TGFβ family signaling in human stem cell self-renewal and differentiation.

Human stem cells are undifferentiated cells with the capacity for self-renewal and differentiation into distinct cell lineages, playing important role in the development and maintenance of diverse tissues and organs. The microenvironment of stem cell provides crucial factors and components that exert significant influence over the determination of cell fate. Among these factors, cytokines from the transforming growth factor β (TGFβ) superfamily, including TGFβ, bone morphogenic protein (BMP), Activin and Nodal, have been identified as important regulators governing stem cell maintenance and differentiation.

Flexible and Stretchable Photoelectrochemical Sensing toward True-to-Life Monitoring of Hydrogen Peroxide Regulation in Endothelial Mechanotransduction.

Hydrogen peroxide (HO) levels play a vital role in redox regulation and maintaining the physiological balance of living cells, especially in cell mechanotransduction. Despite the achievements on strain-induced cellular HO monitoring, the applied voltage for HO electrooxidation possibly gave rise to an abnormal expression and inadequate accuracy, which was still an inescapable concern. Hence, we decorated an interlaced CuO@TiO nanowires (NWs) semiconductor meshwork onto a polydimethylsiloxane film-supported gold nanotubes substrate (Au NTs/PDMS) to construct a flexible photoelectrochemical (PEC) sensing platform.

Reservoir rock typing assessment in a coal-tight sand based heterogeneous geological formation through advanced AI methods.

Geoscientists now identify coal layers using conventional well logs. Coal layer identification is the main technical difficulty in coalbed methane exploration and development. This research uses advanced quantile-quantile plot, self-organizing maps (SOM), k-means clustering, t-distributed stochastic neighbor embedding (t-SNE) and qualitative log curve assessment through three wells (X4, X5, X6) in complex geological formation to distinguish coal from tight sand and shale.

Dual Branch Multi-Level Semantic Learning for Few-Shot Segmentation.

Few-shot semantic segmentation aims to segment novel-class objects in a query image with only a few annotated examples in support images. Although progress has been made recently by combining prototype-based metric learning, existing methods still face two main challenges. First, various intra-class objects between the support and query images or semantically similar inter-class objects can seriously harm the segmentation performance due to their poor feature representations.

TRIM28-mediated nucleocapsid protein SUMOylation enhances SARS-CoV-2 virulence.

Viruses, as opportunistic intracellular parasites, hijack the cellular machinery of host cells to support their survival and propagation. Numerous viral proteins are subjected to host-mediated post-translational modifications. Here, we demonstrate that the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is SUMOylated on the lysine 65 residue, which efficiently mediates SARS2-NP's ability in homo-oligomerization, RNA association, liquid-liquid phase separation (LLPS).

Deubiquitylating Enzymes in Cancer and Immunity.

Deubiquitylating enzymes (DUBs) maintain relative homeostasis of the cellular ubiquitome by removing the post-translational modification ubiquitin moiety from substrates. Numerous DUBs have been demonstrated specificity for cleaving a certain type of ubiquitin linkage or positions within ubiquitin chains. Moreover, several DUBs perform functions through specific protein-protein interactions in a catalytically independent manner, which further expands the versatility and complexity of DUBs' functions.

OVOL1 inhibits breast cancer cell invasion by enhancing the degradation of TGF-β type I receptor.

Ovo-like transcriptional repressor 1 (OVOL1) is a key mediator of epithelial lineage determination and mesenchymal-epithelial transition (MET). The cytokines transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMP) control the epithelial-mesenchymal plasticity (EMP) of cancer cells, but whether this occurs through interplay with OVOL1 is not known. Here, we show that OVOL1 is inversely correlated with the epithelial-mesenchymal transition (EMT) signature, and is an indicator of a favorable prognosis for breast cancer patients.

TGFβ selects for pro-stemness over pro-invasive phenotypes during cancer cell epithelial-mesenchymal transition.

Transforming growth factor β (TGFβ) induces epithelial-mesenchymal transition (EMT), which correlates with stemness and invasiveness. Mesenchymal-epithelial transition (MET) is induced by TGFβ withdrawal and correlates with metastatic colonization. Whether TGFβ promotes stemness and invasiveness simultaneously via EMT remains unclear.

Establishment of Embryonic Zebrafish Xenograft Assays to Investigate TGF-β Family Signaling in Human Breast Cancer Progression.

Transforming growth factor-β (TGF-β) family members have pivotal functions in controlling breast cancer progression, acting not only on cancer cells but also on other cells within the tumor microenvironment. Here we describe embryonic zebrafish xenograft assays to investigate how TGF-β family signaling controls breast cancer cell intravasation, extravasation and regulates tumor angiogenesis. Fluorescently mCherry-labeled breast cancer cells are injected in the perivitelline space or Duct of Cuvier of Tg (fli:EGFP) transgenic Casper zebrafish embryos, in which the zebrafish express enhanced green fluorescent protein in the entire vasculature.

Inhibiting Endothelial Cell Function in Normal and Tumor Angiogenesis Using BMP Type I Receptor Macrocyclic Kinase Inhibitors.

Angiogenesis, i.e., the formation of new blood vessels from pre-existing endothelial cell (EC)-lined vessels, is critical for tissue development and also contributes to neovascularization-related diseases, such as cancer.

Protective effects of recombinant 53-kDa protein of on acute lung injury in mice via alleviating lung pyroptosis by promoting M2 macrophage polarization.

represents an effective treatment for autoimmune and inflammatory diseases. The effects of recombinant (TS) 53-kDa protein (rTsP53) on acute lung injury (ALI) remain unclear. Here, mice were divided randomly into a control group, LPS group, and rTsP53 + LPS group.

The intersection of COVID-19 and cancer: signaling pathways and treatment implications.

The outbreak of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a serious public health concern. Patients with cancer have been disproportionately affected by this pandemic. Increasing evidence has documented that patients with malignancies are highly susceptible to severe infections and mortality from COVID-19.

Protein N-myristoylation: functions and mechanisms in control of innate immunity.

Protein N-myristoylation is an important fatty acylation catalyzed by N-myristoyltransferases (NMTs), which are ubiquitous enzymes in eukaryotes. Specifically, attachment of a myristoyl group is vital for proteins participating in various biological functions, including signal transduction, cellular localization, and oncogenesis. Recent studies have revealed unexpected mechanisms indicating that protein N-myristoylation is involved in host defense against microbial and viral infections.

Targeting TGFβ signal transduction for cancer therapy.

Transforming growth factor-β (TGFβ) family members are structurally and functionally related cytokines that have diverse effects on the regulation of cell fate during embryonic development and in the maintenance of adult tissue homeostasis. Dysregulation of TGFβ family signaling can lead to a plethora of developmental disorders and diseases, including cancer, immune dysfunction, and fibrosis. In this review, we focus on TGFβ, a well-characterized family member that has a dichotomous role in cancer progression, acting in early stages as a tumor suppressor and in late stages as a tumor promoter.

Medication adherence among patients with chronic obstructive pulmonary disease treated in a primary general hospital during the COVID-19 pandemic.

Background: The objective of this study was to investigate medication adherence and the associated influencing factors in patients with chronic obstructive pulmonary disease (COPD) who were treated in a primary general hospital in Shanghai China during the 2019 novel coronavirus (COVID-19) pandemic.

Methods: From March to April 2020, all of the COPD patients treated in our department in the last 7 years were interviewed by telephone. The basic patient data and each questionnaire item were collected, and influencing factors were analyzed by the Chi-square test, U test, and univariate and multivariate logistic regression analyses.

Designed nanomolar small-molecule inhibitors of Ena/VASP EVH1 interaction impair invasion and extravasation of breast cancer cells.

Battling metastasis through inhibition of cell motility is considered a promising approach to support cancer therapies. In this context, Ena/VASP-depending signaling pathways, in particular interactions with their EVH1 domains, are promising targets for pharmaceutical intervention. However, protein-protein interactions involving proline-rich segments are notoriously difficult to address by small molecules.

Myrcene exerts anti-asthmatic activity in neonatal rats via modulating the matrix remodeling.

Myrcene (MC), an organic hydrocarbon, was found to exert anti-inflammatory, analgesic, antimutagenic and antioxidant properties. However, the protective role of MC has not been reported against neonatal asthma. Wistar rats induced with asthma were administered with MC; while asthma control and vehicle control were maintained without MC administration.

Vacancy-Assisted Growth Mechanism of Multilayer Hexagonal Boron Nitride on a FeB Substrate.

The controllable synthesis of large-area and uniform hexagonal boron nitride (h-BN) films has been recently achieved on metal-boron alloy catalysts with the use of N feedstock, representing important progress in an economic and environmentally friendly process. However, the systematic investigation of the growth mechanism is still lacking, which impedes the further development of this method. In this work, on the basis of density functional theory (DFT) calculations and experiments, we reveal the vacancy-assisted growth mechanism of h-BN on FeB substrate.

Reactivation of BMP signaling by suboptimal concentrations of MEK inhibitor and FK506 reduces organ-specific breast cancer metastasis.

TGFβ-SMAD3 signaling is a major driving force for cancer metastasis, while BMP-SMAD1/5 signaling can counteract this response. Analysis of gene expression profiles revealed that an increased TGFβ-SMAD3 and a reduced BMP-SMAD1/5 targeted gene expression signature correlated with shortened distant metastasis free survival and overall survival of patients. At molecular levels, we discovered that TGFβ abolished BMP-induced SMAD1/5 activation in the highly-invasive breast cancer MDA-MB-231 cells, but to a less extent in the non-invasive cancer and normal breast cells.

Vapor-liquid-solid growth of large-area multilayer hexagonal boron nitride on dielectric substrates.

Multilayer hexagonal boron nitride (h-BN) is highly desirable as a dielectric substrate for the fabrication of two-dimensional (2D) electronic and optoelectronic devices. However, the controllable synthesis of multilayer h-BN in large areas is still limited in terms of crystallinity, thickness and stacking order. Here, we report a vapor-liquid-solid growth (VLSG) method to achieve uniform multilayer h-BN by using a molten FeB alloy and N as reactants.

A WRKY transcription factor confers aluminum tolerance via regulation of cell wall modifying genes.

Modification of cell wall properties has been considered as one of the determinants that confer aluminum (Al) tolerance in plants, while how cell wall modifying processes are regulated remains elusive. Here, we present a WRKY transcription factor WRKY47 involved in Al tolerance and root growth. Lack of WRKY47 significantly reduces, while overexpression of it increases Al tolerance.

GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients.

Background: In breast cancer, activation of bone morphogenetic protein (BMP) signaling and elevated levels of BMP-antagonists have been linked to tumor progression and metastasis. However, the simultaneous upregulation of BMPs and their antagonist, and the fact that both promote tumor aggressiveness seems contradictory and is not fully understood.

Methods: We analyzed the transcriptomes of the metastatic 66cl4 and the non-metastatic 67NR cell lines of the 4T1 mouse mammary tumor model to search for factors that promote metastasis.