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Abstract The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach.

With the rapid development of blockchain technology and the popularity of cryptocurrency, phishing scams pose an increasingly severe threat to the security of cryptocurrency transactions. Existing fraud detection methods have not accurately identified phishing behaviors, especially failing to capture key neighbor information and its impact effectively. To address this problem, we proposed a phishing detection framework based on FAAN-GBM (Feature and Attention Augmented Network with Gradient Boosting Machine), which aims to improve phishing fraud detection effectiveness on the Ethereum platform by further refining the extraction of phishing account features. This framework integrates basic features, transaction features, and interaction features of nodes, optimizes feature aggregation through importance analysis and attention mechanism of neighbor node, and uses autoencoders to deepen the nonlinear expression of node features. Through extensive testing on real Ethereum datasets, FAAN-GBM has demonstrated superior performance over existing methods, effectively improving the identification accuracy of phishing fraud nodes. [ABSTRACT FROM AUTHOR]

Honey bees are vital pollinators in agriculture and important model insects. To understand the genetic and molecular aspects in their development, a reverse transcription quantitative polymerase chain (RT-qPCR) is used to investigate the target genes. However, it is essential to use the appropriate reference genes as endogenous controls for accurate normalization of target genes. To identify stable reference genes in two honey bee species, [Apis mellifera (Am) and Apis cerana (Ac)], we evaluated eight candidate reference genes including, actin, atub, ef1α, gapdh, rpl13a, rpl32, rps18 and tif. Worker bees belonging to the two species were collected at each developmental day during the embryonic and postembryonic developmental stages. The tyrosine hydroxylase (th) gene was used as the target gene to validate the selected reference genes. Our results revealed that rpl13a was the most stable reference gene at all developmental stages of Am and Ac. In addition, gene combinations, including Amrpl13a & Amrps18 & Amactin, Amrpl13a & Amrpl32, Acrpl13a & Acrpl32, Acrpl13a & Acrpl32 & Acef1α followed by other combinations effectively normalized the expression of the target genes during the embryonic and postembryonic developmental stages of Am and Ac, respectively. Our findings provide a foundation for standardized RT-qPCR analysis to improve the accuracy of genes normalization during the different developmental stages of honey bees. [ABSTRACT FROM AUTHOR]

Abstract Characterized by an excessively increased uric acid (UA) level in serum, hyperuricemia induces gout and also poses a great threat to renal and cardiovascular systems. It is urgent and meaningful to perform early warning by noninvasive diagnosis, thus conducing to blockage of disease aggravation. Here, guanidinocalix[5]arene (GC5A) is successfully identified from the self‐built macrocyclic library to specifically monitor UA from urine by the indicator displacement assay. UA is strongly bound to GC5A at micromolar‐level, while simultaneously excluding fluorescein (Fl) from the GC5A·Fl complex in the “switch‐on” mode. This method successfully differentiates patients with hyperuricemia from volunteers except for those with kidney dysfunction and targets a volunteer at high risk of hyperuricemia. In order to meet the trend from hospital‐centered to individual‐centered testing, visual detection of UA is studied through a smartphone equipped with a color‐scanning feature, whose adaptability and feasibility are demonstrated in sensing UA from authentic urine, leading to a promising method in family‐centered healthcare style. A high‐throughput and visual detection method is provided here for alarming hyperuricemic by noninvasive diagnosis.

Abstract Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexation of a hypoxia‐responsive macrocycle with small‐molecule radiosensitizer, is reported. To exemplify this tactic, a carboxylated azocalix[4]arene (CAC4A) is devised as molecular container to quantitatively package tumor sensitizer banoxantrone dihydrochloride (AQ4N) through reversible host–guest interaction. Benefited from the selective reduction of azo functional groups under hypoxic microenvironment, the supramolecular prodrug CAC4A•AQ4N exhibits high tumor accumulation and efficient cellular internalization, thereby significantly amplifying radiation‐mediated tumor destruction without appreciable systemic toxicity. More importantly, this supramolecular radiotherapy strategy achieves an ultrahigh sensitizer enhancement ratio (SER) value of 2.349, which is the supreme among currently reported noncovalent‐based radiosensitization approach. Further development by applying different radiosensitizing drugs can make this supramolecular strategy become a general platform for boosting therapeutic effect in cancer radiotherapies, tremendously promising for clinical translation.

Objective To investigate the association between auditory processing and problem behaviors in preschool children, as well as the mediating role of executive function. Methods A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing, China from June to August 2021. They were evaluated using Preschool Auditory Processing Assessment Scale, Conners Parent Symptom Questionnaire, and Behavior Rating Inventory of Executive Functioning-Preschool version. Children with different demographic features were compared in the scores and the abnormality rates of auditory processing, problem behaviors, and executive function. The influencing factors of the total scores of auditory processing, problem behaviors, and executive function were evaluated using multiple linear regression analysis. Whether executive function was a mediating factor between auditory processing and executive function was examined. Results Sex and grade were the main influencing factors for the total score of auditory processing (P<0.05), and sex, grade, parental education level, and family economic status were the main influencing factors for the total scores of problem behaviors and executive function (P<0.05). The auditory processing score (rs= 0.458, P<0.05) and problem behavior score (rs=0.185, P<0.05) were significantly positively correlated with the executive function score, and the auditory processing score was significantly positively correlated with the problem behavior score (rs=0.423, P<0.05). Executive function played a partial mediating role between auditory processing and problem behaviors, and the mediating effect accounted for 33.44% of the total effect. Conclusions Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function. [ABSTRACT FROM AUTHOR]

The diet breadth of generalist herbivores when compared to specialists tends to be associated with greater transcriptional plasticity. Here, we consider whether it may also contribute to variation in host range among two generalists with different levels of polyphagy. We examined two related polyphagous spider mites with different host ranges, Tetranychus urticae (1200 plants) and Tetranychus truncatus (90 plants). Data from multiple populations of both species domesticated on common beans and transferred to new plant hosts (cotton, cucumber, eggplant) were used to investigate transcriptional plasticity relative to population‐based variation in gene expression. Compared to T. truncatus, T. urticae exhibited much higher transcriptional plasticity. Populations of this species also showed much more variable expression regulation in response to a plant host, particularly for genes related to detoxification, transport, and transcriptional factors. In response to the different plant hosts, both polyphagous species showed enriched processes of drug/xenobiotics metabolism, with T. urticae orchestrating a relatively broader array of biological pathways. Through co‐expression network analysis, we identified gene modules associated with host plant response, revealing shared hub genes primarily involved in detoxification metabolism when both mites fed on the same plants. After silencing a shared hub CYP gene related to eggplant exposure, the performance of both species on the original bean host improved, but the fecundity of T. truncatus decreased when feeding on eggplant. The extensive transcriptomic variation shown by T. urticae might serve as a potential compensatory mechanism for a deficiency of hub genes in this species. This research points to nuanced differences in transcriptomic variability between generalist herbivores. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between auditory processing and problem behaviors in preschool children, as well as the mediating role of executive function., Methods: A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing, China from June to August 2021. They were evaluated using Preschool Auditory Processing Assessment Scale, Conners Parent Symptom Questionnaire, and Behavior Rating Inventory of Executive Functioning-Preschool version. Children with different demographic features were compared in the scores and the abnormality rates of auditory processing, problem behaviors, and executive function. The influencing factors of the total scores of auditory processing, problem behaviors, and executive function were evaluated using multiple linear regression analysis. Whether executive function was a mediating factor between auditory processing and executive function was examined., Results: Sex and grade were the main influencing factors for the total score of auditory processing ( P <0.05), and sex, grade, parental education level, and family economic status were the main influencing factors for the total scores of problem behaviors and executive function ( P <0.05). The auditory processing score ( r s =0.458, P <0.05) and problem behavior score ( r s =0.185, P <0.05) were significantly positively correlated with the executive function score, and the auditory processing score was significantly positively correlated with the problem behavior score ( r s =0.423, P <0.05). Executive function played a partial mediating role between auditory processing and problem behaviors, and the mediating effect accounted for 33.44% of the total effect., Conclusions: Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.

Objectives: To investigate the characteristics of auditory processing (AP) in preschool children with attention deficit hyperactivity disorder (ADHD) using Preschool Auditory Processing Assessment Scale (hereafter referred to as "auditory processing scale")., Methods: A total of 41 children with ADHD and 41 typically developing (TD) children were assessed using the auditory processing scale, SNAP-IV rating scale, and Conners' Kiddie Continuous Performance Test (K-CPT). The auditory processing scale score was compared between the TD and ADHD groups. The correlations of the score with SNAP-IV and K-CPT scores were assessed., Results: Compared with the TD group, the ADHD group had significantly higher total score of the auditory processing scale and scores of all dimensions except visual attention ( P <0.05). In the children with ADHD, the attention deficit dimension score of the SNAP-IV rating scale was positively correlated with the total score of the auditory processing scale ( r s30 =0.531, P <0.05; r s27 =0.627, P <0.05) as well as the scores of its subdimensions, including auditory decoding ( r s =0.628, P <0.05), auditory attention ( r s =0.492, P <0.05), and communication ( r s =0.399, P <0.05). The hyperactivity-impulsivity dimension score of the SNAP-IV rating scale was positively correlated with the hyperactivity-impulsivity dimension score of the auditory processing scale ( r s =0.429, P <0.05). In the children with ADHD, the attention deficit dimension score of the K-CPT was positively correlated with the total score ( r s30 =0.574, P <0.05; r s27 =0.485, P <0.05) and the hyperactivity-impulsivity dimension score ( r s =0.602, P <0.05) of the auditory processing scale., Conclusions: Preschool children with ADHD have the risk of AP abnormalities, and the auditory processing scale should be used early for the screening and evaluation of AP abnormalities in children.