High Contrast Bioimaging of Tumor and Inflammation with a Bicyclic Dioxetane Chemiluminescent Probe.

The link between inflammation and the evolution of cancer is well established. Visualizing and tracking both tumor proliferation and the associated inflammatory response within a living organism are vital for dissecting the nexus between these two processes and for crafting precise treatment modalities. We report the creation and synthesis of an advanced NIR chemiluminescence probe that stands out for its exceptional selectivity, extraordinary sensitivity at nanomolar concentrations, swift detection capabilities, and broad application prospects. Crucially, this probe has been successfully utilized to image endogenous ONOO- across different inflammation models, including abdominal inflammation triggered by LPS, subcutaneous inflammatory conditions, and tumors grafted onto mice. These findings highlight the significant promise of chemiluminescence imaging in enhancing our grasp of the intricate interplay between cancer and inflammation and in steering the development of potent, targeted therapeutic strategies.

In Situ Biosynthesis of FeS Nanoparticles Boosts Current Generation in Bioelectrochemical Systems Through Efficient Electron Transfer.

The utility of electrochemical active biofilm in bioelectrochemical systems has received considerable attention for harvesting energy and chemical products. However, the slow electron transfer between biofilms and electrodes hinders the enhancement of performance and still remains challenging. Here, using Fe3O4 /L-Cys nanoparticles as precursors to induce biomineralization, a facile strategy for the construction of an effective electron transfer pathway through biofilm and biological/inorganic interface is proposed, and the underlying mechanisms are elucidated. Taking advantage of an on-chip interdigitated microelectrode array (IDA), the conductive current of biofilm that is related to the electron transfer process within biofilm is characterized, and a 2.10-fold increase in current output is detected. The modification of Fe3O4/L-Cys on the electrode surface facilitates the electron transfer between the biofilm and the electrode, as the bio/inorganic interface electron transfer resistance is only 16% compared to the control. The in-situ biosynthetic Fe-containing nanoparticles (e.g., FeS) enhance the transmembrane EET and the EET within biofilm, and the peak conductivity increases 3.4-fold compared to the control. The in-situ biosynthesis method upregulates the genes involved in energy metabolism and electron transfer from the transcriptome analysis. This study enriches the insights of biosynthetic nanoparticles on electron transfer process, holding promise in bioenergy conversion.

Integrative metagenomic analysis reveals distinct gut microbial signatures related to obesity.

Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes in the gut microbiome in obesity remain to be comprehensively investigated. In this study, we conducted a meta-analysis of metagenomic sequencing data from both obese and non-obese individuals across multiple cohorts, totaling 1351 fecal metagenomes. Our results demonstrate a significant decrease in both the richness and diversity of the gut bacteriome and virome in obese patients. We identified 38 bacterial species including Eubacterium sp. CAG:274, Ruminococcus gnavus, Eubacterium eligens and Akkermansia muciniphila, and 1 archaeal species, Methanobrevibacter smithii, that were significantly altered in obesity. Additionally, we observed altered abundance of five viral families: Mesyanzhinovviridae, Chaseviridae, Salasmaviridae, Drexlerviridae, and Casjensviridae. Functional analysis of the gut microbiome indicated distinct signatures associated to obesity and identified Ruminococcus gnavus as the primary driver for function enrichment in obesity, and Methanobrevibacter smithii, Akkermansia muciniphila, Ruminococcus bicirculans, and Eubacterium siraeum as functional drivers in the healthy control group. Additionally, our results suggest that antibiotic resistance genes and bacterial virulence factors may influence the development of obesity. Finally, we demonstrated that gut vOTUs achieved a diagnostic accuracy with an optimal area under the curve of 0.766 for distinguishing obesity from healthy controls. Our findings offer comprehensive and generalizable insights into the gut bacteriome and virome features associated with obesity, with the potential to guide the development of microbiome-based diagnostics.

PASTICCINO2 interacting with Golgi Anti-Apoptotic Proteins resists endoplasmic reticulum stress dependent on very long-chain fatty acids.

The endoplasmic reticulum (ER) is crucial for maintaining cell homeostasis because it is the primary site for synthesizing secreted and transmembrane proteins and lipids. The unfolded protein response (UPR) is activated to restore ER homeostasis under ER stress. However, the relationship between lipids and the ER stress response in plants is not well understood. Arabidopsis Golgi anti-apoptotic proteins (GAAPs) are involved in resisting ER stress. To elucidate the function of GAAPs, PASTICCINO2 (PAS2), involved in very long-chain fatty acid (VLCFA) synthesis, was found to interact with GAAPs and IRE1. Single pas2 and gaap1/gaap2pas2 double mutants exhibited increased seedling damage and impaired UPR response under chronic ER stress. Site mutation combined with genetic analysis revealed that the role of PAS2 in resisting ER stress depended on its VLCFA synthesis domain. VLCFA contents were upregulated under ER stress, which required GAAPs. Exogenous VLCFAs partially restored the defect in UPR upregulation caused by PAS2 or GAAP mutations under chronic ER stress. These findings demonstrate that the association of PAS2 with GAAPs confers plant resistance to ER stress by regulating VLCFA synthesis and the UPR. This provides a basis for further studies on the connection between lipids and cell fate decisions under stress.

Risk Factors of the Occurrence and Treatment Failure of Refractory Peritoneal Dialysis-Associated Peritonitis: A Single-Center Retrospective Study From China.

BACKGROUND: This study aimed to investigate the clinical characteristics and prognosis of refractory peritoneal dialysis (PD)-associated peritonitis as well as the risk factors of its occurrence and treatment failure. METHODS: A single-center retrospective cohort study was conducted among 519 patients undergoing PD from January 2007 to October 2021. According to the International Society for Peritoneal Dialysis guidelines, all episodes occurred in our center were divided into two groups: refractory and nonrefractory. Demographic, biochemical, and pathogenic bacteria and treatment outcome data were collected. RESULTS: During the 15-year period, 282 episodes of peritonitis occurred in 166 patients undergoing PD. The refractory rate was 34.0% (96/282). Gram-positive organisms were the leading cause of peritonitis (47.9%); however, gram-negative organisms were predominant in refractory peritonitis (34.4%, p = 0.002). Multiple logistic regression revealed that gram-negative organism-based peritonitis, longer PD duration, and female sex were the significant independent predictors of refractory peritonitis. Among 96 refractory episodes, white blood cell (WBC) count, dialysate WBC on Day 3, and PD duration ≥5 years were the independent risk factors of treatment failure. CONCLUSIONS: Gram-negative organism-based peritonitis, longer PD duration, and female sex were the independent risk factors of refractory peritonitis. Refractory peritonitis with higher WBC count, higher dialysate WBC on Day 3, and PD duration ≥5 years increased treatment failure risk and required immediate PD catheter removal. The timely identification of refractory peritonitis with high risk of treatment failure as well as timely PD catheter removal is important.

Discovery and evolution of berberine analogues as anti-Helicobacter pylori agents with multi-target mechanisms.

Thirty protoberberine derivatives, of which twenty five were new, were synthesized and evaluated for their anti-Helicobacter pylori (HP) activities, taking 2,3,10-trimethoxy-9-p-methylbenzylaminoprotopalmatine chloride 1 as the lead. Among them, berberine (BBR) derivative 7c displayed the highest potency against six tested metronidazole (MTZ)-resistant strains and two tested MTZ-susceptible strains with the MIC values of 0.4-1.6 µg/mL with favorable druglike profiles including low toxicity and high stabilities in plasma and artificial gastric fluid. Mechanistic study revealed that 7c might target HP urease with IC50 value of 0.27 µg/mL against Jack bean urease. Furthermore, 7c might change the permeability of the bacterial membrane and direct interact with HP DNA, which also contribute to its bactericidal activity. Therefore, BBR derivatives constituted a new family of anti-HP candidates, with the advantage of good safety profile and multi-target mechanisms, and are worthy for further investigation.

Prevalence of sleep disturbances among intensive care nurses: A systematic review and meta-analysis.

BACKGROUND: Demanding intensive care unit (ICU) work environments may lead to sleep disturbances in nurses, impacting their health and potentially patient safety. Yet, the prevalence remains unclear around the world. AIMS: To quantify the prevalence of sleep disturbances in intensive care nurses. STUDY DESIGN: Systematic review and meta-analysis. A database search was conducted in Embase, PubMed, Web of Science, Scopus and CINAHL from their inception to April 2024 for relevant studies. Data from observational studies (cross-sectional or cohort) that reported the prevalence of sleep disturbances, assessed using the Pittsburgh Sleep Quality Index (PSQI > 5), pooled in random-effects meta-analyses. Subgroup analyses were used to investigate variations in the prevalence estimates in terms of available variables. A Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant protocol was registered in PROSPERO (CRD42023476428). RESULTS: In total, 24 articles were included in this study published from 1996 to 2023. Included studies were from 15 unique countries. Almost all of the studies were descriptive cross-sectional studies (n = 22; 91.7%). The included studies encompassed a range of intensive care nurses, from 42 to 605, involving a total of 3499 intensive care nurses. The reported proportion of intensive care nurses with sleep disturbances ranged from 20.0% to 100.0%, with a median of 76.7% (interquartile range: 62.9-85.7). The pooled prevalence of sleep disturbances in intensive care nurses was 75.1% (95% confidence interval: 37.2-53.1; 95% prediction interval: 30.5-95.4). CONCLUSIONS: Sleep disturbance is a common issue in intensive care nurses. The study results highlight the importance of implementing effective interventions as early as possible to improve ICU sleep quality. RELEVANCE TO CLINICAL PRACTICE: High prevalence of sleep disturbances among intensive care nurses necessitates global interventions. Gender-neutral approaches that acknowledge comparable risks and stable prevalence over time require long-term strategies. Raising awareness through programmes is vital for implementing evidence-based interventions to promote sleep health in intensive care nurses.

Novel molecular hepatocellular carcinoma subtypes and RiskScore utilizing apoptosis-related genes.

Hepatocellular carcinoma (HCC) is the third leading cause of global cancer-related deaths. Despite immunotherapy offering hope for patients with HCC, only some respond to it. However, it remains unclear how to pre-screen eligible patients. Our study aimed to address this issue. In this study, we identified 13 prognostic genes through univariate Cox regression analysis of 87 apoptosis-related genes. Subsequently, these 13 genes were analyzed using ConsensusClusterPlus, and patients were categorized into three molecular types: C1, C2, and C3. A prognostic model and RiskScore were constructed using Lasso regression analysis of 132 significant genes identified between C1 and C3. We utilized quantitative polymerase chain reaction to confirm the model's transcript level in Huh7 and THLE2 cell lines. Both molecular subtypes and RiskScores effectively predicted patients benefiting from immunotherapy. Cox regression analysis revealed RiskScore as the most significant prognosis factor, suggesting its clinical application potential and providing a foundation for future experimental research.

The Association between Serum Total Bilirubin and Severe Headaches or Migraine in American Adults.

BACKGROUND: Studies about the association between bilirubin and migraine were few. Therefore, the purpose of this study was to investigate the association between serum total bilirubin and the prevalence of severe headaches or migraine. METHODS: A multivariable logistic regression was used to assess the association between serum total bilirubin concentration and severe headaches or migraine. We also performed stratified analyses, interaction analyses and multiple interpolations in the sensitivity analysis. RESULTS: This cross-sectional study included 12,552 adults from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. The overall incidence of migraine was 19.99% (2,509/12,552). With every 1 mg/dl increase in bilirubin, the prevalence of migraine decreased by 23% (95% CI: 0.64, 0.93) after adjustment of all related covariates. Similarly, the risk of migraine was reduced by 17% (95% CI: 0.72, 0.97) in the Q4 group (the fourth quartile, highest serum total bilirubin level) compared with the Q1 group (the lowest level). Furthermore, interaction effects by age groups were significant in this relationship (P for interaction = 0.0004). In the Q4 group compared with Q1, inverse associations were observed in those aged ≥40 years (OR: 0.71,95% CI: 0.59, 0.85) in the stratified analysis. CONCLUSION: These findings support an association between serum total bilirubin and severe headaches or migraine, revealing an inverse association between serum total bilirubin quartiles and severe headaches or migraine in American adults. Age could play an important role in this association.

Segment anything in medical images.

Medical image segmentation is a critical component in clinical practice, facilitating accurate diagnosis, treatment planning, and disease monitoring. However, existing methods, often tailored to specific modalities or disease types, lack generalizability across the diverse spectrum of medical image segmentation tasks. Here we present MedSAM, a foundation model designed for bridging this gap by enabling universal medical image segmentation. The model is developed on a large-scale medical image dataset with 1,570,263 image-mask pairs, covering 10 imaging modalities and over 30 cancer types. We conduct a comprehensive evaluation on 86 internal validation tasks and 60 external validation tasks, demonstrating better accuracy and robustness than modality-wise specialist models. By delivering accurate and efficient segmentation across a wide spectrum of tasks, MedSAM holds significant potential to expedite the evolution of diagnostic tools and the personalization of treatment plans.

Small cell lung carcinoma with KIF5B-RET fusion partially responded to the 4th-line therapy with anlotinib: A case report.

BACKGROUND: Small cell lung cancer (SCLC) exhibits a pronounced tendency for metastasis and relapse, and the acquisition of resistance to chemotherapy and radiotherapy, leading to complexity in treatment outcomes. It is crucial to tackle these challenges by advancing targeted therapeutic approaches in ongoing research endeavors. Variant RET fusions have been reported in several solid tumors, but are rarely reported in SCLC. CASE SUMMARY: We present the first case of a KIF5B-RET fusion in a 65-year-old male patient with SCLC. To date, the patient has received the 4th line chemotherapy with anlotinib for one year and has shown a sustained favorable partial response. According to the results of next generation sequencing, this SCLC patient harbors the KIF5B-RET fusion, suggesting that RET fusion could serve as a promising molecular target for SCLC treatment. Next-generation sequencing (NGS) plays a critical role in comprehensively assessing the genotype and phenotype of cancer. CONCLUSION: NGS can provide SCLC patients with personalized and targeted therapy options, thereby improving their likelihood of survival.

Experimental Study on the Mechanism and Law of Low-Salinity Water Flooding for Enhanced Oil Recovery in Tight Sandstone Reservoirs.

Currently, research surrounding low-salinity water flooding predominantly focuses on medium- to high-permeability sandstone reservoirs. Nevertheless, further investigation is necessary to implement this technique with regard to tight sandstone reservoirs. The present study comprises a series of experiments conducted on the crude oil and core of the Ordos Chang 6 reservoir to investigate the influence of ionic composition on low-salinity water flooding in tight oil reservoirs. The change in wettability on the rock surface was analyzed by using the contact angle experiment. The change in recovery rate was analyzed using a core displacement experiment. The reaction between rock fluids was analyzed using an ion chromatography experiment. Additionally, a nuclear magnetic resonance (NMR) experiment was used to analyze the mobilization law of crude oil and the change in wettability on the scale of the rock core. This led to a comprehensive discussion of the law and mechanism of enhancing the recovery rate via low-salinity water flooding from various perspectives. Experiments show that low-salinity water flooding is an effective technique for enhancing recovery in tight sandstone reservoirs. Altering the ionic composition of injected water can improve the water wettability of the rock surface and enhance recovery. Decreasing the mass concentration of Ca2+ or increasing the mass concentration of SO42- can prompt the ion-exchange reaction on the rock surface and detachment of polar components from the surface. Consequently, the wettability of the rock surface strengthens, augmenting the recovery process. Nuclear magnetic resonance experiments evidence that low-salinity water injection, with ion adjustment, significantly alters the interactions between the rock and fluid in tight sandstone reservoirs. As a result, the T2 signal amplitude decreases significantly, residual oil saturation reduces considerably, and the hydrophilic nature of the rock surface increases.

Atomically Dispersed Dual-Metal ORR Catalyst with Hierarchical Porous Structure for Zn-Air Batteries.

The metal-nitrogen-carbon (M-N-C)-based catalysts are promising to replace PGM (platinum group metal) to accelerate oxygen reduction reaction due to their excellent electrocatalytic performance. However, the inferior intrinsic activity and poor active site density confining further improvement in their performance. Modulating the electronic structure and reasonably designing the pore structure are widely acknowledged effective strategies to boost the activity of the M-N-C catalysts. However, it is a great challenge to form abundant pores to regulate the electronic structure via the facile method. Herein, a hierarchical, porous dual-atom catalyst FeNi-NPC-1000 has been architectured by the Na2CO3 template method and bimetallic doping modification strategy. Benefitting from the optimized pore and electronic structure, the as-prepared FeNi-NPC-1000 possesses a high specific surface area (1412.8 m2 g-1) and improved ORR activity (E1/2 = 0.877 V vs RHE), which is superior to that of Pt/C (E1/2 = 0.867 V vs RHE). With the evidence of AC-STEM, XAS, and DFT, the FeNi-N8-C moiety is proven to be the key active site to realize high-efficiency ORR catalysis. When assembled it as an air cathode of ZABs, FeNi-NPC-1000 displays superior discharge performance (Pmax = 367.1 mW cm-2) and a stable battery long-life. This article will provide a new strategy for designing dual-metal atomic catalysts applied in metal-air batteries.

Porin deficiency or plasmid copy number increase mediated carbapenem-resistant Escherichia coli resistance evolution.

This study investigated resistance evolution mechanisms of conjugated plasmids and bacterial hosts under different concentrations of antibiotic pressure. Ancestral strain ECNX52 was constructed by introducing the blaNDM-5-carrying IncX3 plasmid into E. coli C600, and was subjected to laboratory evolution under different concentrations of meropenem pressure. Minimal inhibitory concentrations and conjugation frequency were determined. Fitness of these strains was assessed. Whole genome sequencing and transcriptional changes were performed. Ancestral host or plasmids were recombined with evolved hosts or plasmids to verify plasmid or host factors in resistance evolution. Role of the repA mutation on plasmid copy number was determined. Two out of the four clones (EM2N1 and EM2N3) exhibited four-fold increase in MIC when exposed to a continuous pressure of 2 µg/mL MEM (1/32 MIC), by down regulating expression of outer membrane protein ompF. Besides, all four clones displayed four-fold increase in MIC and higher conjugation frequency when subjected to a continuous pressure of 4 µg/mL MEM (1/16 MIC), attributing to increasing plasmid copy number generated by repA D140Y (GAT→TAT) mutation. Bacterial hosts and conjugative plasmids can undergo resistance evolution under certain concentrations of antimicrobial pressure by reducing the expression of outer membrane proteins or increasing plasmid copy numbers.

Performance evaluation of a newly developed 2019-nCoV nucleic acid detection kit based on Ion Proton sequencing platform and its comparison with the MGI Tech (DNBSEQ-G99) platform.

PURPOSE: To evaluate the performance of a newly developed 2019-nCoV nucleic acid detection kit based on Ion Proton sequencing platform and make comparation with MGI Tech (DNBSEQ-G99) platform. METHODS: References and clinical samples were used to evaluate the precision, agreement rate, limit of detection (LOD), anti-interference ability and analytical specificity. Twenty-seven clinical specimens were used to make comparison between two platforms. RESULTS: The kit showed good intra-assay, inter-assay, inter-day precision between different operators and laboratories, fine agreement rate with references, a relatively low LOD of 1 × 103 copies/ml, anti-interference capability of 5 % whole blood and 1mg/ml mucin and no cross reaction with twenty-nine common clinical pathogens. Consistency of variant classification was observed between two platforms. The WGS from Ion Proton tended to have higher coverage and less missing data. CONCLUSIONS: The newly developed kit has shown satisfactory performances and excellent consistency with DNBSEQ-G99, making it a good alternative choice clinically.

The two-year prognosis of multinodular goiter following radiofrequency ablation: based on all nodule burdens.

OBJECTIVE: Few studies used all nodule burdens to specify the prognosis of multinodular goiter (MNG) following radiofrequency ablation (RFA), so this study addresses this question for MNG after completely ablating dominant nodules. METHODS: The RFA indications for MNG included a total of 2-5 benign nodules with over 50% normal tissue on ultrasound, 1-3 well-defined benign dominant nodules on cytology, largest diameter ≥20 mm and/or with clinical complaints, and patient refusal or unable of surgery. A retrospective study of 185 MNG patients with completely ablated dominant nodules in a single-session RFA was conducted. The efficacy and complications were evaluated at 1, 6, 12 months and yearly thereafter. Based on retreatment risks, progressive disease (PD), stable disease (SD) and complete relief (CR) were introduced to assess all nodule load changes. PD was clarified as having new/non-target nodules newly appeared to ACR TI-RADS≥4, or new/enlarged non-target nodules ≥1 cm. RESULTS: The initial ablation ratios of target nodules were 100% at one month. During a mean 22.38±13.75 months (range, 12-60 months), the VRR of ablated nodules was 98.25% at 24 months without regrowth. Cosmetic and symptomatic scores decreased to 1 and 0, respectively, after 48 months. 9.7% of patients (18/185) had PD and the retreatment rate was 2.2% (4/185). The complication rate was 2.7% (5/185). CONCLUSIONS: RFA provides cosmetic and symptomatic relief for an average of two years. RFA is an useful minimally invasive treatment modality for selected MNG patients.

Clinical and genetic characteristics of myotonia congenita in Chinese population.

Myotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.

GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice.

BACKGROUND: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro. METHODS: Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 µg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight. The sizes and types of muscle fibers and apoptosis were assessed through histological analysis, immunofluorescence staining, and TUNEL staining, respectively. C2C12 myotubes were treated with D-galactose (40 mg/mL) and GLP-2. Protein expression of differentiation-related myogenic differentiation factor D (MyoD), myogenin (MyoG), and myosin heavy chain (Myhc), degradation-related Muscle RING finger 1 (MuRF-1), and muscle atrophy F-box (MAFbx)/Atrogin-1, and apoptosis-related B-cell leukemia/lymphoma 2 (Bcl-2) and Bax, were assessed using western blots. The Pi3k inhibitor LY294002 was applied to investigate whether GLP-2 regulated myogenesis and myotube aging via IGF-1/Pi3k/Akt/FoxO3a signaling pathway. RESULTS: The results demonstrated that GLP-2 significantly reversed the decline in muscles weight, relative grip strength, diameter, and cross-sectional area of muscle fibers induced by D-galactose in mice. Apart from suppressing the expressions of MuRF-1 and Atrogin-1 in the muscles and C2C12 myotubes, GLP-2 significantly increased the expressions of MyoD, MyoG, and Myhc compared to the D-galactose. GLP-2 significantly suppressed cell apoptosis. Western blot analysis indicated that the regulation of GLP-2 may be attributed to the activation of theIGF-1/Pi3k/Akt/FoxO3a phosphorylation pathway. CONCLUSIONS: This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway.

Astaxanthin Alleviates Autoimmune Hepatitis by Modulating CD8+ T Cells: Insights From Mass Cytometry and Single-Cell RNA Sequencing Analyses.

Astaxanthin (ASX) is an oxygen-containing non-vitamin A carotenoid pigment. However, the role of ASX in autoimmune hepatitis (AIH) remains unclear. In this study, a mouse model of AIH is established induced by concanavalin A (ConA). Mass cytometry and single-cell RNA sequencing (scRNA-seq) are used to analyze the potential role of ASX in regulating the immune microenvironment of AIH. ASX treatment effectively alleviated liver damage induced by ConA and downregulated pro-inflammatory cytokines production in mice. Mass cytometry and scRNA-seq analyses revealed a significant increase in the number of CD8+ T cells following ASX treatment. Functional markers of CD8+ T cells, such as CD69, MHC II, and PD-1, are significantly downregulated. Additionally, specific CD8+ T cell subclusters (subclusters 4, 13, 24, and 27) are identified, each displaying distinct changes in marker gene expression after ASX treatment. This finding suggests a modulation of CD8+ T cell function by ASX. Finally, the key transcription factors for four subclusters of CD8+ T cells are predicted and constructed a cell-to-cell communication network based on receptor-ligand interactions probability. In conclusion, ASX holds the potential to ameliorate liver damage by regulating the number and function of CD8+ T cells.