Synthetic lethality between TP53 and ENDOD1

The atypical nuclease ENDOD1 functions with cGAS-STING in innate immunity. Here we identify a previously uncharacterized ENDOD1 function in DNA repair. ENDOD1 is enriched in the nucleus following H2O2 treatment and ENDOD1−/− cells show increased PARP chromatin-association. Loss of ENDOD1 function is synthetic lethal with homologous recombination defects, with affected cells accumulating DNA double strand breaks. Remarkably, we also uncover an additional synthetic lethality between ENDOD1 and p53. ENDOD1 depletion in TP53 mutated tumour cells, or p53 depletion in ENDOD1−/− cells, results in rapid single stranded DNA accumulation and cell death. Because TP53 is mutated in ~50% of tumours, ENDOD1 has potential as a wide-spectrum target for synthetic lethal treatments. To support this we demonstrate that systemic knockdown of mouse EndoD1 is well tolerated and whole-animal siRNA against human ENDOD1 restrains TP53 mutated tumour progression in xenograft models. These data identify ENDOD1 as a potential cancer-specific target for SL drug discovery

Aging Characteristics of Plant Hot-Mix Recycled Asphalt and Its Induced Aging on New Asphalt

In order to explore the aging process and mechanism of new and old asphalt in plant hot-mix recycled asphalt mixture during the mixing and use process, the liquid viscosity test and low-temperature bending creep test are carried out to test the dynamic viscosity, stiffness modulus, creep rate, and low-temperature flexibility of the matrix asphalt, recycled asphalt, and old and new asphalt after rolling thin film oven test (RTFOT) aging and pressurized aging vessel (PAV) aging. The macroscopic performance attenuation law of new and old asphalt during the aging process in thermal regeneration is compared and analyzed. After that, the aging process and mechanism of new and old asphalt are explored by infrared spectroscopy and differential calorimetric analysis scanning. The results show that RTFOT aging and PAV aging make the viscosity of recycled asphalt rise significantly and the low temperature performance decline rapidly. After RTFOT aging and PAV aging of new and old asphalt, the dynamic viscosity and low-temperature performance change range is much higher than that of the matrix asphalt. Some technical indicators are even closer to the recycled asphalt after aging, which proves that its aging speed is faster than that of the matrix asphalt. Meanwhile, the results of infrared spectroscopy and differential scanning calorimetry analysis show that in addition to the independent aging of new asphalt and recycled asphalt, there is also a chemical effect between them–that is, some active groups in recycled asphalt have a more obvious promotion effect on the aging process of new asphalt, here called “induced aging”. This induced aging changes the aging mechanism of the matrix asphalt by changing the aging process of it, which greatly limits the popularization and application of thermal regeneration technology

Surface-enhanced Raman spectra of hemoglobin for esophageal cancer diagnosis

Surface-enhanced Raman scattering (SERS) spectra of hemoglobin from 30 esophageal cancer patients and 30 healthy persons have been detected and analyzed. The results indicate that, there are more iron ions in low spin state and less in high for the hemoglobin of esophageal cancer patients than normal persons, which is consistent with the fact that it is easier to hemolyze for the blood of cancer patients. By using principal component analysis (PCA) and discriminate analysis, we can get a three-dimensional scatter plot of PC scores from the SERS spectra of healthy persons and cancer patients, from which the two groups can be discriminated. The total accuracy of this method is 90%, while the diagnostic specificity is 93.3% and sensitivity is 86.7%. Thus SERS spectra of hemoglobin analysis combined with PCA may be a new technique for the early diagnose of esophageal cancer

PSMA7 Directly Interacts with NOD1 and Regulates its Function

Background/Aims: Recent reports showed that proteasome subunit alpha type-7 (PSMA7) was overexpressed in colorectal cancer. To investigate the mechanism of PSMA7 in promotion of colorectal cancer, we screened for its interaction partners. Methods and Results: This study found that PSMA7 associated with nucleotide-binding oligomerization domain-containing protein 1 (NOD1) by yeast two-hybrid screening, co-immunoprecipitation (IP), and GST-pull down assay. As shown by Western blotting and ubiquitin assay, PSMA7 downregulated the expression of NOD1 in a proteasome-dependent manner. Overexpression of PSMA7 in HCT116 cells resulted in an inhibition of NOD1-mediated apoptosis and NF-κB activation, whereas knockdown of PSMA7 by RNA interference enhanced NOD1 activity. Conclusion: Our data suggest that PSMA7 is a negative regulator of the NOD1, and may promote tumor growth by its inhibitory role on NOD1

High-Entropy Alloy Activating Laves-Phase Network for Multi-Component Metallic Coatings with High Hardness

The low hardness and poor wear resistance of laser-cladding 316L stainless steel impose significant constraints on its practical applications. In this study, a strategy for strengthening laser-cladding 316L stainless steel with WMoTaNb refractory high-entropy alloy as a reinforcement material is proposed. The results confirm that the coating primarily comprises a body-centered cubic (BCC) Fe-based solid solution, a network-distributed hexagonal Fe2X (X = W, Mo, Ta, and Nb) Laves phase, and a diffusely distributed face-centered cubic (FCC) (Ta, Nb)C phase. The Fe-based solid solution distributes along columnar and fine dendrites, while the Laves phase and (Ta, Nb)C phase are in the inter-dendrites. The presence of a significant number of network Laves phases exhibiting high strength and hardness is the primary factor contributing to the enhancement of coating microhardness. The hardness of the composite coating is increased by nearly twice compared to that of the 316L coating, resulting in an improved wear resistance. The present work can shed light on designing and fabricating 316L stainless steel coating with enhanced hardness and wear resistance

Preventive effect and mechanism of Tibetan tea extract on thrombosis in arachidonic acid-induced zebrafish determined via RNA-seq transcriptome profiles.

Thrombosis is a key pathological event in cardiovascular diseases and is also the most important targeting process for their clinical management. In this study, arachidonic acid (AA) was used to induce thrombus formation in zebrafish larvae. Blood flow, red blood cell (RBCs) aggregation and cellular oxidative stress were measured to evaluate the antithrombotic effect of Tibetan tea (TT). Meanwhile, the potential molecular mechanism was further explored by transcriptome sequencing (RNA-seq). The results indicated that TT could significantly restore heart RBCs intensity of thrombotic zebrafish, whilst decreasing RBCs accumulation in the caudal vein. The transcriptome analysis revealed that the preventive effect of TT on thrombosis could be mostly attributed to changes in lipid metabolism related signaling pathways, such as fatty acid metabolism, glycerollipid metabolism, ECM-receptor interaction and steroid biosynthesis signaling pathway. This study demonstrated that Tibetan tea could alleviate thrombosis by reducing oxidative stress levels and regulating lipid metabolism

Heterogeneously-catalyzed aerobic oxidation of furfural to furancarboxylic acid with CuO-Promoted MnO2

A cost-effective and sustainable noble-metal free catalyst system based on ubiquitously available Mn–Cu bimetallic oxides was served as efficient catalysts for furfural selective oxidation to furancarboxylic acid (FA). Interestingly, Mn2Cu1Ox exhibited an excellent furfural conversion of 99% with quantitative selectivity toward FA. Especially, we demonstrate the significant weakening of the Mn–O bonds with the incorporation of CuO into the Mn–Cu oxides, resulting in an improved OL reactivity of Mn2Cu1Ox, which brings about a higher catalytic activity for furfural oxidation. More importantly, Mn2Cu1Ox could exhibit YFA>90% over 5 cycles of reusability test. Through this study, the relationship between the morphology, surface chemistry, and catalytic activity of Mn–Cu bimetallic oxides are elucidated, providing a simple and environmentally friendly catalytic strategy and scientific basis for the development of Mn–Cu bimetallic oxides bioderived molecular aerobic oxidation materials

Down-Regulating the High Level of 17-Beta-Hydroxysteroid Dehydrogenase 13 Plays a Therapeutic Role for Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and there is no specific drug to treat it. Recent results showed that 17-beta-hydroxysteroid dehydrogenase type 13 (HSD17B13) is associated with liver diseases, but these conclusions are controversial. Here, we showed that HSD17B13 was more highly expressed in the livers of NAFLD patients, and high expression was induced in the livers of murine NAFLD models and cultural hepatocytes treated using various etiologies. The high HSD17B13 expression in the hepatocytes facilitated the progression of NAFLD by directly stabilizing the intracellular lipid drops and by indirectly activating hepatic stellate cells. When HSD17B13 was overexpressed in the liver, it aggravated liver steatosis and fibrosis in mice fed with a high-fat diet, while down-regulated the high expression of HSD17B13 by short hairpin RNAs produced a therapeutic effect in the NAFLD mice. We concluded that high HSD17B13 expression is a good target for the development of drugs to treat NAFLD