Diminished social interaction incentive contributes to social deficits in mouse models of autism spectrum disorder

One of the core symptoms of autism spectrum disorder (ASD) is impaired social interaction. Currently, no pharmacotherapies exist for this symptom due to complex biological underpinnings and distinct genetic models which fail to represent the broad disease spectrum. One convincing hypothesis explaining social deficits in human ASD patients is amotivation, however it is unknown whether mouse models of ASD represent this condition. Here we used two highly trusted ASD mouse models (male Shank3‐deficient [Shank3^+/ΔC] mice modeling the monogenic etiology of ASD, and inbred BTBR mice [both male and female] modeling the idiopathic and highly polygenic pathology for ASD) to evaluate the level of motivation to engage in a social interaction. In the behavioral paradigms utilized, a social stimulus was placed in the open arm of the elevated plus maze (EPM), or the light compartment of the light‐dark box (LDB). To engage in a social interaction, mice were thus required to endure innately aversive conditions (open areas, height, and/or light). In the modified EPM paradigm, both Shank3^+/ΔC and BTBR mice demonstrated decreased open‐arm engagement with a social stimulus but not a novel object, suggesting reduced incentive to engage in a social interaction in these models. However, these deficits were not expressed under the less severe aversive pressures of the LDB. Collectively, we show that ASD mouse models exhibit diminished social interaction incentive, and provide a new investigation strategy facilitating the study of the neurobiological mechanisms underlying social reward and motivation deficits in neuropsychiatric disorders.     

miR‐126 reduces trastuzumab resistance by targeting PIK3R2 and regulating AKT/mTOR pathway in breast cancer cells

MicroRNAs (miRNAs) have been found to play a key role in drug resistance. In the current study, we aimed to explore the potential role of miR‐126 in trastuzumab resistance in breast cancer cells. We found that the trastuzumab‐resistant cell lines SKBR3/TR and BT474/TR had low expression of miR‐126 and increased ability to migrate and invade. The resistance, invasion and mobilization abilities of the cells resistant to trastuzumab were reduced by ectopic expression of miR‐126 mimics. In comparison, inhibition of miR‐126 in SKBR3 parental cells had the opposite effect of an increased resistance to trastuzumab as well as invasion and migration. It was also found that miR‐126 directly targets PIK3R2 in breast cancer cells. PIK3R2‐knockdown cells showed decreased resistance to trastuzumab, while overexpression of PIK3R2 increased trastuzumab resistance. In addition, our finding showed that overexpression of miR‐126 reduced resistance to trastuzumab in the trastuzumab‐resistant cells and that inhibition of the PIK3R2/PI3K/AKT/mTOR signalling pathway was involved in this effect. SKBR3/TR cells also showed increased sensitivity to trastuzumab mediated by miR‐126 in vivo. In conclusion, the above findings demonstrated that overexpression of miR‐126 or down‐regulation of its target gene may be a potential approach to overcome trastuzumab resistance in breast cancer cells.     

Association of IFN‐γ polymorphisms with ankylosing spondylitis risk

The case‐control study was designed to investigate the genetic effects of interferon‐gamma (IFN‐γ) rs2069727 and rs1861494 polymorphisms on ankylosing spondylitis (AS) susceptibility in a Chinese Han population. Blood samples were collected from 108 AS patients and 110 healthy controls. IFN‐γ polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Hardy‐Weinberg equilibrium (HWE) test was performed in control group. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using chi‐square test to evaluate the association between AS susceptibility and IFN‐γ polymorphisms, and the results were adjusted by logistic regressive analysis. The frequency of rs2069727 CC genotype was much higher in cases than that in controls, suggested its significant association with increased AS risk (adjusted OR = 5.899, 95% CI = 1.563‐22.261; P = .009). In addition, C allele also showed close association with increased risk of AS (adjusted OR = 2.052, 95% CI = 1.286‐1.704, P  = 0 .003). While the genotype and allele frequencies of IFN‐γ rs1861494 polymorphism were not significantly different between patients and controls (P  > 0.05 for all), IFN‐γ rs2069727 polymorphism is significantly associated with increased AS risk in a Chinese Han Population.     

Caffeoylquinic Acids,Cytotoxic, Antioxidant,Acetylcholinesterase and Tyrosinase Enzyme Inhibitory Activities of Six Inula Species from Bulgaria

Chlorogenic (5‐CQA), 1,5‐, 3,5‐, 4,5‐ and 3,4‐dicaffeoylquinic (DCQA) acids were identified and quantified in the methanol extracts of Inula oculus‐christi L., I. bifrons L., I. aschersoniana Janka var. aschersoniana, I. ensifolia L., I. conyza (Griess .) DC. and I. germanica L. by HPLC analysis. The amount of 5‐CQA varied from 5.48 to 28.44 mg/g DE and the highest content was detected in I. ensifolia. 1,5‐DCQA (4.05–55.25 mg/g DE) was the most abundant dicaffeoyl ester of quinic acid followed by 3,5‐DCQA, 4,5‐DCQA and 3,4‐DCQA. The extract of I. ensifolia showed the highest total phenolic content (119.92±0.95 mg GAE/g DE) and exhibited the strongest DPPH radical scavenging activity (69.41±0.55 %). I. bifrons extract was found to be the most active sample against ABTS^.+ (TEAC 0.257±0.012 mg/mL) and the best tyrosinase inhibitor. The studied extracts demonstrated a low inhibitory effect towards acetylcholinesterase and possessed low cytotoxicity in concentration range from 10 to 300 μg/mL toward non‐cancer (MDCK II) and cancer (A 549) cells.     

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.     

Femtosecond Laser‐Etched MXene Microsupercapacitors with Double‐Side Configuration via Arbitrary On‐ and Through‐Substrate Connections

The capacitance of microsupercapacitors (MSCs) can double if both sides of substrates are used to construct MSCs. Nevertheless, achieving electric connections of MSCs through substrates is a challenge due to the difficulty in precisely positioning each MSC couple that has two of the same MSCs units on two sides. In this work, taking advantage of the synchronous etching on both sides of transparent polyethylene terephthalate substrates by femtosecond laser pulses, a double‐sided configuration is attained with high precision in the alignment of back‐to‐back MSC couples and versatile double‐side MSCs are realized via arbitrary on‐ and through‐substrate connections of MXene MSC units. The MXene double‐side MSC fabricated by the series connection of 12 spiral pattern MXene MSC units with interdigital electrodes of 10 μm width interspace can output a large working voltage of 7.2 V. Additionally, femtosecond laser etching brings the transformation of MXene into titania near‐etched edges with a lateral distance less than 1 µm. Such a small laser‐affected area has little influence on the capacitive performance, which is one of advantages for femtosecond laser over conventional lasers. This research is valuable for one‐step manufacturing of highly integrated MSCs in the field of miniaturized energy storage systems.     

Accessing the Two‐Electron Charge Storage Capacity of MnO2 in Mild Aqueous Electrolytes

Rechargeable batteries based on MnO₂ cathodes, able to operate in mild aqueous electrolytes, have attracted attention due to their appealing features for the design of low‐cost stationary energy storage devices. However, the charge/discharge mechanism of MnO₂ in such media is still a matter of debate. Here, an in‐depth quantitative spectroelectrochemical analysis of MnO₂ thin‐films provides a set of unrivaled mechanistic insights. A major finding is that charge storage occurs through the reversible two‐electron faradaic conversion of MnO₂ into Mn²⁺ in the presence of a wide range of weak Brønsted acids, including the [Zn(H₂O)₆]²⁺ or [Mn(H₂O)₆]²⁺ complexes present in aqueous Zn/MnO₂ batteries. Furthermore, it is shown that buffered electrolytes loaded with Mn²⁺ are ideal to achieve highly reversible conversion of MnO₂ with both high gravimetric capacity and remarkably stable charging/discharging potentials. In the most favorable case, a record gravimetric capacity of 450 mA·h·g^?1 is obtained at a high rate of 1.6 A·g^?1, with a Coulombic efficiency close to 100% and a MnO₂ utilization of 84%. Overall, the present results challenge the common view on MnO₂ the charge storage mechanism in mild aqueous electrolytes and underline the benefit of buffered electrolytes for high‐performance rechargeable aqueous batteries.     

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.