SLC25A3 negatively regulates NLRP3 inflammasome activation by restricting the function of NLRP3.

The NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome activation plays a critical role in innate immune and pathogenic microorganism infections. However, excessive activation of NLRP3 inflammasome will lead to cellular inflammation and tissue damage, and naturally it must be precisely controlled in the host. Here, we discovered that solute carrier family 25 member 3 (SLC25A3), a mitochondrial phosphate carrier protein, plays an important role in negatively regulating NLRP3 inflammasome activation. We found that SLC25A3 could interact with NLRP3, overexpression of SLC25A3 and knockdown of SLC25A3 could regulate NLRP3 inflammasome activation, and the interaction of NLRP3 and SLC25A3 is significantly boosted in the mitochondria when the NLRP3 inflammasome is activated. Our detailed investigation demonstrated that the interaction between NLRP3 and SLC25A3 disrupted the interaction of NLRP3-NEK7, promoted ubiquitination of NLRP3, and negatively regulated NLRP3 inflammasome activation. Thus, these findings uncovered a new regulatory mechanism of NLRP3 inflammasome activation, which provides a new perspective for the therapy of NLRP3 inflammasome-associated inflammatory diseases.

Effectiveness and Safety of Different Patch Materials for Supravalvar Aortic Stenosis (Middle-Term Outcomes).

Background: To determine the effectiveness and safety of different patch materials in the treatment of pediatric patients with congenital supravalvular aortic stenosis (SVAS). Methods: 218 consecutive SVAS patients (age < 14 years) who underwent surgery from Beijing Fuwai and Yunnan Fuwai hospital between 2002 and 2020 were included. Patients were divided into the pericardium patch group (133 (61.0%)), modified patch group (43 (19.7%)) and artificial patch group (42 (19.3%)). The primary safety endpoint was patch-related adverse complications (post-operation patch hemorrhage or aortic sinus aneurysm at 2-year follow-up). The primary effectiveness outcome was the re-operation or restenosis at 2-year follow-up. Multivariable cox regression was used to obtain the hazard ratio (HR). Results: The median age at operation was 43.5 months (IQR 24.0-73.0). Only three patients had patch-related adverse complications, and no difference existed among the three groups (p = 0.763). After a median follow-up of 24.0 months (IQR 6.0-48.0), patients with a pericardium patch had a lower re-operation or restenosis rate compared with the other two groups (pericardium patch vs modified patch, HR = 0.30, 95% CI 0.12-0.77; pericardium patch vs artificial patch, HR = 0.33, 95% CI 0.13-0.82), even in the main subgroup and sensitivity analysis. Conclusions: In pediatric patients, the safety of autologous pericardium patch is acceptable, along with lower rates of middle-term re-operation or restenosis. Clinical Trial Registration: http://www.chictr.org.cn, number: ChiCTR2300067851.

Longitudinal relationship between social participation, depressive symptoms, and activity impairment among older patients with arthritis: a moderated mediation analysis.

BACKGROUND: Arthritis primarily affects older people and is a prominent cause of their activity impairment. This study aimed to examine the mediating role of depressive symptoms in the relationship between social participation and activity impairment, as well as to determine whether sex moderated the mediating effect. METHODS: A total of 2247 older patients with arthritis were included from the China Health and Retirement Longitudinal Study between 2015 and 2018. We first examined a simple mediation model where depressive symptoms were a mediator between social participation and activity impairment. Furthermore, sex was systematically integrated into the model as a moderator. The mediation model and moderated mediation model were analyzed using PROCESS macro. RESULTS: Mediation analysis revealed that the association between social participation and activity impairment was partially mediated by depressive symptoms (B = -0.10, 95% CI = [-0.14, -0.06]) with intermediary effect of 28.6%. Moderated mediation analysis indicated that mediation model was moderated by sex. The indirect effect of social participation on activity impairment among female patients (B = -0.15, 95% CI = [-0.21, -0.09]) was stronger than male patients (B = -0.04, 95% CI = [-0.09, -0.01]). CONCLUSION: Social participation was the key protective factor associated with depressive symptoms and activity impairment among arthritis patients. Encouraging arthritis patients to social participation and improving the depressive symptoms might avoid activity impairment, especially for female patients.

Heterogeneity of social participation in patients three months after total knee arthroplasty: a latent profile analysis.

BACKGROUND: Social participation is an important index of rehabilitation and social reintegration in patients after total knee arthroplasty (TKA). However, most existing studies focus on improving patients' functioning and activities, with only a few examining the social participation among patients after TKA. Therefore, the study aims to investigate the heterogeneity of social participation in patients three months after TKA and analyze subgroup influencing factors, to promote functional exercise and postoperative follow-up in specific patients. METHODS: This cross-sectional study recruited 255 patients who underwent TKA in a Tertiary Hospital in Jinan City, China, from March to July 2022. Three months after having undergone TKA, participants' data were collected using the Numeric Pain Rating Scale, the Chinese version of the Tampa Scale of Kinesiophobia, the 10-item Kessler Psychological Distress Scale, Hospital for Special Surgery Knee-rating Scale, and Impact on Participation and Autonomy Questionnaire. Latent profile analysis was used to identify categories of patients' social participation. Multiple logistic regression analysis was used to analyze the influencing factors of the different subgroups. RESULTS: Three months after TKA, the patients were divided into three subgroups: low social participation group (17.9%), moderate social participation group (40.8%), and high social participation group (41.3%). The vast majority of patients who underwent TKA exhibited moderate-to-high level of social participation. The multiple logistic regression analysis results showed that age, degree of pain, knee function, and kinesiophobia were the influencing factors of the potential profiles of social participation in patients three months after TKA (p < 0.05). CONCLUSION: These results support a distinct categorical feature of social participation among patients three months after undergoing TKA. Medical staff need to provide targeted guidance according to the potential classification characteristics of social participation to improve the level of social participation and promote rehabilitation of patients.

Association Between Insomnia and Cognitive Frailty Among Older Patients With Chronic Heart Failure: Multiple Mediating Effects of Depressive Symptoms and Social Support.

BACKGROUND: Older patients with chronic heart failure (CHF) are prone to insomnia. Studies have shown that insomnia affects the onset of cognitive frailty and is also strongly associated with depressive symptoms and social support. However, information on how these factors interact to influence cognitive frailty remains underexplored. OBJECTIVE: Our aim in this study was to explore the multiple mediating roles of depressive symptoms and social support in the relationship between insomnia and cognitive frailty. METHODS: We recruited 300 hospitalized older patients with CHF to participate in this study. The participants completed the Athens Insomnia Scale, Geriatric Depression Scale, Montreal Cognitive Assessment, FRAIL Scale, and Social Support Rating Scale. The mediation hypothesis was tested using a multiple mediation model and bootstrapping method. RESULTS: In this study, 44% of the patients experienced insomnia, and 51.3% were in a state of cognitive frailty. Our main findings suggest that insomnia has an indirect effect on cognitive frailty through 2 pathways: the multiple mediating effects of depressive symptoms and social support, and a single mediating effect of depressive symptoms. The direct effect of insomnia on cognitive frailty is also significant. CONCLUSIONS: Older patients with CHF who experience insomnia tend to have more severe depressive symptoms, cognitive frailty, and poor social support. Thus, interventions to recognize insomnia early, improve depressive symptoms, and provide social support may reduce cognitive frailty in older patients with CHF. Longitudinal studies are necessary to further refine our findings and address the limitations of the current study.

Anxiety, depression, and post-traumatic stress disorder in nurses exposed to horizontal violence: a network analysis.

BACKGROUND: Horizontal violence can cause serious mental health problems for nurses, particularly anxiety, depression, and post-traumatic stress disorder. However, the intrinsic linkage mechanism between mental symptoms of anxiety, depression, and post-traumatic stress disorder in nurses exposed to horizontal violence is unclear. This study aims to elucidate the characteristics of anxiety, depression, and post-traumatic stress disorder networks among nurses with horizontal violence exposure. METHODS: Data for this cross-sectional study were obtained from the baseline portion of a short longitudinal survey conducted at four tertiary hospitals in Shandong Province, China. A total of 510 nurses with horizontal violence exposure completed the General Information Scale, the Negative Acts Questionnaire, the Seven-item Generalized Anxiety Disorder Scale, the Nine-item Patient Health Questionnaire, and the Four-item SPAN. The network model was constructed using network analysis. The expected influence and the bridge expected influence of nodes were calculated. The stability and accuracy of the network were estimated. RESULTS: The results show that A4 (Trouble relaxing) and P1 (Startle) had the highest expected influence in the network. D9 (Suicidality ideation) and A5 (Restlessness) were the key bridge symptoms. CONCLUSIONS: "Trouble relaxing", "Startle", "Suicidality ideation", and "Restlessness" are all mental symptoms that need to be urgently improved the most in nurses exposed to horizontal violence. Nursing administrators and policymakers should implement mental health intervention programs for these symptoms as early as possible to maximize nurses' mental health.

The association between team cohesion and performance: A network analysis of nurses.

Team cohesion, as a necessary condition for the cooperation and development of a team, has been shown to have a strong association with team performance. However, the mechanism of this internal correlation is unclear and more in-depth studies are lacking. The study aimed to explore the complex links between the dimensions of team cohesion and performance in nurses. A total of 1639 practice nurses from 118 nursing teams were included in this cross-sectional study. Data were collected using the Team Cohesion Scale (including consistency of affection, behavior, and cognition) and the Team Effectiveness Scale (including cooperation satisfaction, and task performance). Using network analysis, the team cohesion and performance network was constructed, and the strength and bridge strength of nodes were calculated. The results showed that the edges between team cohesion and performance dimensions were all positively correlated. Cooperation satisfaction and consistency of affection are the core variables in the network. Interventions targeting cooperation satisfaction and consistency of affection need to be developed at the team level to maximize team cohesion and performance among nurses.

A Universal Self-Propagating Synthesis of Aluminum-Based Oxyhalide Solid-State Electrolytes.

Inorganic solid-state electrolytes (SSEs) play a vital role in high-energy all-solid-state batteries (ASSBs). However, the current method of SSE preparation usually involves high-energy mechanical ball milling and/or a high-temperature annealing process, which is not suitable for practical application. Here, a facile strategy is developed to realize the scalable synthesis of cost-effective aluminum-based oxyhalide SSEs, which involves a self-propagating method by the exothermic reaction of the raw materials. This strategy enables the synthesis of various aluminum-based oxyhalide SSEs with tunable components and high ionic conductivities (over 10-3 S cm-1 at 25 °C) for different cations (Li+, Na+, Ag+). It is elucidated that the amorphous matrix, which mainly consists of various oxidized chloroaluminate species that provide numerous sites for smooth ion migration, is actually the key factor for the achieved high conductivities. Benefit from their easy synthesis, low cost, and low weight, the aluminum-based oxyhalide SSEs synthesized by our approach could further promote practical application of high-energy-density ASSBs.

PD-1 inhibitors combined with paclitaxel and cisplatin in first-line treatment of esophageal squamous cell carcinoma (ESCC): a network meta-analysis.

BACKGROUND: The combinations of PD-1 inhibitors with paclitaxel/cisplatinum (PD-1 + TP) and fluoropyrimidine/cisplatinum (PD-1 + FP) both have been shown to improve overall survival (OS) and progression-free survival (PFS) in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC). However, there is no consensus on which chemotherapy regimen combined with PD-1 has better efficacy. To deal with this important issue in the first-line treatment of patients with ESCC, a network meta-analysis (NMA) was performed. METHODS: Data were collected from eligible studies searched in Medline, Web of Science, PubMed, the Cochrane Library and Embase. The pooled hazard ratio (HR) for the OS, and PFS, odds ratio (OR) for the objective response rate (ORR) and ≥ 3 grade treatment-related adverse events (≥ 3TRAEs) were estimated to evaluate the efficacy of PD-1 inhibitors combined with TP or FP. RESULTS: Five RCTs and one retrospective study involving 3685 patients and evaluating four treatments were included in this NMA. Compared to other treatments, PD-1 + TP was better. For the PFS, the HRs for PD-1 + TP compared to PD-1 + FP, TP and FP were 0.59 (0.44, 0.80), 0.56 (0.51, 0.61) and 0.45 (0.37, 0.56) respectively. For the OS, PD-1 + TP was also a better treatment compared to other treatments. The HRs were 0.74 (0.56, 0.96), 0.64 (0.57, 0.71), 0.53 (0.43, 0.67) respectively. For the ORR, there was no significant difference between PD-1 + TP and PD-1 + FP, and the ORs were 1.2 (0.69, 2.11). Compare with TP and FP, PD-1 + TP had an obvious advantage, ORs were 2.5 (2.04, 3.04) and 2.95 (1.91, 4.63). For ≥ 3TRAEs, PD-1 + TP compared to other treatments, ORs were 1.34 (0.74, 2.46) and 1.13 (0.92, 1.38) and 2.23 (1.35, 3.69). CONCLUSION: PD-1 + TP significantly improved both PFS and OS compared to PD-1 + FP. Taking into account both efficacy and safety, PD-1 + TP may be a superior first-line treatment option for ESCC.

The Predictive Value of a New Inflammatory-Nutritional Score for Quality of Life after Laparoscopic Distal Gastrectomy for Gastric Cancer.

We explored the predictive value of various inflammatory-nutritional indicators for postoperative quality of life (QoL) in gastric cancer (GC) patients undergoing laparoscopic distal gastrectomy (LDG) and developed a novel inflammatory-nutritional score (INS). In this study, 156 GC patients who underwent LDG were included. We used multiple linear regression to analyze the correlation between postoperative QoL and inflammatory-nutritional indicators. Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to construct INS. Hemoglobin was positively correlated with physical functioning (ß =8.5; p = 0.003) and cognitive functioning (ß = 3.5; p = 0.038) 3 mo, after surgery. Prognostic nutritional index (PNI) was positively associated with global health status (ß =5.8; p = 0.043). Albumin-alkaline phosphatase ratio (AAPR) was negatively correlated with emotional functioning 12 mo, after surgery (ß = -5.7; p = 0.024). Neutrophil-lymphocyte ratio (NLR), Lymphocyte- monocyte ratio (LMR), AAPR, hemoglobin and PNI were selected using LASSO regression analysis to construct INS. The C-index values of the model in the training group and the validation group were 0.806 (95% CI, 0.719-0.893) and 0.758 (95% CI: 0.591-0.925), respectively. INS had particular predictive value for postoperative QoL in patients undergoing LDG and provided a reference for risk stratification and clinical practice.

Phellinus igniarius Polysaccharides Ameliorate Hyperglycemia by Modulating the Composition of the Gut Microbiota and Their Metabolites in Diabetic Mice.

Gut microbiota dysbiosis has been reported as a risk factor in the development of type 2 diabetes mellitus (T2DM). Polysaccharides from Phellinus igniarius (P. igniarius) possess various properties that help manage metabolic diseases; however, their underlying mechanism of action remains unclear. Therefore, in this study, we aimed to evaluate the effect of P. igniarius polysaccharides (SH-P) on improving hyperglycemia in mice with T2DM and clarified its association with the modulation of gut microbiota and their metabolites using 16S rDNA sequencing and liquid chromatography-mass spectrometry. Fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. SH-P supplementation alleviated hyperglycemia symptoms in T2DM mice, ameliorated gut dysbiosis, and significantly increased the abundance of Lactobacillus in the gut. Pathway enrichment analysis indicated that SH-P treatment altered metabolic pathways associated with the occurrence and development of diabetes. Spearman's correlation analysis revealed that changes in the dominant bacterial genera were significantly correlated with metabolite levels closely associated with hyperglycemia. Additionally, FMT significantly improved insulin sensitivity and antioxidative capacity and reduced inflammation and tissue injuries, indicating improved glucose homeostasis. These results indicate that the ameliorative effects of SH-P on hyperglycemia are associated with the modulation of gut microbiota composition and its metabolites.

The mediating effects of social support and depressive symptoms on activities of daily living and social frailty in older patients with chronic heart failure.

OBJECTIVES: To investigate the level of social frailty (SF) in older patients with chronic heart failure (CHF) and examine the mediating role of social support and depressive symptoms between activities of daily living and SF. METHODS: Using a convenience sampling method, 205 older patients with CHF were recruited from China between November 2021 and May 2022. Activities of daily living, social support, depressive symptoms, and SF were assessed using a self-administered questionnaire. Data were analyzed using structural equation modeling. RESULTS: The final model obtained a good fit. Activities of daily living in older patients with CHF were directly related to SF. The multiple mediation analysis revealed that the relationship between activities of daily living and SF was mediated by social support (effect: -0.010, 95% CI [-0.021, -0.003]) and depressive symptoms (effect: -0.011, 95% CI [-0.019, -0.005) separately, and serially (effect: -0.007, 95% CI [-0.012, -0.003). CONCLUSIONS: Social support and depressive symptoms are multiple mediating variables in the relationship between activities of daily living and SF. Activities of daily living can improve patients' SF through social support and depressive symptoms.

Research progress of cathepsin B in brain aging and Alzheimer's diseases.

Cathepsin B (CatB), a cysteine protease derived from lysosomes, was initially thought to non-selectively degrade proteins from phagocytosis and autophagy in lysosomes. However, CatB has been demonstrated to selectively degrade and specifically activate target proteins, thereby regulating the process of physiological and pathological responses. The expression, enzymatic activity, and cellular localization of CatB are significantly altered in brain aging and age-related neurodegenerative diseases. Therefore, the pathological function of CatB has attracted much attention in neuroscience research. In this review, we systematically summarize the molecular functions of CatB in brain aging and Alzheimer's disease and discuss the current problems in neuropathological studies of CatB, which lay a foundation for a comprehensive understanding of the pathogenesis of aging and Alzheimer's disease.

The Universal Super Cation-Conductivity in Multiple-cation Mixed Chloride Solid-State Electrolytes.

As exciting candidates for next-generation energy storage, all-solid-state lithium batteries (ASSLBs) are highly dependent on advanced solid-state electrolytes (SSEs). Here, using cost-effective LaCl3 and CeCl3 lattice (UCl3 -type structure) as the host and further combined with a multiple-cation mixed strategy, we report a series of UCl3 -type SSEs with high room-temperature ionic conductivities over 10-3  S cm-1 and good compatibility with high-voltage oxide cathodes. The intrinsic large-size hexagonal one-dimensional channels and highly disordered amorphous phase induced by multi-metal cation species are believed to trigger fast multiple ionic conductions of Li+ , Na+ , K+ , Cu+ , and Ag+ . The UCl3 -type SSEs enable a stable prototype ASSLB capable of over 3000 cycles and high reversibility at -30 °C. Further exploration of the brand-new multiple-cation mixed chlorides is likely to lead to the development of advanced halide SSEs suitable for ASSLBs with high energy density.

Adipose-derived stem cells regulate metabolic homeostasis and delay aging by promoting mitophagy.

Tissues undergo a process of degeneration as the body ages. Mesenchymal stem cells (MSCs) have been found to have major potential in delaying the aging process in tissues and organs. However, the mechanism underlying the anti-aging effects of MSC is not clear which limits clinical applications. In this study, we used adipose-derived mesenchymal stem cells (ADSCs) to perform anti-aging treatments on senescent cells and progeroid animal models. Following intervention with ADSCs, replicative senescence was delayed and metabolic homeostasis was transformed from catabolism to anabolism. Metabolomic tests were used to analyze different metabolites. We found that ADSCs acted to accelerate mitophagy which eliminated intracellular ROS and improved the quality of mitochondria. These processes acted to regulate the cellular metabolic homeostasis and ultimately delayed the process of aging. Allogeneic stem cell therapy in a Progeria animal model (DNA polymerase gamma (POLG) knockin, mitochondrial dysfunction) also showed that ADSC therapy can improve alopecia and kyphosis by promoting mitophagy. Our research confirms for the first time that allogeneic stem cell therapy can improve aging-related symbols and phenotypes through mitochondrial quality control. These results are highly significant for the future applications of stem cells in aging-related diseases.

Three-Dimensional Silver-Containing Polyoxotungstate Frameworks for Photocatalytic Aerobic Oxidation of Benzyl Alcohol.

Photocatalytic organic transformation derived by functionalized polyoxometalate (POM)-based metal-organic frameworks provides a feasible route for fine chemical synthesis. Herein, three kinds of photoactive three-dimensional silver-containing polyoxotungstate frameworks are synthesized with the formulas [Ag3L2(OH)][Na(H2O)0.5][PW12O40]·H2O (1), [Ag4L3][SiW12O40] (2), and [Ag(H2O)][Ag4L3][BW12O40]·9H2O (3) (L = 1,4-di(4H-1,2,4-triazol-4-yl)benzene). In compounds 1-3, the cationic Ag-triazole clusters with diverse nuclei serve as nodes to assemble with rigid bridging ligands (L) and polyoxoanions to extend into stable three-dimensional frameworks, in which Keggin-type anions act as guests or pendants. When using them as heterogeneous photocatalysts, compounds 1-3 show high catalytic activity and selectivity for the photocatalytic aerobic oxidation of benzyl alcohol to benzoic acid under 10 W 365 nm light irradiation. Among them, compound 1 exhibits the highest performance with ca. 99% benzyl alcohol conversion and 99% selectivity of benzoic acid in 9 h. Compounds 2 and 3 show ca. 79 and 88% conversions of benzyl alcohol, respectively, which are higher than those of the individual Keggin-type precursors. Moreover, mechanism investigation suggests that the synergistic cooperation occurring between cationic Ag-triazole clusters and Keggin-type polyoxoanions modulates the energy band structures of compounds 1-3, resulting in the efficient separation of photogenerated carriers and accelerating the aerobic oxidation of benzyl alcohol. This work provides some important guidance for the design and development of efficient POM-based photocatalysts for practical organic transformation.

Polyoxometalate-Incorporated Metal-Organic Network as a Heterogeneous Catalyst for Selective Oxidation of Aryl Alkenes.

Selective oxidation of aryl alkenes is important for chemical synthesis reactions, in which the key lies in the rational design of efficient catalysts. Herein, four polyoxometalate (POM)-incorporated metal-organic networks, with the formulas of [Co(ttb)(H2O)3]2[SiMo12O40]·2H2O (1), [Co(ttb)(H2O)2]2[SiW12O40]·8H2O (2), [Zn(Httb)(H2ttb)][BW12O40]·9H2O (3) and {[Zn(H2O)3(ttb)]4[Zn3(H2O)6]}[H3SiW10.5Zn1.5O40]2·24H2O (4) (ttb = 1,3,5-tri(1,2,4-triazol-1-ylmethyl)-2,4,6-trimethylbenzene), were hydrothermally synthesized and structurally characterized. Structural analysis showed that compound 1 consists of a POM-encapsulated three-dimensional (3-D) supramolecular framework; compound 2 is composed of a POM-supported 3-D coordination network; and compounds 3-4 show POM-incorporated 3-D supramolecular networks. Using selective catalytic oxidation of styrene as the model reaction, compounds 1-4 as heterogeneous catalysts display excellent performance with the double advantages of high styrene conversion and benzaldehyde selectivity owing to the synergistic effect among POM anions and transition metal (TM) centers. Among them, compound 1 exhibits the highest performance with ca. 96% styrene conversion and ca. 99% benzaldehyde selectivity in 3 h. In addition, compound 1 also displays excellent substrate compatibility, good reusability, and structural stability. Thus, a plausible reaction pathway for the selective oxidation of styrene is proposed. This study on the structure-function relationship paves a way for the rational design of POM-based heterogeneous catalysts for important catalysis applications.

Anionic Effect on Enhancing the Stability of a Solid Electrolyte Interphase Film for Lithium Deposition on Graphite.

Graphitic carbons and their lithium composites have been utilized as lithium deposition substrates to address issues such as the huge volume variation and dendritic growth of lithium. However, new problems have appeared, including the severe exfoliation of the graphite particles and the instability of the solid electrolyte interphase (SEI) film when metallic lithium is plated on the graphite. Herein, we enhance the stability of the SEI film on the graphite substrate for lithium deposition in an electrolyte of lithium bis(fluorosulfonyl)imide (LiFSI) dissolved in the carbonate solvent, thereby improving the lithium plating/stripping cycle on it. The FSI- anion was found to be responsible for the formation of a compact SEI film under the lithium plating potential and could protect the graphite substrate. These findings refresh the understanding of the SEI stability and provide a suggestion on the design and development of electrolytes for the lithium batteries.

Competitive Solvation Enhanced Stability of Lithium Metal Anode in Dual-Salt Electrolyte.

The development of lithium metal batteries is hindered by the low Coulombic efficiency and poor cycling stability of the metallic lithium. The introduction of consumptive LiNO3 as an additive can improve the cycling stability, but its low solubility in the carbonate electrolytes makes this strategy impractical for long-term cycling. Herein we propose LiNO3 as a cosalt in the LiPF6-LiNO3 dual-salt electrolyte to enhance the cycling stability of lithium plating/stripping. Competitions among the components and the resultant substitution of NO3- for PF6- in the solvation shell facilitate the formation of a Li3N-rich solid electrolyte interphase (SEI) film and suppress the LiPF6 decomposition. The highly Li+ conductive and stable SEI film effectively tailors the lithium nucleation, suppresses the formation of lithium dendrites, and improves the cycling performance. The competitive solvation has profound importance for the design of a complex electrolyte to meet the multiple requirements of secondary lithium batteries.

Antitumor effects of the small molecule DMAMCL in neuroblastoma via suppressing aerobic glycolysis and targeting PFKL.

BACKGROUND: Neuroblastoma (NB) is a common solid malignancy in children that is associated with a poor prognosis. Although the novel small molecular compound Dimethylaminomicheliolide (DMAMCL) has been shown to induce cell death in some tumors, little is known about its role in NB. METHODS: We examined the effect of DMAMCL on four NB cell lines (NPG, AS, KCNR, BE2). Cellular confluence, survival, apoptosis, and glycolysis were detected using Incucyte ZOOM, CCK-8 assays, Annexin V-PE/7-AAD flow cytometry, and Seahorse XFe96, respectively. Synergistic effects between agents were evaluated using CompuSyn and the effect of DMAMCL in vivo was evaluated using a xenograft mouse model. Phosphofructokinase-1, liver type (PFKL) expression was up- and down-regulated using overexpression plasmids or siRNA. RESULTS: When administered as a single agent, DMAMCL decreased cell proliferation in a time- and dose-dependent manner, increased the percentage of cells in SubG1 phase, and induced apoptosis in vitro, as well as inhibiting tumor growth and prolonging survival in tumor-bearing mice (NGP, BE2) in vivo. In addition, DMAMCL exerted synergistic effects when combined with etoposide or cisplatin in vitro and displayed increased antitumor effects when combined with etoposide in vivo compared to either agent alone. Mechanistically, DMAMCL suppressed aerobic glycolysis by decreasing glucose consumption, lactate excretion, and ATP production, as well as reducing the expression of PFKL, a key glycolysis enzyme, in vitro and in vivo. Furthermore, PFKL overexpression attenuated DMAMCL-induced cell death, whereas PFKL silencing promoted NB cell death. CONCLUSIONS: The results of this study suggest that DMAMCL exerts antitumor effects on NB both in vitro and in vivo by suppressing aerobic glycolysis and that PFKL could be a potential target of DMAMCL in NB.