High aspect ratio cellulose nanofibrils with low crystallinity for strong and tough films.

Cellulose nanofibril (CNF) films with both high strength and high toughness are attractive for applications in energy, packaging, and flexible electronics. However, simultaneously achieving these mechanical properties remains a significant challenge. Herein, a multiscale structural optimization strategy is proposed to prepare high aspect ratio CNFs with reduced crystallinity for strong and tough films. Carboxymethylation coupled with mild mechanical disintegration is employed to modulate the multiscale structure of CNFs. The as-prepared CNFs feature an aspect ratio of >800 and a crystallinity of <60 %. The film prepared using CNFs with a high aspect ratio (~1100) and reduced crystallinity (~54 %) exhibits a tensile strength of 229.9 ± 9.9 MPa and toughness of 22.2 ± 1.4 MJ/m3. The underlying mechanism for balancing these mechanical properties is unveiled. The high aspect ratio of the CNFs facilitates the transfer and distribution of local stress, thus endowing the corresponding film with high strength and toughness. Moreover, the low crystallinity of the CNFs permits the movement of the cellulose chains in the amorphous regions, thereby dissipating energy and finally increasing the film toughness. This work introduces an innovative and straightforward method for producing strong and tough CNF films, paving the way for their broader applications.

Super foldable transparent paper by regulating the multi-scale structure of cellulose fibers.

Transparent cellulose papers have emerged as a promising substrate and/or functional component for next-generation sustainable flexible electronics. However, obtaining transparent paper with folding endurance comparable to that of plastic films such as polyethylene terephthalate (PET) remains a major challenge, which was addressed in this study by modulating the multiscale structure (from molecular structure, aggregation structure to fibrous morphology) of wood fibers. Compared to the natural wood fibers, the modified fibers not only retained their length and cellulose degree of polymerization (DP) to a large extent, but also had lower crystallinity and improved swelling capability, which well preserved the fiber strength and dense intertwined fiber network, and led to stronger inter-fiber interactions in the final transparent paper. The obtained paper (CM-paper) exhibits an optical transparency of 91 % and a folding endurance of 37,466 times, comparable to that of commercial PET (39,955 folds). Furthermore, the underlying mechanism for the superior foldability of the transparent paper was unveiled at three scales is explored. Finally, the potential application of CM-paper in electromagnetic induction electrodes was demonstrated, where the CM-paper electrodes exhibit satisfactory conductivity after repeated rubbing. This work offers an innovative approach to produce transparent papers with outstanding foldability, which is expected to plastic replacement.

The Critical Role of Ca2+ in Improving the Transparency and Strength of High-Filler-Content Nanocellulose/Montmorillonite Nanocomposite Films.

Strong and transparent nanocellulose/montmorillonite (MMT) nanocomposite films with high filler content (≥50 wt %) are emerging as versatile materials for advanced applications due to their excellent optical, barrier, mechanical, and thermal properties, and environmental friendliness. Nonetheless, these films undergo a notable decline in optical and mechanical properties at high MMT loadings. This study first demonstrates that calcium-ion-induced tactoids are the key factor causing disordered structures in nanocomposite films, leading to the degradation of optical and mechanical properties. We then address this issue by employing a Ca2+ removal strategy─dialysis. Through removing 43% of free Ca2+, simultaneous improvements in both properties are observed. For example, in a nanocomposite film with 70 wt % MMT, light transmittance increases from 75.9 to 91.6%, and the tensile strength rises from 100.4 to 139.4 MPa. This work offers insights into developing strong and transparent nanocomposite films with high MMT contents.

NIR-Driven Self-Healing Phase-Change Solid Slippery Surface with Stability and Promising Antifouling and Anticorrosion Properties.

Slippery liquid-infused porous surfaces (SLIPSs) have great potential to replace traditional antifouling coatings due to their efficient, green, and broad-spectrum antifouling performance. However, the lubricant dissipation problem of SLIPS severely restricts its further development and application, and the robust SLIPS continues to be extremely challenging. Here, a composite phase-change lubricant layer consisting of paraffin, silicone oil, and MXene is designed to readily construct a stable and NIR-responsive self-healing phase-change solid slippery surface (PCSSS). Collective results showed that PCSSS could rapidly achieve phase-change transformation and complete self-healing under NIR irradiation and keep stable after high-speed water flushing, centrifugation, and ultrasonic treatment. The antifouling performance of PCSSS evaluated by protein, bacteria, and algae antiadhesion tests demonstrated the adhesion inhibition rate was as high as 99.99%. Moreover, the EIS and potentiodynamic polarization experiments indicated that PCSSS had stable and exceptional corrosion resistance (|Z|0.01Hz = 3.87 × 108 Ω·cm2) and could effectively inhibit microbiologically influenced corrosion. The 90 day actual marine test reveals that PCSSS has remarkable antifouling performance. Therefore, PCSSS presents a novel, facile, and effective strategy to construct a slippery surface with the prospect of facilitating its application in marine antifouling and corrosion protection.

Endoplasmic reticulum stress response modulator OsbZIP39 regulates cadmium accumulation via activating the expression of defensin-like gene OsCAL2 in rice.

Accumulation of cadmium (Cd) in rice is not only harmful to the growth of plants but also poses a threat to human health. Exposure to Cd triggers unfolded protein response (UPR) within cells, a process that is still not completely understood. The study demonstrated that the lack of OsbZIP39, an essential endoplasmic reticulum (ER)-resident regulator of the UPR, resulted in decreased Cd intake and reduced Cd levels in the roots, stems, and grains of rice. Upon exposure to Cd stress, GFP-OsbZIP39 translocated from ER to nucleus, initiating UPR. Further investigation revealed that Cd treatment caused changes in sphingolipid levels in the membrane, influencing the localization and activation of OsbZIP39. Yeast one-hybrid and dual-LUC assays were conducted to validate the interaction between activated OsbZIP39 and the promoter of the defensin-like gene OsCAL2, resulting in an increase in its expression. Different variations were identified in the coding region of OsbZIP39, which may explain the varying levels of Cd accumulation observed in the indica and japonica subspecies. Under Cd treatment, OsbZIP39ind exhibited a more significant enhancement in the transcription of OsCAL2 compared to OsbZIP39jap. Our data suggest that OsbZIP39 positively regulates Cd uptake in rice, offering an encouraging objective for the cultivation of low-Cd rice.

Strong Yet Tough Transparent Paper with Superb Foldability.

Transparent paper manufactured from wood fibers is emerging as a promising, cost-effective, and carbon-neutral alternatives to plastics. However, fully exploring their mechanical properties is one of the most pressing challenges. In this work, a strong yet tough transparent paper with superior folding endurance is prepared by rationally altering the native fiber structure. Microwave-assisted choline chloride/lactic acid deep eutectic solvent (DES) pulping is first utilized to isolate wood fibers from spruce wood. During this process, the S1 layer within the fibers is partially disrupted, forming protruding microfibrils that play a crucial role in enhancing cellulose accessibility. Subsequently, carboxymethylation treatment is applied to yield uniformly swollen carboxymethylated wood fibers (CM fibers), which improves the interaction between CM fibers during papermaking. The as-prepared transparent paper not only shows a 90% light transmittance (550 nm) but also exhibits impressive mechanical properties, including a folding endurance of over 26 000, a tensile strength of 248.4 MPa, and a toughness of 15.6 MJ m-3. This work provides a promising route for manufacturing transparent paper with superior mechanical properties from wood fibers and can extend their use in areas normally dominated by high-performance nonrenewable plastics.

All-Wood-Based Ionic Power Generator with Dual Functions for Alkaline Wastewater Reuse and Energy Harvesting.

Water-induced electricity harvesting has gained much significance for energy sustainability. Bio-based hydrovoltaic materials increase the attractiveness of this strategy. Although promising, it faces a challenge due to its reliance on fresh water and its inherently low power output. Herein, the energy from alkalinity-gradient power generation demonstrated the feasibility of reuse of alkaline wastewater to develop an all-wood-based water-induced electric generator (WEG) based on ion concentration gradients. The intermittent water droplets bring about uneven distribution of electrolyte and endow delignified wood with the difference of ion concentration along aligned cellulose nanochannels, thus supplying electrical power. The practice of using alkali reservoirs, including industrial wastewater, further contributes to electricity generation. The cubic WEG with a side length of 2 cm can produce an ultrahigh open-circuit voltage of about 1.1 V and a short-circuit current of up to 320 µA. A power output of 6.75 µW cm-2 is correspondingly realized. Series-connected WEGs can be used as an energy source for commercial electronics and self-powered systems. Our design provides a double value proposition, allowing for sustainable energy generation and wastewater reuse.

Self-assembled high polypyrrole loading flexible paper-based electrodes for high-performance supercapacitors.

Despite the intriguing features of freestanding flexible electronic devices, such as their binder-free nature and cost-effectiveness, the limited loading capacity of active material poses a challenge to achieving practical high-performance flexible electrodes. We propose a novel approach that integrates multiple self-assembly and in-situ polymerization techniques to fabricate a high-loading paper-based flexible electrode (MXene/Polypyrrole/Paper) with exceptional areal capacitance. The approach enables polypyrrole to form a porous conductive network structure on the surface of paper fiber through MXene grafting via hydrogen bonding and electrostatic interaction, resulting in an exceptionally high polypyrrole loading of 10.0 mg/cm2 and a conductivity of 2.03 S/cm. Moreover, MXene-modified polypyrrole paper exhibits a more homogeneous pore size distribution ranging from 5 to 50 µm and an increased specific surface area of 3.11 m2/g. Additionally, we have optimized in-situ polymerization cycles for paper-based supercapacitors, resulting in a remarkable areal capacitance of 2316 mF/cm2 (at 2 mA/cm2). The capacitance retention rate and conductivity rate maintain over 90 % after undergoing 100 bends.The maximum energy density and cycling stability are characterized to be 83.6 µWh/cm2 and up to 96 % retention after 10,000 cycles. These results significantly outperform those previously reported for paper-based counterparts. Overall, our work presents a facile and versatile strategy for assembling high-loading, paper-based flexible supercapacitors network architecture that can be employed in developing large-scale energy storage devices.

Advanced Marine Antifouling Hydrogels Based on 7-Amino-4-methylcoumarin Fluorescence Driven by Rare-Earth Phosphorescence.

At present, there are very few reports on the combination of phosphorescence and fluorescence in the field of pollution prevention. A composite antibacterial agent was designed to store energy by using the phosphorescence effect of rare earth oxides, emit light at night, and stimulate 7-amino-4-methylcoumarin to produce fluorescence and prevent algae from adhering. When complexed with PVA, it exhibited excellent characteristics as an all-weather autocatalytic phosphorescence-fluorescence antifouling hydrogel. The rare earth phosphorescent powder was prepared in a high-temperature tube furnace, coated with SiO2 on the surface for waterproofing, and then grafted with 7-amino-4-methylcoumarin to obtain a composite antibacterial agent with a phosphorescence-fluorescence effect. The composite antibacterial agent was added with PVA to obtain a hydrogel, which exhibited bactericidal rates of more than 99.98% against both Gram-positive and Gram-negative bacteria after 48 h. The results of fluorescence staining showed that the coverage rate of dead bacteria reached 41.6% after 24 h. The tensile strength of the antifouling hydrogel is up to 1.49 MPa, which is strong enough for real marine environments. Moreover, the algae coverage area of the composite hydrogel under natural light was only 2.7%, representing a 10-fold reduction compared with the control. The antifouling hydrogel has good antipollution and algae suppression performance, which is due to the fact that the rare earth phosphorescent powder when exposed to sunlight can provide a light source to stimulate 7-amino-4-methylcoumarin fluorescence at night and thereby prevent algae adhesion. After testing in the marine field and the real sea test when wrapped in a fishing net, the excellent antifouling performance was demonstrated. The functional hydrogel has great application potential in the protection of seawater-exposed structures, such as bridges and bay ports.

GRSF1 antagonizes age-associated hypercoagulability via modulation of fibrinogen mRNA stability.

Age-associated hypercoagulability is accompanied by the increase of plasma levels of some coagulation factors including fibrinogen which may contribute to the increased risk of cardiovascular, cerebrovascular, and thrombotic diseases in elderly people. However, the underlying mechanism of increased plasma fibrinogen concentration during aging is still elusive. GRSF1 belongs to the heterogeneous nuclear ribonucleoproteins F/H (hnRNP F/H) subfamily. Here, we report that GRSF1 attenuates hypercoagulability via negative modulation of fibrinogen expression. We demonstrated that GRSF1 negatively regulated fibrinogen expression at both mRNA and protein levels. GRSF1 directly interacted with the coding region (CDS) of FGA, FGB, and FGG mRNAs, and decreased their stability thus mitigating fibrinogen expression. We further identified that only a few G-tracts within the Fib C domain of FGA, FGB, and FGG CDS and the qRRM2 domain of GRSF1 were required for their interaction. Moreover, we confirmed hypercoagulability and the decrease of GRSF1 expression level during mice aging. Functionally, GRSF1 overexpression in old mice liver decreased fibrinogen plasma level, reduced hypercoagulability, and mitigated blood coagulation activity, whereas GRSF1 knockdown in young mice liver increased fibrinogen plasma level and promoted blood coagulation activity. Collectively, our findings unveil a novel posttranscriptional regulation of fibrinogen by GRSF1 and uncover a critical role of GRSF1 in regulating blood coagulation activity.

Relationships among sporophytic and gametophytic traits of 27 subtropical montane moss species.

PREMISE: Moss sporophytes differ strongly in size and biomass partitioning, potentially reflecting reproductive and dispersal strategies. Understanding how sporophyte traits are coordinated is essential for understanding moss functioning and evolution. This study aimed to answer: (1) how the size and proportions of the sporophyte differ between moss species with and without a prominent central strand in the seta, (2) how anatomical and morphological traits of the seta are related, and (3) how sporophytic biomass relates to gametophytic biomass and nutrient concentrations. METHODS: We studied the relationships between seta anatomical and morphological traits, the biomass of seta, capsule, and gametophyte, and carbon, nitrogen, and phosphorus concentrations of 27 subtropical montane moss species. RESULTS: (1) Moss species with a prominent central strand in the seta had larger setae and heavier capsules than those without a prominent strand. (2) With increasing seta length, setae became thicker and more rounded for both groups, while in species with a prominent central strand, the ratio of transport-cell area to epidermal area decreased. (3) In both groups, mosses with greater gametophytic biomass tended to have heavier sporophytes, but nitrogen and phosphorus concentrations in the gametophyte were unrelated to sporophytic traits. CONCLUSIONS: Our study highlights that the central strand in the seta may have an important functional role and affect the allometry of moss sporophytes. The coordinated variations in sporophyte morphological and anatomical traits follow basic biomechanical principles of cylinder-like structures, and these traits relate only weakly to the gametophytic nutrient concentrations. Research on moss sporophyte functional traits and their relationships to gametophytes is still in its infancy but could provide important insights into their adaptative strategies.

Exploring the material basis and mechanism of action of clinacanthus nutans in treating renal cell carcinoma based on metabolomics and network pharmacology.

BACKGROUND: Clinacanthus nutans (for abbreviation thereafter) is often used as medicine in the form of fresh juice in the folk to treat many kinds of cancers, including renal cell carcinoma (RCC). It is speculated that its active ingredient may have heat sensitivity, but there are currently no reports on this aspect. Therefore, based on the folk application for fresh juice of C nutans, this study used metabonomics and network pharmacology to explore the material basis and mechanism of action of C nutans against RCC. METHODS: Firstly, untargeted metabolomics profiling was performed by Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry to screen the metabolites down-regulated by heat in the extract of C nutans. Secondly, we collected the targets of metabolites in the Swiss Target Prediction platform. In addition, the targets of RCC were obtained in the GeneCards database. The "component-target-disease" network was established by Cytoscape3.9.0 software. Then we constructed a protein-protein interaction network in the STRING network platform to screen core targets. The gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis of core targets were carried out to predict the relevant pathway of C nutans in the treatment of RCC. Finally, the molecular docking verification of the core targets were carried out. RESULTS: In this study, 35 potential active ingredients and 125 potential targets were obtained. And the core targets were Cellular tumor antigen p53, Signal transducer and activator of transcription 3, and so on. Then, 48 biological processes, 30 cell components, and 36 molecular functions were obtained by gene ontology enrichment analysis. Besides, 44 pathways were obtained by Kyoto encyclopedia of genes and genomes enrichment analysis, including Pathway in cancer, PI3K-Akt signal pathway, P53 signal pathway, and so on. The docking model between the core target and its corresponding components was stable. CONCLUSION: This research is based on the folk application of C nutans, showed its potential active ingredients by metabonomics, and predicted the potential mechanism of C nutans in the treatment of RCC by network pharmacology. It provides new references for follow-up research and new drug development.

Large-scale and stacked transfer of bilayers MoS2devices on a flexible polyimide substrate.

Two-dimensional transition metal dichalcogenides (TMDs), as flexible and stretchable materials, have attracted considerable attention in the field of novel flexible electronics due to their excellent mechanical, optical, and electronic properties. Among the various TMD materials, atomically thin MoS2has become the most widely used material due to its advantageous properties, such as its adjustable bandgap, excellent performance, and ease of preparation. In this work, we demonstrated the practicality of a stacked wafer-scale two-layer MoS2film obtained by transferring multiple single-layer films grown using chemical vapor deposition. The MoS2field-effect transistor cell had a top-gated device structure with a (PI) film as the substrate, which exhibited a high on/off ratio (108), large average mobility (∼8.56 cm2V-1s-1), and exceptional uniformity. Furthermore, a range of flexible integrated logic devices, including inverters, NOR gates, and NAND gates, were successfully implemented via traditional lithography. These results highlight the immense potential of TMD materials, particularly MoS2, in enabling advanced flexible electronic and optoelectronic devices, which pave the way for transformative applications in future-generation electronics.

Dispersing boron nitride nanosheets with carboxymethylated cellulose nanofibrils for strong and thermally conductive nanocomposite films with improved water-resistance.

BNNS (boron nitride nanosheets)-CNF (cellulose nanofibrils) nanocomposite films have attracted increasing attention for advanced thermal management applications. However, the nanocomposite films reported so far generally suffer from unsatisfactory overall performance, especially for thermal conductivity and tensile strength. In this work, a nanocomposite film with excellent overall performance was prepared by using CCNF1.2 (carboxymethylated CNF with 1.2 mmol·g-1 carboxyl content) simultaneously as effective dispersant and reinforcement matrix for BNNS. The high aspect ratio of CCNF1.2 is primarily responsible for its excellent dispersion capability for BNNS, which provides strong steric hindrance repulsion force. Meanwhile, CCNF1.2 manifests the strongest hydrophobic-hydrophobic interactions with BNNS, and its carboxyl groups completely interact with the -OH of BNNS by hydrogen bonding. As a result, the BNNS-CCNF1.2 film (50 wt% BNNS) exhibits compacted aligned structure and superior comprehensive performance (125.0 MPa tensile strength, 17.3 W·m-1·K-1 in-plane thermal conductivity, and improved water resistance). This work demonstrates the effectiveness of CCNF in improving the overall performance of BNNS-CNF films and paves the way for their practical application in the advanced thermal management of next-generation electronic devices.

Combining Ability Analysis of Yield-Related Traits of Two Elite Rice Restorer Lines in Chinese Hybrid Rice.

Hybrid rice breeding is an important strategy for enhancing grain yield. Breeding high-performance parental lines and identifying combining abilities is a top priority for hybrid breeding. Yuenongsimiao (YNSM) and its derivative variety Yuehesimiao (YHSM) are elite restorer lines with a high ability of fertility restoration, from which 67 derived hybrid combinations have been authorized to different degrees in more than 110 instances in China. In this study, we found that YNSM and YHSM contained three candidate restorer-of-fertility (Rf) genes, Rf3, Rf4, and Rf5/Rf1a, that might confer their restoration ability. Subsequently, we investigated heterosis and combining ability of YNSM and YHSM using 50 F1 hybrids from a 5 × 10 incomplete diallelic mating design. Our results indicated that hybrid combinations exhibited significant genetic differences, and the additive effects of the parental genes played a preponderant role in the inheritance of observed traits. The metrics of plant height (PH), 1000-grain weight (TGW), panicle length (PL), and the number of spikelets per panicle (NSP) were mainly affected by genetic inheritance with higher heritability. Notably, the general combining ability (GCA) of YHSM exhibited the largest positive effect on the number of grains per panicle (NGP), NSP, PL, and TGW. Thus, YHSM had the largest GCA effect on yield per plant (YPP). In addition, the GCA of YNSM exhibited a positive impact on YPP, mainly due to the critical contribution of seed setting percentage (SSP). Moreover, YNSM and YHSM exhibited negative GCA effects on PH, implying that YNSM and YHSM could effectively enhance plant lodging resistance by reducing the plant height of the derived hybrids. Remarkably, among the hybrids, Yuanxiang A/YNSM (YXA/YNSM), Shen 08S/Yuemeizhan (S08S/YMZ), and Quan 9311A/YHSM (Q9311A/YHSM) represent promising new combinations with a higher specific combining ability (SCA) effect value on YPP with a value more than 3.50. Our research thus highlights the promising application for the rational utilization of YNSM and YHSM in hybrid rice breeding.

Cellular senescence primes liver fibrosis regression through Notch-EZH2.

Cellular senescence plays a pivotal role in wound healing. At the initiation of liver fibrosis regression, accumulated senescent cells were detected and genes of senescence were upregulated. Flow cytometry combined with single-cell RNA sequencing analyses revealed that most of senescent cells were liver nonparenchymal cells. Removing senescent cells by dasatinib and quercetin (DQ), alleviated hepatic cellular senescence, impeded fibrosis regression, and disrupted liver sinusoids. Clearance of senescent cells not only decreased senescent macrophages but also shrank the proportion of anti-inflammatory M2 macrophages through apoptotic pathway. Subsequently, macrophages were depleted by clodronate, which diminished hepatic senescent cells and impaired fibrosis regression. Mechanistically, the change of the epigenetic regulator enhancer of zeste homolog2 (EZH2) accompanied with the emergence of hepatic senescent cells while liver fibrosis regressed. Blocking EZH2 signaling by EPZ6438 reduced hepatic senescent cells and macrophages, decelerating liver fibrosis regression. Moreover, the promoter region of EZH2 was transcriptionally suppressed by Notch-Hes1 (hairy and enhancer of split 1) signaling. Disruption of Notch in macrophages using Lyz2 (lysozyme 2) Cre-RBP-J (recombination signal binding protein Jκ) f/f transgenic mice, enhanced hepatic cellular senescence, and facilitated fibrosis regression by upregulating EZH2 and blocking EZH2 abrogated the above effects caused by Notch deficiency. Ultimately, adopting Notch inhibitor Ly3039478 or exosome-mediated RBP-J decoy oligodeoxynucleotides accelerated liver fibrosis regression by augmenting hepatic cellular senescence.

Nano-CeO2-Loaded Polyzwitterionic Double-Network High-Strength Hydrogel for Highly Enhanced Synergistic Marine Antifouling.

Although many antibiofouling materials have been developed based on either bacterial-killing or antiadhesion effects, the integration of both the effects in one material remains challenging for achieving highly enhanced synergistic antibiofouling. In this study, we have explored a nano-CeO2-loaded double-network hydrogel by introducing CeO2 nanorods into a polyzwitterionic hydrogel via a simple one-pot method for achieving highly efficient antifouling. First, the CeO2 nanorods dispersed in the hydrogel, as an outstanding nanozyme, have highly efficient bacterial-killing performance. Second, the superhydrophilic polyzwitterionic hydrogel provides a dense hydrated layer on the surface and subsequently excellent broad-spectrum antiadhesion behavior. Most importantly, the bacterial killing and antiadhesion of this hydrogel can work synergistically to largely improve the marine-antifouling performance. Moreover, the double-network structure of this hydrogel, including the covalently cross-linked polyzwitterion hard network and the physically cross-linked poly(vinyl alcohol) soft network, can provide greatly improved mechanical properties (2.44 MPa of tensile strength reaches and 21.87 MPa of compressive strength). As a result, among the existing marine-antifouling hydrogels, the CeO2-loaded polyzwitterionic double-network hydrogel can achieve outstanding antifouling performance, which can sustain for over 6 months in a real marine environment. This work provides a promising marine-antifouling hydrogel, which will also inspire antifouling research of a new strategy and materials.

Molecular design and experimental study of deep eutectic solvent extraction of keratin derived from feathers.

Feather keratin has a complex structure, hard texture and must be treated to improve its bioavailability. In this paper, according to the designability of DES, some deep eutectic solvents (DESs) were prepared to degrade feathers and extract keratin. Calculations by quantum chemical methods showed that DESs were considered molecular scissors with the ability to break initial hydrogen bonds and form new bonds only when the Gibbs free energy change for the degradation process was ΔG < 0, i.e., hydrogen binding energy ΔE < -0.3038 kcal/mol. Then, the degradation mechanism was predicted to provide guidance for the molecular design of DES. Finally, experimental results showed that the same ratio of choline chloride-based DESs had higher catalytic performance, in which [ChCl][P][ZnCl2] 1:5:2 was used with a high yield of keratin of 85.46 %. DES had a high catalytic performance after multiple recycling cycles and this method has no H2S gas generation, which improves the atomic utilization.

Age-related liver endothelial zonation triggers steatohepatitis by inactivating pericentral endothelium-derived C-kit.

Aging leads to systemic metabolic disorders, including steatosis. Here we show that liver sinusoidal endothelial cell (LSEC) senescence accelerates liver sinusoid capillarization and promotes steatosis by reprogramming liver endothelial zonation and inactivating pericentral endothelium-derived C-kit, which is a type III receptor tyrosine kinase. Specifically, inhibition of endothelial C-kit triggers cellular senescence, perturbing LSEC homeostasis in male mice. During diet-induced nonalcoholic steatohepatitis (NASH) development, Kit deletion worsens hepatic steatosis and exacerbates NASH-associated fibrosis and inflammation. Mechanistically, C-kit transcriptionally inhibits chemokine (C-X-C motif) receptor (CXCR)4 via CCAAT enhancer-binding protein α (CEBPA). Blocking CXCR4 signaling abolishes LSEC-macrophage-neutrophil cross-talk and leads to the recovery of C-kit-deficient mice with NASH. Of therapeutic relevance, infusing C-kit-expressing LSECs into aged mice or mice with diet-induced NASH counteracts age-associated senescence and steatosis and improves the symptoms of diet-induced NASH by restoring metabolic homeostasis of the pericentral liver endothelium. Our work provides an alternative approach that could be useful for treating aging- and diet-induced NASH.

Myeloid-specific blockade of Notch signaling ameliorates nonalcoholic fatty liver disease in mice.

Rationale: Macrophages play a central role in the development and progression of nonalcoholic fatty liver disease (NAFLD). Studies have shown that Notch signaling mediated by transcription factor recombination signal binding protein for immunoglobulin kappa J region (RBP-J), is implicated in macrophage activation and plasticity. Naturally, we asked whether Notch signaling in macrophages plays a role in NAFLD, whether regulating Notch signaling in macrophages could serve as a therapeutic strategy to treat NAFLD. Methods: Immunofluorescence staining was used to detect the changes of macrophage Notch signaling in the livers of human patients with NAFLD and choline deficient amino acid-defined (CDAA) diet-fed mice. Lyz2-Cre RBP-Jflox or wild-type C57BL/6 male mice were fed with CDAA or high fat diet (HFD) to induce experimental steatohepatitis or steatosis, respectively. Liver histology examinations were performed using hematoxylin-eosin (H&E), Oil Red O staining, Sirius red staining and immunohistochemistry staining for F4/80, Col1α1 and αSMA. The expression of inflammatory factors, fibrosis or lipid metabolism associated genes were evaluated by quantitative reverse transcription (qRT)-PCR, Western blot or enzyme-linked immunosorbent assay (ELISA). The mRNA expression of liver samples was profiled by using RNA-seq. A hairpin-type decoy oligodeoxynucleotides (ODNs) for transcription factor RBP-J was loaded into bEnd.3-derived exosomes by electroporating. Mice with experimental NAFLD were treated with exosomes loading RBP-J decoy ODNs via tail vein injection. In vivo distribution of exosomes was analyzed by fluorescence labeling and imaging. Results: The results showed that Notch signaling was activated in hepatic macrophages in human with NAFLD or in CDAA-fed mice. Myeloid-specific RBP-J deficiency decreased the expression of inflammatory factors interleukin-1 beta (IL1ß) and tumor necrosis factor alpha (TNFα), attenuated experimental steatohepatitis in mice. Furthermore, we found that Notch blockade attenuated lipid accumulation in hepatocytes by inhibiting the expression of IL1ß and TNFα in macrophages in vitro. Meanwhile, we observed that tail vein-injected exosomes were mainly taken up by hepatic macrophages in mice with steatohepatitis. RBP-J decoy ODNs delivered by exosomes could efficiently inhibit Notch signaling in hepatic macrophages in vivo and ameliorate steatohepatitis or steatosis in CDAA or HFD mice, respectively. Conclusions: Combined, macrophage RBP-J promotes the progression of NAFLD at least partially through regulating the expression of pro-inflammatory cytokines IL1ß and TNFα. Infusion of exosomes loaded with RBP-J decoy ODNs might be a promising therapy to treat NAFLD.