Fenvalerate (FEN), a widely used an agricultural type II pyrethroid pesticide, has been found in the environment and human tissues. Nevertheless, the cardiotoxicity of FEN remains poorly understood. This study aimed to explore the cardiotoxicity of FEN and the potential cardioprotective role of resveratrol (RES, a polyphenolic antioxidant) in zebrafish. In this research, zebrafish embryos were exposed to FEN at concentrations of 0, 3.5 and 7 μg/L from 4 to 96 h post fertilization (hpf) and developmental cardiotoxicity was evaluated. The findings demonstrated that FEN significantly impaired embryonic development, with lower survival and hatching success, diminished spontaneous movement, lower heart rate and body length, as well as an elevated malformation rate. FEN induced both morphological and functional abnormalities in the heart of myl7:egfp zebrafish, along with the downregulation of genes related to cardiac development. FEN also induced oxidative stress by generating excessive reactive oxygen species and disturbing antioxidant enzyme activities, thereby triggering cardiomyocyte apoptosis via upregulated apoptotic gene expression. Remarkably, these cardiotoxic effects were effectively mitigated by RES via its antioxidation, underscoring oxidative stress and apoptosis as important mechanisms of FEN-induced cardiotoxicity in zebrafish. Overall, this study delineated the key mechanisms of FEN-triggered cardiotoxicity and identified RES as a promising candidate for therapeutic intervention.

Copper (Cu) is a necessary micro-element and plays important roles in many biochemical processes. However, excessive Cu intake can lead to multi-organ toxicity, especially in the spleen. To gain further insights into the specific mechanisms of splenic toxicity associated with Cu-induced metabolic disorders, 192 one-day-old chickens were selected and randomly divided into four groups for this study. The broilers were fed with diets containing Cu at final concentrations of 11, 110, 220 and 330 mg/kg for 49 days. The results showed that high dietary Cu caused nuclear shrinkage and mitochondrial vacuolization in the spleen and induced splenic injury through regulating the glutathione metabolism, pentose and gluconate interconversion, tryptophan metabolism and glycerophosphatidylcholine metabolism pathways. Moreover, excess Cu could disorder the mitochondrial dynamics via up-regulating the levels of Drp1, Parkin PINK1, and Dynein, and down-regulating the levels of Mfn1, Mfn2 and OPA1. Cu treatment increased the levels of LC3A, LC3B, mTOR, Beclin1, and ATG5 and decreased the p62 level to promote autophagy of splenocytes. Meanwhile, a high dose of Cu promoted splenocyte apoptosis by increasing the levels of p53, BAK-1, Bax, Cyt C and Caspase-3 and decreasing the level of Bcl-2. These results demonstrated that high dietary Cu could cause autophagy and apoptosis via inducing metabolic disturbances and disordering mitochondrial dynamics in the spleen of broiler chicken.

Myclobutanil (MYC) is a common triazole fungicide widely applied in agriculture. MYC extensively exists in the natural environment and can be detected in organisms. However, little is known about MYC-induced embryonic developmental damage. This study aimed to unravel the cardiotoxicity of MYC and the underlying mechanisms, as well as the cardioprotective effect of curcumin (CUR, an antioxidant polyphenol) using the zebrafish model. Here, zebrafish embryos were exposed to MYC at concentrations of 0, 0.5, 1 and 2 mg/L from 4 to 96 h post fertilization (hpf) and cardiac development was assessed. As results, MYC reduced the survival and hatching rate, body length and heart rate, but increased the malformation rate and spontaneous movement. MYC caused abnormal cardiac morphology and function in myl7:egfp transgenic zebrafish, and downregulated cardiac developmental genes. MYC promoted oxidative stress through excessive reactive oxygen species (ROS) accumulation and suppressed the activities of antioxidant enzymes, triggering cardiomyocytic apoptosis via upregulated expression of apoptosis-related genes. These adverse toxicities could be significantly ameliorated by the antioxidant properties of CUR, indicating that CUR rescued MYC-induced cardiotoxicity by inhibiting oxidative stress and apoptosis. Overall, our study revealed the potential mechanisms of oxidative stress and apoptosis in MYC-induced cardiotoxicity in zebrafish and identified the cardioprotection of CUR in this pathological process.

With the widespread implementation of environmental dredging, the dewaterability of dredged sediment has become a crucial technical requirement. This study investigates the use of a dual flocculant, consisting of cationic polyacrylamide (CPAM) and anionic polyacrylamide (APAM), for sediment pretreatment. The purpose of this research is to assess the effects of the dual flocculant on sediment dewatering performance. The experimental results demonstrate that at a dose of 0.16 %o CPAM and 0.12 %o APAM of total solids in the sediment slurry, the water content of the sediment cake significantly decreases to 23.9 %. This reduction highlights the notable advantages of the dual flocculant in improving dewatering efficiency. The conditioned sediment exhibits lower turbidity (97.7 % reduction) of supernatant and rapid settling-velocity of the floc, indicating effective capture and separation of fine particles from the sediment. Moreover, the enhanced viscoelasticity of the sediment cake signifies a substantial improvement in floc structural strength. These properties collectively contribute to enhanced dewaterability during filtration and compression stages. Furthermore, the optimal dosing sequence of CPAM followed by APAM outperforms the reverse mode, facilitating a more favorable reaction between particles and polymers. Overall, the sequential use of charged polyacrylamide results in significant improvements in sediment dewaterability, cost savings, and secondary pollution prevention.

TiO2-based catalysts with various surface heterostructures (0D, 1D, 2D, and 3D) have been widely researched owing to their cost-effectiveness, high stability, and environmentally friendly nature, and can be used for many applications in various fields, including hydrogen production and pollutant degradation. However, there are also many existing problems limiting their practical application, such as their large band gap and rapid electron–hole recombination rate. Owing to the abundance of recent achievements in materials science, we will summarize the recent structural engineering strategies which provide favorable photocatalytic activity enhancements, such as enhanced visible light absorption, stability, an increased charge–carrier separation rate and improved specific surface area. Among the various structural engineering methods in this review, we will introduce TiO2-based materials with different dimensional structures. Meanwhile, we also discuss recent achievements in synthesis methods and application of TiO2-based catalysts in various fields. We aim to display a comprehensive overview which can be a guide for the development of a new generation of TiO2-based catalysts according to their structural design for enhanced solar energy conversion.

Fenvalerate (FEN), a typical type II pyrethroid pesticide, is widely used in agriculture. FEN has been detected in the environment and human body. However, the neurotoxicity of FEN has not been well elucidated. This study aimed to explore the mechanisms underlying FEN-induced neurotoxicity using the zebrafish (Danio rerio) model. We also investigated whether curcumin (CUR), a polyphenol antioxidant that exhibits neuroprotective properties, can prevent FEN-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 3.5, 7 and 14 μg/L of FEN from 4 to 96 h post fertilization (hpf) and neurotoxicity was assessed. Our results showed that FEN decreased the survival rate, heart rate, body length and spontaneous movement, and increased malformation rate. FEN caused neurobehavioral alterations, including decreased swimming distance and velocity, movement time and clockwise rotation times. FEN also suppressed neurogenesis in transgenic HuC:egfp zebrafish, reduced cholinesterase activity and downregulated the expression of neurodevelopment related genes (elavl3, gfap, gap43 and mbp). In addition, FEN enhanced oxidative stress via excessive reactive oxygen species and antioxidant enzyme inhibition, then triggered apoptosis by upregulation of apoptotic genes (p53, bcl-2, bax and caspase 3). These adverse outcomes were alleviated by CUR, indicating that CUR mitigated FEN-induced neurotoxicity by inhibiting oxidative stress. Overall, this study revealed that CUR ameliorated FEN-induced neurotoxicity via its antioxidant, indicating a promising protection of CUR against environmental pollutant-induced developmental anomalies.

To study the effects of Cu overload on ER quality control in duck cerebrums, 144 ducks were treated with 8 mg/kg, 100 mg/kg, 200 mg/kg and 400 mg/kg Cu added in the feed for 45 days. From histopathological examination, we found that excessive Cu increased the amount of microglia and disintegrated neuron, decreased the number of Nissl bodies, perturbed nerve fibers in duck cerebrums. Cu poisoning also increased Cu, H2O2, T-SOD, and MDA levels, decreased Fe and CAT contents in duck cerebrums. Furthermore, Cu treatment upregulated the mRNA levels of the unfolded protein response genes (PERK, ATF6, and IRE1), ER-associated degradation genes (CNX, Derlin1, and Derlin2), autophagy genes (ATG5, ATG7, ATG10, Beclin1, LC3A, LC3B, and P62), and heat shock response genes (Hsp70 and Hsp90) in duck cerebrums; elevated the protein levels of p-PERK, CNX, SEL1L, Beclin1, P62, and LC3BII/LC3BI in duck cerebrums; increased the numbers of SEL1L and LC3B puncta in duck cerebrums. Thus, our data showed that excessive Cu could cause histopathological damage to duck cerebrums, disrupt the balance of the trace elements, induce oxidative stress and activation of ER quality control, thereby resulting in duck cerebrums damage.

Titanium dioxide nanoparticles (n-TiO2) could enhance the bioavailability and toxicity of coexisting organic contaminants in the aquatic environment. This study attempted to investigate the combined effects of n-TiO2 and difenoconazole (DIF) on the neurodevelopment of zebrafish and the underlying mechanisms. In this study, zebrafish embryos were exposed to n-TiO2 (100 μg/L), DIF (0, 0.1 and 0.5 mg/L) and their mixtures from 4 to 96 h post fertilization (hpf) and neurotoxicity was evaluated. Our results indicated that n-TiO2 adsorbed DIF into the brain of zebrafish and significantly enhanced the bioaccumulation of DIF and n-TiO2 in the 0.5 mg/L co-exposure group. 100 μg/L n-TiO2 was not developmentally toxic to the zebrafish larvae, but it exacerbated DIF-induced neurobehavioral alterations in the zebrafish larvae. n-TiO2 also aggravated DIF-induced suppression of central nervous system (CNS) neurogenesis in Tg (HuC:egfp) zebrafish, motor neuron axon length in Tg (hb9:egfp) zebrafish, and downregulation of neurodevelopmental genes (elavl3, ngn1, gap43, gfap and mbp). In addition, DIF elevated oxidative stress by accumulation of reactive oxygen species (ROS) and inhibition of antioxidant enzymes, and triggered apoptosis by upregulation of p53, bax, bcl-2 and caspase-3, which were markedly intensified in the presence of n-TiO2. Moreover, vitamin C (VC) ameliorated n-TiO2/DIF-induced abnormal locomotor behaviors and neurotoxicity by inhibiting oxidative stress and apoptosis, indicating that oxidative stress and apoptosis are involved in n-TiO2/DIF-induced neurotoxicity. Taken together, our data indicated that n-TiO2 enhanced the accumulation of DIF and heightened oxidative stress and apoptosis, thereby inducing neurotoxicity. This study exemplifies the importance of the toxicity assessment of chemical mixtures and novel insights to mitigate their combined toxicity.

Glioblastoma multiforme (GBM) is an aggressive brain tumor with high risks of recurrence and mortality. Chemoradiotherapy resistance has been considered a major factor contributing to the extremely poor prognosis of GBM patients. Therefore, there is an urgent need to develop highly effective therapeutic agents. Here, we demonstrate the anti-tumor effect of morusin, a typical prenylated flavonoid, in GBM through in vivo and in vitro models. Morusin showed selective cytotoxicity toward GBM cell lines without harming normal human astrocytes when the concentration was less than 20 µM. Morusin treatment significantly induced apoptosis of GBM cells, accompanied by the activation of endoplasmic reticulum (ER) stress, and the appearance of cytoplasmic vacuolation and autophagosomes in cells. Then, we found the ER stress activation and cytotoxicity of morusin were rescued by ER stress inhibitor 4-PBA. Furthermore, morusin arrested cell cycle at the G1 phase and inhibited cell proliferation of GBM cells through the Akt–mTOR–p70S6K pathway. Dysregulation of ERs and cell cycle in morusin exposed GBM cells were confirmed by RNA-seq analysis. Finally, we demonstrated the combination of morusin and TMZ remarkably enhanced ER stress and displayed a synergistic effect in GBM cells, and suppressed tumor progression in an orthotopic xenograft model. In conclusion, these findings reveal the toxicity of morusin to GBM cells and its ability to enhance drug sensitivity to TMZ, suggesting the potential application value of morusin in the development of therapeutic strategies for human GBM.

Background Ferroptosis is a form of iron-dependent cell death with increased free iron and massive lipid peroxidation. The discovery of ferroptosis offers insights into hepatocellular carcinoma (HCC) treatment. However, post-transcriptional regulation mechanisms of ferroptosis in HCC remain to be elucidated. The present study explored ferroptosis-related genes and their post-transcriptional regulation mechanisms in HCC. Methods A ferroptosis score was computed in The Cancer Genome Atlas (TCGA) cohort via gene set variation analysis (GSVA), and ferroptosis-related genes were screened by differential expression and correlation analyses. CircRNA/miRNA-mediated ferroptosis-related genes were predicted, and associations of ferroptosis-related genes with m1A/m5C/m6A regulators were analyzed. Immune cell infiltrations were inferred via CIBERSORT. NUDCD1 expression was examined in L-02, SMMC7721, and HepG2 cells via real time quantitative polymerase chain reaction (RT-qPCR) and western blots. After NUDCD1 was silenced, cell viability, glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) expression, and oxidized glutathione/glutathione (GSSG/GSH) and glutathione (GSH) levels were detected in SMMC7721 and HepG2 cells. Results The ferroptosis score was linked to poor overall survival (OS) of HCC, which was independent of other clinicopathological parameters. Ten ferroptosis-related genes were determined, namely UGT1A6, ATP6V1C1, MAFG, NUDCD1, PPP1R1A, TSKU, CTSB, AIFM2, CTSA, and CTNND2, which were post-transcriptionally regulated by circRNA/miRNA and m1A/m5C/m6A modifications in HCC. Most were significantly linked with most immune cell compositions within the immune microenvironment, and contributed to undesirable clinical outcomes. NUDCD1 was up-regulated in HCC cells, and its loss facilitated the ferroptosis of HCC cells. Conclusions Overall, our findings determined ferroptosis-related genes post-transcriptionally regulated by circRNA/miRNA and m1A/m5C/m6A RNA modifications, and experiments demonstrated that loss of NUDCD1 may facilitate the ferroptosis of HCC cells, which provides novel insights into the regulatory mechanisms of ferroptosis in HCC.

Sliver nanoparticles (AgNPs) are widely used in industry, agriculture, and medicine, potentially resulting in adverse effects on human health and aquatic environments. Here, we investigated the developmental toxicity of zebrafish embryos with acute exposure to AgNPs. Our results demonstrated developmental defects in 4 hpf zebrafish embryos after exposure to different concentrations of AgNPs for 72 h. In addition, RNA-seq profiling of zebrafish embryos after AgNPs treatment. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the differentially expressed genes (DEGs) were enriched in DNA replication initiation, oxidoreductase activity, DNA replication, cellular senescence, and oxidative phosphorylation signaling pathways in the AgNPs-treated group. Notably, we also found that AgNPs exposure could result in the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), the inhibition of superoxide dismutase (SOD), catalase (CAT), and mitochondrial complex I-V activities, and the downregulated expression of SOD, CAT, and mitochondrial complex I-IV chain-related genes. Moreover, the expression of mitochondrion-mediated apoptosis signaling pathway-related genes, such as bax, bcl2, caspase-3, and caspase-9, was significantly regulated after AgNPs exposure in zebrafish. Therefore, these findings demonstrated that AgNPs exposure could cause oxidative stress, induce mitochondrial dysfunction, and ultimately lead to developmental toxicity.

Glioma is the most common type of brain cancer. Chemotherapy combination with surgery and radiotherapy is a standard treatment for patients. Although there are many advances in glioma therapy, the prognosis of glioma patients has not significantly been improved over the past decades. Hence, there is still an urgent need to develop a new therapy to treat glioma. Cell viability was assessed by CellTiter Blue assay; flow cytometry (FCM) was used for detecting cell apoptosis; ROS detection was detected by ROS Assay; H2O2 detection was performed by hydrogen peroxide detection kits; real-time PCR and WB were used to determine gene expression. Using the glioma cell line U251 and U87, we investigated a possible combination inhibitory effect includes metformin and cold atmospheric plasma (CAP). The combination treatment showed a synergistic inhibitory effect on cell viability, significantly inducing cell apoptosis. Furthermore, we also found H2O2 produced by CAP has an important role in the synergistic inhibitory effect, eliminating H2O2 with catalase reversed the synergistic inhibitory effect. In addition, the transcript and protein levels of c-FOS were robustly increased after co-treated with metformin and CAP. Taken together, we propose that pre-treatment of glioma cells with metformin sensitize tumor cells to CAP, which may serve as a potential therapeutic strategy for glioma.

Helicobacter pylori is a gram-negative bacterium that is colonized in the stomach. H. pylori infection can lead to a series of stomach diseases. However, the relationship between H. pylori infection and colorectal cancer is currently controversial. Therefore, we performed this meta-analysis to further understand the relationship between H. pylori infection and colorectal cancer.We conducted a comprehensive retrieval from electronic databases, included the PubMed, Medline, China National Knowledge Infrastructure (CNKI), and China Wanfang Data Knowledge Service Platform databases (Wanfang Databases) through May 1st, 2018. We used the search terms H. pylori and colorectal cancer or colorectal carcinoma and collected all relevant studies to explore the association between H. pylori infection and colorectal cancer.Twenty-seven studies including 14357 cases were included. H. pylori infection was associated with an increased risk of colorectal cancer. A pooled odds ratio (OR) of 1.27 with a 95% CI of 1.17-1.37 (P<0.001) was calculated by using a fixed-effects model (I2=45.5%, P=0.006). The subgroup analysis revealed that H. pylori infection was associated with an increased risk of colorectal cancer in the subgroups of Western countries (OR=1.34, 95% CI: 1.14-1.57) (P<0.001), serological testing (OR=1.20, 95% CI: 1.08-1.34) (P=0.001), multiple methods of testing (OR=2.63, 95% CI: 1.09-6.31) (P=0.031), cross-sectional studies (OR=1.92, 95% CI: 1.17-3.16) (P=0.010) and case-control studies (OR 1.26, 95% CI: 1.16-1.36) (P<0.001).The present meta-analysis provides evidence suggests that a positive association between H. pylori infection and the risk of colorectal cancer.