Fluorescence and photoacoustic (FL/PA) dual-modal probe: Responsive to reactive oxygen species (ROS) for atherosclerotic plaque imaging.

Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O-OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA775 signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications.

Interpreting epidemiologic distribution of total and specific IgE levels for food allergy in Southern China from 2004 to 2023: understanding the mechanisms and focusing on prevention.

BACKGROUND: The burgeoning prevalence of food allergy-related diseases is closely associated with geographical allergen distribution and societal lifestyle paradigms. This study aims to shed light on the distribution patterns of specific IgE (sIgE) and total IgE (tIgE) reactivity to common food allergens in the Southern Chinese populace. METHODS: Employing an analytical technique spanning two decades, we conducted specific IgE and total IgE on serum samples harvested from patients with food allergy-related pathologies at First Affiliated Hospital of Guangzhou Medical University from 2004 to 2023. This comprehensive examination of eight prototypical food allergens: egg white, milk, wheat, sesame, peanut, soybean, shrimp, and crab. RESULTS: Our analysis showed a 100% positivity rate for sIgE and an 86.54% positivity rate for tIgE. Milk had the highest positive response rate, followed by egg white and shrimp. Age-stratified data indicated that milk sensitization peaked in children aged 2 years or younger, while egg white sensitization peaked between 3 and 5 years of age. Sensitization rates for the remaining six allergens increased with age. Additionally, co-sensitization was observed between milk, egg white, crab, and shrimp with other allergens. CONCLUSION: In common allergens of Southern China, egg white, milk, and shrimp ascend as the dominant subjects, underlining their imperative role in food allergy pathogenesis. This landscape-wide allergenic profiling, segregated across age clusters and enhanced by co-sensitization data, augments our power for early diagnosis and strategic intervention in food allergy diseases.

Analysis of changes in bone mineral density and cortical bone thickness after reconstruction of the mandible with fibula, is condyle preservation a critical influence factor?

OBJECTIVE: This study aimed to investigate the features of bone mineral density (BMD) and cortical bone thickness in grafted fibula. MATERIALS AND METHODS: Eighty-six patients who underwent mandibular reconstruction using vascularized fibula flaps were enrolled, all of whom were followed up at 3, 6, and 12 months after surgery. The patients were grouped according to whether the condyle was preserved. BMD and cortical bone thickness were also measured. RESULTS: Condyle-preserved group consisted of 65 patients and condyle-unpreserved group consisted of 21 patients. There was a significant correlation between thickness and BMD, which was significantly correlated with follow-up time. One year after surgery, the BMD of the condyle-preserved group decreased from 1029.61 ± 156.01 mg/cm3 to 978.6 ± 141.90 mg/cm3, and thickness decreased from 3.29 ± 0.65 mm to 2.72 ± 0.72 mm. BMD of the condyle-unpreserved group decreased from 1062.21 ± 126.01 mg/cm3 to 851.26 ± 144.38 mg/cm3, and thickness decreased from 3.46 ± 0.89 mm to 2.56 ± 0.73 mm. In the condyle-preserved and unpreserved groups, the absorption rates of BMD were 3.29 ± 11.97% and 17.09 ± 12.42% at 12 months, respectively, and the rate of thickness was 20.7 ± 11.45% and 26.39 ± 12.23% at 12 months, respectively. CONCLUSION: BMD and thickness showed a decreasing trend over time. Preserving the condyle can slow bone resorption of the fibula. Regarding implant restoration, we recommend doctors to perform the treatment within 6-12 months after surgery in order to effectively manage bone resorption. CLINICAL RELEVANCE: Our study found that condylar preservation can decrease the absorption rate of BMD and cortical bone thickness, helping doctors make better clinical decisions. TRIAL REGISTRATION NUMBER: ChiCTR2300069661 (March 22, 2023).

Matrix stiffness regulates mitochondria-lysosome contacts to modulate the mitochondrial network, alleviate the senescence of MSCs.

The extracellular microenvironment encompasses the extracellular matrix, neighbouring cells, cytokines, and fluid components. Anomalies in the microenvironment can trigger aging and a decreased differentiation capacity in mesenchymal stem cells (MSCs). MSCs can perceive variations in the firmness of the extracellular matrix and respond by regulating mitochondrial function. Diminished mitochondrial function is intricately linked to cellular aging, and studies have shown that mitochondria-lysosome contacts (M-L contacts) can regulate mitochondrial function to sustain cellular equilibrium. Nonetheless, the influence of M-L contacts on MSC aging under varying matrix stiffness remains unclear. In this study, utilizing single-cell RNA sequencing and atomic force microscopy, we further demonstrate that reduced matrix stiffness in older individuals leads to MSC aging and subsequent decline in osteogenic ability. Mechanistically, augmented M-L contacts under low matrix stiffness exacerbate MSC aging by escalating mitochondrial oxidative stress and peripheral division. Moreover, under soft matrix stiffness, cytoskeleton reorganization facilitates rapid movement of lysosomes. The M-L contacts inhibitor ML282 ameliorates MSC aging by reinstating mitochondrial network and function. Overall, our findings confirm that MSC aging is instigated by disruption of the mitochondrial network and function induced by matrix stiffness, while also elucidating the potential mechanism by which M-L Contact regulates mitochondrial homeostasis. Crucially, this presents promise for cellular anti-aging strategies centred on mitochondria, particularly in the realm of stem cell therapy.

Research on the Mechanism of Femtosecond Laser Ablation Concave-Convex Microstructure Transformation.

The phenomenon of femtosecond laser ablation of convex structures from the bottom to the top is interesting. In this study, AZ31B magnesium alloy was used as the substrate to analyze the impact of the laser pulse energy and scanning speed on the morphology of concave-convex microstructures. Subsequently, a unified two-dimensional numerical model incorporating solid, liquid, and gas phases was established, and combined with experimental data, the mechanism and formation process of concave-convex transformation in magnesium alloy under laser ablation were revealed. The results indicate that the transition from concave to convex structures is significantly influenced by the laser scanning speed, whereas the laser pulse energy primarily affects the shape and size of the convex structures. During the ablation process, molten material is expelled and gradually accumulates on both sides of the ablation groove under the action of the recoil pressure. During cooling, the molten material at both ends of the groove merges to form protrusions under the combined effects of internal negative pressure, gravity, and Marangoni forces. Moreover, this method of femtosecond laser ablation for generating convex structures deviates from the traditional single-texture approach to concave structures, potentially broadening the application of laser composite processing surfaces.

Predictive models and treatment efficacy for liver cancer patients with bone metastases: A comprehensive analysis of prognostic factors and nomogram development.

Background: Bone metastasis considerably undermines the prognosis of advanced primary liver cancer patients. Though its impact is well-recognized, the clinical field still lacks robust predictive models that can accurately forecast patient outcomes and aid in treatment effectiveness evaluation. Addressing this gap is paramount for improving patient management and survival. Materials and methods: We conducted an extensive analysis using data from the SEER database (2010-2020). COX regression analysis was applied to identify prognostic factors for primary liver cancer with bone metastasis (PLCBM). Nomograms were developed and validated to predict survival outcomes in PLCBM patients. Additionally, propensity score matching and Kaplan-Meier survival analyses lent additional insight by dissecting the survival advantage conferred by various treatment strategies. Results: A total of 470 patients with PLCBM were included in our study. The median overall survival (OS) and cancer-specific survival (CSS) for these patients were both 5 months. We unveiled several independent prognosticators for OS and CSS, spanning demographic to therapeutic parameters like marital status, cancer grade, histological type, and treatments received. This discovery enabled the formulation of two novel nomograms-now verified to eclipse the predictive prowess of the traditional TNM staging system regarding discrimination and clinical utility. Additionally, propensity score matching analysis showed the effectiveness of surgeries, radiotherapy, and chemotherapy in improving OS and CSS outcomes for PLCBM patients. Conclusions: Our investigation stands out by introducing pioneering nomograms for prognostic evaluation in PLCBM, a leap forward compared to existing tools. Far exceeding mere academic exercise, these nomograms hold immense clinical value, serving as a foundation for nuanced risk stratification systems and delivering dynamic, interactive guides, allowing healthcare professionals and patients to assess individual bone metastasis survival probabilities and personalize treatment selection.

Melt-blown polypropylene nonwoven as an efficient and eco-economic sorbent for pipette tip micro-solid phase extraction for the determination of tyrosine kinase inhibitors.

BACKGROUND: The detection of tyrosine kinase inhibitors (TKIs) in biological fluids is essential due to their critical role in cancer therapy and the variability in individual drug metabolism, which necessitates precise dosing. Traditional methods for analyzing TKIs in biological fluids, such as blood plasma, typically involve complex sample preparation techniques that can be resource-intensive, environmentally burdensome, and not sufficiently sensitive for low-concentration analytes. There is a pressing need for more efficient, economical, and environmentally friendly methods that can enhance sensitivity and throughput without compromising accuracy. RESULTS: This study explores the use of melt-blown polypropylene nonwoven (MBPP), commonly found in face masks, as a novel sorbent for pipette-tip micro-solid phase extraction (PT-µSPE). MBPP demonstrated excellent hydrophobicity and significant mesoporous adsorption capacity. An extraction device was fashioned by inserting a segment of MBPP (15 mg) into a 200 µL disposable plastic pipette tip, which was then attached to a 2.5 mL disposable plastic syringe. The MBPP's fabric form removes the need for a frit, allowing the extraction process to be completed in just 3 min through simple plunger manipulation. The method achieved extraction recoveries ranging from 60.5 % to nearly 100 %. Subsequent method validation using liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed satisfactory linearity (coefficient of determination R2 > 0.993), accuracy (relative recoveries: 86.3%-114.8 %), and precision (relative standard deviation: 3.4%-11.3 %), with detection limits between 0.022 and 0.135 ng mL-1. SIGNIFICANCE: The introduction of MBPP for PT-µSPE represents a significant advancement in the bioanalytical detection of TKIs, offering a highly efficient, cost-effective, and environmentally sustainable method. It compares favorably with existing techniques, offering advantages in terms of cost, environmental impact, and ease of use. This approach has the potential to be widely adopted for routine monitoring of TKIs in clinical settings.

Sex dimorphism and hormesis response to polystyrene microplastic exposure in kinematics and metabolism of Drosophila model based on deep learning.

The emergence of microplastics (MPs) has become a significant focus of environmental pollution, prompting widespread concern regarding its potential toxicity and impact on the environment and organisms. Recent research indicates notable alterations in insect metabolism and behavioral patterns under the influence of MPs. In this study, the fruit fly (Drosophila melanogaster) was employed as a model organism to investigate the effects of polystyrene microplastics (PS-MPs) on insect behavior, with behavioral parameters used to quantify and assess its toxic effects on fruit flies. Five concentrations (0 g/L, 0.1 g/L, 1 g/L, 10 g/L, 20 g/L) of 5 µm PS-MPs were introduced into the environment, and fruit flies were exposed for 20 days, with subsequent recording of their metabolism and locomotion. In the presence of MPs, both male and female fruit flies exhibited decreasing glucose levels, while protein content decreased in male flies, and irregular gait patterns were observed in both genders. Further quantification of gait parameters revealed that male fruit flies experienced reduced velocity, increased stride length, and larger wing beat angles under microplastic exposure, whereas females exhibited pronounced excitatory effects such as increased velocity and wing beat frequency at lower concentrations, which diminished with higher concentrations, indicating a biphasic response and excitatory effects induced by PS-MPs. These findings highlight the significant impact of PS-MPs on fruit fly metabolism and behavioral patterns, raising concerns regarding the use of PS-MPs.

Rapid and convenient determination of α-dicarbonyl compounds via streamlined simultaneous derivatization and extraction coupled with liquid chromatography-fluorescence detection.

α-Dicarbonyl compounds (α-DCs), formed during food heating and storage, are crucial for assessing food safety and quality. However, the low concentration, high reactivity, and absence of chromophores of α-DCs make their detection challenging, often requiring complex derivatization and extraction. This study developed a one-pot method for α-DCs that combines derivatization and magnetic solid-phase extraction. By mixing the sample, 2,3-diaminonaphthalene, and Fe3O4/MWCNTs-OH in a vial, simultaneous derivatization and extraction are achieved. Derivatization converts α-DCs into hydrophobic products, facilitating their adsorption and enabling sensitive liquid chromatography-fluorescence detection. The introduction of the magnetic adsorbent allows phase separation to be easily achieved using an external magnet, simplifying and speeding up the process. The detection limits for six α-DCs (glyoxal, methylglyoxal, diacetyl, 2,3-pentanedione, D-glucosone, and 3-deoxyglucosone) were determined to be in the range of 0.4-3.5 nM. This rapid and convenient analytical approach was successfully applied to analyze α-DCs in juices, coffees, and tea beverages.

Catalytic Enantioselective Synthesis of Boron-Stereogenic and Axially Chiral BODIPYs via Rhodium(II)-Catalyzed C-H (Hetero)Arylation with Diazonaphthoquinones and Diazoindenines.

The molecular engineering of boron dipyrromethenes (BODIPYs) has garnered widespread attention due to their structural diversity enabling tailored physicochemical properties for optimal applications. However, catalytic enantioselective synthesis of structurally diverse boron-stereogenic BODIPYs through intermolecular desymmetrization and BODIPYs with atroposelectivity remains elusive. Here, we showcase rhodium(II)-catalyzed site-specific C-H (hetero)arylations of prochiral BODIPYs and polysubstituted BODIPYs with diazonaphthoquinonesand diazoindenines, providing efficient pathways for the rapid assembly of versatile (hetero)arylated boron-stereogenic and axially chiral BODIPYs through long-range desymmetrization and axial rotational restriction modes. The synthetic application of the procedures has been emphasized by the efficient synthesis of BODIPY derivatives with various functions. Photophysical properties, bioimaging, and lipid droplet-specific targeting capability of tailored BODIPYs are also demonstrated, indicating their promising applications in biomedical research, medicinal chemistry, and material science.

Estradiol Valerate Tablets Caused Rare Severe Drug Eruption: The First Reported Case.

Severe drug eruption is a severe allergic reaction to a drug, usually due to irritation with certain drugs. It may be present as a generalized erythematous maculopapular rash, a pleomorphic rash, with or without blisters and ulcers. To the best of our knowledgeto date, there is no report of estradiol valerate-induced severe drug eruption. A case of rare severe drug eruption after taking estradiol valerate tablets was first reported to promote clinical drug safety management, especially for rare severe adverse reactions. Meanwhile, it is speculated that estrogen dermatitis might be associated with dendritic cell-mediated allergic mechanisms, inflammation-induced expression of estrogen receptor ß, and elevated estrogen levels during pregnancy, according to previous studies. Therefore, pregnant women using this drug need to be focused on. Early and systemic use of glucocorticoids is beneficial to the outcome and prognosis of the disease. It highlights the need for clinicians to be vigilant about rare but serious adverse drug reactions, even with medications that are generally considered safe.

Improving Thermosensitive Bioink Scaffold Fabrication with a Temperature-Regulated Printhead in Robot-Assisted In Situ Bioprinting System.

In situ bioprinting enables precise 3D printing inside the human body using modified bioprinters with thermosensitive bioinks such as gelatin methacrylate (GelMA). However, these devices lack refined temperature-regulated mechanisms essential for ensuring bioink viscosity, as compared to traditional bio-3D printers. Addressing this challenge, this study presents a temperature-regulated printhead designed to improve the fabrication of thermosensitive bioink scaffolds in in situ bioprinting, integrated into a UR5 robotic arm. Featuring a closed-loop system, it achieves a temperature steady error of 1 °C and a response time of approximately 1 min. The effectiveness of the printer was validated by bioprinting multilayer lattice 3D bioscaffolds. Comparisons were made with or without temperature control using different concentrations of GelMA + LAP. The deformation of the bioscaffolds under both conditions was analyzed, and cell culture tests were conducted to verify viability. Additionally, the rheology and mechanical properties of GelMA were tested. A final preliminary in situ bioprinting experiment was conducted on a model of a damaged femur to demonstrate practical application. The fabrication of this printhead is entirely open source, facilitating easy modifications to accommodate various robotic arms. We encourage readers to advance this prototype for application in increasingly complex in situ bioprinting situations, especially those utilizing thermosensitive bioinks.

Multi-omics analysis reveals the key factors involved in the severity of the Alzheimer's disease.

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder with a global impact, yet its pathogenesis remains poorly understood. While age, metabolic abnormalities, and accumulation of neurotoxic substances are potential risk factors for AD, their effects are confounded by other factors. To address this challenge, we first utilized multi-omics data from 87 well phenotyped AD patients and generated plasma proteomics and metabolomics data, as well as gut and saliva metagenomics data to investigate the molecular-level alterations accounting the host-microbiome interactions. Second, we analyzed individual omics data and identified the key parameters involved in the severity of the dementia in AD patients. Next, we employed Artificial Intelligence (AI) based models to predict AD severity based on the significantly altered features identified in each omics analysis. Based on our integrative analysis, we found the clinical relevance of plasma proteins, including SKAP1 and NEFL, plasma metabolites including homovanillate and glutamate, and Paraprevotella clara in gut microbiome in predicting the AD severity. Finally, we validated the predictive power of our AI based models by generating additional multi-omics data from the same group of AD patients by following up for 3 months. Hence, we observed that these results may have important implications for the development of potential diagnostic and therapeutic approaches for AD patients.

Reflections on Small-Class Teaching in Veterinary Medicine Undergraduate Programs in China.

As a cornerstone of higher education in China, the quality of undergraduate teaching is crucial for nurturing high-caliber innovative talents that meet the needs of national and social development. Small-class teaching has emerged as a focal point in the reform of undergraduate education and represents an important approach to cultivating top-notch innovative talents. Veterinary medicine is a scientific discipline that encompasses the prevention, control, diagnosis, and treatment of animal diseases. It also involves efforts to prevent the transmission of animal diseases to humans. The training of professionals in this field should emphasize the integration of theoretical knowledge with practical skills. Therefore, small-class teaching facilitates open communication between educators and students, which is instrumental in fostering a new generation of veterinarians equipped with robust professional knowledge, excellent practical abilities, and strong scientific literacy. This paper provides a preliminary exploration into the strategy and direction of small-class teaching within China's veterinary medicine undergraduate programs by summarizing its characteristics, advantages, and existing challenges. The unique traits of veterinary medicine are also taken into consideration during this analysis.

The influence of { 10 1 ¯ 2 } twinning on the corrosion behavior of AZ31B magnesium alloy.

This study investigates the effect of twinning on the corrosion behavior of AZ31B magnesium alloy using solid solution heat treatment (SHT) and laser shock peening (LSP) techniques. The corrosion characteristics are assessed by scanning electron microscopy (SEM), scanning Kelvin probe force microscopy (SKPFM), zero resistance ammeter (ZRA), scanning vibrating electrode technique (SVET), and electrochemical tests. Results indicate that the twinning region in AZ31B magnesium alloy, enriched with { 10 1 ¯ 2 } tensile twins induced by laser shock, demonstrates increased corrosion susceptibility. This region exhibits higher electrochemical activity and an accelerated corrosion rate compared to the matrix region. Micro-galvanic coupling between the twinned and matrix regions promotes faster dissolution of the alloy. Additionally, the corrosion product film on the surface is extensively cracked and propagates to the matrix corrosion surface, confirming that { 10 1 ¯ 2 } tensile twins provide inadequate protection against corrosion in AZ31B alloy.

Association between long-term exposure to PM2.5 chemical components and metabolic syndrome in middle-aged and older adults.

Background: Previous studies indicated that exposure to ambient fine particulate matter (PM2.5) could increase the risk of metabolic syndrome (MetS). However, the specific impact of PM2.5 chemical components remains uncertain. Methods: A national cross-sectional study of 12,846 Chinese middle-aged and older adults was conducted. Satellite-based spatiotemporal models were employed to determine the 3-year average PM2.5 components exposure, including sulfates (SO4 2-), nitrates (NO3 -), ammonia (NH4 +), black carbon (BC), and organic matter (OM). Generalized linear models were used to investigate the associations of PM2.5 components with MetS and the components of MetS, and restricted cubic splines curves were used to establish the exposure-response relationships between PM2.5 components with MetS, as well as the components of MetS. Results: MetS risk increased by 35.1, 33.5, 33.6, 31.2, 32.4, and 31.4% for every inter-quartile range rise in PM2.5, SO4 2-, NO3 -, NH4 +, OM and BC, respectively. For MetS components, PM2.5 chemical components were associated with evaluated risks of central obesity, high blood pressure (high-BP), high fasting glucose (high-FBG), and low high-density lipoprotein cholesterol (low-HDL). Conclusion: This study indicated that exposure to PM2.5 components is related to increased risk of MetS and its components, including central obesity, high-BP, high-FBG, and low-HDL. Moreover, we found that the adverse effect of PM2.5 chemical components on MetS was more sensitive to people who were single, divorced, or widowed than married people.

MCMVDRP: a multi-channel multi-view deep learning framework for cancer drug response prediction.

Drug therapy remains the primary approach to treating tumours. Variability among cancer patients, including variations in genomic profiles, often results in divergent therapeutic responses to analogous anti-cancer drug treatments within the same cohort of cancer patients. Hence, predicting the drug response by analysing the genomic profile characteristics of individual patients holds significant research importance. With the notable progress in machine learning and deep learning, many effective methods have emerged for predicting drug responses utilizing features from both drugs and cell lines. However, these methods are inadequate in capturing a sufficient number of features inherent to drugs. Consequently, we propose a representational approach for drugs that incorporates three distinct types of features: the molecular graph, the SMILE strings, and the molecular fingerprints. In this study, a novel deep learning model, named MCMVDRP, is introduced for the prediction of cancer drug responses. In our proposed model, an amalgamation of these extracted features is performed, followed by the utilization of fully connected layers to predict the drug response based on the IC50 values. Experimental results demonstrate that the presented model outperforms current state-of-the-art models in performance.

Prognostic prediction signature and molecular subtype for liver cancer: A CTC/CTM­related gene prediction model and independent external validation.

Liver cancer is the second leading cause of tumor-related death worldwide, and a serious threat to lives and health. Circulating tumor cells (CTCs) facilitate the progression of various cancers, including liver cancer. The relationship between CTC/circulating tumor microemboli-related genes (CRGs) and the prognosis of liver cancer is unclear. The aim of the present study was to identify CTC/circulating tumour microemboli-related genes (CRGs) in hepatocellular carcinoma and to investigate their clinical significance. Transcriptomic data from The Cancer Genome Atlas (International Cancer Genome Consortium (ICGC) and GSE117623 databases were combined, and differentially expressed CRGs were identified. These were subsequently analyzed via least absolute shrinkage and selection operator and multivariate Cox analyses, and a five-gene risk signature was constructed. The signature was validated in the ICGC and GSE14520 dataset with survival analysis and receiver operating characteristic curve analysis. Immunocyte infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE), and the somatic mutation rate were also compared between high- and low-risk groups, based on the median predictive index, to further evaluate the immunotherapeutic value of the model. Molecular subtypes of liver cancer were characterized by the non-negative matrix factorization method and potential therapeutic compounds were evaluated for different subtypes. Nomograms were utilized to predict the prognosis of patients, and the signature was compared with previous literature models. Additionally, the biological function of one of the CRGs, tumor protein p53 inducible protein 3 (TP53I3), in liver cancer was further explored through in vitro experiments. Analysis of the prognostic characteristics of the five CRGs led to the identification of two liver cancer subtypes. Patients in the low-risk group had a longer survival compared with those in the high-risk group, and patients in the latter group were associated with a higher TMB, immunocyte infiltration and somatic mutation rate, and lower TIDE scores. The prognostic profile was validated in the ICGC and GSE14520 datasets and exhibited a good predictive performance. In vitro analysis showed that the knockdown of TP53I3 suppressed liver cancer cell proliferation. In summary, CRGs were used to develop a new prognostic signature to predict the prognosis of patients with liver cancer. This signature may be used to assess the prognosis of patients and may provide new insights for clinical management strategies. In addition, TP53I3 is potentially a therapeutic target for liver cancer.

Copper-induced oxidative stress inhibits asexual reproduction of Aurelia coerulea polyps.

OBJECTIVE: Our research aims to investigate the specific mechanisms by which copper inhibits the asexual proliferation of Aurelia coerulea polyps. METHODS: Aurelia coerulea polyps were exposed to various CuSO4 concentrations to study metamorphosis and budding proliferation. Oxidative stress markers (ROS, MDA, CAT, H2O2, T-AOC, SOD) were measured in polyps and early strobilae. Transcriptomic analysis were used to compare differences in gene expression and enrichment pathways between untreated and copper-exposed polyps. Additionally, RT-qPCR was used to analyze the expression of key molecules. Antioxidant L-Ascorbic acid was applied to determine the role of oxidative stress in asexual reproduction of Aurelia coerulea polyps when exposed to copper. RESULTS: Copper inhibited strobilization and budding of Aurelia coerulea polyps in a dose-dependent manner, in which oxidative stress was involved. Transcriptomic data suggested that the DNA replication pathway was significantly enriched in early strobilae compared to polyps. However, copper treatment repealed the difference of DNA replication pathway between early strobilae compared and polyps. Transcriptomic data suggested that alanine, aspartate, and glutamate metabolism pathways were enriched in untreated budding polyps compared to copper-exposed polyps. After applying the antioxidant L-Ascorbic acid to copper-exposed polyps, various oxidative indicators changed to different extents, with increases in ROS, MDA, CAT, H2O2, and SOD and a decrease in T-AOC. Further more, the time required for polyps to develop into early strobila was shortened, indicating that the delay in metamorphosis caused by copper exposure was effectively alleviated. And the budding rate increased, indicating that the inhibition of budding proliferation caused by copper exposure was effectively alleviated. The expression of key genes were consist with the transcriptomic sequencing results. CONCLUSION: Copper exposure causes oxidative stress resulting in the inhibition of asexual reproduction in Aurelia coerulea polyps, including metamorphosis and budding.

Lactate supports Treg function and immune balance via MGAT1 effects on N-glycosylation in the mitochondria.

Current research reports that lactate affects Treg metabolism, although the precise mechanism has only been partially elucidated. In this study, we presented evidence demonstrating that elevated lactate levels enhanced cell proliferation, suppressive capabilities, and oxidative phosphorylation (OXPHOS) in human Tregs. The expression levels of Monocarboxylate Transporters 1/2/4 (MCT1/2/4) regulate intracellular lactate concentration, thereby influencing the varying responses observed in naive Tregs and memory Tregs. Through mitochondrial isolation, sequencing, and analysis of human Tregs, we determined that α-1,3-Mannosyl-Glycoprotein 2-ß-N-Acetylglucosaminyltransferase (MGAT1) served as the pivotal driver initiating downstream N-glycosylation events involving progranulin (GRN) and hypoxia-upregulated 1 (HYOU1), consequently enhancing Treg OXPHOS. The mechanism by which MGAT1 was upregulated in mitochondria depended on elevated intracellular lactate that promoted the activation of XBP1s. This, in turn, supported MGAT1 transcription as well as the interaction of lactate with the translocase of the mitochondrial outer membrane 70 (TOM70) import receptor, facilitating MGAT1 translocation into mitochondria. Pretreatment of Tregs with lactate reduced mortality in a xenogeneic graft-versus-host disease (GvHD) model. Together, these findings underscored the active regulatory role of lactate in human Treg metabolism through the upregulation of MGAT1 transcription and its facilitated translocation into the mitochondria.