RESUMEN

BACKGROUND: Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN. METHODS: Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves. RESULTS: Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (ß 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated. CONCLUSIONS: Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.

Asunto(s)

RESUMEN

To understand the prevalence of cognitive impairment (CI) in middle-aged and elderly individuals in Anhui Province and to develop a CI risk prediction model. From May to June 2022, a multistage, stratified cluster-sampling method was used to select 3200 middle-aged and elderly people over 45 years old in Anhui Province for a questionnaire survey, and the Chinese version of the Mini-Mental State Examination (MMSE) was used to assess cognitive function. SPSS 25.0 was used for univariate and multivariate analyses, and R software was used to establish and validate the nomogram. A total of 3059 valid questionnaires were included, of which 384 were from participants who were diagnosed with CI, and the prevalence rate was 12.6%. Multivariate logistic analysis showed that female sex, advanced age, family history, etc., were closely related to the occurrence of CI. The area under curve (AUC) values in the modeling and validation groups were 0.845 (95% CI: 0.822-0.868) and 0.868 (95% CI: 0.835-0.902), respectively, indicating that the predictive ability of the model was good. The Hosmer-Lemeshow test suggested that the model had good goodness-of-fit, and the decision-curve evaluation nomogram had a high benefit within the threshold, which had a certain clinical importance. The prevalence rate of CI among middle-aged and elderly individuals in Anhui Province was 12.6%. Female sex, elderly age, family history, low educational status, current smoking status, sleep disorders, hypertension, stroke, and diabetes were shown to be risk factors for CI, while exercise was shown to be a protective factor.

Asunto(s)

RESUMEN

Understanding the way cells communicate, co-locate, and interrelate is essential to understanding human physiology. Hematoxylin and eosin (H&E) staining is ubiquitously available both for clinical studies and research. The Colon Nucleus Identification and Classification (CoNIC) Challenge has recently innovated on robust artificial intelligence labeling of six cell types on H&E stains of the colon. However, this is a very small fraction of the number of potential cell classification types. Specifically, the CoNIC Challenge is unable to classify epithelial subtypes (progenitor, endocrine, goblet), lymphocyte subtypes (B, helper T, cytotoxic T), or connective subtypes (fibroblasts, stromal). In this paper, we propose to use inter-modality learning to label previously un-labelable cell types on virtual H&E. We leveraged multiplexed immunofluorescence (MxIF) histology imaging to identify 14 subclasses of cell types. We performed style transfer to synthesize virtual H&E from MxIF and transferred the higher density labels from MxIF to these virtual H&E images. We then evaluated the efficacy of learning in this approach. We identified helper T and progenitor nuclei with positive predictive values of 0.34 ± 0.15 (prevalence 0.03 ± 0.01) and 0.47 ± 0.1 (prevalence 0.07 ± 0.02) respectively on virtual H&E. This approach represents a promising step towards automating annotation in digital pathology.

RESUMEN

BACKGROUND: Surgical site infection (SSI) remains a critical postoperative complication after total hip and knee arthroplasty (THA and TKA). Frailty, a condition characterized by decreased physiological reserve and increased vulnerability to stressors, may influence the risk of SSI in these patients. This meta-analysis aims to evaluate the association between frailty and the incidence of SSI following THA or TKA. METHODS: A systematic search of databases including PubMed, EMBASE, Web of Science, Wanfang, and CNKI was conducted to identify relevant studies. Data were extracted and pooled using a random-effects model to calculate the overall risk ratio (RR) and 95 % confidence intervals (CIs). RESULTS: A total of ten studies comprising 1,036,787 patients met the inclusion criteria. The meta-analysis revealed that frail patients undergoing THA or TKA had a significantly higher risk of developing SSI compared to non-frail patients (RR = 1.64, 95 % CI: 1.39-1.93, p < 0.001, I2 = 66 %). Subgroup analyses indicated that the type of arthroplasty (hip vs. knee) and the method of frailty assessment did not significantly alter the association. Further subgroup analysis suggested that frailty was significantly associated with a higher incidence of deep SSI including joint infection (RR = 1.77, 95 % CI: 1.27-1.48, p < 0.001), but not the incidence of superficial SSI (RR = 1.57, 95 % CI: 0.45-5.42, p = 0.48). The association between frailty and SSI remains in subgroup of multivariate studies only (RR = 1.56, 95 % CI: 1.34 to 1.80, p < 0.001). CONCLUSIONS: Frailty is a potential predictor of SSI following TKA/THA.

RESUMEN

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon­carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid ß (Aß)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aß-induced neuronal damage.

RESUMEN

Sarcopenia is a complex age-associated syndrome of progressive loss of muscle mass and strength. Although this condition is influenced by many factors, age-related changes in immune function including immune cell dynamics, and chronic inflammation contribute to its progression. The complex interplay between the immune system, gut-muscle axis, and autophagy further underscores their important roles in sarcopenia pathogenesis. Immunomodulation has emerged as a promising strategy to counteract sarcopenia. Traditional management approaches to treat sarcopenia including physical exercise and nutritional supplementation, and the emerging technologies of biophysical stimulation demonstrated the importance of immunomodulation and regulation of macrophages and T cells and reduction of chronic inflammation. Treatments to alleviate low-grade inflammation in older adults by modulating gut microbial composition and diversity further combat sarcopenia. Furthermore, some pharmacological interventions, nano-medicine, and cell therapies targeting muscle, gut microbiota, or autophagy present additional avenues for immunomodulation in sarcopenia. This narrative review explores the immunological underpinnings of sarcopenia, elucidating the relationship between the immune system and muscle during ageing. Additionally, the review discusses new areas such as the gut-muscle axis and autophagy, which bridge immune system function and muscle health. Insights into current and potential approaches for sarcopenia management through modulation of the immune system are provided, along with suggestions for future research directions and therapeutic strategies. We aim to guide further investigation into clinical immunological biomarkers and identify indicators for sarcopenia diagnosis and potential treatment targets to combat this condition. We also aim to draw attention to the importance of considering immunomodulation in the clinical management of sarcopenia.

RESUMEN

Ni-rich cathode materials have garnered significant attention attributable to the high reversible capacity and superior rate performance, particularly in the electric vehicle industry. However, the structural degradation experienced during cycling results in rapid capacity decay and deterioration of the rate performance, thereby impeding the widespread application of Ni-rich cathodes. Herein, a Mg/Ti co-doping strategy was developed to boost the structure stability and Li-ion transport kinetics of the Ni-rich cathode material LiNi0.90Co0.05Mn0.05O2 (NCM9055) under long cycle. It is demonstrated that the Mg2+ ions inserted into the lithium layer could serve as pillars, enhancing the stability of the delithiated layer structure. The introduction of robust Ti-O bonding mitigated the detrimental H2-H3 phase transition (∼4.2 V) during cycling. In addition, despite the fact that Mg/Ti co-doping slightly reduces Li+ diffusion coefficient in the modified cathode material (NCM9055-MT), it effectively stabilized the robustness of the layered structure and maintained the Li+ diffusion channel while charging and discharging, thereby improving the Li+ diffusion coefficient after a long cycle. Therefore, the Mg/Ti co-doped cathode materials exhibited an exceptional capacity retention rate of 99.9% (100 cycles, 1 C). Additionally, the Li+ diffusion coefficient of the co-doped NCM9055-MT (2.924 × 10-10 cm2 s-1) after 100 cycles was effectively enhanced compared with the case of undoped NCM9055 (4.806 × 10-11 cm2 s-1). This work demonstrates that the Mg/Ti co-doping approach effectively enhanced the stability of layered Ni-rich cathode materials.

RESUMEN

Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as 'LND') with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn's ileitis and colitis.

Asunto(s)

RESUMEN

Personalized neoantigen vaccines have achieved major advancements in recent years, with studies in melanoma leading progress in the field. Early clinical trials have demonstrated their feasibility, safety, immunogenicity, and potential efficacy. Advances in sequencing technologies and neoantigen prediction algorithms have substantively improved the identification and prioritization of neoantigens. Innovative delivery platforms now support the rapid and flexible production of vaccines. Several ongoing efforts in the field are aimed at improving the integration of large datasets, refining the training of prediction models, and ensuring the functional validation of vaccine immunogenicity.

Asunto(s)

RESUMEN

In the realm of marine environmental engineering, the swift and accurate detection of underwater targets is of considerable significance. Recently, methods based on Convolutional Neural Networks (CNN) have been applied to enhance the detection of such targets. However, deep neural networks usually require a large number of parameters, resulting in slow processing speed. Meanwhile, existing methods present challenges in accurate detection when facing small and densely arranged underwater targets. To address these issues, we propose a new neural network model, YOLOv8-LA, for improving the detection performance of underwater targets. First, we design a Lightweight Efficient Partial Convolution (LEPC) module to optimize spatial feature extraction by selectively processing input channels to improve efficiency and significantly reduce redundant computation and storage requirements. Second, we developed the AP-FasterNet architecture for small targets that are commonly found in underwater datasets. By integrating depth-separable convolutions with different expansion rates into FasterNet, AP-FasterNet enhances the model's ability to capture detailed features of small targets. Finally, we integrate the lightweight and efficient content-aware reorganization (CARAFE) up-sampling operation into YOLOv8 to enhance the model performance by aggregating contextual information over a large perceptual field and mitigating information loss during up-sampling.Evaluation results on the URPC2021 dataset show that the YOLOv8-LA model achieves 84.7% mean accuracy (mAP) on a single Nvidia GeForce RTX 3090 and operates at 189.3 frames per second (FPS), demonstrating that it outperforms existing state-of-the-art methods in terms of performance. This result demonstrates the model's ability to ensure high detection accuracy while maintaining real-time processing capabilities.

RESUMEN

Multiplex immunofluorescence (MxIF) is an advanced molecular imaging technique that can simultaneously provide biologists with multiple (i.e., more than 20) molecular markers on a single histological tissue section. Unfortunately, due to imaging restrictions, the more routinely used hematoxylin and eosin (H&E) stain is typically unavailable with MxIF on the same tissue section. As biological H&E staining is not feasible, previous efforts have been made to obtain H&E whole slide image (WSI) from MxIF via deep learning empowered virtual staining. However, the tiling effect is a long-lasting problem in high-resolution WSI-wise synthesis. The MxIF to H&E synthesis is no exception. Limited by computational resources, the cross-stain image synthesis is typically performed at the patch-level. Thus, discontinuous intensities might be visually identified along with the patch boundaries assembling all individual patches back to a WSI. In this work, we propose a deep learning based unpaired high-resolution image synthesis method to obtain virtual H&E WSIs from MxIF WSIs (each with 27 markers/stains) with reduced tiling effects. Briefly, we first extend the CycleGAN framework by adding simultaneous nuclei and mucin segmentation supervision as spatial constraints. Then, we introduce a random walk sliding window shifting strategy during the optimized inference stage, to alleviate the tiling effects. The validation results show that our spatially constrained synthesis method achieves a 56% performance gain for the downstream cell segmentation task. The proposed inference method reduces the tiling effects by using 50% fewer computation resources without compromising performance. The proposed random sliding window inference method is a plug-and-play module, which can be generalized for other high-resolution WSI image synthesis applications. The source code with our proposed model are available at https://github.com/MASILab/RandomWalkSlidingWindow.git.

RESUMEN

Background: Parkinson's disease (PD) is marked by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and cognitive dysfunctions. The molecular mechanisms underlying synaptic alterations in PD remain elusive, with a focus on the role of Itga5 in synaptic integrity and motor coordination and TAT-Itga5 was designed to suppress PTEN activity in this investigation. Methods: This study utilized MPTP-induced PD animal models to investigate the expression and role of Itga5 in the striatum. Techniques included quantitative PCR, Western blotting, immunostaining, CRISPR-CasRx-mediated knockdown, electrophysiological assays, behavioral tests, and mass spectrometry. Results: Itga5 expression was significantly reduced in MPTP-induced PD models. In these models, a marked decrease in dendritic spine density and a shift towards thinner spines in striatal GABA neurons were observed, suggesting impaired synaptic integration. Knockdown of Itga5 resulted in reduced dendritic branching, decreased mushroom spines, and increased thin spines, altering synaptic architecture. Electrophysiological analyses revealed changes in action potential and spontaneous excitatory postsynaptic currents, indicating altered synaptic transmission. Motor behavior assessments showed that Itga5 deficiency led to impairments in fine motor control and coordination. Furthermore, Itga5 was found to interact with PTEN, affecting AKT signaling crucial for synaptic development and motor coordination. Conclusion: The study demonstrates that Itga5 plays a critical role in maintaining synaptic integrity and motor coordination in PD. The Itga5-PTEN-AKT pathway represents a potential therapeutic target for addressing synaptic and motor dysfunctions in PD.

Asunto(s)

RESUMEN

Introduction: The current study aimed to compare the outcomes of endoscopic and minimally invasive surgical treatment for infected necrotizing pancreatitis. Material and methods: A meta-analysis of clinical studies on minimally invasive operations for necrotic infection was conducted. A systematic review and study inclusion were done on multiple databases. English-language prospective comparison studies were included. Random design was used to analyze research with continuous and dichotomous variables. Results: Ten studies were included in the current study. When compared to minimally invasive surgery, endoscopic procedures showed significant beneficial outcomes regarding low post-operative complication rates (p = 0.006), new onset organ failure (p < 0.001), and pancreatic fistula (p < 0.001). However, there was no significant difference between the two interventions regarding hospital stay, postoperative bleeding, incisional hernia, endocrine insufficiency, and perforation of a visceral organ. Conclusions: Endoscopic therapy appears to have potential advantages over minimally invasive surgery. However, there is no difference between interventions regarding several parameters.

RESUMEN

Background: The interaction between muscle and bone is shown to be clinically important but the underlying mechanisms are largely unknown. The canonical Wnt/ß-catenin signaling pathway is reported to be involved in muscle-bone crosstalk, but its detailed function remains unclear. This systematic review aims to investigate and elucidate the role of the Wnt/ß-catenin signaling pathways in muscle-bone crosstalk. Methods: We conducted a literature search on the Web of Science, PubMed, EBSCO and Embase with keywords "Wnt*", "bone*" and "muscle*". A systematic review was completed according to the guideline of preferred reporting items of systematic reviews and meta-analyses (PRISMA). Data synthesis included species (human, animal or cell type used), treatments involved, outcome measures and key findings with respect to Wnts. Results: Seventeen papers were published from 2007 to 2021 and were extracted from a total of 1529 search results in the databases of Web of Science (468 papers), PubMed (457 papers), EBSCO (371) and Embase (233). 12 Wnt family members were investigated in the papers, including Wnt1, Wnt2, Wnt2b, Wnt3a, Wnt4, Wnt5a, Wnt8a, Wnt8b, Wnt9a, Wnt10a, Wnt10b and Wnt16. Many studies showed that muscles were able to increase or decrease osteogenesis of bone, while bone increased myogenesis of muscle through Wnt/ß-catenin signaling pathways. Wnt3a, Wnt4 and Wnt10b were shown to play important roles in the crosstalk between muscle and bone. Conclusions: Wnt3a, Wnt4 and Wnt10b are found to play important mediatory roles in muscle-bone crosstalk. The role of Wnt4 was mostly found to regulate muscle from the bone side. Whilst the role of Wnt10b during muscle ageing was proposed, current evidence is insufficient to clarify the specific role of Wnt/ß-catenin signaling in the interplay between sarcopenia and osteoporosis. More future studies are required to investigate the exact regulatory roles of Wnts in muscle-bone crosstalk in musculoskeletal disease models such as sarcopenia and osteoporosis. Translational potential of this article: The systematic review provides an extensive overview to reveal the roles of Wnt/ß-catenin signaling pathways in muscle-bone crosstalk. These results provide novel research directions to further understand the underlying mechanism of sarcopenia, osteoporosis, and their crosstalk, finally helping the future development of new therapeutic interventions.

RESUMEN

It is important to ensure the nutritional quality and safe production of rice. Here, plot experiments were used to analyze the effects of three soil amendments-10 t ha-1 of biochar (BC), 1.5 t ha-1 of lime (LM), and 2.25 t ha-1 of silicon-calcium fertilizer (SC)-on the soil characteristics, rice yield and quality of double-cropping rice grown in mildly cadmium-polluted paddy fields. Compared with the control treatment (CK), the BC and SC treatments significantly improved rice processing, appearance and nutritional quality, but reduced cooking quality. All three soil amendments significantly reduced cadmium (Cd) content in brown rice. Soil amendments could significantly increase soil pH and reduce soil available Cd content. The application of the BC and SC treatments increased the content of each nutrient index in the soil (SOM, NN, AP, AK). Correlation analysis showed that the improvement in rice processing, appearance, and nutritional quality was mainly affected by the comprehensive effects of soil SOM, NN, AP and AK; the hygiene quality was mainly affected by soil pH and available Cd. In terms of benefit analysis combined with cost, the SC treatment had the highest benefit effect. Taken together, in mildly cadmium-polluted paddy fields, the application of silicon-calcium fertilizer improved the soil quality, thereby increased the yield and quality of rice, and had the best effect on increasing income.

Asunto(s)

RESUMEN

BACKGROUNDS: Microfibril-associated protein 2 (MFAP2) is a protein presenting in the extracellular matrix that governs the activity of microfibrils through its interaction with fibrillin. While the involvement of MFAP2 in metabolic disorders has been documented, its expression and prognostic significance in triple-negative breast cancer (TNBC) remain unexplored. METHODS: We acquired datasets pertaining to breast cancer (BC) from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Next, a Venn diagram was used to identify the differentially expressed genes (DEGs). The DEGs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), immune and survival analysis. The expressions of MFAP2, PD-1 and PD-L1 were examined by immunohistochemistry and western blot and their relationship with clinical pathological parameters were analyzed by clinical specimen samples from patients with TNBC. Tumor Immune Estimation Resource (TIMER, https://cistrome.shinyapps.io/timer/ ) was adopted to calculate the immune infiltration level of TNBC. The link between gene expression and tumor mutational burden (TMB) was described using Spearman's correlation analysis. RESULTS: We identified 66 differentially expressed genes (DEGs) that were up-regulated. Among these DEGs, MFAP2 was found to be overexpressed in TNBC and was associated with a lower probability of survival. This finding was confirmed through the use of immunohistochemistry and western blot techniques. Additionally, MFAP2 was found to be related to various pathological parameters in TNBC patients. Mechanistically, gene set enrichment analysis (GSEA) revealed that MFAP2 primarily influenced cellular biological behavior in terms of epithelial mesenchymal transition, glycolysis, and apical junction. Notably, MFAP2 expression was positively correlated with the abundance of macrophages, while a negative correlation was observed with the abundance of B cells, CD4 + T cells, CD8 + T cells, neutrophils and dendritic cells through immune analysis. Furthermore, it was observed that MFAP2 displayed a negative correlation not only with tumor mutational burden (TMB), a recognized biomarker for PD-1/PD-L1 immunotherapy, but also with PD-L1 in samples of TNBC. CONCLUSION: MFAP2 may be an important prognostic biomarker for TNBC, as well as a viable target for immunotherapy in this disease.

RESUMEN

Rosacea is a chronic and recurrent inflammatory skin disease affecting the center of the face that causes burning and itching sensations and changes in aesthetics. Liang Xue Wu Hua Tang (LXWHT) is a classic herbal formulation that is efficacious and has been widely used in the clinical treatment of rosacea; however, the pharmacological mechanisms remain unclear. The aim of the present study was to investigate the mechanism of action of LXWHT using network pharmacology and molecular docking. The Traditional Chinese Medicine System Pharmacology database was searched to identify the active ingredients and pharmacological targets of LXWHT, and the GeneCard, Disgenet, and Gene Expression Omnibus databases were applied to screen rosacea-related targets. Cytoscape software was used to visualize the protein-protein interaction network, and network topology analysis was used to identify core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for the core targets. Molecular docking simulations and visualization were performed using Maestro and PyMOL, respectively. A total of 43 active compounds and 28 potential targets for LXWHT treatment of rosacea were selected for analysis. The Gene Ontology/Kyoto Encyclopedia of Genes and Genomes results indicated that LXWHT may exert therapeutic effects on rosacea by intervening in immune pathways including tumor necrosis factor pathway, interleukin-17 pathways, and Toll-like receptor signaling pathways. Chemokine ligand 2, interferon-γ, interleukin-1ß, peroxisome proliferator-activated receptor-γ, and matrix metallopeptidase 9 may be the core therapeutic target. Quercetin, stigmasterol, kaempferol, beta-sitosterol, luteolin, beta-carotene, baicalein, acetin, and isorhamnetin were predicted to be the key active ingredients. LXWHT may exert therapeutic effects in the treatment of rosacea by modulating immunity and angiogenesis, laying the foundation for further research.

Asunto(s)

RESUMEN

Composed of obesity and lipid parameters, the cardiometabolic index (CMI) has emerged as a novel diagnostic tool. Originally developed for diabetes diagnosis, its application has expanded to identifying patients with cardiovascular diseases, such as atherosclerosis and hypertension. However, the relationship between CMI and non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in the US population remains unclear. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017-2020, involving 2996 participants aged 20 years or older. Vibration controlled transient elastography using a FibroScan® system (model 502, V2 Touch) with controlled attenuation parameter measurements identified NAFLD at a threshold of ≥ 274 dB/m, while liver stiffness measurement (LSM) results (median, ≥ 8.2 kPa) indicated fibrosis. A multifactorial logistic regression model explored the relationship between CMI and NAFLD and fibrosis. The effectiveness of CMI in detecting NAFLD and liver fibrosis was assessed through receiver operating characteristic curve analysis. Controlling for potential confounders, CMI showed a significant positive association with NAFLD (adjusted OR = 1.44, 95% CI 1.44-1.45) and liver fibrosis (adjusted OR = 1.84, 95% CI 1.84-1.85). The Areas Under the Curve for predicting NAFLD and fibrosis were 0.762 (95% CI 0.745 ~ 0.779) and 0.664(95% CI 0.633 ~ 0.696), respectively, with optimal cut-off values of 0.462 and 0.527. There is a positive correlation between CMI and NAFLD and fibrosis, which is a suitable and simple predictor of NAFLD and fibrosis.

Asunto(s)

RESUMEN

Lymphocyte activation involves a transition from quiescence and associated catabolic metabolism to a metabolic state with noted similarities to cancer cells such as heavy reliance on aerobic glycolysis for energy demands and increased nutrient requirements for biomass accumulation and cell division 1-3 . Following antigen receptor ligation, lymphocytes require spatiotemporally distinct "second signals". These include costimulatory receptor or cytokine signaling, which engage discrete programs that often involve remodeling of organelles and increased nutrient uptake or synthesis to meet changing biochemical demands 4-6 . One such signaling molecule, IL-4, is a highly pleiotropic cytokine that was first identified as a B cell co-mitogen over 30 years ago 7 . However, how IL-4 signaling mechanistically supports B cell proliferation is incompletely understood. Here, using single cell RNA sequencing we find that the cholesterol biosynthetic program is transcriptionally upregulated following IL-4 signaling during the early B cell response to influenza virus infection, and is required for B cell activation in vivo . By limiting lipid availability in vitro , we determine cholesterol to be essential for B cells to expand their endoplasmic reticulum, progress through cell cycle, and proliferate. In sum, we demonstrate that the well-known ability of IL-4 to act as a B cell growth factor is through a previously unknown rewiring of specific lipid anabolic programs, relieving sensitivity of cells to environmental nutrient availability.