Oncofetal reprogramming drives phenotypic plasticity in WNT-dependent colorectal cancer.

Targeting cancer stem cells (CSCs) is crucial for effective cancer treatment, yet resistance mechanisms to LGR5 CSC depletion in WNT-driven colorectal cancer (CRC) remain elusive. In the present study, we revealed that mutant intestinal stem cells (SCs) depart from their canonical identity, traversing a dynamic phenotypic spectrum. This enhanced plasticity is initiated by oncofetal (OnF) reprogramming, driven by YAP and AP-1, with subsequent AP-1 hyperactivation promoting lineage infidelity.

Structural insights into the activation mechanism of the human zinc-activated channel.

The zinc-activated channel (ZAC) is an atypical mammalian cys-loop receptor (CLR) that is activated by zinc ions and protons, allowing cations to pass through. The molecular mechanism that ligands use to activate ZAC remains elusive. Here, we present three cryo-electron microscopy reconstructions of human ZAC (hZAC) under different conditions.

Single chromatin fiber profiling and nucleosome position mapping in the human brain.

We apply a single-molecule chromatin fiber sequencing (Fiber-seq) protocol designed for amplification-free cell-type-specific mapping of the regulatory architecture at nucleosome resolution along extended ∼10-kb chromatin fibers to neuronal and non-neuronal nuclei sorted from human brain tissue. Specifically, application of this method enables the resolution of cell-selective promoter and enhancer architectures on single fibers, including transcription factor footprinting and position mapping, with sequence-specific fixation of nucleosome arrays flanking transcription start sites and regulatory motifs. We uncover haplotype-specific chromatin patterns, multiple regulatory elements cis-aligned on individual fibers, and accessible chromatin at 20,000 unique sites encompassing retrotransposons and other repeat sequences hitherto "unmappable" by short-read epigenomic sequencing.

Cycling alpha cells in regenerative drug-treated human pancreatic islets may serve as key beta cell progenitors.

Diabetes results from an inadequate number of insulin-producing human beta cells. There is currently no clinically available effective means to restore beta cell mass in millions of people with diabetes. Although the DYRK1A inhibitors, either alone or in combination with GLP-1 receptor agonists (GLP-1) or transforming growth factor β (TGF-β) superfamily inhibitors (LY), induce beta cell replication and increase beta cell mass, the precise mechanisms of action remain elusive.

Differential regulation of brain microvessel transcriptome and brain metabolome by western and heart-healthy dietary patterns in Ossabaw pigs.

Diet is a potentially modifiable neurodegenerative disease risk factor. We studied the effects of a typical Western diet (WD; high in refined carbohydrates, cholesterol and saturated fat), relative to a heart-healthy diet (HHD; high in unrefined carbohydrates, polyunsaturated fat and fiber, and low in cholesterol) on brain microvessel transcriptomics and brain metabolomics of the temporal region in Ossabaw minipigs. Thirty-two pigs (16 male and 16 females) were fed a WD or HHD starting at the age of 4 months for a period of 6 months.

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

Targeting cancer stem cells (CSCs) is crucial for effective cancer treatment . However, the molecular mechanisms underlying resistance to LGR5 CSCs depletion in colorectal cancer (CRC) 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.

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.

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

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. β-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.

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).

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.

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

[This retracts the article DOI: 10.3892/etm.2017.

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.

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.

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.

Copper-Catalyzed Cascade Cyclization Reactions of Diazo Compounds with -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 (Cu-Cu-Cu-Cu) 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.

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.

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.

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.