A designed ZrOCl2/ethylene glycol deep eutectic solvent for efficient lignocellulose valorization.

Deep eutectic solvents (DESs) hold great potential in biorefining because they can efficiently deconstruct the recalcitrant structure of lignocellulose. In particular, inorganic salts with Lewis acids have been proven to be effective at cleaving lignin-carbohydrate complexes. Herein, a Zr-based DES system composed of metal chloride hydrate (ZrOCl2·8H2O) and ethylene glycol (EG) was designed and used for poplar powder pretreatment. Zr4+-based salts provide sufficient acidity for lignocellulose depolymerization. The acidity of the DES was analysed by the Kamlet-Taft solvatochromic parameter, and the results demonstrated that the acidity can be regulated by the DES composition. Under the optimum conditions (ZrOCl2·8H2O:EG molar ratio of 1:2), the DES pretreatment removes nearly 100 % hemicellulose and 94.7 % lignin. The recovered lignin exhibited a low polydispersity of 1.7. The cellulose residues deliver an efficiency of 94.4 % upon enzymatic digestion. Moreover, the DES can be easily recovered with high yield and purity, and the recycled DES still maintains high delignification and enzymatic hydrolysis efficiencies. The proposed DES pretreatment technology is promising for biomass valorization.

Significance of metastatic lymph nodes ratio in overall survival for patients with resected nonsmall cell lung cancer: a retrospective cohort study.

OBJECTIVE: The tumor, node and metastasis stage is widely applied to classify lung cancer and is the foundation of clinical decisions. However, increasing studies have pointed out that this staging system is not precise enough for the N status. In this study, we aim to build a convenient survival prediction model that incorporates the current items of lymph node status. METHODS: We performed a retrospective cohort study and collected the data from resectable nonsmall cell lung cancer (NSCLC) (IA-IIIB) patients from the Surveillance, Epidemiology, and End Results database (2006-2015). The x-tile program was applied to calculate the optimal threshold of metastatic lymph node ratio (MLNR). Then, independent prognostic factors were determined by multivariable Cox regression analysis and enrolled to build a nomogram model. The calibration curve as well as the Concordance Index (C-index) were selected to evaluate the nomogram. Finally, patients were grouped based on their specified risk points and divided into three risk levels. The prognostic value of MLNR and examined lymph node numbers (ELNs) were presented in subgroups. RESULTS TOTALLY,: 40853 NSCLC patients after surgery were finally enrolled and analyzed. Age, metastatic lymph node ratio, histology type, adjuvant treatment and American Joint Committee on Cancer 8th T stage were deemed as independent prognostic parameters after multivariable Cox regression analysis. A nomogram was built using those variables, and its efficiency in predicting patients' survival was better than the conventional American Joint Committee on Cancer stage system after evaluation. Our new model has a significantly higher concordance Index (C-index) (training set, 0.683 v 0.641, respectively; P < 0.01; testing set, 0.676 v 0.638, respectively; P < 0.05). Similarly, the calibration curve shows the nomogram was in better accordance with the actual observations in both cohorts. Then, after risk stratification, we found that MLNR is more reliable than ELNs in predicting overall survival. CONCLUSION: We developed a nomogram model for NSCLC patients after surgery. This novel and useful tool outperforms the widely used tumor, node and metastasis staging system and could benefit clinicians in treatment options and cancer control.

The protective effect of teprenone in TNBS-induced ulcerative colitis rats by modulating the gut microbiota and reducing inflammatory response.

OBJECTIVE: Ulcerative colitis (UC), a chronic and refractory nonspecific inflammatory bowel disease, affects millions of patients worldwide and increases the risk of colorectal cancer. Teprenone is an acylic polyisoprenoid that exerts anti-inflammatory properties in rat models of peptic ulcer disease. This in vitro and in vivo study was designed to investigate the effects of teprenone on UC and to explore the underlying mechanisms. METHODS: Human intestinal epithelial cells (Caco-2 cells) serve as the in vitro experimental model. Lipopolysaccharide (LPS, 1 µg/mL) was employed to stimulate the production of pro-inflammatory cytokines (interleukin [IL]-6, IL-1ß, and tumor necrosis factor [TNF]-α), Toll-like receptor-4 (TLR4), MyD88 expression, and NF-κB activation. A trinitrobenzene sulfonic acid (TNBS)-induced chronic UC rat model was employed for the in vivo assay. RESULTS: Pro-inflammatory cytokine stimulation by LPS in Caco-2 cells was inhibited by teprenone at 40 µg/mL through the TLR4/NF-κB signaling pathway. Teprenone attenuated TNBS-induced UC, decreased myeloperoxidase and malondialdehyde, induced TLR4 expression and NF-κB activation, and increased glutathione and zonula occludens-1 level in the rat colonic tissue. Moreover, Fusobacterium, Escherichia coli, Porphyromonas gingivalis elevation, and Mogibacterium timidum decline in UC rats were inhibited by teprenone. CONCLUSION: Based on our results, the protective effects of teprenone for UC may be related to its ability to modulate the gut microbiota and reduce the inflammatory response.

PTEN expression in human cumulus cells is associated with embryo development competence.

Embryo quality determines the success of in vitro fertilization and embryo transfer (IVF-ET) treatment. Biomarkers for the evaluation of embryo quality have some limitations. Apoptosis in cumulus cells (CCs) is important for ovarian function. PTEN (phosphatase and tensin homolog) is a well known tumour suppressor gene that functions as a mediator of apoptosis and is crucial for mammalian reproduction. In the present study, we analyzed the expression level of PTEN in human CCs and aimed to investigate its association with embryo developmental competence in IVF treatment cycles. The PTEN mRNA level in CCs was measured using real-time fluorescence quantitative PCR. The association of the differential expression of PTEN with embryo quality was analyzed. Our data showed that PTEN mRNA levels were significantly decreased in CCs surrounding mature oocytes compared with immature oocytes. Similar changes were found in the analysis of fertilization and blastocyst formation. The speculation that the measurement of PTEN mRNA levels in human CCs would provide a useful tool for selecting oocytes with greater chances to implant into the uterus needs to be further verified through single-embryo transfer in the future. The proapoptotic mechanism of PTEN in human reproduction needs to be further studied.

Hypoxia-dependent expression of MAP17 coordinates the Warburg effect to tumor growth in hepatocellular carcinoma.

BACKGROUND: Reprogrammed glucose metabolism, also known as the Warburg effect, which is essential for tumor progression, is regarded as a hallmark of cancer. MAP17, a small 17-kDa non-glycosylated membrane protein, is frequently dysregulated in human cancers. However, its role in hepatocellular carcinoma (HCC) remains largely unknown. METHODS: Immunohistochemistry was used to analyze the expression pattern of MAP17 in HCC. Loss-of-function and gain-of-function studies were performed to investigate the oncogenic roles of MAP17 in vitro and in vivo. RNA sequencing, co-immunoprecipitation, immunofluorescence and western blotting were used to study the molecular mechanism of MAP17 affecting the tumor growth and glycolytic phenotype of HCC. RESULTS: An integrative analysis showed that MAP17, a small 17-kDa non-glycosylated membrane protein, is significantly related to the glycolytic phenotype of hepatocellular carcinoma (HCC). Firstly, we found that MAP17 expression is hypoxia-dependent and predicts a poor prognosis in HCC. Genetic silencing of MAP17 reduced the rate of glucose uptake, lactate release, extracellular acidification rate, and expression of glycolytic genes. Ectopic expression of wild type MAP17 but not its PDZ binding domain mutant MAP17-PDZm increased tumor glycolysis. Further research showed that MAP17 knockdown markedly retarded in vivo tumor growth in HCC. Importantly, attenuation of tumor glycolysis by galactose largely hijacked the growth-promoting role of MAP17 in HCC cells. RNA sequencing analysis revealed that MAP17 knockdown leads to transcriptional changes in the ROS metabolic process, cell surface receptor signaling, cell communication, mitotic cell cycle progression, and regulation of cell differentiation. Mechanistically, MAP17 exerted an increased tumoral phenotype associated with an increase in reactive oxygen species (ROS), which activates downstream effectors AKT and HIF1α to enhance the Warburg effect. In HCC clinical samples, there is a close correlation between MAP17 expression and HIF1α or phosphorated level of AKT. CONCLUSIONS: Our results show that MAP17 is a novel glycolytic regulator, and targeting MAP17/ROS pathway may be an alternative approach for the prevention and treatment of HCC.

PTEN Expression in Human Granulosa Cells Is Associated with Ovarian Responses and Clinical Outcomes in IVF.

The ovarian reserve determines the success of in vitro fertilization (IVF) and embryo transfer treatment. It predicts the ovarian response in controlled ovarian hyperstimulation cycles. Apoptosis in granulosa cells surrounding oocytes is important for ovarian function and has been closely associated with follicular atresia. PTEN (encoding phosphatase and tensin homolog) is a well-known tumor suppressor gene that functions as a mediator of apoptosis and is crucial for mammal reproduction. In the present study, we analyzed the expression level of PTEN in human granulosa cells and aimed to investigate its association with the ovarian response and clinical outcomes in IVF. Apoptosis in granulosa cells were analyzed using Annexin V-Allophycocyanin staining after PTEN short hairpin RNA lentivirus transfection. Real-time fluorescent quantitative PCR analysis showed that the PTEN transcript level was significantly higher in poor responders and significantly lower in high responders, compared with that in normal responders. However, PTEN expression in the pregnancy group decreased slightly, but not significantly, compared with that in the non-pregnancy group. The apoptosis rate of granulosa cells declined significantly after 24-h transfection of the PTEN-shRNA lentivirus. These results suggest a fundamental role of PTEN in the regulation of follicular development, and that it might be involved in the pathogenesis of follicular dysplasia and ovarian dysfunction.

Pre-transplant cytoreductive therapy can improve overall survival of patients with MDS-AML but not MDS-EB2 receiving HLA-matched sibling donor peripheral blood stem cell transplantation.

To evaluate whether cytoreductive therapy is needed for myelodysplastic syndromes (MDS) patients with excess blasts type 2 (MDS-EB2) and acute myeloid leukemia derived from MDS (MDS-AML) before HLA-matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT), we retrospectively analyzed 80 cases of MDS-EB2 and MDS-AML patients who received MSD-PBSCT between February 2006 and December 2019 in our hospital. The 3-years overall survival (OS) rate and disease-free survival (DFS) rate were (59.1±5.8)% and (52.5±5.7)%, respectively. The 3-years non-relapse mortality (NRM) rate and relapse rate (RR) were (22.4±0.2)% and (25.4±0.2)%, respectively. Univariate analysis showed that, hematopoietic cell transplantation comorbidity index (HCT-CI) ≥ 2, poor/very poor karyotype and occurrence of grade III-IV acute graft-versus-host disease (aGVHD) are risk factors for OS. Patients received pre-transplant cytoreductive therapy (PCT) and obtained complete remission (CR) had significantly higher OS rate than those who failed to achieve CR (non-CR group) and those who did not receive PCT (non-PCT group) [(80.0±8.3)% versus (38.1±10.6)% versus (56.1±9.3)%, P=0.010]. PCT significantly increased the OS rate [(62.2±10.0)% versus (20.0±17.9)%, P=0.013] for MDS-AML patients but not for MDS-EB2 patients [(59.2±11.1)% versus (62.9±10.1)%, P=0.991]. Our findings suggest reducing tumor burden by cytoreductive therapy to obtain CR before transplant improves OS. For MDS-AML patients, PCT is beneficial, while for MDS-EB2 patients, PCT is not necessary.

Plasma YKL-40: a Potential Biomarker for Tumor Invasion in Esophageal Cancer.

BACKGROUND: YKL-40, a chitinase-like glycoprotein has been identified as a candidate tumor marker. The current study evaluated the clinical significance of plasma YKL-40 in esophageal cancer patients. METHODS: We enrolled 127 esophageal cancer patients, 29 healthy controls. Plasma YKL-40 levels were measured through enzyme linked immunosorbent assay. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficiency of plasma YKL-40 in esophageal cancer patients. The correlations between plasma YKL-40 and clinicopathological characteristics of esophageal were analyzed. RESULTS: Plasma YKL-40 levels were significantly higher in patients with lymph node metastasis than those that were non-metastatic (p = 0.005). Patients with tumor thrombus formation presented with significantly higher YKL-40 levels than those without thrombus formation (160.3 vs. 74.7 ng/mL, p = 0.012). YKL-40 levels in patients with advanced stage (III and IV) were significantly higher than those in the early stages (I and II, p = 0.016). ROC curve analysis showed that the area under curve was 0.909, and the best diagnostic threshold of YKL-40 for esophageal cancer was 80.6 ng/mL with 68.9% sensitivity and 96.6% specificity. CONCLUSIONS: This study indicated that YKL-40 may be a biomarker for esophageal cancer and potential biomarker for identification of invasive esophageal cancer.

Zirconium ion modified melamine sponge for oil and organic solvent cleanup.

Hydrophilic melamine sponge is transferred into hydrophobic melamine sponge by immersing the commercial melamine sponge cubes into zirconium oxychloride aqueous solution and followed by a simple dry process. The hydrophobicity transformation is assigned to the complex bonds constructed by the Zr4+ ions and N atoms, thus reducing the surface polarity. The modified melamine sponge presents excellent absorption capacities toward various oils and organic solvents (70-181 g/g). Its contact angle with water can reach 130° or more, and displays good oil-water selectivity for both heavy oil and light oil. Besides, the sponge has stable chemical properties and good recyclability. This work presents a facile and low-cost method for fabrication of hydrophobic materials that might be used for the cleanup of oil spills.

Comparison of outcomes of haploidentical donor hematopoietic stem cell transplantation supported by third-party cord blood with HLA-matched unrelated donor transplantation.

Previous study indicated that co-infusion of cord blood cells may potentially improve the outcome of haploidentical donor (HID) transplantation. In this study, we analyzed the outcomes of patients who underwent HID transplantation supported by cord blood when compared with HLA-matched unrelated donor (URD) transplantation. Starting in 2015, 40 patients with hematopoietic malignancies underwent HID transplantation and 26 patients underwent URD transplantation. Hematopoietic recovery, the incidences of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD was comparable in the two groups. At two year, the relapse risk in HID group was significantly lower than in URD group (RR 4.630; 95%CI, 1.081-19.839; p = .039). Moreover, HID group have prolonged PFS (RR 2.642; 95%CI, 1.046-6.672; p = .040). In conclusion, HID transplantation supported by cord blood results in better outcomes compared with URD transplantation and it might be a favorable alternative to a HLA-matched URD transplantation.

Differential expression of miR-4492 and IL-10 is involved in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis (CRS) is one of the most common types of respiratory disease and affects a large proportion of the population worldwide. The clinical differences between CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) facilitate studies on the development of polyps. In the present study, next-generation sequencing was performed to identify differentially expressed microRNAs (miRNAs/miRs) in CRSwNP vs. CRSsNP tissues and subsequently validated the expression of selected genes using reverse transcription-quantitative polymerase chain reaction analysis. In total, 6 miRNAs were identified to be downregulated in the CRSwNP samples compared with those in the CRSsNP samples. The predicted targets of these miRNAs were determined to be enriched in a number of signaling pathways, including the ErbB, Ras, cyclic adenosine monophosphate and Janus kinase (Jak)/signal transducer and activator of transcription (STAT) pathways. The expression of miR-4492 and that if its targets predicted by a bioinformatics analysis, tumor necrosis factor α (TNF-α) and interleukin (IL)-10, was validated in 96 clinical specimens. miR-4492 was downregulated and IL-10 was upregulated in CRSwNP vs. CRSsNP tissues, and an inverse correlation between miR-4492 and IL-10 was determined in CRS tissues; however no difference was identified in the expression of TNF-α between the different groups. The present results indicate that the miR-4492/IL-10 interaction in the Jak/STAT signaling pathway may be one of the key mechanisms in CRSwNP.

The combination of Decitabine and EPZ-6438 effectively facilitate adipogenic differentiation of induced pluripotent stem cell-derived mesenchymal stem cells.

As a novel type of mesenchymal stem cell, induced pluripotent stem cell-derived mesenchymal stem cells (iPMSCs) have huge potential for cell therapy. iPMSCs exhibited the typical characteristics of MSCs, whereas the tri-lineage differentiation potential is limited, especially the adipogenic propensity. Here, to reveal the molecular mechanism we carried out the epigenetic comparisons between the iPMSCs and the bone marrow-derived mesenchymal stem cells (BMSCs) and embryonic stem cell-derived mesenchymal stem cells (EMSCs). We found that the iPMSCs was significantly higher than the BMSCs in terms of genome-wide DNA methylation. Meanwhile, the adipogenic gene PPARγ promoter region existed hypermethylation. In addition, compared with EMSCs and BMSCs, iPMSCs had significant differences in the histones epigenetic modification of methylation and acetylation, especially high levels of histone 27 lysine trimethylation (H3K27me3). Furthermore, the epigenetic modifiers Decitabine and EPZ6438 effectively upregulated the gene expression of PPARγ and promoted the adipogenic differentiation of iPMSCs via chromatin remodeling. Taken together, our findings set new metrics to the applications for improving the efficiency and the therapeutic potential of iPMSCs.

A green strategy for preparing durable underwater superoleophobic calcium alginate hydrogel coated-meshes for oil/water separation.

Superhydrophilic and underwater superoleophobic calcium alginate (CA) hydrogel-coated meshes (CAHMs) were prepared via a green dip-coating and self-assembly method without adding any toxic or expensive modifying agents. Since meshes possess intrinsic chemical inert characterisitics, the first CA layer was employed as a precoating and then continually facilitated deposition of CA hydrogel via coordination bonding to form extraordinary underwater superoleophobicity. All results proved that CA was introduced to generate both hydrophilic chemical compositions and rough structures onto resultant mesh surfaces. The obtained meshes, which possessed a underwater oil contact angle (UOCA) of ~154.3° and low oil sliding angle (OSA) of ~7°, could separate various oil/water mixtures with efficiency above 99% and maximum water flux up to 28,108.9 L·m-2·h-1. This separation process was spontaneous and only driven by gravity. Furthermore, as-prepared meshes still maintained high stability under corrosive organic solvents. These outstanding performances made it a promise for oil/water separation in the future.

Role of HGF/c-Met in the treatment of colorectal cancer with liver metastasis.

The system of hepatocyte growth factor (HGF) and its receptor c-Met plays a critical role in tumor invasive growth and metastasis. The mortality rate of colorectal cancer (CRC), one of the most commonly diagnosed malignancies, is increased by it gradual development into metastasis, most frequently in the liver. Overexpression of c-Met, the protein tyrosine kinase receptor for the HCF/scatter factor, has been implicated in the progression and metastasis of human colorectal carcinoma. In this study, we aimed to investigate the role of c-Met in CRC liver metastasis and illustrate the clinical impact of regulating HGF/c-Met signaling in patients with CRC liver metastasis. We found that (I) higher levels of c-Met expression (mRNA and Protein) in CRC liver metastasis than primary CRC by assessing the patient tissue samples; (II) a positive correlation of c-Met expression with tumor stages of CRC liver metastasis, as well as c-Met expression in CRC, live metastasis concurred with regional lymph node metastasis; (III) the clinical impact of downregulation of HGF/c-Met signaling on the reduction of proliferation and invasion in CRC liver metastasis. Therefore, we demonstrate that the regulation of HGF/c-Met pathways may be a promising strategy in the treatment of patients with CRC liver metastasis.

Integrative analysis of gene expression profiles reveals distinct molecular characteristics in oral tongue squamous cell carcinoma.

Oral tongue squamous cell carcinoma (OTSCC) is the most common type of oral cancer. Despite advances in knowledge regarding the genome-scale gene expression pattern of oral cancer, the molecular portrait of OTSCC biology has remained unclear over the last few decades. Furthermore, studies concerning OTSCC gene-expression profiles are limited or inconsistent owing to tissue heterogeneity in single-cohort studies. Consequently, the present study integrated the profile datasets of three cohorts in order to screen for differentially expressed genes (DEGs), and subsequently identified the potential candidate genes and pathways in OTSCC through gene enrichment analysis and protein-protein interaction (PPI) network construction. Using the selected Gene Expression Omnibus datasets GSE13601, GSE31056 and GSE78060, 206 DEGs (125 upregulated and 81 downregulated) were identified in OTSCC, principally associated with extracellular matrix (ECM) organization and the phosphoinositide 3-kinase/protein kinase B signaling pathway. Furthermore, 146/206 DEGs were filtered into the PPI network and 20 hub genes were sorted. Further results indicated that the two most significant modules filtered from the PPI network were associated with ECM organization and human papillomavirus infection, which are important factors affecting OTSCC pathology. Overall, a set of OTSCC-associated DEGs has been identified, including certain key candidate genes that may be of vital importance for diagnosis, therapy and prevention of this disease.

CDX2 inhibits the proliferation and tumor formation of colon cancer cells by suppressing Wnt/ß-catenin signaling via transactivation of GSK-3ß and Axin2 expression.

Caudal-related homeobox transcription factor 2 (CDX2), an intestine-specific nuclear transcription factor, has been strongly implicated in the tumourigenesis of various human cancers. However, the functional role of CDX2 in the development and progression of colorectal cancer (CRC) is not well known. In this study, CDX2 knockdown in colon cancer cells promoted cell proliferation in vitro, accelerated tumor formation in vivo, and induced a cell cycle transition from G0/G1 to S phase, whereas CDX2 overexpression inhibited cell proliferation. TOP/FOP-Flash reporter assay showed that CDX2 knockdown or CDX2 overexpression significantly increased or decreased Wnt signaling activity. Western blot assay showed that downstream targets of Wnt signaling, including ß-catenin, cyclin D1 and c-myc, were up-regulated or down-regulated in CDX2-knockdown or CDX2-overexpressing colon cancer cells. In addition, suppression of Wnt signaling by XAV-939 led to a marked suppression of the cell proliferation enhanced by CDX2 knockdown, whereas activation of this signaling by CHIR-99021 significantly enhanced the cell proliferation inhibited by CDX2 overexpression. Dual-luciferase reporter and quantitative chromatin immunoprecipitation (qChIP) assays further confirmed that CDX2 transcriptionally activates glycogen synthase kinase-3ß (GSK-3ß) and axis inhibition protein 2 (Axin2) expression by directly binding to the promoter of GSK-3ß and the upstream enhancer of Axin2. In conclusion, these results indicated that CDX2 inhibits the proliferation and tumor formation of colon cancer cells by suppressing Wnt/ß-catenin signaling.

Bone Marrow-Derived Mesenchymal Stem Cells Modified with Akt1 Ameliorates Acute Liver GVHD.

BACKGROUND: Liver injury associated with acute graft-versus-host disease (aGVHD) is a frequent and severe complication of hematopoietic stem cell transplantation and remains a major cause of transplant-related mortality. Bone marrow-derived mesenchymal stem cells (BM-MSCs) has been proposed as a potential therapeutic approach for aGVHD. However, the therapeutic effects are not always achieved. In this study, we genetically engineered C57BL/6 mouse BM-MSCs with AKT1 gene and tested whether AKT1-MSCs was superior to control MSCs (Null-MSCs) for cell therapy of liver aGVHD. RESULTS: In vitro apoptosis analyses showed that, under both routine culture condition and high concentration interferon-γ (IFN-γ) (100ng/mL) stimulation condition, AKT1-MSCs had a survival (anti-apoptotic) advantage compared to Null-MSCs. In vivo imaging showed that AKT1-MSCs had better homing capacity and longer persistence in injured liver compared to Null-MSCs. Most importantly, AKT1-MSCs demonstrated an enhanced immunomodulatory function by releasing more immunosuppressive cytokines, such as IL-10. Adoptive transfer of AKT1-MSCs mitigated the histopathological abnormalities of concanavalin A(ConA)-induced liver injury along with significantly lowered serum levels of ALT and AST. The attenuation of liver injury correlated with the decrease of TNF-α and IFN-γ both in liver tissue and in the serum. CONCLUSIONS: In summary, BM-MSCs genetically modified with AKT1 has a survival advantage and an enhanced immunomodulatory function both in vitro and in vivo and thus demonstrates the therapeutic potential for prevention and amelioration of liver GVHD and other immunity-associated liver injuries.

Construction of hydrophobic alginate-based foams induced by zirconium ions for oil and organic solvent cleanup.

Hydrophobic modification of sodium alginate (SA) foams via a simple freeze-drying and post cross-linking induced by zirconium (Zr) ions was developed. All results demonstrated that Zr ions not only constructed surface microstructure but also lowered surface energy of foams, leading to the hydrophobic character. Hydrophobic and oleophilic foams showed excellent adsorption capacities for different oils and organic solvents (11.2-25.9 g/g). Furthermore, SA solution can be also coated on porous substrates, such as melamine sponges (MS) and Nylon strainers (NS), to give hydrophobic modification by Zr ion crosslinking. These excellent performances made them a promising for oil adsorption and cleanup.

Mutations in the P10 region of procaspase-8 lead to chemotherapy resistance in acute myeloid leukemia by impairing procaspase-8 dimerization.

Caspase-8 activation initiates apoptotic signaling cascades, and certain mutations in procasepase-8 have been reported to be associated with the progression and prognosis of different types of tumors. In this study, we have identified four novel mutations, which are highly correlated with chemotherapy resistance and poor prognosis of acute myeloid leukemia (AML) patients, within the P10 subunit of procaspase-8. These newly discovered mutations cause premature termination of translation, resulting in truncated procaspase-8 protein, which is incapable of forming dimer to initiate apoptosis signaling pathway. Further biochemical analysis reveals that the segment of P10 subunit of procaspase-8 consisting of three amino acid residues from L491 to F493 is crucial for the formation of procaspase-8 interdimer, and the aberration of this segment disrupts the dimerization and consequently precludes the activation of caspase-8 and downstream apoptotic signaling pathway. Therefore, the patients with AML who bear these types of P10 mutations were more likely to develop chemotherapy resistance due to impaired apoptotic signaling in cellular system, leading to significantly reduced overall survival (OS) as compared with patients carrying no such types of P10 mutations. Taken together, these newly identified P10 mutations in procaspase-8 could be used as novel biomarkers for predicting response and survival of chemotherapy-treated AML patients, as well as potential therapeutic targets for medical intervention in the future.

BCR-ABL enhances the prolyl isomerase activity of Pin 1 by interacting with DAPK1 in ph+ ALL.

Philadelphia chromosome (Ph)/BCR-ABL-positive (ph+ ) ALL is the most common genetic abnormality associated with ALL and has been shown to confer the worst prognosis to both children and adults. Increasing evidence has revealed that the dysregulation of prolyl isomerase Pin 1 contributes to multicancer development and progression, including ALL, although the underlying molecular mechanisms remain unclear. Here, we report that the expression of Pin 1 was enhanced in ph+ ALL patient samples and was associated positively with the expression of BCR-ABL. Genetically or pharmacologically inhibiting Pin 1 expression or activity produces potent therapeutic efficacy against ph+ ALL. We further demonstrated that BCR-ABL enhances the prolyl isomerase activity of Pin 1 by decreasing the phosphorylated level of Pin 1 at Ser 71 and interacting with DAPK1. The inhibition of BCR-ABL activity by imatinib in human ph+ ALL cells reduces the prolyl isomerase activity of Pin 1, further suggesting a key role of the newly identified BCR-ABL-Pin 1 axis in ph+ ALL progression. Thus, the combined suppression of Pin 1 and BCR-ABL proteins may be exploited as an additional target therapy for ph+ ALL.