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Glucose is essential to the physiological processes of vertebrates. Mammalian physiological stability requires a relatively stable blood glucose level (~5 mM), whereas other vertebrates have greater flexibility in regulating blood glucose (0.5–25 mM). GCGR family receptors play an important role in vertebrate glucose regulation. Here, we examine the evolution of the GCGR family ligand-receptor systems in different species. Comparatively, we discover that the conserved sequences among GCG family ligands lead to the non-specific activation of ligands across species. In particular, we observe that glucagon-like peptide 1 receptor (GLP1R), glucagon-like peptide 2 receptor (GLP2R), and glucagon-like receptor (GCGLR, also called GCRPR) are arbitrarily activated by other members of the ligand family in birds. Moreover, we reveal that Gallus gallus GLP2 (gGLP2) effectively activates mammalian GLP1R and improves glucose tolerance in diabetic mice. Our study has important implications for understanding blood glucose stabilization in vertebrates and demonstrates that gGLP2 may be a potential drug for treating type 2 diabetes.

This paper selects the index data of population, economy and space from 2000 to 2019, establishes an evaluation index system for the level of new urbanization and environmental quality in Qinghai Province, studies the coordination between new urbanization and environmental quality in Qinghai Province by establishing a coupling coordination model, and puts forward countermeasures and suggestions for the coordinated development of new urbanization and environmental quality in Qinghai Province.

Neuropeptide Y (NPY), a 36‐amino‐acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro34]–NPY and [Leu31, Pro34]–NPY, mainly acting on Y1R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N‐terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y2R. However, the recognition mechanisms of Y1R and Y2R with specific agonists remain elusive, thereby hindering subtype receptor‐selective drug development. In this study, we report three cryo‐electron microscopy (cryo‐EM) structures of Gi2‐coupled Y1R and Y2R in complexes with NPY, as well as Y1R bound to a selective agonist [Leu31, Pro34]–NPY. Combined with cell‐based assays, our study not only reveals the conserved peptide‐binding mode of NPY receptors but also identifies an additional sub‐pocket that confers ligand selectivity. Moreover, our analysis of Y1R evolutionary dynamics suggests that this sub‐pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family. [ABSTRACT FROM AUTHOR]

This article discusses the molecular pharmacology of trace amine-associated receptor 1 (TAAR1) and its potential role in advancing antipsychotic drug discovery. Schizophrenia, a chronic mental disorder, is characterized by negative symptoms, positive symptoms, and cognitive impairment. Current antipsychotic drugs have limited efficacy and are associated with side effects. TAAR1 has emerged as a potential therapeutic target for psychiatric disorders, and recent studies have provided insights into the molecular mechanisms and activation characteristics of TAAR1. These findings could contribute to the development of new antipsychotic drugs. [Extracted from the article]

G protein-coupled receptors (GPCRs) are versatile and vital proteins involved in a wide array of physiological processes and responses, such as sensory perception (e.g., vision, taste, and smell), immune response, hormone regulation, and neurotransmission. Their diverse and essential roles in the body make them a significant focus for pharmaceutical research and drug development. Currently, approximately 35% of marketed drugs directly target GPCRs, underscoring their prominence as therapeutic targets. Recent advances in structural biology have substantially deepened our understanding of GPCR activation mechanisms and interactions with G-protein and arrestin signaling pathways. This review offers an in-depth exploration of both traditional and recent methods in GPCR structure analysis. It presents structure-based insights into ligand recognition and receptor activation mechanisms and delves deeper into the mechanisms of canonical and noncanonical signaling pathways downstream of GPCRs. Furthermore, it highlights recent advancements in GPCR-related drug discovery and development. Particular emphasis is placed on GPCR selective drugs, allosteric and biased signaling, polyphamarcology, and antibody drugs. Our goal is to provide researchers with a thorough and updated understanding of GPCR structure determination, signaling pathway investigation, and drug development. This foundation aims to propel forward-thinking therapeutic approaches that target GPCRs, drawing upon the latest insights into GPCR ligand selectivity, activation, and biased signaling mechanisms. [ABSTRACT FROM AUTHOR]

Radiation cooling, as a new terminal mode that has been gradually emerging in recent years, has attracted more and more attention. However, the problem of condensation has become a vital bottleneck restricting the broad application of radiation-cooling technology. This paper used the numerical simulation method of Ansys Fluent to study the effect of different water supply parameters on the concrete radiant roof's heat transfer performance, temperature uniformity analysis, and anti-condensation temperature control strategy. The accuracy of the simulation model was verified by comparing the numerical simulation values and measured values of temperature monitoring points. In thermal performance research, the inlet temperature significantly impacted the cooling capacity and radiant surface temperature compared with the inlet flow velocity. In the uniformity study, the distance between the serpentine pipes area and the concrete edge was easily neglected, which was also an important factor affecting the distribution of temperature uniformity. Regarding anti-condensation and performance improvement research, first supplying water at low temperatures and then dynamically adjusting high-temperature water could effectively avoid condensation and improve the radiant roof's heat transfer performance. The research results could provide technical references for the practical application of radiation roof anti-condensation temperature control technology. [ABSTRACT FROM AUTHOR]

For women with epilepsy of reproductive age, antiseizure medications (ASMs) are associated with an increased risk of offspring malformations. There are safety concerns for most anti-seizure medications in the perinatal period, and there is a clear need to identify safe medications. ASMs must transport through biological barriers to exert toxic effects on the fetus, and transporters play essential roles in trans-barrier drug transport. Therefore, it is vital to understand the distribution and properties of ASM-related transporters in biological barriers. This study reviews the structure, transporter distribution, and properties of the blood-brain, placental, and blood-milk barrier, and summarizes the existing evidence for the trans-barrier transport mechanism of ASMs and standard experimental models of biological barriers. Ideal ASMs in the perinatal period should have the following characteristics: 1) Increased transport through the blood-brain barrier, and 2) Reduced transport of the placental and blood-milk barriers. Thus, only low-dose or almost no antiseizure medication could enter the fetus's body, which could decrease medication-induced fetal abnormalities. Based on the stimulated structure and molecular docking, we propose a development strategy for new ASMs targeting transporters of biological barriers to improve the perinatal treatment of female patients with epilepsy. [ABSTRACT FROM AUTHOR]

In this note, the authors will study how the poles of a linear time‐invariant singularly perturbed system are varied versus singular parameter ε, where the poles of the slow and fast subsystems are assumed to be placed in the prescribed regions. An explicitε$\ \varepsilon $ bound is derived such that the poles of the original full order system remain in these regions. Finally, two examples are illustrated to show the applications of the proposed results. [ABSTRACT FROM AUTHOR]

Summary: The high rates of electricity consumption in data centers become a worldwide concern. Water‐side free cooling is an effective solution to reduce the energy consumed by the data center's cooling system. However, the water‐side free cooling system is not well planned, and the free cooling utilization rate is low in different climate zone. Moreover, the effects of local climatic conditions on the optimal setting parameters have not been researched. In this study, the optimal setting in chilled water supply temperature, temperature difference, and chilled water return temperature is analyzed to enhance the efficiency of the free cooling system. We observed that the optimal setting could reduce annual energy consumption by 23.5%–60.8% in various climate zones and has substantial energy‐saving potential in the subtropical highland climate zone. The results show that the optimal setting parameters are highly affected by the annual accumulative wet‐bulb temperature distribution. Furthermore, considering a monthly analysis of these enhanced parameters, we proposed a dual‐working condition cooling system for the data center's future construction. This research work guides the design of such cooling systems in various climate zones. [ABSTRACT FROM AUTHOR]

We describe a high-peak-power, narrow-linewidth Q-switched Ho:YAG laser at 2097 nm wing-pumped by a high power and high brightness Tm:fiber source at 1931.5 nm. The laser was wavelength locked and spectrum narrowed utilizing a volume Bragg grating as the input coupler, resulting a linewidth of less than 0.1 nm. At 22.7 W of incident pump power, stable pulses of 5.5 mJ pulse energy and 17.5 ns of pulse duration have been generated at repetition frequency of 1 kHz, corresponding to peak-power of 314.3 kW. [ABSTRACT FROM AUTHOR]

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