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In this paper, a low-formaldehyde and environmentally friendly phenol-formaldehyde resin wood adhesive was prepared by directly using lignin to substitute formaldehyde, which was further modified by glucose to improve the physical, mechanical, and curing properties. The results showed that when the replacing amount of lignin to formaldehyde reached 15 wt%, the physical properties of the prepared lignin-based-phenolic resin (LPF) can meet the Chinese national standard, and the bonding strength can increase by 21.9%, from 0.75 MPa to 0.96 MPa, compared with phenolic resin (PF). The addition of glucose boost the performance of wood adhesive, for example, the free phenol content of the obtained glucose-lignin-based phenolic resin (GLPF) significantly reduced by 79.11%, from 5.60–1.17%, the bonding strength (1.19 MPa) of GLPF increased by 19.3% in comparison to LPF, and the curing temperature of GLPF decreased by 13.08%. FT-IR results showed that the main structure of the resin did not change before and after substitution by lignin and modification by glucose. The present study provides a simple and green method for preparing resins.

Transcription factors are frequently aberrantly reactivated in various cancers, including colorectal cancer (CRC). However, as a transcription factor, the role of GMEB2 in cancer is still unclear, and further studies are needed. Here, we aimed to identify the function and mechanism of GMEB2 in regulating the malignant progression of CRC. GMEB2 was found to be highly expressed in online data analyses. We demonstrated that GMEB2 was markedly upregulated at both the mRNA and protein levels in CRC cells and tissues. GMEB2 knockdown inhibited CRC cell growth in vitro and in vivo. Mechanistically, as a transcription factor, GMEB2 transactivated the ADRM1 promoter to increase its transcription. Rescue experiments showed that ADRM1 downregulation partially reversed the promoting effects of GMEB2 on CRC growth in vitro. Moreover, the GMEB2/ADRM1 axis induced nuclear translocation of NF-κB, thus activating NF-κB signalling. Finally, we further revealed that YTHDF1 recognized and bound to the m

Although endocrine therapies targeting estrogen receptor α (ERα) are effective in managing ER positive (+) breast cancer, many patients have primary resistance or develop resistance to endocrine therapies. In addition, ER+ breast cancer with PIK3CA activating mutations and 11q13-14 amplification have poor survival with unclear mechanism. We uncovered that higher expression of deubiquitinase USP35, located in 11q14.1, was associated with ER+ breast cancer and poor survival. Estrogen enhanced USP35 protein levels by downregulating USP35-targeting miRNA-140-3p and miRNA-26a-5p. USP35 promoted the growth of ER+ breast cancer in vitro and in vivo, and reduced the sensitivity of ER+ breast cancer cells to endocrine therapies such as tamoxifen and fulvestrant. Mechanistically, USP35 enhanced ERα stability by interacting and deubiquitinating ERα, and transcriptional activity of ERα by interacting with ERα in DNA regions containing estrogen response element. In addition, AKT, a key effector of PI3K, phosphorylated USP35 at Serine613, which promoted USP35 nuclear translocation, ERα transcriptional activity, and the growth of ER+ breast cancer cells. Our data indicate that USP35 and ERα form a positive feedback loop in promoting the growth of ER+ breast cancer. USP35 may be a treatment target for ER+ breast cancer with endocrine resistance or with PIK3CA mutations or hyperactivation of the PI3K pathway.

Background: Bronchiolar adenoma (BA)/ciliated muconodular papillary tumors (CMPTs) was previously considered to be a benign neoplasm, with the possibility of malignant transformation reported in a few cases. Thus, the exact nature and biological potential of BA/CMPT have not been fully elucidated. We here report a case of mucinous adenocarcinoma (MA) caused by malignant transformation of BA. Case presentation: A 57-year-old woman presented with a 17.0×7.0 mm nodule in the lower lobe of the left lung. Hematoxylin-eosin (H&E) staining and immunohistochemistry were performed. The tumor was composed of two areas: BA area and MA area. In BA area, the tumor was consisted by a bilayered structure of luminal cells and basal cells. Basal cells were positive for CK5/6, p63, and p40, while they were not detected in MA area. The Ki-67 proliferation index was low (1%~2%). Finally, the patient was diagnosed with BA accompanied by MA, and had a favourable outcome.Conclusions: BA is generally considered to be a benign tumor. The present study indicated that BA may be carcinogenic and we should be vigilant for its potentiality of malignant transformation in clinical practice.

In contrast to the extensive but non-recyclable use of tetraalkoxydiboron(4) compounds as stoichiometric reagents in diverse reactions, this article reports an atom-economical reaction using a commercial diboron(4) as the catalyst. The key to success was designing a catalytic cycle for radical [3+2] cycloaddition involving a pyridine cocatalyst to generate from the diboron(4) catalyst and reversibly mediate the transfer of boronyl radicals. In comparison with known [3+2] cycloaddition with transition metal-based catalysts, the current reaction features not only metal-free conditions, inexpen-sive and stable catalysts, and simple operation, but also remarkably broadened substrate scope. In particular, previously unusable cyclopropyl ketones without an activating group and/or alkenes with 1,2-disubstitution and 1,1,2-trisubstitution pattern were successfully used for the first time. Consequently, challenging cyclopentane compounds with various levels of substitution (65 examples, 57 new products, up to six substituents at all five ring atoms) were readily prepared in generally high to excellent yield and diastereoselectivity. The reaction was also successfully applied in con-cise formal synthesis of an anti-obesity drug and building natural product-like complex bridged or spiralcyclic com-pounds. Mechanistic experiments and computational investigation support the proposed radical relay catalysis featuring a pyridine-assisted boronyl radical catalyst. Overall, this work demonstrates the first approach to use tetraalkoxydibo-ron(4) compounds as catalysts and may lead to the development of new, green and efficient transition metal-like boron-catalyzed organic reactions.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that causes a range of social communication and behavioral impairments. ASD typically manifests in young children, often with developmental delay or intellectual disabilities (DD/ID) as comorbidities. Accruing evidence indicates that ASD is highly heritable and genomewide studies on ASD cohorts have defined numerous genetic contributors. Notably, most of these studies have been performed with individuals of European and Hispanic ancestry and thus there is a paucity of genetic analyses of ASD in the East Asian population. Here, we performed whole-exome sequencing on 772 ASD trios from China, combining with a previous study of 369 Chinese ASD trios, to identify de novo variants in a total of 1141 ASD trios. We found that ASD probands without DD/ID carried less disruptive de novo variants, including protein-truncating and missense variants, than ASD with DD/ID. Surprisingly, we showed that expression of genes with de novo variants found in ASD probands without DD/ID were enriched in a specific group of neural progenitor cells, suggesting a potential mechanism underlying high-functioning autism. Importantly, some ASD risk genes from this study are not present in the current ASD gene database, suggesting that there are novel genetic contributors to ASD in East Asian populations. We validated one such novel ASD risk gene – SLC35G1 by showing that mice harboring heterozygous deletion of Slc35g1 exhibited defects in social interaction behaviors. Together, this work nominates novel ASD risk genes and indicates that ASD genetic studies in different geographic populations are essential to reveal the comprehensive genetic architecture of ASD.

Previous studies have shown that the NWe used a human circRNA microarray to detect the expression profiles of circRNAs in 3 pairs of cancer and paracancerous tissues from patients with colorectal cancer (CRC) and 3 pairs of peripheral blood specimens from patients with CRC and healthy individuals. The circRNAs highly expressed in both peripheral blood and tumour tissues of patients with CRC, including circALG1, were screened. A quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis of an expanded sample size was performed to detect the expression level of circALG1 in peripheral blood and tumour tissues of patients with CRC and determine its correlation with clinicopathological features, and circRNA loop-forming validation and stability assays were then conducted. Transwell assays and a nude mouse cancer metastasis model were used to study the function of circALG1 in CRC and the role of altered mCircALG1 was highly expressed in both the peripheral blood and tumour tissues of patients with CRC and was closely associated with CRC metastasis. CircALG1 overexpression promoted the migration and invasion of CRC cells, and circALG1 silencing and reduction of the circALG1 mM

MicroRNAs (miRNAs) and their target genes have been shown to play an important role in gastric cancer but have not been fully clarified. Therefore, our goal was to identify the key miRNA–mRNA regulatory network in gastric cancer by utilizing a variety of bioinformatics analyses and experiments. A total of 242 miRNAs and 1080 genes were screened from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Then, survival-related differentially expressed miRNAs and their differentially expressed target genes were screened. Twenty hub genes were identified from their protein–protein interaction network. After weighted gene co-expression network analysis was conducted, we selected miR-137-3p and its target gene, COL5A1, for further research. We found that miR-137-3p was significantly downregulated and that overexpression of miR-137-3p suppressed the proliferation, invasion, and migration of gastric cancer cells. Furthermore, we found that its target gene, COL5A1, could regulate the expression of another hub gene, FSTL1, by sponging miR-137-3p, which was confirmed by dual-luciferase reporter assays. Knockdown of COL5A1 inhibited the proliferation, invasion, and migration of gastric cancer cells, which could be rescued by the miR-137-3p inhibitor or overexpression of FSTL1. Ultimately, bioinformatics analyses showed that the expression of FSTL1 was highly correlated with immune infiltration.

Lipid droplets (LDs) are dynamic intracellular organelles critical for lipid metabolism. Alterations in the dynamics and functions of LDs during innate immune response to infections and the underlying mechanisms however, remain largely unknown. Herein, we describe the morphological dynamics of LDs in fat body of Drosophila, which vary between transient and sustained bacterial infections. Detailed analysis shows that perilipin1 (plin1), a core gene regulating lipid metabolism of LDs is suppressed by IMD/Relish, an innate immune signaling pathway via Martik (MRT) /Putzig (PZG) complex. During transient immune activation, downregulated plin1 promotes the formation of large LDs, which alleviates immune reaction-induced reactive oxygen species (ROS) stress. Thus, the growth of LDs is likely an active adaptation to maintain redox homeostasis in response to IMD activation. Whereas, under sustained inflammatory conditions, plin1 deficiency accelerates excessive decomposition of large LDs through recruitment of Brummer/ATGL lipase resulting in energy wasting, severe lipotoxicity and then deteriorated pathogenesis. Taken together, our study provides evidence that plin1 has a dual function on LDs'morphology in regulating infection-induced pathogenesis, and Plin1 might be a potential therapeutic target for coordinating inflammation resolution and lipid metabolism.

Due to the high mutation and recombination rates of the influenza virus, current clinically licensed influenza vaccines and anti-influenza drugs provide limited protection against the emerging influenza virus epidemic. Therefore, universal influenza vaccines with high efficacy are urgently needed to ensure human safety and health. Passive immunization of influenza broadly neutralizing antibodies may become an ideal option for controlling influenza infection. CR9114 isolated from the peripheral blood mononuclear cells of healthy donors is a broadly neutralizing monoclonal antibody that targets different types of influenza viruses. As the adenovirus vector is one of the most promising delivery vehicles, we employed the chimpanzee adenoviral vector, AdC68, to express CR9114 as a universal anti-influenza vaccine, termed AdC68-CR9114, and evaluated its antibody expression and its broad spectrum of prophylactic and therapeutic effects in animal models. Based on our findings, AdC68-CR9114-infected cell expressed the broadly neutralizing antibody at a high level in vitro and in vivo, exhibited biological functions, and protected mice from different types of influenza virus infection at different time points. The findings from this study shed light on a new strategy for controlling and preventing influenza infection.

Chimeric Antigen Receptor (CAR)-T cells have great efficacy against CD19+ leukemia but little success for solid tumors. This study explored the effectiveness of third generation anti-HER2 CAR-T cells alone or in combination with anti-PD1 antibody on breast tumor cells expressing HER2 in vitro and in immune competent mouse model. The PDL1-positive mouse mammary tumor cell line 4T1 engineered to express luciferase and human HER2 was used as the target cell line (4T1-Luc-HER2). Anti-HER2 CAR-T cells were generated by transducing mouse spleen T cells with recombinant lentiviruses. ELISA analysis showed that IL-2 and IFN-γ secretion was increased in CAR-T cells co-cultured with the target cells, and the secretion of these two cytokines was increased further with the addition of anti-PD1 antibody. Lactate dehydrogenase assay revealed that CAR-T cells displayed a potent cytotoxicity against the target cells, and the addition of anti-PD1 antibody further enhanced the cytotoxicity. At the effector: target ratio of 16:1, cytotoxicity was 39.8% with CAR-T cells alone, and increased to 49.5% with the addition of anti-PD1 antibody. In immune competent syngeneic mouse model, CAR-T cells were found to be present in tumor stroma, inhibited tumor growth and increased tumor apoptosis significantly. Addition of anti-PD1 antibody further enhanced these anti-tumor activities. Twenty-one days after treatment, tumor weight was reduced by 50.0% and 73.3% in CAR-T group and CAR-T plus anti-PD1 group compared with blank T group. Our results indicate that anti-PD1 antibody can greatly increase the efficacy of anti-HER2 CAR-T against HER2-positive solid tumors.

Rabies continues to poses serious threats to the public health in many countries. The development of novel inexpensive, safe and effective vaccines has become a high priority for rabies control worldwide. We previously generated a novel recombinant rabies vaccine by cloning rabies virus glycoprotein into a chimpanzee adenoviral vector, termed ChAd68-Gp. The present study evaluated the immune responses and protection afforded by this vaccine in beagle dogs. The results demonstrated that intramuscular immunization with both low-dose and high-dose of ChAd68-Gp induced strong immune responses and provided complete protection in beagles even at low-dose. However, when administered orally, high-dose vaccination was protective while low-dose vaccination was ineffective. Further investigation indicated that the low-pH value of gastric juice in the stomach of beagles might decompose the adenovirus. Therefore, suitable formulation for adenovirus-based oral vaccine should be considered and developed. The chimpanzee adenovirus-vectored rabies vaccine ChAd68-Gp warrants extensive test for clinical application.

Non-contact and minimally invasive endoscopic optical imaging is an invaluable diagnostic tool for tissue examination and cancer screening. The point sampling techniques with high sensitivity to the tissue microenvironment are time consuming and often not affordable in clinics. There is a major clinical need for a large field-of-view (FOV) rapid screening method to highlight subtle tissue microstructural alterations. To address this unmet need, we have developed High Spatial Frequency Domain Imaging (HSFDI)-a non-contact imaging modality that spatially maps the tissue microscopic scattering structures over a large field of view (>1cm2). Based on an analytical reflectance model of sub-diffusive light from forward-peaked highly scattering media, HSFDI quantifies the spatially-resolved parameters of the light scattering phase function (i.e., the backscattering probability and the light spreading length) from the reflectance of structured light modulated at high spatial frequencies. Enhanced signal to noise ratio (SNR) is achieved at even ultra-high modulation frequencies with single snapshot multiple frequency demodulation (SSMD). The variations in tissue microstructures, including the strength of the background (pudding) refractive index fluctuation and the prominent scattering structure (plum) morphology, can then be inferred. After validation with optical phantoms, measurements of fresh ex vivo tissue samples revealed significant contrast and differentiation of the phase function parameters between different types and disease states (normal, inflammatory, and cancerous) of tissue whereas tissue absorption and reduced scattering coefficients only show modest changes. HSFDI may provide wide-field images of microscopic structural biomarkers unobtainable with either diffuse light imaging or point-based optical sampling. Potential clinical applications include the rapid screening of excised tissue and the noninvasive examination of suspicious lesions during operation.

The Three-North Afforestation Program (TNAP), initiated in 1978 and scheduled to be completed in 2050, is the world’s largest afforestation project and covers 4.07 x 106 km2 (42.4%) of China. We systematically assessed goals and outcomes of the first 30 years of the TNAP using high-resolution remote sensing and ground survey data. With almost 23 billion dollars invested between 1978 and 2008, the forested area within the TNAP region increased by 1.20 × 107 ha, but the proportion of high quality forests declined by 15.8%. The establishment of shelterbelts improved crop yield by 1.7%, much lower than the 5.9% expected once all crop fields are fully protected by shelterbelts. The area subjected to soil erosion by water decreased by 36.0% from 6.72 × 107 to 4.27 × 107 ha; the largest reductions occurred in areas where soil erosion had been most severe and forests contributed more than half of this improvement. Desertification area increased from 1978 to 2000 but decreased from 2000 to 2008; the 30-year net reduction was 13.0% (4.05×106 ha), with 8.0% being accounted for by afforestation in areas with only slight, prior desertification. In addition to its direct impacts, the TNAP has enhanced people’s awareness of environmental protection and attracted consistent attention and long-term commitment from the Chinese government to the restoration and protection of fragile ecosystems in the vast Three-North region. The significant decline in forest quality, limited success in reducing desertification, and low coverage of shelterbelts are aspects of the TNAP in need of re-assessment, and additional ca. 34 billion dollars will be needed to ensure the completion of the TNAP.

Mixed linage leukemia gene 2 (MLL2) is identified as a novel mutation gene in diffuse large B cell lymphoma (DLBCL). However, the significance of MLL2 protein expression for the prognosis of DLBCL is unclear. In this study, we detected MLL2 protein expression in primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL) samples by using tissue microarray immunohistochemistry, and analyzed the correlation between MLL2 protein expression and tumor proliferation activity. In addition, we investigated clinical significance of MLL2 protein expression for PGI-DLBCL prognosis. We found that there was significant difference in MLL2 protein expression between PGI-DLBCL and reactive hyperplasia of lymph node. High expression of MLL2 protein indicated higher clinical stage. In older patients (>60 years) with PGI-DLBCL, MLL2 protein expression was positively correlated with Ki-67 expression and negatively correlated with patient survival. Our data suggest that MLL2 protein is overexpressed in PGI-DLBCL and appears as a prognostic factor for patients of PGI-DLBCL, especially for those older than 60 years old.

Gastric cancer is a malignant disease of the digestive system with high rates of incidence and mortality. S‑phase kinase‑associated protein 2 (Skp2) is a novel oncogene, which has been identified to be important in tumor progression and metastasis. In order to clarify the role of Skp2 in human gastric cancer, the present study detected the expression of Skp2 in human gastric cancer tissues, and investigated the molecular mechanism of Skp2 in the progression of gastric carcinoma. The results of the initial bioinformatics analysis showed that Skp2 was significantly upregulated in 31 specimens of primary gastric cancer from a UK patient cohort, and in 10 gastric cancer lines of a side population, compared with normal gastric tissues (P

Effects of the Epstein-Barr virus (EBV) on cellular protein expression are essential for viral pathogenesis. To characterize the cellular response to EBV infection, differential proteomes of gastric epithelial AGS cells were analyzed with two-dimensional gel electrophoresis (2-DE) followed by matrix-assisted laser desorption/ionization- time of flight (MALDI-TOF) and liquid chromatography electrospray/ionization ion trap (LC-ESI-IT) mass spectrometry identification. Mass spectrometry identified 9 altered cellular proteins, including 5 up-regulated and 4 down-regulated proteins after EBV infection. Notably 2-DE analysis revealed that EBV infection induced increased expression of heat shock cognate 71 kDa protein, actin cytoplasmic 1, pyridoxine-5'-phosphate oxidase, caspase 9, and t-complex protein 1 subunit alpha. In addition, EBV infection considerably suppressed those cellular proteins of zinc finger protein 2, cyclin-dependent kinase 2, macrophage-capping protein, and growth/ differentiation factor 11. Furthermore, the differential expressional levels of partial proteins (cyclin-dependent kinase 2 and caspase 9) were confirmed by Western blot analysis.Thus, this work effectively provided useful protein-related information to facilitate further investigation of the mechanisms underlying EBV infection and pathogenesis.

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRs) are single-stranded, noncoding RNAs that are important in many biological processes. Although the oncogenic and tumor-suppressive functions of several miRs have been characterized, their precise biological roles remain largely unexplored. In the present study, the role of miR-133b was identified in the regulation of CRC cell proliferation and apoptosis. miR-133b expression was shown to be greatly downregulated in human CRC cells compared to normal colon cells. Downregulation of miR-133b expression was also significant in six of eight human CRC tissues compared with adjacent normal tissues. In the CRC cell lines SW-620 and HT-29, ectopic expression of miR-133b potently affected tumor cell proliferation and apoptosis in vitro and in vivo by direct targeting of the receptor tyrosine kinase MET. Transfection of SW-620 and HT-29 cells with miR-133b significantly suppressed a luciferase-reporter containing the MET-3'-untranslated region. Taken together, these results provide evidence that miR-133b regulated tumor cell proliferation and apoptosis through modulation of the MET signaling pathway.