Decoding ligand recognition and constitutive activation of histamine H3 and H4 receptors.

Histamine H3 receptor (H3R) and H4 receptor (H4R) are key members of the histamine receptor family, with H3R as a potential target for narcolepsy treatments and H4R as a candidate for next-generation antihistamines for inflammatory and allergic diseases. Although progress has been made in understanding the structure of histamine receptors, the detailed mechanisms of ligand recognition and receptor antagonism for H3R and H4R remain unclear. In this study, using cryo-electron microscopy, we present an inactive structure of H4R bound to a selective antagonist, adriforant, and two Gi-coupled structures of H3R and H4R in complex with histamine.

A dual-sensitive nanoparticle-mediated synergistic therapy strategy involving photodynamic therapy, chemotherapy and ICD stimuli to treat breast cancer.

The combination therapy strategy exerts a significant anti-tumour effect by synergistically eliminating tumour cells through the use of two or more treatments. Nanomedicine delivery systems are widely employed in cancer therapy owing to their ability to effectively improve drug solubility and enhance drug targeting. To this end, we have designed and developed a nano-targeted drug delivery platform PAE-PEG-ss-Ce6/DOX nanoparticles (PPCD NPs), for the co-delivery of the photosensitiser chlorin e6 (Ce6) and the chemotherapeutic agent doxorubicin (DOX).

A clickable spherical nucleic acid probe for fluorescence and synchrotron radiation X-ray dual-modality imaging.

In this study, we have developed a dual-mode probe based on click chemistry for spherical nucleic acids (SNAs), achieving extremely specific fluorescence imaging and synchrotron X-ray microscopy of neuronal cells.

High-Resolution Single-Neuron Reconstruction Analysis in Golgi-Stained Brain Tissues.

Understanding the structural and functional organisation of brain networks is a fundamental objective in neuroscience, with three-dimensional (3D) reconstruction of single-neuron morphology serving as a critical foundation. The Golgi staining method, which enables random neuronal labeling and provides high-contrast signals in both optical and X-ray microscopy, remains a valuable tool for morphological analysis. However, its widespread application in large-scale neuronal reconstructions is hindered by signal discontinuities in neuronal branches, high-density labeling, and complex background interference.

Development of Antibody-Based Strategies for Targeted Degradation of Membrane and Extracellular Proteins.

Membrane and extracellular proteins are essential components in various biological processes that ensure cellular function and homeostasis. Their dysregulation is linked to a wide range of diseases, making them pivotal therapeutic targets. Recent innovations in therapeutic strategies have concentrated on targeted protein degradation, particularly via the endocytosis-lysosome pathway, offering a novel approach to restoring balance within cellular systems.

The hybrid nano-platform based on ZIF-8 realises the synergistic therapy of tumour chemo-immunotherapy.

Immunotherapy has attracted widespread attention as a new tumour treatment method. Because of the low response rate, immunotherapy is only effective for some patients. With the continuous exploration of tumour immunity, the concept of immunogenic cell death (ICD) has brought new vitality to many cancer treatment methods, including chemotherapy.

Application of heterologous extracellular vesicles and their analogs in anti-tumor activity research.

Extracellular vesicles and their analogues can mediate intercellular communication for gene regulation, thereby activating corresponding cellular functions, which demonstrates promising applications in disease diagnosis and treatment. Extensive studies have indicated that extracellular vesicles and their analogues exhibit remarkable efficacy in various pharmacological activities, including anti-tumor effects, immune modulation, prevention and treatment of cardiovascular diseases, as well as tissue regeneration. Heterologous extracellular vesicles and their analogues possess diverse biological activities attributed to their compositions, distributions, and mechanisms of action.

Near-Freezing-Temperature Golgi Neuronal Staining for X-ray Imaging of Human Brain.

Achieving detailed neuronal structural information in large-volume brain tissue has been a longstanding challenge in human brain imaging. A key obstacle arises from the trade-off between staining efficiency and tissue autolysis. Traditional Golgi staining, typically conducted at room temperature or 37 °C to optimize staining efficiency, leads to rapid autolysis of brain tissue, resulting in the loss of fine structural details.

Formation and Stabilization of Bulk Nanobubbles Triggered by Ultrasonic Irradiation under Different Conditions.

The generation and stabilization of nanobubbles (NBs) are crucial concerns, considering their great potential for applications in various fields. Nonetheless, research on the stabilization of bulk nanobubbles (BNBs) generation across various systems under ultrasonic irradiation is relatively few. For example, how dissolved gases and different conditions affect the evolution of BNBs in the acoustic field remains unclear.

Functional connectivity and characteristics of cortical brain networks of elderly individuals under different motor cognitive tasks based on functional near-infrared spectroscopy.

Objective: This study aimed to investigate age-related changes in brain functional connectivity during various motor and cognitive tasks, providing evidence for evaluating and intervening in brain aging.

Methods: 15 elderly participants (ELD) and 30 young controls (YOU) were assessed. fNIRS haemodynamic responses were recorded during the Purdue nail board motor task, continuous minus 7 cognitive task, and motor-cognitive dual task.

Preparation of pH-enzyme dual-responsive gel microspheres and their treatment of ulcerative colitis.

Mesalazine (MSZ), a first-line treatment for ulcerative colitis (UC), was formulated into acid-resistant, colon-targeted gel microspheres to reduce upper gastrointestinal tract (GIT) exposure and extend drug retention in the colon. In this study, we used MSZ/hydroxypropyl-β-cyclodextrin (MSZ/HP-β-CD) as the model drug, dopamine-modified sodium alginate (DA-SA) and konjac glucomannan (KGM) as the carrier matrix, and chitosan (CS) as the coating material. The colon-targeted gel microspheres (MSZ/HP-β-CD/DA-SA/KGM/CS) were prepared using the drop method.

Synchrotron-Based X-Ray Molecular Probes for Imaging in Intelligent Biomedicine.

With the construction and operational launch of third-generation synchrotron radiation sources, X-ray molecular probe technology is actively explored and developed, playing an increasingly significant role in modern life sciences. This review provides an overview of synchrotron-based X-ray imaging techniques and emphasizes the applications of X-ray molecular probes across various fields associated with intelligent biomedicine. Building on this foundation, it further discusses future advancements in X-ray molecular probes and forecasts their application trends in intelligent biomedicine, particularly in the realm of personalized treatment.

Lysosome-targeting chimeras containing an endocytic signaling motif trigger endocytosis and lysosomal degradation of cell-surface proteins.

Lysosome-targeting degradation technologies have emerged as a promising therapeutic strategy for the selective depletion of target extracellular and cell-surface proteins by harnessing a cell-surface effector protein such as lysosome-targeting receptors (LTRs) or transmembrane E3 ligases that direct lysosomal degradation. We recently developed a lysosome-targeting degradation platform termed signal-mediated lysosome-targeting chimeras (SignalTACs) that functions independently of an LTR or E3 ligase; these are engineered fusion proteins comprising a target binder, a cell-penetrating peptide (CPP), and a lysosomal sorting signal motif (P1). Herein, we present the next-generation SignalTACs containing a single endocytic signal that bypasses the need for a CPP.

Glucose Transporter-Targeting Chimeras Enabling Tumor-Selective Degradation of Secreted and Membrane Proteins.

Tumor-selective degradation of target proteins has the potential to offer superior therapeutic benefits with maximized therapeutic windows and minimized off-target effects. However, the development of effective lysosome-targeted degradation platforms for achieving selective protein degradation in tumors remains a substantial challenge. Cancer cells depend on certain solute carrier (SLC) transporters to acquire extracellular nutrients to sustain their metabolism and growth.

Harnessing molecular probes for imaging of human epidermal growth factor receptor (HER) family.

The human epidermal growth factor receptor (HER) family plays a critical role in the development, migration, and invasion of various cancers. Currently, the FDA has approved numerous targeting therapies for the HER family consist of small molecule drugs, monoclonal antibodies and antibody-drug conjugates. To facilitate precision therapy using currently approved targeted agents, early detection and quantification of each HER receptor are essential for assessment, treatment, and prognostic purposes.

B-nZVI optimization of strength and heavy metal stability of lead-contaminated soil solidified by Portland cement.

Traditional cement solidifying or stabilizing heavy metal-contaminated sites often face issues like alkalinity loss, cracking, and poor long-term performance. Therefore, bentonite-supported nano-zero-valent iron (B-nZVI) was introduced to optimize the remediation effect of cement in this paper. The effects of B-nZVI, ordinary Portland cement (OPC), and B-nZVI + OPC on the chemical stability of heavy metals and the physical strength of lead-contaminated soil were compared using semi-dynamic leaching methods, BCR tests, unconfined strength analysis, and micro-assisted analysis.

Isolation Techniques, Structural Characteristics, and Pharmacological Effects of Phellinus Polysaccharides: A Review.

Phellinus is a precious perennial medicinal fungus. Its polysaccharides are important bioactive components, and their chemical composition is complex. The polysaccharides are mainly extracted from the fruiting body and mycelium.

Discovery of Novel Peptide Antagonists Targeting GPR55 for Liver Inflammation and Fibrosis.

Liver fibrosis is a condition characterized by aberrant proliferation of connective tissue in the liver resulting from diverse etiological factors. G protein-coupled receptor GPR55 has recently been identified as a regulator of liver diseases. Herein, we report the discovery of a cyclic peptide P1-1 that antagonizes GPR55 and suppresses collagen secretion in hepatic stellate cells.

Complex Pulmonary Arteriovenous Fistula Presented With Ventricular Tachycardia and Type 2 Acute Myocardial Infarction.

Pulmonary arteriovenous fistula (PAVF) is a rare congenital vascular malformation primarily manifested as dyspnea, migraine, ischemic stroke, hemoptysis, and nervous system complications. However, in our case, an 18-year-old male patient with PAVF presented with sudden onset of ventricular tachycardia and type 2 acute myocardial infarction as initial symptoms. A diagnosis was achieved through pulmonary artery computer tomography angiography (CTA) and three-dimensional (3D) computed tomography (CT) reconstruction, revealing a complex and giant PAVF.

Nanoparticle-mediated immunogenic cell death for cancer immunotherapy.

The field of cancer therapy is witnessing the emergence of immunotherapy, an innovative approach that activates the body own immune system to combat cancer. Immunogenic cell death (ICD) has emerged as a prominent research focus in the field of cancer immunotherapy, attracting significant attention in recent years. The activation of ICD can induce the release of damage-associated molecular patterns (DAMPs), such as calreticulin (CRT), adenosine triphosphate (ATP), high mobility group box protein 1 (HMGB1), and heat shock proteins (HSP).

Clickable X-ray Nanoprobes for Nanoscopic Bioimaging of Cellular Structures.

Synchrotron-based X-ray microscopy (XRM) has garnered widespread attention from researchers due to its high spatial resolution and excellent energy (element) resolution. Existing molecular probes suitable for XRM include immune probes and genetic labeling probes, enabling the precise imaging of various biological targets within cells. However, immune labeling techniques are prone to cross-interference between antigens and antibodies.

Stability of tryptophan-containing LOs in flaxseed oil and their response towards γ-tocopherol.

Linusorbs (LOs), significantly influence oil quality and sensory properties of flaxseed oil. Trp-containing LOs exhibit distinct oxidative behavior when γ-tocopherol (γ-T) is present. Polar fractions of crude flaxseed oil were stripped via silica absorption, and reintroduced (LO and γ-T) separately into the oil matrix to investigate their interaction during storage.

Distinct roles of the extracellular surface residues of glucagon-like peptide-1 receptor in β-arrestin 1/2 signaling.

Glucagon-like peptide-1 receptor (GLP-1R) is a prime drug target for type 2 diabetes and obesity. The ligand initiated GLP-1R interaction with G protein has been well studied, but not with β-arrestin 1/2. Therefore, bioluminescence resonance energy transfer (BRET), mutagenesis and an operational model were used to evaluate the roles of 85 extracellular surface residues on GLP-1R in β-arrestin 1/2 recruitment triggered by three representative GLP-1R agonists (GLP-1, exendin-4 and oxyntomodulin).