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Tumor development relies on a complex and aberrant tissue environment in which cancer cells receive the necessary nutrients for growth, survive through immune escape, and acquire mesenchymal properties that mediate invasion and metastasis. Stromal cells and soluble mediators in the tumor microenvironment (TME) exhibit characteristic anti-inflammatory and protumorigenic activities. Ubiquitination, which is an essential and reversible posttranscriptional modification, plays a vital role in modulating the stability, activity and localization of modified proteins through an enzymatic cascade. This review was motivated by accumulating evidence that a series of E3 ligases and deubiquitinases (DUBs) finely target multiple signaling pathways, transcription factors and key enzymes to govern the functions of almost all components of the TME. In this review, we systematically summarize the key substrate proteins involved in the formation of the TME and the E3 ligases and DUBs that recognize these proteins. In addition, several promising techniques for targeted protein degradation by hijacking the intracellular E3 ubiquitin-ligase machinery are introduced.

Internal ribosome entry site (IRES)-dependent translation is a mechanism distinct from 5′ cap-dependent translation. IRES elements are located mainly in the 5′ untranslated regions (UTRs) of viral and eukaryotic mRNAs. However, IRESs are also found in the coding regions of some viral and eukaryotic genomes to initiate the translation of some functional truncated isoforms. Here, five putative IRES elements of human rhinovirus 16 (HRV16) were identified in the coding region of the nonstructural proteins P2 and P3 through fusion with green fluorescent protein (GFP) expression vectors and bicistronic vectors with a hairpin structure. These five putative IRESs were located at nucleotide positions 4286-4585, 5002-5126, 6245-6394, 6619-6718, and 6629-6778 in the HRV16 genome. The functionality of the five IRESs was confirmed by their ability to initiate GFP expression in vitro. This suggests that an alternative mechanism might be used to increase the efficiency of replication of HRV16.

To investigate the feasibility of automatic machine learning (autoML) based on native T1 mapping to predict late gadolinium enhancement (LGE) status in hypertrophic cardiomyopathy (HCM). Ninety-one HCM patients and 44 healthy controls who underwent cardiovascular MRI were enrolled. The native T1 maps of HCM patients were classified as LGE ( +) or LGE (-) based on location-matched LGE images. An autoML pipeline was implemented using the tree-based pipeline optimization tool (TPOT) for 3 binary classifications: LGE ( +) and LGE (-), LGE (-) and control, and HCM and control. TPOT modeling was repeated 10 times to obtain the optimal model for each classification. The diagnostic performance of the best models by slice and by case was evaluated using sensitivity, specificity, accuracy, and microaveraged area under the curve (AUC). Ten prediction models were generated by TPOT for each of the 3 binary classifications. The diagnostic accuracy obtained with the best pipeline in detecting LGE status in the testing cohort of HCM patients was 0.80 by slice and 0.79 by case. In addition, the TPOT model also showed discriminability between LGE (-) patients and control (accuracy: 0.77 by slice; 0.78 by case) and for all HCM patients and controls (accuracy: 0.88 for both). Native T1 map analysis based on autoML correlates with LGE ( +) or (-) status. The TPOT machine learning algorithm could be a promising method for predicting myocardial fibrosis, as reflected by the presence of LGE in HCM patients without the need for late contrast-enhanced MRI sequences. • The tree-based pipeline optimization tool (TPOT) is a machine learning algorithm that could help predict late gadolinium enhancement (LGE) status in patients with hypertrophic cardiomyopathy. • The TPOT could serve as an adjuvant method to detect LGE by using information from native T1 maps, thus avoiding the need for contrast agent. • The TPOT also detects native T1 map alterations in LGE-negative patients with hypertrophic cardiomyopathy.

Background The pathogenesis of kidney stone disease (KSD) is not fully understood, and potential contributing factors remain to be explored. Several studies have revealed that the urinary microbiome (urobiome) of stone formers was distinct from that of healthy individuals using 16S rRNA gene sequencing, most of which only provided microbial identification at the genus level. 2bRAD sequencing for Microbiome (2bRAD-M) is a novel sequencing technique that enables accurate characterization of the low-biomass microbiome at the species resolution. We aimed to apply 2bRAD-M to profile the renal pelvis urobiome of unilateral kidney stone patients and compared the urobiome with and without stone(s). Method A total of 30 patients with unilateral stones were recruited, and their renal pelvis urine from both sides was collected. A ureteroscope was inserted into the renal pelvis with stone(s) and a ureteral catheter was placed into the ureteroscope to collect renal pelvis urine. This procedure was repeated again with new devices to collect the urine of the other side. 2bRAD-M was performed to characterize the renal pelvis urobiome of unilateral stone formers to explore whether microbial differences existed between the stone side and the non-stone side. Results The microbial community composition of the stone side was similar to that of the non-stone side. Paired comparison showed that Corynebacterium was increased and Prevotella and Lactobacillus were decreased in the stone side. Four species (Prevotella bivia, Lactobacillus iners, Corynebacterium aurimucosum, and Pseudomonas sp_286) were overrepresented in the non-stone side. 24 differential taxa were also identified between two groups by linear discriminant analysis effect size (LEfSe). Extensive and close connections among genera and species were observed in the correlation analysis. Moreover, a random forest classifier was constructed using specific enriched species, which can distinguish the stone side from the non-stone side with an accuracy of 71.2%. Conclusion This first 2bRAD-M microbiome survey gave an important hint towards the potential role of urinary dysbiosis in KSD and provided a better understanding of mechanism of stone formation.

On 18 January 2016, the Zhangjiazhuang high-speed railway tunnel in Ledu, Qinghai Province, China, underwent serious deformation and structural damage. A crack formed at the top of the tunnel and the concrete on the crown peeled off. As a result, the tunnel could not be operated for three months. In order to determine the types and spatial distribution of the landslides in the region and the surface deformation characteristics associated with the tunnel deformation, we used field geological and geomorphological surveys, unmanned aerial vehicle image interpretation and differential interferometric synthetic aperture radar (D-InSAR) surface deformation monitoring. Nine ancient and old landslides were identified and analysed in the study area. Surface deformation monitoring and investigation of buildings in several villages on the slope front showed that the tunnel deformation was not related to deep-seated gravitational slope deformation. However, surface deformation monitoring revealed an active NEE-SWW fault in the area intersecting the tunnel at the location of the tunnel rupture. This constitutes a plausible mechanism for the deformation of the tunnel. Our study highlights the need for detailed engineering geomorphological investigations to better predict the occurrence of tunnel deformation events in the future.

Helium ion irradiation at 350 °C was performed to study equilibrium segregation and radiation-induced segregation (RIS) of Cr at grain boundaries in reduced activation ferritic/martensitic steels. Cr concentration at grain boundary was measured by scanning transmission electron microscopy with an energy-dispersive spectrometer. The measured Cr concentration at grain boundaries in heat treated zone was 11.7 and 12.8 wt.% in irradiated zone, respectively, which matched well to the calculated results from Mclean and modified Perk model. Equilibrium segregation and RIS of Cr mechanisms were theoretically analysed. The analysis indicates that as temperature rises, equilibrium Cr segregation decreases monotonically, while RIS of Cr has a bell-shape profile, which increases first and then decreases. It is also shown that at low and high temperatures, equilibrium segregation of Cr is higher than that of RIS; at intermediate temperatures, equilibrium Cr segregation is lower than RIS.

Sponsored search auction has been recently studied and auctioneer’s revenue is an important consideration in probabilistic single-item second-price auctions. Some papers have analyzed the revenue maximization problem on different methods to bundle contexts. In this paper, we propose a more flexible and natural method which is called the bracketing method.We prove that finding a bracketing scheme that maximizes the auctioneer’s revenue is strongly NP-hard. Then, a heuristic algorithm is given. Experiments on three test cases show that the revenue of the optimal bracketing scheme is very close to the optimal revenue without any bundling constraint, and the heuristic algorithm performs very well. Finally, we consider a simpler model that for each row in the valuation matrix, the non-zero cells have the same value. We prove that the revenue maximization problem with K-anonymous signaling scheme and cardinality constrained signaling scheme in this simpler model are both NP-hard.

Woody forage is a new feeding resource used worldwide, and silage is the main long-term storage, mediated by micro-organisms present during their processing. The objectives of our work were to evaluate the fermentation dynamics and to characterize the bacterial community of our typical woody forages. We selected four typical woody forages: paper mulberry (Broussonetia papyrifera), mulberry (Morus alba L.), moringa tree (Moringa oleifera), and Anthocephalus chinensis (Neolamarckia cadamba). The materials were ensiled and sampled after ensiling 1, 3, 5, 7, 15, 30, and 60 days. Our results indicate that woody forages have good forage properties with relatively high crude protein content and low neutral detergent fiber and acid detergent fiber content. However, the water soluble carbohydrate content in paper mulberry was considerably low (18.67 g kg−1), which makes ensiling difficult. The lactic acid and acetic acid contents in each of the four materials were reduced after 3 days of ensiling and increased again after 30 days of ensiling, with the exception of Anthocephalus chinensis. Anthocephalus chinensis and moringa tree were well-preserved after 7 and 60 days of ensiling, respectively, with low pH and ammonia nitrogen content. Cyanobacteria was predominant in moringa tree and Anthocephalus chinensis before ensiling, and Lactobacillus became dominant after 15 days of ensiling. Enterobacter dominated the paper mulberry and mulberry during fermentation process and accelerated their poor silage quality. Therefore, the conformity of bacterial community succession with ensiling parameters guaranteed the final quality of woody forage silages, and this might aid in controlling the manufacturing process.

In this paper, we investigate the sample size requirement for exact recovery of a high order tensor of low rank from a subset of its entries. We show that a gradient descent algorithm with initial value obtained from a spectral method can, in particular, reconstruct a ${d\times d\times d}$ tensor of multilinear ranks $(r,r,r)$ with high probability from as few as $O(r^{7/2}d^{3/2}\log^{7/2}d+r^7d\log^6d)$ entries. In the case when the ranks $r=O(1)$, our sample size requirement matches those for nuclear norm minimization (Yuan and Zhang, 2016a), or alternating least squares assuming orthogonal decomposability (Jain and Oh, 2014). Unlike these earlier approaches, however, our method is efficient to compute, easy to implement, and does not impose extra structures on the tensor. Numerical results are presented to further demonstrate the merits of the proposed approach., 56 pages, 4 figures

This paper addresses the exponential stability for an interconnected system of an nth-order ODE system with the input governed by the Dirichlet boundary of a heat equation, and conversely, the output of the ODE is fluxed into the heat equation. The semigroup approach is adopted to show that the system operator is well-posed. We establish the exponential stability of the system by Riesz basis method. Furthermore, with MATLAB software, some numerical simulations are presented to show the effectiveness of the interconnection between the heat PDE and ODE systems.

The noncovalent interactions, including hydrogen, halogen and pnicogen bonds, are widely known due to their significant role in both chemical reactions and biological phenomena. In this work, the potential acting on an electron in a molecule (PAEM) is introduced to present the strength and regioselectivity of noncovalent interaction. The PAEM height of noncovalent bonds, Dpb, can characterize the strength of the interaction, which has the linear relationships with noncovalent binding distances and binding energies. Here, we employ the molecular face theory (MFT) based on the PAEM to visualize reactive sites for the monomers in noncolvalent bond complexes. The electron density extremes on the molecular face (MF) regarded as the local reactivity descriptor are applied to exhibit the regioselectivity and preferred direction for monomers in hydrogen, halogen and pnicogen binding complexes, in good agreement with the chemical convention and ab initio calculation results. And the overlap distances of MF between dimers have been proposed and obtained to evaluate the strength of noncovalent interaction. The MFT provides a new way to demonstrate the regioselectivity and can be applied to larger and other type molecules in the future.

In the original publication of this article [1], Fig. 6 is wrong and the updated figure is shown below.