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Background: Diabetic kidney disease (DKD) is the main cause of end-stage renal disease and has a high mortality rate. Currently, no effective treatments are available to reduce the progression of kidney damage associated with diabetes. Objectives: To explore the influence and predictive value of the atherogenic index of plasma (AIP) on early chronic kidney disease and liver injury in patients with type 2 diabetes mellitus (T2DM). Methods: Medical records of 1057 hospitalized adult patients with T2DM between January 2021 and December 2022 were collected. The predictive value of AIP, renal function, and liver injury in patients with T2DM were analyzed using Pearson’s correlation, multiple logistic regression, and receiver operating characteristic (ROC) curve analyses. Results: AIP was a sensitive indicator of early liver and kidney injury in patients with T2DM. Patients in the DKD group showed increased AIP that positively correlated with serum creatinine, uric acid, and β2-microglobulin levels. Increased AIP negatively correlated with estimated glomerular filtration rate (eGFR). AIP significantly correlated with alanine aminotransferase and aspartate aminotransferase levels and glutamyl transpeptidase-to-platelet ratio (GPR). An eGFR of 60-100 mL/min/1.73 m 2 significantly increased the risk of DKD as the AIP increased. At lower GPR levels, the risk of DKD significantly increased with increasing AIP. However, no significant difference was found between the 2 groups when the GPR was >0.1407. The ROC curve analysis showed that AIP could predict early liver injury. Conclusions: AIP is directly involved in early liver and kidney injury in T2DM and may be a sensitive indicator for early detection.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide necessitating the development of innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents a promising advancement in the field of oncology offering a novel approach to target and eliminate tumor cells with high specificity and reduced risk of immune-related adverse effects. This paper reviews the mechanism, potential targets, and recent advances in CAR-NK cell therapy for lung cancer, including the design and engineering of CAR-NK cells, preclinical studies, and the outcomes of early-phase clinical trials. We highlight the unique advantages of using NK cells, such as their innate ability to recognize and kill cancer cells and their reduced potential for inducing graft-versus-host disease (GvHD) and cytokine release syndrome (CRS) compared to CAR T-cell therapies. Results from recent studies demonstrate significant antitumor activity in lung cancer models with improved targeting and persistence of CAR-NK cells observed in vitro and in vivo. Finally, we discuss the challenges in optimizing CAR-NK cell therapies, including the potential resistance mechanisms. The paper concludes with an outlook on the future directions of CAR-NK cell research and its implications for lung cancer treatment emphasizing the importance of continued innovation and collaboration in the field.

Abstract Images captured in low light conditions suffer from low visibility, blurred details and strong noise, resulting in unpleasant visual appearance and poor performance of high level visual tasks. To address these problems, existing approaches have attempted to enhance the visibility of low-light images using convolutional neural networks (CNN). However, due to the insufficient consideration of the characteristics of the information of different frequency layers in the image, most of them yield blurry details and amplified noise. In this work, to fully extract and utilize these information, we proposed a novel Adaptive Frequency Decomposition Network (AFDNet) for low-light image enhancement. An Adaptive Frequency Decomposition (AFD) module is designed to adaptively extract low and high frequency information of different granularities. Specifically, the low-frequency information is employed for contrast enhancement and noise suppression in low-scale space and high-frequency information is for detail restoration in high-scale space. Meanwhile, a new frequency loss function are proposed to guarantee AFDNet’s recovery capability for different frequency information. Extensive experiments on various publicly available datasets show that AFDNet outperforms the existing state-of-the-art methods both quantitatively and visually. In addition, our results showed that the performance of the face detection can be effectively improved by using AFDNet as pre-processing.

Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments. The bioassay results demonstrated that spirotryprostatin A derivatives possess good and broad-spectrum antifungal activities. Compound 4d exhibited excellent antifungal activity in vitro, equal to or higher than the positive control ketoconazole, against Helminthosporium maydis, Trichothecium roseum, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, Alternaria brassicae, Alternaria alternate, and Fusarium solan (MICs: 8–32 µg/mL). Compound 4k also displayed remarkable antifungal activity against eight other phytopathogenic fungi, including Fusarium oxysporium f. sp. niveum and Mycosphaerella melonis (MICs: 8–32 µg/mL). The preliminary structure–activity relationships (SARs) were further discussed. Moreover, molecular docking studies revealed that spirotryprostatin A derivatives anchored in the binding site of succinate dehydrogenase (SDH). Therefore, these compounds showed potential as natural compound-based chiral fungicides and hold promise as candidates for further enhancements in terms of structure and properties.

The quality of remote sensing images has been greatly improved by the rapid improvement of unmanned aerial vehicles (UAVs), which has made it possible to detect small objects in the most complex scenes. Recently, learning-based object detection has been introduced and has gained popularity in remote sensing image processing. To improve the detection accuracy of small, weak objects in complex scenes, this work proposes a novel hybrid backbone composed of a convolutional neural network and an adaptive multi-scaled transformer, referred to as HAM-Transformer Net. HAM-Transformer Net firstly extracts the details of feature maps using convolutional local feature extraction blocks. Secondly, hierarchical information is extracted, using multi-scale location coding. Finally, an adaptive multi-scale transformer block is used to extract further features in different receptive fields and to fuse them adaptively. We implemented comparison experiments on a self-constructed dataset. The experiments proved that the method is a significant improvement over the state-of-the-art object detection algorithms. We also conducted a large number of comparative experiments in this work to demonstrate the effectiveness of this method.

BackgroundDiabetes is a common metabolic disease that is associated with gut microbiota dysbiosis and iron metabolism. Salidroside (SAL) is the main ingredient of the traditional Chinese herb Rhodiola, previous studies have shown that SAL could reshape the gut microbiota and limit iron accumulation. Therefore, it is possible that SAL can act as an alternative therapy for diabetes, and its underlying mechanism is worth exploring.MethodsSAL was used to treat diabetic db/db mice. Serum glucose and iron levels and the histopathology of myocardial fibres were evaluated. The gut microbiota composition was determined by 16S rRNA Illumina sequencing technology.ResultsTreatment with SAL significantly reduced blood glucose and ameliorated diabetic cardiomyopathy in diabetic db/db mice, which was accompanied by inhibited ferroptosis and iron accumulation. Furthermore, the 16S rRNA sequencing results showed that SAL induced a change in the gut microbiota composition. Overall, SAL could increase the proportion of probiotic bacteria and decrease Lactobacillus to improve gut microbiota. Specifically, SAL increased the ratio of Bacteroidetes to Firmicutes in diabetic mice. The most significant biomarker was the genus Lactobacillus between the MD group and the SAL group. In addition, COG and KEGG analyses suggested that SAL mainly participated in nutrient metabolism, among them iron metabolism was associated with the abundance of Lactobacillus.ConclusionsSAL could reduce the glucose level and protect against diabetic cardiomyopathy in diabetic mice, which might be mediated by the change in the gut microbiota and the regulation of iron metabolism. The findings suggested that SAL was a promising complementary option for diabetes therapy.

Lightweight corundum-mullite thermal insulation materials were successfully prepared by microwave sintering at low temperature. The effects of sintering temperatures, PMMA microspheres and SiC particles on structure and properties of as-prepared corundum-mullite materials were investigated. The SiC became a hot spot under the action of microwave field, and these local high temperature areas promoted the formation and growth of mullite whiskers. The PMMA microspheres were burn out, leaving pores which could provide space for the growth of mullite whiskers. It was found that the optimal sintering temperature was 1400°C and corresponding porosity, density and bending strength of the samples were 71.2%, 0.99 g/cm3 and 3.85MPa, respectively. The thermal conductivity was from 0.201 to 0.313W/(m•K) between 30°C and 950°C. This work demonstrated that lightweight corundum-mullite materials with low density, high porosity, good thermal shock resistance and excellent thermal insulation properties could be successfully prepared by microwave sintering.

In order to develop chrome-free refractory materials applicable in coal slurry gasification, SiC-CaAl12O19 (SiC-CA6) composite refractories were developed and prepared by using SiC aggregates and CA6 powders as main raw materials. The sintering behaviour of the composites was investigated. After firing at different temperatures under CO atmosphere, the effects of oxidation of SiC aggregates on the sintering behaviour and microstructures of SiC-CA6 composite refractorieswere investigated. SiC-CA6 composites could not be sintered when firing temperature was lower than 1500°C. SiC had a passive oxidation and the oxidation components were able to react with CA6 to form CaAl2Si2O8. The CaAl2Si2O8 melted into liquid when sintering temperature was in the range of 1500-1600°C, which promoted the sintering process of the SiC-CA6 composites. At temperatures above 1600 °C, an active oxidation of SiC occurred. Simultaneously, SiC could also reacted with the SiO2(s,l) to form SiO, leading to the precipitation of Al2O3 and CaO in the liquid to generate plate-like CA6. Above this temperature, the sintering of the SiC-CA6 composite refractories was affected by the growth of CA6 and oxidation of SiC. This work demonstrates that the optimal sintering temperature for the SiC-CA6 composite refractories was 1600°C.

The study aimed to elucidate abscopal effects of thoracic X-ray irradiation on spermatogenesis in mice. Male C57BL/6 mice were randomly divided into sham group and radiation group, and subjected to thorax fractionated X-ray irradiation or sham irradiation with the total dose of 5 Gy/day for each animal for four consecutive days. After irradiation, sperm morphology was observed, and sperm number was counted under microscope, and sperm apoptosis was detected by flow cytometry. Meanwhile, testis index was calculated, testicular morphology was observed using haematoxylin-eosin (HE) staining, and testicular ultrastructure was observed under transmission electron microscopy. The permeability of blood-testis barrier (BTB) was detected by Evans Blue fluorescence colorimetry. The protein levels of Bcl-2 associated X protein (Bax), B-cell leukemia-lymphoma-2 (Bcl-2) and Cleaved caspase 3, promyelocytic leukaemia zinc finger (PLZF) and c-kit proto-oncogene (c-kit) in testes were determined by western blotting (WB). The location of apoptotic cells was confirmed by terminal deoxynucleotidyl transferase (TdT) enzymaticated dUTP nick end labelling (TUNEL) assay. The levels of tumor necrosis factor alpha (TNF-α), transforming growth factor-β1 (TGF-β1), interleukin 10 (IL-10) were measured by enzyme-linked immunosorbent assay (ELISA). The levels of Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) were measured by the biochemical assay kit. Compared with sham group, the sperm quality of mice in radiation group showed decreased number and survival rate, along with increased abnormality and total apoptosis rate. The testis index of irradiated mice was lower, the testicular apoptosis was increased, and their testicular histology and ultrastructure was severely damaged. The permeability of BTB was increased, the level of PLZF in testis was decreased, and the level of c-kit was increased by irradiation. After irradiation, the levels of TNF-α, TGF-β1, IL-10, T-SOD and MDA in testes were significantly changed. Taken together, abscopal effects of thoracic X-ray irradiation on spermatogenesis were obvious, which could decrease sperm quality and damage testicular morphology and increase the permeability of BTB, and a series of inflammation and oxidative stress factors were involved in the process. These findings provide novel insights into prevention and treatment for male reproductive damage induced by clinical thoracic irradiation.

Preparation of mineral polymer materials with fly ash is one of the effective ways to realize the green and comprehensive utilization of fly ash. Using the sol-gel method mineral aggregate material precursor, swe tudied the different sources of silicon and aluminum, synthesis temperature, different Si/Al ratio, different dosages of ethanol, and other influence factors under the conditions of the synthesis, and the structure of the sample using the means of XRD, SEM, TG, IR on the synthesis of silica-alumina precursor sample performance and structure are analyzed. The results showed that the optimum preparation conditions were obtained when the Si/Al ratio was 10:1, the synthesis temperature was 70°C, and the sample was calcined at 850°C for 3 h with the highest synthesis rate of 81.33%. The Si-Al precursors prepared are amorphous—phase amorphous grid—space structures. The infrared analysis indicated that the synthesized sample had a Si-O-Si bond, but the absorption peak and characteristic peak were obviously different under the conditions of different synthesis temperatures, different Si/Al ratios, and different ethanol dosage. For example, at 806 cm−1 and 1,395 cm−1, they correspond to the absorption peak of Si-OH bending vibration and shear bending vibration and plane bending vibration of C-H without complete reaction respectively. SEM observation shows that the size of the synthesized Silicon aluminum precursors sample is small and the distribution is uniform. The in-depth study on the preparation process and reaction mechanism of mineral polymer precursorswill bring broad prospects for the application and development of mineral polymer precursors themselves.

Purpose. Hypoxia has crucial functions in the development and metastasis of cervical cancer by inducing the expression of numerous genes, including microRNA genes. But we know little about how the hypoxia factors and microRNAs orchestrate to regulate hallmarks of cervical cancer cells. Methods. We conducted RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) experiments to investigate the targets of HIF-3α or miR-630. ChIP-qPCR and RT-qPCR were carried out to validate the results of ChIP-seq and RNA-seq. Cellular, molecular, and radiation experiments were conducted to explore the functions of miR-630. Results. In this study, we showed that hypoxia-induced overexpression of HIF-3α increased the expression of dozens of miRNAs, including miR-630. Hypoxia could also directly induce miR-630 expression. ChIP-seq data showed that HIF-3α activates miR-630 expression by directly binding to the promoter of its host gene. Meanwhile, stable overexpression of miR-630 increased the expression of HIF-3α, but repressed the expression of HIF-1α, indicating a positive feedback loop between HIF-3α and miR-630. Consequently, stable overexpression of miR-630 in HeLa cells promotes cancer hallmarks, including radioresistance, inhibition of apoptosis, increased migration and invasion, and EMT-mediated metastasis. Meanwhile, inhibition of miR-630 showed opposite features. Conclusion. Taken together, our findings indicate a novel hypoxia-induced HIF-3α and miR-630 regulatory feedback loop contributing to metastasis and progression of cervical cancer cells and suggest that HIF-3α and miR-630 might act as potential biomarkers and therapeutic targets for cervical cancer in the future.

In the surface field integral equations (SIEs) from three-dimensional homogeneous dielectric objects, the equivalence electric and magnetic currents on the discontinuous interfaces between different homogeneous media are two independent sources. When the SIEs are iteratively solved, as indicated by the published literatures, the multilevel fast multipole algorithm (MLFMA) needs to be implemented respectively for the electric field integral equation (EFIE) and the magnetic field integral equation (MFIE) with these two currents, and hence a few MLFMA implementations are necessary for each homogeneous medium. In this paper, a concise and efficient scheme is proposed for reducing the implementations of the SIEs-MLFMA. First, the summation of the EFIE and MFIE-MLFMA implementations with the two currents can be simplified into one EFIE or MFIE-MLFMA implementation with integrating electric and magnetic currents at the lowest-level aggregation stage. Secondly, the common matrix frameworks consisting of the EFIE and MFIE-MLFMA implementations used in the SIEs can be simplified into one MLFMA implementation with two lowest-level diaggregations. The enhanced MLFMA scheme has excellent applicability to eight kinds of SIEs in wide use. In this way, the resulted SIE-MLFMA scheme performs only once for each homogeneous medium when transforming outgoing wave expansions of the two currents into incoming wave expansions for bottom cubes. Compared with the widely-used implementation approach of the MLFMA one by one for the two currents, it reduces the computation complexity by one half without sacrificing accuracy and adding a little memory requirement. Some examples are presented to validate the enhanced MLFMA scheme.

The partial differential equation learning model is applied to another high-level visual-processing problem: face recognition. A novel feature selection method based on partial differential equation learning model is proposed. The extracted features are invariant to rotation and translation and more robust to illumination changes. In the evaluation of students’ concentration in class, this paper firstly uses the face detection algorithm in face recognition technology to detect the face and intercept the expression data, and calculates the rise rate. Then, the improved model of concentration analysis and evaluation of a college Chinese class is used to recognize facial expression, and the corresponding weight is given to calculate the expression score. Finally, the head-up rate calculated at the same time is multiplied by the expression score as the final concentration score. Through the experiment and analysis of the experimental results in the actual classroom, the corresponding conclusions are drawn and teaching suggestions are provided for teachers. For each face, a large neighborhood set is firstly selected by the k-nearest neighbor method, and then, the sparse representation of sample points in the neighborhood is obtained, which effectively combines the locality of k-nearest neighbor and the robustness of sparse representation. In the sparse preserving nonnegative block alignment algorithm, a discriminant partial optimization model is constructed by using sparse reconstruction coefficients to describe local geometry and weighted distance to describe class separability. The two algorithms obtain good clustering and recognition results in various cases of real and simulated occlusion, which shows the effectiveness and robustness of the algorithm. In order to verify the reliability of the model, this paper verified the model through in-class practice tests, teachers’ questions, and interviews with students and teachers. The results show that the proposed joint evaluation method based on expression and head-up rate has high accuracy and reliability.

The basic helix−loop−helix (bHLH) proteins are a superfamily of transcription factors (TFs) that can bind to specific DNA target sites, playing a central role in a wide range of metabolic, physiological, and developmental processes in higher organisms. However, no systemic analysis of bHLH TFs has been reported in banana, a typical climacteric fruit in tropical and subtropical regions. In our study, 259 MabHLH TF genes were identified in the genome of Musa acuminata (A genome), and phylogenetic analysis indicated that these MabHLHs could be classified into 23 subfamilies with the bHLHs from rice and Arabidopsis. The amino acid sequences of the bHLH domain in all MabHLH protein sequences were quite conserved, especially Arg-12, Arg-13, Leu-23, and Leu-79. Distribution mapping results showed that 258 MabHLHs were localized on the 11 chromosomes in the M. acuminata genome. The results indicated that 40.7% of gene duplication events were located in collinear fragments, and segmental duplications might have played a key role in the expansion of MabHLHs. Moreover, the expression profiles of MabHLHs in different fruit development and ripening stages and under various abiotic and biotic stresses were investigated using available RNA-sequencing data to obtain fruit development, ripening-specific, and stress-responsive candidate genes. Finally, a co-expression network of MabHLHs was constructed by weighted gene co-expression network analysis to elucidate the MabHLHs that might participate in important metabolic biosynthesis pathways in banana during development and the response to stress. A total of 259 MabHLHs were identified, and their sequence features, conserved domains, phylogenetic relationships, chromosomal distributions, gene duplications, expression profiles, and co-expression networks were investigated. This study systematically identified the MabHLHs in the M. acuminata genome at the genome-wide level, providing important candidate genes for further functional analysis. These findings improve our understanding of the molecular basis of developmental and stress tolerance in an important banana cultivar.

While there is growing interest in leader–follower relationships in the leadership literature, little is known about how a leader's framing effect triggers employees' proactive behaviors. This research aims to extend previous knowledge about the effects of leaders' goal framing and uncover their potential impacts on followership behaviors. Drawing on social information processing theory, this study proposes that both types of goal framing (gaining and losing) indirectly influence employees' followership behaviors by mobilizing their sense of work meaning, especially when they have a power dependence on their leaders, using the method of questionnaire measurement, CFA analysis, hierarchical regression analysis, and the bootstrap tested hypotheses. The results show that gain framing indirectly contributes to employees' followership behaviors by enhancing work meaning. Furthermore, this positive indirect relationship is stronger for employees with high power dependence. Yet another finding reveals that loss framing negatively impacts followership behavior by reducing employees' sense of work meaning, which is unaffected by power dependence. From the perspective of the framing effect, this study verifies the influence of goal framing on employees' behaviors and illustrates the effect of work meaning as a mechanism of goal framing on followership behavior. [ABSTRACT FROM AUTHOR]

To mitigate the adverse effects of climate change, the structure of global energy consumption has changed, and renewable energy consumption has increased rapidly, which may have a new impact on sustainable economic development. Against this backdrop, this paper investigates the direct and indirect effects of renewable energy consumption on economic growth, utilizing panel data from 90 countries along the Belt and Road between 2000 and 2019. Employing Granger causality tests and mediating effect models, we detect a bidirectional causal relationship between renewable energy consumption and economic growth, further affirming the feedback hypothesis. Our findings show that renewable energy consumption directly contributes to economic growth. Additionally, we found that renewable energy consumption has an indirect influence on economic growth via its impact on gross capital formation and trade. Drawing on these findings, we offer practical recommendations for the Belt and Road countries to implement appropriate countermeasures. [ABSTRACT FROM AUTHOR]

Developing low-cost and highly efficient electrocatalysts for the hydrogen evolution reaction (HER) has stimulated extensive interest. Molybdenum carbide materials have been proposed as promising alternatives to noble platinum-based catalysts due to their earth abundance and tunable physicochemical characteristics. Here, we report Mo2C@NC/Mo2C hollow microspheres composed of a β-Mo2C core and small β-Mo2C particles embedded within a nitrogen-doped carbon shell and prepared using guanosine and hexaammonium molybdate as precursors via a hydrothermal self-assembly process, which results in outstanding catalytic activity and fast kinetics in hydrogen evolution in both acidic and alkaline solutions. The significant activity improvement of Mo2C@NC/Mo2C can be attributed to the large ratio of exposed active sites and abundant interfacial structures. This work provides a new template-free strategy for the design of a highly active Mo2C@NC/Mo2C hollow microsphere HER catalyst. [ABSTRACT FROM AUTHOR]

We report the utilization of guanosine as a supramolecular precursor that unprecedentedly renders the formation of carbon-based multilayer materials with naturally high-level nitrogen doping. As a proof-of-concept, the porous carbon multilayers after anchoring 0.5 wt% Rh electrocatalysts displayed an excellent hydrogen evolution reaction activity. [ABSTRACT FROM AUTHOR]

Power-line frequency electromagnetic field (PF-EMF) was reported as a human carcinogen by some epidemiological research, but the conclusion is lack of robust experiment evidence. To identify the effects of long-term PF-EMF exposure on cell behavior, Balb/c 3T3 cells in exponential growth phase were exposed or sham-exposed to 50 Hertz (Hz) PF-EMF at 2.3 mT for 2 hours (h) one day, 5 days every week. After 11 weeks exposure, cells were collected instantly. Cell morphology was observed under invert microscope and Giemsa staining, cell viability was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle and apoptosis was examined by flow cytometry, the protein level of Proliferating Cell Nuclear Antigen (PCNA) and CyclinD1 was detected by western blot, cell transformation was examined by soft agar clone assay and plate clone forming test, and cell migration ability was observed by scratch adhesion test. It was found that after PF-EMF exposure, cell morphology, apoptosis, cell migration ability and cell transformation didn't change. However, compared with sham group, cell viability obviously decreased and cell cycle distribution also changed after 11 weeks PF-EMF exposure. Meanwhile, the protein level of PCNA and CyclinD1 significantly decreased after PF-EMF exposure. These data suggested that although long-term 50Hz PF-EMF exposure under this experimental condition had no effects on apoptosis, cell migration ability and cell transformation, it could affect cell proliferation and cell cycle by down-regulation the expression of PCNA and CyclinD1 protein.

A novel, high‐entropy, perovskite‐structured, solid solution La(Fe0.2Co0.2Ni0.2Cr0.2Mn0.2)O3 ceramic was successfully synthesized via high‐temperature solid‐state reaction. The crystal structure, microstructure, infrared emissivity, and thermophysical properties were investigated. The experimental results indicated that La(Fe0.2Co0.2Ni0.2Cr0.2Mn0.2)O3 exhibited an infrared emissivity as high as.92 in the near‐infrared region of.76–2.50 μm. The thermal conductivity was 1.38–1.72 W m−1 K−1 in the temperature range of 25–1200°C. [ABSTRACT FROM AUTHOR]

The hamster has been previously found to be a suitable model to study the changes associated with diet-induced hyperlipidemia in humans. Traditionally, studies of hyperlipidemia utilize serum- or plasma-based biochemical assays and histopathological evaluation. However, unbiased metabonomic technologies have the potential to identify novel biomarkers of disease. Thus, to obtain a better understanding of the progression of hyperlipidemia and discover potential biomarkers, we have used a proton nuclear magnetic resonance spectroscopy ((1)H-NMR)-based metabonomics approach to study the metabolic changes occurring in the plasma, urine and liver extracts of hamsters fed a high-fat/high-cholesterol diet. Samples were collected at different time points during the progression of hyperlipidemia, and individual proton NMR spectra were visually and statistically assessed using two multivariate analyses (MVA): principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). Using the commercial software package Chenomx NMR suite, 40 endogenous metabolites in the plasma, 80 in the urine and 60 in the water-soluble fraction of liver extracts were quantified. NMR analysis of all samples showed a time-dependent transition from a physiological to a pathophysiological state during the progression of hyperlipidemia. Analysis of the identified biomarkers of hyperlipidemia suggests that significant perturbations of lipid and amino acid metabolism, as well as inflammation, oxidative stress and changes in gut microbiota metabolites, occurred following cholesterol overloading. The results of this study substantially broaden the metabonomic coverage of hyperlipidemia, enhance our understanding of the mechanism of hyperlipidemia and demonstrate the effectiveness of the NMR-based metabonomics approach to study a complex disease.