Scorpions, a group of oldest animals with wide distribution in the world, have a long history of medicinal use. Scorpio, the dried body of Buthus martensii, is a rare animal medicine mainly used for the treatment of liver diseases, spasm, and convulsions in children in China. The venom has been considered as the active substance of scorpions. However, little is known about the small molecules in the venom of scorpions. According to the articles published in recent years, scorpions contain amino acids, fatty acids, steroids, and alkaloids, which endow scorpions with antimicrobial, anticoagulant, metabolism-regulating, and antitumor activities. This paper summarizes the small molecule chemical components and pharmacological activities of scorpions, with a view to providing valuable information for the discovery of new active molecules and the clinical use of scorpions.

Antimicrobial peptides (AMPs) are a new type of antibiotic and target a variety of microbes, including antibiotic-resistant strains; thus, AMPs have attracted widespread interest. Scorpion venoms contain many bioactive peptides, including AMPs, and have become an important natural resource of peptide-based drugs. Here, the antibacterial peptide gene Hp1470 from the venom of the scorpion Heterometrus petersii was characterized, and its antibacterial activity was determined. The cDNA sequence of Hp1470 is 300 nt in length and contains an open reading frame (ORF) of 207 nt. The ORF was shown to encode 68 amino acid residues, including a signal peptide (23 aa), a mature peptide (13 aa), a C-terminal posttranslational processing signal (3 aa), and a propeptide (29 aa). Multiple sequence alignment results indicated that Hp1470 is an antibacterial peptide. The mature peptide Hp1470, which has a molecular mass of 1564.09 Da, was further chemically synthesized with a purity of greater than 95%. Antimicrobial assays showed that the synthesized Hp1470 exerted an inhibitory effect on Gram-positive bacteria and clinical drug-resistant strains, including PRSA and MRSA, but not Gram-negative bacteria. Hp1470 was further found to protect mice from MRSA infection, suggesting its potential application as an in vivo antimicrobial agent. Interestingly, Hp1470 only inhibited bacterial growth but did not kill bacteria, which was consistent with scanning electron microscopy results showing that Hp1470 did not lyse the cell membrane of Staphylococcus aureus. Our work provides a new direction for developing antibacterial agents with different modes of action from natural scorpion venoms.

BACKGROUND: Inflammation plays pivotal role in the development of chronic diseases. Reducing chronic inflammation is an important strategy for preventing and managing many chronic diseases. In traditional Chinese medicine, the processed Buthus martensii Karsch (BmK) scorpion (also called \"Quanxie\") has been used to treat chronic inflammatory arthritis and spondylitis for hundreds of years suggests that \"Quanxie\" could potentially be utilized as a resource for identifying new anti-inflammatory compounds. However, the molecular basis and the underline mechanism for the anti-inflammatory effect of processed BmK scorpion are still unclear.
OBJECTIVE: The study aims to determine the potential involvement of macrophage-expressed Kv1.3 in the anti-inflammatory effect of processed BmK scorpion venom, as well as to identify new Kv1.3 blockers derived from processed BmK scorpion.
METHODS: In this study, the in vivo and in vitro anti-inflammatory activities were determined using carrageenan-induced paw edema, LPS-induced sepsis mouse models and LPS-induced macrophage activation model respectively. The effect of processed BmK scorpion water extract, processed BmK venom and BmKK2 on different potassium channels were detected by whole-cell voltage-clamp recordings on transfected HEK293 cells or mouse BMDMs. The cytokines were detected using Q-PCR and competitive enzyme-linked immunosorbent assay. High performance liquid chromatography, SDS-PAGE and peptide Mass Spectrometry analysis were used to isolate and identify the BmKK2. SiRNA, western blotting and flow cytometry were used to analysis the anti-inflammatory mechanism of BmKK2.
RESULTS: Here we demonstrate that BmKK2, a thermostable toxin targeting Kv1.3 is the critical anti-inflammatory component in the processed BmK scorpion. BmKK2 inhibits inflammation by targeting and inhibiting the activity of macrophage Kv1.3, thereby inhibiting the activation of NF-κB-NLRP3 pathway and the subsequent release of inflammatory factors.
CONCLUSIONS: These findings provide new insights into the molecular basis of the anti-inflammatory effects of \"Quanxie\" and highlight the importance of targeting Kv1.3 expressed on macrophages as an anti-inflammatory approach.

Smp24, a cationic antimicrobial peptide identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus, shows variable cytotoxicity on various tumor (KG1a, CCRF-CEM and HepG2) and non-tumor (CD34+, HRECs, HACAT) cell lines. However, the effects of Smp24 and its mode of action on lung cancer cell lines remain unknown. Herein, the effect of Smp24 on the viability, membrane disruption, cytoskeleton, migration and invasion, and MMP-2/-9 and TIMP-1/-2 expression of human lung cancer cells have been evaluated. In addition, its in vivo antitumor role and acute toxicity were also assessed. In our study, Smp24 was found to suppress the growth of A549, H3122, PC-9, and H460 with IC50 values from about 4.06 to 7.07 µM and show low toxicity to normal cells (MRC-5) with 14.68 µM of IC50. Furthermore, Smp24 could induce necrosis of A549 cells via destroying the integrity of the cell membrane and mitochondrial and nuclear membranes. Additionally, Smp24 suppressed cell motility by damaging the cytoskeleton and altering MMP-2/-9 and TIMP-1/-2 expression. Finally, Smp24 showed effective anticancer protection in a A549 xenograft mice model and low acute toxicity. Overall, these findings indicate that Smp24 significantly exerts an antitumor effect due to its induction of membrane defects and cytoskeleton disruption. Accordingly, our findings will open an avenue for developing scorpion venom peptides into chemotherapeutic agents targeting lung cancer cells.

Scorpion fluorescence under ultraviolet light is a well-known phenomenon, and its change is also a known biological feature during the scorpion moulting process. However, the synthesis and transport of fluorescent substances during the moulting stage remain unclear. In this study, in-depth investigations on the global fluorescence changes from the exoskeleton, fluorescence layer, coelomic fluid, and abdomen to the digestive glands indicated that the digestive glands, which occupy most of the space in the abdomen of the scorpion mesosoma segment, were responsible for synthesizing the fluorescent substances. More importantly, these fluorescent substances were produced in advance, before the moulting process, which contributed to the recovery of the fluorescent exoskeleton as early as possible. The synthesized fluorescent substances first entered the coelomic fluid, then successively passed through the inherent epithelial cell layer and two new formed endocuticle and exocuticle layers, and ultimately reached and became enriched in the new formed fluorescent layer, which was protected by the new epicuticle layer. These four new layers were the first to illustrate the structural features of the fluorescent exoskeleton. Due to the very soft body and the inability of the newly moulted scorpion to resist attacks from the predator, this special synthesis and transport strategy of the fluorescent substances could guarantee the rapid formation of the integrated fluorescent exoskeleton during the 24 h after ecdysis, which would be a novel biological feature during the scorpion evolution.

Slit sensillum, a unique sensing organ on the scorpion\'s legs, is composed of several cracks with curved shapes. In fact, it is just its particular morphological distribution and structure that endows the scorpions with ultrasensitive sensing capacity. Here, a scorpion-inspired flexible strain sensor with an ordered concentric circular curved crack array (CCA) was designed and fabricated by using an optimized solvent-induced and template transfer combined method. The morphology of the cracks can be effectively controlled by the heating temperature and the lasting time. Instead of the nonuniform stress distribution induced by disordered cracks, ordered concentric circle curved structures are introduced to generate a uniform stress distribution and larger deformation, which can significantly improve the performance of the strain sensor. Thus, the CCA sensor exhibits ultrahigh sensitivity (GF ∼ 7878.6), excellent stability (over 16 000 cycles), and fast response time (110 ms). Furthermore, the CCA sensor was demonstrated to be feasible for monitoring human motions and detecting noncontact vibration signals, indicating its great potential in human-health monitoring and vibration signal detection applications.

Asthma is one of the most common chronic inflammatory diseases. Although the scorpion and centipede (SC) significantly ameliorates asthma and changes exosomal miRNAs, the molecular mechanism is still obscure. Here, we show that SC improves inflammation in asthmatic mice and increases M2 macrophage-derived exosomes (M2Φ-Exos) by promoting M2 macrophage polarization. The M2Φ-Exos remarkably inhibits airway epithelial cell pyroptosis by reducing the expression of NLRP3, caspase-1, and LI-1β and mitochondrial swelling. Furthermore, miR-30b-5p is up-regulated in M2Φ-Exos compared with M1Φ-Exos. Overexpression of miR-30b-5p in M2Φ-Exos prevents airway epithelial cell pyroptosis, while down-regulation of miR-30b-5p promotes pyroptosis. We also uncover that pyroptosis is increased in asthmatic mice, while SC blocks pyroptosis. Moreover, miR-30b-5p overexpressed M2Φ-Exos further enhances the ameliorative effect of SC, which significantly down-regulates IRF7 expression. Our results collectively reveal that M2Φ-Exos induced by SC could carry miR-30b-5p to mitigate severe asthma by inhibiting airway epithelial cell pyroptosis. Most importantly, our findings may provide a potential clinical application of M2Φ-Exos for treating severe asthma.

Arthropods maintain ecosystem balance while also contributing to the spread of disease. Plant-derived natural repellents represent an ecological method of pest control, but their direct molecular targets in arthropods remain to be further elucidated. Occupying a critical phylogenetic niche in arthropod evolution, scorpions retain an ancestral genetic profile. Here, using a behavior-guided screening of the Mesobuthus martensii genome, we identified a scorpion transient receptor potential (sTRP1) channel that senses Cymbopogon-derived natural repellents, while remaining insensitive to the synthetic chemical pesticide DEET. Scrutinizing orthologs of sTRP1 in Drosophila melanogaster, we further demonstrated dTRPγ ion channel as a chemosensory receptor of natural repellents to mediate avoidance behavior. This study sheds light on arthropod molecular targets of natural repellents, exemplifying the arthropod–plant adaptation. It should also help the rational design of insect control strategy and in conserving biodiversity.

Antimicrobial peptides are widely acknowledged as an alternative class of antimicrobial agents. In this study, a lysine-rich scorpion peptide derivative Pacavin-5K was designed, which showed an improved antibacterial spectrum, significantly higher antibacterial activity, and lower toxicity compared to the native peptide. It also showed an improved thermal and serum stability. Notably, Pacavin-5K significantly decreased the bacterial counts in the wounded region in the mouse cutaneous infection model caused by Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, Pacavin-5K did not induce bacterial resistance associated with its antibacterial mechanism disrupting the membrane. Furthermore, Pacavin-5K could kill the S. aureus cells at the biofilm state. Overall, Pacavin-5K could be a potential alternative antibacterial agent against skin infection caused by S. aureus and P. aeruginosa.

Flexible strain sensors have an irreplaceable role in critical and emerging fields, such as electronic skins, flexible robots, and prosthetics. Although numerous efforts have been made to improve sensor sensitivity to meet specific application scenarios, the signal-to-noise ratio (SNR) is an extremely critical and non-negligible indicator, which takes into account higher sensitivity, meaning that they can also detect the noise signals with high sensitivity. Coincidentally, scorpions with ultrasensitive vibration sensilla also face such a dilemma. Here, it is found that the scorpion ingeniously uses the viscoelastic material in front of its slit sensilla to realize efficient preprocessing of the signal. Its mechanism is that the loss factor of materials changes with frequency, affecting energy storage and transmission. Inspired by this ingenious strategy, a bioinspired strain sensor insensitive to a low strain rate was designed using a two-step template transfer method. As a result, its relative change in resistance reached 110% under the same strain (0.3197%) but with different strain rates (0.1 Hz and ∼20 Hz). The noncontact vibration experiments also show different responses to low-frequency vibration and high-frequency impact. Moreover, it can also be used as a typical flexible strain sensor. Under the tensile state, it has a gauge factor (GF) as high as 4596 upon 0.6% strain, and the response time is 140 ms. Therefore, it is expected that this strain sensor will be used in many important ultraprecision measurement fields, especially when the measured signal is small.