Follicular fluid exosomes regulate OVGP1 secretion in yak oviduct epithelial cells via autophagy in vitro.

After mammalian ovulation, oocytes enter the oviduct, causing oocyte and oviduct changes. Some studies have shown that follicular fluid exosomes (FEVs) play an important role in this regulatory process, but the specific mechanism is remains unclear. Here, we investigate the effect of FEVs on autophagy and on the synthesis and secretion of oviductal glycoprotein 1 (OVGP1) in yak oviduct epithelial cells (OECs). We added FEVs to yak OECs and collected samples at intervals. The effect of autophagy on OVGP1 synthesis and secretion was detected by manipulating the level of autophagy in OECs. The results showed that autophagy gradually increased as early as 6 h after exosome intake level increased, and the increase was most obvious 24 h after. At that time, the synthesis and secretion of OVGP1 also reached its highest levels. When the autophagy level of OECs is changed through the PI3K/AKT/mTOR pathway, OVGP1 synthesis and secretion levels also change, along with the OVGP1 levels in oviduct exosomes also change. More importantly, the addition of FEVs treatment while using 3-MA to inhibit the autophagy level in yak OECs did not change the synthesis and secretion level of OVGP1. Our results indicate that FEVs can affect the synthesis and secretion of OVGP1 by regulating the level of autophagy in OECs, and that the completion of this process may depend on the PI3K/AKT/mTOR pathway, indicating that exosomes and autophagy play important roles in the reproductive physiology of yak OECs. Our results provide new ideas in to characterizing the role of exosomes in yak reproduction.

In Situ Anodic Oxidation Tuning of NiFeV Diselenide to the Core-Shell Heterojunction for Boosting Oxygen Evolution.

Developing non-noble metal-based core-shell heterojunction electrocatalysts with high catalytic activity and long-lasting stability is crucial for the oxygen evolution reaction (OER). Here, we prepared novel core-shell Fe,V-NiSe2@NiFe(OH)x heterostructured nanoparticles on hydrophilic-treated carbon paper with high electronic transport and large surface area for accelerating the oxygen evolution rate via high-temperature selenization and electrochemical anodic oxidation procedures. Performance testing shows that Fe,V-NiSe2@NiFe(OH)x possesses the highest performance for OER compared to as-prepared diselenide core-derived heterojunctions, which only require an overpotential of 243 mV at 10 mA cm-2 and a low Tafel slope of 91.6 mV decade-1 under basic conditions. Furthermore, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) confirm the morphology and elementary stabilities of Fe,V-NiSe2@NiFe(OH)x after long-term chronopotentiometric testing. These advantages are largely because of the strong synergistic effect between the Fe,V-NiSe2 core with high conductivity and the amorphous NiFe(OH)x shell with enriched defects and vacancies. This study also presents a general approach to designing and synthesizing more active core-shell heterojunction electrocatalysts for OER.

Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane Interface from Molecular Dynamics Simulations and Quantum Chemical Calculations.

Allosteric modulators are called promising candidates in G protein-coupled receptor (GPCR) drug development by displaying subtype selectivity and more specific receptor modulation. Among the allosteric sites known to date, cavities at the receptor-lipid interface represent an uncharacteristic binding location that raises many questions about the ligand interactions and stability, the binding site structure, and how all of these are affected by lipid molecules. In this work, we analyze interactions in the allosteric sites of the PAR2, C5aR1, and GCGR receptors in three lipid compositions using molecular dynamics simulations. In addition, we performed quantum chemical calculations involving the symmetry-adapted perturbation theory (SAPT) and the natural population analysis to quantify the strength of intermolecular interactions. We show that besides classical hydrogen bonds, weak polar interactions such as O-HC, O-Br, and long-range electrostatics with the backbone amides contribute to the stability of allosteric modulators at the receptor-lipid interface. The allosteric cavities are detectable in various membrane compositions. The availability of polar atoms for interactions in such cavities can be assessed by water molecules from simulations. Although ligand-lipid interactions are weak, lipid tails play a role in ligand binding pose stability and the size of allosteric cavities. We discuss physicochemical aspects of ligand binding at the receptor-lipid interface and suggest a compound library enriched by weak donor groups for ligand search in such sites.

Generation of onco-enhancer enhances chromosomal remodeling and accelerates tumorigenesis.

Chromatin remodeling impacts the structural neighborhoods and regulates gene expression. However, the role of enhancer-guided chromatin remodeling in the gene regulation remains unclear. Here, using RNA-seq and ChIP-seq, we identified for the first time that neurotensin (NTS) serves as a key oncogene in uveal melanoma and that CTCF interacts with the upstream enhancer of NTS and orchestrates an 800 kb chromosomal loop between the promoter and enhancer. Intriguingly, this novel CTCF-guided chromatin loop was ubiquitous in a cohort of tumor patients. In addition, a disruption in this chromosomal interaction prevented the histone acetyltransferase EP300 from embedding in the promoter of NTS and resulted in NTS silencing. Most importantly, in vitro and in vivo experiments showed that the ability of tumor formation was significantly suppressed via deletion of the enhancer by CRISPR-Cas9. These studies delineate a novel onco-enhancer guided epigenetic mechanism and provide a promising therapeutic concept for disease therapy.

Induced dual-target rebalance simultaneously enhances efficient therapeutical efficacy in tumors.

Multiple gene abnormalities are major drivers of tumorigenesis. NF-κB p65 overactivation and cGAS silencing are important triggers and genetic defects that accelerate tumorigenesis. However, the simultaneous correction of NF-κB p65 and cGAS abnormalities remains to be further explored. Here, we propose a novel Induced Dual-Target Rebalance (IDTR) strategy for simultaneously correcting defects in cGAS and NF-κB p65. By using our IDTR approach, we showed for the first time that oncolytic adenovirus H101 could reactivate silenced cGAS, while silencing GAU1 long noncoding RNA (lncRNA) inhibited NF-κB p65 overactivation, resulting in efficient in vitro and in vivo antitumor efficacy in colorectal tumors. Intriguingly, we further demonstrated that oncolytic adenoviruses reactivated cGAS by promoting H3K4 trimethylation of the cGAS promoter. In addition, silencing GAU1 using antisense oligonucleotides significantly reduced H3K27 acetylation at the NF-κB p65 promoter and inhibited NF-κB p65 transcription. Our study revealed an aberrant therapeutic mechanism underlying two tumor defects, cGAS and NF-κB p65, and provided an alternative IDTR approach based on oncolytic adenovirus and antisense oligonucleotides for efficient therapeutic efficacy in tumors.

Implanting oxophilic metal in PtRu nanowires for hydrogen oxidation catalysis.

Bimetallic PtRu are promising electrocatalysts for hydrogen oxidation reaction in anion exchange membrane fuel cell, where the activity and stability are still unsatisfying. Here, PtRu nanowires were implanted with a series of oxophilic metal atoms (named as i-M-PR), significantly enhancing alkaline hydrogen oxidation reaction (HOR) activity and stability. With the dual doping of In and Zn atoms, the i-ZnIn-PR/C shows mass activity of 10.2 A mgPt+Ru-1 at 50 mV, largely surpassing that of commercial Pt/C (0.27 A mgPt-1) and PtRu/C (1.24 A mgPt+Ru-1). More importantly, the peak power density and specific power density are as high as 1.84 W cm-2 and 18.4 W mgPt+Ru-1 with a low loading (0.1 mg cm-2) anion exchange membrane fuel cell. Advanced experimental characterizations and theoretical calculations collectively suggest that dual doping with In and Zn atoms optimizes the binding strengths of intermediates and promotes CO oxidation, enhancing the HOR performances. This work deepens the understanding of developing novel alloy catalysts, which will attract immediate interest in materials, chemistry, energy and beyond.

Novel biological insights revealed from the investigation of multiscale genome architecture.

Gene expression and cell fate determination require precise and coordinated epigenetic regulation. The complex three-dimensional (3D) genome organization plays a critical role in transcription in myriad biological processes. A wide range of architectural features of the 3D genome, including chromatin loops, topologically associated domains (TADs), chromatin compartments, and phase separation, together regulate the chromatin state and transcriptional activity at multiple levels. With the help of 3D genome informatics, recent biochemistry and imaging approaches based on different strategies have revealed functional interactions among biomacromolecules, even at the single-cell level. Here, we review the occurrence, mechanistic basis, and functional implications of dynamic genome organization, and outline recent experimental and computational approaches for profiling multiscale genome architecture to provide robust tools for studying the 3D genome.

In-depth understanding of higher-order genome architecture in orphan cancer.

The human genome is intertwined, folded, condensed, and gradually constitutes the 3D architecture, thereby affecting transcription and widely involving in tumorigenesis. Incidence and mortality rates for orphan cancers increase due to poor early diagnosis and lack of effective medical treatments, which are now getting attention. In-depth understanding in tumorigenesis has fast-tracked over the last decade, however, the further role and mechanism of 3D genome organization in variant orphan tumorigenesis remains to be fully understood. We summarize for the first time that higher-order genome organization can provide novel insights into the occurrence mechanisms of orphan cancers, and discuss probable future research directions for drug development and anti-tumor therapies.

Direct observation of the dynamic reconstructed active phase of perovskite LaNiO3 for the oxygen-evolution reaction.

Ni-based transition metal oxides are promising oxygen-evolution reaction (OER) catalysts due to their abundance and high activity. Identification and manipulation of the chemical properties of the real active phase on the catalyst surface is crucial to improve the reaction kinetics and efficiency of the OER. Herein, we used electrochemical-scanning tunnelling microscopy (EC-STM) to directly observe structural dynamics during the OER on LaNiO3 (LNO) epitaxial thin films. Based on comparison of dynamic topographical changes in different compositions of LNO surface termination, we propose that reconstruction of surface morphology originated from transition of Ni species on LNO surface termination during the OER. Furthermore, we showed that the change in surface topography of LNO was induced by Ni(OH)2/NiOOH redox transformation by quantifying STM images. Our findings demonstrate that in situ characterization for visualization and quantification of thin films is very important for revealing the dynamic nature of the interface of catalysts under electrochemical conditions. This strategy is crucial for in-depth understanding of the intrinsic catalytic mechanism of the OER and rational design of high-efficiency electrocatalysts.

Effects of Endogenous Non-Starch Nutrients in Acorn (Quercus wutaishanica Blume) Kernels on the Physicochemical Properties and In Vitro Digestibility of Starch.

The present study investigated the multi-scale structure of starch derived from acorn kernels and the effects of the non-starch nutrients on the physicochemical properties and in vitro digestibility of starch. The average polymerization degree of acorn starch was 27.3, and the apparent amylose content was 31.4%. The crystal structure remained as C-type but the relative crystallinity of acorn flour decreased from 26.55% to 25.13%, 25.86% and 26.29% after the treatments of degreasing, deproteinization, and the removal of ß-glucan, respectively. After the above treatments, the conclusion temperature of acorn flour decreased and had a significant positive correlation with the decrease in the crystallinity. The aggregation between starch granules, and the interactions between starch granules and both proteins and lipids, reduced significantly after degreasing and deproteinization treatments. The endogenous protein, fat, and ß-glucan played key roles in reducing the digestibility of acorn starch relative to other compounds, which was dictated by the ability for these compounds to form complexes with starch and inhibit hydrolysis.

Interruption of aberrant chromatin looping is required for regenerating RB1 function and suppressing tumorigenesis.

RB transcriptional corepressor 1 (RB1) is a critical regulatory gene in physiological and pathological processes. Genetic mutation is considered to be the main cause of RB1 inactivation. However, accumulating evidence has shown that not all RB1 dysfunction is triggered by gene mutations, and the additional mechanism underlying RB1 dysfunction remains unclear. Here, we firstly reveal that a CCCTC binding factor (CTCF) mediated intrachromosomal looping served as a regulatory inducer to inactivate RB1. Once the core genomic fragment was deleted by Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR/Cas9), this intrachromosomal looping was disrupted. After the open of chromatin, Enhancer of Zeste Homolog 2 (EZH2) was released and decreased the level of Tri-Methyl-Histone H3 Lys27 (H3K27me3) at the RB1 promoter, which substantially restored the expression of RB protein (pRB) and inhibited tumorigenesis. In addition, targeted correction of abnormal RB1 looping using the small-molecule compound GSK503 efficiently restored RB1 transcription and suppressed tumorigenesis. Our study reveals an alternative transcriptional mechanism underlying RB1 dysfunction independent of gene mutation, and advancing the discovery of potential therapeutic chemicals based on aberrant chromatin looping.

Ascorbic acid protects the toxic effects of aflatoxin B1 on yak oocyte maturation.

High-quality oocytes are a prerequisite for successful fertilization. Mammals feeding on aflatoxin-contaminated feed can cause reproductive toxicity, including follicular atresia, poor oocyte development and maturation, and aberrant epigenetic modifications of oocytes. In addition, the important role of ascorbic acid (AA) in reproductive biology has been confirmed, and AA is widely used as an antioxidant in cell culture. However, the toxic effects of aflatoxin B1 (AFB1 ) on yak oocytes and whether AA has protective effects remain unknown. In this study, we found that exposure to AFB1 impedes meiotic maturation of oocytes, promotes apoptosis by triggering high levels of reactive oxygen species (ROS), and disrupts mitochondrial distribution and actin integrity, resulting in a decrease in the fertilization ability and parthenogenetic development ability of oocytes. In addition, these injuries changed the DNA methylation transferase transcription level of mature oocytes. After adding 50 µg/ml AA, the indices recovered to levels close to those of the control group. The results showed that AA could protect yak oocytes from the toxic effects of AFB1 and improve the quality of oocytes.

Honokiol Reduces Mitochondrial Dysfunction and Inhibits Apoptosis of Nerve Cells in Rats with Traumatic Brain Injury by Activating the Mitochondrial Unfolded Protein Response.

This study was designed to determine the effects and underlying mechanism of honokiol (HNK) on traumatic brain injury (TBI). A rat TBI model was constructed using the modified Feeney free-fall percussion method and treatment with HNK via intraperitoneal injection. The brain tissues of the rats in each group were assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay to detect the level of neuronal apoptosis. Western blots were used to detect the expression levels of apoptosis-related proteins (Bcl-2 and Bax), and ELISAs were used to measure the levels of pro-inflammatory cytokines (IL-18 and IL-1ß) and the activity of caspase-1. In addition, the mitochondrial membrane potential, reactive oxygen species (ROS), and adenosine 5'-triphosphate (ATP) were also measured. Western blots and qRT-PCRs were used to determine the relative expression levels of the mitochondrial unfolded protein response (UPRmt)-related proteins and mRNAs. Based on the experimental results, treatment with HNK was associated with a decrease in the number of TUNEL-positive cells, downregulated Bax expression levels, elevated Bcl-2 expression levels, and inhibition of neuronal apoptosis in the brain tissue of TBI rats. HNK also suppressed neuroinflammation by decreasing IL-1ß and IL-18 levels and caspase-1 activity. Additionally, HNK lowered the mitochondrial membrane potential and ROS levels, increased ATP levels, and improved mitochondrial dysfunction in neural cells. Furthermore, in the investigation of the mechanism of HNK on TBI, we observed that HNK could activate UPRmt by upregulating the mRNA and protein expression levels of HSPA9, CLPP, and HSP60 in the brain tissues of TBI rats. Collectively, HNK reduced mitochondrial dysfunction, inhibited the apoptosis of nerve cells, and attenuated inflammation in the brains of TBI rats. The protective effect of HNK may be achieved through the activation of UPRmt.

Leukemia inhibitory factor enhances the development and subsequent blastocysts quality of yak oocytes in vitro.

Leukemia inhibitory factor (LIF) is a multipotent cytokine of the IL-6 family which plays a critical role in the maturation and development of oocytes. This study evaluated the influence of LIF on the maturation and development ability of yak oocytes, and the quality of subsequent blastocysts under in vitro culture settings. Different concentrations of LIF (0, 25, 50, and 100 ng/mL) were added during the in vitro culture of oocytes to detect the maturation rate of oocytes, levels of mitochondria, reactive oxygen species (ROS), actin, and apoptosis in oocytes, mRNA transcription levels of apoptosis and antioxidant-related genes in oocytes, and total cell number and apoptosis levels in subsequent blastocysts. The findings revealed that 50 ng/mL LIF could significantly increase the maturation rate (p < 0.01), levels of mitochondria (p < 0.01) and actin (p < 0.01), and mRNA transcription levels of anti-apoptotic and antioxidant-related genes in yak oocytes. Also, 50 ng/mL LIF could significantly lower the generation of ROS (p < 0.01) and apoptosis levels of oocytes (p < 0.01). In addition, blastocysts formed from 50 ng/mL LIF-treated oocytes showed significantly larger total cell numbers (p < 0.01) and lower apoptosis rates (p < 0.01) than the control group. In conclusion, the addition of LIF during the in vitro maturation of yak oocytes improved the quality and the competence of maturation and development in oocytes, as well as the quality of subsequent blastocysts. The result of this study provided some insights into the role and function of LIF in vitro yak oocytes maturation, as well as provided fundamental knowledge for assisted reproductive technologies in the yak.

Effect of rapamycin treatment on oocyte in vitro maturation and embryonic development after parthenogenesis in yaks.

Autophagy plays an important role in mammalian oocyte maturation and early embryonic development and rapamycin is well known for inducing autophagy. Although previous studies have reported the effects of rapamycin on oocytes in vitro maturation (IVM) in different species, few studies have been reported on the role of rapamycin in yak oocytes IVM and embryonic development. Therefore, the objective of this study was to examine the effect of rapamycin treatment on yak oocytes IVM and early embryonic development. Specifically, immature yak oocytes during IVM or parthenogenetic (PA) embryos were treated with different rapamycin concentrations to select an optimal dose. Then evaluated its effect on maturation rates, cleavage, and blastocyst formation rates, mitochondrial membrane potential, ROS levels. Related genes and proteins expression in matured oocytes and blastocysts were also evaluated. The results show that 10 nM rapamycin treatment during IVM significantly improved oocyte maturation rates of oocytes and blastocyst formation rates. Treatment with 10 nM rapamycin reduced ROS level but increased mitochondrial membrane potential. Correspondingly, mRNA and protein expressions of LC3, Beclin-1, and Bcl-2 up-regulated while Bax down-regulated in matured yak COCs. When parthenogenetic embryos were treated with different rapamycin concentrations, 10 nM rapamycin treatment showed higher 8-cell and blastocyst formation rates. Also, CDX2, POU5F1, SOX2, and Nanog levels in blastocysts were upregulated. In summary, our findings demonstrate that rapamycin treatment improves oocytes maturation probably by increasing mitochondrial membrane potential, reducing ROS levels, and regulating the apoptosis in mature yak oocytes. Rapamycin treatment also improves embryonic developmental competence in the yak.

Transcriptome sequencing reveals differences between leydig cells and sertoli cells of yak.

In this study, we detected the expression of mRNAs, lncRNAs, and miRNAs in primary cultured leydig cells (LCs) and sertoli cells (SCs) of yak by RNA sequencing technology. A total of 84 differently expression mRNAs (DEmRNAs) (LCs vs. SCs: 15 up and 69 down), 172 differently expression lncRNAs (DElncRNAs) (LCs vs. SCs: 36 up and 136 down), and 90 differently expression miRNAs (DEmiRNAs) (LCs vs. SCs: 72 up and 18 down) were obtained between the two types of cells. GO enrichment and KEGG analysis indicated that the differential expression genes (DEGs) were more enriched in the regulation of actin cytoskeleton, Rap1/MAPK signaling pathway, steroid biosynthesis, focal adhesion, and pathways associated with metabolism. Targeted regulation relationship pairs of 3ß-HSD and MSTRG.54630.1, CNTLN and MSTRG.19058.1, BRCA2 and MSTRG.28299.4, CA2 and novel-miR-148, and ceRNA network of LAMC3-MSTRG.68870.1- bta-miR-7862/novel-miR-151/novel-miR-148 were constructed by Cytoscape software. In conclusion, the differences between LCs and SCs were mainly reflected in steroid hormone synthesis, cell proliferation and metabolism, and blood-testicular barrier (BTB) dynamic regulation, and 3ß-HSD, CNTLN, BRCA2, CA2, and LAMC3 may be the key factors causing these differences, which may be regulated by ncRNAs. This study provides a basic direction for exploring the differential regulation of LCs and SCs by ncRNAs.

Insight Into Chromatin-Enriched RNA: A Key Chromatin Regulator in Tumors.

Chromatin-enriched RNAs (cheRNAs) constitute a special class of long noncoding RNAs (lncRNAs) that are enriched around chromatin and function to activate neighboring or distal gene transcription. Recent studies have shown that cheRNAs affect chromatin structure and gene expression by recruiting chromatin modifiers or acting as bridges between distal enhancers and promoters. The abnormal transcription of cheRNAs plays an important role in the occurrence of many diseases, particularly tumors. The critical effect of cancer stem cells (CSCs) on the formation and development of tumors is well known, but the function of cheRNAs in tumorigenesis, especially in CSC proliferation and stemness maintenance, is not yet fully understood. This review focuses on the mechanisms of cheRNAs in epigenetic regulation and chromatin conformation and discusses the way cheRNAs function in CSCs to deepen the understanding of tumorigenesis and provide novel insight to advance tumor-targeting therapy.

Probe Confined Dynamic Mapping for G Protein-Coupled Receptor Allosteric Site Prediction.

Targeting G protein-coupled receptors (GPCRs) through allosteric sites offers advantages over orthosteric sites in identifying drugs with increased selectivity and potentially reduced side effects. In this study, we developed a probe confined dynamic mapping protocol that allows the prediction of allosteric sites at both the GPCR extracellular and intracellular sides, as well as at the receptor-lipid interface. The applied harmonic wall potential enhanced sampling of probe molecules in a selected area of a GPCR while preventing membrane distortion in molecular dynamics simulations. The specific probes derived from GPCR allosteric ligand structures performed better in allosteric site mapping compared to commonly used cosolvents. The M2 muscarinic, ß2 adrenergic, and P2Y1 purinergic receptors were selected for the protocol's retrospective validation. The protocol was next validated prospectively to locate the binding site of [5-fluoro-4-(hydroxymethyl)-2-methoxyphenyl]-(4-fluoro-1H-indol-1-yl)methanone at the D2 dopamine receptor, and subsequent mutagenesis confirmed the prediction. The protocol provides fast and efficient prediction of key amino acid residues surrounding allosteric sites in membrane proteins and facilitates the structure-based design of allosteric modulators.

Multi-Omics Analysis of the Therapeutic Value of MAL2 Based on Data Mining in Human Cancers.

Recent studies have reported that T-cell differentiation protein 2 (MAL2) is an important regulator in cancers. Here, we downloaded data from multiple databases to analyze MAL2 expression and function in pan-cancers, especially in ovarian cancer (OC). Gene Expression Profiling Interactive Analysis (GEPIA) databases was used to examine MAL2 expression in 13 types of cancer. Kaplan-Meier plotter database was used to analyze the overall survival rate of MAL2 in pan-cancers. The Catalog of Somatic Mutations in Cancer (COSMIC), cBioPortal, and UCSC databases were used to examine MAL2 mutation in human cancers. Metascape, STRING, and GeneMANIA websites were used to explore MAL2 function in OC. Furthermore, ggplot2 package and ROC package were performed to analyze hub gene expression and undertake receiver operating characteristic (ROC) analysis. Drug sensitivity of MAL2 in OC was examined by the GSCALite database. In order to verify the results from databases above, real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting were conducted to detect the expression of MAL2 in OC cells. CRISPR/Cas9 system was used to knockout the MAL2 gene in the OC cell lines HO8910 and OVCAR3, using specific guide RNA targeting the exons of MAL2. Then, we performed proliferation, colony formation, migration, and invasion assays to investigate the impact of MAL2 in OC cell lines in vivo and in vitro. Epithelial-mesenchymal transition (EMT)-associated biomarkers were significantly altered in vitro via western blotting and qRT-PCR. Taken together, we observed that MAL2 was remarkably dysregulated in multiple cancers and was related to patient overall survival (OS), mutation, and drug sensitivity. Furthermore, experimental results showed that MAL2 deletion negatively regulated the proliferation, migration, invasion, and EMT of OC, indicating that MAL2 is a novel oncogene that can activate EMT, significantly promote both the proliferation and migration of OC in vitro and in vivo, and provide new clues for treatment strategies.

Efficient aqueous processing and utilization of high-quality graphene for high performance supercapacitor electrode.

High quality graphene (HQG) offers unconventional properties and is desirable for a variety of applications. However, facile solution processing (especially in water) and chemical bonding of functional components with the aim of achieving high-yield, green, and controllable synthesis of advanced graphene materials are of great concern. Herein, the surface chemistry of HQG is effectively tailored using a hydrophobic-driven assembly of cellulose macromolecules (CM) with various functionalities. In contrast to bulk or nanocellulose modifiers, surface engineering of HQG with densely carboxyl grafted CM renders stable aqueous graphene colloids via electrostatic repulsion. It also enables the use of efficient, low-cost, aqueous-phase synthetic techniques to create new HQG-based materials and devices. Highly exposed and reactive carboxyl and hydroxyl groups lead to in situ formation of evenly distributed Co3O4 nanoparticles on HQG sheets (HQG-COOH-Co3O4). We further demonstrate the potential application of two-dimensional HQG-COOH-Co3O4 heterostructures as supercapacitor electrodes with high power and energy density.