Comparison of disinfectants-induced gene expression profile: Potential adverse effects.

Despite their importance in combating the spread of the COVID-19 pandemic, adverse effects of disinfectants on human health, especially the respiratory system, have been of continuing concern to researchers. Considering that bronchi are the main target of sprayed disinfectants, we here treated the seven major active ingredients in disinfectant products accepted by the US EPA to human bronchial epithelial cells and determined the subtoxic levels. Then, we performed microarray analysis using total RNA obtained at the subtoxic level and designed a network representing disinfectant-induced cellular response using the KEGG pathway analysis technique. Polyhexamethylguanidine phosphate, a lung fibrosis inducer, was used as a reference material to verify the relationship between cell death and pathology. The derived results reveal potential adverse effects along with the need for an effective application strategy for each chemical.

Subtle visual change in a virtual environment induces heterogeneous remapping systematically in CA1, but not CA3.

Environmental change may lead to new memories or modify old ones, but the underlying neural mechanisms are largely unclear. We recorded hippocampal place cells simultaneously from CA1 and CA3 in a virtual reality environment. Compared with CA1, place cells in CA3 are more tolerant of individual landmark changes but undergo orthogonal changes to code distinctively different environments. As visual noise (virtual fog) is introduced to a visually enriched environment, place cells in CA1 split into two subpopulations: in one, place cells maintain their field locations while changing their firing rates to reflect sensory changes; in the other, place cells exhibit global remapping in response to the contextual change. In contrast, place cells in CA3 exhibit mainly rate remapping under the same conditions. Our results suggest that CA1 may simultaneously represent heterogeneous maps of the same environment when subtle visual noise induces both sensory and contextual changes.

Polyhexamethylene guanidine phosphate-induced necrosis may be linked to pulmonary fibrosis.

Following the humidifier disinfectant incident in Korea, polyhexamethylene guanidine phosphate (PHMG-P) has been used to establish lung fibrosis model animals. Herein, we investigated time-dependent changes after a single PHMG-P instillation (22 µg/lung) to identify the underlying pathogenesis and immune response involved in PHMG-P-induced lung fibrosis. Compared to control mice, body weight loss and blood biochemical and hematological changes were more remarkable in PHMG-P-instilled mice, an increase of total cell counts, infiltration of macrophages and neutrophils and necrotic cell death were also more notable in the lungs of PHMG-P-instilled mice. Pathological lesions were detected from Day 1 after exposure, deteriorating with time. In addition, secretion of anti-inflammatory mediators was rapidly inhibited from 6 h after exposure, and level of IL-24, a tissue repair-related cytokine, was up-regulated in the lungs of PHMG-P-instilled mice until Day 21 post-exposure. In vitro tests using BEAS-2B cells showed that PHMG-P disturbed structural and functional homeostasis of organelles and that intracellular ROS increase was considered as an important cause of PHMG-P-induced cell death. Additionally, co-culture with DNA, a polyanionic compound, clearly inhibited PHMG-P-induced necrosis, and increased IL-1ß and TNF-α level and decreased IL-6 and IL-8 levels were observed following exposure to PHMG-P. Meanwhile, IL-8 secretion increased in cells exposed to PHMG-P-induced cell debris. Therefore, we suggest that necrotic cell debris may importantly contribute to the PHMG-P-induced inflammatory response and pathogenesis. In addition, PHMG-P-induced necrosis may be initiated by high affinity between PHMG-P and cell membrane.

Pulmonary inflammation and cellular responses following exposure to benzalkonium chloride: Potential impact of disrupted pulmonary surfactant homeostasis.

Benzalkonium chloride (BKC) is a prototypical quaternary ammonium disinfectant. Previously, we suggested a no lethal dose level (0.005%) and an LD50 range (0.5-0.05%) of BKC following a single pharyngeal aspiration. Herein, we exposed BKC repeatedly by pharyngeal aspiration for 14 days (0.005 and 0.01%, female mice, total five times with interval of two days, 5 mice/group) and 28 days (0, 0.001, 0.005, and 0.01%, male and female mice, weekly, 16 mice/sex/group). Death following 14 days-repeated exposure did not occur. Meanwhile, chronic pathological lesions were observed in the lung tissues of mice exposed to BKC for 28 days. The total number of bronchial alveolar lavage cells increased, and pulmonary homeostasis of immunologic messenger molecules was disturbed. Following, we investigated BKC-induced cellular responses using human bronchial epithelial cells. The cytotoxicity increased rapidly with concentration. Lysosomal volume, NO production, and lipid peroxidation increased in BKC-treated cells, whereas intracellular ROS level decreased accompanying structural and functional damage of mitochondria. We also found that BKC affected the expression level of immune response, DNA damage, and amino acid biosynthesis-related molecules. More interestingly, lamellar body- and autophagosome-like structures were notably observed in cells exposed to BKC, and necrotic and apoptotic cell death were identified accompanying cell accumulation in the G2/M phase. Therefore, we suggest that repeated respiratory exposure of BKC causes pulmonary inflammation and lung tissue damage and that dead and damaged cells may contribute to the inflammatory response. In addition, the formation process of lamellar body-like structures may function as a key toxicity mechanism.

Multiple pathways of alveolar macrophage death contribute to pulmonary inflammation induced by silica nanoparticles.

In our previous study, 20 nm-sized amorphous silica nanoparticles (20-SiNPs), but not 50 nm-sized amorphous silica nanoparticles (50-SiNPs), induced pulmonary inflammatory response in rats exposed repeatedly for 14 days (12.5, 25, and 50 µg/time, total six times). In this study, we tried to clarify the causes of different responses induced by both SiNPs using mice (12.5, 25, and 50 µg/lung) and mouse alveolar macrophage cells. When exposed to alveolar macrophage cells for 24 h, both SiNPs decreased cell viability and enhanced ROS generation compared to controls. The 20- and 50-SiNPs also formed giant and autophagosome-like vacuoles in the cytoplasm, respectively. Structural damage of organelles was more pronounced in 20-SiNPs-treated cells than in 50-SiNPs-treated cells, and an increased mitochondrial membrane potential and mitochondrial calcium accumulation were observed only in the 20-SiNPs-treated cells. Additionally, a single intratracheal instillation of both sizes of SiNPs to mice clearly elevated the relative proportion of neutrophils and inhibited differentiation of macrophages and expression of an adhesion molecule. Meanwhile, interestingly, the total number of pulmonary cells and the levels of pro-inflammatory mediators more notably increased in the lungs of mice exposed to 20-SiNPs compared to 50-SiNPs. Given that accumulation of giant vacuoles and dilation of the ER and mitochondria are key indicators of paraptosis, we suggest that 20-SiNPs-induced pulmonary inflammation may be associated with paraptosis of alveolar macrophages.

Whole Cigarette Smoke Condensates Induce Accumulation of Amyloid Beta Precursor Protein with Oxidative Stress in Murine Astrocytes.

Although cigarette smoking has been postulated to be a potential risk factor for Alzheimer's disease (AD), the toxic mechanism is still unclear. Additionally, astrocytes have been identified as a potential target, given they play multiple roles in maintaining normal brain function. In this study, we explored the toxic mechanism of whole cigarette smoke condensates (WCSC) using murine astrocytes. Cell proliferation, the percentage of cells in the G2/M phase, and LDH concentrations in the cell supernatants were all reduced in WCSC-treated cells. In addition, oxidative stress was induced, together with shortening of processes, structural damage of organelles, disturbances in mitochondrial function, blockage of autophagic signals, accumulation of amyloid ß precursor protein, and loss of chemotactic functions. Based on these results, we hypothesize that dysfunction of astrocytes may contribute to the occurrence of cigarette-smoking-induced AD.

Differential encoding of place value between the dorsal and intermediate hippocampus.

It is widely held that the hippocampus provides a cognitive map in which event-related information, such as an object, location, and their significance, is organized. However, how an organism's motivational experience is coded in the hippocampus is mostly unknown. Here, we investigated whether dorsal and intermediate regions of the hippocampus are differentially involved in representing changes in the motivational significance of a place. Rats were run in tasks in which various rewards with different degrees of palatability were associated with the same locations while single units were simultaneously recorded along the dorsoventral axis of the hippocampus. Place cells in the intermediate hippocampus remapped immediately after motivational significance decreased and shifted their fields dynamically toward high-value locations. In contrast, place cells in the dorsal hippocampus were mostly unresponsive to the same manipulations. Our findings suggest that the motivational significance of place is uniquely coded in the intermediate hippocampus in goal-directed tasks.

Detection of intracellular lamellar bodies as a screening marker for fibrotic lesions.

With the rapid increase in application of disinfectants worldwide as a method to block the spread of coronavirus, many new products are being introduced into the market without thorough verification of their impacts on human health and the environment. In the present study, we aimed to propose a screening marker for materials that can induce fibrotic lung disease using disinfectants, which had been demonstrated as causative materials of chronic inflammation and interstitial fibrosis. We first calculated the corresponding LC50 level based on results from cell viability test and exposed the LC50 level of disinfectants to human bronchial epithelial cells for 24 h. Formation of lamellar body-like structures, cleavage of the nuclear matrix, structural damage of mitochondria were found in the cytosol of the treated cells. We also dosed disinfectants by pharyngeal aspiration to mice to determine the LD0 level. The mice were sacrificed on Day 14 after a single dosing, and lamellar body-like structures were observed in the lung tissue of mice. Herein, we hypothesize that DNA damage and metabolic disturbance may play central roles in disinfectant-induced adverse health effects. Additionally, we propose that formation of lamellar bodies can be a screening marker for interstitial fibrosis.

Goal-directed interaction of stimulus and task demand in the parahippocampal region.

The hippocampus and parahippocampal region are essential for representing episodic memories involving various spatial locations and objects, and for using those memories for future adaptive behavior. The "dual-stream model" was initially formulated based on anatomical characteristics of the medial temporal lobe, dividing the parahippocampal region into two streams that separately process and relay spatial and nonspatial information to the hippocampus. Despite its significance, the dual-stream model in its original form cannot explain recent experimental results, and many researchers have recognized the need for a modification of the model. Here, we argue that dividing the parahippocampal region into spatial and nonspatial streams a priori may be too simplistic, particularly in light of ambiguous situations in which a sensory cue alone (e.g., visual scene) may not allow such a definitive categorization. Upon reviewing evidence, including our own, that reveals the importance of goal-directed behavioral responses in determining the relative involvement of the parahippocampal processing streams, we propose the Goal-directed Interaction of Stimulus and Task-demand (GIST) model. In the GIST model, input stimuli such as visual scenes and objects are first processed by both the postrhinal and perirhinal cortices-the postrhinal cortex more heavily involved with visual scenes and perirhinal cortex with objects-with relatively little dependence on behavioral task demand. However, once perceptual ambiguities are resolved and the scenes and objects are identified and recognized, the information is then processed through the medial or lateral entorhinal cortex, depending on whether it is used to fulfill navigational or non-navigational goals, respectively. As complex sensory stimuli are utilized for both navigational and non-navigational purposes in an intermixed fashion in naturalistic settings, the hippocampus may be required to then put together these experiences into a coherent map to allow flexible cognitive operations for adaptive behavior to occur.

The complete chloroplast genome sequence of Magic Lily (Lycoris squamigera).

Magic Lily (Lycoris squamigera), belonging to the Amaryllidaceae family, is cultivated for ornamental and medicinal purposes. To characterize its genomic information, we obtained the complete chloroplast genome sequence of L. squamigera by assembling Illumina whole genome sequence data. The complete chloroplast genome is 158,482 bp in length which is composed of four unique regions, a large single copy region (LSC) of 86,454 bp, a small single copy region (SSC) of 18,500 bp, and a pair of inverted repeats (IR) of 26,764 bp. The genome annotation predicted 159 genes including 105 protein-coding genes, 46 tRNA genes, and 8 rRNA genes. Phylogenetic tree analysis revealed that L. squamigera clustered with Allium species belonging to the Amaryllidaceae family.