Less confidence, less forgetting: Learning with a humbler teacher in exemplar-free Class-Incremental learning.

Class-Incremental learning (CIL) is challenging due to catastrophic forgetting (CF), which escalates in exemplar-free scenarios. To mitigate CF, Knowledge Distillation (KD), which leverages old models as teacher models, has been widely employed in CIL. However, based on a case study, our investigation reveals that the teacher model exhibits over-confidence in unseen new samples. In this article, we conduct empirical experiments and provide theoretical analysis to investigate the over-confident phenomenon and the impact of KD in exemplar-free CIL, where access to old samples is unavailable. Building on our analysis, we propose a novel approach, Learning with Humbler Teacher, by systematically selecting an appropriate checkpoint model as a humbler teacher to mitigate CF. Furthermore, we explore utilizing the nuclear norm to obtain an appropriate temporal ensemble to enhance model stability. Notably, LwHT outperforms the state-of-the-art approach by a significant margin of 10.41%, 6.56%, and 4.31% in various settings while demonstrating superior model plasticity.

Unveiling Trends: Nanoscale Materials Shaping Emerging Biomedical Applications.

The realm of biomedical materials continues to evolve rapidly, driven by innovative research across interdisciplinary domains. Leveraging big data from the CAS Content Collection, this study employs quantitative analysis through natural language processing (NLP) to identify six emerging areas within nanoscale materials for biomedical applications. These areas encompass self-healing, bioelectronic, programmable, lipid-based, protein-based, and antibacterial materials. Our Nano Focus delves into the multifaceted utilization of nanoscale materials in these domains, spanning from augmenting physical and electronic properties for interfacing with human tissue to facilitating intricate functionalities like programmable drug delivery.

From cells to subcellular organelles: Next-generation cancer therapy based on peptide self-assembly.

Due to the editability, functionality, and excellent biocompatibility of peptides, in situ self-assembly of peptides in cells is a powerful strategy for biomedical applications. Subcellular organelle targeting of peptides assemblies enables more precise drug delivery, enhances selectivity to disease cells, and mitigates drug resistance, providing an effective strategy for disease diagnosis and therapy. This reviewer first introduces the triggering conditions, morphological changes, and intracellular locations of self-assembling peptides. Then, the functions of peptide assemblies are summarized, followed by a comprehensive understanding of the interactions between peptide assemblies and subcellular organelles. Finally, we provide a brief outlook and the remaining challenges in this field.

Lysosomal Peptide Self-Assembly to Control Cell Behavior.

Lysosomes are membrane-enclosed organelles that play key roles in degrading and recycling cellular debris, cellular signaling, and energy metabolism processes. Confinement of amphiphilic peptides in the lysosome to construct functional nanostructures through noncovalent interactions is an emerging approach to tune the homeostasis of lysosome. After briefly introducing the importance of lysosome and its functions, we discuss the advantages of lysosomal nanostructure formation for disease therapy. We next discuss the strategy for triggering the self-assembly of peptides in the lysosome, followed by a concise outlook of the future perspective about this emerging research direction.

A Programmable Peptidic Hydrogel Adjuvant for Personalized Immunotherapy in Resected Stage Tumors.

Adjuvant treatment after surgical resection usually plays an important role in delaying disease recurrence. Immunotherapy displays encouraging results in increasing patients' chances of staying cancer-free after surgery, as reported by recent clinical trials. However, the clinical outcomes of current immunotherapy need to be improved due to the limited responses, patient heterogeneity, nontargeted distribution, and immune-related adverse effects. This work describes a programmable hydrogel adjuvant for personalized immunotherapy after surgical resection. By filling the hydrogel in the cavity, this system aims to address the limited secretion of granzyme B (GrB) during immunotherapy and improve the low immunotherapy responses typically observed, while minimizing immune-related side effects. The TLR7/8 agonist imidazoquinoline (IMDQ) is linked to the self-assembling peptide backbone through a GrB-responsive linkage. Its release could enhance the activation and function of immune cells, which will lead to increased secretion of GrB and enhance the effectiveness of immunotherapy together. The hydrogel adjuvant recruits immune cells, initiates dendritic cell maturation, and induces M1 polarized macrophages to reverse the immunosuppressive tumor microenvironment in situ. In multiple murine tumor models, the hydrogel adjuvant suppresses tumor growth, increases animal survival and long-term immunological memory, and protects mice against tumor rechallenge, leading to effective prophylactic and therapeutic responses. This work provides a potential chemical strategy to overcome the limitations associated with immunotherapy.

Sustainable biosurfactant production from secondary feedstock-recent advances, process optimization and perspectives.

Biosurfactants have garnered increased attention lately due to their superiority of their properties over fossil-derived counterparts. While the cost of production remains a significant hurdle to surpass synthetic surfactants, biosurfactants have been anticipated to gain a larger market share in the coming decades. Among these, glycolipids, a type of low-molecular-weight biosurfactant, stand out for their efficacy in reducing surface and interfacial tension, which made them highly sought-after for various surfactant-related applications. Glycolipids are composed of hydrophilic carbohydrate moieties linked to hydrophobic fatty acid chains through ester bonds that mainly include rhamnolipids, trehalose lipids, sophorolipids, and mannosylerythritol lipids. This review highlights the current landscape of glycolipids and covers specific glycolipid productivity and the diverse range of products found in the global market. Applications such as bioremediation, food processing, petroleum refining, biomedical uses, and increasing agriculture output have been discussed. Additionally, the latest advancements in production cost reduction for glycolipid and the challenges of utilizing second-generation feedstocks for sustainable production are also thoroughly examined. Overall, this review proposes a balance between environmental advantages, economic viability, and societal benefits through the optimized integration of secondary feedstocks in biosurfactant production.

Tuning Phase Transition of Molecular Self-Assembly by Artificial Chaperones through Aromatic-Aromatic Interactions.

The molecular chaperones are essential and play significant roles in controlling the protein phase transition and maintaining physiological homeostasis. However, manipulating phase transformation in biomimetic peptide self-assembly is still challenging. This work shows that an artificial chaperone modulates the energy landscape of supramolecular polymerization, thus controlling the phase transition of amyloid-like assemblies from crystals to hydrogels to solution. The absence of a chaperone allows the NapP to form crystals, while the presence of the chaperone biases the pathway to form nanofibrous hydrogels to soluble oligomers by adjusting the chaperone ratios. Mechanistic studies reveal that the aromatic-aromatic interaction is the key to trapping the molecules in a higher energy fold. Adding the chaperone relieves this restriction, lowers the energy barrier, and transforms the crystal into a hydrogel. This phase transformation can also be achieved in the macromolecular crowding environment, thus providing new insights into understanding molecular self-assembly in multiple component systems.

Controlling Supramolecular Fiber Formation of Nucleopeptide by Guanosine Triphosphate.

Cells use dynamic self-assembly to construct functional structures for maintaining cellular homeostasis. However, using a natural biological small molecule to mimic this phenomenon remains challenging. This work reports the dynamic microfiber formation of nucleopeptide driven by guanosine triphosphate, the small molecule that controls microtubule polymerization in living cells. Deactivation of GTP by enzyme dissociates the fibers, which could be reactivated by adding GTP. Molecular dynamic simulation unveils the mystery of microfiber formation of GBM-1 and GTP. Moreover, the microfiber formation can also be controlled by diffusion-driven GTP gradients across a semipermeable membrane in bulk conditions and the microfluidic method in the defined droplets. This study provides a new platform to construct dynamic self-assembly materials of molecular building blocks driven by GTP.

Deep Learning Empowers the Discovery of Self-Assembling Peptides with Over 10 Trillion Sequences.

Self-assembling of peptides is essential for a variety of biological and medical applications. However, it is challenging to investigate the self-assembling properties of peptides within the complete sequence space due to the enormous sequence quantities. Here, it is demonstrated that a transformer-based deep learning model is effective in predicting the aggregation propensity (AP) of peptide systems, even for decapeptide and mixed-pentapeptide systems with over 10 trillion sequence quantities. Based on the predicted AP values, not only the aggregation laws for designing self-assembling peptides are derived, but the transferability relation among the APs of pentapeptides, decapeptides, and mixed pentapeptides is also revealed, leading to discoveries of self-assembling peptides by concatenating or mixing, as consolidated by experiments. This deep learning approach enables speedy, accurate, and thorough search and design of self-assembling peptides within the complete sequence space of oligopeptides, advancing peptide science by inspiring new biological and medical applications.

Dynamic Control of Cyclic Peptide Assembly to Form Higher-Order Assemblies.

Chirality correction, asymmetry, ring-chain tautomerism and hierarchical assemblies are fundamental phenomena in nature. They are geometrically related and may impact the biological roles of a protein or other supermolecules. It is challenging to study those behaviors within an artificial system due to the complexity of displaying these features. Herein, we design an alternating D,L peptide to recreate and validate the naturally occurring chirality inversion prior to cyclization in water. The resulting asymmetrical cyclic peptide containing a 4-imidazolidinone ring provides an excellent platform to study the ring-chain tautomerism, thermostability and dynamic assembly of the nanostructures. Different from traditional cyclic D,L peptides, the formation of 4-imidazolidinone promotes the formation of intertwined nanostructures. Analysis of the nanostructures confirmed the left-handedness, representing chirality induced self-assembly. This proves that a rationally designed peptide can mimic multiple natural phenomena and could promote the development of functional biomaterials, catalysts, antibiotics, and supermolecules.

Accelerating the prediction and discovery of peptide hydrogels with human-in-the-loop.

The amino acid sequences of peptides determine their self-assembling properties. Accurate prediction of peptidic hydrogel formation, however, remains a challenging task. This work describes an interactive approach involving the mutual information exchange between experiment and machine learning for robust prediction and design of (tetra)peptide hydrogels. We chemically synthesize more than 160 natural tetrapeptides and evaluate their hydrogel-forming ability, and then employ machine learning-experiment iterative loops to improve the accuracy of the gelation prediction. We construct a score function coupling the aggregation propensity, hydrophobicity, and gelation corrector Cg, and generate an 8,000-sequence library, within which the success rate of predicting hydrogel formation reaches 87.1%. Notably, the de novo-designed peptide hydrogel selected from this work boosts the immune response of the receptor binding domain of SARS-CoV-2 in the mice model. Our approach taps into the potential of machine learning for predicting peptide hydrogelator and significantly expands the scope of natural peptide hydrogels.

Optimal preparation of food waste to increase its utility for sophorolipid production by Starmerella bombicola.

Secondary feedstocks, such as food waste (FW), have been used for yeasts (e.g. Starmerella bombicola) to produce sophorolipids (SLs), which are commercially available biosurfactants. However, the quality of FW varies by location and season and may contains chemicals that inhibit SLs production. Therefore, it is crucial to identify such inhibitors and, if possible, remove them, to ensure efficient utilization. In this study, large scale FW was first analysed to determine the concentration of potential inhibitors. Lacticacid, acetic acid and ethanol were identified and found to be inhibitors of the growth of S. bombicola and its SLs production. Various methods were then evaluated for their ability to remove these inhibitors. Finally, a simple and effective strategy for removing inhibitors from FW was developed that complied with the 12 principles of green chemistry and could be adopted by industry for high SLs production.

Recent Progress on Cyclic Peptides' Assembly and Biomedical Applications.

Cyclic peptides are important building blocks for forming functional structures and have been applied in various fields. Considering the significant structural and functional roles of cyclic peptides in materials science and the attributed biophysical advantages, we provide an overview of cyclic peptide types that can self-assemble to form nanotubes, recent progress in stimuli-triggered cyclic peptide assembly, and methods to construct peptide and polymer conjugates based on cyclic peptides with alternative chirality. Specifically, we highlight the roles that stimuli-triggered cyclic peptides and their conjugates play in biomedical applications. Recent progress in other cyclic peptides acting as gelators in drug delivery and biomedicine are also summarized. These cyclic peptides with self-assembly properties are expected to act as adaptive systems for drug delivery and selective disease targeting.

Confinement of Assemblies of Peptides by Chemical Reactions in Living Cells.

The self-assembly of peptides plays an important role in optics, catalysis, medicine, and disease treatment. In recent years, peptide-based materials have exhibited great potential for cancer therapy and disease imaging due to their excellent biocompatibility, structural tenability, and ease of functionality. Peptides could self-assemble into diverse nanostructures in vivo triggered by endogenous stimuli, which initiated chemical reactions and self-assembled to achieve desired biological functions in the tumor microenvironment. This concept introduces the utilization of endogenous triggers to construct functional nanostructures in vivo and their corresponding biological applications. After briefly discussing the representative example of chemical reactions induced self-assembly of peptides in the living system, we describe the several stimuli triggered self-assembly for constructing therapeutic assemblies and serving as an imaging probe. Finally, we give a brief outlook to discuss the future direction of this exciting new field.

Design of biomass-based renewable materials for environmental remediation.

Various materials have been used to remove environmental contaminants for decades and have been an effective strategy for environmental cleanups. The current nonrenewable materials used for this purpose could impose secondary hazards and challenges in further downstream treatments. Biomass-based materials present viable, renewable, and sustainable solutions for environmental remediation. Recent biotechnology advances have developed biomaterials with new capacities, such as highly efficient biodegradation and treatment train integration. This review systemically discusses how biotechnology has empowered biomass-derived and bioinspired materials for environmental remediation sustainably and cost-effectively.

Triggered Self-Sorting of Peptides to Form Higher-Order Assemblies in a Living System.

Biological components (protein, DNA, lipid rafts, etc.) self-sort to form higher-order structures with elegant modulation by endogenous stimuli for maintaining cellular functions in living cells. However, the challenge of producing self-sorted higher-order assemblies of peptides in living systems (cells and tissues) spatiotemporally has yet to be achieved. This work reports the using of a biocompatible strategy to construct self-sorted assemblies of peptides in living cells and tumor-bearing mice. The results show that the designed peptides self-sort to form distinct nanostructures in living cancer cells using an endogenous trigger, as evidenced by confocal laser scanning microscopy and Bio-EM. Wound-healing experiments indicate that the in situ generation of self-sorted nanostructures exhibits a synergistic effect that significantly decreases the migration of cancer cells. In vivo experiments demonstrate that the designed peptides could self-sort in tumor-bearing mice and improve the tumor penetrating ability of the impenetrable component in tumor tissue. We can further program the formation of self-sorted materials through orthogonal triggers by introducing an exogenous trigger (light) and an endogenous trigger independently. Thus, this work provides a strategy to control multiple self-assembling processes in the context of the living system and provides a general strategy to construct self-sorted structures for the emergent properties of materials science.

Controlling Intracellular Enzymatic Self-Assembly of Peptide by Host-Guest Complexation for Programming Cancer Cell Death.

Controlling the enzymatic reaction of macromolecules in living systems plays an essential role in determining the biological functions, which remains challenging in the synthetic system. This work shows that host-guest complexation could be an efficient strategy to tune the enzymatic self-assembly of the peptide. The formed host-guest complexation prevents the enzymatic kinetics of peptide assemblies on the cell surface and promotes cellular uptake of assemblies. For uptake inside cells, the host-guest complex undergoes dissociation in the acidic lysosome, and the released peptide further self-assembles inside the mitochondria. Accumulating assemblies at mitochondria induce the ferroptosis of cancer cells, resulting in cancer cell death in vitro and the tumor-bearing mice model. As the first example of using host-guest complexation to modulate the kinetics of enzymatic self-assembly, this work provides a general method to control enzymatic self-assembly in living cells for selective programming cancer cell death.

Intramitochondrial co-assembly between ATP and nucleopeptides induces cancer cell apoptosis.

Mitochondria are essential intracellular organelles involved in many cellular processes, especially adenosine triphosphate (ATP) production. Since cancer cells require high ATP levels for proliferation, ATP elimination can be a unique target for cancer growth inhibition. We describe a newly developed mitochondria-targeting nucleopeptide (MNP) that sequesters ATP by self-assembling with ATP inside mitochondria. MNP interacts strongly with ATP through electrostatic and hydrogen bonding interactions. MNP exhibits higher binding affinity for ATP (-637.5 kJ mol-1) than for adenosine diphosphate (ADP) (-578.2 kJ mol-1). To improve anticancer efficacy, the small-sized MNP/ADP complex formed large assemblies with ATP inside cancer cell mitochondria. ATP sequestration and formation of large assemblies of the MNP/ADP-ATP complex inside mitochondria caused physical stress by large structures and metabolic disorders in cancer cells, leading to apoptosis. This work illustrates a facile approach to developing cancer therapeutics that relies on molecular assemblies.

Bioconversion of food and lignocellulosic wastes employing sugar platform: A review of enzymatic hydrolysis and kinetics.

Bioenergy and biochemicals can be sustainably produced through fermentation and anaerobic digestion (AD). However, this bioconversion processes could be more economical if the hydrolysis rates of substrates in bioreactors can be accelerated. In this review, the feasibilities of including enzymatic hydrolysis (EH) in various bioconversion systems were studied to facilitate the biological synergy. The reaction kinetics of EH in bioconversion systems comparing pretreated lignocellulosic biomass (LCB) and food waste (FW) substrates were reviewed. Possible strategies to improve the hydrolysis efficiency were explored, including co-cultivation during enzyme production and replacement of pure enzyme with on-site produced fungal mash during EH. Key insights into improvement of current AD and fermentation technologies were summarized and further formed into suggestions of future directions in techno-economic feasibility of biorefinery using mixture of the first-generation food crop feedstock with FW; and/or co-digestion of FW with LCB.

Biomimetic Heterodimerization of Tetrapeptides to Generate Liquid Crystalline Hydrogel in A Two-Component System.

Anisotropic structures made by hierarchical self-assembly and crystallization play an essential role in the living system. However, the spontaneous formation of liquid crystalline hydrogel of low molecular weight organic molecules with controlled properties remains challenging. This work describes a rational design of tetrapeptide without N-terminal modification and chemical conjugation that utilizes intermolecular interactions to drive the formation of nanofiber bundles in a two-component system, which could not be accessed by a single component. The diameter of nanofibers can be simply controlled by varying the enantiomer of electrostatic pairs. Mutation of lysine (K) to arginine (R) results in an over 30-fold increase of mechanical property. Mechanistic studies using different techniques unravel the mechanism of self-assembly and formation of anisotropic liquid crystalline domains. All-atom molecular dynamics simulations reveal that the mixture of heterochiral peptides self-assembles into a nanofiber with a larger width compared to the homochiral assemblies due to the different stacking pattern and intermolecular interactions. The intermolecular interactions show an obvious increase by substituting the K with R, facilitating a more stable assembly and further altering the assembly mechanics and bulk material properties. Moreover, we also demonstrated that the hydrogel properties can be easily controlled by incorporating a light-responsive group. This work provides a method to generate the liquid crystalline hydrogel from isotropic monomers.