A 60Mb/s -64dBm Body Channel Communication Transceiver Utilizing Manchester Code.

Body channel communication (BCC) which uses the human body as the communication channel has shown better energy efficiency and security compared with air channel communication. This article presents a simple, stable, and high transfer rate BCC technique using Manchester encoding, capacitive termination, and digital signal transfer operation. Manchester encoding is used to realize the spectrum migration of the baseband signal, and digital signal transmission simplifies system design and improves signal stability. The chip is fabricated in 65-nm technology. The experimental results show that the proposed transceiver achieved the highest data rates of 60 Mbps and the measured RX sensitivity is -64dBm. And the chip is also used to set up a multi-sensor nodes communication system to realize the data interaction between one hub and eight slave sensors utilizing the human body as the communication medium.

A Mutation-driven oncofetal regression fuels phenotypic plasticity in colorectal cancer.

Targeting cancer stem cells (CSCs) is crucial for effective cancer treatment 1 . However, the molecular mechanisms underlying resistance to LGR5 + CSCs depletion in colorectal cancer (CRC) 2,3 remain largely elusive. Here, we unveil the existence of a primitive cell state dubbed the oncofetal (OnF) state, which works in tandem with the LGR5 + stem cells (SCs) to fuel tumor evolution in CRC. OnF cells emerge early during intestinal tumorigenesis and exhibit features of lineage plasticity. Normally suppressed by the Retinoid X Receptor (RXR) in mature SCs, the OnF program is triggered by genetic deletion of the gatekeeper APC. We demonstrate that diminished RXR activity unlocks an epigenetic circuity governed by the cooperative action of YAP and AP1, leading to OnF reprogramming. This high-plasticity state is inherently resistant to conventional chemotherapies and its adoption by LGR5 + CSCs enables them to enter a drug-tolerant state. Furthermore, through phenotypic tracing and ablation experiments, we uncover a functional redundancy between the OnF and stem cell (SC) states and show that targeting both cellular states is essential for sustained tumor regression in vivo . Collectively, these findings establish a mechanistic foundation for developing effective combination therapies with enduring impact on CRC treatment.

WNTinib is a multi-kinase inhibitor with specificity against ß-catenin mutant hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. ß-Catenin (CTNNB1)-mutated HCC represents 30% of cases of the disease with no precision therapeutics available. Using chemical libraries derived from clinical multi-kinase inhibitor (KI) scaffolds, we screened HCC organoids to identify WNTinib, a KI with exquisite selectivity in CTNNB1-mutated human and murine models, including patient samples. Multiomic and target engagement analyses, combined with rescue experiments and in vitro and in vivo efficacy studies, revealed that WNTinib is superior to clinical KIs and inhibits KIT/mitogen-activated protein kinase (MAPK) signaling at multiple nodes. Moreover, we demonstrate that reduced engagement on BRAF and p38α kinases by WNTinib relative to several multi-KIs is necessary to avoid compensatory feedback signaling-providing a durable and selective transcriptional repression of mutant ß-catenin/Wnt targets through nuclear translocation of the EZH2 transcriptional repressor. Our studies uncover a previously unknown mechanism to harness the KIT/MAPK/EZH2 pathway to potently and selectively antagonize CTNNB1-mutant HCC with an unprecedented wide therapeutic index.

A case of bilateral synchronous double primary lung cancer secondary to bladder cancer: From the next-generation sequencing prospect.

One year following bladder cancer surgery, a 65-year-old man had computed tomography (CT) that revealed bilateral pulmonary nodules. Pulmonary wedge resections were performed after the nodules were found to grow in follow-up. Unusually, we found that these two lesions were not homologous, nor were they metastases from prior bladder cancer, and therefore, synchronous double primary lung cancer (sDPLC) was diagnosed. The immunohistochemical findings excluded the possibility of bladder cancer metastasis, but could not determine whether they were from the same source. Next generation sequencing (NGS) supported the diagnosis sDPLC because they amply demonstrated the two sources' distinct origins. Finally, after discussion with pathologists, this patient was diagnosed as small cell lung carcinoma (SCLC) and received postoperative EP chemotherapy. We also documented a few rather uncommon alterations that might serve as a foundation for further investigation. This case suggests that in addition to immunohistochemical, NGS is also helpful to clarify the etiology and refine the pathological classification of tumors, which has guiding significance for the establishment of precise diagnosis and optimal treatment.

Cognitive skill learning in multiple sclerosis: A meaningful component of the neuropsychological profile.

Cognitive skill learning (CSL) refers to the capacity to improve performance on specific cognitive operations through repeated practice. We hypothesized that high CSL aptitude may promote accumulation of cognitive reserve, and resiliency to cognitive decline, in people with Multiple Sclerosis (MS). Using an adaptive working memory training paradigm, we obtained CSL aptitude indices (amount of improvement on the training task over time) in MS patients for a single session of practice (25-30 min), and longer-term practice (twenty sessions). Neuropsychological performance was assessed with the Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and the Raven's Advanced Progressive Matrices (RAPM). CSL aptitude measures were positively correlated with neuropsychological performance, and had high diagnostic accuracy for classifying cognitive impairment in MS, defined as 1.5 SD below the demographics-corrected normative mean of the SDMT. Positive relationships between CSL aptitude measures and neuropsychological performance tended to be more pronounced for individuals with high estimated cognitive reserve, suggesting that high CSL aptitude is a a factor that promotes the protective effects of cognitive reserve. Furthermore, regression analyses indicated that CSL aptitude is separable from baseline cognitive capacity. The findings suggest that CSL aptitude impacts the neuropsychological profile in MS, and may be a factor underlying variance in cognitive resiliency.

An SCM-G2SFCA Model for Studying Spatial Accessibility of Urban Parks.

The urban park is the main leisure and entertainment place in residents' daily lives. The accessibility of parks is closely related to the physical and mental health of the residents. Although many scholars have conducted a great deal of research on the spatial accessibility of urban parks, they have rarely considered the supply competition among different parks and the impact of multiple travel modes on the spatial accessibility of parks. Therefore, based on Baidu map navigation data, in this paper, the park Baidu score is used to represent the competitive relationship among different parks, and the impact of multiple travel modes on the spatial accessibility of parks is considered. A supply competition and multiple travel modes Gaussian two-step floating catchment area (SCM-G2SFCA) model is established to evaluate the spatial accessibility of the parks in the Wuhou District, Chengdu, China. The results show that (1) compared with traditional methods, the SCM-G2SFCA model can obtain more accurate results using Baidu map navigation data. (2) There are obvious spatial differences in the accessibility distribution of the parks in the Wuhou District, Chengdu, with high accessibility in the south and low accessibility in the north. The Jinyang and Huaxing sub-districts in the southern suburbs have the highest park accessibility and can obtain more adequate park services. The Fangcaojie and Cujin sub-districts in the northern urban areas have the lowest park accessibility and are relatively lacking in park services. The research results of this study have important reference value for the rational planning of urban parks and the improvement of the spatial accessibility of urban parks in the Wuhou District of Chengdu and similar urban areas.

MicroRNA-22 inhibits cell growth and metastasis in breast cancer via targeting of SIRT1.

[This retracts the article DOI: 10.3892/etm.2017.4590.].

Dietary Patterns, Carbohydrates, and Age-Related Eye Diseases.

Over a third of older adults in the U.S. experience significant vision loss, which decreases independence and is a biomarker of decreased health span. As the global aging population is expanding, it is imperative to uncover strategies to increase health span and reduce the economic burden of this age-related disease. While there are some treatments available for age-related vision loss, such as surgical removal of cataracts, many causes of vision loss, such as dry age-related macular degeneration (AMD), remain poorly understood and no treatments are currently available. Therefore, it is necessary to better understand the factors that contribute to disease progression for age-related vision loss and to uncover methods for disease prevention. One such factor is the effect of diet on ocular diseases. There are many reviews regarding micronutrients and their effect on eye health. Here, we discuss the impact of dietary patterns on the incidence and progression of age-related eye diseases, namely AMD, cataracts, diabetic retinopathy, and glaucoma. Then, we focus on the specific role of dietary carbohydrates, first by outlining the physiological effects of carbohydrates on the body and then how these changes translate into eye and age-related ocular diseases. Finally, we discuss future directions of nutrition research as it relates to aging and vision loss, with a discussion of caloric restriction, intermittent fasting, drug interventions, and emerging randomized clinical trials. This is a rich field with the capacity to improve life quality for millions of people so they may live with clear vision for longer and avoid the high cost of vision-saving surgeries.

Exosome-transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma.

BACKGROUND: Receptor tyrosine kinase AXL has been found to be highly expressed in osteosarcoma and positively associated with poor prognosis. There are tumor groups with high or low AXL expression, which had different capabilities of invading vessels and forming distal metastases. Exosome-transmitted lncRNA may be transferred intercellularly to promote tumor cells' proliferation and invasion. METHODS: Exosomes were detected by electron microscopy, particle size analysis, and western blotting. High-throughput sequencing helped to find the highest differentially expressed lncRNA in AXL-associated exosomes. Clone formation, wound healing, transwell assay, and xenograft model in nude mice were performed to evaluate cells' proliferation, migration, and invasion in vitro and in vivo. Lentiviral transfection was used to up- or down-regulate the lncRNA levels in cell lines. Luciferase reporter assay and RNA FISH etchelped to indicate the molecular mechanisms. The results in the cell lines were proved in the osteosarcoma tissues with clinical analysis. RESULTS: The exosomes derived from donor cells with high AXL expression could promote the proliferation and invasion and upregulate AXL expression of the receiver cells with low AXL. Linc00852 was the highest differentially expressed lncRNA in AXL-associated exosomes and was also regulated by AXL expression. Although the mechanisms of linc00852 in nucleus were unrevealed, it could upregulate AXL expression partly by competitively binding to miR-7-5p. The AXL-exosome-linc00852-AXL positive feedback loop might exist between the donor cells and the receiver cells. Clinically, linc00852 was significantly highly expressed in osteosarcoma tissues and positively associated with tumor volumes and metastases, which was also obviously related with AXL mRNA expression. CONCLUSION: AXL-associated exosomal linc00852 up-regulated the proliferation, migration, and invasion of osteosarcoma cells, which would be considered as a new tumor biomarker and a special therapeutic target for osteosarcoma.

Neurophysiological indices of the transfer of cognitive training gains to untrained tasks.

Targeted training of working memory (WM) may improve performance and modulate brain function in untrained cognitive modalities. Demanding cognitive training protocols that do not target WM may also improve performance on untrained cognitive tests, but the delineation between transfer effects that are unique to WM training and effects that are shared among different cognitive training modalities has not been well-established. To address this, we examined the effects of twenty sessions of either WM training (visual n-back task with letter stimuli) or selective attention training (visual search task with letter array stimuli) on brain function during untrained WM and cognitive control tasks. Event-related potentials (ERPs) were obtained at baseline (pretest) and after the training period (posttest) for two untrained tasks - a Spatial 3-back task measuring spatial WM, and a Go/NoGo Flanker task measuring cognitive control. The n-back training group had more pronounced pretest-to-posttest performance improvements on the Spatial 3-back task compared to the search training group. N-back training was also associated with pretest-to-posttest enhancement of N1 amplitude and reduced N2 latency on trials of the task in which where there was a stimulus match, as well as enhancement of a late positive potential (550-750 msec post-stimulus) for all trials of the task. These ERP effects suggest that n-back training resulted in enhancement of attention to spatial locations, earlier onset of conflict monitoring processes, and changes in the engagement of neural activity during the retention interval, respectively. Both groups had faster reaction time on Go trials of the Go/NoGo Flanker task at posttest compared to pretest. Relatively subtle training-related effects were observed for N2 amplitude on this task, in line with the notion that training (particularly n-back training) was associated with improved conflict monitoring. Further, search training resulted in earlier onset of P2 and P3 latency at posttest compared to pretest. Taken together, the ERP findings for both tasks identify specific cognitive processes that are associated with transfer to untrained tasks after distinct forms of cognitive training.

Copper-Catalyzed Cascade Cyclization Reactions of Diazo Compounds with tert-Butyl Nitrite and Alkynes: One-Pot Synthesis of Isoxazoles.

A novel copper-catalyzed [3 + 2] cycloaddition reaction of alkynes with nitrile oxides generated in situ from the coupling reaction of copper carbene and nitroso radical has been developed. The three-component reaction provides a simple and efficient method for the construction of isoxazoles in a highly regioselective manner in a single step. On the basis of the experimental results and density functional theory calculations, a catalytic cycle (CuI-CuII-Cu0-CuI) for this cascade cyclization reaction is proposed.

MicroRNA-22 inhibits cell growth and metastasis in breast cancer via targeting of SIRT1.

MicroRNAs (miRs), which are a class of small non-coding RNAs, are key regulators of gene expression via induction of translational repression or mRNA degradation. However, the molecular mechanism of miR-22 underlying the malignant progression of breast cancer, remains to be elucidated. The present study aimed to explore the regulatory mechanism of miR-22 in breast cancer cell growth and metastasis. Reverse transcription-quantitative polymerase chain reaction data revealed that miR-22 was significantly downregulated in breast cancer tissues, compared with adjacent non-tumor tissues. Furthermore, the miR-22 levels were further decreased in stage III-IV, compared with stage I-II breast cancer. In addition, low miR-22 levels were significantly associated with the poor differentiation, metastasis and advanced clinical stages of breast cancer. Sirtuin1 (SIRT1) was demonstrated to act as a direct target gene of miR-22 and its protein expression negatively regulated by miR-22 in the MCF-7 breast cancer cell line. Furthermore, SIRT1 expression levels were significantly upregulated in breast cancer tissues, compared with adjacent non-tumor tissues. SIRT1 levels were observed to be increased in stage III-IV when compared with stage I-II breast cancer. miR-22 overexpression decreased the proliferation, migration and invasion of MCF-7 cells, whereas overexpression of SIRT1 eliminated the suppressive effects of the miR-22 overexpression on the malignant phenotype of MCF-7 cells. The results of the present study therefore suggested that miR-22 demonstrated suppressive effects on breast cancer growth and metastasis via targeting SIRT1, and thus the miR-22/SIRT1 axis may be used as a novel and potential therapeutic target for breast cancer in the future.

lncRNA DANCR promotes tumor progression and cancer stemness features in osteosarcoma by upregulating AXL via miR-33a-5p inhibition.

lncRNAs regulate the initiation and progression of osteosarcoma, although the mechanism by which this occurs remains unknown. The present study shows that over-expression of the lncRNA DANCR increased osteosarcoma cell proliferation, migration, and invasion in vitro, as well as promoted xenograft tumor growth and lung metastasis in vivo. Mechanistically, DANCR promoted osteosarcoma progression by mediating cancer stem cells (CSCs) features. Moreover, pull-down assays and luciferase reporter assays indicated that DANCR upregulated expression of the receptor tyrosine kinase AXL by competitively binding to miR-33a-5p. Furthermore, DANCR enhanced the expression of proteins downstream of the AXL-Akt pathway. DANCR was consistently significantly increased in osteosarcoma tissues, and its expression was positively correlated with tumor size and metastasis as an independent poor prognostic factor. Furthermore, both in patient tumors and xenograft tumors, DANCR expression was positively related to AXL and negatively related to miR-33a-5p. Taken together, our results suggest that DANCR is a crucial upregulator of osteosarcoma and an independent predictor of prognosis. DANCR increases CSCs function by upregulating AXL via competitively binding to miR-33a-5p, and this function is sequentially performed through the PI3K-Akt signaling pathway.

Cathepsin S silencing induces apoptosis of human hepatocellular carcinoma cells.

This study was to investigate the potential molecular mechanisms underlying the Cathepsin S (CTSS) silencing induced apoptosis of Hepatocellular Carcinoma (HCC) cells with lentivirus-mediated RNA interference. Real-time quantitative PCR and western blot assay were performed to detect the mRNA and protein expression of CTSS, respectively, in 13 HCC cell lines with different metastatic potentials. Results showed MHCC97-H cells had the highest CTSS expression. Therefore, MHCC97-H cells were used in following experiments. Then, lentivirus-mediated RNAi was employed to silence CTSS expression (shCTSS). Annexin V/FITC staining showed NF-κB was activated in shCTSS cells treated with conditioned medium from shCTSS-PAR2 cells. This implies a probable positive correlation between PAR2 and CTSS. In addition, results demonstrated CTSS induced apoptosis of HCC cells and increased their chemosensitivity via regulating NF-κB and activating cleaved caspase-3. Our results indicate that CTSS silencing by lentivirus mediated RNAi can significantly induce apoptosis and chemosensitivity of MHCC97-H cells. This provides an attractive anti-cancer strategy and a novel strategy for the treatment of human HCC.

Silencing cathepsin S gene expression inhibits growth, invasion and angiogenesis of human hepatocellular carcinoma in vitro.

Cathepsin S (Cat S) plays an important role in tumor invasion and metastasis by its ability to degrade extracellular matrix (ECM). Our previous study suggested there could be a potential association between Cat S and hepatocellular carcinoma (HCC) metastasis. The present study was designed to determine the role of Cat S in HCC cell growth, invasion and angiogenesis, using RNA interference technology. Small interfering RNA (siRNA) sequences for the Cat S gene were synthesized and transfected into human HCC cell line MHCC97-H. The Cat S gene targeted siRNA-mediated knockdown of Cat S expression, leading to potent suppression of MHCC97-H cell proliferation, invasion and angiogenesis. These data suggest that Cat S might be a potential target for HCC therapy.