Discovery and Manipulation of van der Waals Polarons in Sb2O3 Ultrathin Molecular Crystal.

Manipulating single electrons at the atomic scale is vital for mastering complex surface processes governed by the transfer of individual electrons. Polarons, composed of electrons stabilized by electron-phonon coupling, offer a pivotal medium for such manipulation. Here, using scanning tunneling microscopy and spectroscopy (STM/STS) and density functional theory (DFT) calculations, we report the identification and manipulation of a new type of polaron, dubbed van der Waals (vdW) polaron, within mono- to trilayer ultrathin films composed of Sb2O3 molecules that are bonded via vdW attractions. The Sb2O3 films were grown on a graphene-covered SiC(0001) substrate via molecular beam epitaxy. Unlike prior molecular polarons, STM imaging observed polarons at the interstitial sites of the molecular film, presenting unique electronic states and localized band bending. DFT calculations revealed the lowest conduction band as an intermolecular bonding state, capable of ensnaring an extra electron through locally diminished intermolecular distances, thereby forming an intermolecular vdW polaron. We also demonstrated the ability to generate, move, and erase such vdW polarons using an STM tip. Our work uncovers a new type of polaron stabilized by coupling with intermolecular vibrations where vdW interactions dominate, paving the way for designing atomic-scale electron transfer processes and enabling precise tailoring of electron-related properties and functionalities.

Di-PEGylated insulin: A long-acting insulin conjugate with superior safety in reducing hypoglycemic events.

Although the discovery of insulin 100 years ago revolutionized the treatment of diabetes, its therapeutic potential is compromised by its short half-life and narrow therapeutic index. Current long-acting insulin analogs, such as insulin-polymer conjugates, are mainly used to improve pharmacokinetics by reducing renal clearance. However, these conjugates are synthesized without sacrificing the bioactivity of insulin, thus retaining the narrow therapeutic index of native insulin, and exceeding the efficacious dose still leads to hypoglycemia. Here, we report a kind of di-PEGylated insulin that can simultaneously reduce renal clearance and receptor-mediated clearance. By impairing the binding affinity to the receptor and the activation of the receptor, di-PEGylated insulin not only further prolongs the half-life of insulin compared to classical mono-PEGylated insulin but most importantly, increases its maximum tolerated dose 10-fold. The target of long-term glycemic management in vivo has been achieved through improved pharmacokinetics and a high dose. This work represents an essential step towards long-acting insulin medication with superior safety in reducing hypoglycemic events.

Stem-Cell-Regenerative and Protective Effects of Squid (Symplectoteuthis oualaniensis) Skin Collagen Peptides against H2O2-Induced Fibroblast Injury.

Recently, there has been a growing interest in collagen peptides derived from marine sources for their notable ability to protect skin cells against apoptosis induced by oxidants. Therefore, the current study aimed to investigate the fundamental properties of collagen peptides, including their physicochemical, thermal, structural, stem-cell-regenerative, and skin-cell-protective effects, in comparison to commercial collagen peptides. The acid-soluble (ASC) and pepsin-soluble (PSC) collagens exhibited three distinct bands on SDS-PAGE, namely α (α1 and α2), ß, and γ chains, confirming a type I pattern. The thermal profiles obtained from TG and DSC analyses confirmed the denaturation of PSC and ASC at temperatures ranging from 51.94 to 56.4 °C and from 52.07 to 56.53 °C, respectively. The purified collagen peptides were analyzed using SDS-PAGE and MALDI-TOF mass spectrometry, revealing a mass range of 900-15,000 Da. Furthermore, the de novo peptide sequence analysis confirmed the presence of the Gly-X-Y repeating sequence in collagen peptides. Collagen peptide treatments significantly enhanced HFF-1 cell proliferation and migration compared to the control group. ELISA results confirmed the potential interactions between collagen peptides and HFF-1 cells through α2ß1, α10ß1, and α11ß1 integrin receptors. Notably, collagen peptide treatment effectively restored the proliferation of HFF-1 cells damaged by H2O2. Consequently, the advantageous characteristics of squid skin collagen peptides highlight their promising role in regenerative medicine.

A cocktail nanovaccine targeting key entry glycoproteins elicits high neutralizing antibody levels against EBV infection.

Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.

Guanine-Rich RNA Sequence Binding Factor 1 Deficiency Promotes Colorectal Cancer Progression by Regulating PI3K/AKT Signaling Pathway.

Background: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified. Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells. Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities. Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management.

Berberine inhibits the progression of breast cancer by regulating METTL3-mediated m6A modification of FGF7 mRNA.

BACKGROUND: Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in breast cancer remain poorly understood. METHODS: Breast cancer cells were cultured and treated with different doses (0, 20, 40, and 60 µM) of BBR for 48 h. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase-like 3 (METTL3), and insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) mRNA levels and protein levels were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Interaction between METTL3 and FGF7 m6A was assessed using methylated RNA immunoprecipitation (MeRIP)-qPCR and RNA immunoprecipitation (RIP) assay. Binding ability between IGF2BP3 and FGF7 mRNA was analyzed using RIP assay. RESULTS: BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis. FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR-treated tumor cells. FGF7 upregulation relieved the repression of BBR on breast cancer cell malignant behaviors. In mechanism, METTL3 stabilized FGF7 mRNA through the m6A-IGF2BP3-dependent mechanism and naturally improved FGF7 expression. BBR treatment inhibited breast cancer growth in vivo. CONCLUSION: BBR treatment blocked breast cancer cell growth and metastasis partly by regulating METTL3-mediated m6A modification of FGF7 mRNA, providing a promising therapeutic target for breast cancer treatment.

Super-resolution radial fluctuations microscopy for optimal resolution and fidelity.

Fluorescence fluctuation super-resolution microscopy (FF-SRM) has emerged as a promising method for the fast, low-cost, and uncomplicated imaging of biological specimens beyond the diffraction limit. Among FF-SRM techniques, super-resolution radial fluctuation (SRRF) microscopy is a popular technique but is prone to artifacts, resulting in low fidelity, especially under conditions of high-density fluorophores. In this Letter, we developed a novel, to the best of our knowledge, combinatory computational super-resolution microscopy method, namely VeSRRF, that demonstrated superior performance in SRRF microscopy. VeSRRF combined intensity and gradient variance reweighted radial fluctuations (VRRF) and enhanced-SRRF (eSRRF) algorithms, leveraging the enhanced resolution achieved through intensity and gradient variance analysis in VRRF and the improved fidelity obtained from the radial gradient convergence transform in eSRRF. Our method was validated using microtubules in mammalian cells as a standard biological model system. Our results demonstrated that VeSRRF consistently achieved the highest resolution and exceptional fidelity compared to those obtained from other algorithms in both single-molecule localization microscopy (SMLM) and FF-SRM. Moreover, we developed the VeSRRF software package that is freely available on the open-source ImageJ/Fiji software platform to facilitate the use of VeSRRF in the broader community of biomedical researchers. VeSRRF is an exemplary method in which complementary microscopy techniques are integrated holistically, creating superior imaging performance and capabilities.

Cationic Lipid Pairs Enhance Liver-to-Lung Tropism of Lipid Nanoparticles for In Vivo mRNA Delivery.

Much of current clinical interest has focused on mRNA therapeutics for the treatment of lung-associated diseases, such as infections, genetic disorders, and cancers. However, the safe and efficient delivery of mRNA therapeutics to the lungs, especially to different pulmonary cell types, is still a formidable challenge. In this paper, we proposed a cationic lipid pair (CLP) strategy, which utilized the liver-targeted ionizable lipid and its derived quaternary ammonium lipid as the CLP to improve liver-to-lung tropism of four-component lipid nanoparticles (LNPs) for in vivo mRNA delivery. Interestingly, the structure-activity investigation identified that using liver-targeted ionizable lipids with higher mRNA delivery performance and their derived lipid counterparts is the optimal CLP design for improving lung-targeted mRNA delivery. The CLP strategy was also verified to be universal and suitable for clinically available ionizable lipids such as SM-102 and ALC-0315 to develop lung-targeted LNP delivery systems. Moreover, we demonstrated that CLP-based LNPs were safe and exhibited potent mRNA transfection in pulmonary endothelial and epithelial cells. As a result, we provided a powerful CLP strategy for shifting the mRNA delivery preference of LNPs from the liver to the lungs, exhibiting great potential for broadening the application scenario of mRNA-based therapy.

Immunoregulatory role of the gut microbiota in inflammatory depression.

Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.

Label-Free Multiplex Profiling of Exosomal Proteins with a Deep Learning-Driven 3D Surround-Enhancing SERS Platform for Early Cancer Diagnosis.

Identification of protein profiling on plasma exosomes by SERS can be a promising strategy for early cancer diagnosis. However, it is still challenging to detect multiple exosomal proteins simultaneously by SERS since the Raman signals of exosomes detected by conventional colloidal nanocrystals or two-dimensional SERS substrates are incomplete and complex. Herein, we develop a novel three-dimensional (3D) surround-enhancing SERS platform, named 3D se-SERS, for the multiplex detection of exosomal proteins. In this 3D se-SERS, proteins and exosomes are covered with "hotspots" generated by the gold nanoparticles, which surround the analytes densely and three-dimensionally, providing sensitive and comprehensive SERS signals. Combining this 3D se-SERS with a deep learning model, we successfully quantitatively profiled seven proteins including CD63, CD81, CD9, CD151, CD171, TSPAN8, and PD-L1 on the surface of plasma exosomes from patients, which can predict the occurrence and advancement of lung cancer. This 3D se-SERS integrating deep learning technique benefits from high sensitivity and significant multiplexing ability for comprehensive analysis of proteins and exosomes, demonstrating the potential of deep learning-driven 3D se-SERS technology for plasma exosome-based early cancer diagnosis.

The characteristics of sexual behavior in blind men in Ganzhou, China: A cross-sectional study.

Visual stimuli play key roles in influencing men sexual behavior. However, few studies have explored the sexual behavior of blind men. To provide more information about blind men for the study of andrology by surveying the characteristics of their current sexual behavior. A questionnaire-based cross-sectional study design was performed. The questionnaire contained questions regarding demographic characteristics of participants, access to sexual knowledge, perception of the sexual partners' beauty, and sexual arousal. Blind men were interviewed face-to-face by the trained investigator. Complete questionnaires were collected from 54 participants, with an average age of 40.57 ±â€…9.80 years old. Eye diseases were the most frequent cause of blindness. In terms of sexual orientation, all participants were heterosexual. Notably, 90.7% of the participants reported to have had a sexual experience. Among those who had engaged in sexual behavior, 93.6% experienced sexual pleasure and 69.4% had a normal erectile function. Overall, 16.7% of the participants received sex education. The participants obtained sexual knowledge mainly through sounds from mobile phones, peer-to-peer communication, sounds of television and radio. Voice was the most frequent perception of the sexual partners' beauty, followed by figure, skin, and body fragrance. In terms of stimuli of sexual arousal, tactile sensation and auditory sensation in that order were the most frequent stimuli of sexual arousal. Stimuli of sexual arousal in blind men are mainly mediated by sound and touch. Blind men understand their sexual partners' beauty through auditory, tactile, and olfactory sensations. Blind men in Ganzhou lack formal and systematic sex education.

Accurate and robust segmentation of cerebral vasculature on four-dimensional arterial spin labeling magnetic resonance angiography using machine-learning approach.

Segmentation of cerebral vasculature on MR vascular images is of great significance for clinical application and research. However, the existing cerebrovascular segmentation approaches are limited due to insufficient image contrast and complicated algorithms. This study aims to explore the potential of the emerging four-dimensional arterial spin labeling magnetic resonance angiography (4D ASL-MRA) technique for fast and accurate cerebrovascular segmentation with a simple machine-learning approach. Nine temporal features were extracted from the intensity-time signal of each voxel, and eight spatial features from the neighboring voxels. Then, the unsupervised outlier detection algorithm, i.e. Isolation Forest, is used for segmentation of the vascular voxels based on the extracted features. The total length of the centerlines of the intracranial arterial vasculature, the dice similarity coefficient (DSC), and the average Hausdorff Distance (AVGHD) on the cross-sections of small- to large-sized vessels were calculated to evaluate the performance of the segmentation approach on 4D ASL-MRA of 18 subjects. Experiments show that the temporal information on 4D ASL-MRA can largely improve the segmentation performance. In addition, the proposed segmentation approach outperforms the traditional methods that were performed on the 3D image (i.e. the temporal average intensity projection of 4D ASL-MRA) and the previously proposed frame-wise approach. In conclusion, this study demonstrates that accurate and robust segmentation of cerebral vasculature is achievable on 4D ASL-MRA by using a simple machine-learning approach with appropriate features.

Characteristics of gut microbiota and its correlation with hs-CRP and somatic symptoms in first-episode treatment-naive major depressive disorder.

OBJECTIVE: Most patients with major depressive disorder (MDD) have somatic symptoms, but little studies pay attention in the microbial-inflammatory mechanisms of these somatic symptoms. Our study aimed to investigate alterations in gut microbiota and its correlation with inflammatory marker levels and somatic symptoms in first-episode treatment-naive MDD. METHODS: Subjects contained 160 MDD patients and 101 healthy controls (HCs). MDD patients were divided into MDD with somatic symptoms group (MDDS) and MDD without somatic symptoms group (MDDN) based on Somatic Self-rating Scale (SSS). 16S ribosomal RNA sequencing were performed to analyze the composition of the fecal microbiota. The inflammatory factors were measured using enzyme linked immunosorbent assay (ELISA). Correlation among the altered gut microbiota, inflammatory factor and severity of clinical symptoms were analysized. RESULTS: Relative to HCs, MDD patients had higher levels of high-sensitivity C-reactive protein (hs-CRP) as well as disordered α-diversity and ß-diversity of gut microbiota. Linear discriminant effect size (LEfSe) analysis showed that MDD patients had higher proportions of Bifidobacterium, Blautia, Haemophilus and lower proportions of Bacteroides, Faecalibacterium, Roseburia, Dialister, Sutterella, Parabacteroides, Bordetella, and Phascolarctobacterium from the genus aspect. Furthermore, correlation analysis showed Bacteroides and Roseburia had negative correlations with the hs-CRP, HAMD-24, the total and factor scores of SSS in all participants. Further, compared with MDDN, the Pielous evenness was higher in MDDS. Random Forest (RF) analysis showed 20 most important genera discriminating MDD-S and MDDN, HCs. The ROC analysis showed that the AUC was 0.90 and 0.81 combining these genera respectively. CONCLUSION: Our study manifested MDD patients showed disordered gut microbiota and elevated hs-CRP levels, and altered gut microbiota was closely associated with hs-CRP, depressive symptoms, and somatic symptoms.

Therapeutic potential: The role of mesenchymal stem cells from diverse sources and their derived exosomes in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetic patients, with its incidence continuously increasing in recent years. DN causes renal tissue damage and functional decline, expedites the aging process of the kidneys, and may ultimately progress leading to end-stage renal disease, severely impacting the patient's quality of life and prognosis. Mesenchymal stem cells (MSCs) are highly valued for their multipotent differentiation, paracrine functions, immunomodulatory effects, and capacity for tissue repair. Particularly, exosomes (Exo) derived from MSCs (MSCs-Exo) are rich in bioactive molecules and facilitate intercellular communication, participating in various physiological and pathological processes. MSCs and MSCs-Exo, in particular, have been demonstrated to have therapeutic effects in DN treatment research by encouraging tissue repair, fibrosis inhibition, and inflammation reduction. Research has shown that MSCs and MSCs-Exo have therapeutic effects in DN treatment by promoting tissue repair, inhibiting fibrosis, and reducing inflammation. Recent studies underscore the potential of MSCs and MSCs-Exo, highlighting their broad applicability in DN treatment. This review aims to provide a comprehensive summary of the scientific developments in treating DN using MSCs and MSCs-Exo from diverse sources, while also exploring their future therapeutic possibilities in detail.

Near-Infrared Light-Excited Quinolinium-Carbazole Small Molecule as Two-Photon Fluorescence Nucleic Acid Probe.

This article reports three new two-photon absorption (TPA) materials that are quinolinium-carbazole derivates. They are 3-(N-methyl-4-ethylquinolinium iodide)-9-ethylcarbazole (M4), 3-(N-methyl-4-ethylquinolinium iodide)-9-ethylcarbazole (H2), and 3-(N-methyl-4-ethylquinolinium iodide)-9-ethylcarbazole (H4). Their TPA cross-sections are 491, 515, and 512 GM, respectively. Under the excitation of near-infrared light, their fluorescence emission is about 650 nm. The compounds can stain nucleic acid DNA with the same level of nuclear localization as Hoechst 33342. Under continuous irradiation with a near-infrared laser, the three new compounds showed less fluorescence decay than DAPI, and the average fluorescence decay rates were 0.016%/s, 0.020%/s, and 0.023%/s. They are expected to become new two-photon fluorescent probes of nucleic acid DNA because of their excellent performance.

Classification of anatomical morphology of cystic duct and its association with gallstone.

BACKGROUND: Gallstones are common lesions that often require surgical intervention. Laparoscopic cholecystectomy is the treatment of choice for symptomatic gallstones. Preoperatively, the anatomical morphology of the cystic duct (CD), needs to be accurately recognized, especially when anatomical variations occur in the CD, which is otherwise prone to bile duct injury. However, at present, there is no optimal classification system for CD morphology applicable in clinical practice, and the relationship between anatomical variations in CDs and gallstones remains to be explored. AIM: To create a more comprehensive clinically applicable classification of the morphology of CD and to explore the correlations between anatomic variants of CD and gallstones. METHODS: A total of 300 patients were retrospectively enrolled from October 2021 to January 2022. The patients were divided into two groups: The gallstone group and the nongallstone group. Relevant clinical data and anatomical data of the CD based on magnetic resonance cholangiopancreatography (MRCP) were collected and analyzed to propose a morphological classification system of the CD and to explore its relationship with gallstones. Multivariate analysis was performed using logistic regression analyses to identify the independent risk factors using variables that were significant in the univariate analysis. RESULTS: Of the 300 patients enrolled in this study, 200 (66.7%) had gallstones. The mean age was 48.10 ± 13.30 years, 142 (47.3%) were male, and 158 (52.7%) were female. A total of 55.7% of the patients had a body mass index (BMI) ≥ 24 kg/m2. Based on the MRCP, the CD anatomical typology is divided into four types: Type I: Linear, type II: n-shaped, type III: S-shaped, and type IV: W-shaped. Univariate analysis revealed differences between the gallstone and nongallstone groups in relation to sex, BMI, cholesterol, triglycerides, morphology of CD, site of CD insertion into the extrahepatic bile duct, length of CD, and angle between the common hepatic duct and CD. According to the multivariate analysis, female, BMI (≥ 24 kg/m2), and CD morphology [n-shaped: Odds ratio (OR) = 10.97, 95% confidence interval (95%CI): 5.22-23.07, P < 0.001; S-shaped: OR = 4.43, 95%CI: 1.64-11.95, P = 0.003; W-shaped: OR = 7.74, 95%CI: 1.88-31.78, P = 0.005] were significantly associated with gallstones. CONCLUSION: The present study details the morphological variation in the CD and confirms that CD tortuosity is an independent risk factor for gallstones.

Photodriven Radical Perfluoroalkylation-Thiolation of Unactivated Alkenes Enabled by Electron Donor-Acceptor Complex.

A clean and direct three-component radical 1,2-difunctionalization of various alkenes with perfluoroalkyl iodides and thiosulfonates enabled by the electron donor-acceptor complex has been developed under light illumination at room temperature. The approach offers a convenient and environmentally friendly route for the simultaneous incorporation of Csp3-Rf and Csp3-S bonds, affording valuable polyfunctionalized alkane derivatives containing fluorine and sulfur in satisfactory yields. Consequently, this methodology holds significant value and practicality in the field of organic synthesis.

CircTBC1D22A inhibits the progression of colorectal cancer through autophagy regulated via miR-1825/ATG14 axis.

Distant metastasis is the main cause of death in patients with colorectal cancer (CRC). A better understanding of the mechanisms of metastasis can greatly improve the outcome of patients with CRC. Accumulating evidence suggests that circRNA plays pivotal roles in cancer progression and metastasis, especially acting as a miRNA sponge to regulate the expression of the target gene. A public database bioinformatics analysis found that miR-1825 was highly expressed in CRC tissues. In this study, miR-1825 was highly expressed in CRC tissues, which was positively correlated with lymph node metastasis and distant metastasis. In vitro and in vivo experiments confirmed that miR-1825 was positively correlated with the proliferation and migration of CRC cells. This event can be inhibited by circTBC1D22A. CircTBC1D22A can directly interact with miR-1825 and subsequently act as a miRNA sponge to regulate the expression of the target gene ATG14, which collectively advances the autophagy-mediated progression and metastasis of CRC.

pH-sensitive cationic nanoparticles for endosomal cell-free DNA scavenging against acute inflammation.

Cell-free DNA (cfDNA) released from dead cells could be a player in some autoimmune disorders by activating Toll-like receptor 9 (TLR9) and inducing proinflammatory cytokines. Cationic nanoparticles (cNPs) address cfDNA clearance, yet challenges persist, including toxicity, low specificity and ineffectiveness against endocytosed cfDNA. This study introduced pH-sensitive cNPs, reducing off-target effects and binding cfDNA at inflammatory sites. This unique approach inhibits the TLR9 pathway, offering a novel strategy for inflammation modulation. Synthesized cNPs, with distinct cationic moieties, exhibit varied pKa values, enhancing cfDNA binding. Comprehensive studies elucidate the mechanism, demonstrating minimal extracellular binding, enhanced endosomal DNA binding, and optimal tumor necrosis factor-α suppression. In a traumatic brain injury mice model, pH-sensitive cNPs effectively suppress inflammatory cytokines, highlighting their potential in acute inflammation regulation.