Temperature change regulates pollen fertility of a PTGMS rice line PA64S by modulating the ROS homeostasis and PCD within the tapetum.

Photoperiod and temperature-sensitive male sterility rice is an important line for two-line hybrid rice, and the changes in the cultivation temperature strictly control its pollen fertility. However, the mechanism by which temperature variation regulates pollen fertility is still unclear. This study obtained stable fertile PA64S(F) and sterile PA64S(S) rice from PA64S by controlling temperature changes. PA64S(F) shows a normal anther development and fertile pollen under low temperature (21°C), and PA64S(S) shows delayed degradation of the tapetum cells, leading to abnormal pollen wall formation and ubisch development under normal temperature (28°C). The accumulation of reactive oxygen species (ROS) positively correlates with the programmed cell death (PCD) process of tapetum cells. The delayed accumulation of ROS in the PA64S(S) tapetum at early stages leads to a delayed initiation of the PCD process. Importantly, we localized ascorbic acid (ASA) accumulation in the tapetum cells and determined that ASA is a major antioxidant for ROS homeostasis. ROS-inhibited accumulation plants (PA64S-ASA) demonstrated pollen sterility, higher ASA and lower ROS accumulation in the tapetum, and the absence of PCD processes in the tapetum cell. Abnormal changes in the tapetum of PA64S(S) rice disrupted metabolic pathways such as lipid metabolism, cutin and wax synthesis, sugar accumulation, and phenylpropane, affecting pollen wall formation and substance accumulation, suggesting that the timely accumulation of ROS is critical for male fertility. This study highlights the central role of ROS homeostasis in fertility alteration and also provides an avenue to address the effect of environmental temperature changes on pollen fertility in rice.

Evaluating the Status and Promising Potential of Robotic Spinal Surgery Systems.

The increasing frequency of cervical and lumbar spine disorders, driven by aging and evolving lifestyles, has led to a rise in spinal surgeries using pedicle screws. Robotic spinal surgery systems have emerged as a promising innovation, offering enhanced accuracy in screw placement and improved surgical outcomes. We focused on literature of this field from the past 5 years, and a comprehensive literature search was performed using PubMed and Google Scholar. Robotic spinal surgery systems have significantly impacted spinal procedures by improving pedicle screw placement accuracy and supporting various techniques. These systems facilitate personalized, minimally invasive, and low-radiation interventions, leading to greater precision, reduced patient risk, and decreased radiation exposure. Despite advantages, challenges such as high costs and a steep learning curve remain. Ongoing advancements are expected to further enhance these systems' role in spinal surgery.

Research Progress on Lignin Depolymerization Strategies: A Review.

As the only natural source of aromatic biopolymers, lignin can be converted into value-added chemicals and biofuels, showing great potential in realizing the development of green chemistry. At present, lignin is predominantly used for combustion to generate energy, and the real value of lignin is difficult to maximize. Accordingly, the depolymerization of lignin is of great significance for its high-value utilization. This review discusses the latest progress in the field of lignin depolymerization, including catalytic conversion systems using various thermochemical, chemocatalytic, photocatalytic, electrocatalytic, and biological depolymerization methods, as well as the involved reaction mechanisms and obtained products of various protocols, focusing on green and efficient lignin depolymerization strategies. In addition, the challenges faced by lignin depolymerization are also expounded, putting forward possible directions of developing lignin depolymerization strategies in the future.

Abscisic Acid Regulates the Occurrence and Recovery of the Striped Leaf Phenotype in Response to Lacking Light at the Base of Sheath in Rice by Modulating Carbohydrate Metabolism.

Rice B03S mutants with intermittent leaf discoloration were developed from the photoperiod- and thermosensitive genic male sterile (PTGMS) rice line Efeng 1S. After these plants were deeply transplanted, the new leaves manifested typical stripe patterns. In this study, deep and shallow transplantation of B03S was carried out, and aluminum shading was performed directly on the leaf sheath. It was determined that the reason for the appearance of the striped leaf trait was that the base of leaf sheath lacked light, at which time the sheath transformed from the source organ to the sink organ in rice. To elucidate the related metabolic changes in glycometabolism and abscisic acid (ABA) biosynthesis and transcriptional regulation in the leaf sheath, ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) combined with transcriptome and real-time quantitative PCR (qPCR) validation were used for analysis after deep and shallow transplantation. The result indicates that the leaf sheath may need to compete with the new leaves for sucrose produced by the photosynthesis of old leaves in response to lacking light at the base of sheath. Moreover, the ABA content increases in the leaf sheath when the gene expression of ABA2 and AAO1 is upregulated at the same time, enhancing the plant's resistance to the adverse condition of shading at the leaf sheath. Furthermore, exogenous spraying of B03S with ABA solution was carried out to help recovery under shading stress. The result indicates that the synthesis of endogenous ABA in the leaf sheath is reduced by spraying ABA. At the same time, ABA regulates sucrose metabolism by inhibiting the expression of the SUS gene. This allows for more sucrose synthesized by the old leaves to be transported to the new leaves, resulting an obvious recovery effect of the strip leaf character due to the re-balance of sugar supply and demand in B03S. These findings improve the understanding of the physiological function and metabolic mechanism of the rice leaf sheath, provide a theoretical basis for uneven leaf coloration in nature, and provide theoretical guidance for rice production via seedling transplantation or direct seeding.

Porous Photocrosslinkable Hydrogel Functionalized with USC Derived Small Extracellular Vesicles for Corpus Spongiosum Repair.

Reconstruction of a full-thickness spongy urethra is difficult because a corpus spongiosum (CS) defect cannot be repaired using self-healing or substitution urethroplasty. Small extracellular vesicles (sEVs) secreted by urine-derived stem cells (USC-sEVs) strongly promote vascular regeneration. In this study, it is aimed to explore whether USC-sEVs promote the repair of CS defects. To prolong the in vivo effects of USC-sEVs, a void-forming photoinduced imine crosslinking hydrogel (vHG) is prepared and mixed with the USC-sEV suspension. vHG encapsulated with USC-sEVs (vHG-sEVs) is used to repair a CS defect with length of 1.5 cm and width of 0.8 cm. The results show that vHG-sEVs promote the regeneration and repair of CS defects. Histological analysis reveals abundant sinusoid-like vascular structures in the vHG-sEV group. Photoacoustic microscopy indicates that blood flow and microvascular structure of the defect area in the vHG-sEV group are similar to those in the normal CS group. This study confirms that the in situ-formed vHG-sEV patch appears to be a valid and promising strategy for repairing CS defects.

Identification of RESP18 Gene Mutations Linked to Hereditary Non-Syndromic Cleft Lip and Palate in a Southern Chinese Family.

BACKGROUND Non-syndromic cleft lip with cleft palate (NSCLP) is one of the most common congenital birth defects worldwide; it causes lifelong problems and imposes burdens on patients and their families. This study aimed to describe the genomic analysis and identification of de novo regulated endocrine-specific protein 18 (RESP18) rs2385404 and rs2385405 gene polymorphisms associated with NSCLP in a southern Chinese family and to improve prevention, treatment, and prognosis of NSCLP. MATERIAL AND METHODS We performed a genome-wide association study (GWAS) to investigate the association of NSCLP phenotype with gene mutation. We investigated a 5-persons NSCLP family to screen the genetic variation of Han nationality in southern Chinese. Whole-genome sequencing (WGS) was used to detect all candidate genetic variants, and whole-exome sequencing (WES) was implemented to further verify mutations. The Clinical Variation Data Base (ClinVar) was employed for screening gene mutations. Finally, Sanger sequencing was applied to verify gene variations. RESULTS The combined analysis of WGS, WES, and ClinVar showed that a total of 9 variation positions overlapped among the 3 study cohorts. Sanger sequencing verified Glu amino acid variation in 2 mutation sites (rs2385404, rs2385405) from the RESP18 gene, which caused abnormal RESP18 function and was associated with hereditary NSCLP. CONCLUSIONS The combined genomic results showed that 2 mutations (rs2385404 and rs2385405) of the RESP18 gene were related to NSCLP in the family. The RESP18 gene may play an important role in the etiology and pathogenesis of cleft lip and palate.

Effects of Commonly used Surfactants, Poloxamer 188 and Tween 80, on the Drug Transport Capacity of Intestinal Glucose Transporters.

Some glycoside drugs can be transported through intestinal glucose transporters (IGTs). The surfactants used in oral drug preparations can affect the function of transporter proteins. This study aimed to investigate the effect of commonly used surfactants, Poloxamer 188 and Tween 80, on the drug transport capacity of IGTs. Previous studies have shown that gastrodin is the optimal drug substrate for IGTs. Gastrodin was used as a probe drug to evaluate the effect of these two surfactants on intestinal absorption in SD rats through pharmacokinetic and in situ single-pass intestinal perfusion. Then, the effects of the two surfactants on the expression of glucose transporters and tight-junction proteins were examined using RT-PCR and western blotting. Additionally, the effect of surfactants on intestinal permeability was evaluated through hematoxylin-eosin staining. The results found that all experimental for Poloxamer 188 (0.5%, 2.0% and 8.0%) and Tween 80 (0.1% and 2.0%) were not significantly different from those of the blank group. However, the AUC(0-∞) of gastrodin increased by approximately 32% when 0.5% Tween 80 was used. The changes in IGT expression correlated with the intestinal absorption of gastrodin. A significant increase in the expression of IGTs was observed at 0.5% Tween 80. In conclusion, Poloxamer 188 had minimal effect on the drug transport capacity of IGTs within the recommended limits of use. However, the expression of IGTs increased in response to 0.5% Tween 80, which significantly enhanced the drug transport capacity of IGTs. However, 0.1% and 2.0% Tween 80 had no significant effect.

TGFß2 Promotes the Construction of Fibrotic and Immunosuppressive Tumor Microenvironment in Pancreatic Adenocarcinoma: A Comprehensive Analysis.

Pancreatic adenocarcinoma (PAAD) was characterized by dense fibrotic stroma and immunosuppressive tumor microenvironment (TME). TGFß signaling pathways are highly activated in human cancers. However, the role of TGFß2 in TME of PAAD remains to be elucidated. In this study, we showed that TGFß2 was expressed at a relatively high level in PAAD tissues or cancer cells. Moreover, its high expression predicted unfavorable prognosis. In PAAD, gene set enrichment analysis showed that TGFß2 correlated positively with leukocyte transendothelial migration, but negatively with aerobic metabolism, including oxidative phosphorylation. Results in Tumor and Immune System Interaction Database showed that TGFß2 correlated with the infiltration of tumor-associated macrophages (TAMs), which could be attributed to that TGFß2 promote CCL2 expression in PAAD. Moreover, correlation analysis showed that TGFß2 could trigger cancer-associated fibroblasts (CAFs) activation in PAAD. The drug sensitivity analysis may indicate that patients with TGFß2 high expression have higher sensitivity to chemotherapeutics, but the sensitivity to targeted drugs is still controversial. TGFß2 could promote expansion of CAFs and infiltration of TAMs, thus participating in the construction of a fibrotic and immunosuppressive TME in PAAD. Targeting TGFß2 could be a promising therapeutic approach, which needs to be elucidated by clinical and experimental evidences.

Effects of Three Kinds of Carbohydrate Pharmaceutical Excipients-Fructose, Lactose and Arabic Gum on Intestinal Absorption of Gastrodin through Glucose Transport Pathway in Rats.

BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway. METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry. RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability. CONCLUSION: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

Advances in laser therapies for the scar. / ç˜¢ç—•çš„æ¿€å ‰æ²»ç–—è¿›å±•.

Scars are classified into 5 types: Superficial scars, hypertrophic scars, atrophic scars, depressed scars, and keloid. These types are primarily characterized by abnormal production of fibroblasts and collagen, as well as the disorderly arrangement of connective tissue. Laser treatment for scars involves the coordinated activation of various signaling pathways and cytokines. However, the exact pathological mechanism for scar formation remains unclear, leading to a lack of radical treatment. Recently, laser treatment has gained popularity as a new minimally invasive approach for scar treatment. The emergence of new theories such as fractional, picosecond laser, and laser-assisted drug delivery has led to continuous advance in laser treatment. Up to now, it has been developed numerous novel treatments, including combined with drug, physical, and other treatments, which have shown superior therapeutic effects. In order to optimize laser treatment in the future, it is crucial to combine new materials with postoperative care. This will help clinicians develop more comprehensive treatment strategies. Therefore, it is important to explore treatment options that have broader applicability.

Visual detection and discrimination of nerve and blood agents using a dual-site fluorescent probe in living cells and mice.

Of all chemical warfare agents (CWAs), only nerve and blood agents cause massive mortality at low concentrations. To better detect and discriminate nerve and blood agents, a reliable detection method is desirable. We report a series of fluorescent probes for nerve and blood agent detection. Among the tested probes, SR-Pip detected nerve and blood agents quickly (within 10 s for nerve agents and 1 min for blood agents). SR-Pip coupled with nerve agent produced a weak orange fluorescence with good sensitivity [limit of detection (LOD)= 5.5 µM]. Upon reaction with blood agent, the fluorescence of SR-Pip changed from orange fluorescence to blue fluorescence with detection limits as low as 9.6 nM. This probe effectively visualised different concentrations of nerve agents in living cells and mice. A portable test kit using SR-Pip instantly detected nerve and blood agents. To the best of our knowledge, SR-Pip is the first fluorescent probe for nerve and blood agent detection.

A pig model of symptomatic spinal epidural hematoma.

PURPOSE: The purpose of this study was to establish an animal model capable of simulating the development and decompression process of symptomatic spinal epidural hematoma (SSEH). METHODS: A total of 16 male Bama miniature pigs were included in this study and randomly allocated into four groups: Group A (4 h 20 mmHg hematoma compression), Group B (4 h 24 mmHg hematoma compression), Group C (4 h 28 mmHg hematoma compression), and Group Sham (control). Real-time intra-wound hematoma compression values were obtained using the principle of connectors. Electrophysiological analyses, including the latency and amplitude of somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP), along with behavioral observations (Tarlov score), were performed to assess this model. RESULTS: ANOVA tests demonstrated significant differences in the latency and relative amplitude of SSEP and MEP between Groups C and Sham after 4 h of hematoma compression and one month after surgery (P < 0.01). Behavioral assessments 8 h after surgery indicated that animals subjected to 28 mmHg hematoma compression suffered the most severe spinal cord injury. Pearson correlation coefficient test suggested a negative correlation between the epidural pressure and Tarlov score (r = -0.700, p < 0.001). With the progression of compression and the escalation of epidural pressure, the latency of SSEP and MEP gradually increased, while the relative amplitude gradually decreased. CONCLUSIONS: When the epidural pressure reaches approximately 24 mmHg, the spinal cord function occurs progressive dysfunction. Monitoring epidural pressure would be an effective approach to assist to identify the occurrence of postoperative SSEH.

Integrated mRNA- and miRNA-sequencing analyses unveil the underlying mechanism of tobacco pollutant-induced developmental toxicity in zebrafish embryos.

Tobacco pollutants are prevalent in the environment, leading to inadvertent exposure of pregnant females. Studies of these pollutants' toxic effects on embryonic development have not fully elucidated the potential underlying mechanisms. Therefore, in this study, we aimed to investigate the developmental toxicity induced by cigarette smoke extract (CSE) at concentrations of 0.25, 1, and 2.5% using a zebrafish embryo toxicity test and integrated transcriptomic analysis of microRNA (miRNA) and messenger RNA (mRNA). The findings revealed that CSE caused developmental toxicity, including increased mortality and decreased incubation rate, in a dose-dependent manner. Moreover, CSE induced malformations and apoptosis, specifically in the head and heart of zebrafish larvae. We used mRNA and miRNA sequencing analyses to compare changes in the expression of genes and miRNAs in zebrafish larvae. The bioinformatics analysis indicates that the mechanism underlying CSE-induced developmental toxicity was associated with compromised genetic material damage repair, deregulated apoptosis, and disturbed lipid metabolism. The enrichment analysis and RT-qPCR show that the ctsba gene plays a crucial function in embryo developmental apoptosis, and the fads2 gene mainly regulates lipid metabolic toxicity. The results of this study improve the understanding of CSE-induced developmental toxicity in zebrafish embryos and contribute insights into the formulation of novel preventive strategies against tobacco pollutants during early embryonic development.

Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance.

BACKGROUND: Despite advances in therapeutic strategies, resistance to immunotherapy and the off-target effects of targeted therapy have significantly weakened the benefits for patients with melanoma. MAIN BODY: Alternative splicing plays a crucial role in transcriptional reprogramming during melanoma development. In particular, aberrant alternative splicing is involved in the efficacy of immunotherapy, targeted therapy, and melanoma metastasis. Abnormal expression of splicing factors and variants may serve as biomarkers or therapeutic targets for the diagnosis and prognosis of melanoma. Therefore, comprehensively integrating their roles and related mechanisms is essential. This review provides the first detailed summary of the splicing process in melanoma and the changes occurring in this pathway. CONCLUSION: The focus of this review is to provide strategies for developing novel diagnostic biomarkers and summarize their potential to alter resistance to targeted therapies and immunotherapy.

Transcript Level and Sequence Matching Are Key Determinants of Off-Target Effects in RNAi.

Double-stranded RNA (dsRNA) pesticides, those based on RNA interference (RNAi) technology utilizing dsRNA, have shown potential for pest control. However, the off-target effects of dsRNA pose limitations to the widespread application of RNAi and raise concerns regarding potential side effects on other beneficial organisms. The precise impact and underlying factors of these off-target effects are still not well understood. Here, we found that the transcript level and sequence matching jointly regulate off-target effects of dsRNA. The much lower expressed target genes were knocked down to a lesser extent than genes with higher expression levels, and the critical sequence identity of off-target effects is approximately 80%. Moreover, off-target effects could be triggered by a contiguous matching sequence length exceeding 15 nt as well as nearly perfectly matching sequences with one or two base mismatches exceeding 19 nt. Increasing the dosage of dsRNA leads to more severe off-target effects. However, the length of mismatched dsRNA, the choice of different RNAi targets, and the location of target sites within the same gene do not affect the severity of off-target effects. These parameters can be used to guide the design of possibly selective sequences for RNAi, optimize the specificity and efficiency of dsRNA, and facilitate practical applications of RNAi for pest control.

A case report and literature review on reactive cutaneous capillary endothelial proliferation induced by camrelizumab in a nasopharyngeal carcinoma patient.

Camrelizumab, a monoclonal antibody, blocks programmed cell death protein-1 from binding to T cells and programmed cell death ligand 1 on tumor cells, thereby ensuring sustained T cell activation and blocking immune escape of various types of cancer, including nasopharyngeal carcinoma. Reactive cutaneous capillary endothelial hyperplasia (RCCEP) is the most common immune-related adverse event in patients treated with camrelizumab. We report a case nasopharyngeal carcinoma in a patient with camrelizumab-induced RCCEP. A 68-year-old man diagnosed with nasopharyngeal carcinoma developed RCCEP at multiple locations after 3 months of camrelizumab treatment. RCCEP of the right lower eyelid affected closure of the right eye. In this report, we also reviewed previous literature on camrelizumab-induced RCCEP. In summary, the mechanism underlying camrelizumab-induced RCCEP remains unclear. RCCEP typically gradually subsides after discontinuing camrelizumab treatment. Larger nodules can be treated with lasers, ligation, or surgery. Although surgical excision is effective, RCCEP may recur in patients undergoing camrelizumab treatment. RCCEP management may not be required in the absence of adverse effects on the patient's daily life.

Neuronal Scaffold Protein ARMS Interacts with Synaptotagmin-4 C2AB through the Ankyrin Repeat Domain with an Unexpected Mode.

The ankyrin repeat-rich membrane spanning (ARMS), a transmembrane neuronal scaffold protein, plays a fundamental role in neuronal physiology, including neuronal development, polarity, differentiation, survival and angiogenesis, through interactions with diverse partners. Previous studies have shown that the ARMS negatively regulates brain-derived neurotrophic factor (BDNF) secretion by interacting with Synaptotagmin-4 (Syt4), thereby affecting neurogenesis and the development and function of the nervous system. However, the molecular mechanisms of the ARMS/Syt4 complex assembly remain unclear. Here, we confirmed that the ARMS directly interacts with Syt4 through its N-terminal ankyrin repeats 1-8. Unexpectedly, both the C2A and C2B domains of Syt4 are necessary for binding with the ARMS. We then combined the predicted complex structural models from AlphaFold2 with systematic biochemical analyses using point mutagenesis to underline the molecular basis of ARMS/Syt4 complex formation and to identify two conserved residues, E15 and W72, of the ARMS, as essential residues mediating the assembly of the complex. Furthermore, we showed that ARMS proteins are unable to interact with Syt1 or Syt3, indicating that the interaction between ARMS and Syt4 is specific. Taken together, the findings from this study provide biochemical details on the interaction between the ARMS and Syt4, thereby offering a biochemical basis for the further understanding of the potential mechanisms and functional implications of the ARMS/Syt4 complex formation, especially with regard to the modulation of BDNF secretion and associated neuropathies.

Knockdown of the glutamate-gated chloride channel gene decreases emamectin benzoate susceptibility in the fall armyworm, Spodoptera frugiperda.

Emamectin benzoate (EB), a derivative of avermectin, is the primary insecticide used to control the fall armyworm (FAW) in China. However, the specific molecular targets of EB against FAW remain unclear. In this study, we cloned the glutamate-gated chloride channel (GluCl) gene, which is known to be a primary molecular target for avermectin. We first investigated the transcript levels of SfGluCl in FAW and found that the expression level of SfGluCl in the head and nerve cord was significantly higher than that in other tissues. Furthermore, we found that the expression level of SfGluCl was significantly higher in eggs than that in other developmental stages, including larvae, pupae, and adults. Additionally, we identified three variable splice forms of SfGluCl in exons 3 and 9 and found that their splice frequencies remained unaffected by treatment with the LC50 of EB. RNAi mediated knockdown of SfGluCl showed a significant reduction of 42% and 65% after 48 and 72 h of dsRNA feeding, respectively. Importantly, knockdown of SfGluCl sifgnificantly reduced LC50 and LC90 EB treatment induced mortality of FAW larvae by 15% and 44%, respectively, compared to the control group feeding by dsEGFP. In contrast, there were no significant changes in the mortality of FAW larvae treated with the control insecticides chlorantraniliprole and spinetoram. Finally, molecular docking simulations revealed that EB bound to the large amino-terminal extracellular domain of SfGluCl by forming five hydrogen bonds, two alkyl hydrophobic interactions and one salt bridge. These findings strongly suggest that GluCl may serve as one of the molecular targets of EB in FAW, shedding light on the mode of action of this important insecticide.

Developmental hazards of 2,2',4,4'-tetrabromodiphenyl ether induced endoplasmic reticulum stress on early life stages of zebrafish (Danio rerio).

Polybrominated diphenyl ether flame retardants are known to have adverse effects on the development of organisms. We investigated the molecular mechanisms associated with the developmental hazards of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in zebrafish, as well as the behavioral and morphological alterations involved, focusing on endoplasmic reticulum stress (ERS), oxidative stress, and apoptosis. Our study revealed behavioral alterations in zebrafish exposed to BDE-47, including impaired motor activity, reduced exploration, and abnormal swimming patterns. In addition, we observed malformations in craniofacial regions and other developmental abnormalities that may be associated with ERS-induced cellular dysfunction. BDE-47 exposure showed apparent changes in ERS, oxidative stress, and apoptosis biomarkers at different developmental stages in zebrafish through gene expression analysis and enzyme activity assays. The study indicated that exposure to BDE-47 results in ERS, as supported by the upregulation of ERS-related genes and increased activity of ERS markers. In addition, oxidative stress-related genes showed different expression patterns, suggesting that oxidative stress is involved in the BDE-47 toxic effects. Moreover, an assessment of apoptotic biomarkers revealed an imbalance in the expression levels of pro- and anti-apoptotic genes, suggesting that BDE-47 exposure activated the apoptotic pathway. These results highlight the complex interactions between ERS, oxidative stress, apoptosis, behavioral alterations, and morphological malformations following BDE-47 exposure in zebrafish. Understanding the mechanisms of toxicity of developmental hazards is essential to elucidate the toxicological effects of environmental contaminants. The knowledge can help develop strategies to mitigate their adverse effects on the health of ecosystems and humans.