Structural basis for the ligand recognition and G protein subtype selectivity of kisspeptin receptor.

Kisspeptin receptor (KISS1R), belonging to the class A peptide-GPCR family, plays a key role in the regulation of reproductive physiology after stimulation by kisspeptin and is regarded as an attractive drug target for reproductive diseases. Here, we demonstrated that KISS1R can couple to the G pathway besides the well-known G pathway. We further resolved the cryo-electron microscopy (cryo-EM) structure of KISS1R-G and KISS1R-G complexes bound to the synthetic agonist TAK448 and structure of KISS1R-G complex bound to the endogenous agonist KP54.

Molecular mechanism of antihistamines recognition and regulation of the histamine H receptor.

Histamine receptors are a group of G protein-coupled receptors (GPCRs) that play important roles in various physiological and pathophysiological conditions. Antihistamines that target the histamine H receptor (HR) have been widely used to relieve the symptoms of allergy and inflammation. Here, to uncover the details of the regulation of HR by the known second-generation antihistamines, thereby providing clues for the rational design of newer antihistamines, we determine the cryo-EM structure of HR in the apo form and bound to different antihistamines.

Structural insights into ligand recognition and selectivity of the human hydroxycarboxylic acid receptor HCAR2.

Hydroxycarboxylic acid receptor 2 (HCAR2) belongs to the family of class A G protein-coupled receptors with key roles in regulating lipolysis and free fatty acid formation in humans. It is deeply involved in many pathophysiological processes and serves as an attractive target for the treatment of cardiovascular, neoplastic, autoimmune, neurodegenerative, inflammatory, and metabolic diseases. Here, we report four cryo-EM structures of human HCAR2-Gi1 complexes with or without agonists, including the drugs niacin (2.

Energy-neutral municipal wastewater treatment based on partial denitrification-anammox driven by side-stream sulphide.

"Low-carbon" has become an important evaluation index of modernisation construction. In the area of wastewater treatment has also caused considerable concern. Anaerobic ammonium oxidation (anammox) is a novel autotrophic nitrogen removal process that provides an opportunity for low-carbon remodelling of municipal wastewater treatment plants (MWTPs).

A review of iron use and recycling in municipal wastewater treatment plants and a novel applicable integrated process.

Chemical methods are expected to play an increasingly important role in carbon-neutral municipal wastewater treatment plants. This paper briefly summarises the enhancement effects of using iron salts in wastewater and sludge treatment processes. The costs and environmental concerns associated with the widespread use of iron salts have also been highlighted.

Cryo-EM structure of orphan G protein-coupled receptor GPR21.

GPR21 belongs to class A orphan G protein-coupled receptor (GPCR). The endogenous ligands for human GPR21 remain unidentified. GPR21 expression is associated with developing type 2 diabetes (T2DM), a multifactorial metabolic disease caused by pancreatic β-cell dysfunction, decreasing insulin production, insulin resistance, and obesity.

The era of personalized treatments: Updates on immunotherapy within urothelial of bladder cancer.

Bladder cancer is a complex disease of the urinary system with high morbidity and mortality. Recently, the introduction of immunotherapies such as immune checkpoint inhibitors (eg, programmed cell death protein 1/programmed death-ligand 1) has proven to be a reliable means of improving survival outcomes, including patients with limited response to conventional treatment. Nevertheless, difficult questions remain in clinical practice, such as how to select appropriate patients for personalized treatment, how to predict and assess therapeutic efficacy in advance, and how to enhance the therapeutic benefits of immunotherapy treatment.

Cryo-EM structure of G-protein-coupled receptor GPR17 in complex with inhibitory G protein.

GPR17 is a class A orphan G protein-coupled receptor (GPCR) expressed in neurons and oligodendrocyte progenitors of the central nervous system (CNS). The signalling of GPR17 occurs through the heterotrimeric Gi, but its activation mechanism is unclear. Here, we employed cryo-electron microscopy (cryo-EM) technology to elucidate the structure of activated GPR17-Gi complex.

Transcription factor YY1 mediates epithelial-mesenchymal transition through the TGFβ signaling pathway in bladder cancer.

Bladder cancer is one of the most aggressive urothelial tumors. Previous studies have suggested that epithelial-mesenchymal transition (EMT) contributes to bladder cancer progression. However, the regulatory network of EMT in bladder cancer remains elusive.

Current status and future perspectives of immunotherapy in bladder cancer treatment.

The treatment strategy of bladder cancer has evolved not only through the traditional modalities of surgery and chemotherapy but also by immunotherapy over the past several decades. Immunotherapies such as intravesical Bacillus Calmette-Guérin (BCG) vaccines and immune checkpoint blockades (ICBs) are sometimes used for treating patients with bladder cancer, especially those who develop resistance to conventional first-line treatments such as surgery and chemotherapy. Unfortunately, it is a limited number of individuals that see clinical benefits from this approach, and complicating matters more is that many of these patients suffer severe immune-related adverse events (irAEs).

Communication Of Cancer Cells And Lymphatic Vessels In Cancer: Focus On Bladder Cancer.

Bladder cancer is one of the most commonly diagnosed cancers worldwide and causes the highest lifetime treatment costs per patient. Bladder cancer is most likely to metastasize through lymphatic ducts, and once the lymph nodes are involved, the prognosis is poorly and finitely improved by current modalities. The underlying metastatic mechanism for bladder cancer is thus becoming a research focus to date.

Extracellular vesicles in urologic malignancies-Implementations for future cancer care.

Extracellular vesicles (EVs), a heterogeneous group of vesicles differing in size and shape, cargo content and function, are membrane-bound and nano-sized vesicles that could be released by nearly all variations of cells. EVs have gained considerable attention in the past decades for their functions in modulating intercellular signalling and roles as potential pools for the novel diagnostic and prognostic biomarkers, as well as therapeutic targets in several cancers including urological neoplasms. In general, human and animal cells both can release distinct types of EVs, including exosomes, microvesicles, oncosomes and large oncosomes, and apoptotic bodies, while the content of EVs can be divided into proteins, lipids and nucleic acids.