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The treatment paradigm of non-small cell lung cancer (NSCLC) has evolved into oncogene-directed precision medicine. Identifying actionable genomic alterations is the initial step towards precision medicine. An important scientific progress in molecular profiling of NSCLC over the past decade is the shift from the traditional piecemeal fashion to massively parallel sequencing with the use of next-generation sequencing (NGS). Another technical advance is the development of liquid biopsy with great potential in providing a dynamic and comprehensive genomic profiling of NSCLC in a minimally invasive manner. The integration of NGS with liquid biopsy has been demonstrated to play emerging roles in genomic profiling of NSCLC by increasing evidences. This review summarized the potential applications of NGS-based liquid biopsy in the diagnosis and treatment of NSCLC including identifying actionable genomic alterations, tracking spatiotemporal tumor evolution, dynamically monitoring response and resistance to targeted therapies, and diagnostic value in early-stage NSCLC, and discussed emerging challenges to overcome in order to facilitate clinical translation in future. [ABSTRACT FROM AUTHOR]

Manufacturing knowledge can be preserved through knowledge accumulation and continuous integration. In order to improve the using efficiency of manufacturing knowledge, these knowledges are stored and used in the way of Knowledge graph. This paper will study the construction of Knowledge graph based on manufacturing process methods and the ability of Knowledge graph to provide services. This kind of manufacturing knowledge capability not only provides the manufacturing realization method of processing technology, but also can correspond to the design realization method of design graphics, providing theoretical support for the integrated realization of design and manufacturing process. [ABSTRACT FROM AUTHOR]

There has been increasing experience in the utilization of intraoperative magnetic resonance imaging (iMRI) for intracranial surgery. Despite this trend, only a few U.S centers have examined the use of this technology for transsphenoidal resection of tumors of the sella.We present the largest series in North America examining the role of iMRI for pituitary adenoma resection. We retrospectively reviewed our institutional experience of 59-patients who underwent transsphenoidal procedures for sellar and suprasellar tumors with iMRI guidance. Of these, 52 patients had a histological diagnosis of pituitary adenoma. The technical results of this subgroup were examined. A 1.5-T iMRI was integrated with the BrainLAB (Feldkirchen, Germany) neuronavigation system. The majority (94%) of tumors in our series were macroadenomas. Seventeen percent of tumors were con?ned to the sella, 49% had suprasellar extensions without involvement of the cavernous sinus, 34% had frank cavernous sinus invasion. All patients underwent at least one iMRI, and 19% require done or more additional sets of intra-operative imaging. In 58% of patients, iMRI led to the surgeon attempting more resection. A gross total resection was obtained in 67% of the patients with planned total resections. There was one case of permanent postoperative diabetes insipidus and no other instances of new hormone replacement. In summary, iMRI was most useful for tumors of the sella with and without suprasellar extension where the information from the iMRI extended the complete resection rate from 40 to 72% and 55 to 88%, respectively. As one would expect, it did not substantially increase the rate of resection of tumors with cavernous sinus invasion. Overall, iMRI was particularly useful in guiding resection safely, aiding in clinical decision making, and allowing identification and preservation of the pituitary stalk and normal pituitary gland. Limitations of the iMRI include a need for additional personnel and training as well as additional operative time, which diminishes over time as personnel learn to optimize workflow efficiency. Additional costs are mitigated in part by using the iMRI as an immediate postoperative scan. Other data emerging from our experience suggest that preservation of normal gland and thus avoidance of hypopituitarism maybe improved by iMRI use, but longer follow-up periods are required to test this conclusion. iMRI can detect unsuspected complications sooner than routine postoperative imaging, potentially leading to improved outcomes. However, larger studies are needed. [ABSTRACT FROM AUTHOR]

Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves angiotensin II (Ang II) to generate Ang-(1-7) which acts mainly through the Mas1 receptor. Here, we identify ACE2 pathway as a critical regulator in the maintenance of thermogenesis and energy expenditure. We found that ACE2 is highly expressed in brown adipose tissue (BAT) and that cold stimulation increases ACE2 and Ang-(1-7) levels in BAT and serum. Ace2 knockout mice (Ace2-/y) and Mas1 knockout mice (Mas1-/-) displayed impaired thermogenesis. Mice transplanted with brown adipose tissue from Mas1-/- display metabolic abnormalities consistent with those seen in the Ace2 and Mas1 knockout mice. In contrast, impaired thermogenesis of Leprdb/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of Ace2 or continuous infusion of Ang-(1-7). Activation of ACE2 pathway was associated with improvement of metabolic parameters, including blood glucose, lipids, and energy expenditure in multiple animal models. Consistently, ACE2 pathway remarkably enhanced the browning of white adipose tissue. Mechanistically, we showed that ACE2 pathway activated Akt/ FoxO1 and PKA pathway, leading to induction of UCP1 and activation of mitochondrial function. Our data propose that adaptive thermogenesis requires regulation of ACE2 pathway and highlight novel potential therapeutic targets for the treatment of metabolic disorders. [ABSTRACT FROM AUTHOR]

Crustacean hyperglycemic hormone (CHH) is a neurohormone found only in arthropods that plays a pivotal role in the regulation of hemolymph glucose levels, molting and stress responses. Although it was determined that a membrane guanylyl cyclase (GC) acts as the CHHreceptor in the Y-organ during ecdysteroidogenesis, the identity of the CHH receptor in the hepatopancreas has not been established. In this study, we identified CHH binding protein (CHHBP), as a potential receptor by screening the annotated unigenes from the transcriptome of Eriocheir sinensis, after removal of the eyestalk. Analysis of the binding affinity between CHH and CHHBP provided direct evidence thatCHHinteracts withCHHBPin a specific bindingmode.Subsequent analysis showed that CHHBP is expressed primarily in the hepatopancreas where it localizes to the cell membrane. In addition, real-time PCR analysis showed that CHHBP transcript levels gradually increase in the hepatopancreas following eyestalk ablation. RNAimediated suppression of CHHBP expression resulted in decreased glucose levels. Furthermore, the reduction of blood glucose induced by CHHBP RNAi reached the same level as that observed in the eyestalk ablation group, suggesting that CHHBP is involved in glucose metabolism regulated by CHH. In addition, compared with the control group, injection of CHH was unable to rescue the decreased glucose levels inCHHBP RNAi crabs.CHH induced transport of 2-NBDGto the outside of cells, with indispensable assistance from CHHBP. Taken together, these findings suggest that CHHBP acts as one type of the primary signal processor of CHH-mediated regulation of cellular glucose metabolism. [ABSTRACT FROM AUTHOR]

The source noise introduced in quantum state preparation of continuous-variable quantum key distribution (CVQKD) needs to be adequately modeled to evaluate its impact. For this purpose, we generalize the entanglement-based scheme of coherent state CVQKD from pure entangled states to mixed entangled states. In the proposed scheme, the source noise is generated via non-maximal entanglement. We prove that the proposed scheme is equivalent to a practical setup with Gaussian source noise. Furthermore, the equivalence is verified by simulation results. [ABSTRACT FROM AUTHOR]

We investigate the security of reverse reconciliation two-way continuous-variable quantum key distribution with source noise at both legitimate sides. Because the source noise originates from imperfect devices, we ascribe it to the legitimate sides rather than the eavesdropper. The trusted model consists of a thermal noise injected into a beam splitter. The expressions of secret key rate are derived against collective entangling cloner attacks for homodyne and heterodyne detections. Simulation results show that by applying the trusted model, the security bound of the reverse reconciliation two-way protocols can be tightened, while the advantage over one-way protocols still maintains. [ABSTRACT FROM AUTHOR]