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.

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.

Low-Permittivity and Low-Temperature Cofired BaSO4-BaF2 Microwave Dielectric Ceramics for High-Reliability Packaged Electronics.

In developing low-temperature cofired ceramic (LTCC) technology for high-density packaging or advanced packaged electronics, matching the coefficient of thermal expansion (CTE) among the packaged components is a critical challenge to improve reliability. The CTEs of solders and organic laminates are usually larger than 16.0 ppm of °C1-, while most low-permittivity (εr) dielectric ceramics have CTEs of less than 10.0 ppm °C1-. Therefore, a good CTE match between organic laminates and dielectric ceramics is required for further LTCC applications. In this paper, we propose a high-CTE BaSO4-BaF2 LTCC as a potential solution for high-reliability packaged electronics. The BaSO4-BaF2 ceramics have the advantages of a wide low-temperature sintering range (650-850 °C), low loss, temperature stability, and Ag compatibility, ensuring excellent performance in LTCC technology. The 95 wt %BaSO4-5 wt %BaF2 ceramic has a εr of 9.1, a Q × f of 40,100 GHz @11.03 GHz (Q = 1/tan δ), a temperature coefficient of the resonant frequency of -11.2 ppm °C1-, a CTE of +21.8 ppm °C1-, and a thermal conductivity of 1.3 W mK-1 when sintered at 750 °C. Furthermore, a dielectric resonant antenna using BaSO4-BaF2 ceramics, a typically packaged component of LTCC and laminate, was designed and used to verify the excellent performance by a gain of 6.0 dBi at a central frequency of 8.97 GHz and a high radiation efficiency of 90% over a bandwidth of 760 MHz. Good match and low thermal stress were found in the packaged components of BaSO4-BaF2 ceramics, organic laminates, and Sn-based solders by finite element analysis, proving the potential of this LTCC for high-reliability packaged electronics.

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.

MAVS deSUMOylation by SENP1 inhibits its aggregation and antagonizes IRF3 activation.

Mitochondrial antiviral signaling protein (MAVS) is an adapter that recruits and activates IRF3. However, the mechanisms underpinning the interplay between MAVS and IRF3 are largely unknown. Here we show that small ubiquitin-like modifier (SUMO)-specific protease 1 negatively regulates antiviral immunity by deSUMOylating MAVS. Upon virus infection, PIAS3-induced poly-SUMOylation promotes lysine 63-linked poly-ubiquitination and aggregation of MAVS. Notably, we observe that SUMO conjugation is required for MAVS to efficiently produce phase-separated droplets through association with a newly identified SUMO-interacting motif (SIM) in MAVS. We further identify a yet-unknown SIM in IRF3 that mediates its enrichment to the multivalent MAVS droplets. Conversely, IRF3 phosphorylation at crucial residues close to SIM rapidly disables SUMO-SIM interactions and releases activated IRF3 from MAVS. Our findings implicate SUMOylation in MAVS phase separation and suggest a thus far unknown regulatory process by which IRF3 can be efficiently recruited and released to facilitate timely activation of antiviral responses.

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.

Novel Method to Achieve Temperature-Stable Microwave Dielectric Ceramics: A Case in the Fergusonite-Structured NdNbO4 System.

Microwave dielectric ceramics with permittivity (εr) ∼ 20 play an important role in massive multiple-input multiple-output (MIMO) technology in 5G. Although fergusonite-structured materials with low dielectric loss are good candidates for 5G application, tuning the temperature coefficient of resonant frequency (TCF) remains a problem. In the present work, smaller V5+ ions (rV = 0.355 Å, with coordination number (CN) = 4) were substituted for Nb5+ (rNb = 0.48 Å with CN = 4) in the Nd(Nb1-xVx)O4 ceramics, which, according to in situ X-ray diffraction data, lowered the fergusonite-to-scheelite phase transition (TF-S) to 400 °C for x = 0.2. The thermal expansion coefficient (αL) of the high-temperature scheelite phase was +11 ppm/°C, whereas for the low-temperature fergusonite phase, it was + 14 < αL < + 15 ppm/°C. The abrupt change in αL, the associated negative temperature coefficient of permittivity (τε), and the minimum value of εr at TF-S resulted in a near-zero TCF ∼ (+7.8 ppm/°C) for Nd(Nb0.8V0.2)O4 (εr ∼ 18.6 and Qf ∼ 70,100 GHz). A method to design near-zero TCF compositions based on modulation of τε and αL at TF-S is thus demonstrated that may also be extended to other fergusonite systems.

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.

Safety of romiplostim and eltrombopag for children with immune thrombocytopenia: a pharmacovigilance study of the FDA adverse event reporting system database.

BACKGROUND: Romiplostim and eltrombopag are thrombopoietin receptor agonists (TPORAs) that have been approved by the FDA on 22 August 2008 and 20 November 2008 for pediatric immune thrombocytopenia (ITP). However, postmarketing pharmacovigilance of TPORAs in children still attracts much attention. We aimed to evaluate the safety of the TPORAs romiplostim and eltrombopag using data from the Adverse Event Reporting System database of FDA (FAERS). RESEARCH DESIGN AND METHODS: We conducted a disproportionality analysis and analyzed data from the FAERS database to characterize the key features of adverse events (AEs) associated with TPO-RAs approved for children under 18 years of age. RESULTS: Since their approval in the market in 2008, 250 and 298 reports of romiplostim and eltrombopag use in children have been published in the FAERS database, respectively. The most frequent AE associated with romiplostim and eltrombopag was epistaxis. Neutralizing antibodies and vitreous opacities showed the strongest signals for romiplostim and eltrombopag, respectively. CONCLUSIONS: The labeled AEs for romiplostim and eltrombopag in children were analyzed. Unlabeled AEs may reflect the potential of new clinical individuals. Early recognition and management of AEs that appear in children treated with romiplostim and eltrombopag are of key importance in clinical practice.

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.

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.

Ectopic overexpression of mulberry MnT5H2 enhances melatonin production and salt tolerance in tobacco.

Soil salinization severely inhibits plant growth and has become one of the major limiting factors for global agricultural production. Melatonin (N-acetyl-5-methoxytryptamine) plays an important role in regulating plant growth and development and in responding to abiotic stresses. Tryptamine-5-hydroxylase (T5H) is an enzyme essential for the biosynthesis of melatonin in plants. Previous studies have identified the gene MnT5H for melatonin synthesis in mulberry (Morus notabilis), but the role of this gene in response to salinity stress in mulberry is remain unclear. In this study, we ectopically overexpressed MnT5H2 in tobacco (Nicotiana tabacum L.) and treated it with NaCl solutions. Compared to wild-type (WT), melatonin content was significantly increased in the overexpression-MnT5H2 tobacco. Under salt stress, the expression of NtCAT, NtSOD, and NtERD10C and activity of catalase (CAT), peroxidase (POD), and the content of proline (Pro) in the transgenic lines were significantly higher than that in WT. The Malondialdehyde (MDA) content in transgenic tobacco was significantly lower than that of WT. Furthermore, transgenic tobacco seedlings exhibited faster growth in media with NaCl. This study reveals the changes of melatonin and related substance content in MnT5H2-overexpressing tobacco ultimately lead to improve the salt tolerance of transgenic tobacco, and also provides a new target gene for breeding plant resistance to salt.

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.

Chromosome-level Genomes Reveal the Genetic Basis of Descending Dysploidy and Sex Determination in Morus Plants.

Multiple plant lineages have independently evolved sex chromosomes and variable karyotypes to maintain their sessile lifestyles through constant biological innovation. Morus notabilis, a dioecious mulberry species, has the fewest chromosomes among Morus spp., but the genetic basis of sex determination and karyotype evolution in this species has not been identified. In this study, three high-quality genome assemblies were generated for Morus spp. [including dioecious M. notabilis (male and female) and Morus yunnanensis (female)] with genome sizes of 301-329 Mb and were grouped into six pseudochromosomes. Using a combination of genomic approaches, we found that the putative ancestral karyotype of Morus species was close to 14 protochromosomes, and that several chromosome fusion events resulted in descending dysploidy (2n = 2x = 12). We also characterized a ∼ 6.2-Mb sex-determining region on chromosome 3. Four potential male-specific genes, a partially duplicatedDNA helicase gene (named MSDH) and three Ty3_Gypsy long terminal repeat retrotransposons (named MSTG1/2/3), were identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation. Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mulberry. In addition, genomic areas containing selective sweeps that distinguish domesticated mulberry from wild populations in terms of flowering and disease resistance were identified. Our study provides an important genetic resource for sex identification research and molecular breeding in mulberry.

Controllable synthesis and structural design of novel all-organic polymers toward high energy storage dielectrics.

As the core unit of energy storage equipment, high voltage pulse capacitor plays an indispensable role in the field of electric power system and electromagnetic energy related equipment. The mostly utilized polymer materials are metallized polymer thin films, which are represented by biaxially oriented polypropylene (BOPP) films, possessing the advantages including low cost, high breakdown strength, excellent processing ability, and self-healing performance. However, the low dielectric constant (ε r < 3) of traditional BOPP films makes it impossible to meet the demand for increased high energy density. Controlled/living radical polymerization (CRP) and related techniques have become a powerful approach to tailor the chemical and physical properties of materials and have given rise to great advances in tuning the properties of polymer dielectrics. Although organic-inorganic composite dielectrics have received much attention in previous studies, all-organic polymer dielectrics have been proven to be the most promising choice because of its light weight and easy large-scale continuous processing. In this short review, we begin with some basic theory of polymer dielectrics and some theoretical considerations for the rational design of dielectric polymers with high performance. In the guidance of these theoretical considerations, we review recent progress toward all-organic polymer dielectrics based on two major approaches, one is to control the polymer chain structure, containing microscopic main-chain and side-chain structures, by the method of CRP and the other is macroscopic structure design of all-organic polymer dielectric films. And various chemistry and compositions are discussed within each approach.

Association Between Neddylation and Immune Response.

Neddylation is a ubiquitin-like post-translational protein modification. It occurs via the activation of the neural precursor cell expressed, developmentally downregulated protein 8 (NEDD8) by three enzymes: activating enzyme, conjugating enzyme, and ligase. NEDD8 was first isolated from the mouse brain in 1992 and was initially considered important for the development and differentiation of the central nervous system. Previously, the downregulation of neddylation was associated with some human diseases, such as neurodegenerative disorders and cancers. In recent years, neddylation has also been proven to be pivotal in various processes of the human immune system, including the regulation of inflammation, bacterial infection, viral infection, and T cell function. Additionally, NEDD8 was found to act on proteins that can affect viral transcription, leading to impaired infectivity. Here, we focused on the influence of neddylation on the innate and adaptive immune responses.

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.

Hemolymph Ecdysteroid Titer Affects Maternal mRNAs during Bombyx mori Oogenesis.

Silkworm larval-pupal metamorphosis and the first half of pupal-adult development occur during oogenesis from previtellogenesis to vitellogenesis and include two peaks of the hemolymph ecdysteroid titer. Moreover, a rise in 20-hydroxyecdysone titer in early pupae can trigger the first major transition from previtellogenesis to vitellogenesis in silkworm oogenesis. In this study, we first investigated the expression patterns of 66 maternal genes in the ovary at the wandering stage. We then examined the developmental expression profiles in six time-series samples of ovaries or ovarioles by reverse transcription-quantitative PCR. We found that the transcripts of 22 maternal genes were regulated by 20-hydroxyecdysone in the isolated abdomens of the pupae following a single injection of 20-hydroxyecdysone. This study is the first to determine the relationship between 20-hydroxyecdysone and maternal genes during silkworm oogenesis. These findings provide a basis for further research into the embryonic development of Bombyx mori.

Cypermethrin induces Sertoli cell apoptosis through mitochondrial pathway associated with calcium.

Cypermethrin, one kind of pyrethroid pesticides, has been shown to act as endocrine-disrupting chemicals (EDCs). The purpose of this study was to explore the roles of Sertoli cell apoptosis through mitochondrial pathway associated with calcium (Ca2+) in cypermethrin-induced male reproductive toxicology. The mouse Sertoli cells TM4 were cultured with 0 µM, 10 µM, 20 µM, 40 µM and 80 µM of cypermethrin. We used flow cytometry, Fluo-4 AM, western blot and JC-1 Assay Kit to examine apoptosis, intracellular Ca2+, expressions of mitochondrial apoptotic pathway-related proteins and mitochondrial membrane potential. We found cypermethrin increased apoptosis rate of TM4 cells significantly and with a significant increase in intracellular Ca2+ concentration. Cypermethrin significantly decreased the protein expressions of cytosolic B-cell lymphoma-2 (Bcl-2) and mitochondrial cytochrome c (Cyt-c). The protein expressions of cytosolic Bcl-2-associated x (Bax), Cyt-c, cleaved caspase-3, calmodulin (CaM), Ca2+/CaM-dependent protein kinases II (CaMKII) and phosphorylated CaMKII were increased significantly in cypermethrin-exposed TM4 cells. Cypermethrin decreased mitochondrial membrane potential significantly. Then, Bcl-2 family and Ca2+/CaM/CaMKII pathway participate in cypermethrin-induced homeostasis. Ca2+ overload activates mitochondrial pathway by increasing permeability of mitochondrial membrane and decreasing mitochondrial membrane potential. We suggest cypermethrin induces Sertoli cell apoptosis involving mitochondrial pathway associated with Ca2+ regulated by Bcl-2 family and Ca2+/CaM/CaMKII pathway. The study provides a new insight into mechanisms involved in cypermethrin-induced male reproductive toxicology.