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Abstract Background The widespread of telehealth has not only improved medical service accessibility and convenience, and has also played an active role in the COVID-19 Epidemic. This suggests that telehealth is becoming increasingly important in both normality and emergency. It is therefore essential to evaluate the use of the technology and its impact on the healthcare system. Objective This paper studied the use of telehealth in China, the socio-demographic characteristics of users, its impact on patients’ choice of first-visit, and potential health inequalities. Methods We obtained 14,944 valid questionnaires from a multistage stratified sample of 41 cities in the Yangtze River Delta, China, and multinomial logit was mainly used. Results The utilization rate of telehealth in the study area was 10.43%. Residents that were younger, more educated, had higher household incomes, were more health literate, used more adequate medical insurance, ordered food delivery more often, and had chronic diseases were more likely to use telehealth. Residents who used telehealth had significantly higher odds of choosing high-level hospital instead of primary care provider as their first visit (B = 0.168, P

Abstract Temporomandibular disorders (TMD) intelligent diagnosis promises to elevate clinical efficiency and facilitate timely TMD management for patients. However, development of TMD intelligent diagnostic tools with high accuracy and sensitivity presents challenges, particularly in sensing minute deformations and ensuring rapid self-recovery. Here we report a biocompatible hydrogel electronic sensor with instantaneous self-recovery (within 2.1 s) and ultra-low detection limit (0.005% strain). It could efficiently diagnose disc displacement with reduction (DDwR) with satisfactory accuracy of 90.00%, and also had a clear indication of the typical clinical manifestations of DDwR and the timing of temporomandibular joint (TMJ) clicking, with a sensitivity of up to 100% in human compared to the diagnostic criteria for TMD (DC/TMD). Furthermore, a predictive model based on waveform features achieved 84.4% accuracy and 86% sensitivity, reducing dependence on physicians. In summary, the hydrogel sensor is expected to become a radiation-free, non-invasive, practical and effective tool for future TMD diagnosis.

Abstract The autophagy pathway regulates the degradation of misfolded proteins caused by heat stress (HS) in the cytoplasm, thereby maintaining cellular homeostasis. Although previous studies have established that autophagy (ATG) genes are transcriptionally upregulated in response to HS, the precise regulation of ATG proteins at the subcellular level remains poorly understood. In this study, we provide compelling evidence for the translocation of key autophagy components, including the ATG1/ATG13 kinase complex (ATG1a, ATG13a), PI3K complex (ATG6, VPS34), and ATG8-PE system (ATG5), to HS-induced stress granules (SGs) in Arabidopsis thaliana. As HS subsides, SGs disassemble, leading to the re-translocation of ATG proteins back to the cytoplasm, thereby facilitating the rapid activation of autophagy to degrade HS-induced ubiquitinated aggregates. Notably, autophagy activation is delayed in the SG-deficient (ubp1abc) mutants during the HS recovery phase, resulting in an insufficient clearance of ubiquitinated insoluble proteins that arise due to HS. Collectively, this study uncovers a previously unknown function of SGs in regulating autophagy as a temporary repository for ATG proteins under HS and provides valuable insights into the cellular mechanisms that maintain protein homeostasis during stress.

The effect of combined induction by Cu(II) and veratrole on the degradation of high molecular weight polyaromatic hydrocarbons (HMW-PAHs) by Fusarium sp. ZH-H2 was investigated. This strain was characterized as F. dlaminii. The combination treatment of Cu(II) with veratrole (CL) improved the degradation efficiency of a mixture of 10 HMW-PAHs by 16 % compared to the control without inducer (CK), by 5 % compared to single Cu(II) induction (C), and by 12 % compared to single veratrole induction (L). In particular, degradation of benzo(g,hi)perylene (BghiP) was improved by 36 % compared to CK and by 52 % compared to L. The CL combination treatment increased lignin peroxidase (LiP) activity by 162 % at day 5 of incubation compared to the control and by 277 % compared to C. Transcriptome analysis revealed that the expression of 910 Fusarium genes had changed as a result of the combination treatment, with 510 up-regulated genes and 443 down-regulated genes. The combined CL treatment not only significantly stimulated Lip activity, but also induced the expression of genes coding for non-ligninolytic enzymes, which contributed to the degradation of PAHs. These included cytochrome P450 monooxygenase (EC:1.–.-.-) and downstream PAH converting enzymes such as aldehyde dehydrogenase (EC:1.2.1.3), NADP-dependent ethanol dehydrogenase (EC:1.1.1.2), ethanol dehydrogenase (EC:1.1.1.156], tryptophan 2,3 dioxygenase (EC:1.13.11.52), gentisate 1,2-dioxygenase (EC:1.13.11.5), salicylate hydroxylase (EC:.14.13.1) β-hexokinase (EC:3.2.1.52), and glutathione transferase (EC: 2.5.1.18). Their increased expression enhanced the HMWPAHs degradation under induction of Cu(II) plus veratrole synergistically. These findings provide new insights in the combined use of these inducers for enhanced microbial remediation of HMW-PAHs in the environment.

Among all natural and synthetic toxins, botulinum neurotoxins (BoNTs), produced by Clostridium botulinum in an anaerobic environment, are the most toxic polymer proteins. Currently, the most effective modalities for botulism prevention and treatment are vaccination and antitoxin use, respectively. However, these modalities are associated with long response time for active immunization, side effects, and donor limitations. As such, the development of more promising botulism prevention and treatment modalities is warranted. Here, we designed an mRNA encoding B9-hFc – a heavy-chain antibody fused to VHH and human Fc that can neutralize BoNT serotype B (BoNT/B) effectively – and assessed its expression in vitro and in vivo. The results confirmed that our mRNA demonstrates good expression in vitro and in vivo. Moreover, a single mRNA lipid nanoparticle injection effectively prevents BoNT/B intoxication in vivo, with effects comparable to those of protein antibodies. In conclusion, we explored and clarified whether mRNA drugs encoding neutralizing antibodies prevent BoNT/B intoxication. Our results provide an efficient strategy for further research on the prevention and treatment of intoxication by botulinum toxin.

Tetanus toxin (TeNT) is one of the most toxic proteins. Neutralizing antibodies against TeNT are effective in prevention and treatment. In this study, 14 anti-tetanus nanobodies were obtained from a phage display nanobody library by immunizing a camel with the C-terminal receptor-binding domain of TeNT (TeNT-Hc) as the antigen. After fusion with the human Fc fragment, 11 chimeric heavy-chain antibodies demonstrated nanomolar binding toward TeNT-Hc. The results of toxin neutralization experiments showed that T83–7, T83–8, and T83–13 completely protected mice against 20 × the median lethal dose (LD50) at a low concentration. The neutralizing potency of T83–7, T83–8, and T83–13 against TeNT is 0.4 IU/mg, 0.4 IU/mg and 0.2 IU/mg, respectively. In the prophylactic setting, we found that 5 mg/kg of T83–13 provided the mice with full protection from tetanus, even when they were injected 14 days before exposure to 20 × LD50 TeNT. T83–7 and T83–8 were less effective, being fully protective only when challenged 7 or 10 days before exposure, respectively. In the therapeutic setting, 12 h after exposure to TeNT, 1 ~ 5 mg/kg of T83–7, and T83–8 could provide complete protection for mice against 5 × LD50 TeNT, while 1 mg/kg T83–13 could provide complete protection 24 h after exposure to 5 × LD50 TeNT. Our results suggested that these antibodies represent prophylactic and therapeutic activities against TeNT in a mouse model. The T83–7, T83–8, and T83–13 could form the basis for the subsequent development of drugs to treat TeNT toxicity.

Cracking is an important factor affecting the durability of concrete. Rheological properties are important performance indicators of the workability of fresh concrete. Ion chelator (CA) is one kind of crystalline admixture, which can enhance crack-healing of concrete by promoting the formation of calcium carbonate in wet environment. Calcium alginate hydrogel (CaAlg) can maintain the humidity of cementitious matrix and promote the crystallization of inorganic minerals. Therefore, in this study, CaAlg bead was prepared to further improve the crack-healing of cementitious materials containing CA. Self-healing performance was evaluated by visual crack closure and water permeability test. Rheological property was measured by rotor rheometer. Healing mechanism of cementitious materials with CA and CaAlg was analyzed. Results showed that with the increase of CaAlg dosage, yield stress and plastic viscosity of paste decreased gradually. Meanwhile, fly ash and slag reduced viscosity of pastes, while silica fume increased the viscosity of pastes. CA could evidently improve the permeability and mechanical properties of mortar, especially for slag mortar. Self-healing performance test and characterization showed that CaAlg could further enhance crack-healing process of mortar with CA, especially for pure cement and slag mortar. Microscopic testing indicates that CaAlg could induce the formation of vaterite and calcite on its surface to further improve crack-healing efficiency.

At present, the error calibration of electricity meters in operation generally adopts an off-site method; that is, the electricity meter is taken out of operation and then calibrated in the laboratory. Off-site calibration, while beneficial, may not fully capture the operational error of the electricity meter due to potential differences in environmental conditions. An on-site calibration device for electricity meters based on pulse detection is designed, which obtains the error of the electricity meter under calibration by comparing the energy pulses of the standard electricity meter with those of the electricity meter under calibration. High-precision voltage and current sampling channels are designed, with a voltage measurement error of less than 0.02% and a current measurement error of less than 0.03%. In response to the non-synchronous sampling problem caused by frequency fluctuations in the on-site verification environment, a fast optimal frequency estimation algorithm is applied to accurately calculate the signal frequency within two cycles. The sampling time interval is adjusted to achieve lock-frequency synchronous sampling, and ensure the accurate calculation of electrical parameters. In order to reduce the complexity of the device circuit structure and equipment cost, a standard electric energy pulses generation method based on digital integration-to-frequency is proposed, which uses software to generate electric energy pulses, with a maximum output frequency of up to 10 kHz. Tests conducted in the laboratory on the developed on-site calibration device for electricity meters show that its accuracy is better than the 0.05 accuracy class, meeting the application requirements for on-site verification of electricity energy meters.

Background: Photodynamic therapy is garnering increasing attention in oral science. Despite its promising potential, further exploration is warranted to delve into the research paradigms and evolving trends within oral science. Therefore, this study aimed to conduct a comprehensive bibliometric analysis of photodynamic therapy in oral science (PDTOS), investigating research landscapes, identifying key contributors, analyzing collaborative networks, pinpointing emerging research directions, and exploring factors influencing high citations. Methods: Research and review articles in PDTOS were retrieved from the Web of Science Core Collection database up to December 31, 2023. The R package ''bibliometrix'' and VOSviewer were utilized for visualizing collaboration networks and keyword co-occurrence, alongside trend analysis. Negative binomial regression was used to model factors affecting citation counts. Results: A total of 2784 articles with significant international collaboration (23.14 %) were analyzed. Brazil, China, the USA, Iran, and Italy led in publications, with predominant USA-European collaborations. The University of Sao Paulo in Brazil was the most published institution in the field. Photodiagnosis and Photodynamic Therapy was the core journal in the field and has the highest number of publications. The main research fields included photodynamic therapy, antibacterial and anticancer treatment, management, and peri‑implant periodontitis, with a recent focus on peri‑implantitis. Factors such as international cooperation, funding, article age, type, author count, and references significantly influenced citations. Conclusions: This research provided valuable insights into PDTOS trends and knowledge structures. These findings underscored a significant increase in the number of PDTOS publications, urging strengthened international cooperation. Emerging research has focused on peri‑implantitis and nano-photosensitizer materials. Authors should consider various citation-related factors in their research endeavors.

The Junín virus (JUNV) is one of the New World arenaviruses that cause severe hemorrhagic fever. Human transferrin receptor 1 (hTfR1) has been identified as the main receptor for JUNV for virus entry into host cells. To date, no treatment has been approved for JUNV. Herein, we investigated 12 anti-hTfR1 VHH (variable domain of the heavy chain of heavy-chain antibody) antibodies and confirmed their interaction with hTfR1. Most of them could bind to the hTfR1 apical domain, which is the glycoprotein 1 (GP1) binding domain of JUNV. Among them, 18N18 exhibited neutralizing activity against both the human immunodeficiency virus (HIV)-vectored lentiviral Junín pseudoviruses and the recombinant vesicular stomatitis virus (VSV)-vectored Junín pseudoviruses. We also verified that 18N18 blocked the interaction between hTfR1 and JUNV GP1. In addition, 18N18 could neutralize another New World arenavirus, the Machupo virus. Using AlphaFold 3-based simulation of 18N18–hTfR1 docking, we determined that 18N18’s binding epitope was located at the JUNV GP1 binding epitope. 18N18 represents a candidate for JUNV treatment and provides a potential approach that could be applied to New World arenaviruses.

Thise study investigated the effect of three lignocellulolytic thermophilic Bacillus strains (F11, Q1, and FP4) on lignocellulose degradation, enzymatic activities, and microbial community structure in composting. The lignin degradation rate reached 36% in the presence of the inoculant, the hemicellulose degradation rate ranged from 43% (F11) to 51% (Q1), and cellulose degradation rates reached 57% in F11 and in FP4, which were significantly higher than the control (CK). The inoculation treatment could explain 28% of the lignin degradation for all three strains. The contribution of FP4 to hemicellulose and cellulose degradation was 30% and 20%, respectively. Compared to CK, lignin peroxidase activity in the water extract of the compost had increased by 66~145% for inoculation treatments, and manganese peroxidase and laccase activity increased by 114% and 78% for Q1. The inoculation stimulated the growth of indigenous bacteria with stronger lignocellulolytic enzyme-producing ability; such shifts in microbial communities were most likely responsible for the improved lignocellulose degradation.

Abstract Botulinum neurotoxin (BoNT) shows high lethality and toxicity, marking it as an important biological threat. The only effective post-exposure therapy is botulinum antitoxin; however, such products have great potential for improvement. To prevent or treat BoNT, monoclonal antibodies (mAbs) are promising agents. Herein, we aimed to construct a bispecific antibody (termed LUZ-A1-A3) based on the anti-BoNT/A human monoclonal antibodies (HMAb) A1 and A3. LUZ-A1-A3 binds to the Hc and L-HN domains of BoNT/A, displaying potent neutralization activity against BoNT/A (124 × higher than that of HMAb A1 or HMAb A3 alone and 15 × higher than that of the A1 + A3 combination). LUZ-A1-A3 provided effective protection against BoNT/A in an in vivo mouse model. Mice were protected from infection with 500 × LD50 of BoNT/A by LUZ-A1-A3 from up to 7 days before intraperitoneal administration of BoNT/A. We also demonstrated the effective therapeutic capacity of LUZ-A1-A3 against BoNT/A in a mouse model. LUZ-A1-A3 (5 μg/mouse) neutralized 20 × LD50 of BoNT/A at 3 h after intraperitoneal BoNT/A administration and complete neutralized 20 × LD50 of BoNT/A at 0.5 h after intraperitoneal BoNT/A administration. Thus, LUZ-A1-A3 is a promising agent for the pre-exposure prophylaxis and post-exposure treatment of BoNT/A.

Abstract Background Contrast-enhanced ultrasound (CEUS) has been recently used for the assessment of cervical lymph node metastasis (LNM) to guide surgical operation in patients with papillary thyroid carcinoma (PTC). However, the specificity and sensitivity of CEUS reported from previous studies are not consistent. The objective of this study was to evaluate the diagnostic value of CEUS for the metastasis of cervical lymph nodes in PTC patients based on data from one regional central hospital. Methods The diagnostic value of CEUS in preoperative LNM of PTC patients was concluded by comparing the results of CEUS on lymph node status with postoperative pathology examination. In addition, this study conducted hierarchical analysis of PTC patients to explore whether tumor size, different lymph node regions, and Hashimoto’s thyroiditis influence the assessment of CEUS. Results This research study ultimately enrolled 965 PTC patients, including 266 males and 699 females with a mean age of 42.27 ± 11.34 years. A total of 527 patients were considered clinical-node negative, and 438 were clinical-node positive before surgery. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS in the assessment of LNM in PTC patients were 56.00%, 71.00%, 57.06%, 69.76% and 62.59%, respectively. For central and lateral lymph nodes, the accuracy of CEUS in PTC patients was 49.43% and 54.30%, respectively. In addition, it was shown that the accuracy of CEUS in PTC patients with Hashimoto’s thyroiditis (HT) slightly decreased to 58.44%, and the accuracy of CEUS in PTC patients with non-HT in turn increased to 64.17%. The accuracy of CEUS in non-papillary thyroid microcarcinoma (PTMC) and PTMC patients was 65.68% and 61.24%, respectively. The accuracy of CEUS in predicting central LNM was significantly different between PTC patients with or without HT (P

IntroductionArbuscular mycorrhizal fungi (AMF) and dark septate endophytic fungi (DSEs) generally coexist in the roots of plants. However, our understanding of the effects of their coexistence on plant growth and stress resistance is limited.MethodsIn the present study, the effects of single and dual inoculation of AMF and DSE on the growth, photosynthetic physiology, glutathione (GSH) metabolism, endogenous hormones, and cadmium (Cd) content of maize under 25 mg•kg-1 Cd stress were investigated.ResultsCompared with that after the non-inoculation treatment, AMF+DSE co-inoculation significantly increased the photosynthetic rate (Pn) of maize leaves; promoted root GSH metabolism; increased the root GSH concentration and activity of γ-glutamyl cysteine synthase (γ-GCS), ATP sulfatase (ATPS) and sulfite reductase (SIR) by 215%, 117%, 50%, and 36%, respectively; and increased the concentration of endogenous hormones in roots, with increases in zeatin (ZR), indole-3 acetic acid (IAA), and abscisic acid (ABA) by 81%, 209%, and 72%, respectively. AMF inoculation, DSE inoculation and AMF+DSE co-inoculation significantly increased maize biomass, and single inoculation with AMF or DSE increased the Cd concentration in roots by 104% or 120%, respectively. Moreover, significant or highly significant positive correlations were observed between the contents of ZR, IAA, and ABA and the activities of γ-GCS, ATPS, and SIR and the glutathione (GSH) content. There were significant or highly significant positive interactions between AMF and DSE on the Pn of leaves, root GSH metabolism, and endogenous hormone contents according to two-way analysis of variance. Therefore, the coexistence of AMF and DSE synergistically enhanced the Cd tolerance of maize.

Goupi plaster, a representative preparation of black plaster, has demonstrated promising effects in treating knee osteoarthritis. However, high temperature used in traditional frying extraction may cause decomposition of its effective components, thus limiting the efficacy. This study aimed to explore the scientific nature of the traditional preparation technology of Goupi plaster, and to compare the effects of different extraction methods on the types of chemical components and the content of index components. The UPLC-Q-Exactive-MS and UPLC-MS/MS technologies which have high efficiency, sensitivity and accuracy, were used to qualitatively and quantitatively analyze the chemical components of Goupi plaster under different preparation processes. The results show that the extraction solvent approach is different from the traditional frying extraction method, and has a positive effect. However, the mechanism of action of Goupi plaster is complex and its pharmacological effects are diverse. Future studies should explore whether it necessary to change the frying extraction method. This experiment provides a theoretical basis that will guide further scientific discussion and research into the frying extraction of Goupi plaster.

BackgroundBotulinum neurotoxin (BoNT) produced by Clostridium botulinum is one of the most potent known toxins. Moreover, BoNT is classified as one of the most important biological warfare agents that threatens the biosafety of the world. Currently, the approved treatment for botulism in humans is the use of polyvalent horse serum antitoxins. However, they are greatly limited because of insufficient supply and adverse reactions. Thus, treatment of human botulism requires the development of effective toxin-neutralizing antibodies. Considering their advantages, neutralizing nanobodies will play an increasing role as BoNTs therapeutics.MethodsHerein, neutralizing nanobodies binding to the heavy chain (Hc) domain of BoNT/B (BHc) were screened from a phage display library. Then, BoNT/B-specific clones were identified and fused with the human Fc fragment (hFc) to form chimeric heavy chain antibodies. Finally, the affinity, specificity, and neutralizing activity of antibodies against BoNT/B in vivo were evaluated.ResultsThe B5-hFc, B9-hFc and B12-hFc antibodies demonstrated high affinity for BHc in the nanomolar range. The three antibodies were proven to have potent neutralizing activity against BoNT/B in vivo.ConclusionThe results demonstrate that inhibiting toxin binding to the host receptor is an efficient strategy and the three antibodies could be used as candidates for the further development of drugs to prevent and treat botulism.

Community-supported agriculture (CSA) has emerged as a pivotal model for sustainable and humanistic agricultural practices, emphasizing the symbiotic relationship between food production, consumption, and sustainable ecosystems. Despite the growing interest, a comprehensive analysis of research themes and trends within the CSA framework remains sparse. This paper undertakes a systematic review of CSA literature from 1999 to 2023, identifying evolving research hotspots, dominant themes, and prospective directions by keyword analysis to corroborate Maslow’s hierarchy of needs theory. The research analysis location is categorized into four temporal phases, revealing a geographical expansion from North America to encompass Asia, Africa, and other continents. This expansion corroborates Maslow’s theory, illustrating a global shift from fulfilling basic physiological needs towards recognizing sustainable practices, particularly in developing regions. The results of temporal trends (5 phases) and the hotspots of keyword analysis support each other by showing a societal shift from basic sustenance to a deeper understanding of nutrition and diet. Most of the recent research keywords are grouped into the “environment” and “health and education” categories, indicating an increasing emphasis on transforming the food system and nutrition education. This review suggests conducting an integrated analysis that links the various stages of the food supply chain with the criteria outlined in the Sustainable Agriculture Matrix (SAM). It highlights that the “environment” theme is a stage of building up esteem and self-realization that needs to be unfolded in the future, given that most research on community-supported agriculture (CSA) focuses on the “economy and society” aspect and consumption stage, which burnish self-morality in the theory of Maslow. Overall, this review proposes an analysis of the relevance among different subject categories and between food supply chain stages, which reveals that the trend of research under CSA development is accorded to the theory of Maslow’s hierarchy of needs and calls for a more holistic approach to agricultural research that considers ecological, health, and social imperatives.

The eigenvalue bounds of interval matrices are often required in some mechanical and engineering fields. In this paper, we improve the theoretical results presented in a previous paper “A property of eigenvalue bounds for a class of symmetric tridiagonal interval matrices” and provide a fast algorithm to find the upper and lower bounds of the interval eigenvalues of a class of symmetric tridiagonal interval matrices.

The erect leaf plays a crucial role in determining plant architecture, with its growth and development regulated by genetic factors. However, there has been a lack of comprehensive studies on the regulatory mechanisms governing wheat lamina joint development, thus failing to meet current breeding demands. In this study, a wheat erect leaf mutant, mths29, induced via fast neutron mutagenesis, was utilized for QTL fine mapping and investigation of lamina joint development. Genetic analysis of segregating populations derived from mths29 and Jimai22 revealed that the erect leaf trait was controlled by a dominant single gene. Using BSR sequencing and map-based cloning techniques, the QTL responsible for the erect leaf trait was mapped to a 1.03 Mb physical region on chromosome 5A. Transcriptome analysis highlighted differential expression of genes associated with cell division and proliferation, as well as several crucial transcription factors and kinases implicated in lamina joint development, particularly in the boundary cells of the preligule zone in mths29. These findings establish a solid foundation for understanding lamina joint development and hold promise for potential improvements in wheat plant architecture.

BackgroundCentral lymph node metastases (CLNM) in papillary thyroid microcarcinoma (PTMC) are common, but management through prophylactic central lymph node dissection (pCLND) remains controversial. In this study, the independent predictors of CLNM in PTMC were retrospectively studied based on ultrasound and pathological data, and we aim to establish the prediction model to predict CLNM in PTMC.MethodsThis study included a total of 1,506 patients who underwent thyroid surgery for PTMC at the First Affiliated Hospital of Chongqing Medical University from 2015 to 2018. Ultrasound and clinicopathological features were summarized and analyzed. Univariate and multivariate analyses were performed to determine the risk factors associated with CLNM. The prediction model is established and verified according to the multivariate analysis results. The Kaplan–Meier curve was used to evaluate the effect of CLNM on survival.ResultsThe CLNM rate was 44.5% (670/1,506). Multivariate analysis showed that men, younger age, smaller diameter, ETE, microcalcification, without Hashimoto’s thyroiditis, and multifocal were independent risk predictors of CLNM. Nomogram has a good discriminative ability (C-index: 0.755 in the validation group), and the calibration effect is good. In the DCA curve, the CLNM prediction model performed better net benefit given any high-risk thresholds. The median follow-up time was 30 months (12–59 months), 116 cases were lost, and the follow-up rate was 92.8% (1,506/1,622). Of the 1,506 patients included, 12 (0.8%) experienced recurrence.ConclusionThe likelihood of CLNM can be objectively quantified before surgery by using this reliable and accurate nomogram that combines preoperative ultrasound with clinicopathological features. Clinicians can use this nomogram to assess central lymph node status in patients with PTMC and consider prophylactic CND in patients with high scores.

Background: Moxibustion, a traditional Chinese medicine approach, stimulates blood circulation by burning wormwood at acupuncture points and is frequently used in conjunction with acupuncture for managing knee osteoarthritis. This review aims to compare the effectiveness of moxibustion and acupuncture in the management of knee osteoarthritis. Methods: Our team conducted a comprehensive search across several databases: PubMed Central, EMBASE, MEDLINE, the Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and the Cochrane Library, covering the timeframe from January 1964 up until April 2022. We implemented a meta-analysis, utilizing a random-effects model, and we've presented the pooled standardized mean difference (SMD) and risk ratio (RR) inclusive of the 95% confidence intervals (CIs), in accordance with the nature of the outcome. Results: 21 studies were included, of which, half were identified as having high risk of bias. The pooled SMD for the pain score was found to be −0.53 (95% CI: −0.91 to −0.15). In-depth analysis focusing on the kind of moxibustion indicated that fire needle moxibustion was more effective in pain reduction (SMD = −0.56; 95% CI: −1.10 to −0.01) compared to alternative moxibustion methods (SMD = −0.47; 95% CI: −0.80 to −0.13). The pooled RR for the success rate in treatment was 1.39 (95% CI: 1.19 to 1.62). Subgroup analysis demonstrated that fire needle moxibustion reported a superior success rate (RR = 1.43; 95% CI: 1.19 to 1.72) in comparison to other types of moxibustion (RR = 1.33; 95% CI: 1.02 to 1.74). Conclusion: Moxibustion, specifically fire needle moxibustion, demonstrated superior effectiveness in managing knee osteoarthritis compared to acupuncture.

Lactobacillus casei HDS-01, isolated from spent brine from sauerkraut, was added to construct a microbial ecosystem for sauerkraut fermentation. High performance liquid chromatography (HPLC), acid-base titration, high-throughput sequencing and real-time quantitative PCR were adopted in combination with traditional enzymatic analysis to investigate the dynamic changes of physicochemical properties and bacterial communities during sauerkraut fermentation. Meanwile, sensory quality and safety of the sauerkraut were evaluated. Results showed that the pH of fermented sauerkraut with L. casei HDS-01 decreased to 3.15±0.08 on the third day and the lactic acid bacteria count was (7.63±0.19) lg CFU/mL at the beginning of fermentation. The key enzyme activities of the lactic acid metabolic pathway were higher in all periods of L. casei HDS-01 fermented sauerkraut than in natural fermented sauerkraut (P

BackgroundHuman adenovirus type 55 (HAdV55) has a re-emerged as pathogen causing an acute respiratory disease presenting as a severe lower respiratory illness that can cause death. To date, there is no HAdV55 vaccine or treatment available for general use.MethodsHerein, a monoclonal antibody specific for HAdV55, mAb 9-8, was isolated from an scFv-phage display library derived from mice immunized with the purified inactived-HAdV55 virions. By using ELISA and a virus micro-neutralization assay, we evaluated the binding and neutralizing activity of mAb 9-8 following humanization. Western blotting analysis and antigen-antibody molecular docking analysis were used to identify the antigenic epitopes that the humanized monoclonal antibody 9-8-h2 recognized. After that, their thermal stability was determined.ResultsMAb 9-8 showed potent neutralization activity against HAdV55. After humanization, the humanized neutralizing monoclonal antibody (9-8-h2) was identified to neutralize HAdV55 infection with an IC50 of 0.6050 nM. The mAb 9-8-h2 recognized HAdV55 and HAdV7 virus particles, but not HAdV4 particles. Although mAb 9-8-h2 could recognize HAdV7, it could not neutralize HAdV7. Furthermore, mAb 9-8-h2 recognized a conformational neutralization epitope of the fiber protein and the crucial amino acid residues (Arg 288, Asp 157, and Asn 200) were identified. MAb 9-8-h2 also showed favorable general physicochemical properties, including good thermostability and pH stability.ConclusionsOverall, mAb 9-8-h2 might be a promising molecule for the prevention and treatment of HAdV55.

High-molecular-weight PAHs (HMW-PAHs) in soil cannot be easily degraded. However, nutrient supplementation could stimulate the growth of exogenously added strains to enhance the degradation of HMW-PAHs in polluted soil. This study evaluated the applicability of Fusarium sp. ZH-H2, a polycyclic aromatic hydrocarbon (PAH)-degrading strain isolated by our research group, for the bioremediation of contaminated soil from the Hebei coal mining area in China. A soil incubation experiment was conducted to investigate the effect of two carbon sources and different carbon, nitrogen, and phosphorus (C:N:P) ratios on the remediation of high-molecular-weight PAHs (HMW-PAHs) in soil by Fusarium sp. ZH-H2, as well as the induction of lignin peroxidase activity. Our findings indicated that the HDF2 treatment (equal parts of humic acid and starch as carbon sources at a 50:1:0.5 C:N:P ratio) enhanced the removal rate of total HMW-PAHs from soil, reaching a maximum removal rate of 37.15 %. The removal rates of Pyr (a 4-ring PAH), BaP (a 5-ring PAH), and BghiP (a 6-ring PAH) were the highest in HDF2 treatment, and the removal rates were 39.51 %, 54.63 %, and 38.60 %, respectively. Compared with the ZH-H2 treatment, different carbon sources and C:N:P ratios significantly induced soil lignin peroxidase activity and the HDF2 treatment also resulted in the highest enzyme activity (up to 34.68 U/L). Furthermore, there was a significant or highly significant linear positive correlation between the removal rate of HMW-PAHs and enzyme activity in all cases. Our findings suggest that the optimal HMW-PAH degradation performance and enhancement of lignin peroxidase activity by ZH-H2 were achieved when both starch and humic acid were used as carbon sources at a C:N:P ratio of 50:1:0.5.

Abstract This paper is concerned with the problem of fault tolerant control for non‐linear systems with sensor faults based on the T‐S fuzzy model approach. First, a fault estimation (FE) observer with L∞ technique is designed to estimate the fault. Second, by using the fault estimation information, which are provided by the fault estimation observer, a novel fault tolerant control scheme with a fault compensation mechanism in the premise part of the fuzzy controller is presented to compensate the effect of the fault and stabilize the system. Different from the existing methods, where the fault compensation mechanism is only established in the consequent part of the controller, in the presented method, the fault compensation mechanism is established in the consequent part as well as the premise part of the fuzzy controller. Then, by using the fault compensation mechanism, the bound of the deviation between the normalized membership functions of the fuzzy model and those of the controller can be reduced such that the fault tolerant control design can be relaxed. In the end, an example is given to illustrate the validity of the developed fault tolerant control scheme.

In a previous study our group identified Bacillus sp. strain M1 as an efficient decomposer of high molecular weight-polycyclic aromatic hydrocarbons (HMW-PAHs). Interestingly, its removal efficiency for benzo[a]pyrene (BaP) was nearly double that of pyrene (Pyr), which was the reverse of what is reported for most other species. Here we compared the differential steps of biosorption, transmembrane transport and biodegradation of Pyr and BaP by strain M1 in order to assist in targeted selection of dominant strains and their degradation efficiency in the remediation of these two HMW-PAHs. The overall biosorption efficiency for BaP was 19% higher than that for Pyr, and the time needed to reach BaP peak adsorption efficiency was 4 days shorter than for Pyr. Transmembrane transport of the PAHs was compared in presence of sodium azide which inhibits ATP synthesis and metabolism. This indicated that both Pyr and BaP entered the cells by the same means of passive transport. Biodegradation of Pyr and BaP did not differ in the early stage of culture, but around days 5–7, the biodegradation efficiency of BaP was significantly (30–61%) higher than that of Pyr. Key enzymes involved in these processes were identified and their activity differed, with intracellular gentisate 1,2-dioxygenase and extracellular polyphenol oxidase as likely candidates to be involved in BaP degradation, while intracellular catechol-1,2- dioxygenase and salicylate hydroxylase are more likely involved in Pyr degradation. These results provide new insights for sustainable environmental remediation of pyrene and benzo(a)pyrene by these bacteria.

Background: The interaction of gas and liquid can produce many interesting phenomena, such as bubbles rising from the bottom of the liquid. The simulation of two-phase fluids is a challenging topic in computer graphics. To animate the interaction of a gas and liquid, MultiFLIP samples the two types of particles, and a Euler grid is used to track the interface of the liquid and gas. However, MultiFLIP uses the fluid implicit particle (FLIP) method to interpolate the velocities of particles into the Euler grid, which suffer from additional noise and instability. Methods: To solve the problem caused by fluid implicit particles (FLIP), we present a novel velocity transport technique for two individual particles based on the affine particle-in-cell (APIC) method. First, we design a weighed coupling method for interpolating the velocities of liquid and gas particles to the Euler grid such that we can apply the APIC method to the simulation of a two-phase fluid. Second, we introduce a narrowband method to our system because MultiFLIP is a time-consuming approach owing to the large number of particles. Results: Experiments show that our method is well integrated with the APIC method and provides a visually credible two-phase fluid animation. Conclusions: The proposed method can successfully handle the simulation of a twophase fluid.

Remaining useful life (RUL) estimation has received extensive attention in many fields, which provides improved decision-making for condition-based maintenance (CBM) and enhances the stability of engineered systems. However, the effective construction of the feature set and design of the high-accuracy prediction model are the main challenges in RUL estimation. Consequently, a novel RUL estimation method is proposed in this paper. Initially, to extract the deep characteristics of the raw sensor data, the modified ensemble empirical mode decomposition (MEEMD), combined with the correlation coefficient threshold to select the sensitive intrinsic mode function (IMF) components, is proposed to reconstruct more representative features. Additionally, maximal information coefficient-based two-step feature selection (TSMIC) method is used to select the optimal feature subset. Ultimately, temporal convolutional network with attention mechanism (TCNA) is proposed to capture long-term time-series information and achieves more precise prediction results. The proposed framework is verified through a case study on aircraft turbofan engines, and comparisons with other state-of-the-art methods are presented. The experimental results of the case study show the effectiveness and superiority of the proposed approach.

A gradual edge-enhanced ghost imaging method with pseudo-thermal light is proposed in both the theory and experiment. In the experiment, a phase object and fractional spiral phase filter are placed symmetrically in the imaging plane of the pseudo-thermal light source in the distributed test and reference beams of the lensless ghost imaging system. The procedure of gradual edge-enhanced ghost imaging is carried out by modulating the fractional topological charge from 0 to 1. We observe that the brightness of the object edge increases with the increase of the fractional topological charge. It is also found that the intensity distribution is uniform and isotropic when the topological charge is an integer; otherwise, the intensity distribution is not uniform. Theoretical analysis is also provided. The proposed gradual edge-enhanced ghost imaging scenario releases the position limitation in the Fourier plane for the filter of the traditional phase filtering imaging process. The method is believed to have prospective applications in microscopic imaging and biomedical detection.

Investigating how aquatic animals respond to hypoxia brought about by changes in environmental temperature may be of great significance to avoid oxidative injury and maintain the quality of farmed fish in the background of global warming. Here, we investigated the effects of hypoxia on oxidative injury and environment-sensing pathway in blood cells of Micropterus salmoides. The total blood cell count (TBCC) and Giemsa staining showed that hypoxia could lead to damage of blood cells. Flow cytometry analysis confirmed that the apoptosis rate, Ca2+ level, NO production and ROS of blood cells were significantly increased under hypoxia stress. Environment-sensing pathways, such as Nrf2 pathway showed that hypoxia resulted in significant up-regulation of hiF-1 alpha subunit (Hif-1α), nuclear factor erythroid 2-related factor 2 (Nrf2) and kelch-1ike ECH- associated protein l (Keap1) expression. Meanwhile, the expression of Hippo pathway-related genes such as MOB kinase activator 1 (MOB1), large tumor suppressor homolog 1/2 (Lats1/2), yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ), protein phosphatase 2A (PP2A) were significantly increased in blood cells after hypoxia exposure. In addition, hypoxia stress also increased the expression of catalase (CAT) and glutathione peroxidase (GPx), but decreased the expression of superoxide dismutase (SOD). Consequently, our results suggested that hypoxia could induce oxidative injury and apoptosis via mediating environment-sensing pathway such as Nrf2/Hippo pathway in blood cells of M. salmoides.

Botulinum neurotoxins (BoNTs) can cause nerve paralysis syndrome in mammals and other vertebrates. BoNTs are the most toxic biotoxins known and are classified as Class A biological warfare agents. BoNTs are mainly divided into seven serotypes A-G and new neurotoxins BoNT/H and BoNT/X, which have similar functions. BoNT proteins are 150 kDa polypeptide consisting of two chains and three domains: the light chain (L, catalytic domain, 50 kDa) and the heavy chain (H, 100 kDa), which can be divided into an N-terminal membrane translocation domain (HN, 50 kDa) and a C-terminal receptor binding domain (Hc, 50 kDa). In current study, we explored the immunoprotective efficacy of each functional molecule of BoNT/F and the biological characteristics of the light chain-heavy N-terminal domain (FL-HN). The two structure forms of FL-HN (i.e., FL-HN-SC: single chain FL-HN and FL-HN-DC: di-chain FL-HN) were developed and identified. FL-HN-SC could cleave the vesicle associated membrane protein 2 (VAMP2) substrate protein in vitro as FL-HN-DC or FL. While only FL-HN-DC had neurotoxicity and could enter neuro-2a cells to cleave VAMP2. Our results showed that the FL-HN-SC had a better immune protection effect than the Hc of BoNT/F (FHc), which indicated that L-HN-SC, as an antigen, provided the strongest protective effects against BoNT/F among all the tested functional molecules. Further in-depth research on the different molecular forms of FL-HN suggested that there were some important antibody epitopes at the L-HN junction of BoNT/F. Thus, FL-HN-SC could be used as a subunit vaccine to replace the FHc subunit vaccine and/or toxoid vaccine, and to develop antibody immune molecules targeting L and HN domains rather than the FHc domain. FL-HN-DC could be used as a new functional molecule to evaluate and explore the structure and activity of toxin molecules. Further exploration of the biological activity and molecular mechanism of the functional FL-HN or BoNT/F is warranted.

BackgroundMost patients with papillary thyroid carcinoma (PTC) have an excellent prognosis. Although central lymph node invasion is frequent, management via central lymph node dissection (CLND) remains controversial. The present study retrospectively investigated independent predictors of pathologic central lymph node negativity (pCLN-) and established a prediction model for pCLN- in clinical lymph node negativity (cN0) PTC.MethodsA total of 2,687 patients underwent thyroid surgery for cN0 PTC from 2013 to 2018 at the First Affiliated Hospital of Chongqing Medical University, and lobectomy plus ipsilateral CLND was the basic surgical extent. Clinicopathological characteristics were reviewed and analyzed. Univariate and multivariate analyses were performed to identify factors related to pCLN-. A prediction model was established based on the results of multivariate analyses.ResultsThe pCLN- rate was 51.5% (1,383/2,687). Multivariate analysis revealed that sex, age, thyroid stimulating hormone (TSH), size, location, laterality, unifocality and extrathyroidal extension negativity (ETE-) were independent predictors of pCLN-. The nomogram showed good discriminative ability (C-index: 0.784 and 0.787 in derivation and validation groups, respectively) and was well calibrated. We quantified the clinical usefulness of the nomogram by decision curve analysis. The median length of follow-up was 30 (range 12– 83) months, and 190 cases were lost, with a follow-up rate of 92.9% (2,497/2,687). Of the 2,687 patients included, 21 (0.8%) experienced recurrence.ConclusionThis nomogram, which integrates available preoperative clinicopathological features and intraoperative frozen biopsy outcomes, is a reliable tool with high accuracy to predict pCLN- in cN0 PTC.

Soil erosion of sloping farmland in the Miyun reservoir area in Beijing has become a serious issue and has threatened the ecological environment and safety of the reservoir area. We used the Taishizhuang Village Non-point Source Pollution Prevention & Control Base in the Miyun reservoir as a study area and performed a comparative analysis of the physicochemical properties of soil of the upper, middle, and lower slopes of the Scutellaria baicalensis + Buchloe dactyloides plot (Treatment 1, T1), Morus alba + Buchloe dactyloides plot (Treatment 2, T2), Salvia miltiorrhiza + Cynodon dactylon plot (Treatment 3, T3), Platycodon grandiflorus + Cynodon dactylon plot (T4), and a barren land control plot (Control check, CK), to explore how different hedgerow patterns affect the soil’s physicochemical properties, anti-erodibility, and fractal characteristics. We found the following: (1) The primary soil mechanical composition included sand particles in the upper slopes, whereas it was soil fine particles in the middle and lower slopes. (2) The fractal dimension of the slope soil showed a significant negative correlation with sand particles (R2 = 0.9791) while being positively correlated with silt particles (R2 = 0.9635) and clay particles (R2 = 0.9408). (3) All hedgerow patterns increased soil nutrients, with the Morus alba + Buchloe dactyloides hedgerow plot increasing the soil total nitrogen (STN), soil total phosphorus (STP), and soil organic matter (SOM) content by 213.89–282.69%, 55.56–58.15%, and 29.77–56.04%, respectively. (4) The Morus alba + Buchloe dactyloides hedgerow plot significantly decreased the soil erodibility factor K value, improved soil anti-erodibility, and reduced soil erosion. (5) The K value of the soil erodibility was significantly negatively correlated with clay particles, soil fractal dimension, and STP (p < 0.01); positively correlated with sand particles; and negatively correlated with silt particles, STN, and SOM. Therefore, the Morus alba + Buchloe dactyloides hedgerow planting contributes to clay particle conservation, soil nutrient content improvement, soil structure optimization, and soil anti-erodibility enhancement.

N6-methyladenosine (m6A), the most common posttranscriptional modification in eukaryotic mRNAs, plays an important role in mRNA splicing, editing, stability, degradation, etc. Since the methylation state is dynamic, methylation sequencing needs to be carried out over different time periods, which brings some difficulties to identify the RNA methyladenine sites. Thus, it is necessary to develop a fast and accurate method to identify the RNA N6-methyladenosine sites in the transcriptome. In this study, we use first-order and second-order Markov models to identify RNA N6-methyladenine sites in three species (Saccharomyces cerevisiae, mouse, and Homo sapiens). These two methods can fully consider the correlation between adjacent nucleotides. The results show that the performance of our method is better than that of other existing methods. Furthermore, the codons encoded by three nucleotides have biases in mRNA, and a second-order Markov model can capture this kind of information exactly. This may be the main reason why the performance of the second-order Markov model is better than that of the first-order Markov model in the m6A prediction problem. In addition, we provide a corresponding web tool called MM-m6APred.

Oil-immersed insulation paper (OIP) bushing is one of the most important equipment in power transmission and distribution systems. Moisture is one of the most serious factors that affect the insulation status of OIP bushing. In this paper, the OIP bushing was assumed to be in a stable and simplicity condition, and then the transient moisture distribution of capacitor core and its effects on the electric field were studied. First, by dissecting a 110 kV OIP bushing, the specific sizes for modelling were obtained. Afterwards, a moisture diffusion model for OIP bushing was established based on COMSOL Multiphysics software, and it was also verified by moisture diffusion experiment. Then, the moisture distribution for different conditions were obtained and analyzed. Finally, a model for the electric field of OIP bushing was established, and then the effects of moisture on the electric field were studied.

The motion control of high-precision electromechanitcal systems, such as micropositioners, is challenging in terms of the inherent high nonlinearity, the sensitivity to external interference, and the complexity of accurate identification of the model parameters. To cope with these problems, this work investigates a disturbance observer-based deep reinforcement learning control strategy to realize high robustness and precise tracking performance. Reinforcement learning has shown great potential as optimal control scheme, however, its application in micropositioning systems is still rare. Therefore, embedded with the integral differential compensator (ID), deep deterministic policy gradient (DDPG) is utilized in this work with the ability to not only decrease the state error but also improve the transient response speed. In addition, an adaptive sliding mode disturbance observer (ASMDO) is proposed to further eliminate the collective effect caused by the lumped disturbances. The micropositioner controlled by the proposed algorithm can track the target path precisely with less than 1 μm error in simulations and actual experiments, which shows the sterling performance and the accuracy improvement of the controller.

Clostridium botulinum produces botulinum neurotoxin (BoNT), which is the most toxic known protein and the causative agent of human botulism. BoNTs have similar structures and functions, comprising three functional domains: catalytic domain (L), translocation domain (HN), and receptor-binding domain (Hc). In the present study, BoNT/E was selected as a model toxin to further explore the immunological significance of each domain. The EL-HN fragment (L and HN domains of BoNT/E) retained the enzymatic activity without in vivo neurotoxicity. Extensive investigations showed EL-HN functional fragment had the highest protective efficacy and contained some functional neutralizing epitopes. Further experiments demonstrated the EL-HN provided a superior protective effect compared with the EHc or EHc and EL-HN combination. Thus, the EL-HN played an important role in immune protection against BoNT/E and could provide an excellent platform for the design of botulinum vaccines and neutralizing antibodies. The EL-HN has the potential to replace EHc or toxoid as the optimal immunogen for the botulinum vaccine.

The BeiDou navigation satellite system (BDS-3) has been deployed and provides positioning, navigation, and timing (PNT) services for users all over the world. On the basis of BDS-2 system signals, BDS-3 adds B1C, B2a, B2b, and other signals to realize compatibility and interoperability with other global navigation satellite systems (GNSS). Network real-time kinematic (RTK) technology is an important real-time regional high-precision GNSS positioning technology. Combined with the network RTK high-precision service platform software developed by the author’s research group and the measured data of a provincial continuously operating reference station (CORS) in Hubei, this paper preliminarily evaluates the network RTK service performance under the new signal system of BDS-3. The results show that single BDS-3 adopts the new signal combination (B1C+B2a) and transition signal combination (B1I+B3I) when providing virtual reference station (VRS) services, the RTK fixation rate of the terminal is above 95%, and the horizontal and elevation accuracies are within 1cm and 2 cm, respectively, which meets the requirements of providing high-precision network RTK services by a single BDS-3 system. In addition, the positioning accuracy of BDS-2 is relatively poor, while the accuracy of BDS-3 is better than global positioning systems (GPS) and BDS-2. The combined processing effect of the B1I+B3I transition signal of BDS-2/3 is optimal, the accuracy of E and N directions is better than 0.5 cm, and the accuracy of U direction is better than 1.5 cm. It can be seen from the atmosphere correction accuracy, regional error modeling accuracy, and network RTK terminal positioning accuracy that the service effect of the B1C+B2a combination is slightly better than that of the B1I+B3I combination. When a single BDS-3 constellation provides network RTK services, it is recommended to use the B1C+B2a combination as the main frequency solution, and when the BDS-2/3 constellation provides service, it is recommended to use the B1I+B3I combination as the main frequency solution.

B1-type human adenoviruses (HAdVs) HAdV-3, HAdV-7, and HAdV-55 have caused epidemics in North America, Asia, and Europe. However, to date, no adenovirus vaccines or antiviral drugs have been approved for general use. In the present work, a scFv-phage immune library was constructed and mouse monoclonal antibody (MMAb) 10G12 was obtained through selection. 10G12 is specific for HAdV-7 and binds the hexon loop1 and loop2 (LP12), resulting in strong neutralization activity against HAdV-7. Additionally, it is stable in serum and buffer at various pH values. The findings provide insight into adenovirus and antibody responses and may facilitate the design and development of adenovirus vaccines and antiviral drugs.

Near-infrared spectroscopy (NIRS) combined with pattern recognition technique has become an important type of non-destructive discriminant method. This review first introduces the basic structure of the qualitative analysis process based on near-infrared spectroscopy. Then, the main pretreatment methods of NIRS data processing are investigated. Principles and recent developments of traditional pattern recognition methods based on NIRS are introduced, including some shallow learning machines and clustering analysis methods. Moreover, the newly developed deep learning methods and their applications of food quality analysis are surveyed, including convolutional neural network (CNN), one-dimensional CNN, and two-dimensional CNN. Finally, several applications of these pattern recognition techniques based on NIRS are compared. The deficiencies of the existing pattern recognition methods and future research directions are also reviewed.

Different from classical Bühlmann and Bühlmann Straub credibility models in which independence between different risks are assumed, this paper takes dependence between risks into consideration and extends the classical Bühlmann model by introducing a common stochastic shock element. What is more, instead of relying on complete information of historical data, we aim to derive the premium using quantile of the available data. By the method of linear regression, we manage to obtain the quantile credibility premium with common effects. Our result is the generalization of existing results in credibility theory. Both quantile credibility model proposed by Pitselis (2013) and credibility premium for models with dependence induced by common effects obtained by Wen et al. (2009) are special cases of our model. Numerical simulations are also presented to illustrate the impact of quantile credibility with common effect.

The rapid movement of low Earth orbit (LEO) satellite can improve geometric diversity, which contributes to the rapid convergence of Global Navigation Satellite System (GNSS) precise point positioning (PPP). However, the LEO onboard receiver clock cannot be used directly by PPP users as the LEO satellite clock because the LEO onboard receiver clock and LEO satellite clock absorb different code delays when receiving and transmitting signals. In this study, a real-time estimation approach for the LEO satellite clock based on ground tracking stations was proposed for the first time. The feasibility for the rapid convergence of the LEO satellite clock was analyzed using the satellite time dilution of precision (TDOP) that one satellite is relative to multiple ground tracking stations. The LEO constellation of 168 satellites and observations for 15 ground tracking stations were simulated to verify the proposed method. The experiment results showed that the average convergence time was 31.21 min for the Global Positioning System (GPS) satellite clock, whereas the value for the LEO satellite clock was only 2.86 min. The average root mean square (RMS) and standard deviation (STD) values after convergence were 0.71 and 0.39 ns for the LEO satellite clock, whereas the values were 0.31 and 0.13 ns for the GPS satellite clock. The average weekly satellite TDOP for the LEO satellite was much smaller than that for the GPS satellite. The average satellite TDOPs for all LEO and GPS satellites were 19.13 and 1294.70, respectively. However, the average delta TDOPs caused by satellite motion for all LEO and GPS satellites were both 0.10. Therefore, the rapid convergence of the LEO satellite clock resulted from the better geometric distribution of the LEO satellite relative to ground stations. Despite errors and the convergence time of the LEO satellite clock, the convergence time and positioning accuracy for LEO-augmented GPS and BeiDou Navigation Satellite System (BDS) PPP with the real-time estimated LEO satellite clock can still reach 10.63 min, 1.94 cm, 1.44 cm, and 4.18 cm in the east, north, and up components, respectively. The improvements caused by LEO satellite for GPS/BDS PPP were 59%, 30%, 31%, and 33%, respectively.

The incidence of dengue virus (DENV) infections has been escalating in tropical and subtropical countries, but there are still no effective therapeutic options. In the present study, a DENV-1-specific human monoclonal antibody (HMAb), 1G5, isolated from single plasma cells obtained from the peripheral blood mononuclear cells of dengue patients was found to have potent neutralization activity against serotype 1 DENV (DENV-1). Its neutralization activity against DENV-2 was not as strong, and it was almost absent for DENV-3 and DENV-4. The results showed that HMAb 1G5 only binds to the envelop protein of intact DENV-1 or the envelop protein under unheated and non-reducing conditions, and that it does not bind to recombinant envelope protein. This could mean that the antibody recognizes a conformational epitope of the envelope protein. Further, the findings showed that HMAb 1G5 potently neutralizes DENV-1 in both the pre- and post-attachment phases of the virus at low concentrations. In vivo studies showed that HMAb 1G5 provides protection from DENV-1 infection in a murine model. In addition, antibody-dependent enhancement that occurs at lower doses of the antibody was completely abrogated by the introduction of Leu-to-Ala mutations (1G5-LALA) or deletion of nine amino acids (1G5-9del) in the Fc region. Therefore, HMAb 1G5 shows promise as a safe and effective agent for prophylactic and therapeutic treatment of DENV-1 infection.

Influenza A virus (IAV) is responsible for severe morbidity and mortality in animals and humans worldwide. miRNAs are a class of small noncoding single-stranded RNA molecules that can negatively regulate gene expression and play important roles in virus-host interaction. However, the roles of miRNAs in IAV infection are still not fully understood. Here, we profiled the cellular miRNAs of A549 cells infected with A/goose/Jilin/hb/2003 (H5N1) and a comparison A/Beijing/501/2009 (H1N1). miRNA microarray and quantitative PCR analysis showed that several miRNAs were differentially expressed in A549 cells during IAV infection. Subsequently, we demonstrated that IAV replication was essential for the regulation of these miRNAs, and bioinformatic analysis revealed that the targets of these miRNAs affected biological processes relevant to IAV replication. Specifically, miR-21-3p was found to be down-regulated in IAV-infected A549 cells and selected for further detailed analysis. Target prediction and functional study illustrated that miR-21-3p repressed the expression of HDAC8 by targeting its 3′UTR. Furthermore, we confirmed miR-21-3p could promote virus replication, which was similar to the result of knocking down HDAC8, indicating that miR-21-3p promoted IAV replication by suppressing HDAC8 expression. Altogether, our results suggest a potential host defense against IAV through down-regulation of miR-21-3p.

Ginger has got increasing worldwide interests due to its extensive biological activities, along with high medical and edible values. But fungal contamination and mycotoxin residues have brought challenges to its quality and safety. In the present study, the relationship of content of mycotoxins accumulation and bioactive components variation in ginger after infection by toxigenic fungi were investigated for the first time to elucidate the influence of fungal contamination on the inherent quality of ginger. After being infected by Aspergillus flavus and Aspergillus carbonarius for different periods, the produced mycotoxins was determined by an immunoaffinity column clean-up based ultra-fast liquid chromatography coupled with tandem mass spectrometry, and the main bioactive components in ginger were analyzed by ultra performance liquid chromatography-photodiode array detection. The results showed that consecutive incubation of ginger with A. flavus and A. carbonarius within 20 days resulted in the production and accumulation of aflatoxins (especially AFB1) and ochratoxin A, as well as the constant content reduction of four bioactive components, which were confirmed through the scanning electron microscope images. Significantly negative correlation was expressed between the mycotoxins accumulation and bioactive components variation in ginger, which might influence the quality and safety of it. Furthermore, a new compound was detected after inoculation for 6 days, which was found in our study for the first time.

For short baseline real-time kinematic (RTK) positioning, the atmosphere and broadcast ephemeris errors can be usually eliminated in double-differenced (DD) processing for synchronous observations. However, in the case of possible communication latency time, these errors may not be eliminated in DD treatments due to their variations during latency time. In addition, the time variation of these errors may present different characteristics among GPS, GLONASS, BDS, and GALILEO due to different satellite orbit and clock types. In this contribution, the formulas for studying the broadcast orbit and clock offset errors and atmosphere error in asynchronous RTK (ARTK) model is proposed, and comprehensive experimental analysis is performed to numerically show time variations of these errors and their impacts on RTK results from short-baselines among four systems. Compared with synchronous RTK, the degradation of position precision for ARTK can reach a few centimeters, but the accuracy degradation to a different degree by different systems. BDS and Galileo usually outperform GPS and GLONASS in ARTK due to the smaller variation of broadcast ephemeris error. The variation of broadcast orbit error is generally negligible compared with the variation of broadcast clock offset error for GPS, BDS, and Galileo. Specifically, for a month of data, the root mean square (RMS) values for the variation of broadcast ephemeris error over 15 seconds are 11.2, 16.9, 7.3, and 3.0 mm for GPS, GLONASS, BDS, and Galileo, respectively. The variation of ionosphere error for some satellites over 15 seconds can reach a few centimeters during active sessions under a normal ionosphere day. In addition, compared with other systems, BDS ARTK shows an advantage under high ionosphere activity, and such advantage may be attributed to five GEO satellites in the BDS constellation.

This paper studies the optimal investment and consumption strategies in a two-asset model. A dynamic Value-at-Risk constraint is imposed to manage the wealth process. By using Value at Risk as the risk measure during the investment horizon, the decision maker can dynamically monitor the exposed risk and quantify the maximum expected loss over a finite horizon period at a given confidence level. In addition, the decision maker has to filter the key economic factors to make decisions. Considering the cost of filtering the factors, the decision maker aims to maximize the utility of consumption in a finite horizon. By using the Kalman filter, a partially observed system is converted to a completely observed one. However, due to the cost of information processing, the decision maker fails to process the information in an arbitrarily rational manner and can only make decisions on the basis of the limited observed signals. A genetic algorithm was developed to find the optimal investment, consumption strategies, and observation strength. Numerical simulation results are provided to illustrate the performance of the algorithm.

Lichong Shengsui Yin (LCSSY) is an effective and classic compound prescription of Traditional Chinese Medicines (TCMs) used for the treatment of ovarian cancer. To investigate its pharmacodynamic basis for treating ovarian cancer, the multi-dimensional spectrum-effect relationship was determined. Four compositions (I to IV) were obtained by extracting LCSSY successively with supercritical CO2 fluid extraction, 75% ethanol reflux extraction, and the water extraction-ethanol precipitation method. Nine samples for pharmacological evaluation and fingerprint analysis were prepared by changing the content of the four compositions. The specific proportions of the four compositions were designed according to a four-factor, three-level L9(34) orthogonal test. The pharmacological evaluation included in vitro tumor inhibition experiments and the survival extension rate in tumor-bearing nude mice. The fingerprint analyzed by chromatographic condition I (high-performance liquid chromatography-photodiode array detec tor，HPLC-PDA) identified 19 common peaks. High-performance liquid chromatography-photodiode array detector-Evaporative Light-scattering Detector (HPLC-PDA-ELSD )hyphenated techniques were used to compensate for the use of a single detector, and the fingerprint analyzed by chromatographic condition II identified 28 common peaks in PDA and 23 common peaks in ELSD. Furthermore, multiple statistical analyses were utilized to calculate the relationships between the peaks and the pharmacological results. The union of the regression and the correlation analysis results were the peaks of X5, X9, X11, X12, X16, X18, Y5, Y8, Y12, Y14, Y20, Z4, Z5, Z6, and Z8. The intersection of the regression and the correlation analysis results were the peaks of X11, X12, X16, X18, Y5, Y12, and Z5. The correlated peaks were assigned by comparing the fingerprints with the negative control samples and reference standard samples, and identifying the structure using high-performance liquid chromatography-mass spectrometry detector(HPLC-MS). The results suggested that the pharmacodynamic basis of LCSSY on anti-ovarian cancer activities were germacrone, furandiene, β-elemene, calycosin-7-glucoside, ononin, epimedin B, icariin, ginsenoside Rc, astragaloside, ginsenoside Rd, astragaloside II, and some unknown components.