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peptide science.

Artificial Crystalline-Amorphous Architecture Enables Continuous Ion Transport in Poly(Vinylidene Fluoride)-Based Solid-State Electrolytes.

Small

Yue-Ming Chen, Min Zuo, Hanghua Wu +9 more

Solid-state polymer electrolytes (SPEs) hold promises for next-generation batteries but are hindered by low ionic conductivities. This issue stems from crystalline regions that block long-range ion transport in amorphous phases, while fully amorphous polymers are mechanically unstable. Here we design an "artificial crystalline-amorphous" architecture that converts the isolated amorphous conduction zones into continuous, long-range pathways. This is achieved by infiltrating a fully amorphous poly (vinylidene fluoride‑co‑chlorotrifluoroethylene) (PVT) into an oriented electrospun fibrous framework of polar semi‑crystalline PVT. The framework serves as an "artificial crystalline phase," offering robust mechanical support and facilitating lithium‑salt dissociation. Simultaneously, the amorphous phase utilizes this microscale network to enable long-range ion conduction. The resulting SPEs exhibit an extremely high ionic conductivity of 1.23 mS cm-1 at 25°C, outperforming most reported all-polymeric-SPEs (10-7 ∼ 10-5 S/cm). Li//Li symmetric cells demonstrate stable cycling over 1300 h at 0.2 mA cm-2, in clear contrast to 60 h for the controlled cell. Furthermore, assembled high-voltage Ni0.8Co0.1Mn0.1O2 (NCM811)//Li full cells also deliver a stable cycling performance at 25°C. This work opens a new route for improving ion transport efficiency by constructing an artificial crystalline-amorphous structure.

LL-37-ApoB-100 Complex Serves as a Biomarker of Coronary Artery Disease.

Arterioscler Thromb Vasc Biol

Yaqun Fang, Zhiye Zhang, Qiqi Cao +20 more

ApoB (apolipoprotein B)-containing lipoproteins are causal risk factors for atherosclerotic coronary artery disease (CAD). Since LL-37 (human cathelicidin peptide) binds to ApoB-100 in this pathological context, we investigated whether the circulating LL-37-ApoB-100 complex could serve as a biomarker for CAD.

Serine protease HtrA promotes Campylobacter jejuni intestinal colonization through degrading antimicrobial peptide LL-37.

Sci Adv

Xiaofei Li, Mengjie Zhang, Zhenzhen Xu +6 more

Campylobacter jejuni (C. jejuni) is a leading cause of human gastroenteritis worldwide and must overcome intestinal innate immunity, including antimicrobial peptide LL-37. However, how C. jejuni responds to LL-37 remains unclear. Here, we showed that C. jejuni infection stimulates intestinal epithelial cells to secrete LL-37, exhibiting effective antibacterial activity against 86.3% of C. jejuni clinical isolates by disrupting essential processes required for bacterial survival. A subset of isolates displays intrinsic resistance, enabling successful intestinal colonization. We further identified conserved serine protease HtrA as the key determinant of resistance. Mechanistically, LL-37 exposure activates transcriptional regulator NssR, which up-regulates htrA expression. Secreted HtrA cleaves LL-37 at Ile20-Val21 site, abolishing its antimicrobial activity and promoting bacterial survival. In light of this mechanism, we developed a noncleavable LL-37I20M/V21R that displays enhanced antibacterial activity and promotes bacterial clearance in mice. Together, our findings uncover mechanistic insights into interactions between human enteric pathogens and antimicrobial peptides and provide a potential strategy for combating C. jejuni infection.

Semaglutide use for hypothalamic obesity and type 2 diabetes mellitus after suprasellar germinoma treatment.

JCEM Case Rep

Kenichi Yokota, Tomoko Nakagawa, Yuta Nakamura +3 more

Hypothalamic obesity (HO) is a severe complication of suprasellar tumors characterized by hyperphagia, rapid weight gain, and resistance to lifestyle interventions. We describe a case of a woman diagnosed with suprasellar germinoma at 16 years of age who was treated with chemotherapy and radiotherapy. Subsequently, she experienced progressive weight gain, increasing from 57 kg to a peak of 138 kg by age 37 years, and developed type 2 diabetes mellitus at age 28 years. At age 38 years, she presented with polydipsia, polyuria, and fatigue, and was admitted for the management of hyperglycemia with class III obesity (123.5 kg; body mass index [BMI], 51.4 kg/m2). Intensive insulin therapy (up to 100 units/day) resolved glucotoxicity. After initiation of semaglutide (titrated from 0.25 to 0.5 mg/week), appetite markedly decreased, and subsequent weight loss was achieved. Three months after discharge, her weight decreased from 131 kg to 112.1 kg, representing an approximate 14% reduction, accompanied by optimized glycemic control. Body composition analysis revealed that weight loss was primarily due to fat mass reduction with relative preservation of muscle mass. This case demonstrates the potential efficacy of semaglutide in patients with HO and type 2 diabetes mellitus after suprasellar germinoma treatment.

Plain language summary: the evoke(+) studies of semaglutide for early Alzheimer's disease.

Neurodegener Dis Manag

Jeffrey L Cummings, Alireza Atri, Mary Sano +9 more

What is this summary about?This article presents a plain language summary of the results from the evoke and evoke+ phase 3 clinical studies, collectively known as the evoke(+) studies, which were published in The Lancet in March 2026.The primary goal of the evoke(+) studies was to understand if oral treatment with up to 14 mg of the drug semaglutide (normally used for the treatment of type 2 diabetes and/or obesity) delayed decline of memory and thinking in people with the early stages of Alzheimer’s disease.A delay in the onset of Alzheimer’s disease has been observed in some previous studies among patients with type 2 diabetes treated with semaglutide, suggesting that this could be a potential treatment for Alzheimer’s disease.The evoke(+) studies compared the effects of semaglutide treatment taken once per day by mouth with a placebo group using clinical tests and blood and cerebral fluid samples that can measure the course of Alzheimer’s disease. People in the trial did not know if they were receiving semaglutide or placebo (e.g. the trials were ‘blinded’).The main test used was change in Clinical Dementia Rating–Sum of Boxes score which assesses thinking, memory, and everyday activities.Change in Alzheimer’s Disease Cooperative Study Activities of Daily Living–Mild Cognitive Impairment score, a measure of activities of daily living in everyday life, was also included in the study. Activities of daily living include those inside and outside the home.What are the key takeaways?Oral semaglutide taken once per day by mouth up to 14 mg did not slow cognitive or functional decline in people with the early stage of Alzheimer’s disease. Therefore, it is not effective as a treatment for the early stages of Alzheimer’s disease.Safety information collected during the studies showed that adverse effects are similar to those observed when semaglutide is taken for other diseases and no new adverse effects were identified.The evoke(+) studies provide information on disease progression and safety that could be used in the future.

Response to Comment on Mann et al. Impact of Oral Semaglutide on Kidney Outcomes in People With Type 2 Diabetes: Results From the SOUL Randomized Trial. Diabetes Care 2026;49:257-265.

Diabetes Care

Johannes F E Mann, Ole Kleist Jeppesen, Nicolas Belmar +2 more

Comment on Mann et al. Impact of Oral Semaglutide on Kidney Outcomes in People With Type 2 Diabetes: Results From the SOUL Randomized Trial. Diabetes Care 2026;49:257-265.

Diabetes Care

Songbei Li

DUAL GIP/GLP-1Ra reduces residual proteinuria in non-diabetic fabry disease.

Nephrol Dial Transplant

Eleonora Riccio, Alessandra Cuomo, Ivana Capuano +4 more

Residual proteinuria remains a major determinant of renal disease progression in Fabry disease (FD) despite optimized enzyme replacement or chaperone therapy and maximal renin-angiotensin system (RAS) blockade. Dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonists exert anti-inflammatory, natriuretic, and antifibrotic effects beyond metabolic control. We evaluated the impact of add-on tirzepatide on residual proteinuria in overweight, non-diabetic Fabry patients receiving optimized background therapy.

Comment on Sattar et al. Weight Reduction With Tirzepatide Varied Meaningfully by Baseline HbA1c Category in Adults With Overweight or Obesity and Type 2 Diabetes in SURMOUNT-2. Diabetes Care 2025;48:e136-e137.

Diabetes Care

Salvatore Corrao

In Vitro Characterization of Agonist and Antagonist Peptide Binding Interaction Kinetics to GLP-1R in HEK293T Cells Using Surface Plasmon Resonance Microscopy.

ACS Med Chem Lett

Miyuki A Thirumurthy, Jesús S Aguilar Díaz de León, Shuchong Pan +1 more

The glucagon peptide 1 receptor (GLP-1R), a class-B-type G protein-coupled receptor (GPCR), is a key therapeutic target for many metabolic disorders, including obesity and type 2 diabetes, due to its central role in glucose homeostasis and insulin secretion. Despite its pharmacological importance, studying the binding kinetics of its multidomain engagement with peptide ligands remains a challenge using purified receptor systems. The isolated forms fail to capture the dynamic behavior of membrane-bound GPCRs in a physiologically relevant context. A deeper understanding of the interaction kinetics of agonist and antagonist binding to GLP-1R domains is essential for rational drug design, as the activation of the receptor depends on distinct binding modes that modulate downstream signaling efficacy. Here we employ surface plasmon resonance microscopy (SPRM) on HEK293T cells overexpressing GLP-1R to visualize and quantify the label-free kinetic interactions of ligands on whole single cells in real time. Using three different agonists (GLP-1, liraglutide, exendin-4) and one antagonist (exendin-9), we demonstrate that the agonists exhibit a two-mode/bivalent binding behavior with C-terminal engagement of the extracellular domain (ECD) and N-terminal engagement of the transmembrane domain (TMD). In contrast, the antagonist exendin-9 binds with a single mode, exclusively to the ECD. Importantly, SPRM resolves not only the presence of dual-domain engagement but also the stability and heterogeneity of these interactions, enabling discrimination between full and partial agonism. Notably, liraglutide displays the highest interaction affinity and the greatest amount of activation through TMD binding, which agrees with its known structural optimization and superior therapeutic performance. This study highlights SPRM as a powerful, label-free platform for probing the on-cell binding kinetics of GPCR interactions with peptides, providing quantitative insights into the activation efficiency of agonists and selectivity of antagonists in ways conventional receptor assays cannot.

The Liraglutide Effects in Atrial Fibrillation (LEAF) Study.

JACC Clin Electrophysiol

Jeffrey J Goldberger, Raul D Mitrani, Joel Fishman +11 more

Atrial fibrillation (AF) ablation continues to offer mediocre outcomes, particularly for persistent AF. Obesity and epicardial adipose tissue (EAT) are associated with AF and ablation outcomes. Risk factor modification (RFM), including weight loss, improves AF treatment outcomes. Liraglutide, a glucagon-like peptide-1 receptor agonist, leads to weight loss and EAT reduction.

Exploring the Use of GLP-1-Based Interventions for Obesity: A Qualitative Analysis of ClinicalTrials.gov Data.

Diabetes Metab Syndr Obes

Nouf M Alourfi, Nasser M Alorfi

Glucagon-like peptide-1 (GLP-1) receptor agonists are a key pharmacological target in obesity management, associated with sustained weight loss and broader metabolic benefits beyond glycaemic control.

Progress in research on the association between mesenchymal stem cell senescence and knee osteoarthritis.

J Orthop Surg Res

Zhicheng Hu, Caixiang Xu, Shiwan Guo

Osteoarthritis (OA) is an age-related disease characterized by cartilage degeneration, subchondral bone remodeling, and chronic low-grade inflammation, with knee osteoarthritis (KOA) being a leading cause of functional impairment and reduced quality of life in middle-aged and elderly individuals. In recent years, advances in stem cell biology and aging research have highlighted the critical role of mesenchymal stem cells (MSCs) in maintaining joint homeostasis, regulating inflammatory responses, and mediating cartilage repair. Accumulating evidence indicates that reductions in MSC quantity and functional decline-particularly age-associated decreases in proliferative capacity, impaired differentiation potential, mitochondrial dysfunction, and activation of the senescence-associated secretory phenotype (SASP)-constitute key biological mechanisms driving KOA onset and progression.This review systematically summarizes the major molecular mechanisms underlying MSC senescence, including telomere shortening, DNA damage accumulation, mitochondrial dysregulation, and SASP activation, and emphasizes the roles of senescent MSCs in impaired cartilage regenerative capacity, disruption of extracellular matrix homeostasis, and imbalance in inflammatory and immune microenvironments. Additionally, we highlight recent research on potential interventions targeting MSC senescence, including senescent cell clearance, metabolic and mitochondrial restoration, MSC-derived exosome therapy, and advances in engineered culture and delivery technologies.In conclusion, MSC senescence represents not only a fundamental pathological basis for KOA development but also a critical target for future OA interventions, providing important theoretical and translational value for advancing regenerative medicine strategies toward clinical application.

Impact of mild autonomous cortisol secretion on metabolism & cardiac morphology in adrenal incidentaloma.

J Hypertens

Yanan Li, Jiang Liu, Xin Zhao +1 more

Mild autonomous cortisol secretion (MACS) leads to the clustered manifestations of hypertension (HT), diabetes, and metabolic syndromes. However, whether the effect of MACS on myocardial remodeling and cardiac function is similar to that of Cushing's syndrome remains unclear. This study aimed to compare the metabolic risks and impact on cardiac structure and function between MACS and Cushing's syndrome.

Differential Impact of Cholecystokinin and Ghrelin on 2-Year Avoidant/Restrictive Food Intake Disorder Symptoms.

J Clin Psychiatry

Vittoria Trolio, Sophie Scharner, Nassim Tabri +12 more

Objective: Individuals with avoidant/restrictive food intake disorder (ARFID) commonly endorse lacking interest in eating/food, difficulties recognizing hunger, and early satiation. Cholecystokinin (CCK) and ghrelin may be important biologic mechanisms in ARFID given their role in appetite signaling. We investigated whether youth with ARFID-lack of interest had greater CCK and lower ghrelin levels compared to youth without this presentation across timepoints and whether greater reductions in CCK and increases in ghrelin were associated with ARFID symptom improvement over a two-year period. Methods: One hundred youth (49% female, mean [SD] age=15.87 [3.89] years, mean [SD] body mass index percentile=37.71 [35.16]) recruited from a single-center clinic and surrounding community, initially meeting DSM-5 criteria for full/subthreshold ARFID completed the Pica, ARFID, and Rumination Disorder Interview at baseline and follow-up over two years (July 2016-September 2022) to determine ARFID diagnosis, presentation type, and severity scores. We obtained fasting plasma levels of CCK and ghrelin at each timepoint. Results: Youth with ARFID-lack of interest had higher CCK than those without this presentation, though there were no differences in fasting ghrelin. Greater decreases in CCK from Baseline to Years 1 and 2 were associated with decreases in lack of interest severity at Years 1 and 2, whereas greater increases in ghrelin from Baseline to Years 1 and 2 were associated with decreases in ARFID severity at Years 1 and 2. Conclusion: In the first longitudinal study of neuroendocrine abnormalities in individuals with ARFID, we found that decreases in CCK and increases in ghrelin were associated with improvements in ARFID symptomology.

Activation of PPARγ and CPT1A Mediates the Hepatoprotective Effect of Ginsenoside CK against NAFLD in Rats.

Biol Proced Online

Danfeng Lan, Guishun Sun, Zhiyong Dong +7 more

Nonalcoholic fatty liver disease (NAFLD) is a significant underlying driver of hepatocellular carcinoma; however, current clinical treatment options remain limited. Ginsenoside CK (CK), a natural bioactive compound, has shown promise in modulating lipid metabolism and protecting liver function. Nevertheless, its therapeutic potential against the pathogenesis of NAFLD and the associated molecular pathways is not fully understood. This study employed an integrated strategy that combines transcriptomic analysis with both in vivo and in vitro validation, utilizing a high-fat diet (HFD)-induced rat model to elucidate the efficacy and molecular mechanisms of CK in ameliorating NAFLD.

Shaping the microvascular network: insights into skeletal muscle angiogenesis.

Open Biol

Thomas Gustafsson, Emmanuel Nwadozi, Andrea Tryfonos +1 more

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a complex and tightly regulated biological process that plays a fundamental role in both physiological and pathological tissue remodeling by facilitating the delivery of oxygen and nutrients. Over recent decades, extensive research has identified a wide array of factors that regulate the balance between endothelial cell quiescence and activation. This review discusses the cellular events and molecular mechanisms that regulate angiogenesis within skeletal muscle, considering dynamic interactions with the extracellular matrix and highlighting the critical involvement of multiple resident and infiltrating cell types-including myofibres, satellite cells, fibro-adipogenic progenitors, immune cells and pericytes. The current understanding of these regulatory networks is examined in both healthy muscle tissue as part of the phenotype changes that occur during exercise and in pathological conditions that affect skeletal muscle angiogenesis. Particular attention is given to introduce data of emerging high-resolution techniques, especially omics-based approaches such as single-cell RNA sequencing (scRNA-seq) of skeletal muscle tissue. These methodologies hold significant promise for elucidating cell-type-specific roles and intercellular interactions that drive angiogenic processes in both physiological and disease contexts. Despite substantial progress, the precise mechanisms governing angiogenesis in skeletal muscle remain only partially understood.

Human cathelicidin peptide LL-37 compacts nucleic acids and alters neutrophil extracellular trap structure.

Sci Rep

Claudia Zielke, Behzad Rad, Josefine E Nielsen +7 more

The human cathelicidin host defense peptide LL-37 is expressed by many cell types, including neutrophils, macrophages, and epithelial cells, and forms complexes with nucleic acids that can have either beneficial or detrimental health effects. We suggest that these differential impacts are directly connected to the extent of nucleic acid binding by LL-37. Here, we use phage λ DNA and techniques such as high-resolution video microscopy, gel electrophoresis, circular dichroism, and displacement assays to show that LL-37 binds non-specifically to dsDNA, condensing it, followed by formation of progressively larger complexes from smaller domains, until "complete" complexation is attained at a (w/w) ratio of DNA/LL-37 of 1:1.7. The morphology of these complexes is concentration-dependent, with relatively low LL-37 amounts yielding loosely aggregated DNA structures and higher LL-37 concentrations leading to well-defined, disc-like complexes of about 150 nm in diameter. The condensation of nucleic acids, which causes a loss of the characteristic B-DNA features, results from interactions of the phosphodiester backbone with cationic amino acid side chains of the peptide at physiological pH, most likely in A-T rich sequences of the nucleic acid. Our results show that the α-helical structure of the peptide with its amphipathic and hydrophobic surfaces is essential. Finally, we show that LL-37 complexation alters the structure of neutrophil extracellular traps (NETs), causing a significant reduction in projected NET area at high LL-37 concentrations. Our data suggest that LL-37 helps prevent nucleic acid dispersal and condenses dsDNA, which may impact the biophysics of NET clearance.

Cost-effectiveness and budget-impact analysis of tirzepatide in heart failure with preserved ejection fraction and obesity in the German health-care system.

Int J Cardiol

Bent Estler, Hanna Fröhlich, Tobias Täger +3 more

Heart failure with preserved ejection fraction is common, obesity-related, and associated with high symptom burden and healthcare use. Tirzepatide, a dual GIP/GLP-1 receptor agonist, improved symptoms and outcomes in SUMMIT, but its acquisition cost raises concerns about value and affordability.

GLP-1 receptor agonists and surgical care: implications for bariatric Procedures, perioperative Outcomes, and nutritional optimization.

Diabetes Res Clin Pract

Zeyad Elawa, Ahmed Khalil, Ahmed Kardousha +2 more

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for obesity and type 2 diabetes and are now frequently encountered in patients undergoing bariatric and other elective surgeries. Their effects on gastric motility, appetite, and nutrient intake have important implications for perioperative safety, surgical outcomes, and nutritional care.