Assembly-Induced Membrane Selectivity of Artificial Model Peptides through Entropy-Enthalpy Competition.

Peptide design and drug development offer a promising solution for combating serious diseases or infections. In this study, using an AI-human negotiation approach, we have designed a class of minimal model peptides against tuberculosis (TB), among which K7W6 exhibits potent efficacy attributed to its assembly-induced function. Comprising lysine and tryptophan with an amphiphilic α-helical structure, the K7W6 sequence exhibits robust activity against various infectious bacteria causing TB (including clinically isolated and drug-resistant strains) both in vitro and in vivo. Moreover, it synergistically enhances the effectiveness of the first-line antibiotic rifampicin while displaying low potential for inducing drug resistance and minimal toxicity toward mammalian cells. Biophysical experiments and simulations elucidate that K7W6's exceptional performance can be ascribed to its highly selective and efficient membrane permeabilization activity induced by its distinctive self-assembly behavior. Additionally, these assemblies regulate the interplay between enthalpy and entropy during K7W6-membrane interaction, leading to the peptide's two-step mechanism of membrane interaction. These findings provide valuable insights into rational design principles for developing advanced peptide-based drugs while uncovering the functional role played by assembly.

Cholesterol Depletion and Membrane Deformation by MeßCD and the Resultant Enhanced T Cell Killing.

Recent studies have demonstrated the crucial role of cholesterol (Chol) in regulating the mechanical properties and biological functions of cell membranes. Methyl-ß-cyclodextrin (MeßCD) is commonly utilized to modulate the Chol content in cell membranes, but there remains a lack of a comprehensive understanding. In this study, using a range of different techniques, we find that the optimal ratio of MeßCD to Chol for complete removal of Chol from a phosphocholine (PC)/Chol mixed membrane with a 1:1 mol ratio is 4.5:1, while the critical MeßCD-to-Chol ratio for membrane permeation falls within the range between 1.5 and 2.4. MeßCD at elevated concentrations induces the formation of fibrils or tubes from a PC membrane. Single lipid tracking reveals that removing Chol restores the diffusion of lipid molecules in the PC/Chol membrane to levels observed in pure PC membranes. Exposure to 5 mM MeßCD for 30 min effectively eliminates Chol from various cell lines, leading to an up to 8-fold enhancement in melittin cytotoxicity over Hela cells and an up to 3.5-fold augmentation of T cell cytotoxicity against B16F10-OVA cells. This study presents a diagram that delineates the concentration- and time-dependent distribution of MeßCD-induced Chol depletion and membrane deformation, which holds significant potential for modulating the mechanical properties of cellular membranes in prospective biomedical applications.

Hybrid Electrolyte with Dual-Anion-Aggregated Solvation Sheath for Stabilizing High-Voltage Lithium-Metal Batteries.

Lithium (Li)-metal batteries (LMBs) with high-voltage cathodes and limited Li-metal anodes are crucial to realizing high-energy storage. However, functional electrolytes that are compatible with both high-voltage cathodes and Li anodes are required for their developments. In this study, the use of a moderate-concentration LiPF6 and LiNO3 dual-salt electrolyte composed of ester and ether co-solvents (fluoroethylene carbonate/dimethoxyethane, FEC/DME), which forms a unique Li+ solvation with aggregated dual anions, that is, PF6 - and NO3 - , is proposed to stabilize high-voltage LMBs. Mechanistic studies reveal that such a solvation sheath improves the Li plating/stripping kinetics and induces the generation of a solid electrolyte interphase (SEI) layer with gradient heterostructure and high Young's modulus on the anode, and a thin and robust cathode electrolyte interface (CEI) film. Therefore, this novel electrolyte enables colossal Li deposits with a high Coulombic efficiency (≈98.9%) for 450 cycles at 0.5 mA cm-2 . The as-assembled LiǁLiNi0.85 Co0.10 Al0.05 O2 full batteries deliver an excellent lifespan and capacity retention at 4.3 V with a rigid negative-to-positive capacity ratio. This electrolyte system with a dual-anion-aggregated solvation structure provides insights into the interfacial chemistries through solvation regulation for high-voltage LMBs.

[Psychological autopsy and its limitation in application].

The suicide were analyzed depending only on the death scene and cadaver features but not on the psychological autopsy (PA) that also enables the determination of the manner of death in China for a long time. There are significant differences between PA and the traditional risk assessment of suicide. The goals of PA are to find out the features of individuality, the patterns of behavior and the possible motives of suicide. The methods of PA involve investigating, collecting and analyzing all related information of the deceased. There are many limitations of PA in application mainly due to the lack of the standard procedures. Although an improved procedure has recently developed by Berman, many problems need to be solved before the actual application of PA in China.

Failure Mechanism and Interface Engineering for NASICON-Structured All-Solid-State Lithium Metal Batteries.

All-solid-state lithium metal batteries (ASSLiMB) have been considered as one of the most promising next-generation high-energy storage systems that replace liquid organic electrolytes by solid-state electrolytes (SSE). Among many different types of SSE, NASICON-structured Li1+ xAl xGe2- x(PO3)4 (LAGP) shows high a ionic conductivity, high stability against moisture, and wide working electrochemical windows. However, it is unstable when it is in contact with molten Li, hence largely limiting its applications in ASSLiMB. To solve this issue, we have studied reaction processes and mechanisms between LAGP and molten Li, based on which a failure mechanism is hence proposed. With better understanding the failure mechanism, a thin thermosetting Li salt polymer, P(AA- co-MA)Li, layer is coated on the bare LAGP pellet before contacting with molten Li. To further increase the ionic conductivity of P(AA- co-MA)Li, LiCl is added in P(AA- co-MA)Li. A symmetric cell of Li/interface/LAGP/interface/Li is prepared using molten Li-Sn alloy and galvanically cycled at current densities of 15, 30, and 70 µA cm-2 for 100 cycles, showing stable low overpotentials of 0.036, 0.105, and 0.257 V, respectively. These electrochemical results demonstrate that the interface coating of P(AA- co-MA)Li can be an effective method to avoid an interfacial reaction between the LAGP electrolyte and molten Li.

Porous Ni0.1Mn0.9O1.45 microellipsoids as high-performance anode electrocatalyst for microbial fuel cells.

A novel bi-component composite of porous self-assembled micro-/nanostructured Ni0.1Mn0.9O1.45 microellipsoids as high-performance anode electrocatalyst for microbial fuel cells (MFCs) is successfully synthesized via a simple coprecipitation reaction in microemulsion and calcination method in air atmosphere. The morphology and structural characterization indicate that the as-fabricated Ni0.1Mn0.9O1.45 product is consist of Mn2O3 and NiMn2O4 (n(Mn2O3): n(NiMn2O4) = 0.35: 0.1) and has a porous microellipsoidal morphology. The microellipsoids are compose of numerous layered micro-/nanostructured blocks and the special porous microellipsoids structure of Ni0.1Mn0.9O1.45 offers a large specific surface area for bacteria adhesion. The porous Ni0.1Mn0.9O1.45 microellipsoids as anode electrocatalyst for MFCs exhibits excellent electrocatalytic activity to promote the extracellular electron transfer (EET) between the anode and bacteria, hence improves the performance of MFC. The MFC equipped with Ni0.1Mn0.9O1.45/CF anode achieves a maximum power density of 1.39 ± 0.02Wm-2, is significantly higher than that of commercial carbon felt anode. This work proposes a new method for the synthesis of high-performance and environmentally friendly anode electrocatalyst for MFCs.

Insight into the capacity fading of layered lithium-rich oxides and its suppression via a film-forming electrolyte additive.

The capacity fading of layered lithium-rich oxide (Li1.2Mn0.54Ni0.13Co0.13O2, LLO) cathodes greatly hinders their practical application in next generation lithium ion batteries. It has been demonstrated in this work that the slow capacity fading of a LLO/Li cell within 120 cycles is mainly caused by electrolyte oxidation and LLO phase transformation with Ni dissolution. After 120 cycles, the dissolution of Mn becomes worse than that of Ni, leading to structural destruction of the generated spinel phase structure of LLO and fast capacity fading. Tripropyl borate (TPB) is proposed as a film-forming electrolyte additive, which shows a great capability to enhance the cycling stability of LLO/Li, with a capacity retention improvement from 21% to 78% after 250 cycles at 0.5C. Electrochemical and physical characterization demonstrated that the TPB-derived SEI film shows great capability to suppress electrolyte oxidation and the structural destruction of the generated spinel phase of LLO.

Female-dependent impaired fear memory of adult rats induced by maternal separation, and screening of possible related genes in the hippocampal CA1.

Early life stress is one of the major susceptible factors for stress-related pathologies like posttraumatic stress disorder (PTSD). Recent studies in rats suggest that rather than being overall unfavorable, early life stress may prepare the organism to perform optimally to stressful environments later in life. In this study, severely adverse early life stress was conducted by six consecutive hours of maternal separation (MS), from PND1 to PND21, and contextual fear conditioning model was used on PND90 to mimic the second stress in adulthood and the re-experiencing symptom of PTSD. It was observed that in this investigation pups experienced MS showed decreased sensibility to contextual fear conditioning in adulthood, and there sex plays an important role. For example, female rats suffered MS had much lower freezing than males and controls. Meanwhile, Morris water maze test indicated that MS did not impair rat's performance of spatial learning and memory. Furthermore, suppression subtractive hybridization (SSH) was used to screen the related genes of fear memory, by examining the changes of mRNA expression in CA1 area between female MS and control rats after contextual fear conditioning. Finally, nine up-regulated and one down-regulated genes, including ß2-MG, MAF, Nd1-L, TorsinA and MACF1 gene were found in this study. It is assumed that the TorsinA, MACF1 and Nd1-L gene may contribute to the decreased sensitivity of PTSD induced by MS.

Retardation of neurobehavioral development and reelin down-regulation regulated by further DNA methylation in the hippocampus of the rat pups are associated with maternal deprivation.

It is known that early life stress has profound effects in early developing hippocampus. Reelin is a large protein that regulates neuronal migration during embryonic development. The expression of reelin persists in brain, but its function is little known. The aim of the present study was to investigate the effects of maternal deprivation (MD) on early neurobehavioral development of rats, and the role of reelin and the potential mechanism underlying regulation of its expression in hippocampus. Rat pups were removed from mothers during the postnatal day (PND) 2-15 for 3h a day. Reflex developments including grasping, gait, righting, cliff avoidance, auditory startle, hot-plate test and negative geotaxis, were tested during the first 3 weeks. The level of reelin mRNA and reelin gene methylation in the hippocampal formation were determined using real-time PCR analysis. As expected, some differences appeared in the measure of neurobehavior and expression of reelin in rat pups. Several significant deficiencies were observed in bodyweight, auditory startle and grasping reflex while a great enhancement in hot-plate test in rat pups suffering from MD. On PND 22, the expression of reelin mRNA reduced in the hippocampus followed by MD. Meanwhile, the changes of DNA methylation showed an opposite trend compared with the reelin expression. The results suggest that MD in early life has harmful effects on neurobehavioral development, and causes the down-regulation of reelin mRNA by further DNA methylation in postnatal hippocampus.