Aspartate Isomerization Regulates in Situ Assembly of Peptides into Supramolecular Probes for Detection of Protein Carboxyl Methyltransferase in Bladder Cancer.

Protein carboxyl methyltransferase (PCMT) restores aspartate isomers in proteins and plays a critical role in cancer prognosis. However, in vivo detection of PCMT remains challenging. Here, we report the aspartate isomerization-regulated in situ assembly of peptides into supramolecular probes within living cells for PCMT detection in bladder cancer.

Host-guest binding between cucurbit[8]uril and amphiphilic peptides achieved tunable supramolecular aggregates for cancer diagnosis.

The manipulation of biocompatible supramolecular nanostructures at subcellular and cellular levels has become one of the increasingly significant topics but remains a formidable challenge in chemical and biological science. In this work, a controllable supramolecular aggregate based on host-guest competitive binding is elaborately constructed using cucurbit[8]uril, methionine-containing amphiphilic peptide, and perylene diimide, displaying oxidation-driven macrocycle-confined fluorescence enhancement for cell imaging and morphological reconstruction for cancer cell death. The experimental results demonstrate that cucurbit[8]uril possesses a high binding affinity with the methionine peptide, while this value sharply decreases after the methionine residue is oxidized to sulfoxide or sulfone.

Self-Assembly in Living Cells: Bottom-Up Syntheses in Natural Factory.

In situ self-assembly in living systems is referred to as the processes that regulate assembly by stimuli-responsive reactions at target sites under physiological conditions. Due to the advantages of precisely forming well-defined nanostructures at pathological lesions, in situ-formed assemblies with tailored bioactivity are promising for the development of next-generation biomedical agents. In this Perspective, we summarize the progress of in situ self-assembly of peptides in living cells with an emphasis on the state-of-the-art strategies regulating assembly processes, establishing complexity within assembly systems, and exploiting their applications in biomedicines.

In Vivo Self-Sorting of Peptides via Assembly Evolution.

Despite significant progress achieved in artificial self-sorting in solution, operating self-sorting in the body remains a considerable challenge. Here, we report an in vivo self-sorting peptide system via an in situ assembly evolution for combined cancer therapy. The peptide consists of two disulfide-connected segments, and , capable of independent assembly into twisted or flat nanoribbons.

Development of a Method for Commercial Style Transfer of Historical Architectural Facades Based on Stable Diffusion Models.

In the sphere of urban renewal of historic districts, preserving and innovatively reinterpreting traditional architectural styles remains a primary research focus. However, the modernization and adaptive reuse of traditional buildings often necessitate changes in their functionality. To cater to the demands of tourism in historic districts, many traditional residential buildings require conversion to commercial use, resulting in a mismatch between their external form and their internal function.

[Spatio-temporal Evolution and Prediction of Carbon Storage in Huaibei City Based on InVEST-PLUS Model].

This study aimed to investigate the impact of spatiotemporal changes in land use on ecosystem carbon storage. The study analyzed the spatiotemporal changes in carbon storage in the study area based on land use data from five periods (1985, 1995, 2005, 2015, and 2020) using the InVEST model. The PLUS model was used to predict land use changes in the study area under four different scenarios (natural development, farmland protection, ecological protection, and double protection of farmland and ecology) in 2035, and the ecosystem carbon storage under different scenarios was estimated.

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.

Self-assembly of peptides in living cells for disease theranostics.

The past few decades have witnessed substantial progress in biomedical materials for addressing health concerns and improving disease therapeutic and diagnostic efficacy. Conventional biomedical materials are typically created through an approach and are usually utilized under physiological environments transfer from preparative media. This transfer potentially gives rise to challenges for the efficient preservation of the bioactivity and implementation of theranostic goals on site.

Sulfatase-Induced In Situ Formulation of Antineoplastic Supra-PROTACs.

Proteolysis targeting chimera (PROTAC) technology is an innovative strategy for cancer therapy, which, however, suffers from poor targeting delivery and limited capability for protein of interest (POI) degradation. Here, we report a strategy for the in situ formulation of antineoplastic Supra-PROTACs via intracellular sulfatase-responsive assembly of peptides. Coassembling a sulfated peptide with two ligands binding to ubiquitin VHL and Bcl-xL leads to the formation of a pro-Supra-PROTAC, in which the ratio of the two ligands is rationally optimized based on their protein binding affinity.

Redox-Regulated In Situ Seed-Induced Assembly of Peptides.

Morphology-transformational self-assembly of peptides allows for manipulation of the performance of nanostructures and thereby advancing the development of biomaterials. Acceleration of the morphological transformation process under a biological microenvironment is important to efficiently implement the tailored functions in living systems. Herein, we report redox-regulated in situ seed-induced assembly of peptides via design of two co-assembled bola-amphiphiles serving as a redox-resistant seed and a redox-responsive assembly monomer, respectively.

Organelle-Mediated Dissipative Self-Assembly of Peptides in Living Cells.

Implementing dissipative assembly in living systems is meaningful for creation of living materials or even artificial life. However, intracellular dissipative assembly remains scarce and is significantly impeded by the challenges lying in precisely operating chemical reaction cycles under complex physiological conditions. Here, we develop organelle-mediated dissipative self-assembly of peptides in living cells fueled by GSH, via the design of a mitochondrion-targeting and redox-responsive hexapeptide.

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.

Arginine Methylation Regulates Self-Assembly of Peptides.

Bio-inspired design of peptides represents one facile strategy for development of supramolecular monomers for self-assembly into well-defined nanostructures. Inspired by methylation of arginine during post-translational modification for manipulating protein functions, herein, the controllable self-assembly of peptides via rational incorporation of methylated arginine residues into bola-amphiphilic peptides is reported. A series of bola-amphiphilic peptides are designed and synthesized either containing natural arginine or methylated arginine and investigate the influence of arginine methylation on peptide assembly.

Bio-inspired switchable soft adhesion for the boost of adhesive surfaces and robotics applications: A brief review.

In nature, millions of creatures, such as geckos, tree frogs, octopuses, etc., have evolved fantastic switchable adhesion capabilities to climb swiftly on vertical even inverted surfaces or hunt for prey easily, adapting to harsh and unpredictable environments. Notably, these fascinating adhesive behaviors depend on interfacial forces (friction, van der Waals force, capillary force, vacuum suction, etc.

Persistent Endoplasmic Reticulum Stress Stimulated by Peptide Assemblies for Sensitizing Cancer Chemotherapy.

Pharmacological targeting of endoplasmic reticulum (ER) stress represents one of important methods for disease therapy, which, however, is significantly suppressed by the ER homeostatic processe. Herein, a proof-of-concept strategy is reported for persistent stimulation of ER stress via preventing ER stress adaptation by utilizing multifunctional peptide assemblies. The strategy is established via creation of peptide assemblies with ER-targeting and chaperone glucose-regulated protein 78 (GRP78)-inhibiting functions.

Stimulus-Responsive Amino Acids Behind In Situ Assembled Bioactive Peptide Materials.

In situ self-assembly of peptides into well-defined nanostructures represents one of versatile strategies for creation of bioactive materials within living cells with great potential in disease diagnosis and treatment. The intimate relationship between amino acid sequences and the assembling propensity of peptides has been thoroughly elucidated over the past few decades. This has inspired development of various controllable self-assembling peptide systems based on stimuli-responsive naturally occurring or non-canonical amino acids, including redox-, pH-, photo-, enzyme-responsive amino acids.

Dual-sensitive antibacterial peptide nanoparticles prevent dental caries.

Dental caries is the most prevalent bacterial biofilm-induced disease. Current clinical prevention and treatment agents often suffer from adverse effects on oral microbiota diversity and normal tissues, predominately arising from the poor biofilm-targeting property of the agents. To address this concern, we herein report dual-sensitive antibacterial peptide nanoparticles pHly-1 NPs upon acid and lipid-binding for treatment of dental caries.

Self-Sorting Peptide Assemblies in Living Cells for Simultaneous Organelle Targeting.

Self-sorting is a common phenomenon in eukaryotic cells and represents one of the versatile strategies for the formation of advanced functional materials; however, developing artificial self-sorting assemblies within living cells remains challenging. Here, we report on the GSH-responsive self-sorting peptide assemblies within cancer cells for simultaneous organelle targeting to promote combinatorial organelle dysfunction and thereby cell death. The self-sorting system was created the design of two peptides E3C16E6 and EVM derived from lipid-inspired peptide interdigitating amphiphiles and peptide bola-amphiphiles, respectively.

Cyclodextrin-Activated Porphyrin Photosensitization for Boosting Self-Cleavable Drug Release.

Supramolecular prodrugs that combine the merits of stimuli-responsiveness and targeting ability in a controllable manner have shown appealing prospects in disease diagnostics and therapeutics. Herein, we report that a new theranostic agent with the host-guest-binding-activated photosensitization has been fabricated by a binary supramolecular assembly consisting of the permethyl-β-cyclodextrin-grafted hyaluronic acid and a combretastatin A-4-appended porphyrin derivative. Illuminated by a red-light source, the production efficiency of singlet oxygen (O) pronouncedly increases by ∼60-fold once the porphyrin core is encapsulated by cyclodextrins.

Self-Amplifying Assembly of Peptides in Macrophages for Enhanced Inflammatory Treatment.

Enzyme-regulated in situ self-assembly of peptides represents one versatile strategy in the creation of theranostic agents, which, however, is limited by the strong dependence on enzyme overexpression. Herein, we reported the self-amplifying assembly of peptides precisely in macrophages associated with enzyme expression for improving the anti-inflammatory efficacy of conventional drugs. The self-amplifying assembling system was created via coassembling an enzyme-responsive peptide with its derivative functionalized with a protein ligand.

Adaptable peptide-based therapeutics modulating tumor microenvironment for combinatorial radio-immunotherapy.

Radiotherapy is one of the conventional tumor treatments, while its abscopal therapeutic efficacy is severely hampered by the immunosuppressive tumor microenvironment. To address this challenge, we herein report on the morphology-adaptable peptide-based therapeutics for efficiently reversing the immunosuppression in the combinatorial radio-immunotherapy through simultaneous checkpoint blocking and induction of immunogenic cell death. The peptide-based therapeutics were created via co-assembling a pentapeptide containing a 4-amino proline residue with its derivatives containing IDO-1 inhibitor NLG919.

Precisely Shaped Self-Adjuvanting Peptide Vaccines with Enhanced Immune Responses for HPV-Associated Cancer Therapy.

Peptide vaccines exhibit great potential in cancer therapy via eliciting antigen-specific host immune response and long-term immune memory to defend cancer cells. However, the low induced immune response of many developing vaccines implies the imperatives for understanding the favorable structural features of efficient cancer vaccines. Herein, we report on the two groups of self-adjuvanting peptide vaccines with distinct morphology and investigate the relationship between the morphology of peptide vaccines and the induced immune response.

Transcription factor OsbZIP49 controls tiller angle and plant architecture through the induction of indole-3-acetic acid-amido synthetases in rice.

Tiller angle is an important determinant of plant architecture in rice (Oryza sativa L.). Auxins play a critical role in determining plant architecture; however, the underlying metabolic and signaling mechanisms are still largely unknown.