Self-Assembling Peptides Alter Cell Death Pathway for Pyroptosis-Enhanced Immune Activation.

Pyroptosis, a pro-inflammatory form of programmed cell death, represents a promising strategy for cancer immunotherapy by eliciting robust antitumor immunity. Herein, we developed Lonidamine-WEWTWY (), a self-assembling peptide-drug conjugate that reprograms the cell death mechanism of Lonidamine from apoptosis to pyroptosis. The conjugate spontaneously forms stable nanofibers that selectively disrupt cancer cell membranes, triggering pyroptosis through membrane damage, reactive oxygen species (ROS) generation, and gasdermin E (GSDME) activation.

Spatially constrained disulfide bond shuffling delays insulin aggregation and enhances neurotoxicity.

Disulfide bond shuffling (DBS) critically influences protein aggregation and stability, yet its spatial constraints and biological implications remain poorly understood. Here, we demonstrate that insulin undergoes DBS within an extended spatial range up to ~19 Å, generating heterogeneous crosslinked oligomers that alter aggregation pathway. While DBS products initially delay aggregation by inhibiting primary nucleation and elongation steps, they ultimately promote the formation of distinct fibrillar structures with enhanced β-sheet content.

The sheet-to-helix transition is a potential gas-phase unfolding pathway for a multidomain protein CRM.

Despite the expansive applications of gas-phase unfolding techniques, the molecular mechanism for the solvent-free forced unfolding pathway which substrate multidomain proteins usually adopt remains elusive at the secondary structure level. Herein, upon carefully selecting CRM as a therapeutically-relevant model system containing multiple secondary structure-separated domains, we systematically examine its solvent-free unfolding pathway. Further-more, utilizing the hybrid of noncovalent chemical probing with niacinamide and ion mobility-mass spectrometry-guided all-atom molecular dynamics simulations, we map a nearly complete unfolding atlas for the conjugate vaccine carrier protein CRM in a domain- and secondary structure-resolved manner.

Toxic Effects of Acute Water Selenium Exposure on : Survival, Physiological Responses, Transcriptome, and Intestinal Microbiota.

Excess selenium (Se) can cause a variety of toxic effects in aquatic animals. However, there is currently a lack of comprehensive studies about the toxicity effects of Se in culture water on shrimp. Based on the 96 h acute toxicity test, which confirmed the 96 h LC of Se (NaSeO) for as 2.

C-Terminal Radical Oxidation Inhibits α-Synuclein Aggregation and Cytotoxicity via an Oxidative Oligomer-Disrupting Pathway.

α-Synuclein (α-Syn) aggregation is a hallmark of Parkinson's disease and other neurodegenerative disorders. This study investigates the impact of controlled radical oxidation on α-Syn aggregation and associated cytotoxicity. Using a microscale low-temperature plasma device for submillisecond radical oxidation, combined with native ion mobility-mass spectrometry and liquid chromatography-tandem mass spectrometry, we demonstrate radical-directed preferential oxidation of the α-Syn C-terminal region.

Making Cells as a "Nirvana Phoenix": Precise Coupling of Precursors Prior to ROS Bursts for Intracellular Synthesis of Quantum Dots.

Rationally coupling natural biochemical reactions for live-cell synthesis of inorganic nanocrystals with fluorescence, such as quantum dots (QDs) especially near-infrared (NIR), holds significant potential for labeling and bioimaging. However, the introduced exogenous reactants and intracellularly produced species, e.g.

Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator.

Double-stranded RNA (dsRNA) binding proteins (dsRBPs) play crucial roles in various cellular processes, especially in the innate immune response. Comprehensive characterization of dsRBPs is essential to understand the intricate mechanisms for dsRNA sensing and response. Traditional methods have predominantly relied on affinity purification, favoring the isolation of strong dsRNA binders.

Inherently anti-metastatic peptide hydrogels for sonodynamic-amplified ferroptosis in cancer therapy.

Cancer metastasis remains a significant challenge in oncology, prompting the exploration of innovative biomaterials to enhance treatment efficacy. While many hydrogels only serve as passive carriers, this study presents two novel self-assembling peptides, and , which form supramolecular hydrogels with intrinsic anti-metastatic properties. We demonstrate a correlation between the nanofibrous morphology of these peptides and their enhanced anti-metastatic activity, mediated by disruption of F-actin organization and impacting pathways related to cancer cell adhesion and actin filament dynamics.

High-Coverage Stereoproteome Mapping Uncovers Pervasive Protein Stereoisomerization Associated with Neurodegeneration.

Protein asymmetry, while crucial for life, can arise from subtle stereoisomerization. However, a comprehensive understanding of the breadth and specificity of the whole stereoproteome (STEP) has been hindered by insufficient stereoisomeric resolution. Here, we introduce an untargeted, STEP discovery protocol for comprehensive STEP profiling and relative quantification.

Investigating the effect of acute toxicity exposure to combined FeSO and FeCl in Litopenaeus vannamei through analysis of survival, metal accumulation, oxidative stress, and intestinal flora.

Marine shrimp have been studied as bioindicators in environmental monitoring of heavy metal pollution. High levels of heavy metal iron (Fe) are potentially toxic and readily accumulate in organisms, causing damage. Up to now, there are few studies about the toxicity of Fe in the water on shrimp.

Sialylation Shields Glycoproteins from Oxidative Stress: Mechanistic Insights into Sialic Acid Oxidation and Structural Stability.

Sialylation, a crucial yet labile protein modification, is increasingly recognized for its role in modulating protein structure, function, and stability. While the impact of oxidative stress on protein integrity is well-established, the protective role of sialylation against such damage remains poorly understood. This study employs a microscale low-temperature plasma device to generate a controlled, deep radical oxidation environment mimicking cellular oxidative stress.

Intrinsic PD-L1 Degradation Induced by a Novel Self-Assembling Hexapeptide for Enhanced Cancer Immunotherapy.

Programmed death-ligand 1 (PD-L1) is a critical immune checkpoint protein that facilitates tumor immune evasion. While antibody-based PD-1/PD-L1 inhibitors have shown promise, their limitations necessitate the development of alternative therapeutic strategies. This work addresses these challenges by developing a hexapeptide, KFM (Lys-Phe-Met-Phe-Met-Lys), capable of both directly downregulating PD-L1 and self-assembling into a ROS-responsive supramolecular hydrogel.

Effects of short-form video app addiction on academic anxiety and academic engagement: The mediating role of mindfulness.

Introduction: The impact of short-form video app addiction on academic performance, including academic anxiety and engagement, has not been adequately explored or addressed.

Method: This study tested the effects of short-form video app addiction on academic anxiety and academic engagement and the mediating role of mindfulness in these relationships. The participants were 1,879 undergraduates in China who completed the Short-Form Video App Addiction Scale, Mindful Attention Awareness Scale, Academic Anxiety Sub-questionnaire of Academic Emotions Questionnaire, and Engagement Scales.

Sialylation-induced stabilization of dynamic glycoprotein conformations unveiled by time-aligned parallel unfolding and glycan release mass spectrometry.

Sialylation, a critical post-translational modification, regulates glycoprotein structure and function by tuning their molecular heterogeneity. However, characterizing its subtle and dynamic conformational effects at the intact glycoprotein level remains challenging. We introduce a glycoform-resolved unfolding approach based on a high-throughput ion mobility-mass spectrometry (IM-MS) platform.

Peptide-IR820 Conjugate: A Promising Strategy for Efficient Vascular Disruption and Hypoxia Induction in Melanoma.

Photothermal therapy (PTT) has emerged as a noninvasive and precise cancer treatment modality known for its high selectivity and lack of drug resistance. However, the clinical translation of many PTT agents is hindered by the limited biodegradability of inorganic nanoparticles and the instability of organic dyes. In this study, a peptide conjugate, IR820-Cys-Trp-Glu-Trp-Thr-Trp-Tyr (), was designed to self-assemble into nanoparticles for both potent PTT and vascular disruption in melanoma treatment.

Assembly of Glycopeptides in Living Cells Resembling Viral Infection for Cargo Delivery.

Self-assembly in living cells represents one versatile strategy for drug delivery; however, it suffers from the limited precision and efficiency. Inspired by viral traits, we here report a cascade targeting-hydrolysis-transformation (THT) assembly of glycosylated peptides in living cells holistically resembling viral infection for efficient cargo delivery and combined tumor therapy. We design a glycosylated peptide via incorporating a β-galactose-serine residue into bola-amphiphilic sequences.

Investigating the Impact of Varied Dietary Protein Levels on : An Exploration of the Intestinal Microbiota and Transcriptome Responses.

This study explored the effects of dietary protein levels on with its intestinal microbiota and transcriptome responses. Previous studies on the effects of dietary protein levels on have focused on growth performance, antioxidant indices, and digestive enzyme activity, but few studies have been conducted at the microbiological and molecular levels. In this study, five isolipid experimental diets with protein levels of 32% (P32), 36% (P36), 40% (P40), 44% (P44), and 48% (P48) were used in an (0.

Plasma-Droplet Fusion-Mass Spectrometry Reveals Sub-Millisecond Protein Unfolding Dynamics Induced by Reactive Oxygen Species.

Investigating the connection between reactive oxygen species (ROS) and oxidative protein unfolding is critical to reveal the mechanisms underlying disease involving elevated ROS and protein misfolding. This could inform the development of therapeutics targeting cells based on their redox status. In this study, we developed a plasma-droplet fusion-mass spectrometry platform to rapidly assess protein resilience to ROS.

Artificial Peptide-Protein Necrosomes Promote Cell Death.

The presence of disordered region or large interacting surface within proteins significantly challenges the development of targeted drugs, commonly known as the "undruggable" issue. Here, we report a heterogeneous peptide-protein assembling strategy to selectively phosphorylate proteins, thereby activating the necroptotic signaling pathway and promoting cell necroptosis. Inspired by the structures of natural necrosomes formed by receptor interacting protein kinases (RIPK) 1 and 3, the kinase-biomimetic peptides are rationally designed by incorporating natural or -amino acids, or connecting -amino acids in a retro-inverso (DRI) manner, leading to one RIPK3-biomimetic peptide PR3 and three RIPK1-biomimetic peptides.

Isolation and Reactivity of Homoleptic Diphosphene Lead Complexes.

Due to their limited capacity for π-backdonation, isolation of π-complexes of main-group elements remains a great challenge. We report herein the synthesis of a homoleptic diphosphene lead complex (2) from the degradation of P with a bis(germylene)-stabilized Pb(0) complex. Structural and computational studies showed that 2 possesses significant π bonding interactions between Pb atom and diphosphene ligands, which is reminiscent of transition-metal diphosphene complexes.

Enhanced Stability Differentiation of Therapeutic Polyclonal Antibodies with All Ion Unfolding-Ion Mobility-Mass Spectrometry.

Compared with monoclonal antibodies, polyclonal antibodies (pAbs) have rather significant characteristics, including lower cost, shorter production cycle, and higher affinity. Therefore, to facilitate their applications in clinic, it is equally critical to comprehensively characterize the conformational stabilities of pAb at the molecular weight-resolved scale, which is technically challenging due to the lack of an effective analytical tool capable of simultaneously providing both stability and molecular weight information within an acceptable error range. Ion mobility-mass spectrometry (IM-MS) has grown as an alternative to rapidly assess protein conformational stability with accurate molecular weight information maintained, especially when equipped with a collision-induced unfolding (CIU) regime.

Expedited Evaluation of Conformational Stability-Heterogeneity Associations for Crude Polyclonal Antibodies in Response to Conjugate Vaccines.

Conjugate vaccines have been demonstrated to be a promising strategy for immunotherapeutic intervention in substance use disorder, wherein a hapten structurally similar to the target drug is conjugated to an immunogenic carrier protein. The antibodies generated following immunization with these species can provide long-lasting protection against overdose through sequestration of the abused drug in the periphery, which mitigates its ability to cross the blood-brain barrier. However, these antibodies exhibit a high degree of heterogeneity in structure.

Site-specific chirality-conferred structural compaction differentially mediates the cytotoxicity of Aβ42.

Growing evidence supports the confident association between distinct amyloid beta (Aβ) isoforms and Alzheimer's Disease (AD) pathogenesis. As such, critical investigations seeking to uncover the translational factors contributing to Aβ toxicity represent a venture of significant value. Herein, we comprehensively assess full-length Aβ42 stereochemistry, with a specific focus on models that consider naturally-occurring isomerization of Asp and Ser residues.