Risk factor differences in five-year progression of Intracranial artery stenosis and cerebral small vessel disease in general population.

BACKGROUND: Intracranial artery stenosis (ICAS) and cerebral small vessel disease (CSVD) are associated with a heavy socioeconomic burden; however, their longitudinal changes remain controversial. METHODS: We conducted a longitudinal analysis on 756 participants of Shunyi Cohort who underwent both baseline and follow-up brain magnetic resonance imaging (MRI) and MR angiography in order to investigate the risk factors for ICAS and CSVD progression in community population. Incident ICAS was defined as new stenosis occurring in at least one artery or increased severity of the original artery stenosis. CSVD markers included lacunes, cerebral microbleeds (CMB), and white matter hyperintensities (WMH). RESULTS: After 5.58 ± 0.49 years of follow-up, 8.5% of the 756 participants (53.7 ± 8.0 years old, 65.1% women) had incident ICAS. Body mass index (BMI) (OR = 1.09, 95% CI = 1.01-1.17, p = 0.035) and diabetes mellitus (OR = 2.67, 95% CI = 1.44-4.93, p = 0.002) were independent risk factors for incident ICAS. Hypertension was an independent risk factor for incident lacunes (OR = 2.12, 95% CI = 1.20-3.77, p = 0.010) and CMB (OR = 2.32, 95% CI = 1.22-4.41, p = 0.011), while WMH progression was primarily affected by BMI (ß = 0.108, SE = 0.006, p = 0.002). A higher LDL cholesterol level was found to independently protect against WMH progression (ß = -0.076, SE = 0.027, p = 0.019). CONCLUSIONS: Modifiable risk factor profiles exhibit different in patients with ICAS and CSVD progression. Controlling BMI and diabetes mellitus may help to prevent incident ICAS, and antihypertensive therapy may conduce to mitigate lacunes and CMB progression. LDL cholesterol may play an inverse role in large arteries and small vessels.

Is bone mineral density in middle-aged and elderly individuals associated with their dietary patterns? A study based on NHANES.

Introduction: Bone mineral density (BMD) is a crucial index for predicting fracture risk and diagnosing osteoporosis. With the global rise in osteoporosis prevalence, understanding the relationship between dietary patterns and BMD is vital for public health. This study aimed to explore the association between various dietary patterns and BMD among adults using data from the National Health and Nutrition Examination Survey (NHANES). Methods: Data were analyzed from 8,416 NHANES participants aged 40 years and older across three non-consecutive survey cycles from 2013 to 2020. Dietary patterns were identified using a combination of factor analysis and cluster analysis. BMD measurements were then assessed, and associations with the identified dietary patterns were analyzed, with adjustments made for demographic variables. Results: The analysis identified three distinct dietary patterns: "Low protein-High Dietary fiber-Vitamin A-Magnesium (LP-HDF-Vit A-Mg)", "High macronutrient-Choline-Selenium (HM-Cho-Se)", and "Low macronutrient-Vitamin D-Calcium (LM-Vit D-Ca)", and then we found that women, older adults, and certain ethnic groups were at higher risk for low BMD. Participants adhering to the "HM-Cho-Se" and "LP-HDF-Vit A-Mg" dietary patterns exhibited significantly higher BMD compared to those following the "LM-Vit D-Ca" pattern. After adjusting for demographic variables, the "HM-Cho-Se" pattern remained positively associated with BMD, while the "LM-Vit D-Ca" pattern showed no significant association with BMD or the risk of low BMD. Discussion: The findings suggest that adherence to the "HM-Cho-Se" dietary pattern may reduce the risk of low BMD, indicating potential synergies between these nutrients for bone health. However, the study has limitations, including the cross-sectional design and potential subjectivity in factor analysis. Future research should focus on longitudinal studies involving diverse age groups to better understand the causal relationship between dietary patterns and BMD. Despite these limitations, the study highlights the importance of dietary factors in maintaining bone health and suggests potential dietary interventions to reduce the risk of low BMD and osteoporosis.

Revealing and reconstructing the 3D Li-ion transportation network for superionic poly(ethylene) oxide conductor.

Understanding the Li-ions conduction network and transport dynamics in polymer electrolyte is crucial for developing reliable all-solid-state batteries. In this work, advanced nano- X-ray computed tomography combined with Raman spectroscopy and solid state nuclear magnetic resonance are used to multi-scale qualitatively and quantitatively reveal ion conduction network of poly(ethylene) oxide (PEO)-based electrolyte (from atomic, nano to macroscopic level). With the clear mapping of the microstructural heterogeneities of the polymer segments, aluminium-oxo molecular clusters (AlOC) are used to reconstruct a high-efficient conducting network with high available Li-ions (76.7%) and continuous amorphous domains via the strong supramolecular interactions. Such superionic PEO conductor (PEO-LiTFSI-AlOC) exhibites a molten-like Li-ion conduction behaviour among the whole temperature range and delivers an ionic conductivity of 1.87 × 10-4 S cm-1 at 35 °Ï¹. This further endows Li electrochemical plating/stripping stability under 50 µA cm-2 and 50 µAh cm-2 over 2000 h. The as-built Li|PEO-LiTFSI-AlOC|LiFePO4 full batteries show a high rate performance and a capacity retention more than 90% over 200 cycling at 250 µA cm-2, even enabling a high-loading LiFePO4 cathode of 16.8 mg cm-2 with a specific capacity of 150 mAh g-1 at 50 °Ï¹.

Self-assembled Fe3O4-COOH @ hydrogen-bonded organic framework composites for magnetic solid-phase extraction of tetracycline in food samples coupled with HPLC determination.

Magnetic solid-phase extraction (MSPE) technology for tetracycline (TCC) was developed by employing the novel and pre-designed Fe3O4-COOH@hydrogen-bonded organic frameworks (HOFs) adsorbents in complex food samples. The HOF shell was grown onto the Fe3O4-COOH core by in-situ self-assembled method. The excellent MSPE performances with less solvent, less adsorbent and time consumption were derived from the hydrogen bonding, π-π and hydrophobic interactions between HOF shell and TCC. Combined with HPLC analysis, Fe3O4@ HOFs adsorbent reduced matrix effects and the established MSPE-HPLC method for TCC gave the linearity of 0.001-6 µg mL-1 with the limit of detection 0.0003 µg mL-1. The recoveries in pure milk, canned yellow peach and carrot were 82.4-103.7 %. The method provided a simple, efficient and dependable alternative to monitor trace TCC antibiotics in food or environmental samples.

CRISPR-based dual-aptamer proximity ligation coupled hybridization chain reaction for precise detection of tumor extracellular vesicles and cancer diagnosis.

Tumor cell-derived extracellular vesicles (TEVs) contain numerous cellular molecules and are considered potential biomarkers for non-invasive liquid biopsy. However, due to the low abundance of TEVs secreted by tumor cells and their phenotypic heterogeneity, there is a lack of sensitive and specific methods to quantify TEVs. Here, we developed a dual-aptamer proximity ligation-coupled hybridization chain reaction (HCR) method for tracing TEVs, exploiting CRISPR to achieve highly sensitive detection. Taking advantage of the high binding affinity of aptamers, the two aptamers (AptEpCAM, AptHER2) exhibited the high selectivity for TEVs recognition. HCR generated long-repeated sequence containing multiple crRNA targetable barcodes, and the signals were further amplified by CRISPR upon recognizing the HCR sequences, thereby enhancing the sensitivity. Under optimal conditions, the developed method demonstrated a favorable linear relationship in the range of 2 × 103-107 particles/µL, with a limit of detection (LOD) of 3.3 × 102 particles/µL. We directly applied our assay to clinical plasma analysis, achieving 100 % accuracy in cancer diagnosis, thus demonstrating the potential clinical applications of TEVs. Due to its simplicity and rapidity, excellent sensitivity and specificity, this method has broad applications in clinical medicine.

Correlation between Circle of Willis configuration and intracranial arterial dolichoectasia, and genetic contributions.

OBJECTIVES: Intracranial arterial dolichoectasia (IADE) is characterized by the dilation, elongation, and tortuosity of intracranial arteries. We aimed to investigate the association between variations of the Circle of Willis (COW) and IADE in the general population, as well as estimate the genetic correlation between COW variations and IADE. METHODS: A total of 981 individuals from a population-based cohort were included. Brain magnetic resonance angiography was performed to assess COW variants and measure the diameters of intracranial arteries. IADE was defined as a total intracranial volume-adjusted diameter ≥ 2 standard deviations. Logistic regression models were used to analyze the association between COW variations and IADE. The heritability and genetic correlation were estimated using genome-wide complex trait analysis (GCTA) based on single nucleotide polymorphism (SNP) array data. RESULTS: The prevalence of IADE was 6.2 %. Hypoplastic/absent A1 segments were associated with an increase in contralateral ICA diameter (ß ± SE, 0.279 ± 0.049; p = 0.001) and a decrease in ipsilateral ICA diameter (ß ± SE, -0.300 ± 0.050; p = 0.001). Fetal-type posterior cerebral artery (FTP) was associated with a larger ICA diameter (ß ± SE, 0.326 ± 0.048; p = 0.001) and a smaller BA diameter (ß ± SE, -0.662 ± 0.043; p = 0.001). FTP revealed a positive genetic correlation with ICA dilation (rG = 0.259 ± 0.175; p = 0.0009) and a negative genetic correlation with BA dilation (rG = -0.192 ± 0.153, p = 0.015). CONCLUSIONS: There was an association between COW variations and larger intracranial arterial diameters in the general population. Genetic factors may play a role in the development of intracranial arterial dilation and the formation of COW variants.

Olfactory toxicity of tetrabromobisphenol A to the goldfish Carassius auratus.

Tetrabromobisphenol A (TBBPA) is one of the most extensively used brominated flame retardants and its increasing use in consumer products has raised concerns about its ecotoxicity. Given the ubiquity of TBBPA in aquatic environments, it is inevitable that these chemicals will enter the olfactory chambers of fish via water currents. Nevertheless, the olfactory toxicity of TBBPA to aquatic organisms and the underlying toxic mechanisms have yet to be elucidated. Therefore, we investigated the olfactory toxicity of TBBPA in the goldfish Carassius auratus, a model organism widely used in sensory biology. Results showed that exposure to TBBPA resulted in abnormal olfactory-mediated behaviors and diminished electro-olfactogram (EOG) responses, indicating reduced olfactory acuity. To uncover the underlying mechanisms of action, we examined the structural integrity of the olfactory epithelium (OE), expression levels of olfactory G protein-coupled receptors (GPCRs), enzymatic activities of ion transporters, and fluctuations in neurotransmitters. Additionally, comparative transcriptomic analysis was employed to investigate the molecular mechanisms further. Our study demonstrates for the first time that TBBPA at environmentally relevant levels can adversely affect the olfactory sensitivity of aquatic organisms by interfering with the transmission of aqueous stimuli to olfactory receptors, impeding the binding of odorants to their receptors, disrupting the olfactory signal transduction pathway, and ultimately affecting the generation of action potentials.

Novel circular RNA hsa_circ_0036683 suppresses proliferation and migration by mediating the miR-4664-3p/CDK2AP2 axis in non-small cell lung cancer.

BACKGROUND: The aim of the present study was to investigate the function of novel circular RNA hsa_circ_0036683 (circ-36683) in non-small cell lung cancer (NSCLC). METHODS: RNA sequencing was used to screen out differentially expressed miRNAs. Expression levels of miR-4664-3p and circ-36683 were evaluated in lung carcinoma cells and tissues by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The effects of miR-4664-3p and circ-36683 on proliferation and migration were assessed using cell counting kit-8 (CCK-8), wound healing and transwell migration assays and xenograft experiments. The targeting relationship of circ-36683/miR-4664-3p/CDK2AP2 was assessed by luciferase reporter assays, western blot, qRT-PCR and argonaute2-RNA immunoprecipitation (AGO2 RIP). Co-immunoprecipitation (Co-IP), 5-ethynyl-2'-deoxyuridine (EdU) staining and CCK-8 were used to validate the indispensable role of CDK2AP2 in suppressing cell proliferation as a result of CDK2AP1 overexpression. RESULTS: By RNA sequencing, miR-4664-3p was screened out as an abnormally elevated miRNA in NSCLC tissues. Transfection of miR-4664-3p could promote cell proliferation, migration and xenograft tumor growth. As a target of miR-4664-3p, CDK2AP2 expression was downregulated by miR-4664-3p transfection and CDK2AP2 overexpression could abolish the proliferation promotion resulting from miR-4664-3p elevation. Circ-36683, derived from back splicing of ABHD2 pre-mRNA, was attenuated in NSCLC tissue and identified as a sponge of miR-4664-3p. The functional study revealed that circ-36683 overexpression suppressed cell proliferation, migration and resulted in G0/G1 phase arrest. More importantly, the antioncogenic function of circ-36683 was largely dependent on the miR-4664-3p/CDK2AP2 axis, through which circ-36683 could upregulate the expression of p53/p21/p27 and downregulate the expression of CDK2/cyclin E1. CONCLUSION: The present study revealed the antioncogenic role of circ-36683 in suppressing cell proliferation and migration and highlighted that targeting the circ-36683/miR-4664-3p/CDK2AP2 axis is a promising strategy for the intervention of NSCLC.

Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking.

BACKGROUND: Hypertrophic scar (HTS) is dermal fibroproliferative disorder, which may cause physiological and psychological problems. Currently, the potential mechanism of WuFuYin (WFY) in the treatment of HTS remained to be elucidated. AIM: To explore the potential mechanism of WFY in treating HTS. METHODS: Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. HTS-related genes were obtained from the GeneCards, DisGeNET, and National Center for Biotechnology Information. The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome (KEGG) enrichment analysis. A protein + IBM-protein interaction (PPI) network was developed using STRING database and Cytoscape. To confirm the high affinity between compounds and targets, molecular docking was performed. RESULTS: A total of 65 core genes, which were both related to compounds and HTS, were selected from multiple databases. PPI analysis showed that CKD2, ABCC1, MMP2, MMP9, glycogen synthase kinase 3 beta (GSK3B), PRARG, MMP3, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) were the hub targets and MOL004941, MOL004935, MOL004866, MOL004993, and MOL004989 were the key compounds of WFY against HTS. The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway. Moreover, by performing molecular docking, we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity. CONCLUSION: The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941, MOL004989, and MOL004993 were the main compounds of WFY in HTS treatment.

Serum anti­KIAA0513 antibody as a common biomarker for mortal atherosclerotic and cancerous diseases.

Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases.

Automated diffusion-weighted image analysis along the perivascular space index reveals glymphatic dysfunction in association with brain parenchymal lesions.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

Analysing substitutions in recent World Cups and European Championships in male and female elite football - influence of new substitution rules.

Substitutions play a key role in modern football and can substantially affect the physical and overall performance of a team, and the recent substitution rule changes are worth investigating. This study explored the characteristics of substitutions, including different substitution rules, game results, sex, competition stages, tournaments and penalty shoot-outs success rates. We analysed data from a total of 3,738 substitutions from the last 10 years (2013-2023) of European Championships and World Cups, both men's and women's games. Non-parametric tests and chi-square tests were used for statistical analysis with the significance level set at p < 0.05. With the 5-substitution rule, 48% more substitutions occurred compared to the 3-substitution rule (4.26 ± 1.07 vs. 2.87 ± 0.43, p < 0.05) with a slight increase in the average substitution time (70.6 ± 14.3 vs. 69.2 ± 14.6 min, p < 0.05), and 10% more substitutions in the men's game compared to the women's game (p < 0.05). The timing of the first substitution was slightly different in the knock-out stage compared to group stage (59.8 ± 14.7 vs. 57.2 ± 13.3 min, p < 0.05), and the timing for the winning team and drawing team was later than for the losing team (p < 0.05). A total of 13.2% goals were scored by substitutes, with no significant difference between the 5-substitution rule (15.9%) vs the 3-substition rule (12.5%) (p > 0.05). Interestingly, substitute players had a lower success rate in penalty shoot-out compared to starters (61 vs. 74%, p < 0.05). Additionally, substitute player goal scorers entered the pitch later (p < 0.05) in male games compared to female games and in knock-out stage games compared to group games. This study highlights the importance of substitution rules and timing in modern elite football matches. The timing of the first substitution, introduction of substitutes in knock-out stages, and a lower success rate of substitute players in penalty shoot-outs are crucial factors to consider. Coaches can use this information to make strategic substitution decisions to improve team performance.

Development and Clinical Applications of Therapeutic Cancer Vaccines with Individualized and Shared Neoantigens.

Neoantigens, presented as peptides on the surfaces of cancer cells, have recently been proposed as optimal targets for immunotherapy in clinical practice. The promising outcomes of neoantigen-based cancer vaccines have inspired enthusiasm for their broader clinical applications. However, the individualized tumor-specific antigens (TSA) entail considerable costs and time due to the variable immunogenicity and response rates of these neoantigens-based vaccines, influenced by factors such as neoantigen response, vaccine types, and combination therapy. Given the crucial role of neoantigen efficacy, a number of bioinformatics algorithms and pipelines have been developed to improve the accuracy rate of prediction through considering a series of factors involving in HLA-peptide-TCR complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. On the other hand, shared neoantigens, originating from driver mutations at hot mutation spots (e.g., KRASG12D), offer a promising and ideal target for the development of therapeutic cancer vaccines. A series of clinical practices have established the efficacy of these vaccines in patients with distinct HLA haplotypes. Moreover, increasing evidence demonstrated that a combination of tumor associated antigens (TAAs) and neoantigens can also improve the prognosis, thus expand the repertoire of shared neoantigens for cancer vaccines. In this review, we provide an overview of the complex process involved in identifying personalized neoantigens, their clinical applications, advances in vaccine technology, and explore the therapeutic potential of shared neoantigen strategies.

Melatonin mitigates cadmium toxicity by promoting root development, delaying root senescence, and regulating cadmium transport in cotton.

Cd ions are absorbed and transported from the soil by crop roots, which are the first organ to be exposed to Cd. This results in an increase in cadmium ions in crops, significantly affecting crop growth and yield. Exogenous melatonin (MT) can help reduce cadmium (Cd) stress in cotton, but the specific contribution of roots to this process remains unclear. In order to address this knowledge gap, an in-situ root phenotyping study was conducted to investigate the the phenotype and lifespan of roots under cadmium stress (Cd) and melatonin treatment (Cd + MT). The results showed that MT alleviated the decreases in plant height, leaf area, SPAD value, stem diameter, stomatal conductance and net photosynthetic rate under Cd stress, which further promoted the biomass accumulation in various cotton organs. What is more, the Cd + MT treatment increased root volume, surface area, and length under Cd stress by 25.63 %, 10.58 %, and 21.89 %, respectively, compared with Cd treatment. Interestingly, compared to Cd treatment, Cd + MT treatment also significantly extended the lifespan of roots and root hairs by 6.68 days and 2.18 days, respectively. In addition, Cd + MT treatment reduced the transport of Cd from roots to shoots, particularly to bolls, and decreased the Cd bioconcentration factor in bolls by 61.17 %, compared to Cd treatment. In conclusion, these findings show that applying MT externally helps reduce Cd stress by delaying root senescence, promoting root development and regulating Cd transport. This method can be an effective approach to managing Cd stress in cotton.

Facile preparation of covalent-organic framework composites for magnetic solid-phase extraction of naphthaleneacetic acid in food prior to HPLC-UV analysis.

Novel magnetic covalent organic frameworks (COFs) were prepared by one-pot synthetic strategy and employed as an efficient adsorbent for magnetic solid-phase extraction (MSPE) of naphthaleneacetic acid (NAA) in food samples. Depending on the predesigned the hydrogen bonding, π-π and hydrophobic interactions of magnetic COFs, the efficient and selective extraction process for NAA was achieved within 15 min. The magnetic COFs adsorbent combined with HPLC-UV was devoted to develop a novel quantitative method for NAA in complex food. The method afforded good coefficient in range of 0.002-10.0 µg mL-1 and low limit of detection was 0.0006 µg mL-1. And the newly established method afforded less adsorbent consumption, wider linearity and lower LODs than the reported analytical methods. Ultimately, the method was successfully applied to determine NAA in fresh pear, tomato and peach juice. The magnetic COFs based MSPE coupled with HPLC-UV method provided a simple, efficient and dependable alternative to monitor trace NAA in food samples.

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer.

Magnesium (Mg) deficiency is associated with increased risk and malignancy in colorectal cancer (CRC), yet the underlying mechanisms remain elusive. Here, we used genomic, proteomic, and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC. Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors, including key driver genes such as KMT2C and ERBB3. Unexpectedly, initiation driver genes of CRC, such as TP53 and APC, displayed higher mutation frequencies in High-Mg tumors. Additionally, proteomic and phosphoproteomic data indicated that low Mg content in tumors may activate epithelial-mesenchymal transition (EMT) by modulating inflammation or remodeling the phosphoproteome of cancer cells. Notably, we observed a negative correlation between the phosphorylation of DBN1 at S142 (DBN1S142p) and Mg content. A mutation in S142 to D (DBN1S142D) mimicking DBN1S142p upregulated MMP2 and enhanced cell migration, while treatment with MgCl2 reduced DBN1S142p, thereby reversing this phenotype. Mechanistically, Mg2+ attenuated the DBN1-ACTN4 interaction by decreasing DBN1S142p, which in turn enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization, ultimately reducing MMP2 expression. These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may be a promising preventive and therapeutic strategy for CRC.

Isolation and Characterization of Meniscus Progenitor Cells From Rat, Rabbit, Goat, and Human.

OBJECTIVE: Meniscus progenitor cells (MPCs) have been identified as promising candidates for meniscus regeneration, and it is crucial for us to understand meniscus injury repair mechanism at the cellular level. In this study, we investigate the biological properties of MPCs isolated from different species using the differential adhesion to fibronectin (DAF) technique. We aim to characterize MPCs in different species and evaluate the feasibility of these models for future meniscal investigation. DESIGN: MPCs were isolated from freshly digested meniscus from rat, rabbit, goat, and human cells using DAF. Biological properties, including proliferation, colony-forming, multilineage differentiation, and migration abilities, were compared in MPCs and their corresponding mixed meniscus cell (MCs) population in each species. RESULTS: MPCs were successfully isolated by the DAF technique in all species. Rat MPCs appeared cobblestone-like, rabbit MPCs were more polygonal, goat MPCs had a spindle-shaped morphology, human MPCs appear more fibroblast-like. Compared with MCs, isolated MPCs showed progenitor cell characteristics, including multilineage differentiation ability and MSC (mesenchymal stem cells) markers (CD166, CD90, CD44, Stro-1) expression. They also highly expressed fibronectin receptors CD49e and CD49c. MPCs also showed greater proliferation capacity and retained colony-forming ability. Except for goat MPCs showed greater migration abilities than MCs, no significant differences were found in the migration ability between MPCs and MCs in other species. CONCLUSION: Our study shows that DAF is an effective method for isolating MPCs from rat, rabbit, goat, and human. MPCs in these species demonstrated similar characteristics, including greater proliferation ability and better chondrogenic potential.

Symbiodiniaceae and Ruegeria sp. Co-Cultivation to Enhance Nutrient Exchanges in Coral Holobiont.

The symbiotic relationship between corals and their associated microorganisms is crucial for the health of coral reef eco-environmental systems. Recently, there has been a growing interest in unraveling how the manipulation of symbiont nutrient cycling affects the stress tolerance in the holobiont of coral reefs. However, most studies have primarily focused on coral-Symbiodiniaceae-bacterial interactions as a whole, neglecting the interactions between Symbiodiniaceae and bacteria, which remain largely unexplored. In this study, we proposed a hypothesis that there exists an inner symbiotic loop of Symbiodiniaceae and bacteria within the coral symbiotic loop. We conducted experiments to demonstrate how metabolic exchanges between Symbiodiniaceae and bacteria facilitate the nutritional supply necessary for cellular growth. It was seen that the beneficial bacterium, Ruegeria sp., supplied a nitrogen source to the Symbiodiniaceae strain Durusdinium sp., allowing this dinoflagellate to thrive in a nitrogen-free medium. The Ruegeria sp.-Durusdinium sp. interaction was confirmed through 15N-stable isotope probing-single cell Raman spectroscopy, in which 15N infiltrated into the bacterial cells for intracellular metabolism, and eventually the labeled nitrogen source was traced within the macromolecules of Symbiodiniaceae cells. The investigation into Symbiodiniaceae loop interactions validates our hypothesis and contributes to a comprehensive understanding of the intricate coral holobiont. These findings have the potential to enhance the health of coral reefs in the face of global climate change.

Contribution of crosstalk of mesothelial and tumoral epithelial cells in pleural metastasis of lung cancer.

Background: Tumor metastasis commonly affects pleura in advanced lung cancer and results in malignant pleural effusion (MPE). MPE is related to poor prognosis, but without systematic investigation on different cell types and their crosstalk at single cell resolution. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) of lung cancer patients with pleural effusion. Next, our data were integrated with 5 datasets derived from individuals under normal, non-malignant disease and lung carcinomatous conditions. Mesothelial cells were re-clustered and their interactions with epithelial cells were comprehensively analyzed. Taking advantage of inferred ligand-receptor pairs, a prediction model of prognosis was constructed. The co-culture of mesothelial cells and malignant epithelial cells in vitro and RNA-seq was performed. Epidermal growth factor receptor (EGFR) antagonist cetuximab was utilized to prevent the lung cancer cells' invasiveness. Spatial distribution of cells in lung adenocarcinoma patients' samples were also analyzed to validate our findings. Results: The most distinctive transcriptome profiles between tumor and control were revealed in mesothelial cells, which is the predominate cell type of pleura. Five subtypes were divided, including one predominately identified in MPE which was characterized by enriched cancer-related pathways (e.g., cell migration) along evolutionary trajectory from normal mesothelial cells. Cancer-associated mesothelial cells (CAMCs) exhibited varied interactions with different subtypes of malignant epithelial cells, and multiple ligands/receptors exhibited significant correlation with poor prognosis. Experimentally, mesothelial cells can increase the migration ability of lung cancer cells through co-culturing. EGFR was the only affected gene in cancer cells that exhibited interaction with mesothelial cells and was associated with poor prognosis. Using EGFR antagonist cetuximab prevented the lung cancer cells' increased invasiveness caused by mesothelial cells. Moreover, epithelial mitogen (EPGN)-EGFR interaction was supported through spatial distribution analysis, revealing the significant proximity between EPGN+ mesothelial cells and EGFR+ epithelial cells. Conclusions: Our findings highlighted the important role of mesothelial cells and their interactions with cancer cells in pleural metastasis of lung cancer, providing potential targets for treatment.

GARNL3 identified as a crucial target for overcoming temozolomide resistance in EGFRvIII-positive glioblastoma.

OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.