Constructing Two-Dimensional Heterostructure Channels with Engineered Biomembrane and Graphene for Precise Scandium Sieving.

The special properties of rare earth elements have effectively broadened their application fields. How to accurately recognize and efficiently separate target rare earth ions with similar radii and chemical properties remains a formidable challenge. Here, we constructed precise two-dimensional (2D) heterogeneous channels using engineered E. coli membranes between graphene oxidse (GO) layers. The difference in binding ability and corresponding conformational change between Lanmodulin (LanM) and rare earth ions in the heterogeneous channel allow for precisely recognizing and sieving of scandium ions (Sc3+). The engineered E. coli membranes not only can protect the integrity of structure and functionality of LanM, the rich lipids and sugars but also help the E. coli membranes closely tile on the GO nanosheets through interaction, preventing swelling and controlling interlayer spacing accurately down to the sub-nanometer. Apparently, the 2D heterogeneous channels showcase excellent selectivity for trivalent ions (SFFe 3+ /Sc 3+≈3), especially for Sc3+ ions in rare earth elements with a high selectivity (SFCe/Sc≈167, SFLa/Sc≈103). The long-term stability and tensile strain tests verify the membrane's outstanding stability. Thus, this simple, efficient, and cost-effective work provides a suggestion for constructing two-dimensional interlayer heterogeneous channels for precise sieving, and the valuable strategy is proposed for the efficient extraction of Sc. This article is protected by copyright. All rights reserved.

CBLC promotes the development of colorectal cancer by promoting ABI1 degradation to activate the ERK signaling pathway.

CBLC (CBL proto-oncogene C) is an E3 ubiquitin protein ligase that plays a key role in cancers. However, the function and mechanism of CBLC in colorectal cancer (CRC) has not been fully elucidated. The aim of this study was to investigate the function of CBLC in CRC and its underlying molecular mechanism. High CBLC levels were certified in tumor tissues of CRC patients, and its expression was positively associated with TNM stage. Next, we explored the role of CBLC in CRC using gain or loss of function. For biological function analysis, CCK-8 cell proliferation, colony formation, flow cytometry, scratch, and transwell assays collectively suggested that CBLC overexpression promoted cell proliferation, cell cycle progression, migration and invasion. As observed, CBLC knockdown exhibited exactly opposite effects, resulting in impaired tumorigenicity in vitro. Xenograft studies displayed that CBLC overexpression accelerated tumor growth and promoted tumor metastasis to the lung, while the inhibitory effects of CBLC knockdown on tumorigenicity and metastasis ability of CRC cells was also confirmed. Furthermore, the molecular mechanism of CBLC in CRC was explored. CBLC induced the activation of ERK signaling pathway, further leading to its pro-tumor role. Notably, CBLC decreased ABI1 (Abelson interactor protein-1, a candidate tumor suppressor) protein levels through its ubiquitin ligase activity, while ABI1 upregulation abolished the effects of CBLC on the tumorigenesis of CRC. Taken together, these results demonstrate that CBLC acts as a tumor promoter in CRC through triggering the ubiquitination and degradation of ABI1 and activating the ERK signaling pathway. CBLC may be a potential novel target for CRC.

Broadband frequency comb generation through cascaded quadratic nonlinearity in thin-film lithium niobate microresonators.

Broadband frequency comb generation through cascaded quadratic nonlinearity remains experimentally untapped in free-space cavities with bulk χ(2) materials mainly due to the high threshold power and restricted ability of dispersion engineering. Thin-film lithium niobate (LN) is a good platform for nonlinear optics due to the tight mode confinement in a nano-dimensional waveguide, the ease of dispersion engineering, large quadratic nonlinearities, and flexible phase matching via periodic poling. Here we demonstrate broadband frequency comb generation through dispersion engineering in a thin-film LN microresonator. Bandwidths of 150 nm (80 nm) and 25 nm (12 nm) for center wavelengths at 1560 and 780 nm are achieved, respectively, in a cavity-enhanced second-harmonic generation (doubly resonant optical parametric oscillator). Our demonstration paves the way for pure quadratic soliton generation, which is a great complement to dissipative Kerr soliton frequency combs for extended interesting nonlinear applications.

Untargeted Metabolomics Based on Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole Orbitrap High-Resolution Mass Spectrometry for Differential Metabolite Analysis of Pinelliae Rhizoma and Its Adulterants.

The present study investigates the chemical composition variances among Pinelliae Rhizoma, a widely used Chinese herbal medicine, and its common adulterants including Typhonium flagelliforme, Arisaema erubescens, and Pinellia pedatisecta. Utilizing the non-targeted metabolomics technique of employing UHPLC-Q-Orbitrap HRMS, this research aims to comprehensively delineate the metabolic profiles of Pinelliae Rhizoma and its adulterants. Multivariate statistical methods including PCA and OPLS-DA are employed for the identification of differential metabolites. Volcano plot analysis is utilized to discern upregulated and downregulated compounds. KEGG pathway analysis is conducted to elucidate the differences in metabolic pathways associated with these compounds, and significant pathway enrichment analysis is performed. A total of 769 compounds are identified through metabolomics analysis, with alkaloids being predominant, followed by lipids and lipid molecules. Significant differential metabolites were screened out based on VIP > 1 and p-value < 0.05 criteria, followed by KEGG enrichment analysis of these differential metabolites. Differential metabolites between Pinelliae Rhizoma and Typhonium flagelliforme, as well as between Pinelliae Rhizoma and Pinellia pedatisecta, are significantly enriched in the biosynthesis of amino acids and protein digestion and absorption pathways. Differential metabolites between Pinelliae Rhizoma and Arisaema erubescens are mainly enriched in tyrosine metabolism and phenylalanine metabolism pathways. These findings aim to provide valuable data support and theoretical references for further research on the pharmacological substances, resource development and utilization, and quality control of Pinelliae Rhizoma.

MORN motif-containing protein OsMORN1 and OsMORN2 are crucial for rice pollen viability and cold tolerance.

The pollen viability directly affects the pollination process and the ultimate grain yield of rice. Here, we identified that the MORN motif-containing proteins, OsMORN1 and OsMORN2, had a crucial role in maintaining pollen fertility. Compared with the wild type (WT), the pollen viability of the osmorn1 and osmorn2 mutants was reduced, and pollen germination was abnormal, resulting in significantly lower spikelet fertility, seed-setting rate, and grain yield per plant. Further investigation revealed that OsMORN1 was localized to the Golgi apparatus and lipid droplets. Lipids associated with pollen viability underwent alterations in osmorn mutants, such as the diacylglyceride (18:3_18:3) was 5.1-fold higher and digalactosyldiacylglycerol (18:2_18:2) was 5.2-fold lower in osmorn1, while the triacylglycerol (TG) (16:0_18:2_18:3) was 8.3-fold higher and TG (16:0_18:1_18:3) was 8.5-fold lower in osmorn2 than those in WT. Furthermore, the OsMORN1/2 was found to be associated with rice cold tolerance, as osmorn1 and osmorn2 mutants were more sensitive to chilling stress than WT. The mutants displayed increased hydrogen peroxide accumulation, reduced antioxidant enzyme activities, elevated malondialdehyde content, and a significantly decreased seedling survival rate. Lipidomics analysis revealed distinct alterations in lipids under low temperature, highlighting significant changes in TG (18:2_18:3_18:3) and TG (18:4_18:2_18:2) in osmorn1, TG (16:0_18:2_18:2) and PI (17:2_18:3) in osmorn2 compared to the WT. Therefore, it suggested that OsMORN1 and OsMORN2 regulate both pollen viability and cold tolerance through maintaining lipid homeostasis.

A Ligand-Directed Spatial Regulation to Structural and Functional Tunability in Aggregation-Induced Emission Luminogen-Functionalized Organic-Inorganic Nanoassemblies.

Aggregation-induced emission luminogen (AIEgen)-functionalized organic-inorganic hybrid nanoparticles (OINPs) are an emerging category of multifunctional nanomaterials with vast potential applications. The spatial arrangement and positioning of AIEgens and inorganic compounds in AIEgen-functionalized OINPs determine the structures, properties, and functionalities of the self-assembled nanomaterials. In this work, a facile and general emulsion self-assembly tactic for synthesizing well-defined AIEgen-functionalized OINPs is proposed by coassembling alkane chain-functionalized inorganic nanoparticles with hydrophobic organic AIEgens. As a proof of concept, the self-assembly and structural evolution of plasmonic-fluorescent hybrid nanoparticles (PFNPs) from concentric circle to core shell and then to Janus structures is demonstrated by using alkane chain-modified AuNPs and AIEgens as building blocks. The spatial position of AuNPs in the signal nanocomposite is controlled by varying the alkane ligand length and density on the AuNP surface. The mechanism behind the formation of various PFNP nanostructures is also elucidated through experiments and theoretical simulation. The obtained PFNPs with diverse structures exhibit spatially tunable optical and photothermal properties for advanced applications in multicolor and multimode immunolabeling and photothermal sterilization. This work presents an innovative synthetic approach of constructing AIEgen-functionalized OINPs with diverse structures, compositions, and functionalities, thereby championing the progressive development of these OINPs.

Benzoselenadiazole-Functionalized H-Bonded Arylamide Foldamers: Solvent-Responsive Properties and Helix Self-Assembly Directed by Chalcogen Bonding in Solid State.

In this study, a series of H-bonded arylamide foldamers bearing benzoselenadiazole ends with solvent-responsive properties have been synthesized. In dichloromethane or dimethyl sulfoxide solvents, the molecules exhibit meniscus or linear structures, respectively, which can be attributed to the unique intramolecular hydrogen bonding behavior evidenced by 1D 1H NMR and 2D NOESY spectra. UV-vis spectroscopy experiments show that the absorption wavelength of H-bonded arylamide foldamers are significantly red-shifted due to the presence of benzoselenadiazole group. In addition, the crystal structures reveal that effective intermolecular dual Se ⋅ ⋅ ⋅ N interactions between benzoselenadiazole groups induce further assembly of the monomers. Remarkably, supramolecular linear and double helices structures are constructed under the synergistic induction of intramolecular hydrogen bonding and intermolecular chalcogen bonding. Additionally, 2D DOSY diffusion spectra and theoretical modelling based on density functional theory (DFT) are performed to explore the persistence of intermolecular Se ⋅ ⋅ ⋅ N interactions beyond the crystalline state.

Significance of immunoglobulins synthesis with central nervous system involvement in Neuro-Behçet's disease.

OBJECTIVES: Demyelination and immunocyte-infiltrated lesions have been found in neuro-Behçet's disease (NBD) pathology. Lacking satisfying laboratory biomarkers in NBD impedes standard clinical diagnostics. We aim to explore the ancillary indicators for NBD diagnosis unveiling its potential etiology. METHODS: 28 NBD with defined diagnosis, 29 patients with neuropsychiatric lupus erythematosus, 30 central nervous system idiopathic inflammatory demyelination diseases (CNS-IIDD), 30 CNS infections, 30 cerebrovascular diseases, and 30 noninflammatory neurological diseases (NIND) were retrospectively enrolled. Immunoglobulins (Ig) in serum and cerebral spinal fluid (CSF) were detected by immunonephelometry and myelin basic protein (MBP) by quantitative enzyme-linked immunosorbent assay. RESULTS: IgA index is almost twice enhanced in NBD than NIND with an accuracy of 0.8488 in differential diagnosis, the sensitivity and specificity of which were 75.00 % and 90.00 % when the cutoff was > 0.6814. The accuracy of CSF Ig and quotient of Ig all exceed 0.90 in discerning NBD with damaged and intact blood-brain barrier (BBB). Clustering analyses divided NBD into two different phenotypes: one with BBB damage has lower Ig synthesis, the other with extra-synthesis in parenchymal sites but with intact BBB. MBP index is significantly correlated with kappa (KAP) index and lambda (LAM) index (r = 0.358, 0.575, P < 0.001), hinting the NBD pathogenesis of CNS demyelination in triggering excessive intrathecal Ig productions and humoral responses. CONCLUSIONS: IgA index acts as a potential diagnostic indicator in differentiating NBD from NIND and CNS-IIDD. Excessive immunoglobulin production induced by CNS inflammation and demyelination might be latent immunopathogenesis of NBD.

Fine Optimization of Colloidal Photonic Crystal Structural Color for Physically Unclonable Multiplex Encryption and Anti-Counterfeiting.

Robust anti-counterfeiting techniques aim for easy identification while remaining difficult to forge, especially for high-value items such as currency and passports. However, many existing anti-counterfeiting techniques rely on deterministic processes, resulting in loopholes for duplication and counterfeiting. Therefore, achieving high-level encryption and easy authentication through conventional anti-counterfeiting techniques has remained a significant challenge. To address this, this work proposes a solution that combined fluorescence and structural colors, creating a physically unclonable multiplex encryption system (PUMES). In this study, the physicochemical properties of colloidal photonic inks are systematically adjusted to construct a comprehensive printing phase diagram, revealing the printable region. Furthermore, the brightness and color saturation of inkjet-printed colloidal photonic crystal structural colors are optimized by controlling the substrate's hydrophobicity, printed droplet volume, and the addition of noble metals. Finally, fluorescence is incorporated to build PUMES, including macroscopic fluorescence and structural color patterns, as well as microscopic physically unclonable fluorescence patterns. The PUMES with intrinsic randomness and high encoding capacity are authenticated by a deep learning algorithm, which proved to be reliable and efficient under various observation conditions. This approach can provide easy identification and formidable resistance against counterfeiting, making it highly promising for the next-generation anti-counterfeiting of currency and passports.

Constructing artificial gap junctions to mediate intercellular signal and mass transport.

Natural gap junctions are a type of channel protein responsible for intercellular signalling and mass communication. However, the scope of applications for these proteins is limited as they cannot be prepared at a large scale and are unable to spontaneously insert into cell membranes in vitro. The construction of artificial gap junctions may provide an alternative strategy for preparing analogues of the natural proteins and bottom-up building blocks necessary for the synthesis of artificial cells. Here we show the construction of artificial gap junction channels from unimolecular tubular molecules consisting of alternately arranged positively and negatively charged pillar[5]arene motifs. These molecules feature a hydrophobic-hydrophilic-hydrophobic triblock structure that allows them to efficiently insert into two adjacent plasma membranes and stretch across the gap between the two membranes to form gap junctions. Similar to natural gap junction channels, the synthetic channels could mediate intercellular signal coupling and reactive oxygen species transmission, leading to cellular activity.

Investigating the Effects of Temperature on Pathogen Propagation in Arabidopsis.

Temperature is one of the most prominent environmental factors that influence plant immunity. Depending on the plant-pathogen system, increased temperature may inhibit or enhance disease resistance or immunity in plants. Measuring the effect of temperature on plant immunity is the first step toward revealing climate effects on plant-pathogen interactions and molecular regulators of temperature sensitivity of plant immunity. Quantification of plant disease resistance or susceptibility under different temperatures can be accomplished by assessing pathogen growth over time in infected plants or tissues. Here, we present a protocol for quantifying pathogen growth in the most studied system of Arabidopsis thaliana and Pseudomonas syringae pathovar tomato (Pst) DC3000. We discuss important factors to consider for assaying pathogen growth in plants under different temperatures. This protocol can be used to assess temperature sensitivity of resistance in different plant genotypes and to various pathovars.

Exosomes derived from induced cardiopulmonary progenitor cells alleviate acute lung injury in mice.

Cardiopulmonary progenitor cells (CPPs) constitute a minor subpopulation of cells that are commonly associated with heart and lung morphogenesis during embryonic development but completely subside after birth. This fact offers the possibility for the treatment of pulmonary heart disease (PHD), in which the lung and heart are both damaged. A reliable source of CPPs is urgently needed. In this study, we reprogrammed human cardiac fibroblasts (HCFs) into CPP-like cells (or induced CPPs, iCPPs) and evaluated the therapeutic potential of iCPP-derived exosomes for acute lung injury (ALI). iCPPs were created in passage 3 primary HCFs by overexpressing GLI1, WNT2, ISL1 and TBX5 (GWIT). Exosomes were isolated from the culture medium of passage 6-8 GWIT-iCPPs. A mouse ALI model was established by intratracheal instillation of LPS. Four hours after LPS instillation, ALI mice were treated with GWIT-iCPP-derived exosomes (5 × 109, 5 × 1010 particles/mL) via intratracheal instillation. We showed that GWIT-iCPPs could differentiate into cell lineages, such as cardiomyocyte-like cells, endothelial cells, smooth muscle cells and alveolar epithelial cells, in vitro. Transcription analysis revealed that GWIT-iCPPs have potential for heart and lung development. Intratracheal instillation of iCPP-derived exosomes dose-dependently alleviated LPS-induced ALI in mice by attenuating lung inflammation, promoting endothelial function and restoring capillary endothelial cells and the epithelial cells barrier. This study provides a potential new method for the prevention and treatment of cardiopulmonary injury, especially lung injury, and provides a new cell model for drug screening.

Cognitive-behavioral therapy for patients with somatoform disorders: A pilot preliminary randomized controlled trial.

Background and objective: Cognitive-behavioral therapy (CBT) for somatoform disorders (SFDs) is understudied in China. Western findings may not be applicable to Chinese culture. This preliminary study evaluated the efficacy of CBT for patients in China, relative to treatment-as-usual (TAU). Methods: Seventy patients with SFDs randomly received either combined CBT and TAU (CBT + TAU), or TAU alone between January 2018 to May 2019. The CBT + TAU group received 12 weekly individual 50-minute CBT sessions. Participants were blindly assessed at 4 timepoints (baseline, week 6, end of treatment: week 12; 12 weeks post-treatment: week 24) using the following outcome measures: SQSS (Self-screening Questionnaire for Somatic Symptoms); PHQ-15 (Patient-Health-Questionnaire-15) and the WI (Whiteley Index); GAD-7 (General Anxiety Disorder-7); HAMD-17 (Hamilton Depression Rating Scale-17); Family Burden Interview Schedule (FBIS); Sheehan Disability Scale (SDS); and the Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). The primary endpoint was the difference between the SQSS total score at week 24 and the baseline. A mixed model for repeated measures was used to analyze inter- and intra-group changes from the baseline. Results: At week 24, The least-squares mean (LSM) change of the total score on the SQSS was -18.87 points and -9.69 points, respectively in the CBT + TAU group and in the TAU group (LSM difference, -9.18 points; 95% confidence interval, -15.72 to -2.64; P = 0.0068). At week 24, the LSM changes from baseline in the WI, HAMD, PHQ15, FBIS and SDS total scores were significantly different between the two groups, however, there was no significant difference in the Q-LES-Q-SF. The SQSS of group effect sizes were 0.63 at 24 weeks. The dropout rates of the CBT + TAU and TAU groups were comparable (22.9% and 19.3%). Conclusions: These preliminary findings suggest that CBT may be helpful for improving the symptoms of patients with SFDs in China.

Fabrication of polydopamine/rGO Membranes for Effective Radionuclide Removal.

In this work, a novel polydopamine/reduced graphene oxide (PDA/rGO) nanofiltration membrane was prepared to efficiently and stably remove radioactive strontium ions under an alkaline environment. Through the incorporation of PDA and thermal reduction treatment, not only has the interlayer spacing of graphene oxide (GO) nanosheets been appropriately regulated but also an improved antiswelling property has been achieved. The dosage of GO, reaction time with PDA, mass ratio of PDA to GO, and thermal treatment temperature have been optimized to achieve a high-performance PDA/rGO membrane. The resultant PDA/rGO composite membrane has exhibited excellent long-term stability at pH 11 and maintains a steady strontium rejection of over 90%. Moreover, the separation mechanism of the PDA/rGO membrane has been systematically investigated and determined to be a synergistic effect of charge repulsion and size exclusion. Results have indicated that PDA/rGO could be considered as a promising candidate for the separation of Sr2+ ions from nuclear industry wastewater.

Nanochannel Stability of Chemically Converted Graphene Oxide Membranes.

Chemically converted graphene oxide laminate membranes, which exhibit stable interlayered nanochannels in aqueous environments, are receiving increasing attention owing to their potential for selective water and ion permeation. However, how the molecular properties of conversion agents influence the stabilization of nanochannels and how effectively nanochannels are stabilized have rarely been studied. In this study, mono-, di-, and tri-saccharide molecules of glucose (Glu), maltose (Glu2), and maltotriose (Glu3) are utilized, respectively, to chemically modify graphene oxide (GO). The aim is to create nanochannels with different levels of stability and investigate how these functional conversion agents affect the separation performance. The effects of the property differences between different conversion agents on nanochannel stabilization are demonstrated. An agent with efficient chemical reduction of GO and limited intercalation in the resulting nanochannel ensures satisfactory nanochannel stability during desalination. The stabilized membrane nanochannel exhibits a permeance of 0.69 L m-2 h-1 bar-1 and excellent Na2SO4 rejection of 96.42%. Furthermore, this optimized membrane nanochannel demonstrates enhanced stability under varying external conditions compared to the original GO. This study provides useful information for the design of chemical conversion agents for GO nanochannel stabilization and the development of nanochannel membranes for precise separation.

Tenovin 3 induces apoptosis and ferroptosis in EGFR 19del non small cell lung cancer cells.

Epidermal growth factor receptor (EGFR) exon 19 deletion is a major driver for the drug resistance of non-small cell lung cancer (NSCLC). Identification small inhibitor capable of selectively inhibiting EGFR-19del NSCLC is a desirable strategy to overcome drug resistance in NSCLC. This study aims to screen an inhibitor for EGFR exon 19 deletion cells and explore its underlying mechanism. High through-put screen was conducted to identify an inhibitor for EGFR-19del NSCLC cells. And tenovin-3 was identified as a selective inhibitor of PC9 cells, an EGFR-19del NSCLC cells. Tenovin-3 showed particular inhibition effect on PC9 cells proliferation through inducing apoptosis and ferroptosis. Mechanistically, tenovin-3 might induce the apoptosis and ferroptosis of PC9 cells through mitochondrial pathway, as indicated by the change of VDAC1 and cytochrome c (cyt c). And bioinformatics analyses showed that the expression levels of SLC7A11 and CPX4 were correlated with NSCLC patient's survival. Our findings provide evidences for tenovin-3 to be developed into a novel candidate agent for NSCLC with EGFR exon 19 deletion. Our study also suggests that inducing ferroptosis may be a therapeutic strategy for NSCLC with EGFR exon 19 deletion.

Visualization Analysis of Artificial Intelligence Literature in Forensic Research.

OBJECTIVES: To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database, to explore research hotspots and developmental trends. METHODS: A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the literature measuring tool CiteSpace. The authors, institution, country (region), title, journal, keywords, cited references and other information of relevant literatures were analyzed. RESULTS: A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries (regions) were identified, with the number of articles published showing an increasing trend year by year. Among them, the United States had the highest number of publications and China ranked the second. Academy of Forensic Science had the highest number of publications among the institutions. Forensic Science International, Journal of Forensic Sciences, International Journal of Legal Medicine ranked high in publication and citation frequency. Through the analysis of keywords, it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technology for sex and age estimation, cause of death analysis, postmortem interval estimation, individual identification and so on. CONCLUSIONS: It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research. Exploring the combination of advanced artificial intelligence technologies with forensic research will be a hotspot and direction for future research.

Modular Strategy for Constructing para-Cage[n]arenes, meta-Cage[n]arenes, and meta-Bimacrocyclic-Arenes.

Here, we present a versatile modular strategy for crafting novel covalent organic cages (para-cage[n]arenes and meta-cage[n]arenes, n = 3,4) and bimacrocycles (meta-bimacrocyclic-arenes) with stable backbones and modifiable rims. These structures can be synthesized from commercially available aromatic multialdehydes in a three-step process: quantitative bromination, Suzuki-Miyaura reaction (yielding over 60%), and a rapid one-pot Friedel-Crafts reaction with paraformaldehyde. Notably, the cage[n]arenes exhibit a well-defined prismatic shape, and the bimacrocyclic-arenes display both dimeric and monomeric configurations.

Investigating acupoint selection and combinations of acupuncture for primary idiopathic tinnitus using data mining.

BACKGROUND: Acupuncture is widely used in the treatment of tinnitus worldwide because of its good efficacy and safety. However, the criteria for selecting acupoint prescriptions and combinations have not been summarized. Therefore, data mining was used herein to determine the treatment principles and the most effective acupoint selection for the treatment of idiopathic tinnitus. METHODS: The clinical research literature of acupuncture in the treatment of idiopathic tinnitus from the establishment of the database to September 1, 2023 in China National Knowledge Infrastructure, China Medical Journal Full-text Database, PubMed, Embase, Cochrane Library and Web of Science databases was retrieved and extracted. Microsoft Excel 2016 was used to establish the acupoint prescription database and the frequency statistics of acupoints, meridians and specific acupoints were carried out. IBM SPSS Statistics 25.0 software was used for cluster analysis of acupoints, and IBM SPSS Modeler18.0 software was used for association rule analysis of acupoints. RESULTS: A total of 112 articles were included, involving 221 acupuncture prescriptions, including 99 acupoints, with a total frequency of 1786 times. The 5 most frequently used acupoints were Tinggong (SI19), Tinghui (GB2), Yifeng (TE17), Ermen (TE21), and Zhongzhu (TE3). The commonly used meridians were Sanjiao meridian of hand-shaoyang, Gallbladder meridian of foot-shaoyang and Small intestine meridian of hand-taiyang. The specific points are mostly Crossing point, Five-shu point and Yuan-primary point. The core acupoint combination of association rules was Ermen (TE21)-Tinggong (SI19)-Tinghui (GB2)-Yifeng (TE17), and 3 effective clustering groups were obtained by cluster analysis of high-frequency acupoints. CONCLUSION: In this study, the published literature on acupuncture treatment of idiopathic tinnitus was analyzed by data mining, and the relationship between acupoints was explored, which provided a more wise choice for clinical acupuncture treatment of idiopathic tinnitus.

Gli1-mediated tumor cell-derived bFGF promotes tumor angiogenesis and pericyte coverage in non-small cell lung cancer.

BACKGROUND: Tumor angiogenesis inhibitors have been applied for non-small cell lung cancer (NSCLC) therapy. However, the drug resistance hinders their further development. Intercellular crosstalk between lung cancer cells and vascular cells was crucial for anti-angiogenenic resistance (AAD). However, the understanding of this crosstalk is still rudimentary. Our previous study showed that Glioma-associated oncogene 1 (Gli1) is a driver of NSCLC metastasis, but its role in lung cancer cell-vascular cell crosstalk remains unclear. METHODS: Conditioned medium (CM) from Gli1-overexpressing or Gli1-knockdown NSCLC cells was used to educate endothelia cells and pericytes, and the effects of these media on angiogenesis and the maturation of new blood vessels were evaluated via wound healing assays, Transwell migration and invasion assays, tube formation assays and 3D coculture assays. The xenograft model was conducted to establish the effect of Gli1 on tumor angiogenesis and growth. Angiogenic antibody microarray analysis, ELISA, luciferase reporte, chromatin immunoprecipitation (ChIP), bFGF protein stability and ubiquitination assay were performed to explore how Gli1 regulate bFGF expression. RESULTS: Gli1 overexpression in NSCLC cells enhanced the endothelial cell and pericyte motility required for angiogenesis required for angiogenesis. However, Gli1 knockout in NSCLC cells had opposite effect on this process. bFGF was critical for the enhancement effect on tumor angiogenesis. bFGF treatment reversed the Gli1 knockdown-mediated inhibition of angiogenesis. Mechanistically, Gli1 increased the bFGF protein level by promoting bFGF transcriptional activity and protein stability. Importantly, suppressing Gli1 with GANT-61 obviously inhibited angiogenesis. CONCLUSION: The Gli1-bFGF axis is crucial for the crosstalk between lung cancer cells and vascular cells. Targeting Gli1 is a potential therapeutic approach for NSCLC angiogenesis.