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The Venus flytrap is a carnivorous plant that catches insects by snapping rapidly and reopening slowly. To understand the mechanism underlying this asymmetrically reversible motion, a three-dimensional laser profiler was used to measure both static morphological information and dynamic movements (500 frames per second) of the Venus flytrap, including its rapid closure and slow re-opening. The mean-curvature differences between the open and closed lobes were recorded and used for morphology and energy evaluations. The effects of geometric parameters such as the length, width, height, and thickness of the lobes on the closing time were analyzed, and the all-or-none motion of the Venus flytrap was examined. Moreover, a mathematical asymmetric-bifurcation buckling model was developed. The Venus flytrap has asymmetric energy states for the closing and opening conditions; therefore, storage of a larger amount of energy makes the re-opening motion slower. These pre-programmed movements of plants can facilitate the development of more intelligent soft robots.

Leveraging the motion and force of individual molecular motors in a controlled manner to perform macroscopic tasks can provide substantial benefits to many applications, including robotics. Nonetheless, although millimetre-scale movement has been demonstrated with synthetic and biological molecular motors, their efficient integration into engineered systems that perform macroscopic tasks remains challenging. Here, we describe an active network capable of macroscopic actuation that is hierarchically assembled from an engineered kinesin, a biomolecular motor, and microtubules, resembling the contractile units in muscles. These contracting materials can be formed in desired areas using patterned ultraviolet illumination, allowing their incorporation into mechanically engineered systems, being also compatible with printing technologies. Due to the designed filamentous assembly of kinesins, the generated forces reach the micronewton range, enabling actuation of millimetre-scale mechanical components. These properties may be useful for the fabrication of soft robotic systems with advanced functionalities. Patterned contracting networks composed of biomolecular motors and filaments achieve millimetre-scale actuation of mechanical structures with light-triggered molecular stimuli.

Eupatorium lindleyanum , a medicinal plant from the Asteraceae family, is renowned for its diverse bioactive compounds, particularly flavonoids, which contribute to its various pharmacological activities. However, the biosynthetic pathway and regulatory mechanisms underlying flavonoid production in Eupatorium lindleyanum remain largely unexplored. In this study, an integrated metabolomic and transcriptomic approach was employed to investigate flavonoid biosynthesis in Eupatorium lindleyanum . Samples from four different tissues (roots, stems, leaves, and flowers) were analysed to identify variations in differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs). A total of 330 differentially accumulated flavonoid metabolites (DFMs) and 53,610 DEGs were identified. A total of 27 key structural genes involved in the flavonoid synthesis pathway, including PAL , 4CL , C3H , F3H , FLS , and ANS , and others were found to be significantly activated in specific tissues. Additionally, 69 transcription factors (TFs) from five families, including AP2/ERF , NAC , WRKY , MYB , and bHLH , were identified as potentially involved in regulating flavonoid biosynthesis. The findings of this study offer crucial information on the genes and metabolites involved in flavonoid metabolism in Eupatorium lindleyanum. The identification of key genes and TFs, along with an understanding of their regulatory networks, can facilitate the development of new cultivars with increased flavonoid contents and improved medicinal value.

Abstract Vascular cognitive impairment (VCI) encompasses a wide spectrum of cognitive disorders, ranging from mild cognitive impairment to vascular dementia. Its diagnosis relies on thorough clinical evaluations and neuroimaging. VCI predominately arises from vascular risk factors (VRFs) and cerebrovascular disease, either independently or in conjunction with neurodegeneration. Growing evidence underscores the prevalence of VRFs, highlighting their potential for early prediction of cognitive impairment and dementia in later life. The precise mechanisms linking vascular pathologies to cognitive deficits remain elusive. Chronic cerebrovascular pathology is the most common neuropathological feature of VCI, often interacting synergistically with neurodegenerative processes. Current research efforts are focused on developing and validating reliable biomarkers to unravel the etiology of vascular brain changes in VCI. The collaborative integration of these biomarkers into clinical practice, alongside routine incorporation into neuropathological assessments, presents a promising strategy for predicting and stratifying VCI. The cornerstone of VCI prevention remains the control of VRFs, which includes multi-domain lifestyle modifications. Identifying appropriate pharmacological approaches is also of paramount importance. In this review, we synthesize recent advancements in the field of VCI, including its definition, determinants of vascular risk, pathophysiology, neuroimaging and fluid-correlated biomarkers, predictive methodologies, and current intervention strategies. Increasingly evident is the notion that more rigorous research for VCI, which arises from a complex interplay of physiological events, is still needed to pave the way for better clinical outcomes and enhanced quality of life for affected individuals.

Aging variance has been evaluated using biological age, yet the multiple organ systems aging clocks of cognitive decline warrants further study. Using brain imaging and physiological phenotypes from the Taizhou Imaging Study and Shanghai Aging Study (N = 1448), we examined composite phenotypic aging and subsequently established aging clocks for brain and four body systems. The study included 1,448 participants from the community, ranging in age from 55 to 92 years. All subjects underwent cognitive assessments at at least three time points. The subjects were divided into three groups according to the cognitive trajectory: low-decline, high-decline, high-stable. Some measures of kidney function, such as creatinine and homocysteine, were significantly associated with cognitive decline. Composite phenotypes such as renal and metabolic altered with cognitive function and could serve as cognitive aging clock features. Our research uncovers new insights into heterogeneous phenotypic and organ aging, promoting the development of comprehensive and tailored strategies to manage cognitive aging.

Background Aging variance has been evaluated using biological age, yet the multiple organ systems aging clocks of cognitive decline warrants further study. Method Using brain imaging and physiological phenotypes from the Taizhou Imaging Study and Shanghai Aging Study (N = 1448), we examined composite phenotypic aging and subsequently established aging clocks for brain and four body systems. Result The study included 1,448 participants from the community, ranging in age from 55 to 92 years. All subjects underwent cognitive assessments at at least three time points. The subjects were divided into three groups according to the cognitive trajectory: low‐decline, high‐decline, high‐stable. Some measures of kidney function, such as creatinine and homocysteine, were significantly associated with cognitive decline. Composite phenotypes such as renal and metabolic altered with cognitive function and could serve as cognitive aging clock features. Conclusion Our research uncovers new insights into heterogeneous phenotypic and organ aging, promoting the development of comprehensive and tailored strategies to manage cognitive aging.

The enormous and thin alveolar epithelium is an attractive site for systemic protein delivery. Considering the excellent biocompatibility of phospholipids with endogenous pulmonary surfactant, we engineered dimyristoylphosphatidylcholine (DMPC)-based liposomes for pulmonary administration, using Cy5.5-labeled bovine serum albumin (BSA-Cy5.5) as a model protein payload. The level of cholesterol (Chol) and surface modification with PEG in inhalable liposomes were optimized iteratively based on the encapsulation efficiency, the release kinetics in the simulated lung fluid, and the uptake in murine RAW 264.7 macrophages. The plasma pharmacokinetics of BSA-Cy5.5-encapsulated liposomes with the composition of DMPC/Chol/PEG at 85:10:5 (molar ratio) was studied in mice following intratracheal aerosolization, in comparison with that of free BSA-Cy5.5 solution. The biodisposition of BSA-Cy5.5 was continuously monitored using whole-body near-infrared (NIR) fluorescence imaging for 10 days. We found that the systemic bioavailability of BSA-Cy5.5 from inhaled liposomes was 22%, which was notably higher than that of inhaled free BSA-Cy5.5. The mean residence time of BSA-Cy5.5 was markedly prolonged in mice administered intratracheally with liposomal BSA-Cy5.5, which is in agreement with the NIR imaging results. Our work demonstrates the great promise of inhalable DMPC-based liposomes to achieve non-invasive systemic protein delivery.

Survival in high-risk pediatric neuroblastoma has remained around 50% for the last 20 years, with immunotherapies and targeted therapies having had minimal impact. Here, we identify the small molecule CX-5461 as selectively cytotoxic to high-risk neuroblastoma and synergistic with low picomolar concentrations of topoisomerase I inhibitors in improving survival in vivo in orthotopic patient-derived xenograft neuroblastoma mouse models. CX-5461 recently progressed through phase I clinical trial as a first-in-human inhibitor of RNA-POL I. However, we also use a comprehensive panel of in vitro and in vivo assays to demonstrate that CX-5461 has been mischaracterized and that its primary target at pharmacologically relevant concentrations, is in fact topoisomerase II beta ( TOP2B ), not RNA-POL I. This is important because existing clinically approved chemotherapeutics have well-documented off-target interactions with TOP2B, which have previously been shown to cause both therapy-induced leukemia and cardiotoxicity—often-fatal adverse events, which can emerge several years after treatment. Thus, while we show that combination therapies involving CX-5461 have promising anti-tumor activity in vivo in neuroblastoma, our identification of TOP2B as the primary target of CX-5461 indicates unexpected safety concerns that should be examined in ongoing phase II clinical trials in adult patients before pursuing clinical studies in children. CX-5461 recently progressed through phase I clinical trial as a first-inhuman inhibitor of RNA-POL I. Here, the authors demonstrate that CX-5461 synergizes with topoisomerase I inhibitors to inhibit neuroblastoma cells and that its primary target in this disease is topoisomerase II beta and not RNA-POL I.

Alfalfa ( Medicago sativa L.), a prominent perennial forage in the legume family, is widely cultivated across Europe and America. Given its substantial economic value for livestock, breeding efforts have focused on developing high-yield and high-quality varieties since the discovery of CMS lines. However, progress is restricted by the limitations of existing CMS lines, necessitating the development of new lines and study of the molecular mechanisms underlying pollen abortion. This study investigates early-stage anther development in cytoplasmic male sterile (CMS) alfalfa lines (MSJN1A) in relation to the isotypic maintainer line (MSJN1B). Histological analyses revealed abnormal degradation of tapetal cells post-meiosis in the CMS line. Notably, during the early mononuclear stage, the central vacuoles in the microspores were absent, leading to evident pollen abortion. These findings suggest that pollen abortion in the CMS line is associated with the delayed disintegration of the tapetum and structural anomalies in microspore vacuoles. Non-targeted metabolome sequencing revealed 401 and 405 metabolites at late tetrad and early mononuclear stages of alfalfa, respectively. Among these, 39 metabolites were consistently upregulated, whereas 85 metabolites were downregulated. Differential analysis revealed 45 and 37 unique metabolites at each respective stage. These metabolites were primarily featured in pathways related to energy, phenylpropane, sucrose and starch, and fatty acid metabolism. Integrated analysis demonstrated that differentially expressed genes and differential metabolites were co-enriched in these pathways. Additionally, quantitative real-time PCR and physiological index analysis confirmed downregulation of key genes involved in anther development, illustrating that changes in upstream gene regulation could significantly impact downstream metabolite levels, ultimately influencing pollen fertility. Pollen abortion is related to abnormal phenylpropane metabolism, fatty acid metabolism and starch and sucrose pathway, which provides reference for further research on the causes of pollen abortion of alfalfa.

Necroptosis is a programmed form of cell death. Receptor-interacting serine/threonine protein kinase l (RIPK1) is a crucial protein kinase that regulates the necroptosis pathway. Increased expression of death receptor family ligands such as tumor necrosis factor (TNF) increases the susceptibility of cells to apoptosis and necroptosis. RIPK1, RIPK3, and mixed-lineage kinase-like domain (MLKL) proteins mediate necrosis. RIPK1-mediated necroptosis further promotes cell death and inflammation in the pathogenesis of liver injury, skin diseases, and neurodegenerative diseases. The N-terminal kinase domain of RIPK1 is significant in the induction of cell death and can be used as a vital drug target for inhibitors. In this paper, we outline the pathways of necroptosis and the role RIPK1 plays in them and suggest that targeting RIPK1 in therapy may help to inhibit multiple cell death pathways.