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In recent years, there has been a growing interest in changes in dynamic mechanical properties of mixed rubber during dynamic shear, yet the influence of vulcanized characteristics on the dynamic shear behavior of vulcanized rubber, particularly the effect of cross-linking density, has received little attention. This study focuses on styrene-butadiene rubber (SBR) and aims to investigate the impact of different cross-linking densities ( D c ) on dynamic shear behavior using molecular dynamics (MD) simulations. The results reveal a remarkable Payne effect, where the storage modulus experiences a significant drop when the strain amplitude (γ 0 ) exceeds 0.1, which can be attributed to the fracture of the polymer bond and the decrease in the molecular chain's flexibility. The influence of various D c values mainly resides at the level of molecular aggregation in the system, where higher D c values impede molecular chain motion and lead to an increase in the storage modulus of SBR. The MD simulation results are verified through comparisons with existing literature.

In the study, a new gene homologous to the known antimicrobial peptide Scygonadin was identified in mud crab Scylla paramamosain and named SCY3 . The full-length sequences of cDNA and genomic DNA were determined. Similar to Scygonadin , SCY3 was dominantly expressed in the ejaculatory ducts of male crab and the spermatheca of post-mating females at mating. The mRNA expression was significantly up-regulated after stimulation by Vibrio alginolyticus , but not by Staphylococcus aureus . The recombinant protein rSCY3 had a killing effect on Micrococcus luteus and could improve the survival rate of mud crabs infected with V. alginolyticus . Further analysis showed that rSCY3 interacted with rSCY1 or rSCY2 using Surface Plasmon Resonance (SPR, a technology for detecting interactions between biomolecules using biosensor chips) and Mammalian Two-Hybrid (M2H, a way of detecting interactions between proteins in vivo). Moreover, the rSCY3 could significantly improve the sperm acrosome reaction (AR) of S. paramamosain and the results demonstrated that the binding of rSCY3, rSCY4, and rSCY5 to progesterone was a potential factor affecting the sperm AR by SCYs on. This study lays the foundation for further investigation on the molecular mechanism of SCYs involved in both immunity and physiological effects of S. paramamosain .

New antimicrobial agents are urgently needed to address the increasing emergence and dissemination of multidrug-resistant bacteria. In the study, a chemically synthesized truncated peptide containing 22-amino acids derived from a C-type lectin homolog SpCTL6 of Scylla paramamosain was screened and found to exhibit broad-spectrum antimicrobial activity, indicating that it is an antimicrobial peptide (AMP), named Sp-LECin. Sp-LECin possessed the basic characteristics of most cationic AMPs, such as positive charge (+4) and a relatively high hydrophobicity (45%). After treatment with Sp-LECin, the disruption of microbial membrane integrity and even leakage of cellular contents was observed by scanning electron microscopy (SEM). In addition, Sp-LECin could bind lipopolysaccharide (LPS), increase the outer and inner membrane permeability and induce reactive oxygen species (ROS) production, ultimately leading to the death of Pseudomonas aeruginosa . Furthermore, Sp-LECin exhibited potent anti-biofilm activity against P. aeruginosa during both biofilm formation and maturation. Notably, Sp-LECin had no obvious cytotoxicity and could greatly improve the survival of P. aeruginosa -infected zebrafish, by approximately 40% over the control group after 72 h of treatment. This study indicated that Sp-LECin is a promising antibacterial agent with the potential to be used against devastating global pathogen infections such as P. aeruginosa.

The abuse of antibiotics leads to the increase of bacterial resistance, which seriously threatens human health. Therefore, there is an urgent need to find effective alternatives to antibiotics, and antimicrobial peptides (AMPs) are the most promising antibacterial agents and have received extensive attention. In this study, a novel potential AMP was identified from the marine invertebrate Scylla paramamosain and named Spampcin. After bioinformatics analysis and AMP database prediction, four truncated peptides (Spa31, Spa22, Spa20 and Spa14) derived from Spampcin were screened, all of which showed potent antimicrobial activity with different antibacterial spectrum. Among them, Spampcin 56-86 (Spa31 for short) exhibited strong bactericidal activity against a variety of clinical pathogens and could rapidly kill the tested bacteria within minutes. Further analysis of the antibacterial mechanism revealed that Spa31 disrupted the integrity of the bacterial membrane (as confirmed by scanning electron microscopy observation, NPN, and PI staining assays), leading to bacterial rupture, leakage of cellular contents (such as elevated extracellular ATP), increased ROS production, and ultimately cell death. Furthermore, Spa31 was found to interact with LPS and effectively inhibit bacterial biofilms. The antibacterial activity of Spa31 had good thermal stability, certain ion tolerance, and no obvious cytotoxicity. It is worth noting that Spa31 could significantly improve the survival rate of zebrafish Danio rerio infected with Pseudomonas aeruginosa , indicating that Spa31 played an important role in anti-infection in vivo. This study will enrich the database of marine animal AMPs and provide theoretical reference and scientific basis for the application of marine AMPs in medical fields.

Hepcidin is widely present in many kinds of fish and is an important innate immune factor. A variety of HAMP2-type hepcidins have strong antimicrobial activity and immunomodulatory functions and are expected to be developed as substitutes for antibiotics. In this study, the antimicrobial activity of Hepc2 from Japanese seabass ( Lateolabrax japonicus ) (designated as LJ-hep2) was investigated using its recombinant precursor protein (rLJ-hep2) expressed in Pichia pastoris and a chemically synthesized mature peptide (LJ-hep2 (66-86) ). The results showed that both rLJ-hep2 and synthetic LJ-hep2 (66-86) displayed broad antimicrobial spectrum with potent activity against gram-negative and gram-positive bacteria, and fungi. Especially, LJ-hep2 (66-86) had stronger antimicrobial activity and exhibited potent activity against several clinically isolated multidrug-resistant bacteria, including Acinetobacter baumannii , Escherichia coli , Pseudomonas aeruginosa , Klebsiella pneumoniae and Enterococcus faecium . Moreover, LJ-hep2 (66-86) exerted rapid bactericidal kinetic (killed tested bacteria within 2 h), induced significant morphological changes and promoted agglutination of E. coli , P. aeruginosa and Aeromonas hydrophila . The activity of LJ-hep2 (66-86) against E. coli , P. aeruginosa and A. hydrophila was stable and remained active when heated for 30 min. In addition, LJ-hep2 (66-86) exhibited no cytotoxicity to the mammalian cell line HEK293T and fish cell lines (EPC and ZF4). In vivo study showed that LJ-hep2 (66-86) could improve the survival rate of marine medaka ( Oryzias melastigma ) by about 40% under the challenge of A. hydrophila , indicating its immunoprotective function. Taken together, both rLJ-hep2 and LJ-hep2 (66-86) have good prospects to be used as potential antimicrobial agents in aquaculture and medicine in the future.

Objective: Blood pressure (BP) data can influence therapeutic decisions for some patients, while non-invasive devices that continuously monitor BP can provide patients with a more comprehensive BP assessment. Therefore, this study proposes a multi-sensor-based small cuffless BP monitoring device that integrates a piezoelectric sensor array and an optical sensor, which can monitor the patient's physiological signals from the radial artery., Method: Based on the Moens-Korteweg (MK) equation of the hemodynamic model, pulse wave velocity (PWV) can be correlated with arterial compliance and BP can be estimated. Therefore, the novel method proposed in this study involves using a piezoelectric sensor array to measure the PWV and an optical sensor to measure the photoplethysmography (PPG) intensity ratio (PIR) signal to estimate the participant's arterial parameters. The parameters measured by multiple sensors were combined to estimate BP based on the P-β model derived from the MK equation., Result: We recruited 20 participants for the BP monitoring experiment to compare the performance of the BP estimation method with the regression model and the P-β model method with arterial compliance. We then compared the estimated BP with a reference device for validation. The results are presented as the error mean ± standard deviation (SD). Based on the regression model method, systolic blood pressure (SBP) was 0.32 ± 5.94, diastolic blood pressure (DBP) was 2.17 ± 6.22, and mean arterial pressure (MAP) was 1.55 ± 5.83. The results of the P-β model method were as follows: SBP was 0.75 ± 3.9, DBP was 1.1 ± 3.12, and MAP was 0.49 ± 2.82., Conclusion: According to the results of our proposed small cuffless BP monitoring device, both methods of estimating BP conform to ANSI/AAMI/ISO 81060-2:20181_5.2.4.1.2 criterion 1 and 2, and using arterial parameters to calibrate the MK equation model can improve BP estimate accuracy. In the future, our proposed device can provide patients with a convenient and comfortable BP monitoring solution. Since the device is small, it can be used in a public place without attracting other people's attention, thereby effectively improving the patient's right to privacy, and increasing their willingness to use it.

The lung cancer threat has become a critical issue for public health. Research has been devoted to its clinical study but only a few studies have addressed the issue from a holistic perspective that included social, economic, and environmental dimensions. Therefore, in this study, risk factors or features, such as air pollution, tobacco use, socioeconomic status, employment status, marital status, and environment, were comprehensively considered when constructing a predictive model. These risk factors were analyzed and selected using stepwise regression and the variance inflation factor to eliminate the possibility of multicollinearity. To build efficient and informative prediction models of lung cancer incidence rates, several machine learning algorithms with cross-validation were adopted, namely, linear regression, support vector regression, random forest, K-nearest neighbor, and cubist model tree. A case study in Taiwan showed that the cubist model tree with feature selection was the best model with an RMSE of 3.310 and an R-squared of 0.960. Through these predictive models, we also found that apart from smoking, the average NO 2 concentration, employment percentage, and number of factories were also important factors that had significant impacts on the incidence of lung cancer. In addition, the random forest model without feature selection and with feature selection could support the interpretation of the most contributing variables. The predictive model proposed in the present study can help to precisely analyze and estimate lung cancer incidence rates so that effective preventative measures can be developed. Furthermore, the risk factors involved in the predictive model can help with the future analysis of lung cancer incidence rates from a holistic perspective.

Scyreprocin is an antimicrobial peptide first identified in the mud crab Scylla paramamosain . Herein, we showed that its recombinant product (rScyreprocin) could significantly inhibit the growth of human lung cancer NCI-H460 cells (H460), but showed no cytotoxicity to human lung fibroblasts (HFL1). rScyreprocin was a membrane-active peptide that firstly induced the generation of reactive oxygen species (ROS) in H460, and led to endoplasmic reticulum stress and Ca 2+ release, which resulted in mitochondrial dysfunction and subsequently activation of caspase-3 cascades, and ultimately led to apoptosis. The comprehensive results indicated that rScyreprocin exerted anticancer activity by disrupting cell membrane and inducing apoptosis. The in vivo efficacy test demonstrated that intratumoral injection of rScyreprocin significantly inhibited the growth of H460 xenografts, which was close to that of the cisplatin (inhibition rate: 69.94% vs. 80.76%). Therefore, rScyreprocin is expected to become a promising candidate for the treatment of lung cancer.

Antimicrobial peptides (AMPs) identified in the reproductive system of animals have been widely studied for their antimicrobial activity, but only a few studies have focused on their physiological roles. Our previous studies have revealed the in vitro antimicrobial activity of two male gonadal AMPs, SCY2 and scyreprocin, from mud crab Scylla paramamosain. Their physiological functions, however, remain a mystery. In this study, the two AMPs were found co-localized on the sperm apical cap. Meanwhile, progesterone was confirmed to induce acrosome reaction (AR) of mud crab sperm in vitro, which intrigued us to explore the roles of the AMPs and progesterone in AR. Results showed that the specific antibody blockade of scyreprocin inhibited the progesterone-induced AR without affecting intracellular Ca 2+ homeostasis, while the blockade of SCY2 hindered the influx of Ca 2+ . We further showed that SCY2 could directly bind to Ca 2+ . Moreover, progesterone failed to induce AR when either scyreprocin or SCY2 function was deprived. Taken together, scyreprocin and SCY2 played a dual role in reproductive immunity and sperm AR. To our knowledge, this is the first report on the direct involvement of AMPs in sperm AR, which would expand the current understanding of the roles of AMPs in reproduction.

The abuse of antibiotics in aquaculture and livestock no doubt has exacerbated the increase in antibiotic-resistant bacteria, which imposes serious threats to animal and human health. The exploration of substitutes for antibiotics from marine animals has become a promising area of research, and antimicrobial peptides (AMPs) are worth investigating and considering as potential alternatives to antibiotics. In the study, we identified a novel AMP gene from the mud crab Scylla paramamosain and named it Sparanegtin. Sparanegtin transcripts were most abundant in the testis of male crabs and significantly expressed with the challenge of lipopolysaccharide (LPS) or Vibrio alginolyticus . The recombinant Sparanegtin (rSparanegtin) was expressed in Escherichia coli and purified. rSparanegtin exhibited activity against Gram-positive and Gram-negative bacteria and had potent binding affinity with several polysaccharides. In addition, rSparanegtin exerted damaging activity on the cell walls and surfaces of P. aeruginosa with rougher and fragmented appearance. Interestingly, although rSparanegtin did not show activity against V. alginolyticus in vitro, it played an immunoprotective role in S. paramamosain and exerted an immunomodulatory effect by modulating several immune-related genes against V. alginolyticus infection through significantly reducing the bacterial load in the gills and hepatopancreas and increasing the survival rate of crabs.

Previous studies have found that the non-invasive blood pressure measurement method based on the oscillometric method is inaccurate when an arrhythmia occurs. Therefore, we propose a high-sensitivity pulse sensor that can measure the hemodynamic characteristics of the pulse wave and then estimate the blood pressure. When an arrhythmia occurs, the hemodynamics of the pulse wave are abnormal and change the morphology of the pulse wave. Our proposed sensor can measure the occurrence of ectopic beats from the radial artery, and the detection algorithm can reduce the error of blood pressure estimation caused by the distortion of ectopic beats that occurs when the pulse wave is measured. In this study, we tested patients with premature atrial contraction (PAC) or premature ventricular contraction (PVC) and analyzed the morphology of the pulse waves when the sensor detected the ectopic beats. We discuss the advantages of using the Moens-Korteweg equation to estimate the blood pressure of patients with arrhythmia, which is different from the oscillometric method. Our research provides a possible arrhythmia detection method for wearable devices and can accurately estimate blood pressure in a non-invasive way during an arrhythmia.

Pubertal molt is a vital stage in the cultivation of mature female crabs in the aquacultural industry of Scylla paramamosain . Since fasting occurs during molting, which requires a large supply of energy, internal energy reserves are critical. However, the dynamics of energy supply during pubertal molt is not clear. This study focuses on the variations of carbohydrates and lipids in serum during the pubertal molt of S. paramamosain via a metabolomics approach. Eleven lipid or carbohydrate metabolic pathways were significantly influenced postmolt. A remarkable decrease in carbohydrates in serum suggested that free sugars were consumed for energy. A significant decrease in glucose and alpha-d-glucosamine 1-phosphate showed that chitin synthesis exhausted glycogen, resulting in insufficient glucose supply. An increase in l-carnitine and acetylcarnitine, and a significant decrease in 15 fatty acyls and 8 glycerophosphocholines in serum indicated that carnitine shuttle was stimulated, and β-oxidation was upregulated postmolt. In addition, astaxanthin, ponasterone A, and riboflavin in serum were significantly decreased postmolt. Eleven potential metabolite biomarkers were identified for pubertal molt. Taken together, carbohydrates and lipids were possibly major energy reserves in pubertal molt. This study suggests that an increase in carbohydrate and lipid levels in crab feed may alleviate the effects of fasting during molt and improve farm productivity in mature female crabs.

An ultrasonic examination is a clinically universal and safe examination method, and with the development of telemedicine and precision medicine, the robotic ultrasound system (RUS) integrated with a robotic arm and ultrasound imaging system receives increasing attention. As the RUS requires precision and reproducibility, it is important to monitor the real-time calibration of the RUS during examination, especially the angle of the probe for image detection and its force on the surface. Additionally, to speed up the integration of the RUS and the current medical ultrasound system (US), the current RUSs mostly use a self-designed fixture to connect the probe to the arm. If the fixture has inconsistencies, it may cause an operating error. In order to improve its resilience, this study proposed an improved sensing method for real-time force and angle calibration. Based on multichannel pressure sensors, an inertial measurement unit (IMU), and a novel sensing structure, the ultrasonic probe and robotic arm could be simply and rapidly combined, which rendered real-time force and angle calibration at a low cost. The experimental results show that the average success rate of the downforce position identification achieved was 88.2%. The phantom experiment indicated that the method could assist the RUS in the real-time calibration of both force and angle during an examination.

Background: Most stroke cases lead to serious mental and physical disabilities, such as dementia and sensory impairment. Chronic diseases are contributory risk factors for stroke. However, few studies considered the transition behaviors of stroke to dementia associated with chronic diseases and environmental risks., Objective: This study aims to develop a prognosis model to address the issue of stroke transitioning to dementia associated with environmental risks., Design: This cohort study used the data from the National Health Insurance Research Database in Taiwan., Setting: Healthcare data were obtained from more than 25 million enrollees and covered over 99% of Taiwan's entire population., Participants: In this study, 10,627 stroke patients diagnosed from 2000 to 2010 in Taiwan were surveyed., Methods: A Cox regression model and corresponding semi-Markov process were constructed to evaluate the influence of risk factors on stroke, corresponding dementia, and their transition behaviors., Main Outcome Measure: Relative risk and sojourn time were the main outcome measure., Results: Multivariate analysis showed that certain environmental risks, medication, and rehabilitation factors highly influenced the transition of stroke from a chronic disease to dementia. This study also highlighted the high-risk populations of stroke patients against the environmental risk factors; the males below 65 years old were the most sensitive population., Conclusion: Experiments showed that the proposed semi-Markovian model outperformed other benchmark diagnosis algorithms (i.e., linear regression, decision tree, random forest, and support vector machine), with a high R 2 of 90%. The proposed model also facilitated an accurate prognosis on the transition time of stroke from chronic diseases to dementias against environmental risks and rehabilitation factors.

Decision tree (DT) analysis was applied in this cross-sectional study to investigate caries experience in children by using clinical and microbiological data obtained from parent-child pairs. Thirty pairs of parents and children were recruited from periodontal and pediatric dental clinics. All participants were clinically examined for caries and periodontitis by a calibrated examiner. Cariogenic and periodontopathic bacteria examinations were conducted. The Kendall rank correlation coefficient was used to measure the association between data variables obtained through clinical and microbiological examinations. A classificatory inductive decision tree was generated using the C4.5 algorithm with the top-down approach. The C4.5 DT analysis was applied to classify major influential factors for children dental caries experience. The DT identified parents' periodontal health classification, decayed, missing, filled permanent teeth (DMFT) index, periodontopathic test (PerioCheck) result, and periodontal pocket depth as the classification factors for children caries experience. 13.3% of children were identified with a low decayed, missing, filled primary teeth (dmft) index (dmft < 3) whose parents had a periodontal pocket depth ≤3.7, PerioCheck score >1, DMFT index <13.5, and periodontal classification >2. The DT model for this study sample had an accuracy of 93.33%. Here, parental periodontal status and parents' DMFT were the factors forming the DT for children's caries experience., Competing Interests: The authors declare no conflict of interest.

Two pairs of diastereoisomeric acetylenic norlignan compounds with PhCH(OR(1))CH(OR(2))CH(2)C triple bond CPh skeleta: (1R, 2R)-1-O-methylnyasicoside (1) and (1S, 2R)-1-O-methylnyasicoside (2), and (1R, 2R)-crassifogenin D (3) and (1S, 2R)- crassifogenin D (4), were isolated from the ethanolic extract of rhizomes of Curculigo crassifolia. Compounds 3 and 4 are new and their structures were elucidated on the basis of spectroscopic evidence and comparisons with literature data.