The human seasonal coronavirus HKU1-CoV, which causes common colds worldwide, relies on the sequential binding to surface glycans and transmembrane serine protease 2 (TMPRSS2) for entry into target cells. TMPRSS2 is synthesized as a zymogen that undergoes autolytic activation to process its substrates. Several respiratory viruses, in particular coronaviruses, use TMPRSS2 for proteolytic priming of their surface spike protein to drive membrane fusion upon receptor binding. We describe the crystal structure of the HKU1-CoV receptor binding domain in complex with TMPRSS2, showing that it recognizes residues lining the catalytic groove. Combined mutagenesis of interface residues and comparison across species highlight positions 417 and 469 as determinants of HKU1-CoV host tropism. The structure of a receptor-blocking nanobody in complex with zymogen or activated TMPRSS2 further provides the structural basis of TMPRSS2 activating conformational change, which alters loops recognized by HKU1-CoV and dramatically increases binding affinity.

In cells, signal transduction heavily relies on the intricate regulation of protein kinases, which provide the fundamental framework for modulating most signaling pathways. Dysregulation of kinase activity has been implicated in numerous pathological conditions, particularly in cancer. The druggable nature of most kinases positions them into a focal point during the process of drug development. However, a significant challenge persists, as the role and biological function of nearly one third of human kinases remains largely unknown.Within this diverse landscape, cyclin-dependent kinases (CDKs) emerge as an intriguing molecular subgroup. In human, this kinase family encompasses 21 members, involved in several key biological processes. Remarkably, 13 of these CDKs belong to the category of understudied kinases, and only 5 having undergone broad investigation to date. This knowledge gap underscores the pressing need to delve into the study of these kinases, starting with a comprehensive review of the less-explored ones.Here, we will focus on the PCTAIRE subfamily of CDKs, which includes CDK16, CDK17, and CDK18, arguably among the most understudied CDKs members. To contextualize PCTAIREs within the spectrum of human pathophysiology, we conducted an exhaustive review of the existing literature and examined available databases. This approach resulted in an articulate depiction of these PCTAIREs, encompassing their expression patterns, 3D configurations, mechanisms of activation, and potential functions in normal tissues and in cancer.We propose that this effort offers the possibility of identifying promising areas of future research that extend from basic research to potential clinical and therapeutic applications.

Chronic wound healing is a major challenge in clinical practice. Secondary dressing damage and antibiotic resistance are the main obstacles for traditional wound dressings. Resina draconis (RD), a natural resin traditionally used in powder form for wound care, is now considered unsuitable due to the lack of gas permeability and moist environment required for wound healing. Here, RD is incorporated in situ by constructing a 3D coiled fibrous scaffold with polycaprolactone/polyethylene oxide. Due to the high porosity of 3D scaffold, the RD-3D dressings have a favorable swelling capacity, providing permeability and moisture for wound repair. Meanwhile, the transformation of RD powder into 3D dressings fully demonstrates capabilities of RD in rapid hemostasis, bactericidal, and inflammation-regulating activities. In vivo evaluations using pressure ulcer and infected wound models confirm the high efficacy of RD-3D dressing in early wound healing, particularly beneficial in the infected wound model compared to recombinant bovine FGF-basic. Further biological analysis shows that resveratrol, loureirin A, and loureirin B, as potentially bioactive components of RD, individually contribute to different aspects of wound healing. Collectively, RD-3D integrated dressings represent a simple, cost-effective, and safe approach to wound healing, providing an alternative therapy for translating medical dressings from bench to bedside.

The FtsEX membrane complex constitutes an essential component of the ABC transporter superfamily, widely distributed among bacterial species. It governs peptidoglycan degradation for cell division, acting as a signal transmitter rather than a substrate transporter. Through the ATPase activity of FtsE, it facilitates signal transmission from the cytosol across the membrane to the periplasm, activating associated peptidoglycan hydrolases. This review concentrates on the latest structural advancements elucidating the architecture of the FtsEX complex and its interplay with lytic enzymes or regulatory counterparts. The revealed three-dimensional structures unveil a landscape wherein a precise array of intermolecular interactions, preserved across diverse bacterial species, afford meticulous spatial and temporal control over the cell division process.

Polycyclic aromatic compounds (PAHs) are persistent organic pollutants of environmental concern due to their potential impacts on food chain, with plants being particularly vulnerable. While plants can uptake, transport, and transform PAHs, the precise mechanisms underlying their localization and degradation are not fully understood. Here, a cultivation experiment conducted with Panicum miliaceum exposed different concentrations of phenanthrene (PHE). Intermediate PHE degradation compounds were identified via GC-MS analysis, leading to the proposal of a phytodegradation pathway featuring three significant benzene ring cleavage steps. Our results showed that P. miliaceum exhibited the ability to effectively degrade high levels of PHE, resulting in the production of various intermediate products through several chemical changes. Examination of the localization and anatomical characteristics revealed structural alterations linked to PHE stress, with an observed enhancement in PHE accumulation density in both roots and shoots as treatment levels increased. Following a 2-week aging period, a decrease in the amount of PHE accumulation was observed, along with a change in its localization. Bioinformatics analysis of the P. miliaceum 2-oxoglutarate-dependent dioxygenase (2-ODD) DAO-like protein revealed a 299 amino acid structure with two highly conserved domains, namely 2OG-FeII_Oxy and DIOX_N. Molecular docking analysis aligned with experimental results, strongly affirming the potential link and direct action of 2-ODD DAO-like protein with PHE. Our study highlights P. miliaceum capacity for PAHs degradation and elucidates the mechanisms behind enhanced degradation efficiency. By integrating experimental evidence with bioinformatics analysis, we offer valuable insights into the potential applications of plant-based remediation strategies for PAHs-contaminated environments.

The emerging wearable plant sensors demonstrate the capability of in-situ measurement of physiological and micro-environmental information of plants. However, the stretchability and breathability of current wearable plant sensors are restricted mainly due to their 2D planar structures, which interfere with plant growth and development. Here, origami-inspired 3D wearable sensors have been developed for plant growth and microclimate monitoring. Unlike 2D counterparts, the 3D sensors demonstrate theoretically infinitely high stretchability and breathability derived from the structure rather than the material. They are adjusted to 100% and 111.55 mg cm-2·h-1 in the optimized design. In addition to stretchability and breathability, the structural parameters are also used to control the strain distribution of the 3D sensors to enhance sensitivity and minimize interference. After integrating with corresponding sensing materials, electrodes, data acquisition and transmission circuits, and a mobile App, a miniaturized sensing system is produced with the capability of in-situ and online monitoring of plant elongation and microclimate. As a demonstration, the 3D sensors are worn on pumpkin leaves, which can accurately monitor the leaf elongation and microclimate with negligible hindrance to plant growth. Finally, the effects of the microclimate on the plant growth is resolved by analyzing the monitored data. This study would significantly promote the development of wearable plant sensors and their applications in the fields of plant phenomics, plant-environment interface, and smart agriculture.

The MUC2 mucin protects the colonic epithelium by a two-layered mucus with an inner attached bacteria-free layer and an outer layer harboring commensal bacteria. CysD domains are 100 amino-acid-long sequences containing 10 cysteines that separate highly O-glycosylated proline, threonine, serine (PTS) regions in mucins. The structure of the second CysD, CysD2, of MUC2 is now solved by nuclear magnetic resonance. CysD2 shows a stable stalk region predicted to be partly covered by adjacent O-glycans attached to neighboring PTS sequences, whereas the CysD2 tip with three flexible loops is suggested to be well exposed. It shows transient dimer interactions at acidic pH, weakened at physiological pH. This transient interaction can be stabilized in vitro and in vivo by transglutaminase 3-catalyzed isopeptide bonds, preferring a specific glutamine residue on one flexible loop. This covalent dimer is modeled suggesting that CysD domains act as connecting hubs for covalent stabilization of mucins to form a protective mucus.

Recent development of high-throughput biotechnologies, such as Hi-C, have enabled genome-wide measurement of chromosomal conformation. The interaction signals among genomic loci are contaminated with noises. It remains largely unknown how well the underlying chromosomal conformation can be elucidated, based on massive and noisy measurements. We propose a new model-based distance embedding (MDE) framework, to reveal spatial organizations of chromosomes. The proposed framework is a general methodology, which allows us to link accurate probabilistic models, which characterize biological data properties, to efficiently recovering Euclidean distance matrices from noisy observations. The performance of MDE is shown through numerical experiments inspired by regular helix structure and random movement of chromosomes. The practical merits of MDE are also demonstrated by applications to real Hi-C data from both human and mouse cells which are further validated by gold standard benchmarks.

A recently developed proteolytic reactor, designed for protein structural investigation, was coupled to ion mobility mass spectrometry to monitor collisional cross section (CCS) evolution of model proteins undergoing trypsin-mediated mono enzymatic digestion. As peptides are released during digestion, the CCS of the remaining protein structure may deviate from the classical 2/3 power of the CCS-mass relationship for spherical structures. The classical relationship between CCS and mass (CCS = A × M2/3) for spherical structures, assuming a globular shape in the gas phase, may deviate as stabilizing elements are lost during digestion. In addition, collision-induced unfolding (CIU) experiments on partially digested proteins provided insights into the CCS resilience in the gas phase to ion activation, potentially due to the presence of stabilizing elements. The study initially investigated a model peptide ModBea (3 kDa), assessing the impact of disulfide bridges on CCS resilience in both reduced and oxidized forms. Subsequently, β-lactoglobulin (2 disulfide bridges), calmodulin (Ca2+ coordination cation), and cytochrome c (heme) were selected to investigate the influence of common structuring elements on CCS resilience. CIU experiments probed the unfolding process, evaluating the effect of losing specific peptides on the energy landscapes of partially digested proteins. Comparisons of the TWCCSN2→He to trend curves describing the CCS/mass relationship revealed that proteins with structure-stabilizing elements consistently exhibit TWCCSN2→He and greater resilience toward CIU compared to proteins lacking these elements. The integration of online digestion, ion mobility, and CIU provides a valuable tool for identifying structuring elements in biopolymers in the gas phase.

The treehoppers (Hemiptera, Membracidae) are known for possessing a large three-dimensional structure called a helmet. Although some ecological functions of the helmet have already been elucidated, the developmental mechanisms underlying the complex and diverse morphology of the helmet are still largely unknown. The process of helmet formation was first described in Antianthe expansa, which possesses a simple roof-shaped helmet. However, the developmental process in species with more complex helmet morphologies remains largely unexplored. Hence, in this study, we used Poppea capricornis, which possesses a more complex helmet structure than A. expansa, to investigate the helmet development using paraffin sections, micro-CT, and scanning electronic microscopy. Our focus was on the overall helmet developmental process common to both species and formation of structures unique to Poppea and its comparison to Antianthe. As a result, we discovered that miniature structures were also formed in Poppea, similar to Antianthe, during the helmet formation. Common structures that were shared between the two species were discernible at this stage. Additionally, we observed that suprahumeral horns and posterior horns, two morphological traits specific to the Poppea helmet that are apparently similar anatomically, are formed through two distinctly different developmental mechanisms. The suprahumeral horns appeared to be formed by utilizing the nymphal suprahumeral bud as a mold, while we could not detect any nymphal structures potentially used for a mold in the posterior horns formation. Our findings suggest that the helmet formation mechanisms of Antianthe and Poppea employ a common mechanism but form species-specific structures by multiple mechanisms.