IL-33-dependent NF-κB activation inhibits apoptosis and drives chemoresistance in acute myeloid leukemia.

BACKGROUND: Despite recent advances in therapeutic regimens, the prognosis of acute myeloid leukemia (AML) remains poor. Following our previous finding that interleukin-33 (IL-33) promotes cell survival along with activated NF-κB in AML, we further investigated the role of NF-κB during leukemia development. METHODS: Flow cytometry was performed to value the apoptosis and proliferation. qRT-PCR and western blot were performed to detect the expression of IL-6, active caspase 3, BIRC2, Bcl-2, and Bax, as well as activated NF-κB p65 and AKT. Finally, xenograft mouse models and AML patient samples were used to verify the findings observed in AML cell lines. RESULTS: IL-33-mediated NF-κB activation in AML cell lines contributes to a reduction in apoptosis, an increase in proliferation rate as well as a decrease in drug sensitivity, which were reversed by NF-κB inhibitor, Bay-117085. Moreover, IL-33 decreased the expression of active caspase-3 while increasing the levels of BIRC2, Bcl-2, and Bax, and these effects were blocked by Bay-117085. Additionally, NF-κB activation induced by IL-33 increases the production of IL-6 and autocrine activation of AKT. Co-culture of bone marrow stroma with AML cells resulted in increased IL-33 expression by leukemia cells, along with decreased apoptosis level and reduced drug sensitivity. Finally, we confirmed the in vivo pro-tumor effect mediated by IL-33/ NF-κB axis using a xenograft model of AML. CONCLUSION: Our data indicate that IL-33/IL1RL1-dependent signaling contributes to AML cell activation of NF-κB, which in turn causes autocrine IL-6-induced activation of pAKT, supporting IL-33/NF-κB/pAKT as a potential target for AML therapy.

The Role of Antisolvents with Different Functional Groups in the Formation of Cs4PbBr6 and CsPbBr3 Particles.

Compared to the high-temperature hot injection (HI) technique, the room-temperature supersaturated recrystallization (SR) approach is more hopeful to realize the industrialized production of CsPbX3 (X = Cl, Br, and I) nanomaterials. However, accurate compositional control of the product is still difficult, and the role and underlying mechanism of antisolvents in the reprecipitation process remain unclear. Herein, CsPbBr3 particles and CsPbBr3/Cs4PbBr6 composites with certain proportions are synthesized using different antisolvents with the SR method. By adjustment of the polarity or functional group of antisolvents, it is found that the functional groups of antisolvents have a major impact on the composition of the products. Furthermore, the influential mechanism of different antisolvents on the compositions of products is investigated by combining electrostatic potential calculations and ultraviolet-visible absorption spectroscopy. It suggests that the interaction between functional groups of antisolvents and organic ligands influences the coordination status of the intermediate Pb-complex and further affects the separating rate of the Pb(II)-intermediate, leading to the formation of products with different compositions. A physicochemical mechanism is proposed to explain the formation of Cs4PbBr6 and CsPbBr3. This work deepens the understanding of the formation mechanism of all-inorganic metal halide perovskite-related materials based on the SR method and provides new routes to achieve their controllable preparation.

Effects of binocular disparity on binocular luminance combination.

This study aimed to examine the effects of binocular disparity on binocular combination of brightness information coming from luminance increments and decrements. The point of subjective equality was determined by asking the observers to judge which stimulus appeared brighter-a bar stimulus with variable disparity or another stimulus with zero disparity. For the bar stimulus, the interocular luminance ratio was varied to trace an equal brightness curve. Binocular disparity had no effect on luminance increments presented on a gray or black background. In contrast, when luminance decrements were presented on a gray background, non-zero disparities elevated points of subjective equality for stimuli with interocular luminance differences. This means that the binocular brightness combination of the two monocular signals shifted from winner-take-all summation toward linear averaging. It has been argued that this effect may be caused by non-zero binocular disparities attenuating interocular suppression, which is deemed to operate normally with zero disparity.

Protective effects of villi mesenchymal stem cells on human umbilical vein endothelial cells by inducing SPOCD1 expression in cases of gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized by a lack of response to insulin in pregnancies, and often accompanied by severe complications. GDM is associated with structural and functional alterations, particularly endothelial dysfunction, in various tissues. This study is aimed to investigate the effect of placental mesenchymal stem cells (MSCs) on the endothelial biological function of human umbilical vein endothelial cells (HUVECs) and their molecular mechanisms. METHODS: Villi mesenchymal stem cells (VMSCs) were co-cultured with HUVECs, and transcriptomic analysis of differential genes was performed in HUVECs under high-glucose induction. Lentiviral transfection was performed to construct HUVECs with stable knockdown or overexpression of SPOCD1. The immunohistochemical assays were used to detect the expression of SPOCD1 in GDM patients. TUNEL fluorescence staining was applied for detection of the HUVEC apoptosis. ß galactosidase staining assay was performed to detect the cell senescence. Electron microscopy was used to detect the cell pyroptosis. qRT-PCR and western blot assays were conducted for identifying the mRNA & protein expressions of genes. RESULTS: VMSCs, when co-cultured with HUVECs, could inhibit the apoptosis, pyroptosis and senescence induced by high-glucose condition in HUVECs. Transcriptomic results showed an upregulation of SPOCD1 expression induced by VMSCs in HUVECs. Overexpression of SPOCD1 inhibited high-level glucose-induced apoptosis, pyroptosis and senescence in HUVECs via the ß-catenin pathway. CONCLUSION: VMSCs induce ß-catenin activation by upregulating the expression of SPOCD1 in HUVECs, which ultimately inhibits high-level glucose-induced apoptosis, pyroptosis and senescence in HUVECs. This observation provides potential therapeutic insight for future GDM treatment.

Efficacy and accuracy of artificial intelligence to overlay multimodal images from different optical instruments in patients with retinitis pigmentosa.

BACKGROUND: Retinitis pigmentosa (RP) represents a group of progressive, genetically heterogenous blinding diseases. Recently, relationships between measures of retinal function and structure are needed to help identify outcome measures or biomarkers for clinical trials. The ability to align retinal multimodal images, taken on different platforms, will allow better understanding of this relationship. We investigate the efficacy of artificial intelligence (AI) in overlaying different multimodal retinal images in RP patients. METHODS: We overlayed infrared images from microperimetry on near-infra-red images from scanning laser ophthalmoscope and spectral domain optical coherence tomography in RP patients using manual alignment and AI. The AI adopted a two-step framework and was trained on a separate dataset. Manual alignment was performed using in-house software that allowed labelling of six key points located at vessel bifurcations. Manual overlay was considered successful if the distance between same key points on the overlayed images was ≤1/2°. RESULTS: Fifty-seven eyes of 32 patients were included in the analysis. AI was significantly more accurate and successful in aligning images compared to manual alignment as confirmed by linear mixed-effects modelling (p < 0.001). A receiver operating characteristic analysis, used to compute the area under the curve of the AI (0.991) and manual (0.835) Dice coefficients in relation to their respective 'truth' values, found AI significantly more accurate in the overlay (p < 0.001). CONCLUSION: AI was significantly more accurate than manual alignment in overlaying multimodal retinal imaging in RP patients and showed the potential to use AI algorithms for future multimodal clinical and research applications.

A Retrospective Study of Clinical and Immunological Features of a Pediatric Population with Talaromyces marneffei Infection.

BACKGROUND: Talaromyces marneffei (T. Marneffei) infection is considered as an indicator of immunosuppression in immunocompromised individuals, leading to multiple organ damage. Our study aimed to evaluate both the clinical characteristics and immunological features of pediatric patients infected with T. marneffei from our institute, providing novel insights into diagnosis and treatment for this life-threatening disease. METHOD: Thirteen pediatric patients with T. marneffei infection were enrolled in Guangzhou Women and Children's Medical Center during 2012 to 2020. Clinical data and laboratory findings were collected and further analyzed. Pearson correlation coefficient was calculated to determine the relationship between serum immunoglobulins (Igs) levels and white blood cell count, or the absolute lymphocyte count. RESULTS: Patients were diagnosed as having T. Marneffei infection mainly based on the results of fungal culture and Gram stain of specimens. The most common presentations were fever (69%), pneumonia (38%) and immunodeficiency (38%). The total levels of Igs (IgE, IgA, and IgM) were positively correlated with both white blood cell count and absolute lymphocyte count. CONCLUSION: Serum Ig expression Pattern in patients diagnosed with T. marneffei infection might serve as an effective prognostic marker which would help with the development of early interventions for children with this fatal disease.

Optical Flow-Based Full-Field Quantitative Blood-Flow Velocimetry Using Temporal Direction Filtering and Peak Interpolation.

The quantitative measurement of the microvascular blood-flow velocity is critical to the early diagnosis of microvascular dysfunction, yet there are several challenges with the current quantitative flow velocity imaging techniques for the microvasculature. Optical flow analysis allows for the quantitative imaging of the blood-flow velocity with a high spatial resolution, using the variation in pixel brightness between consecutive frames to trace the motion of red blood cells. However, the traditional optical flow algorithm usually suffers from strong noise from the background tissue, and a significant underestimation of the blood-flow speed in blood vessels, due to the errors in detecting the feature points in optical images. Here, we propose a temporal direction filtering and peak interpolation optical flow method (TPIOF) to suppress the background noise, and improve the accuracy of the blood-flow velocity estimation. In vitro phantom experiments and in vivo animal experiments were performed to validate the improvements in our new method.

Dysregulated Serum Cytokine Production in Pediatric Patients with ß-Thalassemia Major.

ß-Thalassemia major (ß-TM) is an inherited disorder of hemoglobin (Hb) production, which can cause severe anemia. A compromised immune system has been observed in patients with ß-TM, whereas cytokines have a major role in immune modulation. Interleukin-4 (IL-4), IL-8, IL-13 and transforming growth factor-ß (TGF-ß) are critical in initiating pro-inflammatory responses, and the serum levels of those cytokines may be involved in the pathophysiology of ß-thalassemia (ß-thal). To assess this hypothesis, we studied 23 pediatric patients with ß-TM by measuring serum levels of IL-4, IL-8, IL-13 and TGF-ß, as well as evaluating infection frequency per year, total number of transfusions and serum ferritin (SF) levels, together with age-matched healthy controls. We found that patients with ß-thal had higher IL-8, IL-13 and TGF-ß concentrations than normal controls, whereas markedly decreased serum IL-4 level was documented in patients with ß-TM. Serum IL-4 level of ß-thal patients showed a negative significant correlation with infection frequency, total number of transfusions and SF levels. On the contrary, serum levels of IL-8, IL-13 and TGF-ß exerted a positive relationship with those clinical parameters. Taken together, our study implies that dysregulated cytokine profile might contribute to iron overloads and impair immune cell functions, thus serving as useful biomarkers for diagnosis and evaluation of ß-TM in the future. Our study sheds new light on the pathogenesis of ß-TM.

Liutex-Represented Vortex Spectrum in Turbulence.

The Liutex vector is new quantity introduced to represent the rigid-body rotation part of fluid motion and thus to define and identify vortices in various flows. In this work, the intermittency and power-law similarity of the Liutex vector in homogeneous, isotropic turbulence and a turbulent channel are explored. First, we found that the Liutex vector is more intermittent than the vorticity vector in the considered turbulent flows, which indicates that an iso-surface of a Liutex magnitude with an appropriate threshold could capture the major rotating motions or vortical motions of the flow. Second, the three-dimensional energy spectrums of velocity, vorticity (enstrophy spectrum) and the Liutex vector in homogeneous isotropic turbulence are shown to exhibit power laws of -5/3, 1/3 and 1/3 in the inertial subrange, respectively, whilst the Liutex energy spectrum particularly satisfies an additional -10/3 power law in the viscous subrange. This viscous similarity of the Liutex vector is the only power law that survived from the wall presence and is argued to originate from the fact that the Liutex vector represents the rigid part of fluid motion and is free from any shear contamination. The existence of such a viscous similarity law indicates a certain coherence of the small scales of turbulence and could possibly help understand and model turbulence.

Effect of NOx and RH on the secondary organic aerosol formation from toluene photooxidation.

The secondary organic aerosol (SOA) formation mechanism and physicochemical properties can highly be influenced by relative humidity (RH) and NOx concentration. In this study, we performed a laboratory investigation of the SOA formation from toluene/OH photooxidation system in the presence or absence of NOx in dry and wet conditions. The chemical composition of toluene-derived SOA was measured using Aerodyne high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). It was found that the mass concentration of toluene decreased with increasing RH and NOx concentration. However, the change of SOA chemistry composition (f44, O/C) with increased RH was not consistent in the condition with or without NOx. The light absorption and mass absorption coefficient (MAC) of the toluene-derived SOA only increased with RH in the presence of NOx. In contrast, MAC is invariant with RH in the absence of NOx. HR-ToF-AMS results showed that, in the presence of NOx, the increased nitro-aromatic compounds and N/C ratio concurrently caused the increase of SOA light absorption and O/C in wet conditions, respectively. The relative intensity of CHON and CHOxN family to the total nitrogen-containing organic compounds (NOCs) increased with the increasing RH, and be the major components of NOCs in wet condition. This work revealed a synergy effect of NOx and RH on SOA formation from toluene photooxidation.

Plasmon-driven light harvesting in poly(vinyl alcohol) films for precise surface topography modulation.

Efficient light harvesting is essential for advanced photonic devices. Complex micro/nano surface relief structures can be produced via light-triggered mechanical movement, but limited in organic active molecular units. In this Letter, we propose to embed noble-metal particles into light-inactive polyvinyl alcohol matrix to construct a light harvesting system driven by plasmon for inscription of surface relief gratings. Ultra-small-sized silver nuclei are generated in the polymer by pre-thermal treatment, acting as an accelerator for the subsequent photoinduced particle growth, hydrogen group cleavage, and matrix softening. Based on such properties, a complex plasmonic array carrying ultra-high-density information is achieved with peristrophic multiplexing holography. This Letter paves a bright way to realize data storage, information encryption, and optical microcavity.

Transformable Nanosensitizer with Tumor Microenvironment-Activated Sonodynamic Process and Calcium Release for Enhanced Cancer Immunotherapy.

Despite the promise of sonodynamic processes in cancer therapy, existing sonosensitizers often fail to regulate the generation of reactive oxygen species (ROS) against tumors, potentially leading to off-target toxicity to normal tissues. We report a transformable core-shell nanosonosensitizer (TiO2 @CaP) that reinvigorates ROS generation and dissolves its CaP shell to release Ca2+ in an acidic tumor microenvironment (TME) under ultrasound activation. Thus, TiO2 @CaP acts as a smart nanosonosensitizer that specifically induces mitochondrial dysfunction via overloading intracellular Ca2+ ions to synergize with the sonodynamic process in the TME. TiO2 @CaP substantially enhances immunogenic cell death, resulting in enhanced T-cell recruitment and infiltration into the immunogenic cold tumor (4T1). In conjunction with checkpoint blockade therapy (anti-PD 1), TiO2 @CaP-mediated sonodynamic therapy elicits systemic antitumor immunity, leading to regression of non-treated distant tumors and inhibition of lung metastasis. This work paves the way to development of "smart" TME-activatable sonosensitizers with temporospatial control over antitumor responses.

Genetic Polymorphisms of the IFNLR1 Gene Correlate with HCV Infection and Biochemical Features of Chronic HCV Patients in Yunnan, China.

Hepatitis C virus (HCV) infection could lead to serious liver diseases, but the pathogenic mechanisms were not completely clear. Cytokines play critical roles in infection, and the genetic polymorphisms in the cytokine genes are widely studied in infectious diseases. The variations in the IL28B gene were associated with HCV infection, viral clearance, and biochemical features of patients, but the studies of its receptor (IFNLR1/IL10RB) were rare. In this study, we collected 395 chronic HCV patients and 397 normal controls to investigate the genetic role of the IFNLR1 gene. Eight tagSNPs were genotyped, and the haplotypes were constructed. Genotypes CT (23.80% vs. 17.13%) and TT (75.19% vs. 81.36%) of rs7532146 showed higher and lower frequencies in HCV patients than that in controls (P = .022; P = .039). Haplotypes GGAATCTC (P = .028) and AAAGCCCT (P = .002) were risk factors for HCV infection, but haplotype GAAATCTT (P = .027) played protective role in HCV infection. Moreover, we identified that the ALT level was significantly lower in HCV patients with genotype TT of rs4489498 than those with other genotypes (CC vs. TT: P = .037; CT vs. TT: P = .013). HCV viral load was highest in HCV patients with genotype CC of rs4489498 than in patients with other two genotypes (CC vs. CT: P = .006; CC vs. TT: P = .039). In conclusion, the genotypes and haplotypes in the IFNLR1 gene were associated with HCV infection and biochemical features of Chinese HCV patients.

Genomic dissection of the most prevalent Listeria monocytogenes clone, sequence type ST87, in China.

BACKGROUND: Listeria monocytogenes consists of four lineages that occupy a wide variety of ecological niches. Sequence type (ST) 87 (serotype 1/2b), belonging to lineage I, is one of the most common STs isolated from food products, food associated environments and sporadic listeriosis in China. Here, we performed a comparative genomic analysis of the L. monocytogenes ST87 clone by sequencing 71 strains representing a diverse range of sources, different geographical locations and isolation years. RESULTS: The core genome and pan genome of ST87 contained 2667 genes and 3687 genes respectively. Phylogenetic analysis based on core genome SNPs divided the 71 strains into 10 clades. The clinical strains were distributed among multiple clades. Four clades contained strains from multiple geographic regions and showed high genetic diversity. The major gene content variation of ST87 genomes was due to putative prophages, with eleven hotspots of the genome that harbor prophages. All strains carry an intact CRISRP/Cas system. Two major CRISPR spacer profiles were found which were not clustered phylogenetically. A large plasmid of about 90 Kb, which carried heavy metal resistance genes, was found in 32.4% (23/71) of the strains. All ST87 strains harbored the Listeria pathogenicity island (LIPI)-4 and a unique 10-open read frame (ORF) genomic island containing a novel restriction-modification system. CONCLUSION: Whole genome sequence analysis of L. monocytogenes ST87 enabled a clearer understanding of the population structure and the evolutionary history of ST87 L. monocytogenes in China. The novel genetic elements identified may contribute to its virulence and adaptation to different environmental niches. Our findings will be useful for the development of effective strategies for the prevention and treatment of listeriosis caused by this prevalent clone.

One-Pot Decoration of Graphene with SnO2 Nanocrystals by an Elevated Hydrothermal Process and Their Application as Anode Materials for Lithium Ion Batteries.

Tin dioxide (SnO2), with a high theoretical storage capacity of 782 mAhg-1, is a potential alternative anode for rechargeable lithium ion batteries (LIBs). However, its low electronic conductivity and poor stability during cycling (due to a change in volume) hinder its practical applications for energy storage. Composite materials of SnO2-nanocrystal-decorated graphene, which show excellent electrochemical characteristics, were prepared using a one-pot elevated hydrothermal method at 250 °C without subsequent carbonization treatment. The effects of graphene, solvent composition, and temperature on the morphology, structure, and electrochemical properties of the SnO2/graphene composites were investigated using XRD, SEM, TEM, and N2 adsorption-desorption techniques. The as-prepared SnO2/graphene composites deliver a high initial discharge capacity of 1734.1 mAh g-1 at 200 mA g-1 and exhibit a high reversible capacity of 814.7 mAh g-1 even after 70 cycles at a current density of 200 mA g-1. The composites also exhibit a high rate capability of 596 mAh g-1 at 2000 mAg-1, indicating a long cycle life and promising capability when used as anode materials for lithium ion batteries and suggesting that SnO2/graphene composites have wide application prospects in LIBs.

Effect of nanocavities on Ge nanoclustering and out-diffusion in SiO2.

Germanium nanocrystals (Ge-ncs) were synthesized by implantation of Ge+ ions into the fused silica, followed by a thermal annealing at 1000 °C. High-resolution transmission electron microscopy was employed to characterize both the morphology of the formed Ge-ncs and the evolution of their depth-distribution as a function of annealing durations. The formation of nanocavities in the vicinity of nanocrystal/SiO2 interface is evidenced, as well as their influence on the release of the compressive stress exerted on Ge-ncs by surrounding SiO2. Some Ge-ncs are found inside nanocavities, and can move into the implanted layer through a nanocavity-assisted diffusion mechanism. This finding sheds light on a new process that can explain the non-uniformity of the Ge-nanocrystal spatial distribution.

Defect-induced enhanced photocatalytic activities of reduced α-Fe2O3 nanoblades.

Bicrystalline α-Fe2O3 nanoblades (NBs) synthesized by thermal oxidation of iron foils were reduced in vacuum, to study the effect of reduction treatment on microstructural changes and photocatalytic properties. After the vacuum reduction, most bicrystalline α-Fe2O3 NBs transform into single-layered NBs, which contain more defects such as oxygen vacancies, perfect dislocations and dense pores. By comparing the photodegradation capability of non-reduced and reduced α-Fe2O3 NBs over model dye rhodamine B (RhB) in the presence of hydrogen peroxide, we find that vacuum-reduction induced microstructural defects can significantly enhance the photocatalytic efficiency. Even after 10 cycles, the reduced α-Fe2O3 NBs still show a very high photocatalytic activity. Our results demonstrate that defect engineering is a powerful tool to enhance the photocatalytic performance of nanomaterials.

Structure versus properties in α-Fe2O3 nanowires and nanoblades.

We report structure/property relationships in bicrystalline α-Fe2O3 nanowires (NWs) and nanoblades (NBs), synthesized by thermal oxidation of iron foils with different surface roughness. The electrical properties of individual nanostructures were studied by in situ transmission electron microscopy. Current-voltage (I-V) measurements using gold electrodes showed that a Schottky contact forms between α-Fe2O3 NWs whereas an ohmic contact forms between α-Fe2O3 NBs. The difference in transport properties is attributed to the existence of oxygen vacancies in the coincidence-site-lattice boundary region of α-Fe2O3 NBs. Magnetic measurements indicate that the temperature-dependent zero-field-cooled magnetization rises more rapidly near the Morin transition temperature for α-Fe2O3 NBs than that for NWs. The distinct magnetic properties of the NBs are ascribed to the enhanced magnetic order induced by the structural order in the two-dimensional NBs. These α-Fe2O3 NBs are promising building blocks for electronic and magnetic devices since their 2D geometries facilitate integration into devices with realistic pathways to manufacturing. In addition, our study shows that boundary engineering is an effective approach for tailoring the physical properties of nanomaterials.

Mechanistical investigation on the self-enhanced photocatalytic activity of CuO/Cu2O hybrid nanostructures by density functional theory calculations.

The photocatalytic mechanism of a Cu2O/CuO hybrid system is disclosed in detail by density functional theory (DFT) calculations. The synergistic relationship of the two counterparts is confirmed by hydrogen peroxide (H2O2) formation on the CuO nanowires and dissociation on the Cu2O nanoparticles; this enables the system to self-sufficiently produce hydroxyl radicals, which is highly efficient in the photocatalytic degradation of methyl orange. The exposed surfaces are found to be crucial in the cooperative photocatalytic system, especially the Cu2O(111) surface, in the dissociation of H2O2. The distinct positions of the conduction band minimum and valence band maximum for CuO and Cu2O and synergic surface reactions enable the effective utilization of the electrons and holes generated by visible-light irradiation. Our results will contribute to a greater understanding of the specific mechanism of photodegradation catalyzed by Cu2O/CuO heterostructures, which may lead to promising directions in structure optimization for photocatalysts with high photocatalytic efficiency.

CLOCK/BMAL1 regulates circadian change of mouse hepatic insulin sensitivity by SIRT1.

UNLABELLED: The protein deacetylase, sirtuin 1 (SIRT1), involved in regulating hepatic insulin sensitivity, shows circadian oscillation and regulates the circadian clock. Recent studies show that circadian misalignment leads to insulin resistance (IR); however, the underlying mechanisms are largely unknown. Here, we show that CLOCK and brain and muscle ARNT-like protein 1 (BMAL1), two core circadian transcription factors, are correlated with hepatic insulin sensitivity. Knockdown of CLOCK or BMAL1 induces hepatic IR, whereas their ectopic expression attenuates hepatic IR. Moreover, circadian change of insulin sensitivity is impaired in Clock mutant, liver-specific Bmal1 knockout (KO) or Sirt1 KO mice, and CLOCK and BMAL1 are required for hepatic circadian expression of SIRT1. Further studies show that CLOCK/BMAL1 binds to the SIRT1 promoter to enhance its expression and regulates hepatic insulin sensitivity by SIRT1. In addition, constant darkness-induced circadian misalignment in mice decreases hepatic BMAL1 and SIRT1 levels and induces IR, which can be dramatically reversed by resveratrol. CONCLUSION: These findings offer new insights for coordination of the circadian clock and metabolism in hepatocytes by circadian regulation of hepatic insulin sensitivity via CLOCK/BMAL1-dependent SIRT1 expression and provide a potential application of resveratrol for combating circadian misalignment-induced metabolic disorders.