Water-Regulated Evolution of Inversion, Reinversion, and Amplification of Circularly Polarized Luminescence of Supramolecular Organogels Based on Glutamide-Cyanostilbene Amphiphile.

Water incorporated with supramolecular building blocks in organic solvents can play a key role in the circularly polarized luminescence (CPL) inversion and amplification of supramolecular assemblies. Herein, we demonstrate that fine-tuning the water content regulated the assembly structure evolution and made the circular dichroism and CPL sign of the system undergo intriguing inversion, reinversion, and amplification processes based on a unique and interesting glutamide-cyanostilbene system, as supported by morphology, spectroscopic observations, and time-dependent density functional theory calculation.

HIF-1α Pathway Orchestration by LCN2: A Key Player in Hypoxia-Mediated Colitis Exacerbation.

In this study, we investigated the role of hypoxia in the development of chronic inflammatory bowel disease (IBD), focusing on its impact on the HIF-1α signaling pathway through the upregulation of lipocalin 2 (LCN2). Using a murine model of colitis induced by sodium dextran sulfate (DSS) under hypoxic conditions, transcriptome sequencing revealed LCN2 as a key gene involved in hypoxia-mediated exacerbation of colitis. Bioinformatics analysis highlighted the involvement of crucial pathways, including HIF-1α and glycolysis, in the inflammatory process. Immune infiltration analysis demonstrated the polarization of M1 macrophages in response to hypoxic stimulation. In vitro studies using RAW264.7 cells further elucidated the exacerbation of inflammation and its impact on M1 macrophage polarization under hypoxic conditions. LCN2 knockout cells reversed hypoxia-induced inflammatory responses, and the HIF-1α pathway activator dimethyloxaloylglycine (DMOG) confirmed LCN2's role in mediating inflammation via the HIF-1α-induced glycolysis pathway. In a DSS-induced colitis mouse model, oral administration of LCN2-silencing lentivirus and DMOG under hypoxic conditions validated the exacerbation of colitis. Evaluation of colonic tissues revealed altered macrophage polarization, increased levels of inflammatory factors, and activation of the HIF-1α and glycolysis pathways. In conclusion, our findings suggest that hypoxia exacerbates colitis by modulating the HIF-1α pathway through LCN2, influencing M1 macrophage polarization in glycolysis. This study contributes to a better understanding of the mechanisms underlying IBD, providing potential therapeutic targets for intervention.

High-altitude hypoxia promotes BRD4-mediated activation of the Wnt/ß-catenin pathway and disruption of intestinal barrier.

Hypobaric hypoxia, commonly experienced at elevated altitudes, presents significant physiological challenges. Our investigation is centered on the impact of the bromodomain protein 4 (BRD4) under these conditions, especially its interaction with the Wnt/ß-Catenin pathway and resultant effects on glycolytic inflammation and intestinal barrier stability. By combining transcriptome sequencing with bioinformatics, we identified BRD4's key role in hypoxia-related intestinal anomalies. Clinical parameters of altitude sickness patients, including serum BRD4 levels, inflammatory markers, and barrier integrity metrics, were scrutinized. In vitro studies using CCD 841 CoN cells depicted expression changes in BRD4, Interleukin (IL)-1ß, IL-6, and ß-Catenin. Transepithelial electrical resistance (TEER) and FD4 analyses assessed barrier resilience. Hypoxia-induced mouse models, analyzed via H&E staining and Western blot, provided insights into barrier and protein alterations. Under hypoxic conditions, marked BRD4 expression variations emerged. Elevated serum BRD4 in patients coincided with intensified Wnt signaling, inflammation, and barrier deterioration. In vitro, findings showed hypoxia-induced upregulation of BRD4 and inflammatory markers but a decline in Occludin and ZO1, affecting barrier strength-effects mitigated by BRD4 inhibition. Mouse models echoed these patterns, linking BRD4 upregulation in hypoxia to barrier perturbations. Hypobaric hypoxia-induced BRD4 upregulation disrupts the Wnt/ß-Catenin signaling, sparking glycolysis-fueled inflammation and weakening intestinal tight junctions and barrier degradation.

Metal-ion-triggered symmetry breaking of completely achiral azobenzene amphiphiles in water.

Achieving control over symmetry breaking of completely achiral components in the aqueous phase is a significant challenge in supramolecular chemistry. Herein, we demonstrate that it is possible to construct chiral nanoassemblies by introducing metal ions (Zn2+, Fe3+, Al3+, Cu2+, and Ca2+) into completely achiral azobenzene amphiphiles with key structural factors in the pure aqueous phase. It is found that the coordination interactions, π-π stacking, hydrophilic and hydrophobic interactions, hydrogen bonding, and electrostatic interactions are crucial to the metal-ion-induced symmetry breaking of completely achiral building blocks. This study may provide an intriguing model system for constructing chiral assemblies based on completely achiral molecules.

Designing and preparing supramolecular encapsulation systems based on fraxetin and cyclodextrins for highly selective detection of nicotine.

Herein, a series of water-soluble supramolecular inclusion complexes (ICs) probes were prepared using cyclodextrins (CDs) and fraxetin (FRA) to detect nicotine (NT) with high selectivity in vitro and in vivo. The FRA/CD ICs prepared through the saturated solution method exhibited excellent water solubility, stability, and biocompatibility. A clear host-guest inclusion model was provided by the theoretical calculations. The investigation revealed that NT was able to enter into the cavities of FRA/ß-CD IC and FRA/γ-CD IC, and further formed charge transfer complexes with FRA in the CD cavities, resulting in a rapid and highly selective fluorescence-enhanced response with the lowest detection limits of 1.9 × 10-6 M and 9.7 × 10-7 M, and the linear response ranged from 0.02 to 0.3 mM and 0.01-0.05 mM, respectively. The IC probes showed good anti-interference performance to common interferents or different pH environments, with satisfactory reproducibility and repeatability of response to NT. Furthermore, the potentiality of the probes was confirmed through fluorescence imaging experiments using human lung cancer cells and the lung tissue of mice. This study offers a fresh perspective for detecting NT in environmental and biomedical analysis.

Immune function, gastrointestinal hormone levels, and their clinical significance in patients with gastric ulcers complicated with depression.

BACKGROUND: Gastric ulcer (GU) is a common digestive tract disease, and medical records of GU combined with depression are increasingly common. Currently, the risk factors and pathogenesis of GU complicated with depression remain unclear. Low immune function and gastrointestinal hormone levels may also be significant risk factors. Therefore, this study explored the immune function and gastrointestinal hormone levels in patients with GU combined with depression. AIM: To explore the immune function, gastrointestinal hormone level, and clinical significance of patients with GU combined with depression. METHODS: A retrospective analysis was conducted on 300 patients with GU combined with depression admitted to Guizhou Provincial People's Hospital from January 2021 to June 2022 as the study subjects. According to the Hamilton Depression Scale (HAMD) score, patients were divided into mild-to-moderate (n = 210) and heavy (n = 90) groups. Basic data, immune function indices [immunoglobulin A (IgA), IgM, IgG, serum CD4+ and CD8+ percentage, and CD4+/CD8+ ratio], and gastrointestinal hormone indices [serum gastrin (GAS), cholecystokinin (CCK), and motilin (MTL) levels] were collected. The basic data of the two groups were compared, and the immune function and gastrointestinal hormone indices were analyzed. Multivariate logistic regression was used to analyze the factors influencing the severity of GU complicated with depression. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to analyze the value of the immune function index, gastrointestinal hormone index, and combined index in predicting the severity of GU complicated with depression. RESULTS: There were no marked differences in sex, age, body mass index, abdominal distension, abdominal pain, belching, nausea, vomiting, or sleep disorders between the heavy and mild-to-moderate groups (P > 0.05). There was a marked difference in the family history of depression between the heavy and mild-to-moderate groups (P < 0.05). There were significant differences in serum IgA and IgM levels and serum CD4+, CD8+, and CD4+/CD8+ ratios between the heavy and mild-to-moderate groups (P < 0.05). Multivariate analysis showed that IgA, IgM, GAS, and CCK serum levels influenced the severity of GU with depression (P < 0.05). The AUC of the ROC curve for serum IgA level predicting GU with depression severity was 0.808 [95% confidence interval (CI): 0.760-0.857], the AUC of the serum IgM level was 0.757 (95%CI: 0.700-0.814), the AUC of the serum GAS level was 0.853 (95%CI: 0.810-0.897), the AUC of the serum CCK level was 0.762 (95%CI: 0.709-0.822), the AUC of immune function (IgA, IgM) and gastrointestinal hormone levels (GAS, CCK) for the prediction of GU with depression severity was 0.958 (95%CI: 0.933-0.976). CONCLUSION: Important factors influencing GU complicated with depression are serum IgA, IgM, GAS, and CCK indicators. They can be used as indicators to predict the severity of GU complicated with depression.

Comparison of oral sodium phosphate tablets and polyethylene glycol lavage solution for colonoscopy preparation: a systematic review and meta-analysis of randomized clinical trials.

Objective: To systematically compare the bowel cleaning ability, patient tolerance and safety of oral sodium phosphate tablets (NaPTab) and oral polyethylene glycol electrolyte lavage solution (PEGL) to inform clinical decision making. Methods: PubMed, Embase, CBM, WanFang Data, CNKI, and VIP databases were searched for studies that used randomized controlled trials (RCTs) to compare the roles of NaPTab and PEGL in bowel preparation before colonoscopy. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias in the included papers. A meta-analysis was performed using RevMan 5.3 software. Results: A total of 13 RCTs were eligible for inclusion, including 2,773 patients (1,378 and 1,395 cases in the NaPTab and PEGL groups, respectively). Meta-analysis revealed no significant difference in the cleansing quality of the NaPTab and PEGL groups [RR 1.02, 95% CI (0.96-1.08), P = 0.46]. The incidence of nausea was lower in the NaPTab group than in the PEGL group [RR 0.67, 95% CI (0.58-0.76), p < 0.00001]. Patients rated the taste of NaPTab higher than PEGL [RR 1.33, 95% CI (1.26-1.40), P < 0.00001]. Willingness to repeat the treatment was also higher in the NaPTab group than in the PEGL group [RR 1.52, 95% CI (1.28-1.80), P < 0.00001]. Both serum potassium and serum calcium decreased in both groups after the preparation; however, meta-analysis revealed that both minerals decreased more in the NaPTab group than in the PEGL group [MD = 0.38, 95% CI (0.13-0.62), P = 0.006 for serum potassium and MD = 0.41, 95% CI (0.04-0.77), P = 0.03 for serum calcium]. Meanwhile, serum phosphorus increased in both groups after the preparation; however, levels increased more in the NaPTab group than in the PEGL group [MD 4.51, (95% CI 2.9-6.11), P < 0.00001]. Conclusions: While NaP tablets and PEGL were shown to have a similar cleaning effect before colonoscopy, NaP tablets had improved patient tolerance. However, NaP tablets had a strong effect on serum potassium, calcium, and phosphorus levels. For patients with low potassium, low calcium, and renal insufficiency, NaP tablets should be prescribed with caution. For those at high-risk for acute phosphate nephropathy, NaP tablets should be avoided. Given the low number and quality of included studies, these conclusions will require additional verification by large high-quality studies. Systematic review registration: 10.37766/inplasy2023.5.0013, identifier: NPLASY202350013.

Integrative analysis of ferroptosis-related genes in ulcerative colitis.

OBJECTIVE: The aim of this study was to identify and validate ferroptosis-related markers in ulcerative colitis (UC) to explore new directions for UC diagnosis and treatment. METHODS: We screened UC chips and ferroptosis-related genes from the Gene Expression Omnibus (GEO), FerrDb, and GeneCards databases. The differentially expressed genes (DEGs) and ferroptosis-related DEGs between the UC group and normal controls were analyzed using bioinformatics methods. Enrichment analysis, protein-protein interaction analysis, and hub genes were screened. Peripheral blood chip and animal experiments were used to validate the ferroptosis-related hub genes. Finally, hub gene-transcription factor, hub gene-microRNA (miRNA), and hub gene-drug interaction networks were constructed. RESULTS: Overall, 26 ferroptosis-related DEGs were identified that were significantly enriched in energy pathways and metabolism. We identified ten ferroptosis-related hub genes from the protein-protein interaction network: IL6, PTGS2, HIF1A, CD44, MUC1, CAV1, NOS2, CXCL2, SCD, and ACSL4. In the peripheral blood chip GSE94648, CD44 and MUC1 were upregulated, which was consistent with the expression trend in GSE75214. Animal experiments showed that CD44 expression was significantly increased in the colon. CONCLUSIONS: Our findings indicate that CD44 and MUC1 may be ferroptosis-related markers in UC.

Co-assembled nanotubes with controlled curvature radius using a hydrogen bond regulation strategy.

The design of co-organized nanotube systems with controlled curvature radius that are realized by tilt modulation of co-assembled molecules, induced by the strength of non-covalent interactions in aqueous media, remains a significant challenge. Here, we report success in utilizing a hydrogen bond regulation strategy to stimulate molecular tilt for the formation of nanotubes with controlled curvature radius based on the co-assembly of two kinds of achiral cationic building blocks in aqueous solution. Computations and electron microscopy experiments suggest that the nanotube curvature radius drastically decreases as the tilt angle θ of co-assembled molecules increases with an increase of hydrogen bond strength. Interestingly, a slight change in the co-assembled molecular tilt causes a drastic change in the nanotube curvature radius.

Novel Amino-pillar[5]arene as a Fluorescent Probe for Highly Selective Detection of Au3+ Ions.

A novel fluorescent probe, amino-pillar[5]arene (APA), was prepared via a green, effective, and convenient synthetic method, which was characterized by nuclear magnetic resonance (NMR), infrared (IR), and high-resolution mass spectrometry. The fluorescence sensing behavior of the APA probe toward 22 metal ions in aqueous solutions were studied by fluorescence spectroscopy. The results showed that APA could be used as a selective fluorescent probe for the specificity detection of Au3+ ions. Moreover, the detection characteristics were investigated by fluorescence spectral titration, pH effect, fluorescence competitive experiments, Job's plot analysis, 1H NMR, and IR. The results indicated that detection of Au3+ ions by the APA probe could be achieved in the range of pH 1-13.5 and that other coexisting metal ions did not cause any marked interference. The titration analysis results indicated that the fluorescence intensity decreased as the concentration of Au3+ ions increased, with an excellent correlation (R 2 = 0.9942). The detection limit was as low as 7.59 × 10-8 mol·L-1, and the binding ratio of the APA probe with Au3+ ions was 2:1. Therefore, the APA probe has potential applications for detecting Au3+ ions in the environment and in living organisms.

Adsorption of nicotine in aqueous solution by a defective graphene oxide.

Extensive concerns have been focused on the emerging contaminants including nicotine in the aquatic system recently. Graphene oxide (GO) and modified graphene oxides (GO-COOH and defective GO-COOH) are used as effective adsorbents to remove nicotine from aqueous solution. The adsorption isotherms and kinetics of the adsorbents all fit well with Langmuir model and pseudo-second-order model, respectively. The thermodynamic studies show that the adsorption is an exothermic and spontaneous process. The influence of pH and ionic solution strength on the adsorbents is also investigated. The maximum adsorption capacity can be observed at pH value of ca. 8. The adsorption capacities of nicotine are decreased upon the increase of sodium ion concentration. Among all the adsorbents, the defective GO-COOH adsorbents possess the maximum adsorption capacity of nicotine of 196.5 mg g-1 obtained from Langmuir isotherm. In regeneration experiments, the defective GO-COOH adsorbents can maintain 95.1% of adsorption capacity after five times of cyclic adsorption-desorption processes. The adsorbents are identified by Fourier transform infrared, 13C solid-state magic-angle spinning nuclear magnetic resonance, X-ray photoelectron and Raman spectroscopies to determine the adsorption mechanisms and structure on the adsorbents. It can be deduced that the surpassing performance of defective GO-COOH may be ascribed to the unique adsorption mechanism of defects, the enhanced π-π interaction and cation-π bonding. The highly-efficient and stable features enable the defective GO-COOH a promising adsorbent to eliminate nicotine from water.

Novel 3-substituted N-methylcarbazole-imidazolium salt derivatives: Synthesis and cytotoxic activity.

A series of novel 3-substituted N-methylcarbazole-imidazolium salt derivatives has been prepared and evaluated in vitro against a panel of tumor cell lines (Hep G-2, Hela and PC12). The results suggest that the presence of substituted 2-methyl-imidazole or imidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl or 4-bromophenacyl group were important for improving cytotoxic activity. Compounds 17, 18, 27, and 28 with 4-bromophenacyl and naphthylacyl groups displayed good activities with IC50 values of 0.09-7.20 µm against three tumor cell lines investigated and more active than DDP. Compound 35 exhibited cytotoxic activity selectively against Hela cell.