Background and Aims
Heparin‐binding epidermal growth factor (HB‐EGF), a member of the epidermal growth factor family, plays a pivotal role in the progression of several malignancies, but its role and ...regulatory mechanisms in hepatocellular carcinoma (HCC) remain obscure. Here, we report that transmembrane protease serine 4 (TMPRSS4) significantly enhanced the expression and proteolytic cleavage of HB‐EGF to promote angiogenesis and HCC progression.
Approach and Results
A mechanistic analysis revealed that TMPRSS4 not only increased the transcriptional and translational levels of HB‐EGF precursor, but also promoted its proteolytic cleavage by enhancing matrix metallopeptidase 9 expression through the EGF receptor/Akt/mammalian target of rapamycin/ hypoxia‐inducible factor 1 α signaling pathway. In addition, HB‐EGF promoted HCC proliferation and invasion by the EGF receptor/phosphoinositide 3‐kinase/Akt signaling pathway. The level of HB‐EGF in clinical samples of serum or HCC tissues from patients with HCC was positively correlated with the expression of TMPRSS4 and the microvessel density, and was identified as a prognostic factor for overall survival and recurrence‐free survival, which suggests that HB‐EGF can serve as a potential therapeutic target for HCC. More importantly, we provide a demonstration that treatment with the HB‐EGF inhibitor cross‐reacting material 197 alone or in combination with sorafenib can significantly suppress angiogenesis and HCC progression.
Conclusions
HB‐EGF can be regulated by TMPRSS4 to promote HCC proliferation, invasion, and angiogenesis, and the combination of the HB‐EGF inhibitor cross‐reacting material 197 with sorafenib might be used for individualized treatment of HCC.
Shrimp farming has been the fastest‐growing sector in seawater aquaculture and has contributed to improving the farmers income and the utilization efficiency of aquaculture resources in China. The ...shrimp industry has deployed ever‐improved and innovated methods, from extensive farming to semi‐intensive and intensive farming. Various high‐density intensive culture models, such as high‐land, greenhouse and indoor industrialized culture models, have been used for shrimp pond farming in the coastal area. However, efficiency, environmental and social considerations have led to an increasing adoption of the environmentally‐friendly culture model called integrated multi‐trophic aquaculture (IMTA). This has occurred most rapidly along the northern and central coasts of China. The deployed IMTA culture models reviewed here are shrimp + crab, shrimp + fish, shrimp + sea cucumber, shrimp + jellyfish + clam, shrimp + crab + clam, shrimp + crab + clam + fish and the ridgetail white shrimp polyculture in saline alkaline water, which have been tailored to local conditions and organisms' characteristics. Suitable organism varieties and the maintenance of suitable eco‐friendly water quality have been key to success. The eco‐friendly IMTA culture models described here fully exploit the pond culture resources, to increase production with minimal additional feed and labor inputs, while reducing effluent emissions and treatment cost. The performance of shrimp IMTA models is compared to shrimp monoculture models regarding the economics. An equally important outcome of this publication is making generally accessible the findings from a vast Chinese scientific literature on shrimp culture that has hitherto been unavailable in English.
Background
Thoracic spinal stenosis is a common vertebral degenerative disease, and treatment remains challenging. In recent years, transforaminal endoscopic decompression has been widely used for ...treating lumbar degenerative diseases. However, the efficacy of this procedure for thoracic spinal stenosis has yet to be established. Herein, we report a case of thoracic spinal stenosis treated with transforaminal endoscopic decompression under local anesthesia.
Case report
An 88-year-old man presented with a 1-month history of progressive paralysis and dysesthesia in the bilateral lower extremities. A diagnosis of thoracic spinal stenosis was made, based on physical examination. A two-step percutaneous transforaminal endoscopic thoracic decompression was performed for spinal canal decompression. Over a follow-up of 1 year, a favorable outcome was noted.
Conclusion
Transforaminal endoscopic decompression is a safe and an effective surgical approach for the treatment of thoracic spinal stenosis. For patients with thoracic spinal stenosis, accurate diagnosis and elaborate surgical planning should be highlighted, and the surgical outcome can be favorable.
We investigate a family of dinuclear dysprosium metallocene single‐molecule magnets (SMMs) bridged by methyl and halogen groups Cp′2Dy(μ‐X)2 (Cp′=cyclopentadienyltrimethylsilane anion; 1: X=CH3−; 2: ...X=Cl−; 3: X=Br−; 4: X=I−). For the first time, the magnetic easy axes of dysprosium metallocene SMMs are experimentally determined, confirming that the orientation of them are perpendicular to the equatorial plane which is made up of dysprosium and bridging atoms. The orientation of the magnetic easy axis for 1 deviates from the normal direction (by 10.3°) due to the stronger equatorial interactions between DyIII and methyl groups. Moreover, its magnetic axes show a temperature‐dependent shifting, which is caused by the competition between exchange interactions and Zeeman interactions. Studies of fluorescence and specific heat as well as ab initio calculations reveal the significant influences of the bridging ligands on their low‐lying exchange‐based energy levels and, consequently, low‐temperature magnetic properties.
The single‐molecule magnets (SMMs) Cp′2Dy(μ‐X)2 (Cp′=cyclopentadienyltrimethylsilane anion; X=CH3−, Cl−, Br−, I−) are investigated. For the first time, the magnetic easy axes of dysprosium metallocene SMMs are experimentally determined, confirming that they are oriented perpendicular to the equatorial plane which is made up of dysprosium and bridging atoms.
Autonomous driving, as an emerging technology, is developing rapidly. However, a number of obstacles appear to be holding back the widespread adoption of autonomous driving. Cybersecurity issues, ...which have a significant impact both technically and psychologically on people's willingness to use autonomous driving, are one of the most significant barriers. Attackers have adopted increasingly diverse threat methods, increasing cyber-attacks. Despite these threats, global standards have been developed for road vehicle safety and cybersecurity. These standards are intended to guide manufacturers of automotive systems. For instance, the ISO and SAE have jointly released the international standard ISO/SAE 21434 (Road Vehicles-Cybersecurity Engineering) for road vehicle cybersecurity. However, focusing on the development of onboard systems alone when examining the application of these standards is not sufficient. Currently, we lack a methodology to directly apply the ISO/SAE 21434 standard to automotive system engineering projects. In particular, the overall framework of cybersecurity design for intelligent connected vehicle systems needs to be developed. This paper proposes an overall cybersecurity assurance framework (ODFa<inline-formula><tex-math notation="LaTeX">{}^{2}</tex-math></inline-formula>) based on the ISO/SAE 21434 standard to assist system engineers in understanding security risks, evaluating the feasibility of attack implementation, and determining the trade-off methods for security countermeasures. We illustrate through a case study how this model-based framework may be applied to cybersecurity engineering in intelligent connected vehicles and mobility service platforms. Furthermore, the results of comparative experiments indicate that the proposed strategy optimization algorithm outperforms existing algorithms in terms of time efficiency under certain conditions.
A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 ...EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 × 10(-3) to 1.41 × 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.
•The multi-island genetic algorithm (MIGA) is applied to optimize the configuration of a universal selective solar absorber, which is superior to traditional genetic algorithm (GA) in finding the ...global optimum.•The optimization design is conducted to achieve maximum absorptance A(λ) over solar spectrum and minimum emittance ε(λ) in the mid-infrared band at the same time.•A set of optimal geometric parameters are obtained, with the solar absorptance greater than 0.932 with 96% probability and mid-infrared emittance lower than 0.058 simultaneously.•The optimal absorber is a combination of great characteristics, such as highly spectral selectivity, polarization independence and angle insensitivity.
Based on the demand for ideal selective solar absorbers to harvest a full solar spectrum, we present an auspicious method, the multi-island genetic algorithm (MIGA), to optimize the configuration of a universal selective solar absorber, which can avoid the premature phenomenon and superior to traditional genetic algorithm. The selective solar absorber equipped with the set of optimal geometric parameters exhibits the solar absorptance greater than 0.932 with 96% probability and mid-infrared emittance lower than 0.058 at the same time considering unavoidable 20% fabrication uncertainties in the design variables. In addition, the absorber is a combination of great characteristics, such as polarization independence and angle insensitivity. The hybrid resonance modes of Wood’s anomaly, surface plasmon polariton and magnetic polariton are responsible for the high absorption performance. The MIGA method presented is proved to be an effective and robust tool in the optimization of micro-nano structures with manufacturability for thermal and energy applications.
Cushing's disease, also known as adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (PAs) that cause excess cortisol production, accounts for up to 85% of corticotrophin-dependent ...Cushing's syndrome cases. However, the genetic alterations in this disease are unclear. Here, we performed whole-exome sequencing of DNA derived from 12 ACTH-secreting PAs and matched blood samples, which revealed three types of somatic mutations in a candidate gene, USP8 (encoding ubiquitin-specific protease 8), exclusively in exon 14 in 8 of 12 ACTH-secreting PAs. We further evaluated somatic USP8 mutations in additional 258 PAs by Sanger sequencing. Targeted sequencing further identified a total of 17 types of USP8 variants in 67 of 108 ACTH-secreting PAs (62.04%). However, none of these mutations was detected in other types of PAs (n = 150). These mutations aggregate within the 14-3-3 binding motif of USP8 and disrupt the interaction between USP8 and 14-3-3 protein, resulting in an elevated capacity to protect EGFR from lysosomal degradation. Accordingly, PAs with mutated USP8 display a higher incidence of EGFR expression, elevated EGFR protein abundance and mRNA expression levels of POMC, which encodes the precursor of ACTH. PAs with mutated USP8 are significantly smaller in size and have higher ACTH production than wild-type PAs. In surgically resected primary USP8-mutated tumor cells, USP8 knockdown or blocking EGFR effectively attenuates ACTH secretion. Taken together, somatic gain-of-function USP8 mutations are common and contribute to ACTH overproduction in Cushing's disease. Inhibition of USP8 or EGFR is promising for treating USP8-mutated corticotrophin adenoma. Our study highlights the potentially functional mutated gene in Cushing's disease and provides insights into the therapeutics of this disease.
Pancreatic cancer is highly lethal malignant tumor with characterised rapid progression, invasiveness and resistance to radiochemotherapy. Transforming growth factor-β (TGF-β) signaling plays a dual ...role in both pro-tumorigenic and tumor suppressive of pancreatic cancer, depending on tumor stage and microenvironment. TGF-β signaling components alteration are common in pancreatic cancer, and its leading role in tumor formation and metastases has received increased attention. Many therapies have investigated to target TGF-β signaling in the preclinical and clinical setting. In this review, we highlight the dual roles of TGF-β and touch upon the perspectives on therapeutic target of TGF-β signaling in pancreatic cancer.
MOF-76 exhibits not only high sensitivity for the detection of U(vi), but also high adsorption capacity of 298 mg g(-1) at a low pH value of ∼3.0. Furthermore, the high selectivity for uranium ...adsorption over a series of competing metal ions is also illustrated.
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