced by loss of interfacial stability is a roadblock to their practical use. Here, the use of malonic acid‐decorated fullerene (MA‐C₆₀) with superoxide dismutase activity and water scavenging capability as an electrolyte additive to overcome the structural instability of high‐capacity electrodes that hampers the battery quality is reported. Deactivation of PF₅ by water scavenging leads to the long‐term stability of the interfacial structures of electrodes. Moreover, an MA‐C₆₀‐added electrolyte deactivates the reactive oxygen species and constructs an electrochemically robust cathode‐electrolyte interface for Li‐rich cathodes. This work paves the way for new possibilities in the design of electrolyte additives by eliminating undesirable reactive substances and tuning the interfacial structures of high‐capacity electrodes in LIBs.     

High‐Voltage‐Driven Surface Structuring and Electrochemical Stabilization of Ni‐Rich Layered Cathode Materials for Li Rechargeable Batteries

Layered lithium–nickel–cobalt–manganese oxide (NCM) materials have emerged as promising alternative cathode materials owing to their high energy density and electrochemical stability. Although high reversible capacity has been achieved for Ni‐rich NCM materials when charged beyond 4.2 V versus Li⁺/Li, full lithium utilization is hindered by the pronounced structural degradation and electrolyte decomposition. Herein, the unexpected realization of sustained working voltage as well as improved electrochemical performance upon electrochemical cycling at a high operating voltage of 4.9 V in the Ni‐rich NCM LiNi_0.895Co_0.085Mn_0.02O₂ is presented. The improved electrochemical performance at a high working voltage at 4.9 V is attributed to the removal of the resistive Ni²⁺O rock‐salt surface layer, which stabilizes the voltage profile and improves retention of the energy density during electrochemical cycling. The manifestation of the layered Ni²⁺O rock‐salt phase along with the structural evolution related to the metal dissolution are probed using in situ X‐ray diffraction, neutron diffraction, transmission electron microscopy, and X‐ray absorption spectroscopy. The findings help unravel the structural complexities associated with high working voltages and offer insight for the design of advanced battery materials, enabling the realization of fully reversible lithium extraction in Ni‐rich NCM materials.     

Ecofriendly Chemical Activation of Overlithiated Layered Oxides by DNA‐Wrapped Carbon Nanotubes

Despite their exceptionally high capacity, overlithiated layered oxides (OLO) have not yet been practically used in lithium‐ion battery cathodes due to necessary toxic/complex chemical activation processes and unsatisfactory electrochemical reliability. Here, a new class of ecofriendly chemical activation strategy based on amphiphilic deoxyribose nucleic acid (DNA)‐wrapped multiwalled carbon nanotubes (MWCNT) is demonstrated. Hydrophobic aromatic bases of DNA have a good affinity for MWCNT via noncovalent π–π stacking interactions, resulting in core (MWCNT)‐shell (DNA) hybrids (i.e., DNA@MWCNT) featuring the predominant presence of hydrophilic phosphate groups (coupled with Na⁺) in their outmost layers. Such spatially rearranged Na⁺–phosphate complexes of the DNA@MWCNT efficiently extract Li⁺ from monoclinic Li₂MnO₃ of the OLO through cation exchange reaction of Na⁺–Li⁺, thereby forming Li₄Mn₅O₁₂‐type spinel nanolayers on the OLO surface. The newly formed spinel nanolayers play a crucial role in improving the structural stability of the OLO and suppressing interfacial side reactions with liquid electrolytes, eventually providing significant improvements in the charge/discharge kinetics, cyclability, and thermal stability. This beneficial effect of the DNA@MWCNT‐mediated chemical activation is comprehensively elucidated by an in‐depth structural/electrochemical characterization.     

Replacement of Ca by Ni in a Perovskite Titanate to Yield a Novel Perovskite Exsolution Architecture for Oxygen‐Evolution Reactions

For efficient catalysis and electrocatalysis well‐designed, high‐surface‐area support architectures covered with highly dispersed metal nanoparticles with good catalyst‐support interactions are required. In situ grown Ni nanoparticles on perovskites have been recently reported to enhance catalytic activities in high‐temperature systems such as solid oxide cells (SOCs). However, the micrometer‐scale primary particles prepared by conventional solid‐state reactions have limited surface area and tend to retain much of the active catalytic element within the bulk, limiting efficacy of such exsolution processes in low‐temperature systems. Here, a new, highly efficient, solvothermal route is demonstrated to exsolution from smaller scale primary particles. Furthermore, unlike previous reports of B‐site exsolution, it seems that the metal nanoparticles are exsolved from the A‐site of these perovskites. The catalysts show large active site areas and strong metal‐support interaction (SMSI), leading to ≈26% higher geometric activity (25 times higher mass activity with 1.4 V of E_on‐set) and stability for oxygen‐evolution reaction (OER) with only 0.72 µg base metal contents compared to typical 20 wt% Ni/C and even commercial 20 wt% Ir/C. The findings obtained here demonstrate the potential design and development of heterogeneous catalysts in various low‐temperature electrochemical systems including alkaline fuel cells and metal–air batteries.     

Nonwoven rGO Fiber‐Aramid Separator for High‐Speed Charging and Discharging of Li Metal Anode

Li metal, which has a high theoretical specific capacity and low redox potential, is considered to the most promising anode material for next‐generation Li ion‐based batteries. However, it also exhibits a disadvantageous solid electrolyte interphase (SEI) layer problem that needs to be resolved. Herein, an advanced separator composed of reduced graphene oxide fiber attached to aramid paper (rGOF‐A) is introduced. When rGOF‐A is applied, F^? anions, generated from the decomposition of the LiPF₆ electrolyte during the SEI layer formation process form semi‐ionic C? F bonds along the surface of rGOF. As Li⁺ ions are plated, the “F‐doped” rGO surface induces the formation of LiF, which is known as a component of a chemically stable SEI, therefore it helps the Li metal anode to operate stably at a high current of 20 mA cm^?2 with a high capacity of 20 mAh cm^?2. The proposed rGOF‐A separator successfully achieves a stable SEI layer that could resolve the interfacial issues of the Li metal anode.