Structural basis for ligand recognition of the human hydroxycarboxylic acid receptor HCAR3.

Hydroxycarboxylic acid receptor 3 (HCAR3), a class A G-protein-coupled receptor, is an important cellular energy metabolism sensor with a key role in the regulation of lipolysis in humans. HCAR3 is deeply involved in many physiological processes and serves as a valuable target for the treatment of metabolic diseases, tumors, and immune diseases. Here, we report four cryoelectron microscopy (cryo-EM) structures of human HCAR3-Gi1 complexes with or without agonists: the endogenous ligand 3-hydroxyoctanoic acid, the drug niacin, the highly subtype-specific agonist compound 5c (4-(n-propyl)amino-3-nitrobenzoic acid), and the apo form.

Fine-tuning large language models for chemical text mining.

Extracting knowledge from complex and diverse chemical texts is a pivotal task for both experimental and computational chemists. The task is still considered to be extremely challenging due to the complexity of the chemical language and scientific literature. This study explored the power of fine-tuned large language models (LLMs) on five intricate chemical text mining tasks: compound entity recognition, reaction role labelling, metal-organic framework (MOF) synthesis information extraction, nuclear magnetic resonance spectroscopy (NMR) data extraction, and the conversion of reaction paragraphs to action sequences.

A method for structure determination of GPCRs in various states.

G-protein-coupled receptors (GPCRs) are a class of integral membrane proteins that detect environmental cues and trigger cellular responses. Deciphering the functional states of GPCRs induced by various ligands has been one of the primary goals in the field. Here we developed an effective universal method for GPCR cryo-electron microscopy structure determination without the need to prepare GPCR-signaling protein complexes.

Charge-Powered Electrotaxis for Versatile Droplet Manipulation.

Taxis is an instinctive behavior of living organisms to external dangers or benefits. Here, we report a taxis-like behavior associated with liquid droplets on charged substrates in response to the external stimuli, referred to as droplet electrotaxis. Such droplet electrotaxis enables us to use either solid or liquid (such as water) matter, even a human finger, as stimuli to spatiotemporal precisely manipulate the liquid droplets of various physicochemical properties, including water, ethanol with low surface tension, viscous oil, and so on.

Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor.

The M2 muscarinic receptor (M2R) is a prototypical G-protein-coupled receptor (GPCR) that serves as a model system for understanding GPCR regulation by both orthosteric and allosteric ligands. Here, we investigate the mechanisms governing M2R signaling versatility using cryo-electron microscopy (cryo-EM) and NMR spectroscopy, focusing on the physiological agonist acetylcholine and a supra-physiological agonist iperoxo, as well as a positive allosteric modulator LY2119620. These studies reveal that acetylcholine stabilizes a more heterogeneous M2R-G-protein complex than iperoxo, where two conformers with distinctive G-protein orientations were determined.

Kallikrein-related peptidase-8 (KLK8) aggravated hypoxia-induced right ventricular hypertrophy by targeting P38 MAPK/P53 signaling pathway.

Right ventricular (RV) hypertrophy and further heart failure are major co-morbidities, resulting in the premature death of patients with hypoxic pulmonary hypertension (HPH). The regulatory effects of kallikrein-related peptidase (KLK) family members on cardiac function have been extensively studied. However, to the best of the authors' knowledge, the regulatory effects of KLK8 on RV hypertrophy caused by HPH have yet to be reported.

Down-regulation of microRNA-342-5p or Up-regulation of Wnt3a Inhibits Angiogenesis and Maintains Atherosclerotic Plaque Stability in Atherosclerosis Mice.

Evidence has demonstrated that microRNA-342-5p (miR-342-5p) is implicated in atherosclerosis (AS), but little is known regarding its intrinsic regulatory mechanisms. Here, we aimed to explore the effect of miR-342-5p targeting Wnt3a on formation of vulnerable plaques and angiogenesis of AS. ApoE mice were fed with high-fat feed for 16 w to replicate the AS vulnerable plaque model.

Manipulation of a Nonconductive Droplet in an Aqueous Fluid with AC Electric Fields: Droplet Dewetting, Oscillation, and Detachment.

Electrowetting (EW) is an effective method for droplet manipulation in microfluidics. In traditional EW, a conductive droplet is actuated, which spreads on a solid substrate. Recently, we considered an opposite phenomenon of droplet actuation in EW: inducing nonconductive droplet dewetting and detaching from the substrate.

Actuation of a Nonconductive Droplet in an Aqueous Fluid by Reversed Electrowetting Effect.

Manipulation of a conductive droplet by electrowetting has been a popular topic in microfluidics whereby wettability of the droplet on a solid surface is increased by applying a voltage between the conductive droplet and the insulated surface. However, the opposite phenomenon, e.g.

Thermoelectricity in Heterogeneous Nanofluidic Channels.

Ionic fluids are essential to energy conversion, water desalination, drug delivery, and lab-on-a-chip devices. Ionic transport in nanoscale confinements and complex physical fields still remain elusive. Here, a nanofluidic system is developed using nanochannels of heterogeneous surface properties to investigate transport properties of ions under different temperatures.