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Open AccessA pan-KRAS degrader for the treatment of KRAS-mutant cancers
KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have bee...
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Article
Open AccessThrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson’s disease
The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson’s disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. W...
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Article
Open AccessMulti-modal molecular determinants of clinically relevant osteoporosis subtypes
Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing s...
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Open AccessThe potential role of hydrogen sulfide in cancer cell apoptosis
For a long time, hydrogen sulfide (H2S) has been considered a toxic compound, but recent studies have found that H2S is the third gaseous signaling molecule which plays a vital role in physiological and pathologi...
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Article
Open AccessZbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling
Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF...
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An active glutamine/α-ketoglutarate/HIF-1α axis prevents pregnancy loss by triggering decidual IGF1+GDF15+NK cell differentiation
Deficiency of decidual NK (dNK) cell number and function has been widely regarded as an important cause of spontaneous abortion. However, the metabolic mechanism underlying the crosstalk between dNK cells and ...
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Article
Lactiplantibacillus plantarum attenuates 2,4,6-trinitrobenzenesulfonic acid-induced ulcerative colitis in rats by regulating the inflammatory response, T helper 17 immune response, and intestinal permeability
Ulcerative colitis (UC) is an idiopathic chronic inflammatory bowel disease. The effect of current therapy is far from satisfactory; therefore, it is necessary to develop new UC therapeutic strategies. Lactiplant...
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Article
Open AccessStabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML
Cytarabine (Ara-C) is the first-line drug for the treatment of acute myelogenous leukemia (AML). However, resistance eventually develops, decreasing the efficacy of Ara-C in AML patients. The expression of SAM...
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Article
Open AccessPhase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes
As a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. A long and unstructured C-terminal region of IRS-1 recruits downstream effectors for pr...
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Open AccessLipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters
Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of develo** effective antibodies a...
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Article
FKBP51 modulates hippocampal size and function in post-translational regulation of Parkin
FK506-binding protein 51 (encoded by Fkpb51, also known as Fkbp5) has been associated with stress-related mental illness. To investigate its function, we studied the morphological consequences of Fkbp51 deletion....
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Article
Cholesterylation of Smoothened is a calcium-accelerated autoreaction involving an intramolecular ester intermediate
Hedgehog (Hh) is a morphogen that binds to its receptor Patched 1 and activates Smoothened (SMO), thereby governing embryonic development and postnatal tissue homeostasis. Cholesterol can bind and covalently c...
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Open AccessCancer-derived exosomal HSPC111 promotes colorectal cancer liver metastasis by reprogramming lipid metabolism in cancer-associated fibroblasts
Tumor metastasis is a hallmark of cancer. The communication between cancer-derived exosomes and stroma plays an irreplaceable role in facilitating pre-metastatic niche formation and cancer metastasis. However,...
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Open AccessNLK is required for Ras/ERK/SRF/ELK signaling to tune skeletal muscle development by phosphorylating SRF and antagonizing the SRF/MKL pathway
Serum response factor (SRF) regulates differentiation and proliferation by binding to RhoA-actin-activated MKL or Ras-MAPK-activated ELK transcriptional coactivators, but the molecular mechanisms responsible f...
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Open AccessSelective and competitive functions of the AAR and UPR pathways in stress-induced angiogenesis
The amino acid response (AAR) and unfolded protein response (UPR) pathways converge on eIF2α phosphorylation, which is catalyzed by Gcn2 and Perk, respectively, under different stresses. This close interconnec...
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Article
Open AccessRCN1 induces sorafenib resistance and malignancy in hepatocellular carcinoma by activating c-MYC signaling via the IRE1α–XBP1s pathway
The increasing incidence of hepatocellular carcinoma (HCC) is of great concern globally, but the molecular pathogenesis of these tumors remains unclear. Sorafenib is a first-line drug for the treatment of adva...
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Article
Open AccessSARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 e...
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Article
Epithelium- and endothelium-derived exosomes regulate the alveolar macrophages by targeting RGS1 mediated calcium signaling-dependent immune response
Alveolar macrophages (AM) maintain airway immune balance; however, the regulation of heterogeneity of AMs is incompletely understood. We demonstrate that RGS1 coregulates the immunophenotype of AM subpopulatio...
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Open AccessPermissive effect of GSK3β on profibrogenic plasticity of renal tubular cells in progressive chronic kidney disease
Renal tubular epithelial cells (TECs) play a key role in renal fibrogenesis. After persistent injuries that are beyond self-healing capacity, TECs will dedifferentiate, undergo growth arrest, convert to profib...
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Fra-2/AP-1 regulates melanoma cell metastasis by downregulating Fam212b
Metastatic melanoma remains a challenging disease. Understanding the molecular mechanisms how melanoma becomes metastatic is therefore of interest. Herein we show that downregulation of the AP-1 transcription ...