Comprehensive succinylome analyses reveal that hyperthermia upregulates lysine succinylation of annexin A2 by downregulating sirtuin7 in human keratinocytes.

Background and Objectives: Local hyperthermia at 44°C can clear multiple human papillomavirus (HPV)-infected skin lesions (warts) by targeting a single lesion, which is considered as a success of inducing antiviral immunity in the human body. However, approximately 30% of the patients had a lower response to this intervention. To identify novel molecular targets for anti-HPV immunity induction to improve local hyperthermia efficacy, we conducted a lysine succinylome assay in HaCaT cells (subjected to 44°C and 37°C water baths for 30 min). Methods: The succinylome analysis was conducted on HaCaT subjected to 44°C and 37°C water bath for 30 min using antibody affinity enrichment together with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were validated by western blot (WB), immunoprecipitation (IP), and co-immunoprecipitation (Co-IP). Then, bioinformatic analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, motif characterization, secondary structure, and protein-protein interaction (PPI) was performed. Results: A total of 119 proteins with 197 succinylated sites were upregulated in 44°C-treated HaCaT cells. GO annotation demonstrated that differential proteins were involved in the immune system process and viral transcription. Succinylation was significantly upregulated in annexin A2. We found that hyperthermia upregulated the succinylated level of global proteins in HaCaT cells by downregulating the desuccinylase sirtuin7 (SIRT7), which can interact with annexin A2. Conclusions: Taken together, these data indicated that succinylation of annexin A2 may serve as a new drug target, which could be intervened in combination with local hyperthermia for better treatment of cutaneous warts.

ENO1 regulates IL-1ß-induced chondrocyte inflammation, apoptosis and matrix degradation possibly through the potential binding to CRLF1.

In this study, we aim to investigate the role of enolase 1 (ENO1) in osteoarthritis (OA) pathogenic process and to uncover the underlying mechanism. To this end, we used IL-1ß to induce an in vitro OA­like chondrocyte model in human immortalized chondrocyte C-28/I2 cells. We manipulated the expression of ENO1 and cytokine receptor-like factor 1 (CRLF1) in IL-1ß-induced C-28/I2 cells using siRNA and/or overexpression and tested their effects on IL-1ß-induced pathologies including cell viability, apoptosis and inflammatory cytokine levels (IL-6 and TNF-α), and the expression of extracellular matrix-related enzymes and major mediators in the NF-κB signaling pathway (p-p65, p65, p-IκBα and IκBα). We used co-immunoprecipitation and immunofluorescence imaging to study a possible binding between ENO1 and CRLF1. Our data showed that IL-1ß induction elevated ENO1 and CRLF1 expression in C-28/I2 cells. Silencing ENO1 or CRLF1 inhibited the IL-1ß-induced cell viability damage, apoptosis, inflammation, and extracellular matrix degradation. The inhibitory effect of silencing ENO1 was reversed by CRLF1 overexpression, suggesting a functional connection between ENO1 and CRLF1, which could be attributed to a binding between these two partners. Our study could help validate the role of ENO1 in OA pathogenies and identify novel therapeutic targets for OA treatment.

A Bayesian Tensor Decomposition Method for Joint Estimation of Channel and Interference Parameters.

Bayesian tensor decomposition has been widely applied in channel parameter estimations, particularly in cases with the presence of interference. However, the types of interference are not considered in Bayesian tensor decomposition, making it difficult to accurately estimate the interference parameters. In this paper, we present a robust tensor variational method using a CANDECOMP/PARAFAC (CP)-based additive interference model for multiple input-multiple output (MIMO) with orthogonal frequency division multiplexing (OFDM) systems. A more realistic interference model compared to traditional colored noise is considered in terms of co-channel interference (CCI) and front-end interference (FEI). In contrast to conventional algorithms that filter out interference, the proposed method jointly estimates the channel and interference parameters in the time-frequency domain. Simulation results validate the correctness of the proposed method by the evidence lower bound (ELBO) and reveal the fact that the proposed method outperforms traditional information-theoretic methods, tensor decomposition models, and robust model based on CP (RCP) in terms of estimation accuracy. Further, the interference parameter estimation technique has profound implications for anti-interference applications and dynamic spectrum allocation.

Astrocytic Neuroligin-3 influences gene expression and social behavior, but is dispensable for synapse number.

Neuroligin-3 (Nlgn3) is an autism-associated cell-adhesion molecule that interacts with neurexins and is robustly expressed in both neurons and astrocytes. Neuronal Nlgn3 is an essential regulator of synaptic transmission but the function of astrocytic Nlgn3 is largely unknown. Given the high penetrance of Nlgn3 mutations in autism and the emerging role of astrocytes in neuropsychiatric disorders, we here asked whether astrocytic Nlgn3 might shape neural circuit properties in the cerebellum similar to neuronal Nlgn3. Imaging of tagged Nlgn3 protein produced by CRISPR/Cas9-mediated genome editing showed that Nlgn3 is enriched in the cell body but not the fine processes of cerebellar astrocytes (Bergmann glia). Astrocyte-specific knockout of Nlgn3 did not detectably alter the number of synapses, synaptic transmission, or astrocyte morphology in mouse cerebellum. However, spatial transcriptomic analyses revealed a significant shift in gene expression among multiple cerebellar cell types after the deletion of astrocytic Nlgn3. Hence, in contrast to neuronal Nlgn3, astrocytic Nlgn3 in the cerebellum is not involved in shaping synapses but may modulate gene expression in specific brain areas.

Altered landscape of total RNA, tRNA and sncRNA modifications in the liver and spleen of mice infected by Toxoplasma gondii.

BACKGROUND: Pathogens can impact host RNA modification machinery to establish a favorable cellular environment for their replication. In the present study, we investigated the effect of Toxoplasma gondii infection on host RNA modification profiles and explored how these modifications may influence the host-parasite interaction. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the modification levels of ∼ 80 nt tRNA and 17-50 nt sncRNAs in mouse liver, spleen, and serum using liquid chromatography and tandem mass spectrometry analysis. The results revealed alterations in RNA modification profiles, particularly during acute infection. The liver exhibited more differentially abundant RNA modifications than the spleen. RNA modification levels in serum were mostly downregulated during acute infection compared to control mice. Correlations were detected between different RNA modifications in the liver and spleen during infection and between several RNA modifications and many cytokines. Alterations in RNA modifications affected tRNA stability and protein translation. CONCLUSIONS/SIGNIFICANCE: These findings provide new insight into the role of RNA modifications in mediating the murine host response to T. gondii infection.

Paeoniflorin regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in oxidative stressed melanocytes.

BACKGROUND: The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to resist hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes via nuclear factorE2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. OBJECTIVES: This study was to investigate whether PF exerts anti-oxidative effect through influencing cytoskeleton markers or potential signaling pathway. METHODS: Human Oxidative Stress Plus array was used to identify the differentially expressed genes between H2O2 + PF group and H2O2 only group, in PIG1 and PIG3V melanocyte cell lines respectively. Western blotting was used to verify the PCR array results and to test the protein expression levels of cytoskeleton markers including Ras homolog family member A (RhoA), Rho-associated kinase 1 (ROCK1) and antioxidative marker Nrf2. Small interfering RNA was used to knock down PDZ and LIM domain 1 (PDLIM1). RESULTS: PF increased the expressions of PDLIM1, RhoA and ROCK1 in H2O2-induced PIG1, in contrast, decreased the expressions of PDLIM1 and ROCK1 in H2O2-induced PIG3V. Knockdown of PDLIM1 increased the expressions of RhoA and Nrf2 in PF-pretreated H2O2-induced PIG1, and ROCK1 and Nrf2 in PF-pretreated H2O2-induced PIG3V. CONCLUSIONS: PF regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in H2O2-induced melanocytes. In PIG1, PF promotes PDLIM1 to inhibit RhoA/ROCK1 pathway or activates Nrf2/HO-1 pathway, separately. In PIG3V, PF directly downregulates ROCK1 in PDLIM1-independent manner or upregulates Nrf2 dependent of PDLIM1.

Identification of Potential Ferroptosis Biomarkers and Analysis of Immune Cell Infiltration in Psoriasis Using Machine Learning.

Background: Ferroptosis is a type of cell death characterized by the accumulation of iron-dependent lethal lipid peroxides, which is associated with various pathophysiological processes. Psoriasis is a chronic autoimmune skin disease accompanied by abnormal immune cell infiltration and excessive production of lipid reactive oxygen species (ROS). Currently, its pathogenesis remains elusive, especially the potential role of ferroptosis in its pathophysiological process. Methods: The microarrays GSE13355 (58 psoriatic skin specimens versus 122 healthy skin specimens) and the ferroptosis database were employed to identify the common differentially expressed genes (DEGs) associated with psoriasis and ferroptosis. The functions of common DEGs were investigated through functional enrichment analysis and protein-protein interaction analysis. The potential diagnostic markers for psoriasis among the common DEGs were identified using four machine-learning algorithms. DGIdb was utilized to explore potential therapeutic agents for psoriasis. Additionally, CIBERSORT was employed to investigate immune infiltration in psoriasis. Results: A total of 8 common DEGs associated with psoriasis and ferroptosis were identified, which are involved in intercellular signaling and affect pathways of cell response to stress and stimulation. Four machine-learning algorithms were employed to identify poly (ADP-ribose) polymerase 12 (PARP12), frizzled homolog 7 (FZD7), and arachidonate 15-lipoxygenase (ALOX15B) among the eight common DEGs as potential diagnostic markers for psoriasis. A total of 18 drugs targeting the five common DEGs were identified as potential candidates for treating psoriasis. Additionally, significant changes were observed in the immune microenvironment of patients with psoriasis. Conclusion: This study has contributed to our enhanced comprehension of ferroptosis-related genes as potential biomarkers for psoriasis diagnosis, as well as the alterations in the immune microenvironment associated with psoriasis. Our findings offer valuable insights into the diagnosis and treatment of psoriasis.

Dynamic pathological analysis reveals a protective role against skin fibrosis for TREM2-dependent macrophages.

Rationale: Systemic sclerosis (SSc) is a chronic and incurable autoimmune disease with high mortality rates, and skin fibrosis is one of distinguishing hallmarks in the pathogenesis. However, macrophage heterogeneity regulating skin fibrosis remain largely unknown. Methods: We established mouse disease model and performed single-cell RNA-sequencing (scRNA-seq) to resolve the dynamic and heterogenous characteristics of macrophages in skin fibrosis, and the role of TREM2-dependent macrophages in the pathological process was investigated using knockout mice and intraperitoneal transferring TREM2+ macrophages combining with functional assays. Results: We show that TREM2-expressing macrophages (TREM2+ MФs) accumulate in injured skin of mice treated by bleomycin (BLM) and human SSc, and their gene signatures and functional pathways are identified in the course of disease. Genetic ablation of Trem2 in mice globally accelerates and aggravates skin fibrosis, whereas transferring TREM2hi macrophages improves and alleviates skin fibrosis. Amazingly, we found that disease-associated TREM2+ MФs in skin fibrosis exhibit overlapping signatures with fetal skin counterparts in mice and human to maintain skin homeostasis, but each has merits in skin remodeling and development respectively. Conclusion: This study identifies that TREM2 acts as a functional molecule and a major signaling by which macrophage subpopulations play a protective role against fibrosis, and disease-associated TREM2+ MФs in skin fibrosis might undergo a fetal-like reprogramming similar to fetal skin counterparts.

[Changes of parameters associated with anemia of inflammation in patients with stage â ¢ periodontitis before and after periodontal initial therapy].

OBJECTIVE: To investigate the differences and similarities of parameters associated with anemia of inflammation between patients with stage Ⅲ periodontitis and periodontally healthy volunteers, and to explore the influence of periodontal initial therapy on those indicators. METHODS: Patients with stage Ⅲ periodontitis and periodontally healthy volunteers seeking periodontal treatment or prophylaxis at Department of Periodontology, Peking University School and Hospital of Stomatology from February 2020 to February 2023 were enrolled. Their demographic characteristics, periodontal parameters (including probing depth, clinical attachment loss, bleeding index), and fasting blood were gathered before periodontal initial therapy. Three months after periodontal initial therapy, the periodontal parameters of the patients with stage Ⅲ periodontitis were re-evaluated and their fasting blood was collected again. Blood routine examinations (including white blood cells, red blood cells, hemoglobin, packed cell volume, mean corpuscular volume of erythrocytes, and mean corpuscular hemoglobin concentration) were performed. And ferritin, hepcidin, erythropoietin (EPO) were detected with enzyme-linked immunosorbent assay (ELISA). All data analysis was done with SPSS 21.0, independent sample t test, paired t test, and analysis of covariance were used for comparison between the groups. RESULTS: A total of 25 patients with stage Ⅲ periodontitis and 25 periodontally healthy volunteers were included in this study. The patients with stage Ⅲ periodontitis were significantly older than those in periodontally healthy status [(36.72±7.64) years vs. (31.44±7.52) years, P=0.017]. The patients with stage Ⅲ periodontitis showed lower serum hemoglobin [(134.92±12.71) g/L vs. (146.52±12.51) g/L, P=0.002] and higher serum ferritin [(225.08±103.36) µg/L vs. (155.19±115.38) µg/L, P=0.029], EPO [(41.28±12.58) IU/L vs. (28.38±10.52) IU/L, P < 0.001], and hepcidin [(48.03±34.44) µg/L vs. (27.42±15.00) µg/L, P=0.009] compared with periodontally healthy volunteers. After adjusting the age with the covariance analysis, these parameters (hemoglobin, ferritin, EPO, and hepcidin) showed the same trends as independent-sample t test with statistical significance. Three months after periodontal initial therapy, all the periodontal parameters showed statistically significant improvement. The serum hemoglobin raised [(146.05±15.48) g/L vs. (133.77± 13.15) g/L, P < 0.001], while the serum ferritin [(128.52±90.95) µg/L vs. (221.22±102.15) µg/L, P < 0.001], EPO [(27.66±19.67) IU/L vs. (39.63± 12.48) IU/L, P=0.004], and hepcidin [(32.54±18.67) µg/L vs. (48.18±36.74) µg/L, P=0.033] decreased compared with baseline. CONCLUSION: Tendency of iron metabolism disorder and anemia of inflammation was observed in patients with stage Ⅲ periodontitis, which can be attenuated by periodontal initial therapy.

Effects of time-restricted eating on intrahepatic fat and metabolic health among patients with nonalcoholic fatty liver disease.

OBJECTIVE: The study's objective was to explore whether early time-restricted eating (eTRE) and late time-restricted eating (lTRE) have different impacts on intrahepatic fat and metabolic health among patients with nonalcoholic fatty liver disease (NAFLD). METHODS: This is an 8-week, randomized, parallel-arm, open-label trial. Forty eligible patients were randomly assigned to eTRE (eating between 8:00 a.m. and 4:00 p.m.) or lTRE (eating between 12:00 p.m. and 8:00 p.m.). The primary outcome was the change of intrahepatic fat measured by magnetic resonance image-derived proton density fat fraction. Secondary outcomes included changes in weight, body composition, liver function, and cardiometabolic factors. RESULTS: Forty participants who underwent randomization completed the trial (mean age: 38.25 years). The eTRE group had a -3.24% absolute reduction of intrahepatic fat (95% CI: -4.55% to -1.92%) and there was a -3.51% absolute reduction for the lTRE group (95% CI: -5.10% to -1.92%). Changes in intrahepatic fat were not statistically different between the two groups. Both the eTRE and lTRE groups had similar and significant reductions in weight, visceral fat, subcutaneous fat, liver enzymes, and glucose regulatory indicators. CONCLUSIONS: Among patients with NAFLD, both eTRE and lTRE induced significant reductions in intrahepatic fat and improvements in body composition, liver function, and metabolic health with similar magnitude. These findings suggest that eTRE and lTRE are comparable and feasible strategies for NAFLD management.

Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging.

Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.

Integrated Human Skin Bacteria Genome Catalog Reveals Extensive Unexplored Habitat-Specific Microbiome Diversity and Function.

The skin is the largest organ in the human body. Various skin environments on its surface constitutes a complex ecosystem. One of the characteristics of the skin micro-ecosystem is low biomass, which greatly limits a comprehensive identification of the microbial species through sequencing. In this study, deep-shotgun sequencing (average 21.5 Gigabyte (Gb)) from 450 facial samples and publicly available skin metagenomic datasets of 2069 samples to assemble a Unified Human Skin Genome (UHSG) catalog is integrated. The UHSG encompasses 813 prokaryotic species derived from 5779 metagenome-assembled genomes, among which 470 are novel species covering 20 phyla with 1385 novel assembled genomes. Based on the UHSG, the core functions of the skin microbiome are described and the differences in amino acid metabolism, carbohydrate metabolism, and drug resistance functions among different phyla are identified. Furthermore, analysis of secondary metabolites of the near-complete genomes further find 1220 putative novel secondary metabolites, several of which are found in previously unknown genomes. Single nucleotide variant (SNV) reveals a possible skin protection mechanism: the negative selection process of the skin environment to conditional pathogens. UHSG offers a convenient reference database that will facilitate a more in-depth understanding of the role of skin microorganisms in the skin.

Flexible Ag-S-Te System with Promising Room-Temperature Thermoelectric Performance.

Silver chalcogenides demonstrate great potential as flexible thermoelectric materials due to their excellent ductility and tunable electrical and thermal transport properties. In this work, we report that the amorphous/crystalline phase ratio and thermoelectric properties of the Ag2SxTe1-x (x = 0.55-0.75) samples can be modified by altering the S content. The room-temperature power factor of the Ag2S0.55Te0.45 sample is 4.9 µW cm-1 K-2, and a higher power factor can be achieved by decreasing the carrier concentration as predicted by the single parabolic band model. The addition of a small amount of excessive Te into Ag2S0.55Te0.45 (Ag2S0.55Te0.45+y) not only enhances the power factor by decreasing the carrier concentration but also reduces the total thermal conductivity due to decreased electronic thermal conductivity. Owing to the effectively optimized carrier concentration, the thermoelectric power factor and dimensionless figure of merit zT of the sample with y = 0.007 reaches, respectively, 6.2 µW cm-1 K-2 and 0.39, while the excellent plastic deformability is well maintained, demonstrating its promising potential as a flexible thermoelectric material at room temperature.

Plasma Extracellular Vesicle MicroRNA Analysis of Alzheimer's Disease Reveals Dysfunction of a Neural Correlation Network.

Small extracellular vesicle (sEV) is an emerging source of potential biomarkers of Alzheimer's disease (AD), but the role of microRNAs (miRNAs) in sEV is not well understood. In this study, we conducted a comprehensive analysis of sEV-derived miRNAs in AD using small RNA sequencing and coexpression network analysis. We examined a total of 158 samples, including 48 from AD patients, 48 from patients with mild cognitive impairment (MCI), and 62 from healthy controls. We identified an miRNA network module (M1) that was strongly linked to neural function and showed the strongest association with AD diagnosis and cognitive impairment. The expression of miRNAs in the module was decreased in both AD and MCI patients compared to controls. Conservation analysis revealed that M1 was highly preserved in the healthy control group but dysfunctional in the AD and MCI groups, suggesting that changes in the expression of miRNAs in this module may be an early response to cognitive decline prior to the appearance of AD pathology. We further validated the expression levels of the hub miRNAs in M1 in an independent population. The functional enrichment analysis showed that 4 hub miRNAs might interact with a GDF11-centered network and play a critical role in the neuropathology of AD. In summary, our study provides new insights into the role of sEV-derived miRNAs in AD and suggests that M1 miRNAs may serve as potential biomarkers for the early diagnosis and monitoring of AD.

Proposal of optically tunable and reconfigurable multi-channel bandstop filter using sum-frequency generation in a PPLN waveguide.

A multi-wavelength bandstop filter is proposed and numerically demonstrated using the sum-frequency generation (SFG) process in a waveguide of periodically poled lithium niobate (PPLN). This proposed device achieves channels number reconfigurable, central filtering wavelength of each filtering channel independently tunable and extinction ratios (ERs) equalized via all-optical methods.

Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.

What determines plant species diversity along the Modern Silk Road in the east?

As primary producers, plants provide food, oxygen, and other resources for global ecosystems, and should therefore be given priority in biodiversity protection. Most biodiversity research focuses on biodiversity hotspots, while biodiversity coldspots, such as deserts, are largely ignored. We propose that the factors shaping plant species diversity differ between biodiversity hot spots and cold spots, especially for desert ecosystems. To test this hypothesis, we investigated plant species diversity along the Modern Silk Road in the Northwest China desert, an area characterized by low precipitation, scarce vegetation, a limited number of species, and variable human activities. Surface soil was sampled from 144 plots, environmental DNA (eDNA) was extracted from soil samples, and seed plant species were identified using DNA metabarcoding technology. A total of 671 seed plant species were detected, which was more diverse than indicated by plot survey data. Plant species diversity gradually decreased from east to west along the Silk Road. In this area, temperature determines plant species diversity more than precipitation. Additionally, human activity has altered plant species diversity by introducing crops and invasive plants and eliminating environmentally adapted indigenous plants. Our results demonstrate the potential of eDNA metabarcoding technology for plant species diversity surveying. Desert plants have adapted to dry environments by relying on underground water or utilizing occasional rainfall as ephemerals, which are often not visible during surface surveys because of their short aboveground life cycle but can be detected with eDNA metabarcoding technology. Groundwater maintenance and human activity control are recommended for plant species diversity conservation and desertification control.

A population-based study of precision health assessments using multi-omics network-derived biological functional modules.

Recent technological advances in multi-omics and bioinformatics provide an opportunity to develop precision health assessments, which require big data and relevant bioinformatic methods. Here we collect multi-omics data from 4,277 individuals. We calculate the correlations between pairwise features from cross-sectional data and then generate 11 biological functional modules (BFMs) in males and 12 BFMs in females using a community detection algorithm. Using the features in the BFM associated with cardiometabolic health, carotid plaques can be predicted accurately in an independent dataset. We developed a model by comparing individual data with the health baseline in BFMs to assess health status (BFM-ash). Then we apply the model to chronic patients and modify the BFM-ash model to assess the effects of consuming grape seed extract as a dietary supplement. Finally, anomalous BFMs are identified for each subject. Our BFMs and BFM-ash model have huge prospects for application in precision health assessment.