Profiling the serum protein corona of fibrillar human islet amyloid polypeptide

Amyloids may be regarded as native nanomaterials that form in the presence of complex protein mixtures. By drawing an analogy with the physicochemical properties of nanoparticles in biological fluids, we hypothesized that amyloids should form a protein corona in vivo that would imbue the underlying amyloid with a modified biological identity. To explore this hypothesis we characterized the protein corona of human islet amyloid polypeptide (IAPP) fibrils in FBS using two complementary methodologies developed herein; quartz crystal microbalance and ‘centrifugal capture’, coupled with nano-liquid chromatography tandem mass spectroscopy. Clear evidence for a significant protein corona was obtained. No trends were identified for amyloid corona proteins based on their physicochemical properties, while strong binding with IAPP fibrils occurred for linear proteins or multi-domain proteins with structural plasticity. Proteomic analysis identified amyloid-enriched proteins that are known to play significant roles in mediating cellular machinery and processing, potentially leading to pathological outcomes and therapeutic targets

Emergent topological ordered phase for the Ising-XY Model revealed by cluster-updating Monte-Carlo method

The two-component cold atom systems with anisotropic hopping amplitudes can be phenomenologically described by a two-dimensional Ising-XY coupled model with spatial anisotropy. At low temperatures, theoretical predictions [Phys. Rev. A 72, 053604 (2005)] and [arXiv:0706.1609] indicate the existence of a topological ordered phase characterized by Ising and XY disorder but with 2XY ordering. However, due to ergodic difficulties faced by Monte Carlo methods at low temperatures, this topological phase has not been numerically explored. We propose a linear cluster updating Monte Carlo method, which flips spins without rejection in the anisotropy limit but does not change the energy. Using this scheme and conventional Monte Carlo methods, we succeed in revealing the nature of topological phases with half-vortices and domain walls. In the constructed global phase diagram, Ising and XY type transitions are very close to each other and differ significantly from the schematic phase diagram reported earlier. We also propose and explore a wide range of quantities, including magnetism, superfluidity, specific heat, susceptibility, and even percolation susceptibility, and obtain consistent results. Furthermore, we observe first-order transitions characterized by common intersection points in magnetizations for different system sizes, as opposed to the conventional phase transition where Binder cumulants of various sizes share common intersections. The results are useful to help cold atom experiments explore the half-vortex topological phase.Comment: 14 pages, 14 figures. Accepted by Chinese Physics

Efficacy and safety of transcutaneous electrical acupoint stimulation for the management of primary dysmenorrhoea: Protocol for a randomised controlled trial in China

INTRODUCTION: Primary dysmenorrhoea (PD) is a common menstrual concern with significant physical and psychosocial impacts. The effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) in alleviating PD symptoms remain uncertain due to insufficient evidence. This single-centre, parallel, randomised controlled study intends to evaluate the efficacy and safety of TEAS for PD management. METHODS AND ANALYSIS: 60 participants aged 18-40 years diagnosed with moderate to severe PD will be recruited from Tai\u27an Hospital of Traditional Chinese Medicine (TCM) and randomly assigned to either a TEAS group or a TEAS-sham group (1:1). The TEAS group will undergo 12 sessions of TEAS treatment over two menstrual cycles, with 30 min per session, three sessions weekly. Participants in the TEAS-sham group will receive TEAS stimulation using identical devices and protocols but without current output. The primary outcome is the Visual Analogue Scale (VAS) for pain assessment. Secondary outcomes are Short-Form McGill Pain Questionnaire, total effective rate, uterine artery haemodynamics, prostaglandin and β-endorphin level, mental well-being and quality of life. Adverse events and their potential reasons and the use of analgesics will also be recorded. ETHICS AND DISSEMINATION: This study was approved by the Medical Ethics Committee of Tai\u27an Hospital of TCM. Written informed consent will be obtained from each participant. The results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300071686

Herder Mental Stocking Rate in the Rangeland Regions of Northern China

In 2002, the Chinese government issued the “balancing animals and grass” policy to control the degradation problem of northern China, but these programs have been widely resisted by herders. We proposed that herder had their mental stocking rate, which refers to the number of animals that the herders think they can place or maintain on a piece of rangeland over a specified period of time. It is the mental stocking rate that guides herder on how to adjust livestock-breeding practices. This study surveyed herder opinion of grass-animal balance in the meadow steppe, typical steppe and desert steppe regions of northern China. Most herders admitted that they bred more livestock than ten years ago, whereas they insisted that there was no overstocking in their rangelands and more than half even thought that their rangelands could still carry more livestock when the policy was implemented. Most herders hold that they took into account the carrying capacity of rangelands when making decisions about stock-breeding practices. Herders from three regions nominated the following mental stocking rates; 0.75-1.50, 0.60-1.50, and 0.50-0.75 sheep/ha, insisting these rates were necessary and reasonable

Clinical and genetic features of CNGA3 achromatopsia in preschool children: novel insights into retinal architecture and therapeutic window for clinical trials

PurposeAchromatopsia (ACHM) is a rare genetic disorder with an infantile onset that affects cone photoreceptors. This study aims to provide a comprehensive phenotyping of the retinal structure and identify novel genetic variants in a preschool cohort with ACHM in China.MethodsWe recruited patients with pathogenic genes (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6) known to cause ACHM, all of whom had an age of symptom onset before 6 years of age. Whole exome sequencing, Sanger sequencing, and comprehensive ocular examinations, including optical coherence tomography (OCT), were conducted. Furthermore, retinal outer layer damage was evaluated using a novel modified classification system.ResultsNystagmus (46.13%) and photophobia (46.13%) were the most common initial complaints/reports from parents of our patients. These symptoms are easily noticed early (mean age 0.88 ± 1.07 years at onset of initial symptom). OCT revealed a wide range of degeneration in the outer retina of the fovea, exactly in the interdigitation zone (IZ) and ellipsoid zone (EZ). Retinal outer layer damage was observed in 18 eyes (9 patients), with the modified classification distribution: grade 1 in 1 eye (5.6%), grade 2 in 9 eyes (50.0%), and grade 3 in 8 eyes (44.4%). Eleven novel variants of CNAG3 were identified. The higher grade of outer retinal layer damage was shown in patients with genetic variants, potentially leading to structural changes in the cyclic guanosine monophosphate (cGMP) binding site of the synthesized protein (p = 0.046).ConclusionACHM can manifest at very early stages of life. Mild damage to the outer layers of the retina is a typical change in early-stage ACHM. Patients with genetic variants potentially leading to structural changes in the cGMP binding site of the synthesized protein tend to exhibit more severe retinal phenotypes. Ultimately, our research may aid in formulating guidelines for selecting patients and determining the optimal timing for interventions in upcoming gene replacement therapies

Immunopharmacology of gastric cancer–deciphering immune cell subset responses and nanoparticle-mediated targeting

The diverse landscape of immune cell populations significantly influences therapeutic outcomes in advanced gastric cancer, a leading cause of cancer mortality worldwide. Progress in immunopharmacology, aided by single-cell analytics, increasingly highlights immune complexity and functional heterogeneity. Conventional categories contain diverse subsets, including various T cells (helper, regulatory, memory) and B cells (plasma, memory, regulatory). Innate immune cells like macrophages, natural killer cells, and dendritic cells also exist in various functional states. These subsets exhibit distinct pharmacological response profiles that are often obscured by bulk analyses. This review explores the differential responses of critical immune cell subsets within the gastric cancer tumor microenvironment to current therapeutic modalities, encompassing cytotoxic chemotherapy, molecular targeted agents, and immunotherapies such as checkpoint inhibitors. We delve into the molecular processes underlying subset-specific drug effects, potential mechanisms of therapeutic resistance linked to specific immune cell states, and the influence of the tumor microenvironment on immune subset pharmacology. Furthermore, we discuss the application and potential of nanoparticle-based drug delivery systems specifically engineered to target distinct immune cell subpopulations, aiming to enhance immunomodulatory efficacy, reshape subset repertoires favorably, overcome resistance, and minimize toxicity for more precise and effective treatment of advanced gastric cancer

Exceptional nexus in Bose-Einstein condensates with collective dissipation

In multistate non-Hermitian systems, higher-order exceptional points and exotic phenomena with no analogues in two-level systems arise. A paradigm is the exceptional nexus (EX), a third-order EP as the cusp singularity of exceptional arcs (EAs), that has a hybrid topological nature. Using atomic Bose-Einstein condensates to implement a dissipative three-state system, we experimentally realize an EX within a two-parameter space, despite the absence of symmetry. The engineered dissipation exhibits density dependence due to the collective atomic response to resonant light. Based on extensive analysis of the system's decay dynamics, we demonstrate the formation of an EX from the coalescence of two EAs with distinct geometries. These structures arise from the different roles played by dissipation in the strong coupling limit and quantum Zeno regime. Our work paves the way for exploring higher-order exceptional physics in the many-body setting of ultracold atoms.Comment: accepted by PR

Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity

Aggregation of islet amyloid polypeptide (IAPP), a peptide hormone co-synthesized and co-stored with insulin in pancreatic cells and also co-secreted to the circulation, is associated with beta-cell death in type-2 diabetes (T2D). In T2D patients IAPP is found aggregating in the extracellular space of the islets of Langerhans. Although the physiological environments of these intra- and extra-cellular compartments and vascular systems significantly differ, the presence of proteins is ubiquitous but the effects of protein binding on IAPP aggregation are largely unknown. Here we examined the binding of freshly-dissolved IAPP as well as pre-formed fibrils with two homologous proteins, namely cationic lysozyme (Lys) and anionic alpha-lactalbumin (aLac), both of which can be found in the circulation. Biophysical characterizations and a cell viability assay revealed distinct effects of Lys and aLac on IAPP amyloid aggregation, fibril remodelling and cytotoxicity, pointing to the role of protein “corona” in conferring the biological impact of amyloidogenic peptides. Systematic molecular dynamics simulations further provided molecular and structural details for the observed differential effects of proteins on IAPP amyloidosis. This study facilitates our understanding of the fate and transformation of IAPP in vivo, which are expected to have consequential bearings on IAPP glycemic control and T2D pathology