Design of ultra-wide-field scanning laser fundus imaging system with cascaded conicoid mirrors.

We propose and design a multi-stage cascaded scanning laser ophthalmoscope (SLO) for ultra-wide field (UWF), which uses conicoid mirrors, constructed by conjugation of pupil plane. The vergence uniformity and the angular magnification of a cascaded conicoid mirrors (CCM) system are analyzed recursively and optimized preliminarily to achieve high quality imaging with UWF, and the optimal system with the model eye are obtained by simulation and optimization. Two-stage and three-stage cascaded systems are designed with this method, and the formulas of beam vergence and angular magnification are obtained by theoretical derivation. As compared to the two-stage CCM system, the proposed three-stage cascaded UWF SLO has superior performance in imaging quality. Its average RMS radius of spot diagram is calculated to be 26.372 µm, close to the diffractive limit resolution. The image resolution of human retina can be up to 30 µm with 135° FOV in theory. The three-stage cascaded SLO is more suitable for UWF fundus imaging. This study will be helpful for early screening and accurate diagnosis of various diseases in the peripheral retina.

HIF-2α-induced upregulation of CD36 promotes the development of ccRCC.

Clear cell renal cell carcinoma (ccRCC) is characterized by the abundance of lipid droplets and the activation of the hypoxia-inducible factor (HIF) signaling pathway. However, the lipid reprogramming induced by HIF signaling in ccRCC is not fully understood. In this study, we found that the fatty acid receptor CD36 was highly expressed in human ccRCC tissues and ccRCC cell lines. CD36 overexpression increased fatty acid uptake and lipid droplet formation, and enhanced the proliferation and migration of ccRCC cells in a DGAT1-dependent manner. In contrast, the disruption of endogenous CD36 showed the opposite effects. The upregulated expression of CD36 in ccRCC was associated with hypoxia and HIF-2α activation. Furthermore, we identified CD36 as a new target of the transcription factor HIF-2α. The knockdown of CD36 in ccRCC cells reduced lipid accumulation and also blocked the tumor-promoting effects induced by HIF-2α under hypoxia. Our findings suggest that hypoxia-dependent HIF-2α promotes the remodeling of lipid metabolism and the malignant phenotype of ccRCC via CD36, providing a certain theoretical basis for clarifying the mechanism of ccRCC.

Aerosol exchange between pressure-equilibrium rooms induced by door motion and human movement.

It is now widely recognised that aerosol transport is major vector for transmission of diseases such as COVID-19, and quantification of aerosol transport in the built environment is critical to risk analysis and management. Understanding the effects of door motion and human movement on the dispersion of virus-laden aerosols under pressure-equilibrium conditions is of great significance to the evaluation of infection risks and development of mitigation strategies. This study uses novel numerical simulation techniques to quantify the impact of these motions upon aerosol transport and provides valuable insights into the wake dynamics of swinging doors and human movement. The results show that the wake flow of an opening swinging door delays aerosol escape, while that of a person walking out entrains aerosol out of the room. Aerosol escape caused by door motion mainly happens during the closing sequence which pushes the aerosols out. Parametric studies show that while an increased door swinging speed or human movement speed can enhance air exchange across the doorway, the cumulative aerosol exchange across the doorway is not clearly affected by the speeds.

Surface astigmatism correction using segmented freeform surfaces for a progressive addition lens.

The undesired distribution of irregular surface astigmatism (SA) on the freeform surface has been the major concern of progressive addition lens (PAL) design. Herein, we proposed a segmented freeform surface (SFS) construction method, which relies on the lines of curvature to rule the surface segmentation and then eliminates the difference between principal curvatures to correct the SA. Based on ray tracing and numerical simulation results, the SFS-PAL design has superior performance in image quality within a dynamic field of view over the conventional freeform PAL. To verify the feasibility and the real performance of the new design, we used the diamond turning method with a fast tool servo to realize the rapid prototyping, and then used injection molding for the mass production of the high-quality SFS-PALs.

A challenge in anaerobic digestion of swine wastewater: recalcitrance and enhanced-degradation of dietary fibres.

Dietary fibres are main substances in the pig's feed. Because of the recalcitrance, they could enter swine wastewater and become a serious obstruction factor for the anaerobic digestion process. In this work, three dietary fibres abundant in pig feedstocks: Wheat Bran Fibre (WBF), Alfalfa Fibre (AF) and Rice Chaff Fibre (RCF) were chosen and their anaerobic degradability was determined. The results showed that the biochemical methane potential in 10 days (BMP10) of WBF, AF and RCF was 258, 176 and 86 mL/g-VS, respectively. The size, purity, crystallinity, and lignin coating in particular, were found having influences on the anaerobic biodegradability of dietary fibres. To surprise, a negative rather than positive effect was observed for the direct addition of extraneous cellulase into the anaerobic digestion systems, leading to a longer lag time and a smaller BMP10. The enhancement was achieved for the addition of extraneous bacteria in the form of anaerobic granular sludge (AnGS), shortening the lag time of WBF and AF by 36% and 13%, respectively. By high-throughput sequencing analysis, abundant protein and amino acids degraders found in anaerobic activated sludge (AnAS) could degrade the exogenous enzymes. Abundant members affiliated to the family Anaerolineaceae, and Syntrophobacteraceae in AnGS, related to the cellulolytic and syntrophic activity respectively, probably contribute to the acceleration effect of AnGS.

Liquid Crystal Spatial Light Modulators for Simulating Zonal Multifocal Lenses.

SIGNIFICANCE: To maximize efficiency of the normally lengthy and costly multizone lens design and testing process, it is advantageous to evaluate the potential efficacy of a design as thoroughly as possible prior to lens fabrication and on-eye testing. The current work describes an ex vivo approach of optical design testing. PURPOSE: The aim of this study was to describe a system capable of examining the optical characteristics of multizone bifocal and multifocal optics by subaperture stitching using liquid crystal technologies. METHODS: A liquid crystal spatial light modulator (SLM) was incorporated in each of two channels to generate complementary subapertures by amplitude modulation. Additional trial lenses and phase plates were placed in pupil conjugate planes of either channel to integrate the desired bifocal and multifocal optics once the two optical paths were recombined. A high-resolution Shack-Hartmann aberrometer was integrated to measure the optics of the dual-channel system. Power and wavefront error maps as well as point spread functions were measured and computed for each of three multizone multifocal designs. RESULTS: High transmission modulation was achieved by introducing half-wavelength optical path differences to create two- and five-zone bifocal apertures. Dual-channel stitching revealed classic annular rings in the point spread functions generated from two-zone designs when the outer annular optic was defocused. However, low efficiency of the SLM prevented us from simultaneously measuring the eye + simulator aberrations, and the higher-order diffraction patterns generated by the cellular structure of the liquid crystal arrays limited the visual field to ±0.45 degrees. CONCLUSIONS: The system successfully simulated bifocal and multifocal simultaneous lenses allowing for future evaluation of both objective and subjective evaluation of complex optical designs. However, low efficiency and diffraction phenomena of the SLM limit the utility of this technology for simulating multizone and multifocal optics.

Vertical distribution of aerosol optical properties based on aircraft measurements over the Loess Plateau in China.

Vertical distributions of aerosol optical properties based on aircraft measurements over the Loess Plateau were measured for the first time during a summertime aircraft campaign, 2013 in Shanxi, China. Data from four flights were analyzed. The vertical distributions of aerosol optical properties including aerosol scattering coefficients (σsc), absorption coefficients (σab), Angström exponent (α), single scattering albedo (ω), backscattering ratio (ßsc), aerosol mass scattering proficiency (Qsc) and aerosol surface scattering proficiency (Qsc(')) were obtained. The mean statistical values of σsc were 77.45 Mm(-1) (at 450 nm), 50.72 Mm(-1) (at 550n m), and 32.02 Mm(-1) (at 700 nm). The mean value of σab was 7.62 Mm(-1) (at 550 nm). The mean values of α, ßsc and ω were 1.93, 0.15, and 0.91, respectively. Aerosol concentration decreased with altitude. Most effective diameters (ED) of aerosols were less than 0.8 µm. The vertical profiles of σsc,, α, ßsc, Qsc and Qsc(') showed that the aerosol scattering properties at lower levels contributed the most to the total aerosol radiative forcing. Both α and ßsc had relatively large values, suggesting that most aerosols in the observational region were small particles. The mean values of σsc, α, ßsc, Qsc, Qsc('), σab and ω at different height ranges showed that most of the parameters decreased with altitude. The forty-eight hour backward trajectories of air masses during the observation days indicated that the majority of aerosols in the lower level contributed the most to the total aerosol loading, and most of these particles originated from local or regional pollution emissions.

First fluoride ceramics lasing at 605 nm at ambient temperature fabricated from chemically synthesized powders.

Laser ceramics have emerged as promising candidates of solid-state laser gain media. However, most laser ceramics are currently focused on lasing in the infrared wavelength range. The very limited options of host materials and the increased optical scattering losses at shorter wavelengths within ceramics have greatly limited the development of visible laser ceramics. Here we report visible laser ceramics with a composition of 0.5%Pr3+,5%Y3+:SrF2, in which a visible (orange) laser oscillation at 605 nm has been successfully achieved at room temperature pumped by InGaN blue laser diodes with a maximum slope efficiency of 8.1%. The ceramics were fabricated by vacuum hot pressing (VHP) of wet-chemistry synthesized 0.5%Pr3+,5%Y3+:SrF2 powders, followed by hot isostatic pressing (HIP). It was found that the visible laser ceramics exhibited a lower optical scattering loss along the processing pressure direction of the VHP process, indicating a uniaxial anisotropy in optical transmission within the ceramics. To our best knowledge, the current work is the first report on visible laser ceramics lasing in the orange region at ambient temperature, fabricated from chemically synthesized powders, which could pave the way for future scientific research on and industrial applications of more sophisticated and cost-effective visible laser ceramics.

CYP4G subfamily genes mediate larval integument development in Spodoptera frugiperda.

Cytochrome P450 (CYP) 4G subfamily is closely related to the synthesis of cuticular hydrocarbons, leading to the enhanced desiccation and insecticide resistance of pests. However, functions of CYP4Gs in larval integument development remain unknown in Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), which is a major transboundary migratory pest and become a common pest in China. On the basis of the genome and transcriptome datasets of S. frugiperda, CYP4G74, CYP4G75, CYP4G108, and CYP4G109 were identified, which contained the conserved domains of P450s and CYP4Gs. The spatial and temporal expression analysis showed that CYP4G74 and CYP4G75 were significantly highly expressed in adults and larval integuments, while CYP4G108 and CYP4G109 had low expressions in larval integuments. After silencing CYP4G74 and CYP4G75 by RNA interference, abnormal integument development occurred in larvae, some of which became smaller and dead, indicating important roles of CYP4G74 and CYP4G75 in the synthesis and development of integuments. The results clarify the functions of CYP4Gs in S. frugiperda and provide potential targets for the control of this pest.

The fatty acid receptor CD36 promotes macrophage infiltration via p110γ signaling to stimulate metastasis.

INTRODUCTION: Metabolic regulators are key in controlling immune cell fate in the tumor microenvironment. The accumulation of tumor-associated macrophages (TAMs) in cancer greatly contributes to metastasis and poor outcome. However, the metabolic pathways responsible for TAM accumulation are largely unknown. OBJECTIVE: This study aims to elucidate the role of the fatty acid translocase CD36 in the regulation of TAM accumulation. METHODS: The immune profile was analyzed in patients with liver metastasis by CIBERSORT. Immunohistostaining of CD68 and CD36 was conducted in clinical specimens from patients with liver metastasis. Myeloid-specific CD36 knockout mice and their littermates were used to establish preclinical liver metastasis models. Subsequently, a series of experiments were used to explore the underlying mechanisms of how CD36 regulates TAM population. RESULTS: We found that massive TAM accumulation in patients with liver metastasis is associated with an upregulation of CD36 on TAMs. Liver metastasis is abundantly infiltrated by TAMs that are derived from circulating monocytes, but not tissue-resident macrophages. Myeloid-specific CD36 knockout specifically reduced and inactivated monocyte-differentiated macrophages, resulting in diminished immune suppression and attenuated liver metastasis. The protect effects of CD36 knockout can be abrogated by blockade of macrophage recruitment through CCR2 or the p110γ isoform of PI3K downstream of it. Mechanically, CD36 reprogrammed the lipid metabolism of macrophages, in which sphingolipids were significantly downregulated, that contributed to weakened lipid raft-dependent activation of p110γ. CONCLUSION: CD36 expands TAM population by promoting the recruitment of circulating monocytes through CCL2/CCR2/p110γ signaling. Our findings provide evidence for targeting CD36 as a therapeutic strategy against liver metastasis.

Fibril structure of human islet amyloid polypeptide.

Misfolding and amyloid fibril formation by human islet amyloid polypeptide (hIAPP) are thought to be important in the pathogenesis of type 2 diabetes, but the structures of the misfolded forms remain poorly understood. Here we developed an approach that combines site-directed spin labeling with continuous wave and pulsed EPR to investigate local secondary structure and to determine the relative orientation of the secondary structure elements with respect to each other. These data indicated that individual hIAPP molecules take up a hairpin fold within the fibril. This fold contains two ß-strands that are much farther apart than expected from previous models. Atomistic structural models were obtained using computational refinement with EPR data as constraints. The resulting family of structures exhibited a left-handed helical twist, in agreement with the twisted morphology observed by electron microscopy. The fibril protofilaments contain stacked hIAPP monomers that form opposing ß-sheets that twist around each other. The two ß-strands of the monomer adopt out-of-plane positions and are staggered by about three peptide layers (∼15 Å). These results provide a mechanism for hIAPP fibril formation and could explain the remarkable stability of the fibrils. Thus, the structural model serves as a starting point for understanding and preventing hIAPP misfolding.

Expressions and functions of RR-1 cuticular protein genes in the integument of Mythimna separata.

As the most outer layer between itself and the environment, integuments are necessary for insects with various important functions. Cuticular proteins (CPs) are the main components in integuments, while the functions of CP genes remain unknown in Mythimna separata (Walker), which is a devastating agricultural pest. In this study, 79 CP genes were identified from the transcriptomes of larval integuments, 57 of which were from the family containing conserved Rebers & Riddiford (R&R) consensus (CPR family). Amongst these CPRs, 44 genes belonged to the subfamily with RR-1 motif (RR-1 genes) and clustered into three clades, with the top 15 most abundant RR-1 genes identified based on fragments per kilobase per million mapped fragments (FPKM) values. RT-qPCR analysis showed that most of RR-1 genes such as MsCPR1-4 were highly expressed at larval stages and in their integuments. The expression levels of RR-1 genes were generally decreased at the beginning but increased at the late stage of molting process. RNAi was applied for six RR-1 genes, and MsCPR1-4 were knocked down significantly. Silence of MsCPR2 resulted in abnormal integument formed after molting, while knockdown of MsCPR3 and MsCPR4 led to failure of molting, respectively. No phenotype was obtained for the RNAi of MsCPR1. Therefore, the expression of RR-1 genes and their functions were analyzed in the development of integuments in M. separata, providing new insights of RR-1 genes and potential targets for the development of growth regulators and new insecticides for M. separata.

One-year myopia control efficacy of cylindrical annular refractive element spectacle lenses.

PURPOSE: To evaluate the 1-year myopia control efficacy of a spectacle lens with annular cylindrical microstructures. METHODS: A total of 118 consecutive eligible children aged 8-12 years with -1.00 D to -4.00 D of spherical component myopia and <1.50 D astigmatism were enrolled between August 2020 and November 2020 at the Eye Hospital of Wenzhou Medical University. Participants were randomly assigned to wear cylindrical annular refractive element (CARE) (n = 61) or single-vision (n = 57) spectacle lenses. Cycloplegic autorefraction (spherical equivalent refraction [SER]) and axial length (AL) were measured at baseline and 6-month intervals. Adaptation and compliance questionnaires were administered during all visits. RESULTS: Among 118 randomized participants, 96 (81.4%) were included in the analyses (mean [SE] age, 10.4 [0.6] years; 49 [51.0%] were female; mean [SE] spherical equivalent refractive error, -2.67 [0.66] D; mean [SE] axial length, 24.75 [0.77] mm). Adjusted 1-year myopia progression was -0.56 D for CARE and -0.71 D for single-vision spectacle lenses. The difference in progression was 0.14 D (95% CI, -0.04 to 0.32) for CARE vs single vision. Adjusted 1-year eye growth was 0.27 mm for CARE and 0.35 mm for single vision. The difference in eye growth was 0.09 mm (95% CI, -0.15 to -0.02) for CARE vs single vision. All groups adapted to their lenses with no reported adverse events, complaints, or discomfort. CONCLUSIONS: Among children with myopia, treatment with cylindrical annular refractive element spectacle lenses significantly reduced the rate of axial elongation over 1 year compared with single-vision spectacle lenses.

Idealized models of protofilaments of human islet amyloid polypeptide.

Fibrils formed by assembly of human islet amyloid polypeptide (hIAPP) are found in most patients with type II diabetes. Structurally, these fibrils are composed of multiple protofilaments and are characterized by extended beta sheets, variable helical twists, and different morphologies. We have previously derived models for the hIAPP protofilament using simulations constrained by data from EPR spectroscopy. In the current work, these models were used as a basis for generating idealized hIAPP protofilaments with symmetrical geometrical properties using a new algorithm, MFIBRIL. We show good agreement of the idealized protofilaments with experimental data for amino acid side chain orientations and geometrical features including the inter-ß sheet distance and the protofilament radius. These idealized protofilaments can be used in MFIBRIL to generate fibril models that may be experimentally testable at the molecular level. MFIBRIL can also be used for building structures of any repetitive molecular assembly starting with a single building block obtained from any source.

Effects of black carbon aerosol on air quality and vertical meteorological factors in early summer in Beijing.

Black carbon (BC) aerosols have effects on the atmospheric thermal vertical structure due to its radiation absorption characteristics, hereby influencing the boundary layer characteristics and pollutant diffusion. This study focuses on the BC effects under different atmospheric conditions on air quality and vertical meteorological conditions. Four days flight observation combined with surface wind profiler radar data were used to investigate the vertical profiles of BC and wind speed over Beijing urban area in early summer. The vertical profiles of BC concentration and wind speed in the boundary layer had a negative correlation, both having abrupt changes near the boundary layer height under stagnant weather conditions. The chemical transport model showed the increase of BC under stagnant conditions could cause aggravation of the stability of the boundary layer, thereby increasing the accumulation of pollutants. In particular, BC leads to the changes in the temperature profile, which will modify relative humidity and indirectly lead to the changes in the vertical profile of aerosol optical properties. However, if the early accumulation of BC was absent under more turbulent conditions, the effects of BC on air quality and meteorological conditions were limited.

Circulating soluble CD36 as a novel biomarker for progression and prognosis of HBV-related liver diseases.

Background: Our previous study suggested CD36 may be a positive regulator of hepatitis B virus (HBV) replication in vitro. Therefore, the present study aimed to investigate whether circulating soluble CD36 (sCD36) could serve as a diagnostic and prognostic biomarker for HBV-related liver diseases based on the clinic collected data. Methods: A total of 282 subjects were divided into healthy controls (HC, n = 47), chronic hepatitis B (CHB, n = 68), HBV-related liver cirrhosis (HBV-LC, n = 167). Soluble CD36 in plasma was measured by ELISA, and monocyte or platelet CD36 expression was determined by flow cytometry. Results: There was a step-wise increase of sCD36 with the progression of chronic HBV infection, and it was the highest in the HBV- LC group with liver failure (1.50, IQR:1.04-2.00) as compared with HC (0.38, IQR:0.27-0.38), CHB (0.75, IQR:0.40-1.13), and HBV-LC without liver failure (1.02, IQR,0.61-1.35) group. Circulating sCD36 was not correlated with serum HBV DNA levels, but correlated with liver function parameters. Additionally, ROC analysis confirmed sCD36 could be used to predict liver failure for HBV-LC patients, which yielded an AUC of 0.775 with 71.0% sensitivity and 72.2% specificity. Multivariate logistic regression analysis revealed sCD36 is an independent risk factor in predicting liver failure. Moreover, plasma sCD36 in HBV-LC patients was significantly correlated with prognostic indices, including MELD, MELD-Na and CHILD-PUGH scores. On the other hand, CD36 expression on monocytes or platelets was positively correlated with plasma sCD36 levels, whereas they were not strongly associated with the disease severity. Conclusion: Circulating sCD36 could be used as a novel noninvasive biomarker for predicting liver failure and prognosis in chronic HBV infected patients.

Normative Data and Determinants of Macular, Disc, and Peripapillary Vascular Density in Healthy Myopic Children Using Optical Coherence Tomography Angiography.

Objective: To establish a normative database for the vascular density (VD) in macular, disc, and peripapillary regions in healthy myopic children and to evaluate associated ocular features with optical coherence tomography angiography (OCTA). Methods: This was an observational, prospective and cross-sectional study. 776 Chinese healthy myopic children (375 boys and 401 girls) were enrolled, mean (±SD) age 9.84 ± 1.98 (range 6-16) years. En-face angiogram OCTA was performed on 6 mm × 6 mm retinal and 4.5 mm × 4.5 mm disc regions. VD measurements in the macular retina were segmented into the four regions: superficial capillary plexus (SCP), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and choriocapillaris (CC). Correlations between macular, disc, and peripapillary VD and possible influencing factors [age, gender, axial length (AL), spherical equivalent refraction (SER), right/left eye, and signal strength index (SSI)] were assessed by Pearson's correlation and multivariate regression analysis. Results: For macular scans, the corrected VD in the ICP region was (48.25 ± 4.24)% for the whole macular retina. The macular ICP VD in most sections was lower than the SCP, DCP, and CC (all P < 0.001). The corrected VD in CC was (72.96 ± 4.42)% for the whole macular retina. The macular CC VD in every section was all higher than the SCP, ICP, and DCP (all P < 0.001). The size of foveal avascular zone (FAZ) and foveal VD 300 (FD-300) was 0.28 mm2± 0.10 mm2 and (58.43 ± 4.17)% respectively. For disc scans, the corrected VD was (58.04 ± 2.73)% for the whole disc area. Both AL and SER were strongly correlated with ICP, DCP, and CC VD in all regions (all P < 0.01). Larger SSI was correlated with a lower VD in the SCP and ICP, and a higher VD in DCP and CC (all P < 0.01). Conclusion: Vascular density values provide large scale normative data on macular, disc, and peripapillary vascular parameters in a large sample of healthy myopic children with OCTA measured in the four different retinal plexuses and regions. The VD in different regions had various influencing factors; mainly a close correlation with AL and SSI.

Deformed Mediated Larval Incisor Lobe Development Causes Differing Feeding Behavior between Oriental Armyworm and Fall Armyworm.

Mandibular incisor lobes are important for insect feeding behavior, living habits and niche. However, the molecular regulation of insect incisor lobe development remains unknown. In this study, we found that two maize pests, oriental armyworm Mythimna separata and fall armyworm Spodoptera frugiperda, have different feeding patterns in maize, which are closely associated with the different development patterns of their incisor lobes. Different from first to sixth instar S. frugiperda, which feed on leaf tissues and whorls with sharp incisor lobes, older instars of M. separata feed from leaf margins with no incisor lobes. Hox gene Deformed (Dfd) is important for head appendages, but its function in incisor lobe development is not clear. Here, Dfds were identified from two armyworm species, and both were expressed highly in heads and eggs. Interestingly, the expression levels of MsDfd were relatively high in larval mandibles and decreased dramatically from fourth-instar mandibles in M. separata. Knockdown of MsDfd resulted in malformed mandibles with no incisor lobe in M. separata, making the larvae unable to perform window-feeding. However, RNAi of SfDfd did not affect the mandibles and window-feeding pattern of S. frugiperda, indicating the different roles of Dfd in these two species. Moreover, the mortality of new first instar M. separata increased after feeding dsMsDfd but did not for S. frugiperda feeding dsSfDfd. These findings revealed that Dfd mediated the larval mandibular incisor lobe morphology, affecting its feeding pattern in M. separata, broadening the knowledge of Dfd functions in insect mandibles and feeding behavior.

Underlying function regulators of anaerobic granular sludge: Starvation and dormancy.

Anaerobic granular sludge (AnGS) is the core of anaerobic granular sludge bed system. In this study, the effect and its mechanism of stopping substrate supply on function of AnGS were investigated. The cutoff of exogenous substrate supply triggered AnGS to enter the dormant state. Some methanization microorganisms sporulated. The number and activity of methanization microorganisms based on 16S rDNA and 16S rRNA/16S rDNA ratio declined and stayed at 45.5% and 0.06% (bacteria), 48.7% and 0.39% (archaea) of the initial vegetative value, respectively. The resuming of exogenous substrate supply promoted AnGS to restore the vegetative state. The spores disappeared. The specific methanization activity of AnGS returned to the original level of 35.82 mL-CH4/g-VSS·d, but the delay time for gas production (DTGS) was prolonged from 9.54 to 18.04 h (0-132 d). The dormancy of methanization microorganisms was the main cause for the fluctuation of apparent function and the stability of intrinsic function of AnGS under starvation stress. The dormancy stabilized the structure and sustained the methanization community of AnGS via the reduction of EPS (structure binder/energy reserve) consumption.

CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing.

OBJECTIVE: Enhanced de novo lipogenesis (DNL) in hepatocytes is a major contributor to nonalcoholic fatty liver disease (NAFLD). Fatty acid translocase (FAT/CD36) is involved in the pathogenesis of NAFLD through facilitating free fatty acids uptake. Here, we explored the effects of CD36 on DNL and elucidated the underlying mechanisms. METHODS: We generated hepatocyte-specific CD36 knockout (CD36LKO) mice to study in vivo effects of CD36 on DNL under high-fat diet (HFD). Lipid deposition and DNL were analyzed in primary hepatocytes isolated from CD36LKO mice or HepG2 cells with CD36 overexpression. RNA sequence, co-immunoprecipitation, and proximity ligation assay were carried out to determine its role in regulating DNL. RESULTS: Hepatic CD36 expression was upregulated in NAFLD mice and patients, and CD36LKO mice exhibited attenuated HFD-induced hepatic steatosis and insulin resistance. We identified hepatocyte CD36 as a key regulator for DNL in the liver. Sterol regulatory element-binding protein 1 (SREBP1) and its downstream lipogenic enzymes such as FASN, ACCα, and ACLY were significantly downregulated in the liver of HFD-fed CD36LKO mice, whereas overexpression CD36 stimulated insulin-mediated DNL and lipid droplet formation in vitro. Mechanistically, CD36 was activated by insulin and formed a complex with insulin-induced gene-2 (INSIG2) that disrupts the interaction between SREBP cleavage-activating protein (SCAP) and INSIG2, thereby leading to the translocation of SREBP1 from ER to Golgi for processing. Furthermore, treatment with 25-hydroxycholesterol or betulin molecules shown to enhance SCAP-INSIG interaction, reversed the effects of CD36 on SREBP1 cleavage. CONCLUSIONS: Our findings identify a previously unsuspected role of CD36 in the regulation of hepatic lipogenic program through mediating SREBP1 processing by INSIG2, providing additional evidence for targeting CD36 in NAFLD.