Multi-Functional Repair and Long-Term Preservation of Paper Relics by Nano-MgO with Aminosilaned Bacterial Cellulose.

Paper relics, as carrieres of historical civilization's records and inheritance, could be severely acidic and brittle over time. In this study, the multi-functional dispersion of nanometer magnesium oxide (MgO) carried by 3-aminopropyl triethoxysilane-modified bacterial cellulose (KH550-BC) was applied in the impregnation process to repair aged paper, aiming at solving the key problems of anti-acid and strength recovery in the protection of ancient books. The KH550-BC/MgO treatment demonstrated enhanced functional efficacy in repairing aged paper, attributed to the homogeneous and stable distribution of MgO within the nanofibers of BC networks, with minimal impact on the paper's wettability and color. Furthermore, the treatment facilitated the formation of adequate alkali reserves and hydrogen bonding, resulting in superior anti-aging properties in the treated paper during prolonged preservation. Even after 30 days of hygrothermal aging tests, the paper repaired by KH550-BC/MgO was still in a gently alkaline environment (pH was about 7.56), alongside a 32.18% elevation compared to the untreated paper regarding the tear index. The results of this work indicate that KH550-BC/MgO is an effective reinforcement material for improving the long-term restoration of ancient books.

Improvement of interface bonding of bacterial cellulose reinforced aged paper by amino-silanization.

The aging of paper seriously threatens the service life of cultural heritage documents. Bacterial cellulose (BC), which has a good fiber aspect ratio and is rich in hydroxyl groups, is suitable for strengthening aged paper. However, a single BC added was not ideal for paper restoration, since only strengthening was not able to resist the persistent acidification of ancient book. In this work, BC was functionalized by 3-aminopropyltriethoxysilane (APTES) to develop the interface bonding with aged paper. Fourier transform infrared (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and elemental analysis identified the successful amino-silanization of BC. The modification parameters were optimized as the concentration of APTES of 5 wt%, the reaction time of 4 h, and the reaction temperature of 80 °C based on a considerable improvement in the strength properties without obvious appearance impact on reinforced papers. Moreover, the pH value of the repaired paper was achieved at 8.03, ensuring the stability of the anti-aging effect. The results confirmed that APTES-BC had great potential applications in ancient books conservation.

Long-term consequences of regulatory T-cell-specific knockout of Notch2 in immune homeostasis.

AIMS: To investigate the long-term alterations in immune function and spontaneous inflammation in mice following specific knockout of Notch2 (Notch2KO) in Treg cells. MAIN METHODS: A Treg cell-specific Notch2 knockout mouse model was constructed, and the mice were named Notch2KO mice. The pathological changes and inflammatory cell infiltration in the lungs, skin, and liver of the mice at 2, 6, 9, and 12 months of age were evaluated by HE staining. The expression of Th1/Th2/Th17/Treg transcription factors was detected by Western blotting. The proportion of CD4 + T-cell subsets was determined by flow cytometry. The levels of Th1/Th2/Th17/Treg cytokines were measured by enzyme-linked immunosorbent assays (ELISAs). KEY FINDINGS: The expression level of Notch2 in Treg cells from the Notch2KO mice was significantly decreased compared with that in Treg cells from the control mice (P < 0.05). HE staining showed that compared with the control mice, the Notch2KO mice displayed spontaneous inflammation and had a large amount of inflammatory cell infiltration in the lungs and skin (P < 0.05). The number of Treg cells, the expression level of Foxp3, and the level of IL-10 were reduced in the Notch2KO mice compared with the control mice (P < 0.05), and these metrics further decreased with increasing age (P < 0.05). In contrast, the number of Th1/Th2 cells, the expression level of T-bet/GATA3, and the levels of Th1 cytokines (IFN-γ)/Th2 cytokines (IL-4, IL-5, and IL-13) were significantly increased in the Notch2KO mice (P < 0.05), and these metrics further increased with increasing age (P < 0.05). There was no significant change in the number of Th17 cells, the expression of RORγt, or the level of IL-17. Further analysis showed that the balance of Th1/Th2 and Treg/Th17 cells in the Notch2KO mice was shifted, and the ratio showed a downward trend over time (P < 0.05). SIGNIFICANCE: The number and function of Treg cells can be severely inhibited by a specific knockout of Notch2 in Treg cells, leading to immune disorders that gradually worsen over time.

Superhydrophobic and deacidified cellulose/CaCO3-derived granular coating toward historic paper preservation.

Deacidification and surface self-cleaning are of great significance for the long-term preservation of historic literature. Herein, a superhydrophobic self-cleaning coating, derived from nanocellulose coated with CaCO3 particles is constructed via chemical vapor deposition (CVD) for the first time for the preservation of historic paper. The static contact angle of superhydrophobic paper reached more than 150° and the minimum sliding angle was 6.4°. Deacidification effect was achieved with a desired pH value in the range from 7.50 to 7.77 and the maximum alkali storage was up to 1.235 mol/kg. It is found that the low-cost CaCO3 nanoparticles can not only remove the acid substances, but also gave the paper function of self-cleaning, which is very great significant for the protection of paper-based relics.

Enhancing the HSV-1-mediated antitumor immune response by suppressing Bach1.

BACKGROUND: In 2015, herpes simplex virus 1 (HSV-1)-derived talimogene laherparepvec (T-VEC) was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment. However, its antitumor application is limited to local treatment of melanoma, and there is a lack of understanding of the mechanisms underlying the regulation of HSV-1 replication in cancer cells and the associated antitumor immunity. We hypothesized that increasing the replication capacity of HSV-1 in tumor cells would enhance the antitumor effect of this virus. METHODS: We systematically identified IFN-stimulated genes induced by HSV-1 by performing functional screens and clarified the mechanism by which BACH1 acts against HSV-1. Then, we tested the effect of BACH1 deficiency on immunogenic cell death induced by HSV-1. Furthermore, we investigated the antitumor effect of BACH1 deficiency on HSV-1 in MCA205 and B16 murine tumor models. RESULTS: We identified eight IFN-stimulated genes (ISGs) controlling HSV-1 replication, among which BTB and CNC homology 1 (BACH1) suppressed HSV-1 replication by inhibiting the transcription of ICP4, ICP27, and UL39. Loss of Bach1 function not only increased HSV-1 proliferation but also promoted HSV-1-induced cell apoptosis, HMGB1 secretion, and calreticulin exposure in tumor cells. More importantly, hemin, an FDA-approved drug known to downregulate BACH1, significantly enhanced HSV-1-mediated antitumor activity with increased T lymphocyte infiltration at the tumor site. CONCLUSIONS: Our studies uncovered a novel antiviral activity of BACH1 and provided a new strategy for improving the clinical efficiency of the oncolytic virus HSV-1.

Transcriptome and Metabolome Analyses Provide Insights into the Watercore Disorder on "Akibae" Pear Fruit.

Watercore is a physiological disorder that commonly occurs in sand pear cultivars. The typical symptom of watercore tissue is transparency, and it is often accompanied by browning, breakdown and a bitter taste during fruit ripening. To better understand the molecular mechanisms of watercore affecting fruit quality, this study performed transcriptome and metabolome analyses on watercore pulp from "Akibae" fruit 125 days after flowering. The present study found that the "Akibae" pear watercore pulp contained higher sorbitol and sucrose than healthy fruit. Moreover, the structure of the cell wall was destroyed, and the content of pectin, cellulose and hemicellulose was significantly decreased. In addition, the content of ethanol and acetaldehyde was significantly increased, and the content of polyphenol was significantly decreased. Watercore induced up-regulated expression levels of sorbitol synthesis-related (sorbitol-6-phosphate dehydrogenase, S6PDH) and sucrose synthesis-related genes (sucrose synthesis, SS), whereas it inhibited the expression of sorbitol decomposition-related genes (sorbitol dehydrogenase, SDH) and sorbitol transport genes (sorbitol transporter, SOT). Watercore also strongly induced increased expression levels of cell wall-degrading enzymes (polygalactosidase, PG; ellulase, CX; pectin methylesterase, PME), as well as ethanol synthesis-related (alcohol dehydrogenase, ADH), acetaldehyde synthesis-related (pyruvate decarboxylase, PDC) and polyphenol decomposition-related genes (polyphenol oxidase, PPO). Moreover, the genes that are involved in ethylene (1-aminocyclopropane- 1-carboxylate oxidase, ACO; 1-aminocyclopropane- 1-carboxylate synthase, ACS) and abscisic acid (short-chain alcohol dehydrogenase, SDR; aldehyde oxidase, AAO) synthesis were significantly up-regulated. In addition, the bitter tasting amino acids, alkaloids and polyphenols were significantly increased in watercore tissue. Above all, these findings suggested that the metabolic disorder of sorbitol and sucrose can lead to an increase in plant hormones (abscisic acid and ethylene) and anaerobic respiration, resulting in aggravated fruit rot and the formation of bitter substances.

Study on the chemical modification of alkali lignin towards for cellulase adsorbent application.

The research of cost-efficient lignin-based adsorbents is a practical strategy for the recovery of cellulase. In this study, alkali lignin was modified to increase the phenolic hydroxyl (Ph-OH) content for cellulase adsorption applications. After phenolation, compared with the lignin reference, the maximum adsorption cellulase capacity of lignoresorcinol (LigR) and lignopyrogallol (LigP) was improved from 76.5 mg/g to 842.1 mg/g and 911.4 mg/g, respectively. The enzyme activity of the adsorbed cellulase on LigR was higher than that on LigP, which could migrate to the fresh substrates during enzymatic hydrolysis. The adsorbed cellulase could be easily recovered from two lignin-based adsorbents by adjusting pH. The distinct cellulase adsorption behavior of two lignin-based adsorbents was closely related to the high Ph-OH contents and low S/G ratio in phenolated lignin samples characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Heteronuclear Single Quantum Coherence-Nuclear Magnetic Resonance (HSQC-NMR).

A new and highly efficient conservation treatment for deacidification and strengthening of aging paper by in-situ quaternization.

Ancient papers, facing the threat of acidification, aging and microbial corrosion, need to be repaired due to their significance of history, art and culture research. In this work, a new and highly efficient approach was proposed to deacidify and strengthen aging paper by in-situ quaternization for the conservation, in which MgO nanoparticles dispersed in hexamethyldisiloxane was coated on the paper surface and the aqueous alkaline solution and the 2, 3-epoxypropyl trimethyl ammonium chloride/isopropyl alcohol/water mixture were sprayed in a closed reactor. Results showed that properties of ageing papers were improved after MSCE-8/2 treatment. The pH value was in the range of 7.5-9.0 and the maximum amount of alkali storage was 220 mmol/Kg. The tensile strength and folding endurance were increased by 28.05% and 80%, respectively. The fluctuation range of brightness and chromatic aberration was 0.14 and 1.27. Moreover, treated paper also had the great anti-bacteria and anti-aging effects.

Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells.

MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed 'small RNA zipper'. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30-50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer cells. In addition, we demonstrate that the miR-221 zipper attenuates doxorubicin resistance with higher efficiency than anti-miR-221 in human breast cancer cells. Taken together, small RNA zippers are a miRNA inhibitor, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes.

Cutting edge: all-trans retinoic acid sustains the stability and function of natural regulatory T cells in an inflammatory milieu.

Recent studies have demonstrated that plasticity of naturally occurring CD4(+)Foxp3(+) regulatory T cells (nTregs) may account for their inability to control chronic inflammation in established autoimmune diseases. All-trans retinoic acid (atRA), the active derivative of vitamin A, has been demonstrated to promote Foxp3(+) Treg differentiation and suppress Th17 development. In this study, we report a vital role of atRA in sustaining the stability and functionality of nTregs in the presence of IL-6. We found that nTregs treated with atRA were resistant to Th17 and other Th cell conversion and maintained Foxp3 expression and suppressive activity in the presence of IL-6 in vitro. atRA decreased IL-6R expression and signaling by nTregs. Of interest, adoptive transfer of nTregs even from arthritic mice treated with atRA suppressed progression of established collagen-induced arthritis. We suggest that nTregs treated with atRA may represent a novel treatment strategy to control established chronic immune-mediated inflammatory diseases.

Protective effect of heparin-coated circuits on the platelets during cardiopulmonary bypass.

To observe the protective effect of heparin-coated circuits (HCC) on the platelet function during cardiopulmonary bypass (CPB), 23 patients with heart valve replacement were studied. The system heparin dose was 3 mg/kg in the control group (n = 15) and heparin-coated circuits in the HCC group (n = 8). Platelet count, alpha-granule membrane protein-140 (GMP-140) concentrations were determined before CPB, at 60 min of CPB, 30 and 60 min after protamine administration, first 12 h after CPB, respectively. At end of CPB the arterial filters in the circuits were observed by electron microscopy. The amount of first 12-h postoperative blood loss was measured. There was significant reduction in platelet loss during and after CPB in the HCC group in contrast to the control group during CPB (P<0.05). During the first 12 h, postoperative blood loss was reduced in the HCC group as compared with that in the control group (218+/-61 ml, vs. 332+/-118 ml, P<0.05). Electron microscopy showed that in the HCC group the filter meshes and their fringes were clear and fragments of floccules were occasionally seen, without adherent cells or only few adherent cells on their surfaces, whereas several cellular and fibrous components were found to adhere to the surfaces of the filter meshes in the control group. This study indicates that heparin-coated circuits might reduce the platelet loss and activation during CPB and improve hemocompatibility of cardiopulmonary bypass equipment.