FGD5 in basal cells induces CXCL14 secretion that initiates a feedback loop to promote murine mammary epithelial growth and differentiation.

The interactions of environmental compartments with epithelial cells are essential for mammary gland development and homeostasis. Currently, the direct crosstalk between the endothelial niche and mammary epithelial cells remains poorly understood. Here, we show that faciogenital dysplasia 5 (FGD5) is enriched in mammary basal cells (BCs) and mediates critical interactions between basal and endothelial cells (ECs) in the mammary gland.

Targeting IL-17A enhances imatinib efficacy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia.

Dysregulated hematopoietic niches remodeled by leukemia cells lead to imbalances in immunological mediators that support leukemogenesis and drug resistance. Targeting immune niches may ameliorate disease progression and tyrosine kinase inhibitor (TKI) resistance in Philadelphia chromosome-positive B-ALL (Ph B-ALL). Here, we show that T helper type 17 (Th17) cells and IL-17A expression are distinctively elevated in Ph B-ALL patients.

Spatial Distribution Characteristics of Suitable Planting Areas for Species under Climate Change in China.

Planting suitability determines the distribution and yield of crops in a given region which can be greatly affected by climate change. In recent years, many studies have shown that carbon dioxide fertilization effects increase the productivity of temperate deciduous fruit trees under a changing climate, but the potential risks to fruit tree planting caused by a reduction in suitable planting areas are rarely reported. In this study, Maxent was first used to investigate the spatial distribution of five species in China, and the consistency between the actual production area and the modeled climatically suitable area under the current climatic conditions were determined.

Monitoring and analysis of desertification surrounding Qinghai Lake (China) using remote sensing big data.

Desertification is one of the most serious ecological environmental problems in the world. Monitoring the spatiotemporal dynamics of desertification is crucial for its control. The region around Qinghai Lake, in the northeastern part of the Qinghai-Tibet Plateau in China, is a special ecological function area and a climate change sensitive area, making its environmental conditions a great concern.

Insulin induces insulin receptor degradation in the liver through EphB4.

Insulin signaling is essential for glucose metabolism, and insulin decreases insulin receptor (InsR) levels in a dose-dependent and time-dependent manner. However, the regulatory mechanisms of InsR reduction upon insulin stimulation remain poorly understood. Here, we show that Eph receptor B4 (EphB4), a tyrosine kinase receptor that modulates cell adhesion and migration, can bind directly to InsR, and this interaction is markedly enhanced by insulin.

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration.

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF.

TRIB3‒GSK-3 interaction promotes lung fibrosis and serves as a potential therapeutic target.

Pulmonary fibrosis (PF) is a chronic, progressive, fatal interstitial lung disease with limited available therapeutic strategies. We recently reported that the protein kinase glycogen synthase kinase-3 (GSK-3) interacts with and inactivates the ubiquitin-editing enzyme A20 to suppress the degradation of the transcription factor CCAAT/enhancer-binding protein beta (C/EBP) in alveolar macrophages (AMs), resulting in a profibrotic phenotype of AMs and promoting the development of PF. Here, we showed that chronic lung injury upregulated the stress response protein tribbles homolog 3 (TRIB3), which interacted with GSK-3 and stabilized GSK-3 from ubiquitination and degradation.

The chemokine CCL1 triggers an AMFR-SPRY1 pathway that promotes differentiation of lung fibroblasts into myofibroblasts and drives pulmonary fibrosis.

Recruitment of immune cells to the site of inflammation by the chemokine CCL1 is important in the pathology of inflammatory diseases. Here, we examined the role of CCL1 in pulmonary fibrosis (PF). Bronchoalveolar lavage fluid from PF mouse models contained high amounts of CCL1, as did lung biopsies from PF patients.

Associations Between Diabetes and Idiopathic Pulmonary Fibrosis: a Study-level Pooled Analysis of 26 Million People.

Context: Diabetes mellitus (DM) is a systemic disease characterized by chronic hyperglycemia associated with inflammation and oxidative stress, and the lung may be a target organ of diabetic microvascular damage. Several studies have indicated a positive association between idiopathic pulmonary fibrosis (IPF) and diabetes with controversial findings.

Objective: Primary outcomes were to compare the prevalence of DM among individuals with IPF to non-IPF controls, and the prevalence of IPF among individuals with DM to non-DM controls.

Autophagic Flux Detection: Significance and Methods Involved.

Macroautophagy is an important biological process in eukaryotic cells by which longevity proteins, misfolded proteins, and damaged organelles are degraded. The autophagy process consists of three key steps: (1) the formation of autophagosomes; (2) the fusion of the autophagosomes with lysosomes; and (3) the degradation of the contents of autolysosomes. If any of the three steps is impaired, autophagy will not be able to complete its biological function.

Faciogenital Dysplasia 5 supports cancer stem cell traits in basal-like breast cancer by enhancing EGFR stability.

Most basal-like breast cancers (BLBCs) are triple-negative breast cancers (TNBCs), which have the worst prognosis and distant metastasis-free survival among breast cancer subtypes. Now, no targeted therapies are available for patients with BLBC due to the lack of reliable and effective molecular targets. Here, we performed the BLBC tissue microarray-based immunohistochemical analysis and showed that Faciogenital Dysplasia 5 (FGD5) abundance is associated with poor prognosis in BLBCs.

TRIB3 promotes MYC-associated lymphoma development through suppression of UBE3B-mediated MYC degradation.

The transcription factor MYC is deregulated in almost all human cancers, especially in aggressive lymphomas, through chromosomal translocation, amplification, and transcription hyperactivation. Here, we report that high expression of tribbles homologue 3 (TRIB3) positively correlates with elevated MYC expression in lymphoma specimens; TRIB3 deletion attenuates the initiation and progression of MYC-driven lymphoma by reducing MYC expression. Mechanistically, TRIB3 interacts with MYC to suppress E3 ubiquitin ligase UBE3B-mediated MYC ubiquitination and degradation, which enhances MYC transcriptional activity, causing high proliferation and self-renewal of lymphoma cells.

PML-RARα interaction with TRIB3 impedes PPARγ/RXR function and triggers dyslipidemia in acute promyelocytic leukemia.

Although dyslipidemia commonly occurs in patients with acute promyelocytic leukemia (APL) in response to anti-APL therapy, the underlying mechanism and the lipid statuses of patients with newly diagnosed APL remain to be addressed. : We conducted a retrospective study to investigate the lipid profiles of APL patients. PML-RARα transgenic mice and APL cells-transplanted mice were used to assess the effects of APL cells on the blood/liver lipid levels.

G-Protein-Coupled Estrogen Receptor 1 Promotes Gender Disparities in Hepatocellular Carcinoma via Modulation of SIN1 and mTOR Complex 2 Activity.

Due to its intricate heterogeneity and limited treatment, hepatocellular carcinoma (HCC) has been considered a major cause of cancer-related mortality worldwide. Increasing evidence indicates that G-protein-coupled estrogen receptor 1 (GPER1) can promote estrogen-dependent hepatocellular proliferation by activating AKT signaling. The mTOR complex 2 (mTORC2), whose integrity and activity are modulated by its subunit Sin1, controls the activation of AKT by phosphorylation at position S473.

TRIB3-EGFR interaction promotes lung cancer progression and defines a therapeutic target.

High expression or aberrant activation of epidermal growth factor receptor (EGFR) is related to tumor progression and therapy resistance across cancer types, including non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are first-line therapy for NSCLC. However, patients eventually deteriorate after inevitable acquisition of EGFR TKI-resistant mutations, highlighting the need for therapeutics with alternative mechanisms of action.

Autophagy and Others Respiratory Diseases.

Besides COPD, pulmonary fibrosis, and asthma, autophagy also participates in the development of many other respiratory diseases. Cystic fibrosis is an innate lung disease. Unlike idiopathic pulmonary fibrosis, cystic fibrosis has unique pathogenesis.

Asthma and Autophagy.

Asthma is one of the most common diseases of the respiratory system, with typical pathogenesis and pathological changes. The current research shows that autophagy is mainly involved in the pathogenesis of asthma by regulating the body's innate and adaptive immune responses. At the same time, a large number of epidemiological studies have shown that multiple autophagy genes affect the risk of asthma at the level of genetic polymorphism.