Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics.

In vivo pharmacology and optogenetics hold tremendous promise for dissection of neural circuits, cellular signaling, and manipulating neurophysiological systems in awake, behaving animals. Existing neural interface technologies, such as metal cannulas connected to external drug supplies for pharmacological infusions and tethered fiber optics for optogenetics, are not ideal for minimally invasive, untethered studies on freely behaving animals. Here, we introduce wireless optofluidic neural probes that combine ultrathin, soft microfluidic drug delivery with cellular-scale inorganic light-emitting diode (µ-ILED) arrays. These probes are orders of magnitude smaller than cannulas and allow wireless, programmed spatiotemporal control of fluid delivery and photostimulation. We demonstrate these devices in freely moving animals to modify gene expression, deliver peptide ligands, and provide concurrent photostimulation with antagonist drug delivery to manipulate mesoaccumbens reward-related behavior. The minimally invasive operation of these probes forecasts utility in other organ systems and species, with potential for broad application in biomedical science, engineering, and medicine.

Decrotonylation of cGAS K254 prompts homologous recombination repair by blocking its DNA binding and releasing PARP1.

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, also exhibits nuclear genomic localization and is involved in DNA damage signaling. In this study, we investigated the impact of cGAS crotonylation on the regulation of the DNA damage response, particularly homologous recombination repair, following exposure to ionizing radiation (IR). Lysine 254 of cGAS is constitutively crotonylated by the CREB-binding protein; however, IR-induced DNA damage triggers sirtuin 3 (SIRT3)-mediated decrotonylation. Lysine 254 decrotonylation decreased the DNA-binding affinity of cGAS and inhibited its interaction with PARP1, promoting homologous recombination repair. Moreover, SIRT3 suppression led to homologous recombination repair inhibition and markedly sensitized cancer cells to IR and DNA-damaging chemicals, highlighting SIRT3 as a potential target for cancer therapy. Overall, this study revealed the crucial role of cGAS crotonylation in the DNA damage response. Furthermore, we propose that modulating cGAS and SIRT3 activities could be potential strategies for cancer therapy.

Arabidopsis CHROMATIN REMODELING 19 acts as a transcriptional repressor and contributes to plant pathogen resistance.

Chromatin remodelers act in an ATP-dependent manner to modulate chromatin structure and thus genome function. Here, we report that the Arabidopsis (Arabidopsis thaliana) remodeler CHROMATIN REMODELING19 (CHR19) is enriched in gene body regions, and its depletion causes massive changes in nucleosome position and occupancy in the genome. Consistent with these changes, an in vitro assay verified that CHR19 can utilize ATP to slide nucleosomes. A variety of inducible genes, including several important genes in the salicylic acid (SA) and jasmonic acid (JA) pathways, were transcriptionally upregulated in the chr19 mutant under normal growth conditions, indicative of a role of CHR19 in transcriptional repression. In addition, the chr19 mutation triggered higher susceptibility to the JA pathway-defended necrotrophic fungal pathogen Botrytis cinerea, but did not affect the growth of the SA pathway-defended hemibiotrophic bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Expression of CHR19 was tissue-specific and inhibited specifically by SA treatment. Such inhibition significantly decreased the local chromatin enrichment of CHR19 at the associated SA pathway genes, which resulted in their full activation upon SA treatment. Overall, our findings clarify CHR19 to be a novel regulator acting at the chromatin level to impact the transcription of genes underlying plant resistance to different pathogens.

Unveiling the Morphology of Carbon-Supported Ru Nanoparticles by Multiscale Modeling.

Simulating the behavior of metal nanoparticles on supports is crucial for boosting their catalytic performance and various nanotechnology applications; however, such simulations are limited by the conflicts between accuracy and efficiency. Herein, we introduce a multiscale modeling strategy to unveil the morphology of Ru supported on pristine and N-doped graphene. Our multiscale modeling started with the electronic structures of a supported Ru single atom, revealing the strong metal-support interaction around pyridinic nitrogen sites. To determine the stable configurations of Ru2-13 clusters on three different graphene supports, global energy minimum searches were performed. The sintering of the global minimum Ru13 clusters on supports was further simulated by ab initio molecular dynamics (AIMD). The AIMD data set was then collected for deep potential molecular dynamics to study the melting of Ru nanoparticles. This study presents comprehensive descriptions of carbon-supported Ru and develops modeling approaches that bridge different scales and can be applied to various supported nanoparticle systems.

Sulfonic Acid-Functionalized Tetraphenylethylene-Amplified Electrochemiluminescence by Regulating π-π Interaction.

The electrochemiluminescence (ECL) effectiveness of the tris(bipyridine) ruthenium(II) (Ru(bpy)32+) system is hampered by aggregation-caused quenching (ACQ) in optoelectronic systems as a result of π-π accumulation of the aromatic ring structure. In this work, a negatively charged tetraphenylvinyl molecule (TPE-2SO3Na, TPE-4SO3Na) was synthesized to modify the electrode interface, and the π-π accumulation between Ru(bpy)32+ molecules was transformed into the π-π interaction between Ru(bpy)32+ and TPE molecules. Interestingly, the ECL signal intensity of the Ru(bpy)32+-tripropylamine (TPA) system in the presence of TPE-2SO3Na was increased by about 15 times due to the π-π action and electrostatic action. In comparison with traditional physical packaging with porous zeolites, metal-organic frameworks (MOFs), and covalent organic frameworks (COFs), the fabricated electrode interface modification strategy was simple and efficient to avoid π-π accumulation in aqueous solutions. Our success will inspire other researchers to investigate the supramolecular interaction (π-π interaction, electrostatic interaction, hydrophilic interaction, and host-guest interaction) at the electrode interface to amplify the ECL intensities of Ru(bpy)32+.

Unveiling facial kinship: The BioKinVis dataset for facial kinship verification and genetic association studies.

Facial image-based kinship verification represents a burgeoning frontier within the realms of computer vision and biomedicine. Recent genome-wide association studies have underscored the heritability of human facial morphology, revealing its predictability based on genetic information. These revelations form a robust foundation for advancing facial image-based kinship verification. Despite strides in computer vision, there remains a discernible gap between the biomedical and computer vision domains. Notably, the absence of family photo datasets established through biological paternity testing methods poses a significant challenge. This study addresses this gap by introducing the biological kinship visualization dataset, encompassing 5773 individuals from 2412 families with biologically confirmed kinship. Our analysis delves into the distribution and influencing factors of facial similarity among parent-child pairs, probing the potential association between forensic short tandem repeat polymorphisms and facial similarity. Additionally, we have developed a machine learning model for facial image-based kinship verification, achieving an accuracy of 0.80 in the dataset. To facilitate further exploration, we have established an online tool and database, accessible at http://120.55.161.230:88/.

TNKS1BP1 mediates AECII senescence and radiation induced lung injury through suppressing EEF2 degradation.

BACKGROUND: Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. RESULTS: Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. CONCLUSIONS: Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.

Understanding Water Diffusion Behaviors in Epoxy Resin through Molecular Simulations and Experiments.

The unclear understanding of the water diffusion behavior posts a big challenge to the manipulation of water absorption properties in epoxy resins. Herein, we investigated the water diffusion behavior and its relationship with molecule structures inside an epoxy resin mainly by the nonequilibrium molecular dynamics and experiments. It is found that at the initial rapid water absorption stage, bound water and free water both contribute, while at the later slow water absorption stage, free water plays a dominant role. The observed evolution of free water and bound water cannot be explained by the traditional Langmuir model. In addition, molecule polarity, free volume, and segment mobility can all influence the water diffusion process. Hence, the epoxy resin with low polarity and high molecular segment mobility is endowed with higher diffusion coefficients. The saturated water absorption content is almost dependent on the polarity. The understanding of how water diffuses and what decides the diffusion process is critical to the rational design of molecule structures for improving the water resistance in epoxy resin.

Retinal Arterial Macroaneurysm Combined with Branch Retinal Artery Occlusion: Literature Review.

PURPOSE: Summarizing the causes of retinal arterial microaneurysm (RAM) combined with branch retinal artery occlusion (BRAO). METHODS: The case reports of RAM combined with BRAO were searched in PubMed, Web of Science, and CNKI databases before May 1, 2024. A total of 9 participants from 9 case reports were included to analyze factors leading to complications. RESULTS: The reasons for this complication are as follows: complications during photocoagulation therapy. Intraretinal hemorrhage and exudation result in compression of adjacent or distal arteries, resulting in BRAO. Embolus dislodgement or intra-arterial embolus formation can block the artery, damage the wall, and provide conditions for the development of RAM. In addition, it is necessary to be alert to the optic-disc macroaneurysm, if hemorrhage or embolus formation in the macroaneurysm will affect the blood supply of the downstream artery, affecting a large range of the retina. CONCLUSIONS: Based on the review of case reports, we found that RAM and BRAO can cause each other. Acute vision loss can result when a complication occurs. In addition, retinal vascular diseases can reflect the whole body, suggesting that ophthalmologists need to pay attention not only to the patient's fundus but also to the patient's systemic diseases.

A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation.

BACKGROUND: This article reports an extremely rare case of lipoprotein glomerulopathy (LPG) with apolipoprotein E gene (APOE) Chicago mutation in a young Chinese male. Only five cases or families with APOE Chicago mutations have been reported in the literature. CASE PRESENTATION: The young male patient is manifested with nephrotic syndrome, accompanied by hyperlipidemia with a preferable increase in triglycerides and elevated ApoE level. Renal biopsy of the patient showed highly dilated glomerular capillaries filled with vacuolar lipids, segmentally fused podocyte foot processes, vacuolar degeneration of renal tubular epithelial cells and absence of electron-dense material, which indicates the diagnosis of LPG. Whole-exome gene sequencing identified the heterozygous mutation of NM_000041.4:c.494G > C (p.Arg165Pro), which is in the exon 4 of the APOE gene and also known as APOE Chicago mutation, a rare mutation of LPG. Further family pedigree gene analysis clarified that the mutation was inherited from the patient's mother, who does not have high ApoE levels or renal manifestations. This is also consistent with the incomplete penetrance of APOE gene mutations in LPG. Under lipid-lowering treatments, including a low-fat diet and fenofibrate, the patient's urinary protein was partially controlled, and the albumin level was recovered. CONCLUSION: Patients with nephrotic syndrome and elevated ApoE levels should be prompted into renal biopsy to avoid delay of appropriate treatment and unnecessary use of glucocorticoids. This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing. The timely diagnosis and treatment improved the patient's symptoms. This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.

Air pollution and the risk of incident chronic kidney disease in patients with diabetes: An exposure-response analysis.

Impact of air pollution on incident chronic kidney disease (CKD) in diabetic patients is insufficiently studied. We aimed to examine exposure-response associations of PM2.5, PM10, PM2.5-10, NO2, and NOX with incident CKD in diabetic patients in the UK. We also widened exposure level of PM2.5 and examined PM2.5-CKD association in diabetic patients across the entire range of global concentration. Based on data from UK biobank cohort, we applied Cox proportional hazards models and the shape constrained health impact function to investigate the associations between air pollutants and incident CKD in diabetic patients. Global exposure mortality model was applied to combine the PM2.5-CKD association in diabetic patients in the UK with all other published associations. Multiple air pollutants were positively associated with incident CKD in diabetic patients in the UK, with hazard ratios (HRs) of 1.034 (95 %CI: 1.015-1.053) and 1.021 (95 %CI: 1.007-1.036) for every 1 µg/m3 increase in PM2.5 and PM10 concentration, and 1.113 (95 %CI: 1.053-1.177) and 1.058 (95 %CI: 1.027-1.091) for every 10 µg/m3 increase in NO2 and NOX concentration, respectively. For PM2.5-10, associations with CKD in diabetic patients did not reach the statistical significance. Exposure-response associations with CKD in diabetic patients showed a near-linear trend for PM2.5, PM10, NO2, and NOX in the UK, whereas PM2.5-DKD associations in the globe exhibited a non-linear increasing trend. This study supports that air pollution could significantly increase the risk of CKD onset in diabetic patients.

Molecular mechanism of selenium against lead-induced apoptosis in chicken brainstem relating to heat shock protein, selenoproteins, and inflammatory cytokines.

Extensive application of lead (Pb) brought about environmental pollution and toxic reactions of organisms. Selenium (Se) has the effect of antagonizing Pb poisoning in humans and animals. However, it is still unclear how Pb causes brainstem toxicity. In the present study, we wanted to investigate whether Se can alleviate Pb toxicity in chicken brainstems by reducing apoptosis. One hundred and eighty chickens were randomly divided into four groups, namely the control group, the Se group, the Pb group, and the Se/Pb group. Morphological examination, ultrastructural observation, relative mRNA expressions of genes on heat shock proteins (HSPs); selenoproteins; inflammatory cytokines; and apoptosis-related factors were investigated. The results showed that Pb exposure led to tissue damage and apoptosis in chicken brainstems. Furthermore, an atypical expression of HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90); selenoprotein family glutathione peroxidase (GPx) 1, GPx2, GPx3, and GPx4), thioredoxin reductases (Txnrd) (Txnrd1, Txnrd2, and Txnrd3), dio selenoprotein famliy (diodothyronine deiodinases (Dio)1, Dio2, and Dio3), as well as other selenoproteins (selenoprotein (Sel)T, SelK, SelS, SelH, SelM, SelU, SelI, SelO, Selpb, selenoprotein n1 (Sepn1), Sepp1, Sepx1, Sepw1, 15-kDa selenoprotein (Sep15), and selenophosphate synthetases 2 (SPS2)); inflammatory cytokines (Interleukin 2 (IL-2), IL-4, IL-6, IL-12ß, IL-17, and Interferon-γ (IFN-γ)); and apoptosis-related genes (B-cell lymphoma-2 (Bcl-2), tumor protein 53 (p53), Bcl-2 Associated X (Bax), Cytochrome c (Cyt c), and Caspase-3) were identified. An inflammatory reaction and apoptosis were induced in chicken brainstems after exposure to Pb. Se alleviated the abnormal expression of HSPs, selenoproteins, inflammatory cytokines, and apoptosis in brainstem tissues of chickens treated with Pb. The results indicated that HSPs, selenoproteins, inflammatory, and apoptosis were involved in Se-resisted Pb poisoning. Overall, Se had resistance effect against Pb poisoning, and can be act as an antidote for Pb poisoning in animals.

The effects of Tripterygium wilfordii Hook F on renal outcomes in type 2 diabetic kidney disease patients with severe proteinuria: a single-center cohort study.

AIM: Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD. METHODS: Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes. RESULTS: By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111-0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081-0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018). CONCLUSION: In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.

Aggregation-induced emission-active micelles: synthesis, characterization, and applications.

Aggregation-induced emission (AIE)-active micelles are a type of fluorescent functional materials that exhibit enhanced emissions in the aggregated surfactant state. They have received significant interest due to their excellent fluorescence efficiency in the aggregated state, remarkable processability, and solubility. AIE-active micelles can be designed through the self-assembly of amphipathic AIE luminogens (AIEgens) and the encapsulation of non-emissive amphipathic molecules in AIEgens. Currently, a wide range of AIE-active micelles have been constructed, with a significant increase in research interest in this area. A series of advanced techniques has been used to characterize AIE-active micelles, such as cryogenic-electron microscopy (Cryo-EM) and confocal laser scanning microscopy (CLSM). This review provides an overview of the synthesis, characterization, and applications of AIE-active micelles, especially their applications in cell and in vivo imaging, biological and organic compound sensors, anticancer drugs, gene delivery, chemotherapy, photodynamic therapy, and photocatalytic reactions, with a focus on the most recent developments. Based on the synergistic effect of micelles and AIE, it is anticipated that this review will guide the development of innovative and fascinating AIE-active micelle materials with exciting architectures and functions in the future.

Regulating Sulfur Redox Kinetics by Coupling Photocatalysis for High-Performance Photo-Assisted Lithium-Sulfur Batteries.

Challenges such as shuttle effect have hindered the commercialization of lithium-sulfur batteries (LSBs), despite their potential as high-energy-density storage devices. To address these issues, we explore the integration of solar energy into LSBs, creating a photo-assisted lithium-sulfur battery (PA-LSB). The PA-LSB provides a novel and sustainable solution by coupling the photocatalytic effect to accelerate sulfur redox reactions. Herein, a perovskite quantum dot-loaded MOF material serves as a cathode for the PA-LSB, creating built-in electric fields at the micro-interface to extend the lifetime of photo-generated charge carriers. The band structure of the composite material aligns well with the electrochemical reaction potential of lithium-sulfur, enabling precise regulation of polysulfides in the cathode of the PA-LSB system. This is attributed to the selective catalysis of the liquid-solid reaction stage in the lithium-sulfur electrochemical process by photocatalysis. These contribute to the outstanding performance of PA-LSBs, particularly demonstrating a remarkably high reversible capacity of 679 mAh g-1 at 5 C, maintaining stable cycling for 1500 cycles with the capacity decay rate of 0.022 % per cycle. Additionally, the photo-charging capability of the PA-LSB holds the potential to compensate for non-electric energy losses during the energy storage process, contributing to the development of lossless energy storage devices.

Synthesis of Phase Junction Cadmium Sulfide Photocatalyst under Sulfur-Rich Solution System for Efficient Photocatalytic Hydrogen Evolution.

Photocatalyst with excellent semiconductor properties is the key point to realize the efficient photocatalytic hydrogen evolution (PHE). As a representative binary metal sulfide (BMS) semiconductor, cadmium sulfide (CdS) possesses suitable bandgap of 2.4 eV and negative conduction band potential, which has a great potential to realize efficient visible-light PHE performance. In this work, CdS with unique cubic/hexagonal phase junction is facilely synthesized through a sulfur-rich butyldithiocarbamate acid (BDCA) solution process. The results illustrate that the phase junction can efficiently enhance the separation and transfer of photogenerated electron-hole pairs, resulting in an excellent PHE performance. In addition, the sulfur-rich property of BDCA solution leads to the absence of additional sulfur sources during the synthesis of CdS photocatalyst, which greatly simplifies the fabrication process. The optimal PHE rate of the BDCA-synthesized phase junction CdS photocatalyst is 7.294 mmol g-1  h-1 and exhibits a favorable photostability. Moreover, density function theory calculations indicated that the apparent redistribution of charge density in the cubic/hexagonal phase junction regions gives a suitable hydrogen adsorption capacity, which is responsible for the enhanced PHE activity.

LANA regulates miR-155/GATA3 signaling axis by enhancing c-Jun/c-Fos interaction to promote the proliferation and migration of KSHV-infected cells.

Kaposi's sarcoma (KS) is the second most common tumor in people infected with human immunodeficiency virus worldwide, but its pathogenesis is still unclear. In this study, we discovered that the expression of GATA-binding protein 3 (GATA3) was lowly expressed in KS tissues and KSHV-infected cells, while microRNA-155 (miR-155) was highly expressed in KS serum and KSHV-infected cells. miR-155 promoted the proliferation, migration and invasion of KSHV infection by targeting GATA3. Further, The KSHV-encoded protein, the Latency associated nuclear antigen (LANA), promotes the proliferation, migration and invasion of KSHV-infected cells by regulating the miR-155/GATA3 axis. Regarding the molecular mechanism, c-Jun and c-Fos interact to form a complex. LANA upregulates the expression of c-Jun and c-Fos and enhances the formation of c-Jun/c-Fos complex. The complex binds to the -95∼-100 bp site of miR-155 promoter and transcriptionally activates miR-155. All in all, LANA enhances the c-Jun/c-Fos interaction, resulting in enhanced transcriptional regulation of miR-155 by the c-Jun/c-Fos complex, thereby downregulating GATA3 and promoting the proliferation, migration and invasion of KSHV-infected cells. The discovery of LANA/c-Jun/c-Fos/miR-155/GATA3 further refines the pathogenesis of KS, potentially opening a new avenue for developing effective drugs against KS.

Transcriptome analysis of largemouth bass (Micropterus salmoides) challenged with LPS and polyI:C.

Largemouth bass (Micropterus salmoides) is a worldwide commercially important aquatic species. In recent years, pathogenic diseases cause great economic losses and hinder the industry of largemouth bass. To further understand the immune response against pathogens in largemouth bass, splenic transcriptome libraries of largemouth bass were respectively constructed at 12 h post-challenged with phosphate-buffered saline (PBS), lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (polyI:C) by using RNA sequencing technology (RNA-seq). RNA libraries were constructed using 9 RNA splenic samples isolated from three biological replicates of the three groups and sequenced on the DNBSEQ platform. A total number of 86,306 unigenes were obtained. Through pairwise comparisons among the three groups, we identified 11,295 different expression genes (DEGs) exhibiting significant differences at the transcript level. There were 7, 7, and 13 signal pathways were significantly enriched in LPS-PBS comparison, polyI:C-PBS comparison, and LPS-polyI:C comparison, respectively, indicating that the immune response to different pathogens was distinct in largemouth bass. To the best of our knowledge, this is the first report on the immune response of largemouth bass against different pathogen-associated molecular patterns (PAMPs) stimuli using transcriptomic analysis. Our results provide a valuable resource and new insights to understanding the immune characteristics of largemouth bass against different pathogens.

Nano-selenium protects grass carp hepatocytes against 4-tert-butylphenol-induced mitochondrial apoptosis and necroptosis via suppressing ROS-PARP1 axis.

4-tert-butylphenol (4-tBP) is a monomer widely used in the synthesis of industrial chemicals, and posed a high risk to aquatic animals. Our study focused on toxic phenotype and mechanism of detoxification in grass carp hepatocytes (L8824) after 4-tBP-treatment. In this experiment, L8824 displayed hallmark phenotypes of apoptosis and necroptosis after 4-tBP exposure, as evidenced by changes in cell morphology, increased rates of apoptosis and necrosis, the loss of MMP, the accumulation of ROS, and changes in associated factors (PARP1, JNK, Bid, Bcl-2, Bax, AIFM1, CytC, Caspase 9, APAF1, Caspase 3, TNF-α, TNFR1, RIPK1, RIPK3, and MLKL). Furthermore, we found that 4-tBP-induced apoptosis and necroptosis were reversed by pretreating with N-Acetylcysteine (a ROS scavenger) and 3-Aminobenzamide (a PARP1 inhibitor), indicating that 4-tBP induced the onset of mitochondrial apoptosis and necroptosis in L8824 via activating ROS-PARP1 axis. Nano-selenium (Nano-Se) is a novel form of Se with a noteworthy antioxidant capacity. Here, Nano-Se was found to have preventive, therapeutic, and resistance effects on 4-tBP-induced L8824 apoptosis and necroptosis. Nano-Se co-treatment with 4-tBP was an optimal way to alleviate 4-tBP-induced apoptosis and necroptosis. We demonstrated for the first time that Nano-Se protected L8824 against 4-tBP-induced mitochondrial apoptosis and necroptosis through ROS-PARP1 pathway. This study will provide a new theoretical basis for 4-tBP toxicology researches and aquatic animal protection.

Cadmium exposure caused cardiotoxicity in common carps (Cyprinus carpio L.): miR-9-5p, oxidative stress, energetic impairment, mitochondrial division/fusion imbalance, inflammation, and autophagy.

Cadmium (Cd), a toxic heavy metal pollutant, is a threat to human and eatable fish health. Common carps are widely cultivated and eaten by humans. However, there are no reports about Cd-damaged common carp hearts. Our experiment attempted to investigate the cardiotoxicity of Cd to common carps by establishing a common carp Cd exposure model. Our results showed that Cd injured hearts. Moreover, Cd treatment induced autophagy via miR-9-5p/Sirt1/mTOR/ULK1 pathway. Cd exposure caused oxidant/antioxidant imbalance and oxidative stress; and led to energetic impairment. Energetic impairment partook in oxidative stress-mediated autophagy through AMPK/mTOR/ULK1 pathway. Furthermore, Cd caused mitochondrial division/fusion imbalance and resulted in inflammatory injury via NF-κB-COX-2-PTGEs and NF-κB-COX-2-TNF-α pathways. Oxidative stress mediated mitochondrial division/fusion imbalance, further induced inflammation and autophagy via OPA1/NF-κB-COX-2-TNF-α-Beclin1 and OPA1/NF-κB-COX-2-TNF-α/P62 pathways under Cd treatment. Taken together, miR-9-5p, oxidative stress, energetic impairment, mitochondrial division/fusion imbalance, inflammation, and autophagy participated in the mechanism of Cd-cardiotoxicity to common carps. Our study revealed harmful effect of Cd on hearts, and provided new information for researches of environmental pollutant toxicity.