Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.

A Statovirus-like virus from respiratory tracts of patients, China.

The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.

Epidemiological behaviour and interventions of malaria in Niger, 2010-2019: a time-series analysis of national surveillance data.

BACKGROUND: Malaria remains a significant public health concern in Niger, with the number of cases increasing from 592,334 in 2000 to 3,138,696 in 2010. In response, a concerted campaign against the disease has been initiated. However, the implementation of these malaria interventions and their association with epidemiological behaviour remains unclear. METHODS: A time-series study was conducted in Niger from 2010 to 2019. Multiple data sources concerning malaria were integrated, encompassing national surveillance data, Statistic Yearbook, targeted malaria control interventions, and meteorological data. Incidence rate, mortality rate, and case fatality ratio (CFR) by different regions and age groups were analysed. Joinpoint regression models were used to estimate annual changes in malaria. The changes in coverage of malaria interventions were evaluated. RESULTS: Between 2010 to 2019, the incidence rate of malaria decreased from 249.43 to 187.00 cases per 1,000 population in Niger. Niamey had a high annual mean incidence rate and the lowest CFR, while Agadez was on the contrary. Joinpoint regression analysis revealed a declining trend in malaria incidence for all age groups except the 10-24 years group, and the mortality rate and the CFR initially decreased followed by an increase in all age groups. Niger has implemented a series of malaria interventions, with the major ones being scaled up to larger populations during the study period. CONCLUSIONS: The scale-up of multi-interventions in Niger has significantly reduced malaria incidence, but the rise in mortality rate and CFR addresses the challenges in malaria control and elimination. Malaria endemic countries should enhance surveillance of malaria cases and drug resistance in Plasmodium, improve diagnosis and treatment, expand the population coverage of insecticide-treated bed nets and seasonal malaria chemoprevention, and strengthen the management of severe malaria cases.

Genomic Characteristics of Emerging Intraerythrocytic Anaplasma capra and High Prevalence in Goats, China.

Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.

Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

Profile and dynamics of infectious diseases: a population-based observational study using multi-source big data.

BACKGROUND: The current surveillance system only focuses on notifiable infectious diseases in China. The arrival of the big-data era provides us a chance to elaborate on the full spectrum of infectious diseases. METHODS: In this population-based observational study, we used multiple health-related data extracted from the Shandong Multi-Center Healthcare Big Data Platform from January 2013 to June 2017 to estimate the incidence density and describe the epidemiological characteristics and dynamics of various infectious diseases in a population of 3,987,573 individuals in Shandong province, China. RESULTS: In total, 106,289 cases of 130 infectious diseases were diagnosed among the population, with an incidence density (ID) of 694.86 per 100,000 person-years. Besides 73,801 cases of 35 notifiable infectious diseases, 32,488 cases of 95 non-notifiable infectious diseases were identified. The overall ID continuously increased from 364.81 per 100,000 person-years in 2013 to 1071.80 per 100,000 person-years in 2017 (χ2 test for trend, P < 0.0001). Urban areas had a significantly higher ID than rural areas, with a relative risk of 1.25 (95% CI 1.23-1.27). Adolescents aged 10-19 years had the highest ID of varicella, women aged 20-39 years had significantly higher IDs of syphilis and trichomoniasis, and people aged ≥ 60 years had significantly higher IDs of zoster and viral conjunctivitis (all P < 0.05). CONCLUSIONS: Infectious diseases remain a substantial public health problem, and non-notifiable diseases should not be neglected. Multi-source-based big data are beneficial to better understand the profile and dynamics of infectious diseases.

Increased postprandial nonesterified fatty acid efflux from adipose tissue in prediabetes is offset by enhanced dietary fatty acid adipose trapping.

The mechanism of increased postprandial nonesterified fatty acid (NEFA) appearance in the circulation in impaired glucose tolerance (IGT) is due to increased adipose tissue lipolysis but could also be contributed to by reduced adipose tissue (AT) dietary fatty acid (DFA) trapping and increased "spillover" into the circulation. Thirty-one subjects with IGT (14 women, 17 men) and 29 with normal glucose tolerance (NGT, 15 women, 14 men) underwent a meal test with oral and intravenous palmitate tracers and the oral [18F]-fluoro-thia-heptadecanoic acid positron emission tomography method. Postprandial palmitate appearance (Rapalmitate) was higher in IGT versus NGT (P < 0.001), driven exclusively by Rapalmitate from obesity-associated increase in intracellular lipolysis (P = 0.01), as Rapalmitate from DFA spillover was not different between the groups (P = 0.19) and visceral AT DFA trapping was even higher in IGT versus NGT (P = 0.02). Plasma glycerol appearance was lower in IGT (P = 0.01), driven down by insulin resistance and increased insulin secretion. Thus, we found higher AT DFA trapping, limiting spillover to lean organs and in part offsetting the increase in Rapalmitate from intracellular lipolysis. Whether similar findings occur in frank diabetes, a condition also characterized by insulin resistance but relative insulin deficiency, requires further investigation (Clinicaltrials.gov: NCT04088344, NCT02808182).NEW & NOTEWORTHY We found higher adipose tissue dietary fatty acid trapping, limiting spillover to lean organs, that in part offsets the increase in appearance rate of palmitate from intracellular lipolysis in prediabetes. These results point to the adaptive nature of adipose tissue trapping and dietary fatty acid spillover as a protective mechanism against excess obesity-related palmitate appearance rate from intracellular adipose tissue lipolysis.

Engineering of Yolk/Core-Shell Structured Nanoreactors for Thermal Hydrogenations.

Heterogeneous hydrogenation reactions are of great importance for chemical upgrading and synthesis, but still face the challenges of controlling selectivity and long-term stability. To improve the catalytic performance, many hydrogenation reactions utilize special yolk/core-shell nanoreactors (YCSNs) with unique architectures and advantageous properties. This work presents the developmental and technological challenges in the preparation of YCSNs that are potentially useful for hydrogenation reactions, and provides a summary of the properties of these materials. The work also addresses the scientific challenges in applications of these YCSNs in various gas and liquid-phase hydrogenation reactions. The catalyst structures, catalytic performance, structure-performance relationships, reaction mechanisms, and unsolved problems are discussed too. Also, a brief outlook and opportunities for future research in this field are presented. This work on the advancements in YCSNs might inspire the creation of new materials with desired structures for achieving maximal hydrogenation performances.

Altering Hydrogenation Pathways in Photocatalytic Nitrogen Fixation by Tuning Local Electronic Structure of Oxygen Vacancy with Dopant.

To avoid the energy-consuming step of direct N≡N bond cleavage, photocatalytic N2 fixation undergoing the associative pathways has been developed for mild-condition operation. However, it is a fundamental yet challenging task to gain comprehensive understanding on how the associative pathways (i.e., alternating vs. distal) are influenced and altered by the fine structure of catalysts, which eventually holds the key to significantly promote the practical implementation. Herein, we introduce Fe dopants into TiO2 nanofibers to stabilize oxygen vacancies and simultaneously tune their local electronic structure. The combination of in situ characterizations with first-principles simulations reveals that the modulation of local electronic structure by Fe dopants turns the hydrogenation of N2 from associative alternating pathway to associative distal pathway. This work provides fresh hints for rationally controlling the reaction pathways toward efficient photocatalytic nitrogen fixation.

Age-dependent Gender Differences in COVID-19 in Mainland China: Comparative Study.

BACKGROUND: The ongoing pandemic of novel coronavirus disease 2019 (COVID-19) is challenging the global public health system. Sex differences in infectious diseases are a common but neglected problem. METHODS: We used the national surveillance database of COVID-19 in mainland China to compare gender differences in attack rate (AR), proportion of severe and critical cases (PSCC), and case fatality rate (CFR) in relation to age, affected province, and onset-to-diagnosis interval. RESULTS: The overall AR was significantly higher in females than in males (63.9 vs 60.5 per 1 million persons; P ˂ .001). In contrast, PSCC and CFR were significantly lower among females (16.9% and 4.0%) than among males (19.5% and 7.2%), with odds ratios of 0.87 and 0.57, respectively (both P ˂ .001). The female-to-male differences were age dependent, and were significant among people aged 50-69 years for AR and in patients aged 30 years or older for both PSCC and CFR (all P ≤ .001). The AR, PSCC, and CFR varied greatly from province to province. However, female-to-male differences in AR, PSCC, and CFR were significant in the epicenter, Hubei province, where 82.2% confirmed cases and 97.4% deaths occurred. After adjusting for age, affected province, and onset-to-diagnosis interval, the female-to-male difference in AR, PSCC, and CFR remained significant in multivariate logistic regression analyses. CONCLUSIONS: We elucidate an age-dependent gender dimorphism for COVID-19, in which females have higher susceptibility but lower severity and fatality. Further epidemiological and biological investigations are required to better understand the sex-specific differences for effective interventions.

Overexpression of kinesin superfamily members as prognostic biomarkers of breast cancer.

BACKGROUND: Kinesin superfamily (KIFs) has a long-reported significant influence on the initiation, development, and progress of breast cancer. However, the prognostic value of whole family members was poorly done. Our study intends to demonstrate the value of kinesin superfamily members as prognostic biomarkers as well as a therapeutic target of breast cancer. METHODS: Comprehensive bioinformatics analyses were done using data from TCGA, GEO, METABRIC, and GTEx. LASSO regression was done to select tumor-related members. Nomogram was constructed to predict the overall survival (OS) of breast cancer patients. Expression profiles were testified by quantitative RT-PCR and immunohistochemistry. Transcription factor, GO and KEGG enrichments were done to explore regulatory mechanism and functions. RESULTS: A total of 20 differentially expressed KIFs were identified between breast cancer and normal tissue with 4 (KIF17, KIF26A, KIF7, KIFC3) downregulated and 16 (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF20B, KIF22, KIF23, KIF24, KIF26B, KIF2C, KIF3B, KIF4A, KIFC1) overexpressed. Among which, 11 overexpressed KIFs (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF23, KIF2C, KIF4A, KIFC1) significantly correlated with worse OS, relapse-free survival (RFS) and distant metastasis-free survival (DMFS) of breast cancer. A 6-KIFs-based risk score (KIF10, KIF15, KIF18A, KIF18B, KIF20A, KIF4A) was generated by LASSO regression with a nomogram validated an accurate predictive efficacy. Both mRNA and protein expression of KIFs are experimentally demonstrated upregulated in breast cancer patients. Msh Homeobox 1 (MSX1) was identified as transcription factors of KIFs in breast cancer. GO and KEGG enrichments revealed functions and pathways affected in breast cancer. CONCLUSION: Overexpression of tumor-related KIFs correlate with worse outcomes of breast cancer patients and can work as potential prognostic biomarkers.

KCTD12 promotes G1/S transition of breast cancer cell through activating the AKT/FOXO1 signaling.

BACKGROUND: Sustaining proliferation is the most fundamental step for breast cancer tumor genesis. Accelerated proliferation is usually linked to the uncontrolled cell cycle. However, the internal and external factors linked to the activation of breast cancer cell cycle are still to be investigated. METHODS: quantitative PCR (qPCR) and Western blotting assay were used to detect the expression of potassium channel tetramerization domain containing 12 (KCTD12) in breast cancer. MTT and colony formation assays were performed to evaluate the effect of KCTD12 on cell proliferation of breast cancer. Anchorage-independent growth assay was used to examine the in vitro tumorigenesis of breast cancer cells. Flow cytometry assay, qPCR, and Western blotting were used to investigate the detailed mechanisms of KCTD12 on breast cancer progression. RESULTS: Herein, the result showed that the level of KCTD12 is significantly decreased in breast cancer tissues and cells, and lower level of KCTD12 predicts poorer survival for patients with breast cancer. Further cell function tests illustrated that downregulation of KCTD12 significantly promotes cell proliferation and in vitro tumor genesis. Besides, molecular biologic experiments showed that downregulation of KCTD12 can enhance the G1/S transition through activating the AKT/FOXO1 signaling. CONCLUSION: Our study inferred that downregulation of KCTD12 can be a novel factor for poor prognosis in breast cancer.

Mechanism and catalytic performance for direct dimethyl ether synthesis by CO2 hydrogenation over CuZnZr/ferrierite hybrid catalyst.

Direct synthesis of dimethyl ether (DME) by CO2 hydrogenation has been investigated over three hybrid catalysts prepared by different methods: co-precipitation, sol-gel, and solid grinding to produce mixed Cu, ZnO, ZrO2 catalysts that were physically mixed with a commercial ferrierite (FER) zeolite. The catalysts were characterized by N2 physisorption, X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), temperature programmed desorption of CO2 (CO2-TPD), temperature programmed desorption of NH3 (NH3-TPD), and temperature programmed H2 reduction (H2-TPR). The results demonstrate that smaller CuO and Cu crystallite sizes resulting in better dispersion of the active phases, higher surface area, and lower reduction temperature are all favorable for catalytic activity. The reaction mechanism has been studied using in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Methanol appears to be formed via the bidentate-formate (b-HCOO) species undergoing stepwise hydrogenation, while DME formation occurs from methanol dehydration and reaction of two surface methoxy groups.

Hollow Carbon Sphere Nanoreactors Loaded with PdCu Nanoparticles: Void-Confinement Effects in Liquid-Phase Hydrogenations.

Nanoreactors with hollow structures have attracted great interest in catalysis research due to their void-confinement effects. However, the challenge in unambiguously unraveling these confinement effects is to decouple them from other factors affecting catalysis. Here, we synthesize a pair of hollow carbon sphere (HCS) nanoreactors with presynthesized PdCu nanoparticles encapsulated inside of HCS (PdCu@HCS) and supported outside of HCS (PdCu/HCS), respectively, while keeping other structural features the same. Based on the two comparative nanoreactors, void-confinement effects in liquid-phase hydrogenation are investigated in a two-chamber reactor. It is found that hydrogenations over PdCu@HCS are shape-selective catalysis, can be accelerated (accumulation of reactants), decelerated (mass transfer limitation), and even inhibited (molecular-sieving effect); conversion of the intermediate in the void space can be further promoted. Using this principle, a specific imine is selectively produced. This work provides a proof of concept for fundamental catalytic action of the hollow nanoreactors.

Hitherto-Unexplored Photodynamic Therapy of Ag2 S and Enhanced Regulation Based on Polydopamine In Vitro and Vivo.

Given their superior penetration depths, photosensitizers with longer absorption wavelengths present broader application prospects in photodynamic therapy (PDT). Herein, Ag2 S quantum dots were discovered, for the first time, to be capable of killing tumor cells through the photodynamic route by near-infrared light irradiation, which means relatively less excitation of the probe compared with traditional photosensitizers absorbing short wavelengths. On modification with polydopamine (PDA), PDA-Ag2 S was obtained, which showed outstanding capacity for inducing reactive oxygen species (increased by 1.69 times). With the addition of PDA, Ag2 S had more opportunities to react with surrounding O2 , which was demonstrated by typical triplet electron spin resonance (ESR) analysis. Furthermore, the PDT effects of Ag2 S and PDA-Ag2 S achieved at longer wavelengths were almost identical to the effects produced at 660 nm, which was proved by studies in vitro. PDA-Ag2 S showed distinctly better therapeutic effects than Ag2 S in experiments in vivo, which further validated the enhanced regulatory effect of PDA. Altogether, a new photosensitizer with longer absorption wavelength was developed by using the hitherto-unexplored photodynamic function of Ag2 S quantum dots, which extended and enhanced the regulatory effect originating from PDA.

Introduction of F446I mutation in the K13 propeller gene leads to increased ring survival rates in Plasmodium falciparum isolates.

BACKGROUND: Mutations in the Plasmodium falciparum k13 gene are associated with artemisinin (ART) resistance. However, it is unclear whether the F446I mutation, the most prevalent allele at the China-Myanmar border and north of Myanmar, is associated with ART resistance. Therefore, the aim of this study was to investigate the role of this mutation in ART resistance by generating transgenic parasites expressing the F446I mutant allele. METHODS: The transgenic parasites carrying the F446I or C580Y mutation in both 3D7 and FCC1/HN isolates were generated by single crossing-over recombination and verified using PCR and gene sequencing. The ring-stage survival assay of 0-3 h (RSA0-3 h) was used to evaluate ART susceptibility of the transgenic parasites in vitro. RESULTS: Four transgenic parasite lines named 3D7F446I mut, 3D7C580Y mut, FCC1/HNF446I mut and FCC1/HNC580Y mut were successfully generated. These parasite lines showed no changes in the expression level of k13 when compared with their parent parasite isolates. However, introduction of the F446I mutation in k13 of the 3D7 and FCC1/HN isolates led to elevated ring survival rates detected using RSA0-3 h when subjected to both 700 and 20 nM concentrations of dihydroartemisinin. The survival rates were similar to those detected in the parasite lines with the C580Y mutation. CONCLUSIONS: Insertion of the F446I mutation in k13 led to increased ring survival, suggesting that this mutation may be associated with ART resistance and could be used as a molecular marker for monitoring ART-resistant parasites. The results also highlights the importance of surveillance of F446I mutants for containing the resistant parasite.

Transcription of the var genes from a freshly-obtained field isolate of Plasmodium falciparum shows more variable switching patterns than long laboratory-adapted isolates.

BACKGROUND: Antigenic variation in Plasmodium falciparum involves switching among multicopy var gene family and is responsible for immune evasion and the maintenance of chronic infections. Current understanding of var gene expression and switching patterns comes from experiments conducted on long laboratory-adapted strains, with little known about their wild counterparts. METHODS: Genome sequencing was used to obtain 50 var genes from a parasite isolated from the China-Myanmar border. Four clones with different dominant var genes were cultured in vitro in replicates for 50 generations. Transcription of the individual var gene was detected by real-time PCR and then the switching process was analysed. RESULTS: The expression of multicopy var genes is mutually exclusive in clones of a wild P. falciparum isolate. The activation of distinct primary dominant var genes leads to different and favoured switching patterns in the four clones. The on/off rates of individual var genes are variable and the choice of subsequent dominant var genes are random, which results in the different switching patterns among replicates of each clonal wild P. falciparum isolate with near identical initial transcription profiles. CONCLUSIONS: This study suggests that the switching patterns of var genes are abundant, which consist of both conserved and random parts.

Automatic ARDS surveillance with chest X-ray recognition using convolutional neural networks.

OBJECTIVE: This study aims to design, validate and assess the accuracy a deep learning model capable of differentiation Chest X-Rays between pneumonia, acute respiratory distress syndrome (ARDS) and normal lungs. MATERIALS AND METHODS: A diagnostic performance study was conducted using Chest X-Ray images from adult patients admitted to a medical intensive care unit between January 2003 and November 2014. X-ray images from 15,899 patients were assigned one of three prespecified categories: "ARDS", "Pneumonia", or "Normal". RESULTS: A two-step convolutional neural network (CNN) pipeline was developed and tested to distinguish between the three patterns with sensitivity ranging from 91.8% to 97.8% and specificity ranging from 96.6% to 98.8%. The CNN model was validated with a sensitivity of 96.3% and specificity of 96.6% using a previous dataset of patients with Acute Lung Injury (ALI)/ARDS. DISCUSSION: The results suggest that a deep learning model based on chest x-ray pattern recognition can be a useful tool in distinguishing patients with ARDS from patients with normal lungs, providing faster results than digital surveillance tools based on text reports. CONCLUSION: A CNN-based deep learning model showed clinically significant performance, providing potential for faster ARDS identification. Future research should prospectively evaluate these tools in a clinical setting.

Adipocyte hypertrophy associates with in vivo postprandial fatty acid metabolism and adipose single-cell transcriptional dynamics.

Adipocyte hypertrophy is associated with metabolic complications independent of obesity. We aimed to determine: 1) the association between adipocyte size and postprandial fatty acid metabolism; 2) the potential mechanisms driving the obesity-independent, hypertrophy-associated dysmetabolism in vivo and at a single-cell resolution. Tracers with positron emission tomography were used to measure fatty acid metabolism in 40 men and women with normal or impaired glucose tolerance (NCT02808182), and single nuclei RNA-sequencing (snRNA-seq) to determine transcriptional dynamics of subcutaneous adipose tissue (AT) between individuals with AT hypertrophy vs. hyperplasia matched for sex, ethnicity, glucose-tolerance status, BMI, total and percent body fat, and waist circumference. Adipocyte size was associated with high postprandial total cardiac fatty acid uptake and higher visceral AT dietary fatty acid uptake, but lower lean tissue dietary fatty acid uptake. We found major shifts in cell transcriptomal dynamics with AT hypertrophy that were consistent with in vivo metabolic changes.