Integrative study of lung cancer adeno-to-squamous transition in EGFR TKI resistance identifies RAPGEF3 as a therapeutic target.

Although adeno-to-squamous transition (AST) has been observed in association with resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in clinic, its causality, molecular mechanism and overcoming strategies remain largely unclear. We here demonstrate that squamous transition occurs concomitantly with TKI resistance in PC9-derived xenograft tumors. Perturbation of squamous transition via DNp63 overexpression or knockdown leads to significant changes in TKI responses, indicative of a direct causal link between squamous transition and TKI resistance.

Partition-based k-space synthesis for multi-contrast parallel imaging.

Purpose: Multi-contrast magnetic resonance imaging is a significant and essential medical imaging technique. However, multi-contrast imaging has longer acquisition time and is easy to cause motion artifacts. In particular, the acquisition time for a T2-weighted image is prolonged due to its longer repetition time (TR).

Recent advances in nanoadjuvant-triggered STING activation for enhanced cancer immunotherapy.

The development of effective cancer treatments is a popular in contemporary medical research. Immunotherapy, the fourth most common cancer treatment method, relies on activating autoimmune function to eradicate tumors and exhibits advantages such as a good curative effect and few side effects. In recent years, tumor vaccines that activate the stimulator of interferon genes (STING) pathway are being actively researched in the field of immunotherapy; however, their application is still limited because of the rapid clearance rate of tumor-related lymph nodes and low efficiency of antigen presentation.

Harnessing polysialic acid (PSA)-embedded exudate-absorbing hydrogel for on-demand trigeminal neuralgia treatment.

A key characteristic of trigeminal neuralgia (TN) is cytokine-enriched exudate and a "reactive oxygen species (ROS) storm" generated from the inflammatory cascade, resulting in demyelination of the sensory root of the trigeminal nerve, tissue swelling, and intense electric shock-like pain. The clinically approved drug carbamazepine (CBZ) is capable of inhibiting pain, reducing inflammatory factors, and alleviating oxidative stress, but its clinical application is restricted by its systemic toxicity. Herein, we developed an exudate-absorbing hydrogel incorporating polysialic acid (PSA) and CBZ (F127@PSA@CBZ) for on-demand TN treatment.

Crystal structure of the alternative complex III from the phototrophic bacterium Chloroflexus aurantiacus.

Alternative complex III (ACIII) is a multi-subunit quinol:electron acceptor oxidoreductase that couples quinol oxidation with transmembrane proton translocation in bacterial respiratory and photosynthetic electron transport chains. Four ACIII cryoelectron microscopy (cryo-EM) structures are known. However, the effects of cryo-EM versus X-ray crystallography structure determination on ACIII structure are unclear.

Living Therapeutics for Synergistic Hydrogen-Photothermal Cancer Treatment by Photosynthetic Bacteria.

Hydrogen gas (H) therapy, recognized for its inherent biosafety, holds significant promise as an anti-cancer strategy. However, the efficacy of H treatment modalities is compromised by their reliance on systemic gas administration or chemical reactions generation, which suffers from low efficiency, poor targeting, and suboptimal utilization. In this study, living therapeutics are employed using photosynthetic bacteria Rhodobacter sphaeroides for in situ H production combined with near-infrared (NIR) mediated photothermal therapy.

Targeting the MET gene: unveiling therapeutic opportunities in immunotherapy within the tumor immune microenvironment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) represents the most prevalent histological subtype of lung cancer. Within this disease, the MET gene emerges as a critical therapeutic target, exhibiting various forms of dysregulation. Although MET tyrosine kinase inhibitors, HGF/c-MET targeting antibodies, and antibody-drug conjugates constitute the primary treatment modalities for patients with MET-altered NSCLC, numerous questions remain regarding their optimal application.

The Causal Effect of Urate Level on Female Infertility: A Mendelian Randomization Study.

Background/objective: This study aimed to investigate the causal relationship between urate level and female infertility using Mendelian randomization (MR) analysis.

Methods: To identify instrumental variables, we selected independent genetic loci associated with serum urate levels in individuals of European ancestry, utilizing data from large-scale genome-wide association studies (GWAS). The GWAS dataset included information on serum urate levels from 288,649 CKDGen participants.

The potential of nanosystems in disrupting adenosine signaling pathways for tumor immunotherapy.

Introduction: Adenosine (ADO) is a naturally occurring nucleoside primarily synthesized through the hydrolysis of extracellular adenosine triphosphate. Within the tumor microenvironment, ADO levels substantially increase, resulting in suppressed immune responses.

Areas Covered: Nanosystems offer a promising approach for precise drug delivery to tumor lesions.

Chimerization of human ESC-derived extraembryonic cells with the mouse blastocyst.

It has been reported that human embryonic stem cells (hESCs) treated with BMP4 and inhibitors of TGFβ signaling (A83-01) and FGF signaling (PD173074), called BAP, can efficiently differentiate to extraembryonic (ExE) cells . Due to restricted access to human embryos, it is ethically impossible to test the developmental potential of ExE cells . Here, we demonstrate that most ExE cells expressed molecular markers for both trophoblasts (TBs) and amniotic cells (ACs).

Large-scale structural covariance networks changes relate to executive function deficit in betel quid-dependent chewers.

Previous studies demonstrate deficits in executive function for betel quid-dependent (BQD) patients. Large-scale structural covariance network (SCN) based on gray matter (GM) morphometry may be able to explore the neural mechanism of executive dysfunction in BQD individuals. This study aims to identify spatial covariance patterns of GM volume and to investigate their association with executive dysfunction in BQD individuals.

Targeting esophageal carcinoma: molecular mechanisms and clinical studies.

Esophageal cancer (EC) is identified as a predominant health threat worldwide, with its highest incidence and mortality rates reported in China. The complex molecular mechanisms underlying EC, coupled with the differential incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) across various regions, highlight the necessity for in-depth research targeting molecular pathogenesis and innovative treatment strategies. Despite recent progress in targeted therapy and immunotherapy, challenges such as drug resistance and the lack of effective biomarkers for patient selection persist, impeding the optimization of therapeutic outcomes.

The role of liquid-liquid phase separation in the disease pathogenesis and drug development.

Misfolding and aggregation of specific proteins are associated with liquid-liquid phase separation (LLPS), and these protein aggregates can interfere with normal cellular functions and even lead to cell death, possibly affecting gene expression regulation and cell proliferation. Therefore, understanding the role of LLPS in disease may help to identify new mechanisms or therapeutic targets and provide new strategies for disease treatment. There are several ways to disrupt LLPS, including screening small molecules or small molecule drugs to target the upstream signaling pathways that regulate the LLPS process, selectively dissolve and destroy RNA droplets or protein aggregates, regulate the conformation of mutant protein, activate the protein degradation pathway to remove harmful protein aggregates.

Regimens combining radiation and immunotherapy for cancer: latest updates from 2024 ASCO Annual Meeting.

Combination of immunotherapy with radiotherapy is under active investigation. The PACIFIC trial firmly established the treatment paradigm of consolidation immunotherapy following definitive chemoradiotherapy, inspiring a series of similar or exploratory combination regimens. This summary highlighted six reports updated in the 2024 ASCO Annual Meeting.

Efficient removal of ammonia-nitrogen in wastewater by zeolite molecular sieves prepared from coal fly ash.

Zeolite molecular sieves are potential adsorbents for wastewater treatment, characterized by high efficiency, simple process, easy regeneration, and low treatment cost. In this study, zeolite A molecular sieves were prepared using coal fly ash (CFA), which is an effective method for the utilization of CFA. The results showed that the CFA-based zeolite molecular sieves synthesized under optimized conditions exhibited excellent adsorption and removal rates (> 40%) for ammonia-nitrogen in wastewater of different concentrations and properties.

Investigating the impact of the inflammatory immune microenvironment and steroids or COX-2 inhibitors usage on immunotherapy in advanced esophageal squamous cell carcinoma (ESCC): a propensity score matched analysis.

Purpose: The research aimed to evaluate the connection between pre-treatment inflammatory biomarkers and clinical results in advanced esophageal squamous cell carcinoma (ESCC) receiving immune checkpoint inhibitors.

Materials And Methods: Between 2019 and 2022, we analyzed 354 individuals diagnosed with metastatic ESCC who underwent immunotherapy. The study sought to evaluate the impact of specific inflammatory biomarkers (Neutrophil/Lymphocyte Ratio (NLR), C-reactive protein to albumin ratio (CRP/ALB) and Glasgow Prognostic Score (GPS), Cyclooxygenase-2 (COX-2) inhibitors or steroids usage on the effectiveness and survival outcomes of immunotherapy in advanced ESCC.