Improving Classification Performance in Dendritic Neuron Models through Practical Initialization Strategies.

A dendritic neuron model (DNM) is a deep neural network model with a unique dendritic tree structure and activation function. Effective initialization of its model parameters is crucial for its learning performance. This work proposes a novel initialization method specifically designed to improve the performance of DNM in classifying high-dimensional data, notable for its simplicity, speed, and straightforward implementation. Extensive experiments on benchmark datasets show that the proposed method outperforms traditional and recent initialization methods, particularly in datasets consisting of high-dimensional data. In addition, valuable insights into the behavior of DNM during training and the impact of initialization on its learning performance are provided. This research contributes to the understanding of the initialization problem in deep learning and provides insights into the development of more effective initialization methods for other types of neural network models. The proposed initialization method can serve as a reference for future research on initialization techniques in deep learning.

Yellow leaf green tea modulates the AMPK/ACC/SREBP1c signaling pathway and gut microbiota in high-fat diet-induced mice to alleviate obesity.

BACKGROUND: Yellow leaf green tea (YLGT) is a new variety of Camellia sinensis (L.) O. Ktze, which has yellow leaves and the unique qualities of 'three green through three yellow'. The present study aimed to investigate the anti-obesity effect of YLGT in mice fed a high-fat diet (HFD) and to explore the potential mechanisms by regulating the AMPK/ACC/SREBP1c signaling pathways and gut microbiota. RESULTS: The results showed that YLGT aqueous extract reduced body weight, hepatic inflammation, fat accumulation and hyperlipidemia in HFD-induced C57BL/6J mice, and also accelerated energy metabolism, reduced fat synthesis and suppressed obesity by activating the AMPK/CPT-1α signaling pathway and inhibiting the FAS/ACC/SREBP-1c signaling pathway. Fecal microbiota transplantation experiment further confirmed that the alteration of gut microbiota (e.g. increasing unclassified_Muribaculaceae and decreasing Colidextribacter) might be an important cause of YLGT water extract inhibiting obesity. CONCLUSION: In conclusion, YLGT has a broad application prospect in the treatment of obesity and the development of anti-obesity function beverages. © 2024 Society of Chemical Industry.

Genetic contribution of synapse-associated protein 97 to cerebellar functional connectivity changes in first-episode schizophrenia.

Our previous study data suggested that the synapse-associated protein 97 (SAP97) rs3915512 polymorphism is significantly related to clinical performance in schizophrenia. The cerebellum exhibits abundant expression of SAP97, which is involved with negative symptoms, cognition and emotion in schizophrenia. As functional dysconnectivity with the cortical-subcortical-cerebellar circuitry has been widely shown in patients with schizophrenia, cortical-subcortical-cerebellar dysconnectivity can therefore be considered a possible intermediate phenotype that connects risk genes with schizophrenia. In this study, resting-state functional magnetic resonance imaging (fMRI) was applied to evaluate whether the SAP97 rs3915512 polymorphism changes cortical/subcortical-cerebellar resting-state functional connectivity (RSFC) in 104 Han Chinese subjects (52 first-episode schizophrenia (FES) patients and 52 matched healthy controls (HCs)). To examine RSFC between cortical/subcortical regions and the cerebellum, a ROI (region of interest)-wise functional connectivity analysis was conducted. The association between abnormal cortical/subcortical-cerebellar connectivity and clinical manifestation was further assessed in FES patients with different genotypes. The interactive effect of disease and genotype on RSFC was found between the frontal gyrus (rectus) and cerebellum. A positive correlation was suggested between RSFC in the cerebellum and the hostility scores in FES patients with the A allele, and no correlation was found in FES patients with the TT genotype. The current findings identified that SAP97 may be involved in the process of mental symptoms in FES patients via cerebellar connectivity depending on the rs3915512 polymorphism genotype.

Semantic matching based legal information retrieval system for COVID-19 pandemic.

Recently, the pandemic caused by COVID-19 is severe in the entire world. The prevention and control of crimes associated with COVID-19 are critical for controlling the pandemic. Therefore, to provide efficient and convenient intelligent legal knowledge services during the pandemic, we develop an intelligent system for legal information retrieval on the WeChat platform in this paper. The data source we used for training our system is "The typical cases of national procuratorial authorities handling crimes against the prevention and control of the new coronary pneumonia pandemic following the law", which is published online by the Supreme People's Procuratorate of the People's Republic of China. We base our system on convolutional neural network and use the semantic matching mechanism to capture inter-sentence relationship information and make a prediction. Moreover, we introduce an auxiliary learning process to help the network better distinguish the relation between two sentences. Finally, the system uses the trained model to identify the information entered by a user and responds to the user with a reference case similar to the query case and gives the reference legal gist applicable to the query case.

Schixator, a new FXa inhibitor from Schistosoma japonicum with antithrombotic effect and low bleeding risk.

Schistosoma japonicum is a parasitic worm that lives in the mesenteric vein of its host and feeds on blood, suggesting that it might be a natural resource of novel anticoagulants. Here, by comprehensive analyses of the genomic sequences of Schistosoma japonicum, a new Kunitz-type gene precursor was identified. The Kunitz-type gene precursor codes for an 18-residue signal peptide and a 60-residue mature peptide. The Kunitz peptide was functionally expressed, and it had apparent inhibitory activity towards the intrinsic coagulation pathway but no effect on the extrinsic coagulation pathway even at the high concentration of 3 µM. Enzyme and inhibitor experiments further showed that the Kunitz domain peptide was a potent and selective FXa inhibitor, so it was named Schixator (Schistosoma FXa inhibitor). Schixator inhibits coagulation factor FXa with a Ki of 2.66 nM, but had weak inhibitory activity towards chymotrypsin, FXIa, plasma kallikrein, and plasmin, and no inhibitory activity towards trypsin, elastase, FIIa or FXIIa. In vivo, the intravenous administration of Schixator into mice dramatically decreased the number of thrombi in the carotid artery in an FeCl3-induced thrombus formation model without producing bleeding complications. To the best of our knowledge, Schixator is the first potent and selective FXa inhibitor from parasitic worms with antithrombotic effects and a low bleeding risk that provides a new clue for lead drug discovery against thrombosis-associated human diseases.

The residues 4 to 6 at the N-terminus in particular modulate fibril propagation of ß-microglobulin.

The ΔN6 truncation is the main posttranslational modification of ß-microglobulin (ßM) found in dialysis-related amyloid. Investigation of the interaction of wild-type (WT) ßM with N-terminally truncated variants is therefore of medical relevance. However, it is unclear which residues among the six residues at the N-terminus are crucial to the interactions and the modulation of amyloid fibril propagation of ßM. We herein analyzed homo- and heterotypic seeding of amyloid fibrils of WT human ßM and its N-terminally-truncated variants ΔN1 to ΔN6, lacking up to six residues at the N-terminus. At acidic pH 2.5, we produced amyloid fibrils from recombinant, WT ßM and its six truncated variants, and found that ΔN6 ßM fibrils exhibit a significantly lower conformational stability than WT ßM fibrils. Importantly, under more physiological conditions (pH 6.2), we assembled amyloid fibrils only from recombinant, ΔN4, ΔN5, and ΔN6 ßM but not from WT ßM and its three truncated variants ΔN1 to ΔN3. Notably, the removal of the six, five or four residues at the N-terminus leads to enhanced fibril formation, and homo- and heterotypic seeding of ΔN6 fibrils strongly promotes amyloid fibril formation of WT ßM and its six truncated variants, including at more physiological pH 6.2. Collectively, these results demonstrated that the residues 4 to 6 at the N-terminus particularly modulate amyloid fibril propagation of ßM and the interactions of WT ßM with N-terminally truncated variants, potentially indicating the direct relevance to the involvement of the protein's aggregation in dialysis-related amyloidosis.

Stochastic growth tree networks with an identical fractal dimension: Construction and mean hitting time for random walks.

There is little attention paid to stochastic tree networks in comparison with the corresponding deterministic analogs in the current study of fractal trees. In this paper, we propose a principled framework for producing a family of stochastic growth tree networks T possessing fractal characteristic, where t represents the time step and parameter m is the number of vertices newly created for each existing vertex at generation. To this end, we introduce two types of generative ways, i.e., Edge-Operation and Edge-Vertex-Operation. More interestingly, the resulting stochastic trees turn out to have an identical fractal dimension d = ln ⁡ 2 ( m + 1 ) / ln ⁡ 2 regardless of the introduction of randomness in the growth process. At the same time, we also study many other structural parameters including diameter and degree distribution. In both extreme cases, our tree networks are deterministic and follow multiple-point degree distribution and power-law degree distribution, respectively. Additionally, we consider random walks on stochastic growth tree networks T and derive an expectation estimation for mean hitting time ⟨ H ⟩ in an effective combinatorial manner instead of commonly used spectral methods. The result shows that on average, the scaling of mean hitting time ⟨ H ⟩ obeys ⟨ H ⟩ = | T |, where | T | represents vertex number and exponent λ is equivalent to 1 + ln ⁡ 2 / ln ⁡ 2 ( m + 1 ). In the meantime, we conduct extensive experimental simulations and observe that empirical analysis is in strong agreement with theoretical results.

Random growth scale-free networked models with an identical degree distribution and a tunable assortativity index.

In this work, we propose two kinds of graphic operations by using triangle configuration, based on which we establish a family of random growth networked models G(t;p) where notations t and p represent time step and probability parameter, respectively. By studying some fundamental structural parameters both analytically and numerically, we show that (1) all the realizations G(t;p) follow the same power-law degree distribution with exponent γ=2+ln⁡3/ln⁡2 regardless of probability p and thus have scale-free feature; (2) each model G(t;p) has a relatively high clustering coefficient; and (3) while network G(t;1) has a small average path length, it is not a unique model possessing small-world property mainly because its diameter D(t;1) does not reach the theoretical lower bound. Next, we make use of assortativity index R to quantify the tendency of forming connection between vertices and observe that (1) model G(t;0) exhibits disassortative mixing because the corresponding index R(t;0) is non-positive, and (2) model G(t;1) is in the opposite direction. As a result, we demonstrate that random model G(t;p) has a tunable quantity R(t;p) controlled by probability p. In addition, we exactly determine the total number of spanning trees of deterministic models G(t;1) and G(t;0) and also calculate the entropy of spanning trees.

Identification of the scorpion venom-derived antimicrobial peptide Hp1404 as a new antimicrobial agent against carbapenem-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is becoming a troublesome issue worldwide, and anti-CRAB drug research and development is urgently needed. To identify new anti-CRAB drug leads, we investigated seven scorpion venom-derived α-helical peptides that differ in their sequence composition and length. Three peptides, Hp1404, ctriporin and Im5, showed antimicrobial activities against Acinetobacter baumannii. Further antimicrobial assays revealed that Hp1404 exhibited the best cell selectivity with high anti-CRAB and low hemolytic activities. Fluorescence assays demonstrated that Hp1404 can induce dose-dependent disruptions of the bacterial cell membrane, implying a membrane-lytic mode of action. Taken together, our work sheds light on the potential of the scorpion venom-derived peptide Hp1404 for the development of novel antimicrobial agents against CRAB infections.

Association study of a genetic variant in the long intergenic noncoding RNA (linc01080) with schizophrenia in Han Chinese.

BACKGROUND: Schizophrenia is currently considered to be a polygene-related disease with unknown etiology. This research will verify whether the single nucleotide polymorphism (SNP) of the long intergenic noncoding RNA01080 (linc01080) contributes to the susceptibility and phenotypic heterogeneity of schizophrenia, with a view to providing data support for the prevention and individualized treatment of this disease. METHOD: The SNP rs7990916 in linc01080 were genotyped in 1139 schizophrenic and 1039 controls in a Southern Chinese Han population by the improved multiplex ligation detection reaction (imLDR) technique. Meanwhile, we assessed and analyzed the association between this SNP and schizophrenics' clinical symptoms, and the cognitive function. RESULT: There was no significant difference in genotype distribution, allele frequency distribution, gender stratification analysis between the two groups. However, the SNP of rs7990916 was significantly associated with the age of onset in patients with schizophrenia (P = 8.22E-07), patients with T allele had earlier onset age compared with CC genotype carriers. In terms of cognitive function, patients with T allele scored lower than CC genotype carriers in the Tower of London score and symbol coding score in the Brief assessment of Cognition (BACS), and the difference was statistically significant (P = 0.014, P = 0.022, respectively). CONCLUSION: Our data show for the first time that linc01080 polymorphism may affect the age of onset and neurocognitive function in patients with schizophrenia.

High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis.

BACKGROUND: The application of n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) supplementation for major depressive disorder (MDD) has been widely discussed in recent years, but its efficacy and application are still controversial. This network meta-analysis was conducted to compare the efficacy of different dosages of n-3 PUFAs on MDD patients in the early period of treatment. METHODS: Randomized controlled trials (RCTs) exploring the efficacy of n-3 PUFA supplementation for patients with MDD were retrieved from the databases of Pubmed, Embase and the Cochrane Library. RCTs comparing the efficacy of n-3 PUFA for adult (≥18 years) MDD patients without comorbidity were eligible for our study. The score of depressive symptoms in early therapy period of the treatment (≤9 weeks) was extracted. Standardized mean deviations (SMDs) of all the sores from the eligible RCTs were synthesized in a pairwise meta-analysis in frequentist framework and a random-effects network meta-analysis in Bayesian framework for the overall and subgroups (high- and low-dose) efficacy of n-3 PUFAs. RESULTS: A total of 910 MDD patients in 10 trials with 3 adjuvant therapy strategies (high-dose n-3 PUFAs, low-dose n-3 PUFAs and placebo) were included. Results of pairwise meta-analysis showed that n-3 PUFAs were superior to placebo (SMD: 1.243 ± 0.596; 95% CI: 0.060 ~ 2.414). Results of the network meta-analysis showed that both the high (SMD: 0.908 ± 0.331; 95% CI: 0.262 ~ 1.581) and the low-dose (SMD: 0.601 ± 0.286; 95% CI: 0.034 ~ 1.18) n-3 PUFAs were superior to placebo, and the efficacy of high-dose n-3 PUFAs is superior to that of low-dose. CONCLUSIONS: High-dose n-3 PUFAs supplementation might be more superior than low-dose in the early therapy period for MDD. More head-to-head clinical trials need to be carried out to provide more direct comparison and enhance the evidence of the efficacy of n-3PUFAs for MDD.

Random growth networks with exponential degree distribution.

A great variety of complex networks can be well represented as random graphs with some constraints: for instance, a provided degree distribution, a smaller diameter, and a higher clustering coefficient. Among them, the degree distribution has attracted considerable attention from various science communities in the last few decades. In this paper, we focus mainly on a family of random graphs modeling complex networks that have an exponential degree distribution; i.e., P(k)∼ exp(αk), where k is the degree of a vertex, P(k) is a probability for choosing randomly a vertex with degree equal to k, and α is a constant. To do so, we first introduce two types of operations: type-A operation and type-B operation. By both the helpful operations, we propose an available algorithm A for a seminal model to construct exactly solvable random graphs, which are able to be extended to a graph space S(p,pc,t) with probability parameters p and pc satisfying p+pc=1. Based on the graph space S(p,pc,t), we discuss several topological structure properties of interest on each member N(p,pc,t) itself and find model N(p,pc,t) to exhibit the small-world property and assortative mixing. In addition, we also report a fact that in some cases, two arbitrarily chosen members might have completely different other topological properties, such as the total number of spanning trees, although they share a degree distribution in common. Extensive experimental simulations are in strong agreement with our analytical results.

Nonsiliceous Mesoporous Materials: Design and Applications in Energy Conversion and Storage.

In this work, the progress in the design of nonsiliceous mesoporous materials (nonSiMPMs) over the last five years from the perspectives of the chemical composition, morphology, loading, and surface modification is summarized. Carbon, metal, and metal oxide are in focus, which are the most promising compositions. Then, representative applications of nonSiMPMs are demonstrated in energy conversion and storage, including recent technical advances in dye-sensitized solar cells, perovskite solar cells, photocatalysts, electrocatalysts, fuel cells, storage batteries, supercapacitors, and hydrogen storage systems. Finally, the requirements and challenges of the design and application of nonSiMPMs are outlined.

Bldesin, the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities.

Fungus defensin is a kind of important natural peptide resource, such as plectasin from the soil fungus Pseudoplectania nigrella with potential application in the antimicrobial peptide lead drug discovery. Here, a fungus defensin named Bldesin with Kv1.3 channel and serine protease inhibitory activities was first explored. By GST-Bldesin fusion expression and enterokinase cleaving strategy, recombinant Bldesin was obtained successfully. Antimicrobial assays showed that Bldesin had potent activity against Gram-positive Staphylococcus aureus, but had no effect on Gram-negative Escherichia coli. Electrophysiological experiments showed that Bldesin had Kv1.3 channel inhibitory activity. Serine protease inhibitory associated experiments showed that Bldesin had unique chymotrypsin protease inhibitory, elastase protease inhibitory, and serine protease-associated coagulation inhibitory activities. To the best of our knowledge, Bldesin is the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities and highlighted novel pharmacological effects of fungus-derived defensin peptides.

Macromolecular crowding favors the fibrillization of ß2-microglobulin by accelerating the nucleation step and inhibiting fibril disassembly.

Hemodialysis-associated amyloidosis (HAA) involves the fibrillization of ß2-microglobulin (ß2M) and occurs in crowded physiological environments. However, how macromolecular crowding affects amyloid formation of ß2M remains elusive. Here we study the effects of macromolecular crowding on amyloid formation and fibril disassembly of wild-type human ß2M and its pathogenic mutant ΔN6. At strongly acidic pH2.5, the presence of a strong crowding agent (Ficoll 70 or dextran 70) not only dramatically accelerates the fibrillization of both wild-type ß2M and its ΔN6 variant by reducing the lag time to a large extent, indicating the acceleration of the nucleation phase, but also remarkably increases the amount of ß2M fibrils. At weakly acidic pH6.2, such an enhancing effect of macromolecular crowding on fibril formation is only observed for pathogenic mutant ΔN6, but not for wild-type ß2M which does not form amyloid fibrils in the absence and presence of a crowding agent. Thus, we propose that the monomers of ß2M form the nuclei, which is enhanced by macromolecular crowding, followed by the step of fibril elongation. Furthermore, at physiological pH, macromolecular crowding remarkably inhibits ß2M fibril disassembly by decreasing rate constants corresponding to fast and slow stages of fibril disaggregation. Our data demonstrate that macromolecular crowding favors the fibrillization of ß2M by accelerating the nucleation step and inhibiting fibril disassembly. Our findings provide clear evidence for the pathology of HAA that macromolecular crowding should be taken into account.

miR-137: a new player in schizophrenia.

Schizophrenia is a complex genetic disease and characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are critical to neurodevelopment and adult neuronal processes by modulating the activity of multiple genes within biological networks. MiR-137 as a brain-enriched microRNA, plays important roles in regulating embryonic neural stem cells (NSCs) fate determination, neuronal proliferation and differentiation, and synaptic maturation. Its dysregulation causes changes in the gene expression regulation network of the nervous system, thus inducing mental disorders. Recently, miR-137 has been confirmed as a gene related to schizophrenia susceptibility. In the following review, we summarize the expression pattern, epigenetic regulation and functions of miR-137. A more complete picture of the miR-137, which is dysregulated in psychiatric illness, may improve our understanding of the molecular mechanisms underlying schizophrenia.

Pre-trained language models in medicine: A survey.

With the rapid progress in Natural Language Processing (NLP), Pre-trained Language Models (PLM) such as BERT, BioBERT, and ChatGPT have shown great potential in various medical NLP tasks. This paper surveys the cutting-edge achievements in applying PLMs to various medical NLP tasks. Specifically, we first brief PLMS and outline the research of PLMs in medicine. Next, we categorise and discuss the types of tasks in medical NLP, covering text summarisation, question-answering, machine translation, sentiment analysis, named entity recognition, information extraction, medical education, relation extraction, and text mining. For each type of task, we first provide an overview of the basic concepts, the main methodologies, the advantages of applying PLMs, the basic steps of applying PLMs application, the datasets for training and testing, and the metrics for task evaluation. Subsequently, a summary of recent important research findings is presented, analysing their motivations, strengths vs weaknesses, similarities vs differences, and discussing potential limitations. Also, we assess the quality and influence of the research reviewed in this paper by comparing the citation count of the papers reviewed and the reputation and impact of the conferences and journals where they are published. Through these indicators, we further identify the most concerned research topics currently. Finally, we look forward to future research directions, including enhancing models' reliability, explainability, and fairness, to promote the application of PLMs in clinical practice. In addition, this survey also collect some download links of some model codes and the relevant datasets, which are valuable references for researchers applying NLP techniques in medicine and medical professionals seeking to enhance their expertise and healthcare service through AI technology.

Cationicity Enhancement on the Hydrophilic Face of Ctriporin Significantly Reduces Its Hemolytic Activity and Improves the Antimicrobial Activity against Antibiotic-Resistant ESKAPE Pathogens.

The ESKAPE pathogen-associated antimicrobial resistance is a global public health issue, and novel therapeutic strategies are urgently needed. The short cationic antimicrobial peptide (AMP) family represents an important subfamily of scorpion-derived AMPs, but high hemolysis and poor antimicrobial activity hinder their therapeutic application. Here, we recomposed the hydrophilic face of Ctriporin through lysine substitution. We observed non-linear correlations between the physiochemical properties of the peptides and their activities, and significant deviations regarding the changes of antimicrobial activities against different bacterial species, as well as hemolytic activity. Most importantly, we obtained two Ctriporin analogs, CM5 and CM6, these two have significantly reduced hemolytic activity and more potent antimicrobial activities against all tested antibiotic-resistant ESKAPE pathogens. Fluorescence experiments indicated they may perform the bactericidal function through a membrane-lytic action model. Our work sheds light on the potential of CM5 and CM6 in developing novel antimicrobials and gives clues for optimizing peptides from the short cationic AMP family.

Function and Mechanism of Antiviral Wasp Venom Peptide Protopolybia-MP III and Its Derivatives against HSV-1.

Viruses are one of the leading causes of human disease, and many highly pathogenic viruses still have no specific treatment drugs. Therefore, producing new antiviral drugs is an urgent matter. In our study, we first found that the natural wasp venom peptide Protopolybia-MP III had a significant inhibitory effect on herpes simplex virus type 1 (HSV-1) replication in vitro by using quantitative real-time PCR (qPCR), Western blotting, and plaque-forming assays. Immunofluorescence analysis showed Protopolybia-MP III could enter cells, and it inhibited multiple stages of the HSV-1 life cycle, including the attachment, entry/fusion, and post-entry stages. Furthermore, ultracentrifugation and electron microscopy detected that Protopolybia-MP III significantly suppressed HSV-1 virion infectivity at different temperatures by destroying the integrity of the HSV-1 virion. Finally, by comparing the antiviral activity of Protopolybia-MP III and its mutants, a series of peptides with better anti-HSV-1 activity were identified. Overall, this work found the function and mechanism of the antiviral wasp venom peptide Protopolybia-MP III and its derivatives against HSV-1 and laid the foundation for the research and development of wasp venom-derived antiviral candidate peptide drugs.

Differential potassium channel inhibitory activities of a novel thermostable degradation peptide BmKcug1a-P1 from scorpion medicinal material and its N-terminal truncated/restored peptides.

Thermally stable full-length scorpion toxin peptides and partially degraded peptides with complete disulfide bond pairing are valuable natural peptide resources in traditional Chinese scorpion medicinal material. However, their pharmacological activities are largely unknown. This study discovered BmKcug1a-P1, a novel N-terminal degraded peptide, in this medicinal material. BmKcug1a-P1 inhibited hKv1.2 and hKv1.3 potassium channels with IC50 values of 2.12 ± 0.27 µM and 1.54 ± 0.28 µM, respectively. To investigate the influence of N-terminal amino acid loss on the potassium channel inhibiting activities, three analogs (i.e., full-length BmKcug1a, BmKcug1a-P1-D2 and BmKcug1a-P1-D4) of BmKcug1a-P1 were prepared, and their potassium channel inhibiting activities on hKv1.3 channel were verified by whole-cell patch clamp technique. Interestingly, the potassium channel inhibiting activity of full-length BmKcug1a on the hKv1.3 channel was significantly improved compared to its N-terminal degraded form (BmKcug1a-P1), while the activities of two truncated analogs (i.e., BmKcug1a-P1-D2 and BmKcug1a-P1-D4) were similar to that of BmKcug1a-P1. Extensive alanine-scanning experiments identified the bonding interface (including two key functional residues, Asn30 and Arg34) of BmKcug1a-P1. Structural and functional dissection further elucidated whether N-terminal residues of the peptide are located at the bonding interface is important in determining whether the N-terminus significantly influences the potassium channel inhibiting activity of the peptide. Altogether, this research identified a novel N-terminal degraded active peptide, BmKcug1a-P1, from traditional Chinese scorpion medicinal material and elucidated how the N-terminus of peptides influences their potassium channel inhibiting activity, contributing to the functional identification and molecular truncation optimization of full-length and degraded peptides from traditional Chinese scorpion medicinal material Buthus martensii Karsch.