Genus_Ruminococcus and order_Burkholderiales affect osteoporosis by regulating the microbiota-gut-bone axis.

Background: This study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments. Methods: We conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1ß, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed. Results: A positive correlation was observed between g_Ruminococcus1 and the risk of osteoporosis, while O_Burkholderiales showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the O_Burkholderiales was significantly reduced, while the abundance of g_Ruminococcus was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of O_Burkholderiales is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of g_Ruminococcus shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors. Conclusion: O_Burkholderiales and g_Ruminococcus may regulate the development of osteoporosis through the microbiota-gut-bone axis.

A biodegradable and flexible neural interface for transdermal optoelectronic modulation and regeneration of peripheral nerves.

Optoelectronic neural interfaces can leverage the photovoltaic effect to convert light into electrical current, inducing charge redistribution and enabling nerve stimulation. This method offers a non-genetic and remote approach for neuromodulation. Developing biodegradable and efficient optoelectronic neural interfaces is important for achieving transdermal stimulation while minimizing infection risks associated with device retrieval, thereby maximizing therapeutic outcomes. We propose a biodegradable, flexible, and miniaturized silicon-based neural interface capable of transdermal optoelectronic stimulation for neural modulation and nerve regeneration. Enhancing the device interface with thin-film molybdenum significantly improves the efficacy of neural stimulation. Our study demonstrates successful activation of the sciatic nerve in rodents and the facial nerve in rabbits. Moreover, transdermal optoelectronic stimulation accelerates the functional recovery of injured facial nerves.

Trends in maternal and child health in China and its urban and rural areas from 1991 to 2020: a joinpoint regression model.

The long-term trends in maternal and child health (MCH) in China and the national-level factors that may be associated with these changes have been poorly explored. This study aimed to assess trends in MCH indicators nationally and separately in urban and rural areas and the impact of public policies over a 30‒year period. An ecological study was conducted using data on neonatal mortality rate (NMR), infant mortality rate (IMR), under-five mortality rate (U5MR), and maternal mortality ratio (MMR) nationally and separately in urban and rural areas in China from 1991 to 2020. Joinpoint regression models were used to estimate the annual percentage changes (APC), average annual percentage changes (AAPC) with 95% confidence intervals (CIs), and mortality differences between urban and rural areas. From 1991 to 2020, maternal and child mortalities in China gradually declined (national AAPC [95% CI]: NMRs - 7.7% [- 8.6%, - 6.8%], IMRs - 7.5% [- 8.4%, - 6.6%], U5MRs - 7.5% [- 8.5%, - 6.5%], MMRs - 5.0% [- 5.7%, - 4.4%]). However, the rate of decline nationally in child mortality slowed after 2005, and in maternal mortality after 2013. For all indicators, the decline in mortality was greater in rural areas than in urban areas. The AAPCs in rate differences between rural and urban areas were - 8.5% for NMRs, - 8.6% for IMRs, - 7.7% for U5MRs, and - 9.6% for MMRs. The AAPCs in rate ratios (rural vs. urban) were - 1.2 for NMRs, - 2.1 for IMRs, - 1.7 for U5MRs, and - 1.9 for MMRs. After 2010, urban‒rural disparity in MMR did not diminish and in NMR, IMR, and U5MR, it gradually narrowed but persisted. MCH indicators have declined at the national level as well as separately in urban and rural areas but may have reached a plateau. Urban‒rural disparities in MCH indicators have narrowed but still exist. Regular analyses of temporal trends in MCH are necessary to assess the effectiveness of measures for timely adjustments.

Association between influenza vaccination and one-year all-cause and cardiovascular mortality risk: A self-controlled case series and matched case-control study.

Debates surrounding the efficacy of influenza vaccination for survival benefits persist, and there is a lack of data regarding its duration of protection. A self-controlled case series (SCCS) and a 1:4 matched case-control study were conducted using the National Health Interview Survey (NHIS) and public-use mortality data from 2005 to 2018 in the United States. The SCCS study identified participants who received influenza vaccination within 12 months before the survey and subsequently died within 1 year of postvaccination. The matched case-control study paired participants who died during the influenza season at the time of survey with four survivors. Among 1167 participants in the SCCS study, there was a 46% reduction in all-cause mortality and a 43% reduction in cardiovascular mortality within 29-196 days of postvaccination. The greatest protection was observed during days 29-56 (all-cause mortality: RI: 0.19; 95% CI: 0.12-0.29; cardiovascular mortality: RI: 0.28; 95% CI: 0.14-0.56). Among 626 cases and 2504 controls included in the matched case-control study, influenza vaccination was associated with a reduction in all-cause mortality (OR: 0.74, 95% CI: 0.60-0.92) and cardiovascular mortality (OR: 0.64, 95% CI: 0.44-0.93) during the influenza season. This study highlights the importance of influenza vaccination in reducing the risks of all-cause and cardiovascular mortality, with effects lasting for approximately 6 months.

Upconversion-based hydrogel kit with Python-assisted analysis platform for sample-to-result detection of organophosphorus pesticide.

On-site quantitative analysis of pesticide residues is crucial for monitoring environmental quality and ensuring food safety. Herein, we have developed a reliable hydrogel portable kit using NaYbF4@NaYF4: Yb, Tm upconversion nanoparticles (UCNPs) combined with MnO2 nanoflakes. This portable kit is integrated with a smartphone reader and Python-assisted analysis platform to enable sample-to-result analysis for chlorpyrifos. The novel UCNPs maximizes energy donation to MnO2 acceptor by employing 100 % of activator Yb3+ in the nucleus for NIR excitation energy collection and confining emitter Tm3+ to the surface layer to shorten energy transfer distance. Under NIR excitation, efficient quenching of upconversion blue-violet emission by MnO2 nanoflakes occurs, and the quenched emission is recovered with acetylcholinesterase-mediated reactions. This process allows for the determination of chlorpyrifos by inhibiting enzymatic activity. The UCNPs/MnO2 were embedded to fabricate a hydrogel portable kit, the blue-violet emission images captured by smartphone were converted into corresponding gray values by Python-assisted superiority chart algorithm which achieves a real-time rapid quantitative analysis of chlorpyrifos with a detection limit of 0.17 ng mL-1. At the same time, pseudo-color images were also added by Python in "one run" to distinguish images clearly. This sensor detection with Python-assisted analysis platform provides a new perspective on pesticide monitoring and broadens the application prospects in bioanalysis.

Enhanced sodium-storage performances of crumpled MXene nanosheets via alkali treatment-induced active ammonium ions.

Ti3C2Tx MXene demonstrates excellent potential as an anode material for sodium-ion capacitors. However, the narrow interlayer spacing and self-stacking phenomenon limit its applicability. In this study, we demonstrate an easy two-step method involving freezing and crumpling of MXene nanosheets to improve their Na-ion storage via the addition of ammonium ions (referred to as FCM nanosheets). Flat MXene particles aggregate and undergo folding in an alkaline solution. Ammonium ions can penetrate the gaps between MXene nanosheets, expanding interlayer spaces and inducing the formation of folds. Compared to MXene nanosheets, FCM nanosheets exhibit improved ion transfer kinetics and additional high capacity owing to the intercalated ammonium ions. The manufactured FCM anode exhibits remarkable electrochemical properties, including a high specific capacity of 313 mAhg-1 and stability over 15,000 cycles.

Glutathione­iron hybrid nanozyme-based colorimetric sensor for specific and stable detection of thiram pesticide on fruit juices.

Given the potential dangers of thiram to food safety, constructing a facile sensor is significantly critical. Herein, we presented a colorimetric sensor based on glutathione­iron hybrid (GSH-Fe) nanozyme for specific and stable detection of thiram. The GSH-Fe nanozyme exhibits good peroxidase-mimicking activity with comparable Michaelis constant (Km = 0.551 mM) to the natural enzyme. Thiram pesticides can specifically limit the catalytic activity of GSH-Fe nanozyme via surface passivation, causing the change of colorimetric signal. It is worth mentioning that the platform was used to prepare a portable hydrogel kit for rapid qualitative monitoring of thiram. Coupling with an image-processing algorithm, the colorimetric image of the hydrogel reactor is converted into the data information for accurate quantification of thiram with a detection limit of 0.3 µg mL-1. The sensing system has good selectivity and high stability, with recovery rates in fruit juice samples ranging from 92.4% to 106.9%.

24-h urinary sodium and potassium excretions, plasma metabolomic profiles, and cardiometabolic biomarkers in the United States adults: a cross-sectional study.

BACKGROUND: High-sodium and low-potassium intakes are associated with a higher risk of hypertension and cardiovascular disease, but there are limited data on the circulating metabolomics profiles of 24-h urinary sodium and potassium excretions in free-living individuals. OBJECTIVES: We aimed to characterize the metabolomics signatures of a high-sodium and low-potassium diet in a cross-sectional study. METHODS: In 1028 healthy older adults from the Women's and Men's Lifestyle Validation Studies, we investigated the association of habitual sodium and potassium intakes measured by 2 to 4 24-h urine samples with plasma metabolites (quantified using liquid chromatography-tandem mass spectrometry) and metabolomic pathways. Our primary exposures were energy-adjusted 24-h urinary sodium excretion, potassium excretion, and sodium-to-potassium ratio, calculated based on energy expenditure derived from the doubly labeled water method. We then assessed the partial correlations of their metabolomics scores, derived from elastic net regressions, with cardiometabolic biomarkers. RESULTS: Higher sodium excretion was associated with 38 metabolites including higher piperine, phosphatidylethanolamine, and C5:1 carnitine. In pathway analysis, higher sodium excretion was associated with enhanced biotin and propanoate metabolism and enhanced degradation of lysine and branched-chain amino acids (BCAAs). Metabolites associated with higher potassium and lower sodium-to-potassium ratio included quinic acid and proline-betaine. After adjusting for confounding factors, the metabolomics score for sodium-to-potassium ratio positively correlated with fasting insulin (Spearman's rank correlation coefficient ρ = 0.27), C-peptide (ρ = 0.30), and triglyceride (ρ = 0.46), and negatively with adiponectin (ρ = -0.40), and high-density lipoprotein cholesterol (ρ = -0.42). CONCLUSIONS: We discovered metabolites and metabolomics pathways associated with a high-sodium diet, including metabolites related to biotin, propanoate, lysine, and BCAA pathways. The metabolomics signature for a higher sodium low-potassium diet is associated with multiple components of elevated cardiometabolic risk.

[Effects of plumbagin on proliferation and apoptosis of human hepatocellular carcinoma cells based on CKB/p53 signaling pathway].

To investigate the effects of plumbagin on the proliferation and apoptosis of human hepatoma Huh-7 cells and its mechanism based on the creatine kinase B(CKB)/p53 signaling pathway. Huh-7 cells were treated with plumbagin from 1 to 12 µmol·L~(-1) for cell counting kit-8(CCK-8) assay, and 1, 3, and 6 µmol·L~(-1) were determined as low, medium, and high concentrations of plumbagin for subsequent experiments. CKB gene was knocked out in Huh-7 cells by clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)-9 gene editing technology. CKB overexpression lentivirus was transfected into Huh-7 cells to up-regulate the expression of CKB. Cell proliferation and apoptosis were detected by plate cloning assay and flow cytometry. The mRNA expression of CKB was detected by quantitative real-time PCR(qRT-PCR). CKB, p53, mouse double minute 2 homolog(MDM2), B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), and caspase-3 protein were detected by Western blot(WB). The results showed that plumbagin significantly inhibited the proliferation of Huh-7 cells and induced cell apoptosis. Compared with the control group, the apoptosis level was significantly increased in the plumbagin group, while the apoptosis level was significantly decreased in the plumbagin combined with the apoptosis inhibitor group. Plumbagin significantly down-regulated the protein expression levels of CKB, Bcl-2, and MDM2 and up-regulated the protein expression levels of p53, Bax, and caspase-3. Knockdown of the CKB gene decreased the proliferative ability of Huh-7 cells, increased the apoptotic rate, decreased the expression levels of Bcl-2 and MDM2 proteins, and increased the expression levels of p53, Bax, and caspase-3 proteins. After up-regulation of CKB expression, the proliferation ability of Huh-7 cells was enhanced, and the protein expression levels of Bcl-2 and MDM2 were elevated. The protein expression levels of p53, Bax, and caspase-3 were decreased. In addition, plumbagin reversed the effect of overexpression of CKB on the proliferation and apoptosis of Huh-7 cells. In conclusion, plumbagin significantly inhibited the proliferative ability of Huh-7 cells, and the mechanism may be related to the inhibition of CKB expression, activation of the p53 signaling pathway, and regulation of the expression of mitochondrial-associated apoptotic proteins, ultimately inducing cell apoptosis.

Multifunctional fluorescence/photoacoustic bimodal imaging of γ-glutamyltranspeptidase in liver disorders under different triggering conditions.

Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.

Development of Novel Phosphonodifluoromethyl-Containing Phosphotyrosine Mimetics and a First-In-Class, Potent, Selective, and Bioavailable Inhibitor of Human CDC14 Phosphatases.

Together with protein tyrosine kinases, protein tyrosine phosphatases (PTPs) control protein tyrosine phosphorylation and regulate numerous cellular functions. Dysregulated PTP activity is associated with the onset of multiple human diseases. Nevertheless, understanding of the physiological function and disease biology of most PTPs remains limited, largely due to the lack of PTP-specific chemical probes. In this study, starting from a well-known nonhydrolyzable phosphotyrosine (pTyr) mimetic, phosphonodifluoromethyl phenylalanine (F2Pmp), we synthesized 7 novel phosphonodifluoromethyl-containing bicyclic/tricyclic aryl derivatives with improved cell permeability and potency toward various PTPs. Furthermore, with fragment- and structure-based design strategies, we advanced compound 9 to compound 15, a first-in-class, potent, selective, and bioavailable inhibitor of human CDC14A and B phosphatases. This study demonstrates the applicability of the fragment-based design strategy in creating potent, selective, and bioavailable PTP inhibitors and provides a valuable probe for interrogating the biological roles of hCDC14 phosphatases and assessing their potential for therapeutic interventions.

Wavefunction matching for solving quantum many-body problems.

Ab initio calculations have an essential role in our fundamental understanding of quantum many-body systems across many subfields, from strongly correlated fermions1-3 to quantum chemistry4-6 and from atomic and molecular systems7-9 to nuclear physics10-14. One of the primary challenges is to perform accurate calculations for systems where the interactions may be complicated and difficult for the chosen computational method to handle. Here we address the problem by introducing an approach called wavefunction matching. Wavefunction matching transforms the interaction between particles so that the wavefunctions up to some finite range match that of an easily computable interaction. This allows for calculations of systems that would otherwise be impossible owing to problems such as Monte Carlo sign cancellations. We apply the method to lattice Monte Carlo simulations15,16 of light nuclei, medium-mass nuclei, neutron matter and nuclear matter. We use high-fidelity chiral effective field theory interactions17,18 and find good agreement with empirical data. These results are accompanied by insights on the nuclear interactions that may help to resolve long-standing challenges in accurately reproducing nuclear binding energies, charge radii and nuclear-matter saturation in ab initio calculations19,20.

Ultra-thin FeCoNi-LDH hollow nanoflower as solid-phase microextraction coating for targeted capture of six pesticides by electrostatic adsorption.

Pesticides are common pollutants that cause detriment to the ecological environmental safety and health of human due to their toxicity, volatility and bioaccumulation. In this work, an ultra-thin polymetallic layered double hydroxide (FeCoNi-LDH) with hollow nanoflower structure composite was synthesized using ZIF-67 as a self-sacrificial template, which was used as solid-phase microextraction (SPME) coating for the targeted capture pesticides, which could be combined with high-performance liquid chromatography (HPLC) to sensitive inspection pesticides in real water samples. Orthogonal experimental design (OAD) was applied to ensure the best SPME condition. Additionally, the adsorption properties were evaluated by chemical thermodynamics and kinetics. Under the optimized conditions, high adsorption capacity was obtained (117.0-21.5 mg g-1). A wide linear range (0.020-1000.0 µg L-1), low detection limit (0.008-0.172 µg L-1) and excellent reproducibility were obtained under the established method. This research provided a new strategy for designing hollow materials with multiple cations for the adsorption of anion or organic pollutants.

AuNi bimetallic aerogel with ultra-high stability applied in smart and portable biosensing.

Glucose detection is of significant importance in providing information to the human health management. However, conventional enzymatic glucose sensors suffer from a limited long-term stability due to the losing activity of the enzymes. In this work, the AuNi bimetallic aerogel with a well-defined nanowire network is synthesized and applied as the sensing nanomaterial in the non-enzymatic glucose detection. The three-dimensional (3D) hierarchical porous structure of the AuNi bimetallic aerogel ensures the high sensitivity of the sensor (40.34 µA mM-1 cm-2). Theoretical investigation unveiled the mechanism of the boosting electrocatalytic activity of the AuNi bimetallic aerogel toward glucose. A better adhesion between the sensing nanomaterial and the screen-printing electrodes (SPEs) is obtained after the introduction of Ni. On the basis of a wide linearity in the range of 0.1-5 mM, an excellent selectivity, an outstanding long-term stability (90 days) as well as the help of the signal processing circuit and an M5stack development board, the as-prepared glucose sensor successfully realizes remote monitoring of the glucose concentration. We speculate that this work is favorable to motivating the technological innovations of the non-enzymatic glucose sensors and intelligent sensing devices.

Synthesis of Bio-Base Fluorescence Carbon Dots for Selective Detection of Tartrazine and Sunset Yellow in Food Samples.

A green, economical and simple method for the preparation of water-soluble, high-fluorescent carbon quantum dots (CQDs) has been developed via hydrothermal process using pomelo peels as carbon source. The synthesized CQDs were characterized by transmission electron microscopy (TEM), X-ray diffraction(XRD), Fourier transform infrared spectroscopy (FTIR), UV - vis absorption spectra and fluorescence spectrophotometer. The results reveal that the as-prepared C-dots were spherical shape with an average diameter of 2.64 nm and emit bright blue photoluminescence (PL) with a quantum yield of approximately 3.63%. The surface of the C-dots was rich in hydroxyl groups and presented various merits including excellent photostability, low toxicity, and satisfactory solubility. Additionally, we found that two widely used synthetic food colorants, tartrazine and sunset yellow, could result in a strong fluorescence quenching of the C-dots, The possible mechanisms are caused by different ratios of inner filter and static quenching effects. According to this property, This study attempts to establish an analytical method for the determination of tartrazine and sunset yellow using carbon quantum dots as fluorescent probe. A linear relationship was found in the range of 0-100 µM tartrazine and sunset yellow with the detection limit(3σ/k) of 0.65 nM and 1.7 nM. The relative standard deviation (RSD) was 3.5% (tartrazine) and 3.0% (sunset yellow).This observation was further successfully applied for the determination of tartrazine and sunset yellow in food samples collected from local markets, and the recovery rates of the two ranges from 79% to 117.8 and 81 -103.5%, respectively. suggesting its great potential toward food routine analysis.

Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach.

Diabetic foot ulcers (DFUs) are a prevalent and profoundly debilitating complication that afflicts individuals with diabetes mellitus (DM). These ulcers are associated with substantial morbidity, recurrence rates, disability, and mortality, imposing substantial economic, psychological, and medical burdens. Timely detection and intervention can mitigate the morbidity and disparities linked to DFU. Nevertheless, current therapeutic approaches for DFU continue to grapple with multifaceted limitations. A growing body of evidence emphasizes the crucial role of cellular senescence in the pathogenesis of chronic wounds. Interventions that try to delay cellular senescence, eliminate senescent cells (SnCs), or suppress the senescence-associated secretory phenotype (SASP) have shown promise for helping chronic wounds to heal. In this context, targeting cellular senescence emerges as a novel therapeutic strategy for DFU. In this comprehensive review, we look at the pathology and treatment of DFU in a systematic way. We also explain the growing importance of investigating SnCs in DFU and highlight the great potential of senotherapeutics that target SnCs in DFU treatment. The development of efficacious and safe senotherapeutics represents a pioneering therapeutic approach aimed at enhancing the quality of life for individuals affected by DFU.

Single-cell transcriptome revealed dysregulated RNA-binding protein expression patterns and functions in human ankylosing spondylitis.

Objective: To explore the expression characteristics and regulatory patterns of RBPs in different immune cell types of AS, and to clarify the potential key role of RBPs in the occurrence and development of AS disease. Methods: PBMC sample data from scRNA-seq (HC*29, AS*10) and bulk RNA-seq (NC*3, AS*5) were selected for correlation analysis. Results: (1) Compared with the HC group, the numbers of B, DC (dendritic cells), CD14+ Mono and CD8+ T cells were increased in AS group, while the numbers of platelet (platelets), CD8+ NKT, CD16+ Mono (non-classical monocytes), Native CD4+ T and NK were decreased. (2) Through the analysis of RBP genes in B cells, some RBPs were found to play an important role in B cell differentiation and function, such as DDX3X, SFPQ, SRRM1, UPF2. (3) It may be related to B-cell receptor, IgA immunity, NOD-like receptor and other signaling pathways; Through the analysis of RBP genes in CD8+ T cells, some RBPs that play an important role in the immune regulation of CD8+ T were found, such as EIF2S3, EIF4B, HSPA5, MSL3, PABPC1 and SRSF7; It may be related to T cell receptor, TNF, IL17 and other signaling pathways. (4) Based on bulk RNA-seq, it was found that compared with HC and AS patients, differentially expressed variable splicing genes (RASGs) may play an important role in the occurrence and development of AS by participating in transcriptional regulation, protein phosphorylation and ubiquitination, DNA replication, angiogenesis, intracellular signal transduction and other related pathways. Conclusion: RBPs has specific expression characteristics in different immune cell types of AS patients, and has important regulatory functions. Its abnormal expression and regulation may be closely related to the occurrence and development of AS.

Aptamer AS411 interacts with the KRAS promoter/hnRNP A1 complex and shows increased potency against drug-resistant lung cancer.

G-quadruplex (G4) aptamers that can competitively binding protein with oncogene promoter G4 hold promise for cancer treatment. In this study, a neutral cytidinyl lipid, DNCA, was shown to transfect and deliver G4 aptamers (AS1411, TBA) into tumour cells, including multidrug-resistant tumour cells, and their nuclear localizations were clearly detected. Both AS1411/DNCA and TBA/DNCA showed excellent antitumour efficacies in the drug-resistant non-small cell lung cancer cell line A549/TXL at a low concentration (100 nM). Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was identified as a new target of AS1411 and TBA. The binding affinities were measured, and the Kd values of AS1411/hnRNP A1 and TBA/hnRNP A1 were 17.5 nM and 21.1 nM, respectively. Then the expression of KRAS mRNA in A549/TXL cells was found to be higher than that in A549 cells, and KRAS mRNA was reduced by approximately 40% after administration of AS1411 or TBA in A549/TXL cells. Further, it was confirmed for the first time that AS1411 targeted not only hnRNP A1 but also the KRAS promoter/hnRNP A1 complexes. And although TBA cannot target the KRAS promoter/hnRNP A1 complexes, the biolayer interferometry (BLI) experiment showed that TBA and AS1411 have similar effects on several key proteins in tumour cells, especially hnRNP A1. Molecular docking and molecular dynamics simulation showed that AS1411 and the KRAS promoter bound to the same domain of hnRNP A1 protein, while TBA bound to another domain.

Correction: Aptamer AS1411 interacts with the KRAS promoter/hnRNP A1 complex and shows increased potency against drug-resistant lung cancer.

[This corrects the article DOI: 10.1039/D3MD00752A.].