Structural and mechanistic insights into dual activation of cagrilintide in amylin and calcitonin receptors.

The global obesity epidemic and its associated metabolic disorders urgently require more effective therapeutic interventions, particularly multi-pathway targeting therapies. Cagrilintide (Cagri), functioning as a dual amylin receptor (AMYRs) and calcitonin receptor (CTR) agonist (DACRA), demonstrates significant efficacy in obesity treatment, although its structural activation mechanism remains unclear. This study elucidates the non-selective activation mechanism by determining cryo-EM structures of Cagri bound to AMYR-G and CTR-G complexes.

[Analysis on acupoint compatibility regularity and application characteristics of moxibustion in the treatment of cognitive disorders].

Objectives: To summarize the acupoint compatibility regularity and application characteristics of moxibustion in the treatment of cognitive impairment disorders through data mining technology.

Methods: Eligible clinical studies of moxibustion for treatment of cognitive disorders were searched from databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and SinoMed from the inception of the databases to August 3, 2024 and according to our inclusion and exclusion criteria. Then, a new database for moxibustion treatment of cognitive impairment disorders was established to conduct the standardized processing and frequency analysis using Microsoft Excel 2019.

Increased blood urea nitrogen levels and compromised peripheral nerve function in patients with type 2 diabetes.

Background: Increased blood urea nitrogen (BUN) levels have been demonstrated to be associated with broader metabolic disturbances and the incidence of type 2 diabetes (T2D), potentially playing a role in the development of diabetic complications, including diabetic peripheral neuropathy.

Aim: To examine the relationship between BUN levels and peripheral nerve function in patients with T2D.

Methods: This observational study involved the systematic recruitment of 585 patients with T2D for whom BUN levels and estimated glomerular filtration rate were measured.

Glucagon: a potential protective factor against peripheral nerve compromise in patients with type 2 diabetes and obesity.

Background: Increased glucagon levels are now recognized as a pathophysiological adaptation to counteract overnutrition in type 2 diabetes (T2D). This study aimed to elucidate the role of glucagon in peripheral nerve function in patients with T2D with different body mass indices (BMIs).

Methods: We consecutively enrolled 174 individuals with T2D and obesity (T2D/OB, BMI ≥ 28 kg/m), and 480 individuals with T2D and nonobesity (T2D/non-OB, BMI < 28 kg/m), all of whom underwent oral glucose tolerance tests to determine the area under the curve for glucagon (AUC).

A revision of Chinese endemic Neptis hesione Leech, 1890 with a new species described from Hainan Island (Lepidoptera, Nymphalidae).

The taxonomic status of subspecies belonging to Neptis hesione Leech, 1890 is reviewed. The population from Taiwan Island, once regarded as a subspecies of N. hesione, is treated as an independent species based on morphological and genetic distinctions, i.

A revision of the genus Thaumantis Hübner, [1826] from China (Lepidoptera, Nymphalidae, Satyrinae).

N/A.

Reexamination of the taxonomic status of Coladenia agni (de Nicéville, [1884]) from Hainan, China reveals a new subspecies (Lepidoptera, Hesperiidae).

By reexamining the taxonomic status of Coladenia agni (de Nicéville, [1884]) from different localities, the insular population from Hainan Island is described as a new subspecies, i.e., C.

An EED/PRC2-H19 Loop Regulates Cerebellar Development.

EED (embryonic ectoderm development) is a core subunit of the polycomb repressive complex 2 (PRC2), which senses the trimethylation of histone H3 lysine 27 (H3K27). However, its biological function in cerebellar development remains unknown. Here, we show that EED deletion from neural stem cells (NSCs) or cerebellar granule cell progenitors (GCPs) leads to reduced GCPs proliferation, cell death, cerebellar hypoplasia, and motor deficits in mice.

Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor.

Prolactin-releasing peptide (PrRP) is an RF-amide neuropeptide that binds and activates its cognate G protein-coupled receptor, prolactin-releasing peptide receptor (PrRPR), also known as GPR10. PrRP and PrRPR are highly conserved across mammals and involved in regulating a range of physiological processes, including stress response, appetite regulation, pain modulation, cardiovascular function, and potentially reproductive functions. Here we present cryo-electron microscopy structures of PrRP-bound PrRPR coupled to G or G heterotrimer, unveiling distinct molecular determinants underlying the specific recognition of the ligand's C-terminal RF-amide motif.

Association of Questionnaire-Based Physical Activity Analysis and Body Composition Dynamics in Type 2 Diabetes: A Cross-Sectional Study.

Background: Physical activity (PA) exerts an important influence on glycemic control in type 2 diabetes (T2D) patients. Alterations in body composition in patients with T2D may be involved in the overall pathophysiologic process, but PAs and alterations in body composition have been poorly studied.

Methods: A total of 615 patients with T2D were selected by convenient sampling.

Structural basis for activation of somatostatin receptor 5 by cyclic neuropeptide agonists.

Somatostatin receptor 5 (SSTR5) is an important G protein-coupled receptor and drug target for neuroendocrine tumors and pituitary disorders. This study presents two high-resolution cryogenicelectron microscope structures of the SSTR5-G complexes bound to the cyclic neuropeptide agonists, cortistatin-17 (CST17) and octreotide, with resolutions of 2.7 Å and 2.

Mechanisms of ligand recognition and activation of melanin-concentrating hormone receptors.

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 predominately couples to inhibitory G protein, G, and MCHR2 can only couple to G. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with G and MCH-activated MCHR2 with G at the global resolutions of 3.

Aloperine-Type Alkaloids with Antiviral and Antifungal Activities from the Seeds of L.

As a continuous flow investigation of novel pesticides from natural quinolizidine alkaloids, the chemical compositions of the seeds of were thoroughly researched. Fifteen new aloperine-type alkaloids (-) as well as six known aloperine-type alkaloids (-) were obtained from the extract of . The structures of - were confirmed via HRESIMS, NMR, UV, IR, ECD calculations, and X-ray diffraction.

A late eating midpoint is associated with increased risk of diabetic kidney disease: a cross-sectional study based on NHANES 2013-2020.

Background: Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood.

A new species of the genus Celaenorrhinus Hbner, [1819] from Hainan, China (Lepidoptera, Hesperiidae).

A new species, Celaenorrhinus qianhanae Li & Liu sp. nov., is described from Hainan, China.

A new subspecies of Aporia procris Leech, 1890 hidden in Sichuan, China (Lepidoptera, Pieridae).

Further information on the distribution of Aporia procris Leech, 1890 is provided. The population of A. procris from the upper Dadu River, W.

Quinolizidine Alkaloids and Isoflavones from the Herb of and Their Antiviral, Antifungal, and Insecticidal Activities.

As part of our ongoing investigation of natural bioactive substances from the genus of the tribe Fabaceae for agricultural protection, the chemical constituents of the herb were systematically investigated, which led to the isolation of 39 quinolizidine alkaloids (QAs) (-), including 14 new QAs (-) and 14 isoflavones (-). Their structures were elucidated through comprehensive spectroscopic data analysis (IR, UV, NMR, HRESIMS), ECD calculations, and X-ray crystallography. The antitomato spotted wilt virus (TSWV) and antifungal (against , , , and ) and insecticidal (against and ) activities of the isolated compounds were screened using the lesion counting method, mycelial inhibition assay, and spray method, respectively.

An LRH-RSL4 feedback regulatory loop controls the determinate growth of root hairs in Arabidopsis.

Root hairs are tubular-shaped outgrowths of epidermal cells essential for plants acquiring water and nutrients from the soil. Despite their importance, the growth of root hairs is finite. How this determinate growth is precisely regulated remains largely unknown.

Left epigastric isolated tumor fed by the inferior phrenic artery diagnosed as ectopic hepatocellular carcinoma: A case report.

Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the main cause of cancer-related death worldwide. Ectopic HCC, an extremely rare type of HCC, exhibits a wide range of clinical signs and radiographic features, making preoperative identification challenging.

Case Summary: A 47-year-old man underwent routine abdominal color ultrasonography, which identified an asymptomatic tumor in the left upper abdomen.

Probiotics Increase Intramuscular Fat and Improve the Composition of Fatty Acids in Sunit Sheep through the Adenosine 5'-Monophosphate-Activated Protein Kinase (AMPK) Signaling Pathway.

This experiment aims to investigate the impact of probiotic feed on growth performance, carcass traits, plasma lipid biochemical parameters, intramuscular fat and triglyceride content, fatty acid composition, mRNA expression levels of genes related to lipid metabolism, and the activity of the enzyme in Sunit sheep. In this experiment, 12 of 96 randomly selected Sunit sheep were assigned to receive the basic diet or the basic diet supplemented with probiotics. The results showed that supplementation with probiotics significantly increased the loin eye area, and decreased plasma triglycerides and free fatty acids, increasing the content of intramuscular fat and triglycerides in the muscle and improving the composition of the fatty acids.

Conserved class B GPCR activation by a biased intracellular agonist.

Class B G-protein-coupled receptors (GPCRs), including glucagon-like peptide 1 receptor (GLP1R) and parathyroid hormone 1 receptor (PTH1R), are important drug targets. Injectable peptide drugs targeting these receptors have been developed, but orally available small-molecule drugs remain under development. Here we report the high-resolution structure of human PTH1R in complex with the stimulatory G protein (G) and a small-molecule agonist, PCO371, which reveals an unexpected binding mode of PCO371 at the cytoplasmic interface of PTH1R with G.

Development and validation of a nomogram for predicting severe respiratory syncytial virus-associated bronchiolitis.

Background: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and is related to the severity of the disease. This study aimed to develop and validate a nomogram for predicting severe bronchiolitis in infants and young children with RSV infection.

Methods: A total of 325 children with RSV-associated bronchiolitis were enrolled, including 125 severe cases and 200 mild cases.