IDR-targeting compounds suppress HPV genome replication via disruption of phospho-BRD4 association with DNA damage response factors.

Compounds binding to the bromodomains of bromodomain and extra-terminal (BET) family proteins, particularly BRD4, are promising anticancer agents. Nevertheless, side effects and drug resistance pose significant obstacles in BET-based therapeutics development. Using high-throughput screening of a 200,000-compound library, we identified small molecules targeting a phosphorylated intrinsically disordered region (IDR) of BRD4 that inhibit phospho-BRD4 (pBRD4)-dependent human papillomavirus (HPV) genome replication in HPV-containing keratinocytes. Proteomic profiling identified two DNA damage response factors-53BP1 and BARD1-crucial for differentiation-associated HPV genome amplification. pBRD4-mediated recruitment of 53BP1 and BARD1 to the HPV origin of replication occurs in a spatiotemporal and BRD4 long (BRD4-L) and short (BRD4-S) isoform-specific manner. This recruitment is disrupted by phospho-IDR-targeting compounds with little perturbation of the global transcriptome and BRD4 chromatin landscape. The discovery of these protein-protein interaction inhibitors (PPIi) not only demonstrates the feasibility of developing PPIi against phospho-IDRs but also uncovers antiviral agents targeting an epigenetic regulator essential for virus-host interaction and cancer development.

BMP4 Regulates EMT to be Involved in non-Syndromic Cleft lip With or Without Palate.

OBJECTIVE: In the previous study, we identified bone morphogenetic protein 4 (BMP4) responsible for non-syndromic cleft lip with or without cleft palate (NSCL/P). We aimed to elucidate the effects and mechanisms of BMP4 on epithelial-mesenchymal transition (EMT) through Smad1 signaling pathway to be involved in NSCL/P. METHODS: The human oral epidermoid carcinoma cells (KBs) were transfected with plasmids or small interfering RNA (siRNA) to build the models. The migration of the cells was evaluated by transwell assay. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expressions of BMP4, E-cadherin, N-cadherin, EMT-related transcription factors snal1 and snal2, matrix metalloproteinase 2 (MMP2), MMP9, Smad1, and phosphorylated Smad1. RESULTS: In the overexpression group, the migration number of cells was increased significantly. The protein expression of E-cadherin was decreased significantly, while the protein expression level of the N-cadherin was increased significantly. The protein and mRNA expressions of MMP2, MMP9, snal1, and snal2 were significantly higher. The expression level of Smad1 was not significantly changed, while the phosphorylation of Smad1 was significantly increased. In the BMP4-siRNA group, the migrating number cells was significantly decreased. The protein expression of E-cadherin was increased significantly, while the expression of N-cadherin was significantly decreased. The protein and mRNA expressions of MMP2, MMP9, snal1, and snal2 were significantly lower than that of the control group. The expressions of Smad1 and phosphorylation of Smad1 were not significantly changed. CONCLUSIONS: BMP4 enhances cell migration and promotes cell EMT through Smad1 signaling pathway. Abnormal BMP4 mediates migration and EMT through other relevant signaling pathways resulting in NSCL/P. The study provides new insight into the mechanisms of NSCL/P associated with BMP4.n.

A mathematical model with aberrant growth correction in tissue homeostasis and tumor cell growth.

Cancer is usually considered a genetic disease caused by alterations in genes that control cellular behaviors, especially growth and division. Cancer cells differ from normal tissue cells in many ways that allow them to grow out of control and become invasive. However, experiments have shown that aberrant growth in many tissues burdened with varying numbers of mutant cells can be corrected, and wild-type cells are required for the active elimination of mutant cells. These findings reveal the dynamic cellular behaviors that lead to a tissue homeostatic state when faced with mutational and nonmutational insults. The current study was motivated by these observations and established a mathematical model of how a tissue copes with the aberrant behavior of mutant cells. The proposed model depicts the interaction between wild-type and mutant cells through a system of two delay differential equations, which include the random mutation of normal cells and the active extrusion of mutant cells. Based on the proposed model, we performed qualitative analysis to identify the conditions of either normal tissue homeostasis or uncontrolled growth with varying numbers of abnormal mutant cells. Bifurcation analysis suggests the conditions of bistability with either a small or large number of mutant cells, the coexistence of bistable steady states can be clinically beneficial by driving the state of mutant cell predominance to the attraction basin of the state with a low number of mutant cells. This result is further confirmed by the treatment strategy obtained from optimal control theory.

Cypermethrin induces apoptosis of Sertoli cells through the endoplasmic reticulum pathway.

Cypermethrin, an extensively used pyrethroid pesticide, is regarded as one of many endocrine-disrupting chemicals (EDCs) with anti-androgenic activity to damage male reproductive systems. We previously found cypermethrin-induced apoptosis in mouse Sertoli cells TM4. We hypothesized cypermethrin-induced TM4 apoptosis by the endoplasmic reticulum (ER) pathway. This study aimed to explore the roles of the ER pathway in cypermethrin-induced apoptosis in TM4 cells. The cells were treated with cypermethrin for 24 h at various concentrations (0 µM, 10 µM, 20 µM, 40 µM, and 80 µM). Flow cytometry was used to test for apoptosis. Western blot was used to test protein expressions in the ER stress pathway. The results showed that the apoptosis rate of TM4 cells increased with increased concentrations of cypermethrin, and a significant difference was detected in the 80-µM group. The protein expressions of glucose-regulated protein 78 (GRP78), protein kinase R (PKR)-like ER kinase (PERK), p-PERK, α subunit of eukaryotic initiation factor (eIF2α), p-eIF2α, activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), caspase-12, caspase-9, and caspase-3 increased with increased concentrations of cypermethrin. The results suggested cypermethrin-induced apoptosis in TM4 cells regulated by the ER pathway involving PERK-eIF2α-ATF4-CHOP. The study provides a new insight into cypermethrin-induced apoptosis in Sertoli cells.

TIM-3 regulates the NETs-mediated dendritic cell activation in myeloperoxidase-ANCA-associated vasculitis.

OBJECTIVES: T cell immunoglobulin and mucin domain 3 (TIM-3) has been reported as an important regulatory molecule on T cells and plays a pivotal role in autoimmune diseases, but the impact on dendritic cells (DCs) is poorly explored. The formation of neutrophil extracellular traps (NETs) is considered as strongly implicated in the pathogenesis of autoimmune diseases, such as in myeloperoxidase-antineutrophil cytoplasmic autoantibody associated vasculitis (MPO-AAV). This study thus aimed to investigate the potential regulation roles of TIM-3 in the regulation of NETs-mediated DC activation in MPO-AAV. METHODS: Twenty untreated patients with MPO-AAV and 20 healthy controls were enrolled in this study. The expressions of TIM-3 and toll-like receptor 4 (TLR4) in peripheral blood dendritic cells were analysed by flow cytometry, and the release of NETs by neutrophils was evaluated by immunofluorescence. In animal experiments, we measured the DC activation markers after the stimulation of NETs. Furthermore, we detected the NETs-mediated DC activation after TIM-3 blockade. RESULTS: Here we found an increased spontaneous NET production in MPOAAV patients. We also revealed a markedly reduced expression of TIM-3 and an increased expression of TLR4 on DCs of active MPO-AAV patients. We found the NETs could induce the activation of DCs and promote Toll-like receptor 4 expression on DC surface. More interestingly, the blockade of TIM-3 could further enhance the NETs-mediated DC cytokine expression. CONCLUSIONS: Our results demonstrated DC surface TIM-3 plays an important role in maintaining the NETs mediated immune homeostasis in MPO-AAV, suggesting an important role in MPOAAV development.

Cadmium-induced apoptosis through reactive oxygen species-mediated mitochondrial oxidative stress and the JNK signaling pathway in TM3 cells, a model of mouse Leydig cells.

Cadmium (Cd) is a heavy metal that widely exists in the environment and industry, and which causes serious damages to reproductive system. Recent studies have reported that cadmium induces apoptosis of various germ cells in testes, resulting in male infertility. However, the exact mechanism of cadmium-induced apoptosis remains unclear. In this study, we hypothesized that reactive oxygen species (ROS)-mediated c-jun N-terminal kinase (JNK) signaling pathway was involved in cadmium-induced apoptosis in TM3 cells, a model of mouse Leydig cells. TM3 cells were exposed for various times to a range of cadmium concentrations. We found that cadmium reduced TM3 cell viability and increased apoptosis in a time- and dose- dependent manner. Moreover, the levels of ROS generation and the phosphorylation of JNK were elevated by cadmium treatment. In addition, the nuclear transcription factor c-jun was significantly activated, which led to increased expression of downstream c-jun targets and Bcl-2 was decreased, accompanied with downstream activation of apoptosis-related proteins such as Cleaved-Caspase3 and Cleaved-PARP. However, pretreatment with the ROS inhibitor N-acetyl-L-cysteine (NAC) and JNK inhibitor JNK-IN-8, ROS, JNK and cadmium-induced TM3 cell apoptosis were remarkably suppressed. Based on above-mentioned results, this study provides a mechanistic understanding of cadmium induced TM3 cell apoptosis through the ROS/JNK signaling pathways.

The anti-androgenic effects of cypermethrin mediated by non-classical testosterone pathway activation of mitogen-activated protein kinase cascade in mouse Sertoli cells.

Previous studies have demonstrated that the anti-androgenic effects of cypermethrin (CYP) are associated with testosterone (T) - related signaling pathway. This study was to investigate the effects of CYP on mouse Sertoli cells (TM4) and clarify whether the mechanisms were mediated by non-classical T signaling pathway activating mitogen-activated protein kinase (MAPK) cascade. The Cell Counting Kit 8 (CCK8) and Real-Time Cell Analysis iCELLigence (RTCA-iCELLigence) system were performed to detect the effects of 10 µM, 20 µM, 40 µM and 80 µM CYP on the viability and proliferation of TM4. The mammalian two hybrid assay, quantitative Real-Time PCR (qRT-PCR) and western blot were conducted to analyze the key genes and proteins involved in T-mediated MAPK signaling pathway. CYP was found to inhibit the viability and proliferation of TM4. Additionally, CYP disturbed the functions of Sertoli cells by inhibiting inhibin B (INH B) expression and facilitating androgen binding protein (ABP) and transferrin (TF) expression. Moreover, CYP suppressed the interaction of AR and Src kinase and inhibited androgen-mediated phosphorylation of Src, epidermal growth factor receptor (EGFR), extracellular-regulated kinase1/2 (ERK1/2) and transcription factor cAMP response element binding protein (CREB). Furthermore, the androgen-induced mRNA and protein expression of CREB-regulated gene early growth response factor (Egr1) decreased after treated with CYP. It is indicated that CYP inhibits the viability and proliferation of Sertoli cells and non-classical T signaling pathway activation of MAPK cascade is involved in anti-androgenic effect of CYP. This study provides a novel insight into the CYP-induced reproductive toxicity.

Expression Analysis of mRNA Decay of Maternal Genes during Bombyx mori Maternal-to-Zygotic Transition.

Maternal genes play an important role in the early embryonic development of the silkworm. Early embryonic development without new transcription depends on maternal components stored in the egg during oocyte maturation. The maternal-to-zygotic transition (MZT) is a tightly regulated process that includes maternal mRNAs elimination and zygotic transcription initiation. This process has been extensively studied within model species. Each model organism has a unique pattern of maternal transcriptional clearance classes in MZT. In this study, we identified 66 maternal genes through bioinformatics analysis and expression analysis in the eggs of silkworm virgin moths (Bombyx mori). All 66 maternal genes were expressed in vitellogenesis in day eight female pupae. During MZT, the degradation of maternal gene mRNAs could be divided into three clusters. We found that eight maternal genes of cluster 1 remained stable from 0 to 3.0 h, 17 maternal genes of cluster 2 were significantly decayed from 0.5 to 1.0 h and 41 maternal genes of cluster 3 were significantly decayed after 1.5 h. Therefore, the initial time-point of degradation of cluster 2 was earlier than that of cluster 3. The maternal gene mRNAs decay of clusters 2 and 3 is first initiated by maternal degradation activity. Our study expands upon the identification of silkworm maternal genes and provides a perspective for further research of the embryo development in Bombyx mori.

iTRAQ-Based Quantitative Proteomic Analysis of Digestive Juice across the First 48 Hours of the Fifth Instar in Silkworm Larvae.

The silkworm is an oligophagous insect for which mulberry leaves are the sole diet. The nutrients needed for vital activities of the egg, pupal, and adult stages, and the proteins formed in the cocoon, are all derived from the larval stages. The silkworm feeds and grows quickly during the larval stages. In particular, the amount of leaf ingested and digested quickly increases from the ecdysis to the gluttonous stage in the fifth instar period. In this study, we used the iTRAQ proteomic technique to identify and analyze silkworm larval digestive juice proteins during this period. A total of 227 proteins were successfully identified. These were primarily serine protease activity, esterase activity, binding, and serine protease inhibitors, which were mainly involved in the digestion and overcoming the detrimental effects of mulberry leaves. Moreover, 30 genes of the identified proteins were expressed specifically in the midgut. Temporal proteomic analysis of digestive juice revealed developmental dynamic features related to molecular mechanisms of the principal functions of digesting, resisting pathogens, and overruling the inhibitory effects of mulberry leaves protease inhibitors (PIs) with a dynamic strategy, although overruling the inhibitory effects has not yet been confirmed by previous study. These findings will help address the potential functions of digestive juice in silkworm larvae.

Metal Selenides as Efficient Counter Electrodes for Dye-Sensitized Solar Cells.

Solar energy is the most abundant renewable energy available to the earth and can meet the energy needs of humankind, but efficient conversion of solar energy to electricity is an urgent issue of scientific research. As the third-generation photovoltaic technology, dye-sensitized solar cells (DSSCs) have gained great attention since the landmark efficiency of ∼7% reported by O'Regan and Grätzel. The most attractive features of DSSCs include low cost, simple manufacturing processes, medium-purity materials, and theoretically high power conversion efficiencies. As one of the key materials in DSSCs, the counter electrode (CE) plays a crucial role in completing the electric circuit by catalyzing the reduction of the oxidized state to the reduced state for a redox couple (e.g., I3-/I-) in the electrolyte at the CE-electrolyte interface. To lower the cost caused by the typically used Pt CE, which restricts the large-scale application because of its low reserves and high price, great effort has been made to develop new CE materials alternative to Pt. A lot of Pt-free electrocatalysts, such as carbon materials, inorganic compounds, conductive polymers, and their composites with good electrocatalytic activity, have been applied as CEs in DSSCs in the past years. Metal selenides have been widely used as electrocatalysts for the oxygen reduction reaction and light-harvesting materials for solar cells. Our group first expanded their applications to the DSSC field by using in situ-grown Co0.85Se nanosheet and Ni0.85Se nanoparticle films as CEs. This finding has inspired extensive studies on developing new metal selenides in order to seek more efficient CE materials for low-cost DSSCs, and a lot of meaningful results have been achieved in the past years. In this Account, we summarize recent advances in binary and mutinary metal selenides applied as CEs in DSSCs. The synthetic methods for metal selenides with various morphologies and stoichiometric ratios and deposition methods for CE films are described. We emphasize that the in situ growth method exhibits advantages over other methods for fabricating stable and efficient CEs. We focus on the effect of morphology on the electocatalytic and photovoltaic performance. Application of transparent metal selenide CEs in bifacial DSSCs and the superiority of in situ-grown metal selenide nanosheet fiber CEs used for fiber DSSCs are presented. In addition, we show that metal selenides with a hollow sphere structure can function not only as an efficient electrocatalyst but also as a light-scattering layer. Finally, we present our views on the current challenges and future development of metal selenide CE materials.

Toll-like receptor 4 gene polymorphisms influence milk production traits in Chinese Holstein cows.

The research reported in this Research Communication aimed to describe the influence of Toll-like receptor 4 gene polymorphisms on milk production traits in Chinese Holstein cows. Toll-like receptor 4 (TLR4) is an important member of the toll-like receptor gene family that is widely found in various organisms. Since TLR4 can identify molecular patterns from various pathogenic microorganisms and induce natural and acquired immunity, it plays an important role in disease resistance in dairy cows. Two single nucleotide polymorphisms (SNPs) of TLR4 (c.-226 G > C and c.2021 C > T) that were previously found to be associated with health traits were genotyped using Sequenom MassARRAY (Sequenom Inc., San Diego, CA) for Chinese Holstein cows (n = 866). The associations between SNPs or their haplotypes and milk production traits and somatic cell count were analyzed by the generalized linear model procedure of Statistics Analysis System software (SAS). The c.-226 G > C and c.2021 C > T showed low linkage disequilibrium (r2 = 0·192). There was no association between these two SNPs and SCC, but significant effects were found for SNP c.-226 G > C on test-day milk yield, fat content, protein content, and total solid and milk urea nitrogen (P T and the SNP haplotypes on test-day milk yield, fat content, protein content, lactose content and total solids (P C was located within several potential transcription factor binding sites, including transcription factor AP-2. The polymorphisms c.-226 G > C and c.2021 C > T had significant effects on the milk production for Chinese Holstein, and these SNP could be used for molecular marker-assisted selection of milk production.

Cypermethrin inhibits interleukin-6-induced androgen receptor transactivation through signal transducer and activator of transcription 3.

The insecticide cypermethrin has been considered as an endocrine-disrupting chemicals (EDCs) with anti-androgenic activity by interfering with interleukin-6 (IL-6) - induced ligand-independent AR signaling. The purpose of this study was to clarify whether the signal transducer and activator of transcription 3 (STAT3) was involved in the antagonism effect of cypermethrin. In this study, the Western blot was to test the level of STAT3 phosphorylation and the mammalian two-hybrid assay was developed to assess the AR-STAT3 interaction. The date showed that IL-6 increased the phosphorylation level of STAT3 and enhanced the AR-STAT3 interaction. Cypermethrin did not affect the phosphorylation level of STAT3 induced by IL-6, while suppressed the AR-STAT3 interaction induced by IL-6 significantly at the concentration of 10-5 M (p < 0.05). The study indicates cypermethrin inhibits IL-6-induced AR signaling by suppressing the interaction between the AR and STAT3. We provide a novel mechanism of cypermethrin-mediated antagonism on IL-6-induced AR activation associated with STAT3.

Isomeric Sc2O@C78 Related by a Single-Step Stone-Wales Transformation: Key Links in an Unprecedented Fullerene Formation Pathway.

It has been proposed that the fullerene formation mechanism involves either a top-down or bottom-up pathway. Despite different starting points, both mechanisms approve that particular fullerenes or metallofullerenes are formed through a consecutive stepwise process involving Stone-Wales transformations (SWTs) and C2 losses or additions. However, the formation pathway has seldomly been defined at the atomic level due to the missing-link fullerenes. Herein, we present the isolation and crystallographic characterization of two isomeric clusterfullerenes Sc2O@C2v(3)-C78 and Sc2O@D3h(5)-C78, which are closely related via a single-step Stone-Wales (SW) transformation. More importantly, these novel Sc2O@C78 isomers represent the key links in a well-defined formation pathway for the majority of solvent-extractable clusterfullerenes Sc2O@C2n (n = 38-41), providing molecular structural evidence for the less confirmed fullerene formation mechanism. Furthermore, DFT calculations reveal a SWT with a notably low activation barrier for these Sc2O@C78 isomers, which may rationalize the established fullerene formation pathway. Additional characterizations demonstrate that these Sc2O@C78 isomers feature different energy bandgaps and electrochemical behaviors, indicating the impact of SW defects on the energetic and electrochemical characteristics of metallofullerenes.

Identification of susceptibility genes in non-syndromic cleft lip with or without cleft palate using whole-exome sequencing.

BACKGROUND: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is among the most common congenital malformations. The etiology of NSCL/P remains poorly characterized owing to its complex genetic heterogeneity. The objective of this study was to identify genetic variants that increase susceptibility to NSCL/P. MATERIAL AND METHODS: Whole-exome sequencing (WES) was performed in 8 fetuses with NSCL/P in China. Bioinformatics analysis was performed using commercially available software. Variants detected by WES were validated by Sanger sequencing. RESULTS: By filtering out synonymous variants in exons, we identified average 8575 nonsynonymous single nucleotide variants (SNVs). We subsequently compared the SNVs against public databases including NCBI dbSNP build 135 and 1000 Genomes Project and obtained an average of 203 SNVs. Total 12 reported candidate genes were verified by Sanger sequencing. Sanger sequencing also confirmed 16 novel SNVs shared by two or more samples. CONCLUSIONS: We have found and confirmed 16 susceptibility genes responsible for NSCL/P, which may play important role in the etiology of NSCL/P. The susceptibility genes identified in this study will not only be useful in revealing the etiology of NSCL/P but also in diagnosis and treatment of the patients with NSCL/P.

Haplotype-resolved chromosomal-level genome assembly reveals regulatory variations in mulberry fruit anthocyanin content.

Understanding the intricate regulatory mechanisms underlying the anthocyanin content (AC) in fruits and vegetables is crucial for advanced biotechnological customization. In this study, we generated high-quality haplotype-resolved genome assemblies for two mulberry cultivars: the high-AC 'Zhongsang5801' (ZS5801) and the low-AC 'Zhenzhubai' (ZZB). Additionally, we conducted a comprehensive analysis of genes associated with AC production. Through genome-wide association studies (GWAS) on 112 mulberry fruits, we identified MaVHAG3, which encodes a vacuolar-type H+-ATPase G3 subunit, as a key gene linked to purple pigmentation. To gain deeper insights into the genetic and molecular processes underlying high AC, we compared the genomes of ZS5801 and ZZB, along with fruit transcriptome data across five developmental stages, and quantified the accumulation of metabolic substances. Compared to ZZB, ZS5801 exhibited significantly more differentially expressed genes (DEGs) related to anthocyanin metabolism and higher levels of anthocyanins and flavonoids. Comparative analyses revealed expansions and contractions in the flavonol synthase (FLS) and dihydroflavonol 4-reductase (DFR) genes, resulting in altered carbon flow. Co-expression analysis demonstrated that ZS5801 displayed more significant alterations in genes involved in late-stage AC regulation compared to ZZB, particularly during the phase stage. In summary, our findings provide valuable insights into the regulation of mulberry fruit AC, offering genetic resources to enhance cultivars with higher AC traits.

Cypermethrin induces Sertoli cell apoptosis through endoplasmic reticulum-mitochondrial coupling involving IP3R1-GRP75-VDAC1.

A widely used type II pyrethroid pesticide cypermethrin (CYP) is one of endocrine disrupting chemicals (EDCs) with anti-androgenic activity to induce male reproductive toxicology. However, the mechanisms have not been fully elucidated. This study was to explore the effects of CYP on apoptosis of mouse Sertoli cells (TM4) and the roles of endoplasmic reticulum (ER)-mitochondria coupling involving 1,4,5-trisphosphate receptor type1-glucose-regulated protein 75-voltage-dependent anion channel 1 (IP3R1-GRP75-VDAC1). TM4 were cultured with different concentrations of CYP. Flow cytometry, calcium (Ca2+) fluorescent probe, transmission electron microscopy and confocal microscopy, and western blot were to examine apoptosis of TM4, mitochondrial Ca2+, ER-mitochondria coupling, and expressions of related proteins. CYP was found to increase apoptotic rates of TM4 significantly. CYP was shown to significantly increase expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP). Concentration of mitochondrial Ca2+ was increased by CYP treatment significantly. CYP significantly enhanced ER-mitochondria coupling. CYP was shown to increase expressions of IP3R, Grp75 and VDAC1 significantly. We suggest that CYP induces apoptosis in TM4 cells by facilitating mitochondrial Ca2+ overload regulated by ER-mitochondria coupling involving IP3R1-GRP75-VDAC1. This study identifies a novel mechanism of CYP-induced apoptosis in Sertoli cells.

Fuzzy optimal control of multilayer coverage based on radon exhalation dynamics in uranium tailings.

Radon exhalation from uranium tailings has seriously affected environmental safety and human health. Many uncertain parameters, such as diffusion coefficient, porosity, percolation rate, material particle size, etc., are related to the diffusion and migration of radon. Moreover, cover materials, cover layers, and cover thickness are the main instruments to control radon exhalation, and the radon reduction effect of single-layer mulching is often inferior to that of the multilayer. Hence, achieving radon control with multilayer coverage under uncertain environment is an urgent problem that must be solved in the area of nuclear safety and radiation environment. In an attempt to address the issue, a dynamic model of radon exhalation with multilayer coverage is constructed using radon percolation-diffusion migration equation, and triangular membership functions inscribe the model parameters; the objective functions of the left and right equations of the model are constructed, and their extreme value intervals are obtained using immunogenetic algorithm. Then, subject to the total cost and thickness of multilayer covering materials, the fuzzy objective and constraint models of radon exhalation are constructed, and the fuzzy aggregation function is reconstructed according to the importance of the fuzzy objective and constraint models, where ultimately, the optimal radon control decision by swarm intelligence algorithm under different possibility levels and importance conditions can be obtained. An example is then used to validate the effectiveness of the radon exhalation model, and to demonstrate that fuzzy optimization provides a database of decision-making schemes regarding multilayer coverage, and guidance for optimal control and flexible construction management.

Hotspots and research trends of the 'dark side of creativity' in the last decade.

Creativity can function as a catalyst for social development; however, it also possesses a destructive potential. In recent years, scholars have discovered that creativity harbors a dark side, counterbalancing its positive aspects. This study aims to offer a comprehensive understanding of the dynamics surrounding research on the 'dark side of creativity', disseminate the findings, and provide a valuable reference for future researchers in the field. To achieve this objective, bibliometric methods were employed to visualize the overall landscape of the literature, identify prevailing topics, significant works, highly cited authors, and forecast future trends. The following conclusions were drawn: (1) Society presently places substantial importance on investigating the 'dark side of creativity'. (2) Research exploring this facet of creativity spans across multiple disciplines, fields, and geographical locations. (3) The 'dark side of creativity' exhibits a close association with psychological states and the social environment. (4) Investigations into the 'dark side of creativity' reveal a scientific, diversified, and open research trajectory. (5) Future research is expected to focus on themes such as 'anxiety', 'malevolent creativity', 'COVID-19', 'trait', 'gender', 'depression', 'strategy' as emerging trends.

Influencing factors of meaning in life in patients with advanced lung cancer undergoing radiochemotherapy: A cross-sectional survey.

AIM: To examine the factors that influence meaning in life (MiL) in patients with advanced lung cancer who are undergoing radiochemotherapy. METHODS: A cross-sectional, multivariate stepwise regression analysis and structural equation modeling were used to examine factors influencing MiL in 231 patients with lung cancer in an oncology department of a tertiary hospital in China. Their mood state, family care, social support, and psychological distress were measured. RESULTS: Sex, marital status, and family income significantly affected MiL (p < .05). MiL was significantly correlated (p < .01) with psychological distress (r = -.203), and most significantly (F = 66.883, p < .01; 46.2% of MiL) with mood state (r = -.631), family care (r = .384), and social support (r = .410). CONCLUSION: To enhance MiL, nurses need to consider patients' mood states and family/social support, as well as tailor patient care toward different sexes and backgrounds. Clinical staff should pay attention to the psychological changes, family care, and social support of patients with advanced lung cancer.

Depressing relaxation and conduction loss of polar polymer materials by inserting bulky charge traps for superior energy storage performance in high-pulse energy storage capacitor applications.

Polymer-based dielectrics are chiefly used in high-pulse energy storage capacitors for their high breakdown strength, prominent processability, and low cost. Nevertheless, state-of-the-art commercial polymer-based dielectrics such as biaxially oriented polypropylene (BOPP), cannot satisfy the high energy density requirement in many fields because of their low permittivity. Limited success has been achieved in developing polar polymeric dielectrics with high energy density because of the quickly increased energy loss from polarization relaxation and charge conduction under a high electric field and temperature. To achieve high energy density and low loss in polar polymer dielectrics simultaneously, electron-deficient vinyl quinoline (VQQ) units are pre-copolymerized with methyl methacrylate (MMA) followed by blending with a PMMA matrix. The bulky and electron-deficient VQQs have successfully depressed the relaxation of PMMA and significantly decreased charge conduction under an elevated electric field. As a result, a rather high energy discharging efficiency (over 90%) could be finely maintained up to 800 MV m-1, and an energy density of 16.1 J cm-3 could be obtained, which are much better than those of reported polymer dielectrics. The strong space charge trapping effect of the low content of VQQ is well addressed by thermally stimulated depolarization currents (TSDC) and density functional theory analysis (DFT) of increasing breakdown strength, energy density and discharging efficiency. This work offers a promising strategy for achieving high energy density and low loss in polar polymer dielectrics for their commercial application in energy storage capacitors.