PTPN23-dependent activation of PI3KC2α is a therapeutic vulnerability of BRAF-mutant cancers.

BRAF mutations drive initiation and progression of various tumors. While BRAF inhibitors are effective in BRAF-mutant melanoma patients, intrinsic or acquired resistance to these therapies is common. Here, we identify non-receptor-type protein tyrosine phosphatase 23 (PTPN23) as an alternative effective target in BRAF-mutant cancer cells.

A multicenter, randomized, open label, two formulation, crossover bioequivalence trial of doxorubicin hydrochloride liposomal injection in Chinese patients with metastatic breast cancer.

Purpose: The primary objectives of this trial were aimed at exploring the pharmacokinetic profiles and the human bioequivalence of an intravenous liposomal injection of doxorubicin hydrochloride in comparison with a reference formulation in Chinese patients diagnosed with metastatic breast cancer.

Methods: To achieve these goals, the trial employed a randomized, open-label, two-formulation crossover dosing strategy among Chinese patients with metastatic breast cancer. Pharmacokinetic (PK) evaluation was conducted through the collection of blood samples, and the liquid chromatography tandem mass spectrometry (LC/MS/MS) method was leveraged to quantify plasma concentrations of both liposome-encapsulated doxorubicin and non-encapsulated doxorubicin in patients.

Controlled ovarian hyperstimulation with or without letrozole for fertility preservation in breast cancer patients: study protocol for a randomised controlled trial.

Introduction: Multimodal anticancer therapies greatly damage the fertility of breast cancer patients, which raises urgent demand for fertility preservation. The standard options for fertility preservation are oocyte and embryo cryopreservation; both require controlled ovarian hyperstimulation (COH). However, there are safety concerns regarding breast cancer relapse due to the elevated serum estradiol levels during COH.

Endothelial STING-JAK1 interaction promotes tumor vasculature normalization and antitumor immunity.

Stimulator of interferon genes (STING) agonists have been developed and tested in clinical trials for their antitumor activity. However, the specific cell population(s) responsible for such STING activation-induced antitumor immunity have not been completely understood. In this study, we demonstrated that endothelial STING expression was critical for STING agonist-induced antitumor activity.

Ultrasound-activated erythrocyte membrane-camouflaged Pt (II) layered double hydroxide enhances PD-1 inhibitor efficacy in triple-negative breast cancer through cGAS-STING pathway-mediated immunogenic cell death.

Immunogenic cell death (ICD) offers a promising avenue for the treatment of triple-negative breast cancer (TNBC). However, optimizing immune responses remains a formidable challenge. This study presents the design of RBCm@Pt-CoNi layered double hydroxide (RmPLH), an innovative sonosensitizer for sonodynamic therapy (SDT), aimed at enhancing the efficacy of programmed cell death protein 1 (PD-1) inhibitors by inducing robust ICD responses.

Impacts of genomic alterations on the efficacy of HER2-targeted antibody-drug conjugates in patients with metastatic breast cancer.

Background: HER2-targeted antibody-drug conjugates (ADCs) have revolutionized the treatment landscape of metastatic breast cancer. However, the efficacy of these therapies may be compromised by genomic alterations. Hence, this study aims to identify factors predicting sensitivity to HER2 ADC in metastatic breast cancer.

Direct reprogramming of human fibroblasts into hair-inducing dermal papilla cell-like cells by a single small molecule.

Dermal papilla cells (DPCs) are a crucial subset of mesenchymal cells in the skin responsible for regulating hair follicle development and growth, making them invaluable for cell-based therapies targeting hair loss. However, obtaining sufficient DPCs with potent hair-inducing abilities remains a persistent challenge. In this study, the Food and Drug Administration (FDA)-approved drug library was utilized to screen small molecules capable of reprogramming readily accessible human skin fibroblasts into functional DPCs.

DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer.

Hyperactivation of ribosome biogenesis (RiBi) drives cancer progression, yet the role of RiBi-associated proteins (RiBPs) in breast cancer (BC) is underexplored. In this study, we perform a comprehensive multi-omics analysis and reveal that assembly and maturation factors (AMFs), a subclass of RiBPs, are upregulated at both RNA and protein levels in BC, correlating with poor patient outcomes. In contrast, ribosomal proteins (RPs) do not show systematic upregulation across various cancers, including BC.

CD4+ T helper 2 cell-macrophage crosstalk induces IL-24-mediated breast cancer suppression.

CD4+ T cells contribute to antitumor immunity and are implicated in the efficacy of cancer immunotherapies. In particular, CD4+ T helper 2 (Th2) cells were recently found to block spontaneous breast carcinogenesis. However, the antitumor potential of Th2 cells in targeting established breast cancer remains uncertain.

Metabolic Atlas of Human Eyelid Infiltrative Basal Cell Carcinoma.

Purpose: Eyelid infiltrative basal cell carcinoma (iBCC) is the most common malignant tumor affecting the ocular adnexa, but studies on metabolic changes within its microenvironment and heterogeneity at the tumor invasive area are limited. This study aims to analyze metabolic differences among iBCC cell types using single-cell and spatial metabolomics analysis and to examine metabolic environment at the tumor invasive area.

Methods: Single-cell transcriptomic data of human basal cell carcinoma (BCC) were clustered and visualized using Uniform Manifold Approximation and Projection.

The Role of Extracellular Vesicles in the Development and Treatment of Psoriasis: Narrative Review.

Psoriasis is a chronic inflammatory polygenic disease with significant impacts on skin and joints, leading to substantial treatment challenges and healthcare costs. The quest for novel therapeutic avenues has recently highlighted extracellular vesicles (EVs) due to their potential as biomarkers and therapeutic agents in autoimmune diseases, including psoriasis. EVs are nano-sized, lipid membrane-bound particles secreted by cells that have emerged as promising tools for targeted drug delivery, owing to their unique structure.

The Midas Touch by Iridium: A Second Near-Infrared Aggregation-Induced Emission-Active Metallo-Agent for Exceptional Phototheranostics of Breast Cancer.

Developing small organic molecular phototheranostic agents with second near-infrared (NIR-II) aggregation-induced emission (AIE) is paramount for the phototriggered diagnostic imaging and synchronous in situ therapy of cancer via an excellent balance of the excited states energy dissipations. In this study, a multifunctional iridium(III) complex is exploited by the coordination of an AIE-active N^N ancillary ligand with a trivalent iridium ion. The resultant complex DPTPzIr significantly outperforms its parent ligand in terms of absorption/emission wavelengths, reactive oxygen species (ROS) production, and photothermal conversion, which simultaneously endow DPTPzIr nanoparticles with matched absorption peak to commercial 808 nm laser, the longest NIR-II emission peak (above 1100 nm) among those previously reported AIE iridium(III) complexes, potentiated type-I ROS generation, and as high as 60.

Aging-induced immune microenvironment remodeling fosters melanoma in male mice via γδ17-Neutrophil-CD8 axis.

Aging is associated with increased tumor metastasis and poor prognosis. However, how an aging immune system contributes to the process is unclear. Here, single-cell RNA sequencing reveals that in male mice, aging shifts the lung immune microenvironment towards a premetastatic niche, characterized by an increased proportion of IL-17-expressing γδT (γδ17) and neutrophils.

Association between geriatric nutritional risk index and adverse outcomes in critical ill patients with chronic obstructive pulmonary disease: a cohort study of 2824 older adults.

Objectives: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, particularly among the elderly, resulting in high rates of intensive care unit (ICU) admissions. Malnutrition is common in elderly patients and has been associated with poor prognosis in patients with COPD. However, its impact in the ICU setting remains incompletely defined.

Identification of a novel immune checkpoint-related gene signature predicts prognosis and immunotherapy in breast cancer and experiment verification.

Breast cancer (BRCA) is one of the pivotal causes of female death worldwide. And the morbidity and mortality of breast cancer have increased rapidly. Immune checkpoints are important to maintain immune tolerance and are regarded as important therapeutic targets.

Bulk and Single-Cell Transcriptome Analyses Unravel Gene Signatures of Mitochondria-Associated Programmed Cell Death in Diabetic Foot Ulcer.

Mitochondrial programmed cell death (PCD) plays a critical role in the pathogenesis of diabetic foot ulcers (DFU). In this study, we performed a comprehensive transcriptome analysis to identify potential hub genes and key cell types associated with PCD and mitochondria in DFU. Using intersection analysis of PCD- and mitochondria-related genes, we identified candidate hub genes through protein-protein interaction and random forest analysis.

Assessing Wound Healing in Vivo Using a Dual-Function Phosphorescent Probe Sensitive to Tissue Oxygenation and Regenerating Collagen.

Levels of tissue oxygenation and collagen regeneration are critical indicators in the early evaluation of wound healing. Traditionally, these factors have been assessed using separate instruments and different methodologies. Here, we adopt the spatially averaged phosphorescence lifetime approach using Re-diimine complexes (Re-probe) to enable simultaneous quantification of these two critical factors in healing wounds.

Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common form of non-Hodgkin lymphoma (NHL) that occurs worldwide. To discover risk factors and pathogenesis of DLBCL, we performed the largest GWAS of DLBCL to date in samples of East Asian ancestry, consisting of 2,888 patients with DLBCL and 12,458 controls. The meta-analysis identified three novel loci, rs2233434 on 6p21.

[The effectiveness of CT-MRI image fusion technology in the preoperative assessment of middle ear cholesteatoma].

To evaluate the effectiveness of CT-MRI image fusion technology in the preoperative assessment of middle ear cholesteatoma. The clinical data of patients with middle ear cholesteatoma who underwent surgery at Guangdong Provincial People's Hospital from September 2018 to January 2020 were retrospectively analyzed. Preoperative CT and MRI of the patients were automatically fused using the open-source software 3D Slicer, followed by 3D reconstruction of the fused inner ear structures.

[Expert consensus on endoscopic surgery for the pediatric middle ear cholesteatoma based on the classification of cholesteatoma location].

Pediatric middle ear cholesteatoma is an aggressive keratotic lesion caused by abnormal proliferation of keratinised squamous epithelium in the temporal bone, with the characteristics of high postoperative recurrence rate, poor hearing effect and poor quality of life. Endoscopic surgery is able to deal with the majority of pediatric middle ear cholesteatoma cases with the features of minimal trauma and wide surgical field. However, endoscopic surgical treatment still has problems in standardization.

The assessment of dupilumab in children with moderate-to-severe asthma and comorbid type 2 inflammatory diseases.

Background: Dupilumab inhibiting the signaling of interleukin(IL)-4 and IL-13 was recommended for the treatment of severe asthma in children ≥ 6 years old according to the Global Initiative for Asthma (GINA,2024).This study aimed to analyse the efficacy and safety of dupilumab in paediatric patients with moderate-to-severe asthma and comorbid type 2 inflammatory disease in a real-world population.

Methods: We evaluated the medical records of paediatric patients with moderate-to-severe asthma and comorbid type 2 inflammatory diseases, such as atopic dermatitis (AD) and allergic rhinitis (AR), receiving dupilumab treatment.

Amygdalin alleviates psoriasis-like lesions by improving skin barrier function.

Psoriasis is a chronic, relapsing, inflammatory skin disease that is caused by the immune system. Amygdalin possesses immune-modulating and anti-inflammatory effects. To explore the possible effects of amygdalin on psoriasis and its pathogenesis of action, we examined the effects of amygdalin on imiquimod-induced psoriasis, tape-stripping-induced skin barrier disruption, and investigated the potential mechanism of action in vitro.

High frequency of melanoma in /.

Melanoma, the deadliest form of skin cancer characterized by high therapy resistance, has undergone extensive investigation through the utilization of BRAF-driven melanoma animal models. However, there exists a paucity of animal models for the rare hereditary melanoma resulting from germline mutations. Here, employing CRISPR/Cas9 technology, we generated on a knockout background to model human germline mutation-induced hereditary melanoma.

Fibroblast Growth Factor Receptor 4 Promotes Triple-Negative Breast Cancer Progression via Regulating Fatty Acid Metabolism Through the AKT/RYR2 Signaling.

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Previous studies have found that fibroblast growth factor receptor 4 (FGFR4) plays a crucial role in tumor development and metastasis. However, the potential role and underlying mechanisms of FGFR4 in the progression of TNBC remain unclear.

NIR-II Light-Driven Multifunctional Nanozymes PS@CS for Efficient Therapy against Melanoma and Post-tumor Surgery Infection.

Melanoma, the most prevalent form of skin cancer, is primarily treated with surgical intervention. However, complete tumor cell removal is challenging, and surgical wounds are prone to infection, complicating treatment and increasing costs. The successful treatment of melanoma generally requires multifunctional agents that are coordinated in tumor therapy and wound healing.