Self-terminating, heterogeneous solid-electrolyte interphase enables reversible Li-ether cointercalation in graphite anodes.

Ether solvents are suitable for formulating solid-electrolyte interphase (SEI)-less ion-solvent cointercalation electrolytes in graphite for Na-ion and K-ion batteries. However, ether-based electrolytes have been historically perceived to cause exfoliation of graphite and cell failure in Li-ion batteries. In this study, we develop strategies to achieve reversible Li-solvent cointercalation in graphite through combining appropriate Li salts and ether solvents. Specifically, we design 1M LiBF4 1,2-dimethoxyethane (G1), which enables natural graphite to deliver ~91% initial Coulombic efficiency and >88% capacity retention after 400 cycles. We captured the spatial distribution of LiF at various length scales and quantified its heterogeneity. The electrolyte shows self-terminated reactivity on graphite edge planes and results in a grainy, fluorinated pseudo-SEI. The molecular origin of the pseudo-SEI is elucidated by ab initio molecular dynamics (AIMD) simulations. The operando synchrotron analyses further demonstrate the reversible and monotonous phase transformation of cointercalated graphite. Our findings demonstrate the feasibility of Li cointercalation chemistry in graphite for extreme-condition batteries. The work also paves the foundation for understanding and modulating the interphase generated by ether electrolytes in a broad range of electrodes and batteries.

Influence of Interlayer Cation Ordering on Na Transport in P2-Type Na0.67-xLiy Ni0.33-zMn0.67+zO2 for Sodium-Ion Batteries.

P2-type Na2/3Ni1/3Mn2/3O2 (PNNMO) has been extensively studied because of its desirable electrochemical properties as a positive electrode for sodium-ion batteries. PNNMO exhibits intralayer transition-metal ordering of Ni and Mn and intralayer Na+/vacancy ordering. The Na+/vacancy ordering is often considered a major impediment to fast Na+ transport and can be affected by transition-metal ordering. We show by neutron/X-ray diffraction and density functional theory (DFT) calculations that Li doping (Na2/3Li0.05Ni1/3Mn2/3O2, LFN5) promotes ABC-type interplanar Ni/Mn ordering without disrupting the Na+/vacancy ordering and creates low-energy Li-Mn-coordinated diffusion pathways. A structure model is developed to quantitatively identify both the intralayer cation mixing and interlayer cationic stacking fault densities. Quasielastic neutron scattering reveals that the Na+ diffusivity in LFN5 is enhanced by an order of magnitude over PNNMO, increasing its capacity at a high current. Na2/3Ni1/4Mn3/4O2 (NM13) lacks Na+/vacancy ordering but has diffusivity comparable to that of LFN5. However, NM13 has the smallest capacity at a high current. The high site energy of Mn-Mn-coordinated Na compared to that of Ni-Mn and higher density of Mn-Mn-coordinated Na+ sites in NM13 disrupts the connectivity of low-energy Ni-Mn-coordinated diffusion pathways. These results suggest that the interlayer ordering can be tuned through the control of composition, which has an equal or greater impact on Na+ diffusion than the Na+/vacancy ordering.

Risdiplam-Treated Infants with Type 1 Spinal Muscular Atrophy versus Historical Controls.

BACKGROUND: Type 1 spinal muscular atrophy (SMA) is a progressive neuromuscular disease characterized by an onset at 6 months of age or younger, an inability to sit without support, and deficient levels of survival of motor neuron (SMN) protein. Risdiplam is an orally administered small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein in blood. METHODS: We conducted an open-label study of risdiplam in infants with type 1 SMA who were 1 to 7 months of age at enrollment. Part 1 of the study (published previously) determined the dose to be used in part 2 (reported here), which assessed the efficacy and safety of daily risdiplam as compared with no treatment in historical controls. The primary end point was the ability to sit without support for at least 5 seconds after 12 months of treatment. Key secondary end points were a score of 40 or higher on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; range, 0 to 64, with higher scores indicating better motor function), an increase of at least 4 points from baseline in the CHOP-INTEND score, a motor-milestone response as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2), and survival without permanent ventilation. For the secondary end points, comparisons were made with the upper boundary of 90% confidence intervals for natural-history data from 40 infants with type 1 SMA. RESULTS: A total of 41 infants were enrolled. After 12 months of treatment, 12 infants (29%) were able to sit without support for at least 5 seconds, a milestone not attained in this disorder. The percentages of infants in whom the key secondary end points were met as compared with the upper boundary of confidence intervals from historical controls were 56% as compared with 17% for a CHOP-INTEND score of 40 or higher, 90% as compared with 17% for an increase of at least 4 points from baseline in the CHOP-INTEND score, 78% as compared with 12% for a HINE-2 motor-milestone response, and 85% as compared with 42% for survival without permanent ventilation (P<0.001 for all comparisons). The most common serious adverse events were pneumonia, bronchiolitis, hypotonia, and respiratory failure. CONCLUSIONS: In this study involving infants with type 1 SMA, risdiplam resulted in higher percentages of infants who met motor milestones and who showed improvements in motor function than the percentages observed in historical cohorts. Longer and larger trials are required to determine the long-term safety and efficacy of risdiplam in infants with type 1 SMA. (Funded by F. Hoffmann-La Roche; FIREFISH ClinicalTrials.gov number, NCT02913482.).

Recent Progress in Anti-Tumor Nanodrugs Based on Tumor Microenvironment Redox Regulation.

The growth state of tumor cells is strictly affected by the specific abnormal redox status of the tumor microenvironment (TME). Moreover, redox reactions at the biological level are also central and fundamental to essential energy metabolism reactions in tumors. Accordingly, anti-tumor nanodrugs targeting the disruption of this abnormal redox homeostasis have become one of the hot spots in the field of nanodrugs research due to the effectiveness of TME modulation and anti-tumor efficiency mediated by redox interference. This review discusses the latest research results of nanodrugs in anti-tumor therapy, which regulate the levels of oxidants or reductants in TME through a variety of therapeutic strategies, ultimately breaking the original "stable" redox state of the TME and promoting tumor cell death. With the gradual deepening of study on the redox state of TME and the vigorous development of nanomaterials, it is expected that more anti-tumor nano drugs based on tumor redox microenvironment regulation will be designed and even applied clinically.

In-Situ Self-Assembly Dipole Shielding Layer Toward Efficient and Stable Inorganic Perovskite Solar Cells.

Despite CsPbI2.75Br0.25 inorganic perovskites exhibit high potential for single-junction and/or tandem solar cells, unexpected non-radiative recombination, and mismatched interfacial band alignment within the inorganic perovskite solar cells (PSCs) disadvantageously affect their photovoltaic performance. Rational design of the dipole shielding layer (DSL) is vital to realize a win-win situation for the defect passivation and band alignment. Herein, A-site dipole molecules, that is, neopentylamine and 2-methylbutylamine, are employed for in-situ self-assembly of a thus-far unreported DSL at the interface between 3D perovskite and hole transport layer. The as-prepared DSL demonstrates a 2D RP phase perovskite and the lattice-matching structurally-stable DSL@3D perovskite enables to alleviate the unexpected surface defects and suppress the spontaneous non-radiative recombination by means of effectively tuning the surface work function via regulating the dipole moment length and Van der Waals gap. Accordingly, the top dipole-modified inorganic PSCs exhibit a champion power conversion efficiency (PSC) as high as 19.77% and a fill factor over 83%. Equally importantly, the corresponding solar cells demonstrate a remarkable enhanced stability, maintaining 90% of its initial efficiency for more than 1200 h without encapsulation under a 20% ± 5% relative humidity.

Localized high-concentration electrolytes get more localized through micelle-like structures.

Liquid electrolytes in batteries are typically treated as macroscopically homogeneous ionic transport media despite having a complex chemical composition and atomistic solvation structures, leaving a knowledge gap of the microstructural characteristics. Here, we reveal a unique micelle-like structure in a localized high-concentration electrolyte, in which the solvent acts as a surfactant between an insoluble salt in a diluent. The miscibility of the solvent with the diluent and simultaneous solubility of the salt results in a micelle-like structure with a smeared interface and an increased salt concentration at the centre of the salt-solvent clusters that extends the salt solubility. These intermingling miscibility effects have temperature dependencies, wherein a typical localized high-concentration electrolyte peaks in localized cluster salt concentration near room temperature and is used to form a stable solid-electrolyte interphase on a Li metal anode. These findings serve as a guide to predicting a stable ternary phase diagram and connecting the electrolyte microstructure with electrolyte formulation and formation protocols of solid-electrolyte interphases for enhanced battery cyclability.

A critical role for transcription factor Smad4 in T cell function that is independent of transforming growth factor ß receptor signaling.

Transforming growth factor-beta (TGF-ß) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-ß signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-ßR) deletion and compromised T-cell-mediated tumor rejection. Although Smad4 was dispensable for T cell generation, homeostasis, and effector function, it was essential for T cell proliferation after activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-ßR-independent role for Smad4 in promoting T cell function, autoimmunity, and anti-tumor immunity.

Measurement properties of the EQ-5D-Y-3L, PedsQL 4.0, and PROMIS-25 Profile v2.0 in pediatric patients with spinal muscular atrophy.

OBJECTIVE: The objective of this study was to examine the psychometric properties of the EQ-5D-Y-3 L, Patient Reported Outcomes Measurement System 25-item version profile v2.0 (PROMIS-25), and Pediatric Quality of Life Inventory™ version 4.0 Generic Core Scale (PedsQL 4.0) in Chinese pediatric patients with spinal muscular atrophy (SMA). METHODS: The data used in this study were obtained via a web-based cross-sectional survey. Parents of pediatric patients with SMA completed the proxy-reported EQ-5D-Y-3 L, PedsQL 4.0, and PROMIS-25 measures. Information about socioeconomic and health status was also obtained. The ceiling and floor effects, factorial structure, convergent validity, and known-group validity of the three measures were assessed. RESULTS: Three hundred and sixty-three parents of children aged from 5 to 12 completed the questionnaires. Strong floor effects were observed for the physical function components of the PROMIS-25 (41.3%) and PedsQL 4.0 (67.8%). For EQ-5D-Y-3 L, 84.6% of the respondents reported having "a lot of" problems with the dimensions "walking" and "looking after myself." Minimal ceiling or floor effects were observed for the EQ-5D-Y-3 L index value. The confirmatory factor analysis supported a six-factor structure for the PROMIS-25, but did not support a four-factor structure for the PedsQL 4.0. All hypothesized correlations of the dimensions among the three measures were confirmed, with coefficients ranging from 0.28 to 0.68. Analysis of variance showed that EQ-5D-Y-3 L demonstrated better known-group validity than the other two measures in 14 out of 16 comparisons. CONCLUSIONS: The EQ-5D-Y-3 L showed better discriminant power than the other two measures. The physical health dimensions of all three measures showed the significant floor effects. These findings provide valuable insights into the effectiveness of these measures at capturing and quantifying the impact of SMA on patients' health-related quality of life.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Biosafe cerium oxide nanozymes protect human pluripotent stem cells and cardiomyocytes from oxidative stress.

BACKGROUND: Cardiovascular diseases (CVDs) have the highest mortality worldwide. Human pluripotent stem cells (hPSCs) and their cardiomyocyte derivatives (hPSC-CMs) offer a valuable resource for disease modeling, pharmacological screening, and regenerative therapy. While most CVDs are linked to significant over-production of reactive oxygen species (ROS), the effects of current antioxidants targeting excessive ROS are limited. Nanotechnology is a powerful tool to develop antioxidants with improved selectivity, solubility, and bioavailability to prevent or treat various diseases related to oxidative stress. Cerium oxide nanozymes (CeONZs) can effectively scavenge excessive ROS by mimicking the activity of endogenous antioxidant enzymes. This study aimed to assess the nanotoxicity of CeONZs and their potential antioxidant benefits in stressed human embryonic stem cells (hESCs) and their derived cardiomyocytes (hESC-CMs). RESULTS: CeONZs demonstrated reliable nanosafety and biocompatibility in hESCs and hESC-CMs within a broad range of concentrations. CeONZs exhibited protective effects on the cell viability of hESCs and hESC-CMs by alleviating excessive ROS-induced oxidative stress. Moreover, CeONZs protected hESC-CMs from doxorubicin (DOX)-induced cardiotoxicity and partially ameliorated the insults from DOX in neonatal rat cardiomyocytes (NRCMs). Furthermore, during hESCs culture, CeONZs were found to reduce ROS, decrease apoptosis, and enhance cell survival without affecting their self-renewal and differentiation potential. CONCLUSIONS: CeONZs displayed good safety and biocompatibility, as well as enhanced the cell viability of hESCs and hESC-CMs by shielding them from oxidative damage. These promising results suggest that CeONZs may be crucial, as a safe nanoantioxidant, to potentially improve the therapeutic efficacy of CVDs and be incorporated into regenerative medicine.

Added Value of Frequency of Imaging Markers for Prediction of Outcome After Intracerebral Hemorrhage: A Secondary Analysis of Existing Data.

BACKGROUND: Frequency of imaging markers (FIM) has been identified as an independent predictor of hematoma expansion in patients with intracerebral hemorrhage (ICH), but its impact on clinical outcome of ICH is yet to be determined. The aim of the present study was to investigate this association. METHODS: This study was a secondary analysis of our prior research. The data for this study were derived from six retrospective cohorts of ICH from January 2018 to August 2022. All consecutive study participants were examined within 6 h of stroke onset on neuroimaging. FIM was defined as the ratio of the number of imaging markers on noncontrast head tomography (i.e., hypodensities, blend sign, and island sign) to onset-to-neuroimaging time. The primary poor outcome was defined as a modified Rankin Scale score of 3-6 at 3 months. RESULTS: A total of 1253 patients with ICH were included for final analysis. Among those with available follow-up results, 713 (56.90%) exhibited a poor neurologic outcome at 3 months. In a univariate analysis, FIM was associated with poor prognosis (odds ratio 4.36; 95% confidence interval 3.31-5.74; p < 0.001). After adjustment for age, Glasgow Coma Scale score, systolic blood pressure, hematoma volume, and intraventricular hemorrhage, FIM was still an independent predictor of worse prognosis (odds ratio 3.26; 95% confidence interval 2.37-4.48; p < 0.001). Based on receiver operating characteristic curve analysis, a cutoff value of 0.28 for FIM was associated with 0.69 sensitivity, 0.66 specificity, 0.73 positive predictive value, 0.62 negative predictive value, and 0.71 area under the curve for the diagnosis of poor outcome. CONCLUSIONS: The metric of FIM is associated with 3-month poor outcome after ICH. The novel indicator that helps identify patients who are likely within the 6-h time window at risk for worse outcome would be a valuable addition to the clinical management of ICH.

Carbon dioxide production index (VCO2i) predicts hyperlactatemia during cardiopulmonary bypass in pediatric carDiac surGery (pGDP- VCO2i): Study protocol for a nested case-control trial.

BACKGROUND: Hyperlactatemia (HL) during cardiopulmonary bypass (CPB) is relatively frequent in infants and associates with increased morbidity and mortality. Studies on adults have shown that carbon dioxide production index (VCO2i) during CPB is linked to the occurrence of HL, with 'critical thresholds' for VCO2i reported to be 60 mL/min/m2. However, considering infants have a higher metabolic rate and lower tolerance to hypoxia, the critical threshold of VCO2i in infants cannot be replied to the existing adults' standards. The objective of this study is to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in infants. METHODS: VCO2i predicts hyperlactatemia during cardiopulmonary bypass in pediatric cardiac surgery (pGDP-VCO2i) is a nested case-control study. A cohort of consecutive pediatric patients of less than 3 years of age, undergoing congenital cardiac surgeries between May 2021 and December 2023 in West China Hospital will be enrolled. The VCO2i levels of each patient will be recorded every 5 min during CPB. The primary outcome is the rate of HL. The infants will be divided into two groups based on the presence or not of HL. Pre- and intraoperative factors will be tested for independent association with HL. Then, we will make an analysis, and the critical value of VCO2i will be obtained. The postoperative outcome of patients with or without HL will be compared. DISCUSSION: This will be the first trial to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in pediatrics. The results of this study are expected to lay a foundation for clinical application of goal-directed perfusion (GDP) management strategy, and optimize the perfusion strategy and improve the prognosis of pediatric patients undergoing cardiac surgery. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100044296 on 16 March 2021.

[Mechanism of Biejiajian Pills against non-alcoholic steatohepatitis based on lipidomics].

This study aims to explore the potential mechanism of Biejiajian Pills in the treatment of non-alcoholic steatohepatitis(NASH) based on lipidomics. A mouse model of NASH was induced by high-fat/high cholesterol diet, and the mice of the normal group were fed with a normal diet. The therapeutic efficacy of Biejiajian Pills against NASH was evaluated through biochemical indexes in both of serum and liver, as well as the hepatic histopathology. Lipid metabolites in the liver were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)-based lipidomics. Then the partial least-squares discriminant analysis, t-test and receiver operating characteristic curve analysis were performed to screen the differential lipid metabolites and the main biomarkers. The proteins and genes involved in the lipid metabolism and inflammatory response were detected by Western blot and qPCR. The results demonstrated that Biejiajian Pills notably lowered the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) in the serum and the levels of triglyceride(TG) and total cholesterol(TC) in the liver tissue. In addition, Biejiajian Pills alleviated the lipid accumulation, hepatocyte ballooning, and liver fibrosis. Lipidomics revealed that Biejiajian Pills regulated the content of 11 biomarkers including phosphatidyl choline(PC), phosphatidyl ethanolamine(PE), sphingomyelin(SM), and ceramide(Cer). The results of Western blot and qPCR demonstrated that Biejiajian Pills regulated the expression of sterol regulatory element-binding protein 1(SREBP1), peroxisome proliferator-activated receptor gamma(PPARγ) and phospho-AMP-activated protein kinase(p-AMPK), and the mRNA level of fatty acid translocase 36 gene(Cd36), Pparγ, cardiolipin synthase 1 gene(Crls1), and phospholipase Cß2 gene(Plcß2). Furthermore, Biejiajian Pills displayed inhibitory effects on phospho-p38 MAPK(p-p38 MAPK) and phospho-ERK1/2(p-ERK1/2) and the mRNA levels of interleukin-6 gene(Il-6), interleukin-1ß gene(Il-1ß) and tumor necrosis factor-α gene(Tnf-α). In conclusion, Biejiajian Pills could alleviate the lipid metabolism disorders and regulate the expression of SREBP1, PPARγ, and p-AMPK and the mRNA levels of pro-inflammatory cytokines.

DeepASDPred: a CNN-LSTM-based deep learning method for Autism spectrum disorders risk RNA identification.

BACKGROUND: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by difficulty communicating with society and others, behavioral difficulties, and a brain that processes information differently than normal. Genetics has a strong impact on ASD associated with early onset and distinctive signs. Currently, all known ASD risk genes are able to encode proteins, and some de novo mutations disrupting protein-coding genes have been demonstrated to cause ASD. Next-generation sequencing technology enables high-throughput identification of ASD risk RNAs. However, these efforts are time-consuming and expensive, so an efficient computational model for ASD risk gene prediction is necessary. RESULTS: In this study, we propose DeepASDPerd, a predictor for ASD risk RNA based on deep learning. Firstly, we use K-mer to feature encode the RNA transcript sequences, and then fuse them with corresponding gene expression values to construct a feature matrix. After combining chi-square test and logistic regression to select the best feature subset, we input them into a binary classification prediction model constructed by convolutional neural network and long short-term memory for training and classification. The results of the tenfold cross-validation proved our method outperformed the state-of-the-art methods. Dataset and source code are available at https://github.com/Onebear-X/DeepASDPred is freely available. CONCLUSIONS: Our experimental results show that DeepASDPred has outstanding performance in identifying ASD risk RNA genes.

Reversible Switch in Charge Storage Enabled by Selective Ion Transport in Solid Electrolyte Interphase.

Solid-electrolyte interphases (SEIs) in advanced rechargeable batteries ensure reversible electrode reactions at extreme potentials beyond the thermodynamic stability limits of electrolytes by insulating electrons while allowing the transport of working ions. Such selective ion transport occurs naturally in biological cell membranes as a ubiquitous prerequisite of many life processes and a foundation of biodiversity. In addition, cell membranes can selectively open and close the ion channels in response to external stimuli (e.g., electrical, chemical, mechanical, and thermal), giving rise to "gating" mechanisms that help manage intracellular reactions. We wondered whether the chemistry and structure of SEIs can mimic those of cell membranes, such that ion gating can be replicated. That is, can SEIs realize a reversible switching between two electrochemical behaviors, i.e., the ion intercalation chemistry of batteries and the ion adsorption of capacitors? Herein, we report such SEIs that result in thermally activated selective ion transport. The function of open/close gate switches is governed by the chemical and structural dynamics of SEIs under different thermal conditions, with precise behaviors as conducting and insulating interphases that enable battery and capacitive processes within a finite temperature window. Such an ion gating function is synergistically contributed by Arrhenius-activated ion transport and SEI dissolution/regrowth. Following the understanding of this new mechanism, we then develop an electrochemical method to heal the SEI layer in situ. The knowledge acquired in this work reveals the possibility of hitherto unknown biomimetic properties of SEIs, which will guide us to leverage such complexities to design better SEIs for future battery chemistries.

circ_rac GTPase-Activating Protein 1 Facilitates Stemness and Metastasis of Non-Small Cell Lung Cancer via Polypyrimidine Tract-Binding Protein 1 Recruitment to Promote Sirtuin-3-Mediated Replication Timing Regulatory Factor 1 Deacetylation.

Circular RNAs have been identified as diagnostic and therapeutic targets for various tumors. The expression of circ_rac GTPase-activating protein 1 (circRACGAP1) is reported to drive the development of non-small cell lung cancer (NSCLC). This study further explored the potential mechanism of circRACGAP1-mediated development of NSCLC. The circRACGAP1 level was detected by quantitative RT-PCR. Sphere formation, CD133-positive cell percentage, and expression of octamer-binding transcription factor 4, Sox2, Nanog, and CD133 were detected to evaluate stemness of NSCLC. Migration and invasion were determined using wound healing and transwell assays. Protein expression was measured using Western blotting. The molecular mechanism was evaluated using RNA pull-down, RNA immunoprecipitation, and coimmunoprecipitation assays. In vivo tumor growth and metastasis were determined in nude mice. circRACGAP1 was highly expressed in NSCLC and was associated with stemness marker Sox2 expression. The stemness, metastasis, and epithelial mesenchymal transformation were repressed in circRACGAP1-depleted NSCLC cells. Mechanistically, circRACGAP1 recruited RNA-binding protein polypyrimidine tract-binding protein 1 to enhance the stability and expression of sirtuin-3 (SIRT3), which subsequently led to replication timing regulatory factor 1 (RIF1) deacetylation and activation of the Wnt/ß-catenin pathway. circRACGAP1 overexpression counteracted SIRT3 or RIF1 knockdown-mediated inhibition in stemness and metastasis of NSCLC cells. The in vivo tumor growth and metastasis were repressed by circRACGAP1 depletion. Patients with NSCLC with a higher serum exosomal circRACGAP1 level had a lower overall survival rate. In conclusion, circRACGAP1 facilitated stemness and metastasis of NSCLC cells through the recruitment of polypyrimidine tract-binding protein 1 to promote SIRT3-mediated RIF1 deacetylation. Our results uncover a novel regulatory mechanism of circRACGAP1 in NSCLC and identify circRACGAP1 as a promising therapeutic target.

Comparative proteome profiles of Polygonatum cyrtonema Hua rhizomes (Rhizoma Ploygonati) in response to different levels of cadmium stress.

BACKGROUND: The Polygonatum cyrtonema Hua rhizomes (also known as Rhizoma Polygonati, RP) are consumed for their health benefits. The main source of the RP is wild P. cyrtonema populations in the Hunan province of China. However, the soil Cadmium (Cd) content in Huanan is increasing, thus increasing the risks of Cd accumulation in RP which may end up in the human food chain. To understand the mechanism of Cd accumulation and resistance in P. cyrtonema, we subjected P. cyrtonema plants to four levels of Cd stress [(D2) 1, (D3) 2, (D4) 4, and (D5) 8 mg/kg)] compared to (D1) 0.5 mg/kg. RESULTS: The increase in soil Cd content up to 4 mg/kg resulted in a significant increase in tissue (root hair, rhizome, stem, and leaf) Cd content. The increase in Cd concentration variably affected the antioxidant enzyme activities. We could identify 14,171 and 12,115 protein groups and peptides, respectively. There were 193, 227, 260, and 163 differentially expressed proteins (DEPs) in D2, D3, D4, and D5, respectively, compared to D1. The number of downregulated DEPs increased with an increase in Cd content up to 4 mg/kg. These downregulated proteins belonged to sugar biosynthesis, amino acid biosynthesis-related pathways, and secondary metabolism-related pathways. Our results indicate that Cd stress increases ROS generation, against which, different ROS scavenging proteins are upregulated in P. cyrtonema. Moreover, Cd stress affected the expression of lipid transport and assembly, glycolysis/gluconeogenesis, sugar biosynthesis, and ATP generation. CONCLUSION: These results suggest that an increase in soil Cd content may end up in Huangjing. Cadmium stress initiates expression changes in multiple pathways related to energy metabolism, sugar biosynthesis, and secondary metabolite biosynthesis. The proteins involved in these pathways are potential candidates for manipulation and development of Cd stress-tolerant genotypes.

Temperature Dependent Hydrogen Bond Toward High Emission in an Emerging Indium-Based Perovskite.

Low-dimensional organic-inorganic hybrid perovskites (OIHPs) with broadband emission attract immense scientific interest due to their potential application for the next generation of solid-state lighting. However, due to low exciton utilization, organic cations generally adjust structure rather than contribute the band edge to affect optical properties. Based on this, OIHPs are usually allowed to obtain a low photoluminescence quantum yield (PLQY). Herein, a good charge transfer carrier (p-phenylenediamine, PPDA) as organic cation is rationally employed and a novel indium-based perovskite is synthesized. By coupling with H2 O molecules, a strong interaction between organic and inorganic components is realized by hydrogen bonding, which has good transportability and greatly improves the exciton utilization. The regions of hydrogen bonding show high electron mobility, combined with the induced recombination center, improving the progress of charge relaxation. As a result, the regulation of hydrogen bond strength based on the microstructure optimization directly determines the optical emission intensity, realizing nearly 100% PLQY. Further, the polyhydrogen bond structure makes each component a stronger interaction, showing high stability in polar, organic, and acidic solvent, as well as long-term storing, which represents one of the highest overall performances for lighting in OIHPs.

Electrochemically induced amorphous-to-rock-salt phase transformation in niobium oxide electrode for Li-ion batteries.

Intercalation-type metal oxides are promising negative electrode materials for safe rechargeable lithium-ion batteries due to the reduced risk of Li plating at low voltages. Nevertheless, their lower energy and power density along with cycling instability remain bottlenecks for their implementation, especially for fast-charging applications. Here, we report a nanostructured rock-salt Nb2O5 electrode formed through an amorphous-to-crystalline transformation during repeated electrochemical cycling with Li+. This electrode can reversibly cycle three lithiums per Nb2O5, corresponding to a capacity of 269 mAh g-1 at 20 mA g-1, and retains a capacity of 191 mAh g-1 at a high rate of 1 A g-1. It exhibits superb cycling stability with a capacity of 225 mAh g-1 at 200 mA g-1 for 400 cycles, and a Coulombic efficiency of 99.93%. We attribute the enhanced performance to the cubic rock-salt framework, which promotes low-energy migration paths. Our work suggests that inducing crystallization of amorphous nanomaterials through electrochemical cycling is a promising avenue for creating unconventional high-performance metal oxide electrode materials.

Suppressed farnesoid X receptor by iron overload in mice and humans potentiates iron-induced hepatotoxicity.

BACKGROUND AND AIMS: Iron overload (IO) is a frequent finding in the general population. As the major iron storage site, the liver is subject to iron toxicity. Farnesoid X receptor (FXR) regulates bile acid metabolism and is implicated in various liver diseases. We aimed to determine whether FXR plays a role in regulating iron hepatotoxicity. APPROACH AND RESULTS: Human and mouse hepatocytes were treated with ferric ammonium citrate or iron dextran (FeDx). Mice were orally administered ferrous sulfate or injected i.p. with FeDx. Wild-type and Fxr-/- mice were fed an iron-rich diet for 1 or 5 weeks. Mice fed an iron-rich diet were coadministered the FXR agonist, GW4064. Forced expression of FXR was carried out with recombinant adeno-associated virus 1 week before iron-rich diet feeding. Serum levels of bile acids and fibroblast growth factor 19 (FGF19) were quantified in adults with hyperferritinemia and children with ß-thalassemia. The data demonstrated that iron suppressed FXR expression and signaling in human and mouse hepatocytes as well as in mouse liver and intestine. FXR deficiency potentiated iron hepatotoxicity, accompanied with hepatic steatosis as well as dysregulated iron and bile acid homeostasis. FXR negatively regulated iron-regulatory proteins 1 and 2 and prevented hepatic iron accumulation. Forced FXR expression and ligand activation significantly suppressed iron hepatotoxicity in iron-fed mice. The FXR agonist, GW4064, almost completely restored dysregulated bile acid signaling and metabolic syndrome in iron-fed mice. Conjugated primary bile acids were increased and FGF19 was decreased in serum of adults with hyperferritinemia and children with ß-thalassemia. CONCLUSIONS: FXR plays a pivotal role in regulating iron homeostasis and protects mice against iron hepatotoxicity. Targeting FXR may represent a therapeutic strategy for IO-associated chronic liver diseases.