Dipeptidyl peptidase-IV (DPP-4) enzyme inhibitors are a promising category of diabetes medications. Bioactive peptides, particularly those derived from bovine milk proteins, play crucial roles in inhibiting the DPP-4 enzyme. This study describes a comprehensive strategy for DPP-4 inhibitory peptide discovery and validation that combines machine learning and virtual proteolysis techniques. Five machine learning models, including GBDT, XGBoost, LightGBM, CatBoost, and RF, were trained. Notably, LightGBM demonstrated superior performance with an AUC value of 0.92 ± 0.01. Subsequently, LightGBM was employed to forecast the DPP-4 inhibitory potential of peptides generated through virtual proteolysis of milk proteins. Through a series of in silico screening process and in vitro experiments, GPVRGPF and HPHPHL were found to exhibit good DPP-4 inhibitory activity. Molecular docking and molecular dynamics simulations further confirmed the inhibitory mechanisms of these peptides. Through retracing the virtual proteolysis steps, it was found that GPVRGPF can be obtained from β-casein through enzymatic hydrolysis by chymotrypsin, while HPHPHL can be obtained from κ-casein through enzymatic hydrolysis by stem bromelain or papain. In summary, the integration of machine learning and virtual proteolysis techniques can aid in the preliminary determination of key hydrolysis parameters and facilitate the efficient screening of bioactive peptides.

Vehicle skin is the key component in maintaining the aerodynamic shape of the vehicle. A deformable high-speed vehicle needs to adjust its shape in real time to realize optimum aerodynamic efficiency and to withstand extreme heat flow induced by high-speed flight, which requires the skin to possess large strain and high-temperature resistance. Traditional vehicle skin cannot satisfy both of the requirements. Biomimetic flexible skin for deformable high-speed vehicles (DHSV-bio-FS) combines flexible material fabrication with transpiration cooling technology, which can simulate human skin sweat cooling, and has the characteristics of large strain and high-temperature resistance. The thermal protection performance of the prepared prototype of DHSV-bio-FS was evaluated by simulation and wind tunnel experiments at 40% tensile strain with liquid water as coolant. Simulation results suggest that the surface temperature of the DHSV-bio-FS at 40% tensile strain is consistent with the temperature of the coolant (350 K) in a 3,000 K high-temperature gas environment. In addition, the prepared prototype DHSV-bio-FS survived for 1,200 s in a high-temperature gas environment of 200 kW/m² in wind tunnel experiments. This paper verifies the reliability of DHSV-bio-FS in a high-temperature gas environment and can be deployed in applications of flexible skin for deformable high-speed vehicles (DHSV-FS).

The tricarboxylic acid (TCA) cycle is capable of providing sufficient energy for the physiological activities under aerobic conditions. Although tumor metabolic reprogramming places aerobic glycolysis in a dominant position, the TCA cycle remains indispensable for tumor cells as a hub for the metabolic linkage and interconversion of glucose, lipids, and certain amino acids. TCA intermediates such as citrate, α-ketoglutarate, succinate, and fumarate are altered in tumors, and they regulate the tumor metabolism, signal transduction, and immune environment to affect tumorigenesis and tumor progression. This article provides a comprehensive review of the modifications occurring in tumor cells in relation to the intermediates of the TCA cycle, which affects tumor pathogenesis and current therapeutic strategy for therapy through targeting TCA cycle in cancer cells.

Messenger RNA (mRNA) has emerged as an innovative therapeutic modality, offering promising avenues for the prevention and treatment of a variety of diseases. The tremendous success of mRNA vaccines in effectively combatting coronavirus disease 2019 (COVID-19) evidences the unlimited medical and therapeutic potential of mRNA technology. Overcoming challenges related to mRNA stability, immunogenicity, and precision targeting has been made possible by recent advancements in lipid nanoparticles (LNPs). This review summarizes state-of-the-art LNP-mRNA-based therapeutics, including their structure, material compositions, design guidelines, and screening principles. Additionally, we highlight current preclinical and clinical trends in LNP-mRNA therapeutics in a broad range of treatments in ophthalmological conditions, cancer immunotherapy, gene editing, and rare-disease medicine. Particular attention is given to the translation and evolution of LNP-mRNA vaccines into a broader spectrum of therapeutics. We explore concerns in the aspects of inadequate extrahepatic targeting efficacy, elevated doses, safety concerns, and challenges of large-scale production procedures. This discussion may offer insights and perspectives on near- and long-term clinical development prospects for LNP-mRNA therapeutics.

Recent years have witnessed numerous technical breakthroughs in connected and autonomous vehicles (CAVs). On the one hand, these breakthroughs have significantly advanced the development of intelligent transportation systems (ITSs); on the other hand, these new traffic participants introduce more complex and uncertain elements to ITSs from the social space. Digital twins (DTs) provide real-time, data-driven, precise modeling for constructing the digital mapping of physical-world ITSs. Meanwhile, the metaverse integrates emerging technologies such as virtual reality/mixed reality, artificial intelligence, and DTs to model and explore how to realize improved sustainability, increased efficiency, and enhanced safety. More recently, as a leading effort toward general artificial intelligence, the concept of foundation model was proposed and has achieved significant success, showing great potential to lay the cornerstone for diverse artificial intelligence applications across different domains. In this article, we explore the big models embodied foundation intelligence for parallel driving in cyber-physical-social spaces, which integrate metaverse and DTs to construct a parallel training space for CAVs, and present a comprehensive elucidation of the crucial characteristics and operational mechanisms. Beyond providing the infrastructure and foundation intelligence of big models for parallel driving, this article also discusses future trends and potential research directions, and the “6S” goals of parallel driving.

Due to the breaking of time-reversal and parity symmetries and the presence of non-conservative microscopic interactions, active spinner fluids and solids respectively exhibit nondissipative odd viscosity and nonstorage odd elasticity, engendering phenomena unattainable in traditional passive or active systems. Here, we study the effects of odd viscosity and elasticity on phase behaviors of active spinner systems. We find the spinner fluid under a simple shear experiences an anisotropic gas–liquid phase separation driven by the odd-viscosity stress. This phase separation exhibits equilibrium-like behavior, with both binodal-like and spinodal curves and critical point. However, the formed dense liquid phase is unstable, since the odd elasticity instantly takes over the odd viscosity to condense the liquid into a solid-like phase. The unusual phase behavior essentially arises from the competition between thermal fluctuations and the odd response-induced effective attraction. Our results demonstrate that the cooperation of odd viscosity and elasticity can lead to exotic phase behavior, revealing their fundamental roles in phase transition.

Poly (adenosine 5′-diphosphate-ribose) polymerase inhibitors (PARPi) are increasingly important in the treatment of ovarian cancer. However, more than 40% of BRCA1/2-deficient patients do not respond to PARPi, and BRCA wild-type cases do not show obvious benefit. In this study, we demonstrated that progesterone acted synergistically with niraparib in ovarian cancer cells by enhancing niraparib-mediated DNA damage and death regardless of BRCA status. This synergy was validated in an ovarian cancer organoid model and in vivo experiments. Furthermore, we found that progesterone enhances the activity of niraparib in ovarian cancer through inducing ferroptosis by up-regulating palmitoleic acid and causing mitochondrial damage. In clinical cohort, it was observed that progesterone prolonged the survival of patients with ovarian cancer receiving PARPi as second-line maintenance therapy, and high progesterone receptor expression combined with low glutathione peroxidase 4 (GPX4) expression predicted better efficacy of PARPi in patients with ovarian cancer. These findings not only offer new therapeutic strategies for PARPi poor response ovarian cancer but also provide potential molecular markers for predicting the PARPi efficacy.

The flexible and conformal interconnects for electronic systems as a potential signal transmission device have great prospects in body-worn or wearable applications. High-efficiency wave propagation and conformal structure deformation around human body at radio communication are still confronted with huge challenges due to the lack of methods to control the wave propagation and achieve the deformable structure simultaneously. Here, inspired by the kirigami technology, a new paradigm to construct spoof plasmonic interconnects (SPIs) that support radiofrequency (RF) surface plasmonic transmission is proposed, together with high elasticity, strong robustness, and multifunction performance. Leveraging the strong field-confinement characteristic of spoof surface plasmons polaritons, the Type-I SPI opens its high-efficiency transmission band after stretching from a simply connected metallic surface. Meanwhile, the broadband transmission of the kirigami-based SPI exhibits strong robustness and excellent stability undergoing complex deformations, i.e., bending, twisting, and stretching. In addition, the prepared Type-II SPI consisting of 2 different subunit cells can achieve band-stop transmission characteristics, with its center frequency dynamically tunable by stretching the buckled structure. Experimental measurements verify the on-off switching performance in kirigami interconnects triggered by stretching. Overcoming the mechanical limitation of rigid structure with kirigami technology, the designer SPIs exhibit high stretchability through out-of-plane structure deformation. Such kirigami-based interconnects can improve the elastic functionality of wearable RF electronics and offer high compatibility to large body motion in future body network systems.

Gout, a common form of arthritis, is characterized by the deposition of monosodium urate (MSU) crystals in joints. MSU deposition in synovial tissues would initiate arthritis flares and recurrence, causing irreversible joint damage. However, the dynamic deposition of MSU crystals in tissues lacks experimental observation. In this study, we used chemical-specific, label-free stimulated Raman scattering (SRS) microscopy to investigate the spatiotemporal deposition and morphological characteristics of MSU crystals in human synovial organoids. Our findings revealed a critical 12-h window for MSU deposition in the lining layer of gouty synovium. Moreover, distinctive inflammatory reactions of the lining and sublining synovial layers in gout using SRS microscopy were further verified by immunofluorescence. Importantly, we identified a crucial proinflammatory role of sublining fibroblast-like synoviocytes, indicating a need for targeted medication treatment on these cells. Our work contributes to the fundamental understanding of MSU-based diseases and offers valuable insights for the future development of targeted gout therapies.