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Abstract Global trends toward green energy have empowered the extensive application of high‐performance energy storage systems. With the worldwide spread of electric vehicles (EVs), lithium‐ion batteries (LIBs) capable of fast‐charging have become increasingly important. Nonetheless, state‐of‐the‐art LIBs have failed to satisfy the demands of prospective customers, including rapid charging, extended cycle life, and high energy density. Addressing these challenges through innovations in material science and other advanced battery technologies is essential for meeting the growing demands of prospective customers. Besides the choice of active materials, electrolyte formulation has a significant impact on the fast‐charging performance and cycle life of LIBs over a wide range of temperatures. The liquid electrolyte is typically composed of lithium salts to provide an ion source, solvents to carry Li+ ions, and functional additives to build a stable solid electrolyte interphase (SEI). To enable the fast movement of Li+ ions, the liquid electrolytes should have low viscosity and high ionic conductivity. Meanwhile, SEI layers must be thin, uniform and ionically conductive. Furthermore, the low binding energy of the solvent facilitates desolvation of the solvation sheath, enabling fast Li+ ion transport to the anode during fast charging. This review provides the latest insights into rapid Li+ ion transport during fast charging, focusing on ensuring a deeper understanding of liquid electrolyte chemistry. The involvement of existing electrolyte mechanisms in materials discovery will develop electrolyte engineering techniques to improve the fast‐charging performance of batteries over a wide temperature range and will also facilitate the development of EV‐adoptable advanced electrodes.

Abstract Lithium metal anode (LMA) emerges as a promising candidate for lithium (Li)‐based battery chemistries with high‐energy‐density. However, inhomogeneous charge distribution from the unbalanced ion/electron transport causes dendritic Li deposition, leading to “dead Li” and parasitic reactions, particularly at high Li utilization ratios (low negative/positive ratios in full cells). Herein, an innovative LMA structural model deploying a hyperporous/hybrid conductive architecture is proposed on single‐walled carbon nanotube film (HCA/C), fabricated through a nonsolvent induced phase separation process. This design integrates ionic polymers with conductive carbon, offering a substantial improvement over traditional metal current collectors by reducing the weight of LMA and enabling high‐energy‐density batteries. The HCA/C promotes uniform lithium deposition even under rapid charging (up to 5 mA cm−2) owing to its efficient mixed ion/electron conduction pathways. Thus, the HCA/C demonstrates stable cycling for 200 cycles with a low negative/positive ratio of 1.0 when paired with a LiNi0.8Co0.1Mn0.1O2 cathode (areal capacity of 5.0 mAh cm−2). Furthermore, a stacked pouch‐type full cell using HCA/C realizes a high energy density of 344 Wh kg−1cell/951 Wh L−1cell based on the total mass of the cell, exceeding previously reported pouch‐type full cells. This work paves the way for LMA development in high‐energy‐density Li metal batteries.

Abstract Electrolyte additives with multiple functions enable the interfacial engineering of Li‐metal batteries (LMBs). Owing to their unique reduction behavior, additives exhibit a high potential for electrode surface modification that increases the reversibility of Li‐metal anodes by enabling the development of a hierarchical solid electrolyte interphase (SEI). This study confirms that an adequately designed SEI facilitates the homogeneous supply of Li+, nonlocalized Li deposition, and low electrolyte degradation in LMBs while enduring the volume fluctuation of Li‐metal anodes on cycling. An in‐depth analysis of interfacial engineering mechanisms reveals that multilayered SEI structures comprising mechanically robust LiF‐rich species, electron‐rich P–O species, and elastic polymeric species enabled the stable charge and discharge of LMBs. The polymeric outer SEI layer in the as‐fabricated multilayered SEI could accommodate the volume fluctuation of Li‐metal anodes, significantly enhancing the cycling stability Li||LiNi0.8Co0.1Mn0.1O2 full cells with an electrolyte amount of 3.6 g Ah−1 and an areal capacity of 3.2 mAh cm−2. Therefore, this study confirms the ability of interfacial layers formed by electrolyte additives and fluorinated solvents to advance the performance of LMBs and can open new frontiers in the fabrication of high‐performance LMBs through electrolyte‐formulation engineering.

The rapidly increasing prevalence of obesity and overweight, especially in children and adolescents, has become a serious societal issue. Although various genetic and environmental risk factors for pediatric obesity and overweight have been identified, the problem has not been solved. In this study, we examined whether environmental nanoplastic (NP) pollutants can act as environmental obesogens using mouse models exposed to NPs derived from polystyrene and polypropylene, which are abundant in the environment. We found abnormal weight gain in the progeny until 6 weeks of age following the oral administration of NPs to the mother during gestation and lactation. Through a series of experiments involving multi-omic analyses, we have demonstrated that NP-induced weight gain is caused by alterations in the lipid composition (lysophosphatidylcholine/phosphatidylcholine ratio) of maternal breast milk and he gut microbiota distribution of the progeny. These data indicate that environmental NPs can act as obesogens in childhood.

Abstract The pulverization of lithium metal electrodes during cycling recently has been suppressed through various techniques, but the issue of irreversible consumption of the electrolyte remains a critical challenge, hindering the progress of energy-dense lithium metal batteries. Here, we design a single-ion-conductor-based composite layer on the lithium metal electrode, which significantly reduces the liquid electrolyte loss via adjusting the solvation environment of moving Li+ in the layer. A Li||Ni0.5Mn0.3Co0.2O2 pouch cell with a thin lithium metal (N/P of 2.15), high loading cathode (21.5 mg cm−2), and carbonate electrolyte achieves 400 cycles at the electrolyte to capacity ratio of 2.15 g Ah−1 (2.44 g Ah−1 including mass of composite layer) or 100 cycles at 1.28 g Ah−1 (1.57 g Ah−1 including mass of composite layer) under a stack pressure of 280 kPa (0.2 C charge with a constant voltage charge at 4.3 V to 0.05 C and 1.0 C discharge within a voltage window of 4.3 V to 3.0 V). The rational design of the single-ion-conductor-based composite layer demonstrated in this work provides a way forward for constructing energy-dense rechargeable lithium metal batteries with minimal electrolyte content.

Abstract Background Spastin significantly influences microtubule regulation in neurons and is implicated in the pathogenesis of hereditary spastic paraplegia (HSP). However, post-translational regulation of the spastin protein remains nebulous. The association between E3 ubiquitin ligase and spastin provides a potential therapeutic strategy. Results As evidenced by protein chip analysis, FBXL17 inversely correlated with SPAST-M1 at the protein level in vitro and, also in vivo during embryonic developmental stage. SPAST-M1 protein interacted with FBXL17 specifically via the BTB domain at the N-terminus of SPAST-M1. The SCFFBXL17 E3 ubiquitin ligase complex degraded SPAST-M1 protein in the nuclear fraction in a proteasome-dependent manner. SPAST phosphorylation occurred only in the cytoplasmic fraction by CK2 and was involved in poly-ubiquitination. Inhibition of SCFFBXL17 E3 ubiquitin ligase by small chemical and FBXL17 shRNA decreased proteasome-dependent degradation of SPAST-M1 and induced axonal extension. The SPAST Y52C mutant, harboring abnormality in BTB domain could not interact with FBXL17, thereby escaping protein regulation by the SCFFBXL17 E3 ubiquitin ligase complex, resulting in loss of functionality with aberrant quantity. Although this mutant showed shortening of axonal outgrowth, low rate proliferation, and poor differentiation capacity in a 3D model, this phenotype was rescued by inhibiting SCFFBXL17 E3 ubiquitin ligase. Conclusions We discovered that a novel pathway, FBXL17-SPAST was involved in pathogenicity of HSP by the loss of function and the quantitative regulation. This result suggested that targeting FBXL17 could provide new insight into HSP therapeutics.

Background: Nutritional status and sarcopenia affects the prognosis of head and neck cancers including hypopharyngeal cancer. Hypopharyngeal cancer patients tend to exhibit sarcopenia, which is associated with poor treatment outcomes. This study aims to determine the correlation between nutritional status and sarcopenia, and their prognostic role in surgically treated hypopharyngeal cancer. Materials and Methods: Patients who had been diagnosed with squamous cell carcinoma originating from the hypopharynx and underwent surgery between January 2009 and December 2019 were enrolled in this study. The median neutrophil‐to‐lymphocyte ratio and prognostic nutritional index (PNI) of the cohort were considered the cut‐off values. Sarcopenia was evaluated by measuring skeletal muscle index (SMI) at the third lumbar vertebra. Clinical and serological factors predictive of survival outcomes were evaluated. Results: Patients with high PNI showed better 5‐year Overall survival (OS) (52.8% vs. 27.2%, p = 0.001) and disease‐free survival (DFS) (59.6% vs. 44.6%, p = 0.033) than those with low PNI. Likewise, patients with low SMI showed worse 5‐year OS (25.0% vs. 60.9%, p = 0.002) and DFS (42.4% vs. 68.7%, p = 0.034) than patients with high SMI. Among the patients with high PNI, those with sarcopenia displayed significantly worse OS than those with high SMI (78.0% vs. 34.4%, p = 0.049). High PNI with high SMI presented better overall (p = 0.010) and DFS (p = 0.055) than any other group. Conclusions: Both sarcopenia and PNI were associated with the prognosis of hypopharyngeal cancer. Considering that PNI and sarcopenia indicate the nutritional status, nutritional status may be a significant risk factor. Therefore, nutritional support that ameliorates sarcopenia may improve survival outcomes in surgically treated patients with hypopharyngeal cancer. [ABSTRACT FROM AUTHOR]

Introduction: Despite the emergence of atezolizumab and bevacizumab (A + B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A + B treatment. Methods: This multicentre retrospective study included consecutive patients with HCC who were treated with the A + B regimen from September 2020 to December 2022. Patients were categorized into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs. Results: This study included 150 patients with HCC, with a mean age of 63.3 years. Among them, 93.3% of patients were classified as Barcelona Clinic Liver Cancer stage C, 52.0% had portal vein tumour thrombosis (PVTT), and 60.7% extrahepatic spread. Patients were classified as follows: group 1 (n = 84) had no irAEs, group 2 (n = 37) had mild irAEs (grade 1-2), and group 3 (n = 29) had severe irAEs (grade ≥3). The median overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation (TTD) were 13.6, 5.7, and 3.6 months, respectively. Group 2 demonstrated significantly superior OS compared to group 1 (9.5 months) and group 3 (5.6 months), with a median OS of 23.0 months (p < 0.001). Furthermore, group 2 demonstrated significantly better outcomes in terms of PFS and TTD compared to both group 1 and group 3 (p < 0.001 for both). Multivariate analysis identified mild irAEs (hazard ratio [HR], 0.353; p = 0.010), ALBI grade 1 (HR, 0.389; p = 0.006), Child-Pugh class A (HR, 0.338; p = 0.002), and the absence of PVTT (HR, 0.556; p = 0.043) as independent predictors of better OS. Conclusion: Our study highlights the significant impact of irAE severity on the outcomes of patients with HCC receiving A + B. Notably, the occurrence of mild irAEs was independently associated with favourable survival, suggesting their potential role as surrogate indicators of HCC prognosis. [ABSTRACT FROM AUTHOR]

As people age, the risk and progression of colorectal cancer (CRC), along with cholesterol levels, tend to increase. Nevertheless, epidemiological studies on serum lipids and CRC have produced conflicting results. We previously demonstrated that the reduction of squalene epoxidase (SQLE) due to accumulated cholesterol within cells accelerates CRC progression through the activation of the β‐catenin pathway. This study aimed to investigate the mechanism by which age‐related cholesterol accumulation within tissue accelerates CRC progression and to assess the clinical significance of SQLE in older individuals with elevated CRC risk. Using machine learning‐based digital image analysis with fluorescence‐immunohistochemistry, we assessed SQLE, GSK3βpS9 (GSK3β activity inhibition through serine 9 phosphorylation at GSK3β), p53 wild‐type (p53WT), and p53 mutant (p53MT) levels in CRC tissues. Our analysis revealed a significant reduction in SQLE, p53WT, and p53MT and increase in GSK3βpS9 levels, all associated with the substantial accumulation of intra‐tissue cholesterol in aged CRCs. Cox analysis underscored the significant influence of SQLE on overall survival and progression‐free survival in grade 2–3 CRC patients aged over 50. SQLE and GSK3βpS9 consistently exhibited outstanding prognostic and diagnostic performance, particularly in older individuals. Furthermore, combining SQLE with p53WT, p53MT, and GSK3βpS9 demonstrated a robust diagnostic ability in the older population. In conclusion, we have identified that individuals aged over 50 face an increased risk of CRC progression due to aging‐linked cholesterol accumulation within tissue and the subsequent reduction in SQLE levels. This study also provides valuable biomarkers, including SQLE and GSK3βpS9, for older patients at elevated risk of CRC. [ABSTRACT FROM AUTHOR]

Lithium metal anode (LMA) emerges as a promising candidate for lithium (Li)‐based battery chemistries with high‐energy‐density. However, inhomogeneous charge distribution from the unbalanced ion/electron transport causes dendritic Li deposition, leading to "dead Li" and parasitic reactions, particularly at high Li utilization ratios (low negative/positive ratios in full cells). Herein, an innovative LMA structural model deploying a hyperporous/hybrid conductive architecture is proposed on single‐walled carbon nanotube film (HCA/C), fabricated through a nonsolvent induced phase separation process. This design integrates ionic polymers with conductive carbon, offering a substantial improvement over traditional metal current collectors by reducing the weight of LMA and enabling high‐energy‐density batteries. The HCA/C promotes uniform lithium deposition even under rapid charging (up to 5 mA cm−2) owing to its efficient mixed ion/electron conduction pathways. Thus, the HCA/C demonstrates stable cycling for 200 cycles with a low negative/positive ratio of 1.0 when paired with a LiNi0.8Co0.1Mn0.1O2 cathode (areal capacity of 5.0 mAh cm−2). Furthermore, a stacked pouch‐type full cell using HCA/C realizes a high energy density of 344 Wh kg−1cell/951 Wh L−1cell based on the total mass of the cell, exceeding previously reported pouch‐type full cells. This work paves the way for LMA development in high‐energy‐density Li metal batteries. [ABSTRACT FROM AUTHOR]

Lithium-excess 3d-transition-metal layered oxides (Li1+xNiyCozMn1-x-y-zO2, >250 mAh g-1) suffer from severe voltage decay upon cycling, which decreases energy density and hinders further research and development. Nevertheless, the lack of understanding on chemical and structural uniqueness of the material prevents the interpretation of internal degradation chemistry. Here, we discover a fundamental reason of the voltage decay phenomenon by comparing ordered and cation-disordered materials with a combination of X-ray absorption spectroscopy and transmission electron microscopy studies. The cation arrangement determines the transition metal-oxygen covalency and structural reversibility related to voltage decay. The identification of structural arrangement with de-lithiated oxygen-centred octahedron and interactions between octahedrons affecting the oxygen stability and transition metal mobility of layered oxide provides the insight into the degradation chemistry of cathode materials and a way to develop high-energy density electrodes.

Abstract The neural circuits of the infant brain are rapidly established near 6 months of age, but neurodevelopmental disorders can be diagnosed only at the age of 2–3 years using existing diagnostic methods. Early diagnosis is very important to alleviate life-long disability in patients through appropriate early intervention, and it is imperative to develop new diagnostic methods for early detection of neurodevelopmental disorders. We examined the serum level of secretogranin II (SCG2) in pediatric patients to evaluate its potential role as a biomarker for neurodevelopmental disorders. A plasmonic immunosensor performing an enzyme-linked immunosorbent assay (ELISA) on a gold nanodot array was developed to detect SCG2 in small volumes of serum. This nanoplasmonic immunosensor combined with tyramide signal amplification was highly sensitive to detect SCG2 in only 5 μL serum samples. The analysis using the nanoplasmonic immunosensor revealed higher serum SCG2 levels in pediatric patients with developmental delay than in the control group. Overexpression or knockdown of SCG2 in hippocampal neurons significantly attenuated dendritic arborization and synaptic formation. These results suggest that dysregulated SCG2 expression impairs neural development. In conclusion, we developed a highly sensitive nanoplasmonic immunosensor to detect serum SCG2, a candidate biomarker for the early diagnosis of neurodevelopmental disorders.