Neurotoxicity of hexaconazole on rat brain: The aspect of biological rhythm.

Hexaconazole is a widely used and frequently detected fungicide which is also reported to be persistent in environment. The toxicity of Hex to non-organisms such as reproductive toxicity, endocrine disrupting toxicity, and carcinogenic toxicity had been reported. However, study on the Hex-induced neurotoxicity is rare and the mechanism is still unclear. Therefore, in this study, environmental related concentrations of Hex were chosen to investigate the effects of Hex on nervous system from the aspect of biological rhythm under 90 d sub-chronic exposure. The results showed that Hex significantly affected the cognitive function of rats resulting in the deterioration of learning and memory ability and induced oxidative stress in rat brain. Moreover, the notable changes of neurotransmitters in rat brain suggested the disorder of nerve signaling conduction induced by Hex. The influence of Hex on biological rhythm was further detected which showed that levels of rhythm regulatory genes and proteins significantly disturbed at four monitored time periods. Based on these results, it was supposed that the underlying mechanism of Hex-induced cognitive dysfunction might through oxidative stress pathway. Our findings could systematically and comprehensively clarify the effects of Hex on nervous system and were helpful for prevention neurological diseases induced by triazole pesticides.

MTH1 inhibition synergizes with ROS-inducing agents to trigger cervical cancer cells undergoing parthanatos.

Cervical cancer cells possess high levels of reactive oxygen species (ROS); thus, increasing oxidative stress above the toxicity threshold to induce cell death is a promising chemotherapeutic strategy. However, the underlying mechanisms of cell death are elusive, and efficacy and toxicity issues remain. Within DNA, 8-oxo-7,8-dihydroguanine (8-oxoG) is the most frequent base lesion repaired by 8-oxoguanine glycosylase 1 (OGG1)-initiated base excision repair. Cancer cells also express high levels of MutT homolog 1 (MTH1), which prevents DNA replication-induced incorporation of 8-oxoG into the genome by hydrolyzing 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP). Here, we revealed that ROS-inducing agents triggered cervical cancer to undergo parthanatos, which was mainly induced by massive DNA strand breaks resulting from overwhelming 8-oxoG excision by OGG1. Furthermore, the MTH1 inhibitor synergized with a relatively low dose of ROS-inducing agents by enhancing 8-oxoG loading in the DNA. In vivo, this drug combination suppressed the growth of tumor xenografts, and this inhibitory effect was significantly decreased in the absence of OGG1. Hence, the present study highlights the roles of base repair enzymes in cell death induction and suggests that the combination of lower doses of ROS-inducing agents with MTH1 inhibitors may be a more selective and safer strategy for cervical cancer chemotherapy.

Sub-chronic exposure to hexaconazole affects the lipid metabolism of rats through mTOR-PPAR-γ/SREBP1 signaling pathway mediated by oxidative stress.

Hexaconazole (Hex) is a widely used and high frequency detected triazole fungicide in agricultural products and environment which may pose potential toxicity to the nontargeted organisms. Hex had been reported to affect lipid homeostasis while the mechanism was undefined. This study aims to explore the characteristic lipidomic profiles and clarify the underlying signaling pathways of Hex-induced lipid metabolism disorder in rat liver. The results showed that sub-chronic exposure to environmental related concentrations of Hex caused histopathological changes, oxidative stress, fat accumulation, lipid biochemical parameter increase in rats. Moreover, the untargeted lipidomic analysis showed that the levels of TAG, PC, and PE and the pathway of glycerophospholipid metabolism were heavily altered by Hex. We further analyzed the lipid metabolism related genes and proteins which revealed that Hex exposure increased amount of lipogenesis by activating oxidative stress-mediated mTOR-PPAR-γ/SREBP1 signaling pathways. The imbalance of lipid homeostasis induced by Hex exposure might further lead to obesity, cardiovascular diseases (CVDs), and hyperlipidemia. Our results provided systematic and comprehensive evidence for the mechanism of Hex-induced lipid metabolism disorder at environmental concentrations and supplied a certain basis for its health risks assessment.

An Ultraflexible Electrode Array for Large-Scale Chronic Recording in the Nonhuman Primate Brain.

Single-unit (SU) recording in nonhuman primates (NHPs) is indispensible in the quest of how the brain works, yet electrodes currently used for the NHP brain are limited in signal longevity, stability, and spatial coverage. Using new structural materials, microfabrication, and penetration techniques, we develop a mechanically robust ultraflexible, 1 µm thin electrode array (MERF) that enables pial penetration and high-density, large-scale, and chronic recording of neurons along both vertical and horizontal cortical axes in the nonhuman primate brain. Recording from three monkeys yields 2,913 SUs from 1,065 functional recording channels (up to 240 days), with some SUs tracked for up to 2 months. Recording from the primary visual cortex (V1) reveals that neurons with similar orientation preferences for visual stimuli exhibited higher spike correlation. Furthermore, simultaneously recorded neurons in different cortical layers of the primary motor cortex (M1) show preferential firing for hand movements of different directions. Finally, it is shown that a linear decoder trained with neuronal spiking activity across M1 layers during monkey's hand movements can be used to achieve on-line control of cursor movement. Thus, the MERF electrode array offers a new tool for basic neuroscience studies and brain-machine interface (BMI) applications in the primate brain.

Effect of Processing on Reduction in Chiral Pesticide Hexaconazole for Kiwifruit Juice.

In this study, the residue levels of chiral pesticide hexaconazole during kiwifruit juice processing (peeling, homogenization, and sterilization) were investigated by using high-performance liquid chromatography (HPLC), and the dietary risk during these processes was also assessed. Hexaconazole was applied at dosages of 173.33 and 346.66 mg/L (recommended and double recommended dosage) in kiwifruit. In the peeling process, 87.7% to 89.2% of the residues were decreased after peeling. Levels of hexaconazole residues in homogenization and sterilization processes further increased from 0.49% to 24.3% and from 0.2% to 3.0%, respectively. Processing factors (PFs) for (+)- and (-)-hexaconazole after peeling, homogenization, and sterilization were 0.12, 0.88, 0.99 for low-dose treatment and 0.12, 0.87, 0.99 for high-dose treatment, respectively. The enantioselectivity of hexaconazole during these procedures was evaluated by enantiomeric fractions (EFs) values, which were around 0.5 throughout all the procedures, indicating that hexaconazole enantiomers had similar dissipation behaviors during kiwifruit juice processing. The RQc of hexaconazole in pre-peeling samples was significantly greater than 100% under two dosages, while the peeling process can notably decrease the values to an acceptable level. The results of this study could provide guidance for agriculture applications and kiwi commodity production to decrease the risk of hexaconazole residue.

Quantitative analysis of the current status and research trends of biochar research - A scientific bibliometric analysis based on global research achievements from 2003 to 2023.

Biochar has excellent physical and chemical properties such as porosity, high carbon content, high cation exchange capacity, and rich surface functional groups and has been widely used in environmental remediation. Over the past 20 years, although various reviews have described the application of biochar as an environmentally friendly multifunctional material in environmental remediation, no comprehensive summary and analysis of the research trends in this field exists. To promote the rapid and stable development of the field of biochar, the current state of research on biochar is clarified using the bibliometric method in this report, and potential development directions and challenges for the future are identified. All relevant biochar literature from 2003-2023 was collected from the Chinese National Knowledge Infrastructure and Web of Science Core Collection. A total of 6,119 published Chinese papers and 25,174 English papers were selected for the quantitative analysis. CiteSpace, VOSviewer, and Scimago graphics software was used to summarize the numbers of papers published over the years, as well as the countries, institutions, and authors that published the most articles. Secondly, using keyword co-occurrence and emergence analysis, the recognized research hotspots in different areas such as adsorbents, soil remediation, catalytic oxidation, supercapacitors, and "biochar-microbial" synergy were analyzed. Finally, the prospects and challenges of biochar were assessed to provide new perspectives for further promoting its development in technological, economic, environmental, and other aspects.

Optimal policy for uncertainty estimation concurrent with decision making.

Decision making often depends on vague information that leads to uncertainty, which is a quantity contingent not on choice but on probability distributions of sensory evidence and other cognitive variables. Uncertainty may be computed in parallel and interact with decision making. Here, we adapt the classic random-dot motion direction discrimination task to allow subjects to indicate their uncertainty without having to form a decision first. The subjects' choices and reaction times for perceptual decisions and uncertainty responses are measured, respectively. We then build a value-based model in which decisions are based on optimizing value computed from a drift-diffusion process. The model accounts for key features of subjects' behavior and the variation across the individuals. It explains how the addition of the uncertainty option affects perceptual decision making. Our work establishes a value-based theoretical framework for studying uncertainty and perceptual decisions that can be readily applied in future investigations of the underlying neural mechanism.

Stereoselective Iron-Catalyzed Alkylation of Enamides with Cyclopropanols via Oxidative C(sp2)-H Functionalization.

Established herein is a radical-mediated C-H alkylation of enamides with cyclopropanols. An environmentally benign catalytic system with iron salt and air is used to permit the oxidative coupling process. The protocol demonstrates a broad substrate scope, allowing the stereoselective synthesis of alkylated enamides. The value of this strategy is further reflected by late-stage diversification of complex cyclopropanol-containing molecules and downstream transformations. Mechanistic studies reveal the dual role of iron salt in the reaction.

Accumulation of evidence during decision making in OCD patients.

Decision-making often entails the accumulation of evidence. Previous studies suggested that people with obsessive-compulsive disorder (OCD) process decision-making differently from healthy controls. Both their compulsive behavior and obsessive thoughts may influence the evidence accumulation process, yet the previous studies disagreed on the reason. To address this question, we employed a probabilistic reasoning task in which subjects made two alternative forced choices by viewing a series of visual stimuli. These stimuli carried probabilistic information toward the choices. While the OCD patients achieved similar accuracy to the control, they took longer time and accumulated more evidence, especially in difficult trials in which the evidence strength was low. We further modeled the subjects' decision making as a leaky drifting diffusion process toward two collapsing bounds. The control group showed a higher drifting rate than the OCD group, indicating that the OCD group was less sensitive to evidence. Together, these results demonstrated that the OCD patients were less efficient than the control at transforming sensory information into evidence. However, their evidence accumulation was comparable to the healthy control, and they compensated for their decision-making accuracy with longer reaction times.

Reward salience but not spatial attention dominates the value representation in the orbitofrontal cortex.

The orbitofrontal cortex (OFC) encodes value and plays a key role in value-based decision-making. However, the attentional modulation of the OFC's value encoding is poorly understood. We trained two monkeys to detect a luminance change at a cued location between a pair of visual stimuli, which were over-trained pictures associated with different amounts of juice reward and, thus, different reward salience. Both the monkeys' behavior and the dorsolateral prefrontal cortex neuronal activities indicated that the monkeys actively directed their spatial attention toward the cued stimulus during the task. However, the OFC's neuronal responses were dominated by the stimulus with higher reward salience and encoded its value. The value of the less salient stimulus was only weakly represented regardless of spatial attention. The results demonstrate that reward and spatial attention are distinctly represented in the prefrontal cortex and the OFC maintains a stable representation of reward salience minimally affected by attention.