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The main vectors of Zika virus (ZIKV) and dengue virus (DENV) are Aedes aegypti and Ae. albopictus, with Ae. aegypti being more competent. However, the underlying mechanisms remain unclear. Here, we find Ae. albopictus shows comparable vector competence to ZIKV/DENV with Ae. aegypti by blood-feeding after antibiotic treatment or intrathoracic injection. This suggests that midgut microbiota can influence vector competence. Enterobacter hormaechei_B17 (Eh_B17) is isolated from field-collected Ae. albopictus and conferred resistance to ZIKV/DENV infection in Ae. aegypti after gut-transplantation. Sphingosine, a metabolite secreted by Eh_B17, effectively suppresses ZIKV infection in both Ae. aegypti and cell cultures by blocking viral entry during the fusion step, with an IC50 of approximately 10 μM. A field survey reveals that Eh_B17 preferentially colonizes Ae. albopictus compared to Ae. aegypti. And field Ae. albopictus positive for Eh_B17 are more resistant to ZIKV infection. These findings underscore the potential of gut symbiotic bacteria, such as Eh_B17, to modulate the arbovirus vector competence of Aedes mosquitoes. As a natural antiviral agent, Eh_B17 holds promise as a potential candidate for blocking ZIKV/DENV transmission. Here the authors show that arbovirus vector competence of Aedes mosquitoes is modulated by the midgut microbiota and identify the metabolite sphingosine from the gut symbiotic bacterium Enterobacter hormaechei_B17 (Eh_B17) as a factor mediating resistance to ZIKV and DENV infection. [ABSTRACT FROM AUTHOR]

Harmony Search (HS) algorithm is a swarm intelligence algorithm inspired by musical improvisation. Although HS has been applied to various engineering problems, it faces challenges such as getting trapped in local optima, slow convergence speed, and low optimization accuracy when applied to complex problems. To address these issues, this paper proposes an improved version of HS called Equilibrium Optimization-based Harmony Search Algorithm with Nonlinear Dynamic Domains (EO-HS-NDD). EO-HS-NDD integrates multiple leadership-guided strategies from the Equilibrium Optimizer (EO) algorithm, using harmony memory considering disharmony and historical harmony memory, while leveraging the hidden guidance direction information from the Equilibrium Optimizer. Additionally, the algorithm designs a nonlinear dynamic convergence domain to adaptively adjust the search space size and accelerate convergence speed. Furthermore, to balance exploration and exploitation capabilities, appropriate adaptive adjustments are made to Harmony Memory Considering Rate (HMCR) and Pitch Adjustment Rate (PAR). Experimental validation on the CEC2017 test function set demonstrates that EO-HS-NDD outperforms HS and nine other HS variants in terms of robustness, convergence speed, and optimization accuracy. Comparisons with advanced versions of the Differential Evolution (DE) algorithm also indicate that EO-HS-NDD exhibits superior solving capabilities. Moreover, EO-HS-NDD is applied to solve 15 real-world optimization problems from CEC2020 and compared with advanced algorithms from the CEC2020 competition. The experimental results show that EO-HS-NDD performs well in solving real-world optimization problems. [ABSTRACT FROM AUTHOR]

Background: Anti-disialoganglioside (anti-GD2) monoclonal antibodies are effective immunotherapeutic drugs for treating neuroblastoma, yet their toxicity spectrum is unclear. Objective: This study aimed to assess the toxicity profiles of three anti-GD2 monoclonal antibodies (dinutuximab, dinutuximab β, and naxitamab) in clinical applications by mining and evaluating the adverse drug reaction (ADR) signals from the US Food and Drug Administration Adverse Event Reporting System. Methods: Data in the US Food and Drug Administration Adverse Event Reporting System from the time anti-GD2 monoclonal antibodies became available in the market to the first quarter of 2023 were searched. The signals of anti-GD2 monoclonal antibody-associated ADRs were quantified using four types of algorithms, including the reporting odds ratio, the proportional reporting ratio, the combination of the proportional reporting ratio and χ2 statistic method used by the UK Medicines and Healthcare Products Regulatory Agency, and the Bayesian confidence propagation neural network. The ADRs were categorized by System Organ Class based on the Medical Dictionary for Regulatory Activities, and were sorted according to the frequency and signal strength of ADRs. Results: A total of 370 adverse drug event reports with anti-GD2 monoclonal antibodies listed as the 'primary suspected drugs' were identified, with 116 ADR signals detected, of which 22 were not in the drug labels. Among the adverse drug event reports, 276 reports concerned dinutuximab/dinutuximab β as primary suspected drugs with 90 ADR signals, involving 19 System Organ Classes, of which 21 signals were not in the label; 94 adverse drug event reports concerned naxitamab as the primary suspected drug with 26 ADR signals, involving 11 System Organ Classes, of which one was not in the label. For dinutuximab/dinutuximab β-related ADRs, the top five most frequent were "fever", "abdominal pain", "elevated aspartate aminotransferase (AST)", "elevated alanine aminotransferase (ALT)" and "hypotension"; the top five most intensive signals were "hypoalbuminemia", "elevated AST", "capillary leakage syndrome", "hypoxia" and "elevated ALT". For naxitamab-related ADRs, the top five most frequent were "hypotension", "pain", "urticarial", "hypertension" and "rash"; the top five most intensive signals were "hypotension", "urticaria", "hypoxemia", "bronchospasm" and "hypertension". Involved System Organ Classes included "investigations" and "respiratory, thoracic and mediastinal disorders" containing the most types of ADR signals in dinutuximab/dintuximab β-related ADRs and naxitamab-related ADRs, respectively. Conclusions: Our study comprehensively analyzed the toxicity profiles of anti-GD2 monoclonal antibodies and provides an important reference for clinical monitoring and ADR identification of these drugs. [ABSTRACT FROM AUTHOR]

This article, published in the journal Cell Discovery, discusses the potential vulnerability of the African swine fever virus (ASFV) and the identification of its major protective antigen, p72. The authors used flow cytometry to sort plasmablasts from infected swine and produced recombinant monoclonal antibodies (mAbs) for structural and functional investigations. They determined the epitopes of the antibodies and found that they recognize conformational epitopes on the exposed regions of p72. The study provides insights into the neutralization mechanism of ASFV and offers a framework for the development of vaccines to combat the virus. [Extracted from the article]

Harmony search (HS) is a new swarm intelligent algorithm inspired by the process of music improvisation. Over the past decade, HS algorithm has been applied to many practical engineering problems. However, for some complex practical problems, there are some remaining issues such as premature convergence, low optimization accuracy and slow convergence speed. To address these issues, this paper proposes a novel intelligent global harmony search algorithm based on improved search stability strategy (NIGHS). In the search process, NIGHS uses the adaptive mean of harmony memory library to build a stable trust region around the global best harmony, and proposes a new coupling operation based on linear proportional relation, so that the algorithm can adaptively adjust the ability of exploration and exploitation in the search process and avoid premature convergence. In addition, the dynamic Gauss fine-tuning is adopted in the stable trust region to accelerate the convergence speed and improve the optimization accuracy. The common CEC2017 test functions are employed to test the proposed algorithm, the results show that NIGHS algorithm has a faster convergence speed and better optimization accuracy compared to the HS algorithm and its improved versions. [ABSTRACT FROM AUTHOR]

In July 2019, a novel viral strain (JH2019C603) was isolated from sentinel cattle in Jinghong City, in the subtropical region of Yunnan Province, China. The virus replicated and caused cytopathological effects in both Aedes albopictus (C6/36) and Baby Hamster Syrian Kidney (BHK-21) cells. Agarose gel electrophoresis analysis revealed a viral genome comprised of 10 segments of double-stranded RNA, with a 1-2-2-1-1-1-1-1 migration pattern. Complete genome sequences of the JH2019C603 virus were determined through full-length cDNA amplification. Phylogenetic analysis based on the amino acid (aa) sequences of RNA-dependent RNA Polymerase (Pol), Major subcore (T2) and Major core-surface (T13) showed that JH2019C603 clustered with Yonaguni orbivirus (YONOV) from Japan, with aa identities relative to YONOV of 97.7% (Pol), 99.0% (T2) and 98.5% (T13). However, phylogenetic analysis based on the aa sequences of the outer capsid protein one and two (OC1 and OC2) showed that JH2019C603 formed an independent branch in the phylogenetic tree, and its aa identity with YONOV was only 55.4% (OC1) and 80.8% (OC2), respectively. Compared with the prototype of YONOV, a notable sequence deletion was observed in the 3′ non-coding region of NS1, with the NS1 of JH2019C603 encoded within segment 7 (Seg-7), in contrast to YONOV, which contains NS1 in Seg-6. These results indicate that JH2019C603 belongs to the YONOV lineage and might be a novel serotype or a highly variant strain of YONOV. These findings will facilitate the identification of new isolates and clarify their geographical distribution, epidemiology, genetic diversity and possible disease associations. [ABSTRACT FROM AUTHOR]

Organophosphorus flame retardants (OPFRs) are widely used in various industrial manufacturing processes; thus, their environmental impact in agglomerated industrial areas is of great concern. In this study, seventeen kinds of OPFRs and five kinds of organophosphate diesters (Di-OPs) in water and upper sediment samples from two urban rivers in the agglomerated industrial area of Shenzhen city, China, were investigated. The results showed that the total concentrations of detectable OPFRs ranged from 3438.83 to 12,838.87 ng/L with an average of 6494.94 ng/L in water samples and from 47.16 to 524.46 ng/g (dry weight, dw) with an average of 181.48 ng/g dw in sediment. The values were higher than those in other rivers worldwide. Tris(2-chloroethyl) phosphate (TCEP) is the predominant OPFRs in water and upper sediment, up to 10,664.23 ng/L in water and 414.12 ng/g dw in sediment. The total concentration of OPFRs of sediment samples in the Maozhou River was around twice as high as in the Guanlan River. The results indicated that the level of OPFRs was associated with the industrial activity intensity. Di-OPs exhibited lower concentrations than their parent compounds, and can be attributed to the degradation/metabolism of their parent compounds in the river. The sediment–water partition of OPFRs is significantly correlated with their log Kow values. Risk assessment revealed moderate ecological risks posed by OPFRs in water to aquatic organisms. The present study revealed the pollution status of OPFRs in rivers from agglomerated industrial and residential areas. [ABSTRACT FROM AUTHOR]

Complex system optimization is an emerging research topic in the field of evolutionary computation, whose goal is to handle complex systems with multiple coupled subsystems, each including multiple objectives and multiple constraints in real-world applications. This paper proposes a multi-system genetic algorithm (MSGA), stemming from implicit parallelism in population-based search algorithms, to solve multiple coupled subsystems simultaneously in a complex system. The proposed MSGA is composed of within-subsystem evolution and cross-subsystem migration operators. The objective of the former is to optimize each subsystem by appropriate search strategies, and the objective of the latter is to exchange information between multiple subsystems by migration, which is based on the similarity probability of objectives and constraints, and the intersection probability of solutions in different subsystems. During migration across subsystems, three statistical approaches of measuring similarity and three metrics of solution intersection in information theory are used to calculate these probabilities. Performance is tested on a set of multi-subsystem benchmark functions, and the simulation results show that cross-subsystem migration plays the key role for the performance of MSGA. Furthermore, the proposed MSGA is compared with other competitive algorithms, and results show that it is a promising multi-system optimization algorithm. In summary, the contribution of this paper is the introduction of multi-system optimization to the EA community. [ABSTRACT FROM AUTHOR]

Purpose: China is currently one of the countries with the largest increased number of new cancer cases in the world, but cancer pain management (CPM) is still inadequate. This study uses a questionnaire to demonstrate the status and differences in knowledge, attitude and practice (KAP) of CPM among healthcare workers (HCWs) in developed regions of China, to find deficiencies and priorities for improvement, from which areas and advantages of the role of pharmacists and mobile devices can be explored.Methods: This study used data from a questionnaire on CPM from March to June 2019. The study population consisted of a total of 515 HCWs in four first-tier developed cities in China. The questionnaire has four major components, analysis of differences in KAP of different occupations through one-way analysis of variance (ANOVA).Results: Among the respondents, the physicians had the highest knowledge scores toward CPM, pharmacists had the lowest practice scores. Around half of the respondents indicated that their hospital or department have a pharmacist participating in CPM. Physicians and nurses were more likely to expect pharmacists to provide drug counseling. The HCWs interviewed most expect that the mobile-based pain management system can automatically screen and mark patients with pain.Conclusion: From this study, it can be suggested that pharmacists and nurses in the CPM team should actively promote relevant knowledge. Besides, pharmacists should focus on improving practical ability such as increasing the frequency of pain assessment. Multidisciplinary collaboration and the introduction of mobile devices can improve and refine the CPM. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication. [ABSTRACT FROM AUTHOR]

In December 2017, a squirrel (Callosciurus phayrei) died 2 days after capture in Kunming, and its intestinal tract, heart, liver, spleen, lung, and kidney were subjected to metagenomics analysis. Reassembly and verification by reverse transcription PCR of contigs generated by next-generation sequencing yielded a 5176-nt sequence, which was designated "squirrel bocaparvovirus" (SQBOV). Phylogenetic trees based on the aa sequences of NS1, NP1, and VP1 showed that SQBOV formed an independent branch in the bocaparvovirus phylogenetic tree. The amino acid sequence identity of the NS1 of SQBOV to those of other bocaparvoviruses was below the threshold of 85% that is used to demarcate species within the genus, indicating that it should be considered a member of a new bocaparvovirus species. To our knowledge, this is the first report of a bocaparvovirus in squirrels. Our findings will enable further studies of viral diversity in rodents and of the genetic diversity and host range of bocaparvoviruses. [ABSTRACT FROM AUTHOR]

In 2013, seven virus strains were isolated from Culex tritaeniorhynchus and C. quinquefasciatus collected in Guangxi Province, China. The viruses caused cytopathological effects (CPE) only in C6/36 cells, and not in mammalian cells, e.g. BHK21 and Vero cells. Comparative genomic analysis revealed that the genomes of the seven virus strains ranged from 9589 to 9595 nt with G+C contents of 37.51-37.59%, and nucleotide sequence similarity > 99.8%. The nucleotide sequence homology of the seven virus strains with a Tanay virus isolate was 79.8-80.0%, while the corresponding amino acid homology of ORF1, ORF2, and ORF3 was 79.8-80, 73.9-4.6, and 93.4-94.3%, respectively. In phylogenetic analysis, based on the RdRP amino acid sequence, the seven virus strains were located on the same evolutionary branch, yet distinct from Tanay virus isolated from the Philippines. These results indicated that the seven virus strains isolated from Guangxi represent a new Tanay virus, “Tanay-like virus”, within the genus Sandewavirus of the newly proposed taxon Negevirus. This was the first isolation of Tanay virus in China. [ABSTRACT FROM AUTHOR]

Botulism is a severe and potentially lethal paralytic disease caused by several botulinum neurotoxin-producing Clostridia spp. In China, the majority of the cases caused by botulism were from less-developed rural areas. Here, we designed specific substrate peptides and reconfigured gold nanoparticle-based lateral flow test strip (LFTS) to develop an endopeptidase-based lateral flow assay for the diagnosis of botulism. We performed this lateral flow assay on botulinum neurotoxin-spiked human serum samples. The as-prepared LFTS had excellent performance in the detection of botulinum neurotoxin using only 1 μL of simulated serum, and its sensitivity and specificity were comparable to that of mouse lethality assay. Moreover, the assay takes only half a day and does not require highly trained laboratory staff, specialized facility, or equipment. Finally, our LFTS can be potentially extended to other serotypes of BoNTs by designing specific substrate peptides against the different types of BoNTs. Overall, we demonstrate a strategy by which LFTS and endopeptidase activity assays can be integrated to achieve facile and economic diagnosis of botulism in resource-limited settings. [ABSTRACT FROM AUTHOR]

Herein, we firstly demonstrate the design and the proof-of-concept use of a capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection. The micropillar array substrate was etched and coated with a gold film by microelectromechanical systems (MEMS) process to integrate into a lateral flow test strip. The detection of abrin solutions of various concentrations was performed by the as-prepared microfluidic chip. It was shown that the correlation between the abrin concentration and SERS signal was found to be linear within the range of 0.1 ng/mL to 1 μg/mL with a limit of detection of 0.1 ng/mL. Our microfluidic chip design enhanced the operability of SERS-based immunodiagnostic techniques, significantly reducing the complication and cost of preparation as compared to previous SERS-based works. Meanwhile, this design proved the superiority to conventional lateral flow test strips in respect of both sensitivity and quantitation and showed great potential in the diagnosis and treatment for abrin poisoning as well as on-site screening of abrin-spiked materials. [ABSTRACT FROM AUTHOR]

Diffusion plays a critical role in establishing functional bio/solid soft interfaces for bioassays, biosensors, and biofuel cells. An understanding of micro-diffusion near the interface is significant for developing high-performance bioassays, biosensors, and biofuel cells. Herein, we explored micro-diffusion behavior at different temperature gaps in microfluidic chip and enzyme-linked immunosorbent assay (ELISA) microplates. It exhibited that temperature gap could distinctly promote directional diffusion of molecules in microfluidic chip from high concentration zone to low concentration zone. In addition, experimental results of specially designed ELISA also partly confirmed that the temperature gap could effectively improve the performance of ELISA by 54.5%. In compared with conventional ELISA, the as-prepared temperature-gap functional module in microfluidic chip has obvious advantages of miniaturization, integration, customization, and low cost. All in all, the current work indicates that temperature-gap function has great potential in biomedical detection, food safety, and so on. It can be utilized to develop novel biological detection approaches and related instruments or microfluidic chips. [ABSTRACT FROM AUTHOR]

Alphaviruses are enveloped RNA viruses that contain several human pathogens. Due to intrinsic heterogeneity of alphavirus particles, a high resolution structure of the virion is currently lacking. Here we provide a 3.5 Å cryo-EM structure of Sindbis virus, using block based reconstruction method that overcomes the heterogeneity problem. Our structural analysis identifies a number of conserved residues that play pivotal roles in the virus life cycle. We identify a hydrophobic pocket in the subdomain D of E2 protein that is stabilized by an unknown pocket factor near the viral membrane. Residues in the pocket are conserved in different alphaviruses. The pocket strengthens the interactions of the E1/E2 heterodimer and may facilitate virus assembly. Our study provides structural insights into alphaviruses that may inform the design of drugs and vaccines. Alphaviruses are enveloped RNA viruses that contain several human pathogens. Here, the authors use block-based reconstruction method and provide a 3.5 Å cryo-EM structure of sindbis virus that identifies a conserved hydrophobic pocket near the viral membrane that is stabilized by an unknown pocket factor. [ABSTRACT FROM AUTHOR]

In order to improve the automation and reliability of the mechanized transplanting, a vegetable seedling automatic conveying system was designed. The functional execution component of the system consists of a tank-wheel storage seedling mechanism, a seedling tray conveyor, and a hanging cup circulating conveying mechanism. Combined with the communication technology between host computer and programmable logic controller (PLC), the user interface software of automatic conveying system for potted vegetable was developed by using Visual Studio to control and monitor the transmission progress. The PVDF pressure sensor was used to detect the pressure change of the seedling storage disk to obtain the information of the loading seedling tray. The limit switch and stroke switch were combined to obtain the information of the push rod and feed plate. The timing of each component is controlled by the PLC controller combined with the feedback information of each sensor. The test results show the effect of taking an individual seedling is excellent, the error rate of the pushing mechanism is about 2.08%, and the success rate was 97.91%. [ABSTRACT FROM AUTHOR]

Potent inhibitors to reverse Botulinum neurotoxins (BoNTs) activity in neuronal cells are currently not available. A better understanding of the substrate recognition mechanism of BoNTs enabled us to design a novel class of peptide inhibitors which were derivatives of the BoNT/A substrate, SNAP25. Through a combination of in vitro, cellular based, and in vivo mouse assays, several potent inhibitors of approximately one nanomolar inhibitory strength both in vitro and in vivo have been identified. These compounds represent the first set of inhibitors that exhibited full protection against BoNT/A intoxication in mice model with undetectable toxicity. Our findings validated the hypothesis that a peptide inhibitor targeting the two BoNT structural regions which were responsible for substrate recognition and cleavage respectively could exhibit excellent inhibitory effect, thereby providing insight on future development of more potent inhibitors against BoNTs. [ABSTRACT FROM AUTHOR]