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Abstract Background Glutathione S-transferases (GSTs) are a superfamily of multifunctional enzymes in living organisms with metabolic and detoxification functions, which can detoxify exogenous and endogenous compounds and thereby reduce the damage caused by toxic substances to the body. Ticks are obligate blood-sucking ectoparasites that can transmit various pathogens, and the characterization of tick-derived GSTs may help improve current understanding of the molecular mechanism of tick resistance to insecticides. In this study, a novel GST gene, named HrGSTm1, was identified from Hyalomma rufipes. Methods Sequence analysis was performed by using bioinformatics techniques. A prokaryotic expression system was used to obtain the recombinant expression protein rHrGSTm1. Detection of spatiotemporal expression patterns of target genes and their response to the toxicity of cyhalothrin on female H. rufipes was performed by using a quantitative PCR platform. The optimal enzymological parameters of rHrGSTm1 using glutathione as substrate were calculated. The antioxidant capacity of the recombinant protein was evaluated by DPPH• (1,1-Diphenyl-2-picrylhydrazyl radical 2,2-Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl). Knockdown of the HrGSTm1 genes through RNA interference was used to analyze their effects on the physiological parameters of ticks. The changes in HrGSTm1 messenger RNA expression patterns under cypermethrin stress were analyzed. Results The complementary DNA sequence of HrGSTm1 contained a 672-bp open reading frame, which potentially encoded 223 amino acids. The predicted molecular weight was 25.62 kDa, and the isoelectric point 8.22. HrGSTm1 is a Mu-class GST, belonging to the cytoplasmic GSTs with no signal peptide observed. The V max and K m of rHrGSTm1 were 3.367 ± 0.81 uM and 2.208 ± 0.76 uM, respectively, and its activities were dependent on different temperatures and pH conditions; the scavenging rate of rHrGSTm1 to DPPH• reached 76.4% at 1.25 mg/ml. Variable expressions of HrGSTm1 were observed under various treatment periods and in different tissues, with the highest appearing in eggs (analysis of variance [ANOVA], F (2, 9) = 279.9, P

Abstract Background The protein ferritin, which plays an important role in the maintenance of iron homeostasis, is indispensable for iron detoxification, resistance to oxidative stress and innate immunity. Ticks, which are obligate blood-sucking ectoparasites, have to deal with a large amount of iron when they take a blood meal. Methods Sequence analysis was undertaken using bioinformatics. A recombinant (r) expression vector, rferritin, was constructed for a prokaryotic expression system. A quantitative polymerase chain reaction platform was used to detect the spatial and temporal expression patterns of target genes and their responses to a low temperature environment. Knockdown of the ferritin genes through RNA interference was used to analyze their effects on physiological parameters of ticks. Results Two ferritin genes, HrFer1 and HrFer2, were cloned from the tick Hyalomma rufipes. Their open reading frames are 519 base pairs (bp) and 573 bp in length, and number of coding amino acids 170 and 190, respectively. The phylogenetic tree showed that HrFer1 and HrFer2 have a close evolutionary relationship with the H subunit of ferritin. In vitro experiments showed that rHrFer1 and rHrFer2 had concentration-dependent iron chelating activity. The relative expression of the two ferritin genes was higher in the ovary and midgut of H. rufipes. RNA interference results demonstrated that HrFer1 and HrFer2 expression had a significant effect on engorged body weight, number of eggs laid, and mortality of H. rufipes, and that HrFer2 also had a significant effect on feeding duration. Furthermore, the relative expression of ferritin decreased significantly in a low temperature environment, suggesting that HrFer1 and HrFer2 play a regulatory role in the cold stress response of H. rufipes. Conclusions The results of the present study improve our understanding of the involvement of ferritins in tick blood-feeding. Graphical Abstract

Maize gross primary productivity (GPP) contributes the most to the global cropland GPP, making it crucial to accurately estimate maize GPP for the global carbon cycle. Previous research validated machine learning (ML) methods using remote sensing and meteorological data to estimate plant GPP, yet they disregard vegetation physiological dynamics driven by phenology. Leaf nitrogen content per unit leaf area (i.e., specific leaf nitrogen (SLN)) greatly affects photosynthesis. Its maximum allowable value correlates with a phenological factor conceptualized as normalized maize phenology (NMP). This study aims to validate SLN and NMP for maize GPP estimation using four ML methods (random forest (RF), support vector machine (SVM), convolutional neutral network (CNN), and extreme learning machine (ELM)). Inputs consist of vegetation index (NDVI), air temperature, solar radiation (SSR), NMP, and SLN. Data from four American maize flux sites (NE1, NE2, and NE3 sites in Nebraska and RO1 site in Minnesota) were gathered. Using data from three NE sites to validate the effect of SLN and MMP shows that the accuracy of four ML methods notably increased after adding SLN and MMP. Among these methods, RF and SVM achieved the best performance of Nash–Sutcliffe efficiency coefficient (NSE) = 0.9703 and 0.9706, root mean square error (RMSE) = 1.5596 and 1.5509 gC·m−2·d−1, and coefficient of variance (CV) = 0.1508 and 0.1470, respectively. When evaluating the best ML models from three NE sites at the RO1 site, only RF and CNN could effectively incorporate the impact of SLN and NMP. But, in terms of unbiased estimation results, the four ML models were comprehensively enhanced by adding SLN and NMP. Due to their fixed relationship, introducing SLN or NMP alone might be more effective than introducing both simultaneously, considering the data redundancy for methods like CNN and ELM. This study supports the integration of phenology and leaf-level photosynthetic factors in plant GPP estimation via ML methods and provides a reference for similar research.

In this paper, we design a hydrostatic electroactive soft actuator (HESA) inspired by octopus transverse musculature. We introduce the advantage of laser processing technology in HESA fabrication compared with existing similar actuators and discuss the effect of laser processing on the outer membrane of the actuator. In addition, a mathematical model is established for the single channel of the actuator, and the geometric parameters of the actuator are optimized by mathematical model simulation and experiments. We demonstrate the motion effect of the actuator. Our experiments show that the single piece of the actuator can achieve 32.2% strain in the axial direction and 7.8% strain in the radius direction. Furthermore, we stack three actuators together and describe their motion characteristics at different frequencies. The stacked actuators can realize axial elongation, radial shrinkage, and bend, which covers all the motion modes of the octopus biological transverse musculature. This study may lay a foundation for implementing the biomimetic soft actuator mimicking the octopus’s transverse musculature, which is one less discussed but crucial muscular composition in the octopus-inspired arm research.

As obligate blood-feeding ectoparasites, ticks secrete a great diversity of antithrombin molecules during feeding. In this study, a novel antithrombin gene named Doenitin-1 was characterized from the tick Haemaphysalis doenitzi. It has an open reading frame size of 426 bp; it encodes 141 amino acids and has a predicted molecular weight of 15.8 kDa. The fibrinogen coagulation test showed that the time of coagulation was increased significantly with increase in rDoenitin-1 protein concentration, and the activated partial thromboplastin time (APTT) and prothrombin time (PT) assays showed that rDoenitin-1 significantly prolonged the coagulation time of APTT, indicating that rDoenitin-1 has an anticoagulant activity in vitro. In addition, rDoenitin-1 presents a significant inhibitory activity in thrombin and cathepsin G. The hemolysis rate of rDoenitin-1 in healthy human blood cells was 4.25%, and no obvious hemolysis activity was observed. The comparison with other life stages shows that the higher expression occurs in adults, and tissue comparison indicated a higher expression in the midgut. The RNAi results indicated that interference of Doenitin-1 significantly reduced the engorgement rate and egg hatchability of H. doenitzi, and that the engorged body weight was slightly reduced. In conclusion, the results suggested that the novel gene Doenitin-1 functions in blood-feeding of H. doenitzi and performs various functions during feeding and reproduction of H. doenitzi. Doenitin-1 may be a potential vaccine candidate for tick control and for developing new antithrombotic drugs in the future.

A multi-frequency patch antenna with double-sided parallel-strip line (DSPSL) periodic offset structure is proposed. The designed antenna consists of a simple rectangular patch as well as an embedded one-dimensional DSPSL periodic offset structure, which is employed to replace the traditional rectangular microstrip patch antenna. The periodic DSPSL structure is characterized leaky wave structure. After the periodic DSPSL structure is embedded, the resonance frequency of rectangular patch is offset, and the leaky wave characteristics can determine the number and position of new operating frequencies. As an application, a tri-band antenna is manufactured and these three operating frequencies can be calculated by the derived formulas studied in this communication. Experiment results suggest that the antenna can work at 4.28, 4.78, and 6.42 GHz, respectively. The results of simulated, measured and calculated show high consistency.

For the false data injection attack (FDIA) in the consensus-based distributed estimation, the information of weight matrix is critical for both attackers and defenders. In this paper, we study the impact of the weight matrix on the FDIA and the attack mitigation techniques. We first propose a learning-based cooperative FDIA strategy, where malicious nodes acquire the information of weight matrix cooperatively and launch the attack covertly. Two types of FDIA, the sudden FDIA and the dynamic FDIA, are considered to tamper the consensus result of the network to a pre-designed false value. Moreover, using the obtained information of weight matrix, a real-time surveillance and response mechanism is constructed to enhance the covertness of FDIA strategy. Since the surveillance and response mechanism can bypass existing FDIA detection methods, we further investigate the attack mitigation techniques against the learning-based cooperative FDIA. A real-time FDIA detection method and a reassessment mechanism with a punishment scheme are presented to resist the surveillance and response mechanism in the learning-based cooperative FDIA. Comprehensive simulation results verify that the attacker can obtain the information of weight matrix, and tamper the consensus result to a false value by launching the learning-based cooperative FDIA. And the real-time FDIA detection method can detect the malicious nodes efficiently and promptly.

Tick saliva, an essential chemical secretion of the tick salivary gland, is indispensable for tick survival owing to the physiological influence it exerts on the host defence mechanisms via the instrumentality of its cocktail of pharmacologically active molecules (proteins and peptides). Much research about tick salivary proteome has been performed, but how most of the individual salivary proteins are utilized by ticks to facilitate blood acquisition and pathogen transmission is not yet fully understood. In addition, the phosphorylation of some proteins plays a decisive role in their function. However, due to the low phosphorylation level of protein, especially for a small amount of protein, it is more difficult to study phosphorylation. Maybe, for this reason, the scarcity of works on the phosphorylated tick salivary proteomes still abound. Here, we performed a phosphoproteomic analysis of Haemaphysalis longicornis tick saliva via TiO2 enrichment and the most advanced Thermo Fisher Orbitrap Exploris 480 mass spectrometer for identification. A total of 262 phosphorylated tick saliva proteins were identified and were subjected to functional annotation/enrichment analysis. Cellular and metabolic process terms accounted for the largest proportion of the saliva proteins, with the participation of these proteins in vital intracellular and extracellular transport-oriented processes such as vesicle-mediated transport, exocytic process, cell adhesion, and movement of cell/subcellular component. “Endocytosis”, “Protein processing in endoplasmic reticulum”, and “Purine metabolism” were the most significantly enriched pathways. The knockdown (RNAi) of Tudor domain-containing protein (TCP), actin-depolymerizing factors (ADF), programmed cell death protein (PD), and serine/threonine-protein kinase (SPK) resulted in the dissociation of collagen fibers and the pilosebaceous unit, increased inflammatory infiltrates/granulocytes (possibly heterophiles), and the depletion of the epithelium. Ticks injected with SPK dsRNA engorged normally but with a change in skin colour (possibly an autoimmune reaction) and the failure to produce eggs pointing to a possible role of SPK in reproduction and host immune modulation. Ticks injected with ADF dsRNA failed to acquire blood, underscoring the role of ADF in facilitating tick feeding. The results of this study showed the presence of phosphorylation in tick saliva and highlight the roles of salivary phosphoproteins in facilitating tick feeding.

Recently, chemodynamic therapy (CDT) has represented a new approach for cancer treatment with low toxicity and side effects. Nonetheless, it has been a challenge to improve the therapeutic effect through increasing the amount of reactive oxygen species (ROS). Herein, we increased the amount of ROS agents in the Fenton-like reaction by loading dihydroartemisinin (DHA) which was an artemisinin (ART) derivative containing peroxide groups, into magnetic nanoparticles (MNP), thereby improving the therapeutic effect of CDT. Blank MNP were almost non-cytotoxic, whereas three MNP loading ART-based drugs, MNP-ART, MNP-DHA, and MNP-artesunate (MNP-AS), all showed significant killing effect on breast cancer cells (MCF-7 cells), in which MNP-DHA were the most potent. What’s more, the MNP-DHA showed high toxicity to drug-resistant breast cancer cells (MCF-7/ADR cells), demonstrating its ability to overcome multidrug resistance (MDR). The study revealed that MNP could produce ferrous ions under the acidic condition of tumor microenvironment, which catalyzed DHA to produce large amounts of ROS, leading to cell death. Further experiments also showed that the MNP-DHA had significant inhibitory effect on another two aggressive breast cancer cell lines (MDA-MB-231 and MDA-MB-453 cells), which indicated that the great potential of MNP-DHA for the treatment of intractable breast cancers.

A backward to forward scanning periodic microstrip leaky wave antenna (MLWA) is presented. The proposed antenna consists of a long rectangular patch with alternating shorting pin on each side, which connects the antenna patch and the ground plane to form periodic shorting circuits. There are two pairs of slots alternately spaced on the long patch to suppress the open stop band (OSB). The OSB problem was initially reduced by optimizing the structural parameters, and the slotting on the patch further improved it. The measured radiation pattern in the y-z plane shows that the antenna can scan electronically from 142° to 39° toward the end-fire (+z direction) when the operating frequency changes from 6 GHz to 12.9 GHz. The measured gain is greater than 5 dBi over the entire operating band.

Distributed estimation and tracking of interested objects over wireless sensor networks (WSNs) is a hot research topic. Since network topology possesses distinctive structural parameters and plays an important role for the performance of distributed estimation, we first formulate the communication overhead reduction problem in distributed estimation algorithms as the network topology optimization in this paper. The effect of structural parameters on the algebraic connectivity of a network is overviewed. Moreover, aiming to reduce the communication overhead in Kalman consensus filter (KCF)-based distributed estimation algorithm, we propose a network topology optimization method by properly deleting and adding communication links according to nodes’ local structural parameters information, in which the constraint on the communication range of two nodes is incorporated. Simulation results show that the proposed network topology optimization method can effectively improve the convergence rate of KCF algorithm and achieve a good trade-off between the estimate error and communication overhead.

Abstract Neck pain due to cervical facet joint pain has a prevalence of 36–60% in chronic neck pain. Pulsed radiofrequency for such pain has been verified. After proper patient selection, pulsed radiofrequency of the cervical facet joints provide long-term pain relief in a routine clinical setting. In the patient selection, clinical and sagittal alignment parameters are rarely discussed for the outcome. In the present study, we analyzed the factors from the clinical data and sagittal alignment parameters and investigated the associated predictors of pulsed radiofrequency for cervical facet joint pain. There were 204 patients with cervical facet joint pain who received a medial branch block and pulsed radiofrequency between 2015 and 2020 after excluding patients with neurological symptoms and other confounding factors. The patients were classified into good and poor outcome groups based on the improvement of the pain score(visual analog scale). Clinical and radiological data were analyzed. Multivariable logistic model showed that the predictors were cervical lordosis including two methods (odds ratio [OR] 0.92, 95% confidence interval [CI]: 0.89–0.96 for C2–C7 Cobb angle; OR 0.91, 95% CI: 0.88–0.95 for the angle measured by the Jackson method), ossification of the nuchal ligament, number of diseased facet joints, anterior cervical discectomy with fusion, and adjacent facet joint after anterior cervical discectomy with fusion. With the results, we demonstrated that the outcome were related to cervical lordosis including two methods, formation of ossification of nuchal ligament, the number of diseased facet joints, post anterior cervical discectomy with fusion, and adjacent facet joint post anterior cervical discectomy with fusion. The corresponding optimal cutoff for discriminating a poor outcome was 7° for the C2–C7 Cobb angle and − 2° for the angle measured using the Jackson method.

Abstract The effects of anonymity on utilization review has never been examined in the real world. This study aimed to evaluate the impact of removing anonymity protection for claims reviewers on their review decisions. Using a single-blinded repeated measures design, we randomly selected 1457 claims cases (with 12,237 orders) that had been anonymously reviewed and reimbursed in 2016 and had them re-reviewed in a signed review program in 2017 under the Taiwanese National Health Insurance scheme. The signed review policy significantly decreased the likelihood of a deduction decision at the case and the order level (P

The incidence and prevalence of inflammatory bowel disease have been increasing for decades and IBD has become a worldwide disease. Epidemiology studies demonstrated higher incidence rates in the more westernized countries. The change of habitual diets in these countries is perceived as the reason for the development of IBD. Besides, molecular biological studies showed some pathogenic substances produced after digestion of daily diet decrease the diversity of intestinal microbiota and cause dysbiosis of microbiome. Then, chronic inflammation occurs in some genetically susceptible subjects and IBD developed. As a result, many researchers started to investigate the potential therapeutic effects of nutrients and dietary intervention on the clinical course and pathogenesis of IBD. Carbohydrates, fats, proteins and fibers are investigated and their molecular roles in the inflammatory process are discovered gradually. The undigested carbohydrates are proved to cause overgrowth of colonic bacteria and inflammation occurs by altering colonic microbiome. ω-3 poly-unsaturated fatty acids are more favored over ω-6 poly-unsaturated fatty acids due to its less pro-inflammatory properties. High fibers produce more short-chain fatty acids in colon and facilitate the diversity of colonic microbiota. Moreover, some dietary interventions were designed and studied with promising results. Low FODMAP is recommended in IBS and is also suggested in patients of IBD with IBS-like symptoms. Specific Carbohydrate Diet was designed for celiac disease at first and is proved to be effective to decrease inflammation and to induce remission by decreasing non-digested carbohydrates into colon. Exclusive Enteral Nutrition has been investigated and is suggested to be the first line of management in pediatric CD in many literatures. Paleolithic diet and semi-vegetarian diet are evaluated and might be beneficial in some clinical settings. These findings are promising but limited to the evidence without high quality level. Some more well-designed studies with randomization and double-blind are needed and the primary endpoints should be more focused on the decrease of inflammation in pathology and mucosal healing in endoscopy instead of relief of the symptoms.

Abstract Background Developing a universal strategy to improve the specificity and sensitivity of PEGylated nanoaparticles (PEG-NPs) for assisting in the diagnosis of tumors is important in multimodality imaging. Here, we developed the anti-methoxypolyethylene glycol (mPEG) bispecific antibody (BsAb; mPEG × HER2), which has dual specificity for mPEG and human epidermal growth factor receptor 2 (HER2), with a diverse array of PEG-NPs to confer nanoparticles with HER2 specificity and stronger intensity. Result We used a one-step formulation to rapidly modify the nanoprobes with mPEG × HER2 and optimized the modified ratio of BsAbs on several PEG-NPs (Lipo-DiR, SPIO, Qdot and AuNP). The αHER2/PEG-NPs could specifically target MCF7/HER2 cells (HER2++) but not MCF7/neo1 cells (HER2+/−). The αHER2/Lipo-DiR and αHER2/SPIO could enhance the sensitivity of untargeted PEG-NPs on MCF7/HER2 (HER2++). In in vivo imaging, αHER2/Lipo-DiR and αHER2/SPIO increased the specific targeting and enhanced PEG-NPs accumulation at 175% and 187% on 24 h, respectively, in HER2-overexpressing tumors. Conclusion mPEG × HER2, therefore, provided a simple one-step formulation to confer HER2-specific targeting and enhanced sensitivity and contrast intensity on HER2 positive tumors for multimodality imaging.

BackgroundAging-related hypogonadism in men is related to the deterioration of overall health. Those with this disease rarely receive treatment. The hypertriglyceridemic waist (HTGW) phenotype is a tool for predicting abnormalities of cardiovascular metabolism. However, the relationship between the HTGW phenotype and hypogonadism remains undetermined. This study aimed to determine the association between HTGW phenotype and hypogonadism in different age groups.MethodsData of this cross-sectional study were obtained from MJ Health Screening Center in Taiwan from 2007 to 2016. The HTGW phenotype was divided into four categories based on whether the waist circumference (WC) and triglyceride levels were normal. WC of ResultsOverall, 6442 male participants were divided into three age groups: ConclusionHTGW phenotype was highly associated with hypogonadism in Taiwanese adult men. More attention should be paid to men aged

Esophageal cancer has a dismal prognosis with a five-year survival rate below 20%. Recently, immunotherapy has become a new standard of care for this cancer; therefore, we aimed to examine the programmed death ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) tissues before and after concurrent chemoradiation therapy (CCRT). In total, 64 patients with pre-CCRT ESCC specimens were examined for PD-L1 expression, with twenty-three of them having a partial response (N = 23) or stable disease (N = 1) after CCRT while post-CCRT tissue specimens were collected. All of them were tested for PD-L1 and 15 of them also had CD8 expression in the paired ESCC samples. The prevalence of PD-L1 positivity was 54.7% and we found a trend of decreased PD-L1 expression and increased CD8 positive signal after CCRT. High pre-CCRT PD-L1 H-score in tumors was related to poor prognosis (adjusted hazard ratio = 2.81; p = 0.02), although CD8 signal was not associated with overall survival either in pre- or post-CCRT treatment. In conclusion, we found that PD-L1 expression tended to decrease in CCRT responders and our result supports PD-L1 expression in tumor as a predictor of ESCC prognosis.

Oceanic currents, biological traits, and geological evidence from historical climate change have shaped the distribution of genetic diversity and demographic history in Macrobrachium japonicum. In this study, we investigated the phylogeographic structures and demographic history of M. japonicum in Taiwan and the Ryukyu Islands by the partial mitochondrial COI gene. The topology of the haplotype minimum-spanning network revealed a star-like structure, which suggested a recent range expansion. With the apparent lack of strong dispersal barriers to gene flow between ocean basins, amphidromous prawns, as marine organisms with larvae of high dispersal abilities, are generally expected to show genetic homogeneity. Divergence data suggested that M. japonicum populations diverged 0.462 ± 0.164 myr. Complex patterns of asymmetrical gene flow indicate that variation in dispersal ability is affected by the dominant Kuroshio Current systems of the Pacific Ocean. Analysis of its demographic history revealed that M. japonicum underwent a decline in size following a recent population expansion based on ABC analysis. Bayesian skyline plot analyses of all populations indicated that the expansion of M. japonicum was estimated to have occurred in 175 Kya and that the effective population size rapidly increased by approximately 50 Kya. The results of this study may offer both practical and theoretical value for the further study of conservation genetics, management, and sustainable resource utilization.

Mechanism of copper nanostructuring by oxides and hydroxide formation during anodizing is not fully understood. At the same time, the search for novel copper anodizing regimes and electrolytes is ongoing due to multiple potential applications. In this work copper anodizing in two electrode setups, in stirred 0.01 M solution of NaHCO3 at 20 °C and at voltages ranging from 5 to 40 V was explored. The morphology and composition of prepared materials were studied using FE-SEM imaging and XRD measurements. Anodizing at potentials in a range of 15–30 V led to formation of nanowires composed of crystalline Cu2O, CuO, Cu(OH)2 and malachite Cu2CO₃(OH)2. The latter was formed due to anion incorporation from the electrolyte. The diameter of nanowires strongly depended on the applied voltage, and was 35 ± 6 nm for samples prepared at 15 V, and 45 ± 9 nm for 30 V. At higher applied voltages oscillations of current density were observed, suggesting partial delamination of the formed oxidized layer, with subsequent self-healing.