Efficient remediation of different concentrations of Cr-contaminated soils by nano zero-valent iron modified with carboxymethyl cellulose and biochar.

Nano zero-valent iron (nZVI) is widely used in soil remediation due to its high reactivity. However, the easy agglomeration, poor antioxidant ability and passivation layer of Fe-Cr coprecipitates of nZVI have limited its application scale in Cr-contaminated soil remediation, especially in high concentration of Cr-contaminated soil. Herein, we found that the carboxymethyl cellulose on nZVI particles could increase the zeta potential value of soil and change the phase of nZVI. Along with the presence of biochar, 97.0% and 96.6% Cr immobilization efficiency through CMC-nZVI/BC were respectively achieved in high and low concentrations of Cr-contaminated soils after 90-days remediation. In addition, the immobilization efficiency of Cr(VI) only decreased by 5.1% through CMC-nZVI/BC treatment after 10 weeks aging in air, attributing to the strong antioxidation ability. As for the surrounding Cr-contaminated groundwater, the Cr(VI) removal capacity of CMC-nZVI/BC was evaluated under different reaction conditions through column experiments and COMSOL Multiphysics. CMC-nZVI/BC could efficiently remove 85% of Cr(VI) in about 400 hr when the initial Cr(VI) concentration was 40 mg/L and the flow rate was 0.5 mL/min. This study demonstrates that uniformly dispersed CMC-nZVI/BC has an excellent remediation effect on different concentrations of Cr-contaminated soils.

Identifying potential therapeutic targets in lung adenocarcinoma: a multi-omics approach integrating bulk and single-cell RNA sequencing with Mendelian randomization.

Our research aimed to identify new therapeutic targets for Lung adenocarcinoma (LUAD), a major subtype of non-small cell lung cancer known for its low 5-year survival rate of 22%. By employing a comprehensive methodological approach, we analyzed bulk RNA sequencing data from 513 LUAD and 59 non-tumorous tissues, identifying 2,688 differentially expressed genes. Using Mendelian randomization (MR), we identified 74 genes with strong evidence for a causal effect on risk of LUAD. Survival analysis on these genes revealed significant differences in survival rates for 13 of them. Our pathway enrichment analysis highlighted their roles in immune response and cell communication, deepening our understanding. We also utilized single-cell RNA sequencing (scRNA-seq) to uncover cell type-specific gene expression patterns within LUAD, emphasizing the tumor microenvironment's heterogeneity. Pseudotime analysis further assisted in assessing the heterogeneity of tumor cell populations. Additionally, protein-protein interaction (PPI) network analysis was conducted to evaluate the potential druggability of these identified genes. The culmination of our efforts led to the identification of five genes (tier 1) with the most compelling evidence, including SECISBP2L, PRCD, SMAD9, C2orf91, and HSD17B13, and eight genes (tier 2) with convincing evidence for their potential as therapeutic targets.

Cobalt germanium hydroxides with asymmetric electron distribution and surface hydroxyl groups for superb catalytic degradation performances.

Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) are attractive approaches for solving the global problem of water pollution, due to the generation of highly-active reactive oxygen species (ROS). Therefore, highly-efficient PMS activation is crucial for promoting the catalytic degradation of environmental pollutants. Here, bimetallic CoGeO2(OH)2 nanosheets with abundant surface hydroxyl groups (CGH) were synthesized via a simple hydrothermal route for PMS activation and degradation of various organic contaminants for the first time. The abundant surface hydroxyl groups (≡Co-OH/≡Ge-OH) could promptly initiate PMS to generate highly-active species: singlet oxygen (1O2), sulfate radicals (SO4·-) and hydroxyl radicals (HO•), while the asymmetric electron distribution among Co-O-Ge bonds derived from the higher electronegativity of Ge than Co further enhances the quick electron transfer to promote the redox cycle of Co2+/Co3+ and Ge2+/Ge4+, thereby achieving an outstanding catalytic capability. The optimal catalyst exhibits nearly 100 % catalytic degradation performance of dyes (Methylene blue, Rhodamine B, Methyl orange, Orange II, Methyl green) and antibiotics (Norfloxacin, Bisphenol A, Tetracycline) over a wide pH range of 3-11 and under different coexisting anion conditions (Cl-, HCO3-, NO3-, HA), suggesting the excellent adaptability for practical usage. This study could potentially lead to novel perspectives on the remediation of water areas such as groundwater and deep-water areas.

The impact of retrotransposons on castor bean genomes.

Castor bean (Ricinus communis L.) is an important oil crop. However, the influence of transposable elements (TEs) on the dynamics of castor bean evolution awaits further investigation. This study explored the role of transposable elements in the genomes of wild castor bean accessions from Ethiopia (Rc039) and Kenya (WT05) as well as in the cultivated variety (Hale). The distribution and composition of repeat sequences in these three lineages exhibited relative consistency, collectively accounting for an average of 36.7% of the genomic sequences. Most TE families displayed consistent lengths and compositions across these lineages. The dynamics of TEs significantly differed from those of genes, showing a lower correlation between the two. Additionally, the distribution of TEs on chromosomes showed an inverse trend compared to genes. Furthermore, Hale may have originated from the ancestor of Rc039. The divergent evolutionary paths of TEs compared to genes indicate the crucial role of TEs in shaping castor bean genetics and evolution, providing insights into the fields of castor bean and plant genomics research.

Tumor-Specific Nano-Herb Delivery System with High L-Arginine Loading for Synergistic Chemo and Gas Therapy against Cervical Cancer.

Cancer metastasis poses significant challenges in current clinical therapy. Osthole (OST) has demonstrated efficacy in treating cervical cancer and inhibiting metastasis. Despite these positive results, its limited solubility, poor oral absorption, low bioavailability, and photosensitivity hinder its clinical application. To address this limitation, a glutathione (GSH)-responded nano-herb delivery system (HA/MOS@OST&L-Arg nanoparticles, HMOA NPs) is devised for the targeted delivery of OST with cascade-activatable nitric oxide (NO) release. The HMOA NPs system is engineered utilizing enhanced permeability and retention (EPR) effects and active targeting mediated by hyaluronic acid (HA) binding to glycoprotein CD44. The cargoes, including OST and L-Arginine (L-Arg), are released rapidly due to the degradation of GSH-responsive mesoporous organic silica (MOS). Then abundant reactive oxygen species (ROS) are produced from OST in the presence of high concentrations of NAD(P)H quinone oxidoreductase 1 (NQO1), resulting in the generation of NO and subsequently highly toxic peroxynitrite (ONOO-) by catalyzing guanidine groups of L-Arg. These ROS, NO, and ONOO- molecules have a direct impact on mitochondrial function by reducing mitochondrial membrane potential and inhibiting adenosine triphosphate (ATP) production, thereby promoting increased apoptosis and inhibiting metastasis. Overall, the results indicated that HMOA NPs has great potential as a promising alternative for the clinical treatment of cervical cancer.

Novel therapeutic targets: bifidobacterium-mediated urea cycle regulation in colorectal cancer.

BACKGROUND AND PURPOSE: Colorectal cancer (CRC) is a widespread malignancy with a complex and not entirely elucidated pathogenesis. This study aims to explore the role of Bifidobacterium in the urea cycle (UC) and its influence on the progression of CRC, a topic not extensively studied previously. EXPERIMENTAL APPROACH: Utilizing both bioinformatics and experimental methodologies, this research involved analyzing bacterial abundance in CRC patients in comparison to healthy individuals. The study particularly focused on the abundance of BA. Additionally, transcriptomic data analysis and cellular experiments were conducted to investigate the impact of Bifidobacterium on ammonia metabolism and mitochondrial function, specifically examining its regulation of the key UC gene, ALB. KEY RESULTS: The analysis revealed a significant decrease in Bifidobacterium abundance in CRC patients. Furthermore, Bifidobacterium was found to suppress ammonia metabolism and induce mitochondrial dysfunction through the regulation of the ALB gene, which is essential in the context of UC. These impacts contributed to the suppression of CRC cell proliferation, a finding corroborated by animal experimental results. CONCLUSIONS AND IMPLICATIONS: This study elucidates the molecular mechanism by which Bifidobacterium impacts CRC progression, highlighting its role in regulating key metabolic pathways. These findings provide potential targets for novel therapeutic strategies in CRC treatment, emphasizing the importance of microbiota in cancer progression.

Antitumorigenic potential of Lactobacillus-derived extracellular vesicles: p53 succinylation and glycolytic reprogramming in intestinal epithelial cells via SIRT5 modulation.

OBJECTIVE: Colorectal cancer progression involves complex cellular mechanisms. This study examines the effects of Lactobacillus plantarum-derived extracellular vesicles (LEVs) on the SIRT5/p53 axis, focusing on glycolytic metabolic reprogramming and abnormal proliferation in intestinal epithelial cells. METHODS: LEVs were isolated from Lactobacillus plantarum and incubated with Caco-2 cells. Differential gene expression was analyzed through RNA sequencing and compared with TCGA-COAD data. Key target genes and pathways were identified using PPI network and pathway enrichment analysis. Various assays, including RT-qPCR, EdU staining, colony formation, flow cytometry, and Western blotting, were used to assess gene expression, cell proliferation, and metabolic changes. Co-immunoprecipitation confirmed the interaction between SIRT5 and p53, and animal models were employed to validate in vivo effects. RESULTS: Bioinformatics analysis indicated the SIRT5/p53 axis as a critical pathway in LEVs' modulation of colorectal cancer. LEVs were found to inhibit colorectal cancer cell proliferation and glycolytic metabolism by downregulating SIRT5, influencing p53 desuccinylation. In vivo, LEVs regulated this axis, reducing tumor formation in mice. Clinical sample analysis showed that SIRT5 and p53 succinylation levels correlated with patient prognosis. CONCLUSION: Lactobacillus-derived extracellular vesicles play a pivotal role in suppressing colonic tumor formation by modulating the SIRT5/p53 axis. This results in decreased glycolytic metabolic reprogramming and reduced proliferation in intestinal epithelial cells.

A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch.

Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.

Activation and antitumor immunity of CD8+ T cells are supported by the glucose transporter GLUT10 and disrupted by lactic acid.

CD8+ T cell activation leads to the rapid proliferation and differentiation of effector T cells (Teffs), which mediate antitumor immunity. Although aerobic glycolysis is preferentially activated in CD8+ Teffs, the mechanisms that regulate CD8+ T cell glucose uptake in the low-glucose and acidic tumor microenvironment (TME) remain poorly understood. Here, we report that the abundance of the glucose transporter GLUT10 is increased during CD8+ T cell activation and antitumor immunity. Specifically, GLUT10 deficiency inhibited glucose uptake, glycolysis, and antitumor efficiency of tumor-infiltrating CD8+ T cells. Supplementation with glucose alone was insufficient to rescue the antitumor function and glucose uptake of CD8+ T cells in the TME. By analyzing tumor environmental metabolites, we found that high concentrations of lactic acid reduced the glucose uptake, activation, and antitumor effects of CD8+ T cells by directly binding to GLUT10's intracellular motif. Disrupting the interaction of lactic acid and GLUT10 by the mimic peptide PG10.3 facilitated CD8+ T cell glucose utilization, proliferation, and antitumor functions. The combination of PG10.3 and GLUT1 inhibition or anti-programmed cell death 1 antibody treatment showed synergistic antitumor effects. Together, our data indicate that GLUT10 is selectively required for glucose uptake of CD8+ T cells and identify that TME accumulated lactic acid inhibits CD8+ T cell effector function by directly binding to GLUT10 and reducing its glucose transport capacity. Last, our study suggests disrupting lactate-GLUT10 binding as a promising therapeutic strategy to enhance CD8+ T cell-mediated antitumor effects.

LncRNA HOTAIRM1 promotes radioresistance in nasopharyngeal carcinoma by modulating FTO acetylation-dependent alternative splicing of CD44.

BACKGROUND: Radiotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC); however, almost 20% of patients experience treatment failure due to radioresistance. Therefore, understanding the mechanisms of radioresistance is imperative. HOTAIRM1 is deregulated in various human cancers, yet its role in NPC radioresistance are largely unclear. METHODS: This study investigated the association between HOTAIRM1 and radioresistance using CCK8, flow cytometry, and comet assays. Additionally, xenograft mice and patient-derived xenografts (PDX) models were employed to elucidate the biological functions of HOTAIRM1, and transcriptomic RNA sequencing was utilized to identify its target genes. RESULTS: Our study revealed an upregulation of HOTAIRM1 levels in radioresistant NPC cell lines and tissues. Furthermore, a positive correlation was noted between high HOTAIRM1 expression and increased NPC cell proliferation, reduced apoptosis, G2/M cell cycle arrest, and diminished cellular DNA damage following radiotherapy. HOTAIRM1 modulates the acetylation and stability of the FTO protein, and inhibiting FTO elevates the m6A methylation level of CD44 precursor transcripts in NPC cells. Additionally, silencing the m6A reading protein YTHDC1 was found to increase the expression of CD44V. HOTAIRM1 enhances NPC cell resistance to ferroptosis and irradiation through the HOTAIRM1-FTO-YTHDC1-CD44 axis. Mechanistically, HOTAIRM1 interacts with the FTO protein and induces m6A demethylation of the CD44 transcript. The absence of m6A modification in the CD44 transcript prevents its recognition by YTHDC1, resulting in the transition from CD44S to CD44V. An abundance of CD44V suppresses ferroptosis induced by irradiation and contributes to NPC radioresistance. CONCLUSIONS: In conclusion, the results in this study support the idea that HOTAIRM1 stimulates CD44 alternative splicing via FTO-mediated demethylation, thereby attenuating ferroptosis induced by irradiation and promoting NPC radioresistance.

Meibography signal intensity as a novel image biomarker for meibomian gland function: evidence from cross-sectional and longitudinal analyses.

Background: Meibomian gland dysfunction (MGD), one of the most common ocular surface diseases, can induce dry eye and reduce patients' quality of life. Methodological limitations have resulted in contradictory interpretations of gland function. This study sought to investigate the correlation between meibography signal intensity (SI) and meibomian gland (MG) function and to validate an MGD classification strategy based on different levels of SI. Methods: A multicenter, cross-sectional analysis was conducted on 817 eyes from 361 patients with MGD and 52 healthy controls. Additionally, 78 eyes from 39 patients with MGD who had undergone LipiFlow treatment were recruited for longitudinal analyses. The SI value was obtained via meibography using an automated analyzer, and all participants underwent ocular surface examinations. A cross-sectional analysis was performed to determine SI distribution and its relationship to clinical characteristics via a generalized estimating equation model. Longitudinal analyses were conducted on the treatment cohort using a mixed-effects model to explore the outcome in different SI levels. Results: Regression analysis revealed significant correlations between SI and lipid layer thickness (ß=0.016), meibum expressibility (ß=-0.676), meibum quality (ß=-0.251), and fluorescein-stained tear-film break-up time (FBUT) (ß=0.064) (all P values <0.001 for the above associations). Low-level SI MGD cases exhibited the most severe clinical signs, including the worst meibum expressibility (16% for level 3) and quality scores (19% for level 3), the shortest FBUT (3.82±0.13 s), and the thinnest lipid layer (65.68±2.58 nm), (all P values <0.05, respectively). Patients with medium SI showed the lowest ocular surface disease index (OSDI) value (26.64±1.06), the longest FBUT (4.56±0.08 s), and the thickest lipid layer (80.20±2.90 nm). After treatment, the high SI values reduced significantly at each follow-up point compared to baseline (all P values <0.05). The medium SI group demonstrated the greatest improvement in symptoms and signs, followed by the high SI group, and the low SI group. Conclusions: Automated measurements of SI can effectively reflect MG secretory activity. The proposed low, medium, and high SI classifications represent different functional subtypes of MGD.

CCR3 knockdown attenuates prolonged underwater operations-induced cognitive impairment via alleviating microglia-mediated neuroinflammation.

Maintaining cognitive integrity is crucial during underwater operations, which can significantly impact work performance and risk severe accidents. However, the cognitive effects of underwater operations and their underlying mechanism remain elusive, posing great challenges to the medical protection of professionals concerned. Here, we found that a single underwater operation session affects cognition in a time-dependent model. Prolonged exposure elicits significant cognitive impairment and hippocampal dysfunction, accompanied by increased neuroinflammation. Furthermore, RNA sequencing (RNA-seq) analysis revealed the involvement of neuroinflammation and highlighted the critical role of CCR3. Knockdown of CCR3 significantly rescued cognitive impairment and hippocampal dysfunction and reversed the upregulation of pro-inflammatory cytokines, by switching the activated microglia from a pro-inflammatory to a neuroprotective phenotype. Taken together, these results highlighted the time-dependent effects of a single underwater operation session on cognitive function. Knocking down CCR3 can attenuate neuroinflammation by regulating polarization of activated microglia, thereby alleviating prolonged underwater operations-induced cognitive impairment.

Exploring the diagnostic and prognostic significance of circulating tumor cells in stage II-IV colorectal cancer using a nano-based detection method.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality globally, underscoring the urgency for a noninvasive and effective biomarker to enhance patient prognosis. Circulating tumor cells (CTCs), a potential marker for real-time tumor monitoring, are limited in clinical utility due to the low sensitivity of existing detection methods. Previously, we introduced a novel Nano-based CTCs detection method that relies on the electrical properties of cell surfaces, thus eliminating thereby obviating the need for specific molecular biomarkers. In this study, we employed this technique to evaluate the diagnostic and prognostic value of CTCs in stage II-IV CRC. METHODS: A total of 194 participants were included, consisting of 136 CRC patients and 58 healthy individuals. The peripheral blood of the participants was collected, and CTCs enumeration was performed utilizing the Nano-based detection method that we newly developed. The Receiver Operating Characteristic (ROC) curve and multivariate Cox proportional-hazards analysis were employed to assess the effectiveness of CTCs for diagnosing CRC and predicting patient prognosis. RESULTS: The Nano-based method demonstrated an ability to differentiate CRC patients from healthy individuals with a sensitivity of 84.6% and a specificity of 94.8%. Furthermore, baseline CTCs levels were predictive of progression-free survival (PFS) in CRC patients, with lower levels associated with longer PFS compared to higher levels (4.5 months vs. 8.0 months at 15 CTCs/mL, p = 0.016; 4.4 months vs. 8.0 months at 20 CTCs/mL, p = 0.028). We also explored the dynamic changes in the number of CTCs after 1-5 cycles of chemotherapy. Patients with increasing CTCs levels typically experienced disease progression (PD), while those with decreasing levels often achieved a partial response (PR) or maintained stable disease (SD). These findings suggest that the dynamic fluctuations in CTCs counts are closely tied to the clinical course of the disease. CONCLUSION: Our study indicates the potential of Nano-based CTCs detection in diagnosing and predicting outcomes for patients with stage II-IV CRC.

Impact of federal antipsychotic use policy in nursing homes on new diagnoses for approved indications in dementia residents.

BACKGROUND: Federal policies targeting antipsychotic use among nursing home (NH) residents may have increased reporting of diagnoses for approved uses, including schizophrenia, Tourette's syndrome, and Huntington's Disease (called "exclusionary diagnoses" because they exclude residents from the antipsychotic quality metric). We assessed changes in new exclusionary diagnoses among long-stay NH admissions specifically with dementia following federal policies. METHODS: Retrospective, quarterly, interrupted time-series analysis (2009-2018) of new long-stay NH residents with dementia and no exclusionary diagnoses reported before NH admission. The National Partnership and the addition of facility level antipsychotic use to the Five Star Quality Rating system were key time exposures. Outcome was quarterly facility level predicted percentage of exclusionary diagnoses within 2 years of admission stratified by NH characteristics. RESULTS: For 264,095 long-stay admissions, mean percentage of new exclusionary diagnoses was 2.2% before the Partnership. After the Partnership, there was an unadjusted increase in the percentage over time (slope change, 0.044, p = 0.018), but the percentage never exceeded 2.9%. The Partnership contributed to a one-time decrease in diagnoses in NHs with an intermediate percentage of Black residents (-1.29%, p = 0.004). Before the Partnership, diagnoses were increasing among not-for-profit relative to for-profit NHs (0.044; p = 0.012), but after the Partnership, the pattern reversed. For-profit NHs saw an increase (+0.034, p = 0.002); not-for-profit NHs experienced a decrease (-0.014, p = 0.039). Quality Rating modifications had no significant effect. CONCLUSIONS: Exclusionary diagnosis reporting among long-stay NH residents with dementia, the group most at risk from antipsychotics, did not increase in response to federal policies. Evaluation of reasons for the observed increase in exclusionary diagnoses among non-dementia NH residents is warranted along with continued attention to how to incentivize the appropriate use of medications in residents with dementia that is crucial for high-quality NH care.

GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain: A Phase 3 Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China. Objective: To evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP. Design, Setting, and Participants: This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose. Intervention: In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment. Main Outcomes and Measures: The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences. Results: Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was -2.24 (1.55) for the 40-mg/d and -2.16 (1.79) for 80-mg/d groups and -1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common. Conclusions and Relevance: Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04647773.

A novel multimodal aptasensor for Patulin detection in fruit products based on high-performance RuMOF@hydrogel and versatile pericarp-derived carbonized polymer dots.

Patulin (PAT) is a widespread fruit toxin. Trace-level PAT exposure can cause serious harm to human health. Herein, a multimodal PAT aptasensor was designed based on Ru(bpy)32+-based metal organic framework composited hydrogel (RuMOF@hydrogel) and versatile banana peel-derived carbonized polymer dots (BPPDs). RuMOF@hydrogel modified magnetic-electrode exhibited excellent anodic and cathodic electrochemiluminescence (ECL) emission and stability. Meanwhile, the BPPDs could enhance anodic ECL of RuMOF@hydrogel, and also show excellent fluorescence (FL) and photothermal (PT) properties. With the aid of PAT-triggered hybridization chain reaction and magnetic separation, ECL, FL, and PT responses could be recorded concurrently. The detection limit can reach as low as 0.25 fg mL-1. The ratiometric ECL quantitation ensured the sensitivity and accuracy of this assay. And visual FL and portable PT modes contributed to the utility. Furthermore, this aptasensor demonstrated better performances than HPLC in fruit products and the protocol can be extended to determine various contaminants in foods.

Rosmarinic Acid Alleviates Radiation-Induced Pulmonary Fibrosis by Downregulating the tRNA N7-Methylguanosine Modification-Regulated Fibroblast-to-Myofibroblast Transition Through the Exosome Pathway.

Background: Radiation-induced pulmonary fibrosis (RIPF) is a common complication after radiotherapy in thoracic cancer patients, and effective treatment methods are lacking. The purpose of this study was to investigate the protective effect of rosmarinic acid (RA) on RIPF in mice as well as the mechanism involved. Methods: m7G-tRNA-seq and tRNA-seq analyses were conducted to identify m7G-modified tRNAs. Western blotting, immunohistochemistry, northwestern blotting, northern blotting, immunofluorescence, wound-healing assays and EdU experiments were performed to explore the molecular mechanism by which RA regulates fibroblast-to-myofibroblast transformation (FMT) by affecting the exosomes of lung epithelial cells. Ribo-seq and mRNA-seq analyses were used to explore the underlying target mRNAs. Seahorse assays and immunoprecipitation were carried out to elucidate the effects of RA on glycolysis and FMT processes via the regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) acetylation. Results: We found that RA had an antifibrotic effect on the lung tissues of RIPF model mice and inhibited the progression of FMT through exosomes derived from lung epithelial cells. Mechanistically, RA reduced the transcription and translation efficiency of sphingosine kinase 1 in lung fibroblasts by decreasing N7-methylguanosine modification of tRNA, downregulating the expression of tRNAs in irradiated lung epithelial cell-derived exosomes, and inhibiting the interaction between sphingosine kinase 1 and the N-acetyltransferase 10 protein in fibroblasts. Furthermore, the acetylation and cytoplasmic translocation of PFKFB3 were reduced by exosomes derived from irradiated lung epithelial cells, which following RA intervention. This suppression of the FMT process, which is triggered by glycolysis, and ultimately decelerating the progression of RIPF. Conclusion: These findings suggest that RA is a potential therapeutic agent for RIPF.

Qianggu concentrate: unlocking bone protection power via antioxidative SIRT1/NRF2/HO-1 pathways in type 2 diabetic osteoporosis.

Background: Qianggu Concentrate (QGHJ), a traditional Chinese medicine, is extensively used to treat Type 2 Diabetic Osteoporosis (T2DOP). Despite its widespread use, research on its therapeutic mechanisms within T2DOP is notably scarce. Objective: To explore QGHJ's osteoprotection in T2DOP rats and BMSCs, focusing on the antioxidant activation of SIRT1/NRF2/HO-1 and NRF2 nuclear migration. Methods: QGHJ constituent analysis was performed using UPLC-HRMS. Safety, bone-health efficacy, and glucose metabolic effects in T2DOP rats were evaluated via general condition assessments, biomarker profiling, micro-CT, biomechanics, staining methods, and ELISA, supplemented by RT-qPCR and Western blot. BMSCs' responses to QGHJ under oxidative stress, including viability, apoptosis, and osteogenic differentiation, were determined using CCK-8, flow cytometry, ALP/ARS staining, and molecular techniques. The modulation of the SIRT1/NRF2/HO-1 pathway by QGHJ was explored through oxidative stress biomarkers, immunofluorescence, and Western blot assays. Results: UPLC-HRMS identified flavonoids, monoterpenes, and isoflavones as QGHJ's key compounds. In vivo, QGHJ proved safe and effective for T2DOP rats, enhancing bone mineral density, microenvironment, and biomechanical properties without impairing vital organs. It modulated bone markers PINP, TRACP 5b, RUNX2 and PPARγ, favoring bone anabolism and reduced catabolism, thus optimizing bone integrity. QGHJ also regulated glycemia and mitigated insulin resistance. In vitro, it preserved BMSCs' viability amidst oxidative stress, curbed apoptosis, and fostered osteogenesis with regulated RUNX2/PPARγ expression. Mechanistic insights revealed QGHJ activated the SIRT1/NRF2/HO-1 pathway, augmented NRF2 nuclear translocation, and enhanced the antioxidative response, promoting bone health under stress. Conclusion: In T2DOP rat and BMSCs oxidative stress models, QGHJ's bone protection is anchored in its antioxidative mechanisms via the SIRT1/NRF2/HO-1 pathway activation and NRF2 nuclear translocation.

The Effect of Unhealthy Food Packaging Information Boundaries on Consumer Purchasing Intentions.

Existing studies have examined unhealthy food packaging information, mainly focusing on aspects such as the content, color, and text, whilst paying less attention to the boundaries of information. This paper investigates unhealthy foods through three experiments, revealing that the presence (vs. absence) of packaging information boundaries on unhealthy foods has a negative impact on consumers' purchasing intentions (p = 0.040) (Experiment 1). The feeling of constraint mediates this effect (ß = -0.078, CI: [-0.1911, -0.0111]) (Experiment 2). Additionally, consumers with an independent self-construal exhibit reduced purchasing intentions when unhealthy food packaging information boundaries are present (vs. absent) (p < 0.001), whereas those with an interdependent self-construal show increased purchasing intentions under the same conditions (p = 0.024) (Experiment 3). This paper reveals the psychological mechanism and boundary conditions of unhealthy food packaging information boundaries affecting consumers' purchasing intention and provides practical inspiration for government policy-making related to unhealthy food packaging.

Effect of capsular polysaccharide phase variation on biofilm formation, motility and gene expression in Vibrio vulnificus.

Vibrio vulnificus, a significant marine pathogen, undergoes opaque (Op)-translucent (Tr) colony switching based on whether capsular polysaccharide (CPS) is produced. CPS phase variation is sometime accompanied by genetic variation or down-regulation of particular genes, such as wzb. In addition, CPS prevents biofilm formation and is important to the virulence of V. vulnificus. However, the extent to which there is a difference in gene expression between Tr and Op colonies and the impact of CPS phase variation on other behaviors of V. vulnificus remain unknown. In this work, the data have shown that CPS phase variation of V. vulnificus is affected by incubation time. Tr and Op strains exhibited similar growth rates. However, Tr strains had enhanced biofilm formation capacities but reduced swimming motility compared to Op strains. The RNA-seq assay revealed 488 differentially expressed genes, with 214 downregulated and 274 upregulated genes, between Tr and Op colonies. Genes associated with Tad pili and CPS were downregulated, whereas those involved in flagellum were upregulated, in Tr colonies compared with Op colonies. In addition, 9 putative c-di-GMP metabolism-associated genes and 28 genes encoding putative regulators were significantly differentially expressed, suggesting that CPS phase variation is probably strictly regulated in V. vulnificus. Moreover, 8 genes encoding putative porins were also differentially expressed between the two phenotypic colonies, indicating that bacterial outer membrane was remodeled during CPS phase variation. In brief, this work highlighted the gene expression profiles associated with CPS phase variation, but more studies should be performed to disclose the intrinsic mechanisms in the future.