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Although the physicochemical properties of antimicrobial peptides (AMPs) and anticancer peptides (ACPs) are very similar, it remains unclear which specific parameter(s) of ACPs confer the major anticancer activity. By answering how to construct a short AMP/ACP that could easily be synthesized in the most cost effective way plus conferring a maximum anticancer effect is a very important scientific breakthrough in the development of protein/peptide drugs. In this study, an 18-amino-acids antimicrobial peptide, AcrAP1 (named AP1-Z1), was used as a template. Bioinformatics algorithms were then performed to design its six mutants (AP1-Z3a, AP1-Z3b, AP1-Z5a, AP1-Z5b, AP1-Z7, and AP1-Z9). After a series of in vitro experiments plus intensive computational analysis, the data demonstrated that AP1-Z5a and AP1-Z5b induced both apoptosis and anti-angiogenic effects to achieve the maximum anticancer activity. Specifically, the most effective mutant, AP1-Z5b, exhibited high selectivity for the charged membrane in molecular dynamics simulations. These findings clearly demonstrated that both charge and hydrophobicity play an important role and are necessary to reach an optimum equilibrium for optimizing the anticancer activity of AMPs. Overall, the present study provides a very crucial theoretical basis and important scientific evidence on the key physicochemical parameters of ACP drugs development. Keywords: antimicrobial peptides, anticancer peptides, molecular dynamics, angiogenesis, apoptosis, drug discovery and development, targeted therapy

Abstract Background The leptin receptor-deficient knockout (db/db) mouse is a well-established model for studying type II diabetes mellitus (T2DM). T2DM is an important risk factor of intervertebral disc degeneration (IVDD). Although the relationship between type I diabetes and IVDD has been reported by many studies, few studies have reported the effects of T2DM on IVDD in db/db mice model. Methods Mice were separated into 3 groups: wild-type (WT), db/db, and IGF-1 groups (leptin receptor-deficient mice were treated with insulin-like growth factor-1 (IGF-1). To observe the effects of T2DM and glucose-lowering treatment on IVDD, IGF-1 injection was used. The IVD phenotype was detected by H&E and safranin O fast green staining among db/db, WT and IGF-1 mice. The levels of blood glucose and weight in mice were also recorded. The changes in the mass of the trabecular bone in the fifth lumbar vertebra were documented by micro-computed tomography (micro-CT). Tunnel assays were used to detect cell apoptosis in each group. Results The weight of the mice were 27.68 ± 1.6 g in WT group, which was less than 57.56 ± 4.8 g in db/db group, and 52.17 ± 3.7 g in IGF-1 injected group (P

Gastric neuroendocrine carcinoma (GNEC) is rare cancer detected in the stomach. Previously, we demonstrated that the poorer prognosis of GNEC patients compared with gastric adenocarcinoma (GAC) patients was probably due to the lack of response to chemotherapy. Thus, it is crucial to study the specific GNEC gene expression pattern and investigate chemoresistance mechanism of GNEC. The transcriptome of GNEC patients was compared with that of GAC patients using RNA-seq. The KEGG analysis was employed to explore the specific differential expression gene function enrichment pattern. In addition, the transcriptomes of two GNEC cell lines, ECC10 and ECC12, were also compared with those of two GAC cell lines, MGC-803 and AGS, using RNA-seq. Comparing patient samples and cell lines transcriptome data, we try to uncover the potential targets and pathways which may affect the chemoresistance of GNEC. By combing all transcriptome data, we identified 22 key genes that were specifically up-regulated in GNEC. This panel of genes probably involves in the chemoresistance of GNEC. From our current experimental data, NeuroD1, one of the 22 genes, is associated with the prognosis of GNEC patients. Knockdown of NeuroD1 enhanced the sensitivity to irinotecan of GNEC cell lines. Our research sheds light in identifying a panel of novel therapeutic target specifically for GNEC clinical treatment which has not been reported before.

As a cutting-edge technique for denoising and feature extraction, singular spectrum analysis (SSA) has been applied successfully for feature mining in hyperspectral images (HSI). However, when applying SSA for in situ feature extraction in HSI, conventional pixel-based 1-D SSA fails to produce satisfactory results, while the band-image-based 2D-SSA is also infeasible especially for the popularly used line-scan mode. To tackle these challenges, in this article, a novel 1.5D-SSA approach is proposed for in situ spectral-spatial feature extraction in HSI, where pixels from a small window are used as spatial information. For each sequentially acquired pixel, similar pixels are located from a window centered at the pixel to form an extended trajectory matrix for feature extraction. Classification results on two well-known benchmark HSI datasets and an actual urban scene dataset have demonstrated that the proposed 1.5D-SSA achieves the superior performance compared with several state-of-the-art spectral and spatial methods. In addition, the near real-time implementation in aligning to the HSI acquisition process can meet the requirement of online image analysis for more efficient feature extraction than the conventional offline workflow.

According to the findings of a sheep breeding farm in Shaanxi, China, 2.53% (15/594) of sheep exhibited respiratory (clinical) symptoms such as dyspnoea, nasal discharge, wet cough, fever, and progressive emaciation. Although multi-drug treatment strategies (including ampicillin, tylosin, florfenicol, and ceftiofur) have been attempted to improve clinical outcomes, they have only been met with limited success, with a mortality rate of 40%. Ultimately, Aeromonas veronii (A. veronii) was identified as the causative pathogen for respiratory disease. The rates of symptomatic and asymptomatic sheep positive to A. veronii were 64.28% (95% CI 52.25–76.31%) and 8.02% (95% CI 6.96–9.08%), respectively. Pathogenicity tests demonstrated that the A. veronii is pathogenic to sheep and mice. The results of the antibiotic susceptibility tests revealed that the strain was sensitive to cefotaxime, gentamicin, and enrofloxacin and resistant to ampicillin, ceftiofur, amoxicillin, kanamycin, neomycin, streptomycin, tetracycline, florfenicol, and tylosin. We suggest that the combination of cefotaxime and gentamicin is an effective treatment based on the results of an antimicrobial susceptibility test, which exhibited good therapeutic efficacy. To the best of our knowledge, this is the first report in which pathogenic A. veronii has been documented as the cause of death in sheep in China. We concluded that pathogenic A. veronii poses a potential risk to the industry of sheep husbandry. This study’s findings can help guide prevention and treatment plans for A. veronii infection in sheep.

Epidermal growth factor receptor (EGFR) mutations were found in 30%-40% of non–small cell lung cancer (NSCLC) patients, who often responded well to EGFR tyrosine kinase inhibitors (EGFR-TKIs) as exemplified by erlotinib and gefitinib in the past decades. However, EGFR mutation-led drug resistance usually occurred upon prolonged treatment with EGFR-TKI. Herein, we study the anticancer effects of EGFR-TKI in combination with a newly developed antibody, A9(B8), to target a disintegrin and metalloprotease (ADAM) 17 that was overexpressed in NSCLC patients. NSCLC cell lines with different EGFR mutations were used to evaluate the drug combination. We have found that the EGFR-TKI-A9(B8) combination exhibited enhanced anticancer effects in NCI-H1975 cells harboring L858R and T790M mutations, which were due to simultaneous suppression of extracellular signal–regulated kinases phosphorylation. Our results suggested that targeting ADAM17 could potentiate the anticancer effects of EGFR-TKI against NSCLC and overcome drug resistance due to EGFR mutations.

Accurately monitoring the quantity and quality of urban vegetation contributes to regional greening efforts and improves the understanding of vegetation's impact on the environment. However, factors such as building shadows and synthetic materials can greatly obstruct vegetation estimates. Additionally, vegetation indices (VIs) saturate quickly in high biomass conditions, complicating vegetation quality assessments. To address these issues, we propose a new vegetation index, namely the hyperspectral image-based vegetation index (HSVI). HSVI is built in three steps: band selection, saturable band reconstruction, and index structure redefinition. Firstly, we select four representative bands and construct an enhanced vegetation index (EVI) to eliminate the interference of complex urban surface factors. Secondly, we reconstruct the easily saturable band (760 nm) through an exponential function to form an optimized enhanced vegetation index (OEVI). Finally, the index structure is redefined by adding the denominator of the sum of the red edge (689 nm) and green (520 nm) bands to OEVI to further enhance the spectral information of vegetation and eliminate the saturation problem typical of VIs. Three datasets with different geomorphological features (Shanghai Theatre Academy, Dazhu Mountain, and the University of Houston) are used to compare the performance of HSVI with six VIs widely adopted in urban ecological research, i.e., the difference vegetation index (DVI), the normalized difference vegetation index (NDVI), the simple ratio (SR), the optimized soil-adjusted vegetation index (OSVAI), the modified transformed vegetation index (MTVI2) and the wide-dynamic-range vegetation index (WDRVI). The results show that the vegetation extraction accuracy of HSVI is more than 90%, which is significantly higher than those of the other VIs. Additionally, HSVI also solves the VIs saturation issue. Therefore, HSVI shows high potential usefulness for urban ecological research applications.

In the last two decades, proteases have become a primary and vital target in drug discovery [...]

Background: Virtual reality (VR) technology is increasingly used in stroke rehabilitation. This study aimed to investigate the effectiveness of using the glasses-free VR training to improve motor function of upper limb in patients with stroke. Methods: Twelve patients with stroke were recruited to participate in the intervention of 3 weeks. At the baseline and post intervention, two times of evaluation including Fugl-Meyer upper-extremity scale (FMS-UE), transcranial magnetic stimulation (TMS) measurement and motion evaluation were performed. Results: No significant difference was observed between two groups at baseline evaluation. After the intervention, the FMS-UE scores presented a greater improvement in the VR group compared with the control group. TMS measurement showed that there was significant difference in cortex latency and central motor conduction time between two groups after the intervention, but no significant difference in the amplitude of motor event potential was observed. In addition, there was a significant correlation between game scores and FMS-UE scores. Conclusions: The novel glasses-free VR training was at least as effective as conventional occupational therapy in upper limb motor function, improving nerve conduction time and corticospinal excitability in patient with stroke.

BackgroundThe second human pegivirus (HPgV-2) and hepatitis C virus (HCV) belong to the Flaviviridae family and share some common genome features. However, the two viruses exhibit significantly different genetic diversity. The comparison of intrahost dynamics of HPgV-2 and HCV that mainly reflect virus-host interactions is needed to elucidate their intrahost difference of genetic diversity and the possible mechanisms.MethodsIntrahost single nucleotide variations (iSNVs) were identified by means of next-generation sequencing from both cross-sectional and longitudinal samples from HPgV-2- and HCV-coinfected patients. The levels of human cytokines were quantified in the patient before and after HCV elimination by the treatment of direct-acting antivirals (DAA).ResultsUnlike HCV, the viral sequences of HPgV-2 are highly conserved among HPgV-2-infected patients. However, iSNV analysis confirmed the intrahost variation or quasispecies of HPgV-2. Almost all iSNVs of HPgV-2 did not accumulate or transmit within host over time, which may explain the highly conserved HPgV-2 consensus sequence. Intrahost variation of HPgV-2 mainly causes nucleotide transition in particular at the 3rd codon position and synonymous substitutions, indicating purifying or negative selection posed by host immune system. Cytokine data further indicate that HPgV-2 infection alone may not efficiently stimulate innate immune responses since proinflammatory cytokine expression dramatically decreased with elimination of HCV.ConclusionThis study provided new insights into the intrahost genomic variations and evolutionary dynamics of HPgV-2 as well as the impact of host immune selection and virus polymerase on virus evolution. The different genetic diversity of HPgV-2 and HCV makes HPgV-2 a potential new model to investigate RNA virus diversity and the mechanism of viral polymerase in modulating virus replication.

Gastric cancer (GC) is a common upper gastrointestinal tumor. Death-associated protein kinase (DAPK1) was found to participate in the development of various malignant tumors. However, there are few reports on DAPK1 in gastric cancer. In this study, the TCGA and GEO datasets were used to explore the expression and role of DAPK1 in gastric cancer. The functions of DAPK1 in gastric cancer were determined by proliferation, migration and invasion assays. In addition, genes co-expressed with DAPK1 in gastric cancer were estimated through the WGCNA and correlation analysis. A DAPK1-related gene prognostic model was constructed using the Cox regression and lasso analyses. The expression of DAPK1 was significantly up-regulated in gastric cancer tissues. Kaplan–Meier analysis showed that low expression of DAPK1 was a favorable prognostic factor of overall survival and disease-free survival for gastric cancer patients. Functional experiments demonstrated that DAPK1 can promote the migration and invasion of gastric cancer cells. WGCNA, correlation analysis, Cox regression, and lasso analyses were applied to construct the DAPK1-related prognostic model. The prognostic value of this prognostic model of DAPK1-related genes was further successfully validated in an independent database. Our results indicated that DAPK1 can promote gastric cancer cell migration and invasion and established four DAPK1-related signature genes for gastric cancer that could independently predict the survival of GC patients.

Cardiac complications are common in antiretroviral therapy-treated (ART-treated) acquired immune deficiency syndrome (AIDS) patients, and the incidence increases with age. Myocardial injury in ART-treated AIDS patients with a relatively longer disease duration has been evaluated. However, there is no relevant study on whether patients with a short AIDS duration have cardiac dysfunction. Thirty-seven ART-treated males with AIDS and eighteen healthy controls (HCs) were prospectively included for CMR scanning. Clinical data and laboratory examination results were collected. The ART-treated males with AIDS did not have significantly reduced biventricular ejection fraction, myocardial edema, or late gadolinium enhancement. Compared with the HCs, the biventricular volume parameters and left ventricle myocardial strain indices in ART-treated males with AIDS were not significantly reduced (all p > 0.05). ART-treated males with AIDS were divided into subgroups according to their CD4+ T-cell counts (p > 0.05). In Pearson correlation analysis, CD4+ T-cell counts were not significantly correlated with biventricular volume parameters or left ventricular myocardial strain indices. In conclusion, ART-treated males with AIDS receiving ART therapy with a short disease duration (less than 3 years) might not develop obvious cardiac dysfunction as evaluated by routine CMR, so it is reasonable to appropriately extend the interval between cardiovascular follow-ups to more than 3 years.

Abstract Background Candida arthritis is extremely rare and also represents a major challenge of diagnosis and treatment. Here we reported a rare case of recurrent arthritis caused by Candida parapsilosis. Case presentation A 56-year-old Chinese male suffered from recurrent pain and swelling in his right knee after several times of “small needle-knife” acupuncture and corticosteroid injection of the joint. Candida parapsilosis was cultured in his synovial fluid and identified by sequencing of its Internal Transcribed Spacer (ITS) gene. Here we present the radiological characteristics, arthroscopic pictures, and synovium pathology of this patient. Also, blood test and chemical analysis of his synovial fluid were listed as well as the ITS sequence of this Candida species identified. The patient underwent thorough arthroscopic debridement and then set on fluconazole 400 mg daily for 12 months. His symptoms resolved and no relapse was observed on the last follow-up. Additionally, a brief but comprehensive review of C. parapsilosis arthritis episodes from past to now were studied. Conclusion With the detailed clinical information reported in this case and our literature review, we hope they would add to our knowledge of C. parapsilosis arthritis - its clinical settings, laboratory features, radiological characteristics, arthroscopic findings and experience of management.

The onsite next generation sequencing (NGS) of Ebola virus (EBOV) genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin, transmission, and evolution of this virus. Herein, we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015, during the late phase of the outbreak. The surviving EBOV patients had a recovery process characterized by decreasing viremia, fever, and biochemical parameters. EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection, including the previously described short stretches of 13 serial T>C mutations. Remarkably, within individual patients, samples collected during the early phase of infection possessed Ts at these nucleotide sites, whereas they were replaced by Cs in samples collected in the later phase, suggesting that these short stretches of T>C mutations could emerge independently. In addition, up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently. Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions.

We optimized conditions for preparation of ginseng wine and explored hepatoprotective effects of ginsenosides against alcohol-induced liver injury in mice by transcriptomics analyses. Mice were treated by daily intragastric administration of water, 55%-ethanol, or ginseng-wine. Results showed that mRNA levels of Adh1 and Cyp2e1, which encode the two enzymes involved in the conversion of alcohol to acetaldehyde, were increased by alcohol intake and were significantly attenuated by ginsenosides. The mRNA level of Cat, which encodes another enzyme in alcohol metabolism, showed the opposite change. Thus, ginsenosides might influence alcohol metabolism by suppressing the CYP2E1 and ADH pathways, and enhancing the CAT pathway to prevent acetaldehyde and peroxide accumulation, respectively. Alcohol consumption also enhanced mRNA levels of Srebp-1c, Gsta2 and Tlr4, which encode transcription factors important in lipogenesis, oxidative stress, and inflammation, respectively. These increases in expression were also attenuated by ginsenosides. The results were further verified by qRT-PCR and western blotting.

Documents have revealed that leaves, barks and woods from oak trees are rich in phenols, yet little is known about them in Mongolian oak (Quercus mongolica) cups, the by-product waste with large biomass. In the present work, composition analysis through total phenols, flavonoids and tannins, and condensed tannins, and HPLC profiles and antioxidant assessment by DPPH, ABTS, reducing power, ORAC and CAA were performed to evaluate oak cup crude extracts and the resulting four fractions (Fr. I, Fr. II, Fr. III and Fr. IV) prepared by HPD-100 macroporous resin chromatography. Among the optimal 50% ethanol crude extract (ECE) and its subsequent four fractions, Fr. II, on the basis of the oak cups, collected the majority of total phenols, flavonoids and tannins, and condensed tannins from ECE though lower contents of all compositions than those in Fr. III when based on the extract with an exception of condensed tannins. And the highlight of Fr. II is that it possessed the strongest antioxidant ability from the perspective of extract. These findings imply that composition of condensed tannins as well as its contents might take dominate role in antioxidant ability of oak cups. This was further corroborated through HPLC profiles as compositions in ECE and the four fractions are all distinguished from each other. HPLC also exhibited the great enrichment of ellagic acid in Fr. III. Moreover, the correlation analysis indicated that there is exclusive correlation existed between total flavonoids and antioxidant assays among all composition analysis including ellagic acid, which further confirmed the main influencing factor to antioxidant ability of oak cup may be composition of condensed tannins as well as its contents because the condensed tannins were constituted by flavonoid units, and ellagic acid may not be a strong antioxidant contributor in oak cups. Therefore, Fr. II should be chosen as the best fraction to be further explored. In addition, this established HPD-100 macroporous resin chromatography procedure could be developed as a simple and effective procedure for preparation of ellagic acid from oak cups. Keywords: Mongolian oak (Quercus mongolica) cups, Flavonoids, Condensed tannins, Antioxidant activities, Macroporous resin, HPLC

Abstract Background There exist differences in morphological traits and phytochemical compositions between field- and mountain-cultivated Panax ginseng (FCG and MCG), which might be attributed to variations of terpenoids metabolism adapting to different growth conditions. The present work aims to uncover these variations. Results Among 26,648 differentially expressed genes, 496 genes distributed in seven dominant terpenoids pathways were identified. Diterpenoids and triterpenoids biosynthesis genes were significantly higher-expressed in FCG root. Conversely, biosynthesis of carotenoids was significantly more active in MCG root. Additionally, terpenoids backbones, monoterpenoids, sesquiterpenoids, and terpenoid-quinones biosyntheses were neither obviously inclined. Our determination also revealed that there were more gibberellins and steroids accumulated in FCG root which might be responsible for its quick vegetative growth, and enriched abscisic acid and germacrenes as well as protopanaxatriol-type ginsenosides might be major causes of enhanced stress-resistance in MCG root. Conclusions The study firstly provided an overview of terpenoids metabolism in roots of FCG and MCG in elucidating the underlying mechanisms for their different morphological appearances and phytochemical compositions.

The rapid development of wind energy has brought a lot of uncertainty to the power system. The accurate ultra-short-term wind power prediction is the key issue to ensure the stable and economical operation of the power system. It is also the foundation of the intraday and real-time electricity market. However, most researches use one prediction model for all the scenarios which cannot take the time-variant and non-stationary property of wind power time series into consideration. In this paper, a Markov regime switching method is proposed to predict the ultra-short-term wind power of multiple wind farms. In the regime switching model, the time series is divided into several regimes that represent different hidden patterns and one specific prediction model can be designed for each regime. The Toeplitz inverse covariance clustering (TICC) is utilized to divide the wind power time series into several hidden regimes and each regime describes one special spatiotemporal relationship among wind farms. To represent the operation state of the wind farms, a graph autoencoder neural network is designed to transform the high-dimensional measurement variable into a low-dimensional space which is more appropriate for the TICC method. The spatiotemporal pattern evolution of wind power time series can be described in the regime switching process. Markov chain Monte Carlo (MCMC) is used to generate the time series of several possible regime numbers. The Kullback-Leibler (KL) divergence criterion is used to determine the optimal number. Then, the spatiotemporal graph convolutional network is adopted to predict the wind power for each regime. Finally, our Markov regime switching method based on TICC is compared with the classical one-state prediction model and other Markov regime switching models. Tests on wind farms located in Northeast China verified the effectiveness of the proposed method.

In this article, the networked filtering problem for a class of robotic manipulators with semi-Markov type parameters is investigated under the passivity framework. In particular, the mode-dependent quantization and event-triggered communication scheme are both proposed for increasing the network transmission efficiency. Sufficient stability conditions are first derived by choosing mode-dependent Lyapunov–Krasovskii functionals. Then, the mode-dependent filter gains and the event-triggering parameters are further designed with the help of matrix convex optimization. In the end, a simulation example is provided such that the effectiveness of the proposed filtering method can be well demonstrated.

Tripterygium wilfordii is a vine from the Celastraceae family that is used in traditional Chinese medicine (TCM). The active ingredient, celastrol, is a friedelane-type pentacyclic triterpenoid with putative roles as an antitumor, immunosuppressive, and anti-obesity agent. Here, we report a reference genome assembly of T. wilfordii with high-quality annotation using a hybrid sequencing strategy. The total genome size obtained is 340.12 Mb, with a contig N50 value of 3.09 Mb. We successfully anchored 91.02% of sequences into 23 pseudochromosomes using high-throughput chromosome conformation capture (Hi–C) technology. The super-scaffold N50 value was 13.03 Mb. We also annotated 31,593 structural genes, with a repeat percentage of 44.31%. These data demonstrate that T. wilfordii diverged from Malpighiales species approximately 102.4 million years ago. By integrating genome, transcriptome and metabolite analyses, as well as in vivo and in vitro enzyme assays of two cytochrome P450 (CYP450) genes, TwCYP712K1 and TwCYP712K2, it is possible to investigate the second biosynthesis step of celastrol and demonstrate that this was derived from a common ancestor. These data provide insights and resources for further investigation of pathways related to celastrol, and valuable information to aid the conservation of resources, as well as understand the evolution of Celastrales.

The monoclonal antibody against CTLA-4, Ipilimumab, is a first-in-class immune-checkpoint inhibitor approved for treatment of advanced melanoma in adults but not extensively studied in children. In light of the fact that the immune response early in life differs from that of adults, we have applied a human in vitro model stimulating CD4+ T-cells from neonates, children (1–5 years), and adults antigen-specifically with Staphylococcus aureus (S. aureus) for assessment of CTLA-4 blockade early in life. We show that T-cell proliferation as well as frequencies of antigen-specific T-cells (CD40L+CD4+) were enhanced in neonatal T-cells upon CTLA-4 blockade showing a larger variance within the group (F-test p

Joint sparse representation classification (JSRC) is a representative spectral–spatial classifier for hyperspectral images (HSIs). However, the JSRC is inappropriate for highly heterogeneous areas due to the spatial information being extracted from a fixed-sized neighborhood block, which is often unable to conform to the naturally irregular structure of land cover. To address this problem, a superpixel-based JSRC with nonlocal weighting, i.e., superpixel-based nonlocal weighted JSRC (SNLW-JSRC), is proposed in this paper. In SNLW-JSRC, the superpixel representation of an HSI is first constructed based on an entropy rate segmentation method. This strategy forms homogeneous neighborhoods with naturally irregular structures and alleviates the inclusion of pixels from different classes in the process of spatial information extraction. Afterwards, the superpixel-based nonlocal weighting (SNLW) scheme is built to weigh the superpixel based on its structural and spectral information. In this way, the weight of one specific neighboring pixel is determined by the local structural similarity between the neighboring pixel and the central test pixel. Then, the obtained local weights are used to generate the weighted mean data for each superpixel. Finally, JSRC is used to produce the superpixel-level classification. This speeds up the sparse representation and makes the spatial content more centralized and compact. To verify the proposed SNLW-JSRC method, we conducted experiments on four benchmark hyperspectral datasets, namely Indian Pines, Pavia University, Salinas, and DFC2013. The experimental results suggest that the SNLW-JSRC can achieve better classification results than the other four SRC-based algorithms and the classical support vector machine algorithm. Moreover, the SNLW-JSRC can also outperform the other SRC-based algorithms, even with a small number of training samples.

The effect of intercritical tempering temperature (TT) on the microstructure evolution and mechanical properties of 3.6Mn medium manganese steel, which contained martensite and austenite, was investigated by X-ray diffraction, electron backscattering diffraction and transmission electron microscopy, as well as Thermo-Calc calculation. The results showed that the volume fraction of reversed austenite (RA) increased firstly and then decreased with the increasing TT in the range of 550~650 °C. When the TT was below 620 °C, lath-like RA with good stability was mainly displayed between martensite laths and its size is about 100 nm. When the TT was higher than 650 °C, larger-size and block RA was formed in the martensite block boundaries, and part of the RA transformed into fresh martensite during cooling. The yield strength and tensile strength of the experimental steels decreased gradually as the TT increased, but the tensile strength increased gradually with the formation of block RA and fresh martensite. Lath-like RA could significantly improve the toughness and plasticity with slight loss of yield strength, but block RA decreased slightly them.

Amphibian skin secretion is an ideal source of antimicrobial peptides that are difficult to induce drug resistance to due to their membrane-targeting mechanism as a new treatment scheme. In this study, a natural antimicrobial peptide Temporin-1CEh was identified by molecular cloning and mass spectrometry from the skin secretions of the Chinese forest frog (Rana chensinensis). Through the study of the structure and biological activity, it was found that Temporin-1CEh was a helical peptide from the Temporin family, and possessed good anti-Gram-positive bacteria activity through the mechanism of membrane destruction. Seven analogues were further designed to obtain broad-spectrum antimicrobial activity and higher stability in different physiological conditions. The results showed that T1CEh-KKPWW showed potent antibacterial activity with significantly increasing the activity against Gram-negative bacteria in vitro and in vivo with low haemolysis. In addition, T1CEh-KKPWW2 showed high sensitivity to the pH, serum or salts conditions, which applied a branched structure to allow the active units of the peptide to accumulate. Even though the haemolytic activity was increased, the stable antibacterial activity made this novel analogue meet the conditions to become a potential candidate in future antimicrobial and antibiofilm applications.

Background Increasing studies demonstrated that the cardiac involvements are related to coronavirus disease 2019 (COVID‐19). Thus, we investigated the clinical characteristics of patients with COVID‐19 and further determined the risk factors for cardiac involvement in them. Methods and Results We analyzed data from 102 consecutive laboratory‐confirmed and hospitalized patients with COVID‐19 (52 women aged 19–87 years). Epidemiologic and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, chest imaging findings, management methods, and clinical outcomes were collected. Patients were divided into acute cardiac injury, with and without cardiac marker abnormities groups according to different level of cardiac markers. In this research, cardiac involvement was found in 72 of the 102 (70.6%) patients: tachycardia (n=20), electrocardiography abnormalities (n=23), echocardiography abnormalities (n=59), elevated myocardial enzymes (n=55), and acute cardiac injury (n=9). Eight patients with acute cardiac injury were aged >60 years; seven of them had ≥2 underlying comorbidities (hypertension, diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease, and chronic kidney disease). Novel coronavirus pneumonia was much more severe in the patients with acute cardiac injury than in patients with nondefinite acute cardiac injury (P

Background: Despite an increase in the familiarity of the medical community with the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19), there is presently a lack of rapid and effective risk stratification indicators to predict the poor clinical outcomes of COVID-19 especially in severe patients.Methods: In this retrospective single-center study, we included 117 cases confirmed with COVID-19. The clinical, laboratory, and imaging features were collected and analyzed during admission. The Multi-lobular infiltration, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyper-Tension and Age (MuLBSTA) Score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score were used to assess the death and intensive care unit (ICU) risks in all patients.Results: Among of all 117 hospitalized patients, 21 (17.9%) patients were admitted to the ICU care, and 5 (4.3%) patients were died. The median hospital stay was 12 (10–15) days. There were 18 patients with MuLBSTA score ≥ 12 points and were all of severe type. In severe type, ICU care and death patients, the proportion with MuLBSTA ≥ 12 points were greater than that of CURB65 score ≥ 3 points (severe type patients, 50 vs. 27.8%; ICU care, 61.9 vs. 19.0%; death, 100 vs. 40%). For the MuLBSTA score, the ROC curve showed good efficiency of diagnosis death (area under the curve [AUC], 0.956; cutoff value, 12; specificity, 89.5%; sensitivity, 100%) and ICU care (AUC, 0.875; cutoff value, 11; specificity, 91.7%; sensitivity, 71.4%). The K–M survival analysis showed that patients with MuLBSTA score ≥ 12 had higher risk of ICU (log-rank, P = 0.001) and high risk of death (log-rank, P = 0.000).Conclusions: The MuLBSTA score is valuable for risk stratification and could effectively screen high-risk patients at admission. The higher score at admission have higher risk of ICU care and death in patients infected with COVID.

The rapid expansion of Acinetobacter baumannii clinical isolates exhibiting resistance to most or all available antibiotics is a global concern. Current treatments for infections caused by this bacterium have become less effective, and the need to explore new alternative therapies is urgent. Depolymerases derived from phages are emerging as attractive anti-virulence agents. In this study, a previously isolated A. baumannii phage (designated as vB_AbaM_IME285) was characterized, and genomic study was carried out using various bioinformatics tools. A gene predicted as encoding for the depolymerase was cloned and expressed, and the depolymerase activity of the recombinant enzyme (Dp49) was identified both in vitro and in experimental mice. The results showed that phage IME285 formed translucent halos around the plaques when inoculated onto a lawn of the host bacteria, exibiting depolymerase activity against this strain. On the basis of complete genome sequencing and bioinformatics analysis, ORF49 was speculated to be a gene encoding for the putative capsule depolymerase. The expressed recombinant Dp49 displayed an effective depolymerase activity and had a spectrum of activity similar to its parental phage IME285, which was active against 25 out of 49 A. baumannii strains. It was found that Dp49 greatly improved the inhibitory effect of serum on bacterial growth in vitro, and the administration of this enzyme significantly increased the survival rates of A. baumannii-infected mice in the animal experiment. In conclusion, the phage-encoded depolymerase Dp49 might be a promising alternative means of controlling infections mediated by multidrug-resistant A. baumannii.

Chimeric antigen receptor (CAR)-modified natural killer (NK) cell therapy represents a kind of promising anti-cancer treatment because CAR renders NK cells activation and recognition specificity toward tumor cells. An immune checkpoint molecule, B7-H3, plays an inhibitory role in modulation of NK cells. To enhance NK cell functions, we generated NK-92MI cells carrying anti-B7-H3 CAR by lentiviral transduction. The expression of anti-B7-H3 CAR significantly enhanced the cytotoxicity of NK-92MI cells against B7-H3-positive tumor cells. In accordance with enhanced cytotoxicity, the secretions of perforin/granzyme B and expression of CD107a were highly elevated in anti-B7-H3 CAR-NK-92MI cells. Moreover, compared to unmodified NK-92MI cells, anti-B7-H3 CAR-NK-92MI cells effectively limited tumor growth in mouse xenografts of non-small cell lung cancer and significantly prolonged the survival days of mice. This study provides the rationale and feasibility of B7-H3-specific CAR-NK cells for application in adoptive cancer immunotherapy.

Targeting PD-L1 and PD-1 interactions is a relatively new therapeutic strategy used to treat cancer. Inhibitors of PD-1/PD-L1 include peptides, small molecule chemical compounds, and antibodies. Several approved antibodies targeting PD-1 or PD-L1 have been patented with good curative effect in various cancer types in clinical practices. While the current antibody therapy is facing development bottleneck, some companies have tried to develop PD-L1 companion tests to select patients with better diagnosis potential. Meanwhile, many companies have recently synthesized small molecule inhibitors of PD-1/PD-L1 interactions and focused on searching for novel biomarker to predict the efficacy of anti-PD-1/PD-L1 drugs. This review summarized clinical studies and patent applications related to PD-1/PD-L1 targeted therapy and also discussed progress in inhibitors of PD-1/PD-L1.

The aim of this manuscript is to tackle the tracking problem for uncertain semi-Markov systems. More precisely, the mode-dependent event-triggering communication approach is introduced for networked controller design procedure, which can considerably increase the signal transmission efficiency. Based on the Lyapunov–Krasovski method, mode-dependent sufficient conditions are derived and the tracking errors could achieve the asymptotic mean-square stability, and mode-dependent controllers could be further calculated by convex optimization. A numerical simulation with application to vertical take-off and landing helicopter would be performed for verifying the availability and usefulness.

Summary: Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53−/− mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53−/− B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53−/− B cells and reduced stability of L-selectin on Cd53−/− T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53−/− mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.

Tourism is a globalized industry. Health, wellness and medical tourism are recognized as one of the most developed and thriving in the tourism industry. The purpose of this study is to explore the key factors of medical tourism and discuss its relation with tourism attraction and re-visit intention. The results reveal that: (1) The key criteria are doctor’s expertise and reputation, health evaluation, international certified doctors and staffs, the safety of medication quality, quality of medical treatment, high healthcare quality, service orientation of medical staff, advanced medical treatment, availability of medications, on-site pharmacy and prescription assistance, waiting time for medical treatment from time to first contact to real treatment, quality of required treatment, and hospital contact information. (2) The key criteria have a significant positive influence on tourism attraction and re-visit intention. (3) Tourism attraction has no influence on re-visit intention.

Abstract Amphibian venom-derived peptides have high potential in the field of anticancer drug discovery. We have isolated a novel Bowman-Birk proteinase inhibitor (BBI)-type peptide from the skin secretion of Pelophylax esculentus (PE) named PE-BBI, and evaluated its bio-functions and anti-cancer activity in vitro. PE-BBI is a heptadecapeptide with C-terminal amidation. The mRNA sequence and primary structure of PE-BBI were identified using RT-PCR and LC/MS, respectively. A trypsin inhibitory assay was used to characterize the serine proteinase inhibitory activity of synthetic PE-BBI. PE-BBI’s myotropic activity was analyzed using isolated rat bladder and rat-tail artery smooth muscle tissues, and the anti-cancer ability of PE-BBI using human colorectal cancer cells. PE-BBI’s mechanism of action was investigated using Discovery studio software. PE-BBI showed trypsin inhibitory activity (Ki = 310 ± 72 nM), strong myotropic activity, and cytotoxicity that were specific to cancer cells, and no side effect to normal epithelial cells. The docking stimulation showed that PE-BBI had high affinity to several members of human kallikrein related peptidase (KLK) family. This finding helps to enrich our understanding of BBI peptides’ mode of action. Moreover, the data presented here validates frog secretions as sources of potential novel proteinase inhibitors for cancer treatment.

Abstract A flavonoids-rich extract of Scutellaria baicalensis shoots and its eight high content flavonoids were investigated for their inhibitory effects against α-glucosidase and α-amylase. Results show that abilities of the extract in inhibiting the two enzymes were obviously higher than those of acarbose. Moreover, inhibitory abilities of all the eight individual flavonoids against the two enzymes show exactly a same order (i.e., apigenin > baicalein > scutellarin > chrysin > apigenin-7-O-glucuronide > baicalin > chrysin-7-O-glucuronide > isocarthamidin-7-O-glucuronide), and their structure–activity relationship could be well-interpretated by the refined assign-score method. Furthermore, based on the inhibitory abilities and their contents in the extract, it was found that the eight flavonoids made predominant contributions, among which baicalein and scutellarin played roles as preliminary contributors, to overall inhibitory effects of the extract against the two enzymes. Beyond these, contributions of the eight flavonoids to the overall enzyme inhibitory activity were compared with those to the overall antioxidant activity characterized in our recent study, and it could be inferred that within the basic flavonoid structure the hydroxyl on C-4′ of ring B was more effective than that on C-6 of ring A in enzyme inhibitory activities while they behaved inversely in antioxidant activities; scutellarin and apigenin contributed more to the overall enzyme inhibitory activity, and baicalin and scutellarin, to the overall antioxidant activity of the extract; and flavonoids of the extract, apart from directly inhibiting enzymes, might also be conducive to curing type 2 diabetes via scavenging various free radicals caused by increased oxidative stresses.

Investigation of flavonoids-rich extract from Scutellaria baicalensis shoots shows that 15 of the 19 flavonoids detected with UPLC-Q-TOF-MS were identified, and it exhibited high antioxidant abilities with IC50 at 70.81, 35.34 and 33.27 μg/mL in DPPH, ABTS and CAA assays, respectively. An order of antioxidant abilities in scavenging DPPH· and ABTS+· of eight high content flavonoids in the extract was the same, and it could be well-explained by a preliminary assign-score method we created in structure-activity relationship analyses specific for flavonoids, revealing that double bonds and phenolic hydroxyls on rings A and B are augmentors, and sugar moiety is an attenuator influencing antioxidant capacity but might contribute positively in CAA assays. In addition, three of the eight flavonoids (baicalein, baicalin and scutellarin) made contributions of 58.33%, 60.36% and 51.41% to overall antioxidant activity of the flavonoids-rich extract in DPPH, ABTS and CAA assays, respectively, thus were determined as the primary or marker flavonoids of Scutellaria baicalensis shoots.

Venomous reptiles especially serpents are well known for their adverse effects after accidental conflicts with humans. Upon biting humans these serpents transmit arrays of detrimental toxins with diverse physiological activities that may either lead to minor symptoms such as dermatitis and allergic response or highly severe symptoms such as blood coagulation, disseminated intravascular coagulation, tissue injury, and hemorrhage. Other complications like respiratory arrest and necrosis may also occur. Bungarotoxins are a group of closely related neurotoxic proteins derived from the venom of kraits (Bungarus caeruleus) one of the six most poisonous snakes in India whose bite causes respiratory paralysis and mortality without showing any local symptoms. In the current study, by employing various pharmacoinformatic approaches, we have explored the antidote properties of 849 bioactive phytochemicals from 82 medicinal plants which have already shown antidote properties against various venomous toxins. These herbal compounds were taken and pharmacoinformatic approaches such as ADMET, docking and molecular dynamics were employed. The three-dimensional modelling approach provides structural insights on the interaction between bungarotoxin and phytochemicals. In silico simulations proved to be an effective analytical tools to investigate the toxin–ligand interaction, correlating with the affinity of binding. By analyzing the results from the present study, we proposed nine bioactive phytochemical compounds which are, 2-dodecanol, 7-hydroxycadalene, indole-3-(4'-oxo)butyric acid, nerolidol-2, trans-nerolidol, eugenol, benzene propanoic acid, 2-methyl-1-undecanol, germacren-4-ol can be used as antidotes for bungarotoxin. Keywords: Toxins, Bungarotoxin, Molecular docking, Pharmacokinetic profiling, Drug design, Molecular dynamics

Acer truncatum leaves (ATL) have long been used in China as a substitutional tea with health benefits. However, little is known about the antioxidant capacities as well as its bioactive components. The present study was to investigate constitutive phenolic compositions and evaluate antioxidant activities of ATL through its whole growing season. The results showed that all seasonal ATL samples contained remarkable phenols, tannins and flavonoids, and exhibited high antioxidant capacities. Constitutive levels of total phenols, tannins and flavonoids, and three individual phenolic compounds, namely 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), methyl gallate (MG), and quercetin-3-O-l-rhamnoside (QR), and DPPH· and ABTS+· scavenging capacities were all significantly higher in both the beginning (S4) and ending (S11) months than those in the middle months (S5–S10), resulting in a consistent seasonal saddle-shaped pattern. Since S4 and S11 showed significant differences in oxygen radical absorbance capacity (ORAC) values but not in total flavonoids, and there was no significant correlation between ORAC and total flavonoids, it can be inferred that total flavonoids contributed less to the ORAC values than total phenols and tannins did. Correlation analyses further revealed that total phenols, tannins and flavonoids were the main contributors to antioxidant ability, and PGG, MG and QR were found to be the key components of phenols (including tannins and flavonoids) in ATL. Gallic acid was first discovered in ATL, and high levels of PGG and QR (both higher than 1 g/100 g d.w. in April) were corroborated through HPLC analysis. Impressive antioxidant abilities of S4 and S11 were further demonstrated by cellular antioxidant assay, and flavonoids showed stronger antioxidant capacity in the cellular level than other phenolic compositions. In conclusion, seasonal dynamics of constitutive levels of phenolic components lead to alterations of antioxidant capacities in ATL, and November and April were the ideal harvesting time with highest levels of phenols and antioxidant capacity.

Precision glass molding (PGM) technology is a cost-efficient process for the production of micro/nanostructured glass components with complex surface geometries. The stress distribution, surface profile, and reduced refractive index of the molded lens are based on the lens being fully formed. The process of the deformation of the glass preform is rarely discussed, especially in the case of multi-machining parameters in the experiment. The finite element method (FEM) was adopted to analyze the glass preform deformation. Due to the phenomenon of incomplete deformation of the glass preforms in the experiments, two groups of finite element simulations with different boundary conditions were carried out with MSC.Marc software, to reveal the relationship between the deformation progress and the parameters settings. Based on the simulation results, a glass preform deformation model was established. The error between the model result and the simulation result was less than 0.16. The establishment method of the glass preform deformation model and the established model can be used as a reference in efficiently optimizing PGM processing parameters when the designed lens has two different base radii of curvature.

In this paper, the characteristics of water pollution in Yitong River were analyzed by the comprehensive pollution index method. Combined with the pore water concentration gradient method and Fick’s first law, the release characteristics of nutrients at the sediment–water interface of Yitong River (Jilin Province, China) were studied. The results showed that the distribution trend of nitrogen and phosphorus content in the overlying and interstitial water of the Yitong River was the same, and the highest values appeared at the S3 and S5 points in the urban section. The water quality was mainly affected by nitrogen pollutants in domestic sewage. The evaluation results of the water quality comprehensive pollution index showed that the pollution degree of interstitial water in urban areas was much higher than that of the overlying water, and the endogenous nitrogen and phosphorus pollutants had the risk of diffusion to the overlying water. The exchange flux analysis of ammonia nitrogen (NH4+-N), total dissolved nitrogen (TDN), and total dissolved phosphorus (TDP) in water showed that the diffusion flux of NH4+-N ranged from 0.03 to 6.52 mg·(m2·d)−1, and the sediment was the “source” of ammonia nitrogen pollutants. The range of TDN diffusion flux was −1.57 to 11.6 mg·(m2·d) −1, and the difference between points was large. The sediment was both the “source” and “sink” of nitrogen pollutants. The range of TDP diffusion flux was −0.05 to 0.22 mg·(m2·d) −1. Except for point S8, the TDP diffused from sediment into the water body. Among all the sampling points, the diffusion fluxes of NH4+-N, TDN, and TDP at the S3 point were the largest, the release rate of endogenous pollutants was the most rapid, and the pollution to the water quality was the most serious. The results are of great significance to the exchange flux of nutrients at the sediment–water interface of rivers and the prevention and control of water eutrophication. It also provides a reference for the study of nutrient exchange flux at the sediment–water interface of rivers and other surface water bodies worldwide.

As the novel coronavirus SARS-CoV-2 spread around the world, multiple waves of variants emerged, thus leading to local or global population shifts during the pandemic. A new variant named Omicron (PANGO lineage B.1.1.529), which was first discovered in southern Africa, has recently been proposed by the World Health Organization to be a Variant of Concern. This variant carries an unusually large number of mutations, particularly on the spike protein and receptor binding domain, in contrast to other known major variants. Some mutation sites are associated with enhanced viral transmission, infectivity, and pathogenicity, thus enabling the virus to evade the immune protective barrier. Given that the emergence of the Omicron variant was accompanied by a sharp increase in infection cases in South Africa, the variant has the potential to trigger a new global epidemic peak. Therefore, continual attention and a rapid response are required to decrease the possible risks to public health.

Human case studies suggest that Zika virus can be transmitted independently of mosquitoes and sexual contact. Here, the authors show intranasal Zika infection in different animal models and show that contact transmission of Zika virus occurs in guinea pigs.

Micro/nano- BN co-doped epoxy composites were prepared and their thermal conductivity, breakdown strength at power frequency and voltage endurance time under high frequency bipolar square wave voltage were investigated. The thermal conductivity and breakdown performance were enhanced simultaneously in the composite with a loading concentration of 20 wt% BN at a micro/nano proportion of 95/5. The breakdown strength of 132 kV/mm at power frequency, the thermal conductivity of 0.81 W·m−1·K−1 and voltage endurance time of 166 s were obtained in the composites, which were approximately 28%, 286% and 349% higher than that of pristine epoxy resin. It is proposed that thermal conductive pathways are mainly constructed by micro-BN, leading to improved thermal conductivity and voltage endurance time. A model was introduced to illustrate the enhancement of the breakdown strength. The epoxy composites with high thermal conductivity and excellent breakdown performance could be feasible for insulating materials in high-frequency devices.

Lubricating oil monitoring technology is a commonly used method in aeroengine condition monitoring, which includes particle counting technology, as well as spectral and ferrography technology in offline monitoring. However, these technologies only analyze the characteristics of wear particles and rely on physical and chemical analysis techniques to monitor the oil quality. In order to further advance offline monitoring technology, this paper explores the potential role of differences in wear particle kinematic characteristics in recognizing changes in wear particle diameter and oil viscosity. Firstly, a kinematic force analysis of the wear particles in the microfluid was carried out. Accordingly, a microfluidic channel conducive to observing the movement characteristics of particles was designed. Then, the wear particle kinematic analysis system (WKAS) was designed and fabricated. Secondly, a real-time tracking velocity measurement algorithm was developed by using the Gaussian mixture model (GMM) and the blob-tracking algorithm. Lastly, the WKAS was applied to a pin–disc tester, and the experimental results show that there is a corresponding relationship between the velocity of the particles and their diameter and the oil viscosity. Therefore, WKAS provides a new research idea for intelligent aeroengine lubricating oil monitoring technology. Future work is needed to establish a quantitative relationship between wear particle velocity and particle diameter, density, and oil viscosity.

Cancer has always been a threat to human health with its high morbidity and mortality rates. Traditional therapy, including surgery, chemotherapy and radiotherapy, plays a key role in cancer treatment. However, it is not able to prevent tumor recurrence, drug resistance and treatment side effects, which makes it a very attractive challenge to search for new effective and specific anticancer drugs. Nature is a valuable source of multiple pharmaceuticals, and most of the anticancer drugs are natural products or derived from them. Marine-derived compounds, such as nucleotides, proteins, peptides and amides, have also shed light on cancer therapy, and they are receiving a fast-growing interest due to their bioactive properties. Their mechanisms contain anti-angiogenic, anti-proliferative and anti-metastasis activities; cell cycle arrest; and induction of apoptosis. This review provides an overview on the development of marine-derived compounds with anticancer properties, both their applications and mechanisms, and discovered technologies.

Kunitz-like trypsin inhibitors are one of the most noteworthy research objects owing to their significance in pharmacological studies, including anticarcinogenic activity, obesity regulation and anticoagulation. In the current study, a novel Kunitz-like trypsin inhibitor, Kunitzin-AH, was isolated from the skin secretion of Amolops hainanensis. The novel peptide displayed a modest trypsin inhibitory activity with the inhibitor constant (Ki) value of 1.18 ± 0.08 µM without inducing damage to healthy horse erythrocytes. Then, a series of shortened variants of Kunitzin-AH were designed by truncating a peptide loop and site mutation inside the loop to illustrate the structure–activity relationship of the trypsin inhibition function. Among the variants, a significant decrease was observed for the Cys-Cys loop domain, while the extension of an Arg at N-terminus (RCKAAFC) retained the inhibitory activity, indicating that the -RCK-motif is essential in forming the reactive domain for exerting the inhibitory activity. Furthermore, substitutions of Ala by hydrophobic or hydrophilic residues decreased the activity, indicating suitable steric hindrance provides convenience for the combination of trypsin. Additionally, the conformational simulation of the analogues processed with Chimera and Gromacs and further combination simulations between the peptides and trypsin conducted with HDOCK offered a potential opportunity for the natural trypsin inhibitory drug design. The truncated sequence, AH-798, may be a good replacement for the full-length peptide, and can be optimized via cyclization for further study.