Inhibition of piezo1 prevents chronic cerebral hypoperfusion-induced cognitive impairment and blood brain barrier disruption.

Chronic cerebral hypoperfusion (CCH) plays a critical role in the onset and progression of vascular dementia (VD), which is now recognized as the second most common form of dementia after Alzheimer's disease (AD). The mechanosensitive piezo1 channel has been identified to play important roles in several neurological disorders. However, the roles and possible mechanisms of piezo1 in CCH-induced cognitive decline and blood brain barrier (BBB) disruption, as well as the underlying mechanisms remain elusive. In this study, the CCH model was established by bilateral common carotid artery occlusion in rats and by oxygen and glucose deprivation/reoxygenation (OGD/R) in bEnd.3 cells. The results demonstrated that the antagonist of piezo1 GsMTx4 ameliorated CCH-induced cognitive dysfunction and mitigated cerebral edema. Furthermore, this study indicated that GsMTx4 improved the permeability and integrity of BBB and protected cerebral microvasculature after CCH. In vitro, GsMTx4 improved cell viability, promoted the ability of cell motility and migration, and inhibited the degradation of BBB integrity-related proteins by inhibiting NLRP3 inflammasome activation. In addition, NLRP3 agonist abolished the beneficial effects of GsMTx4. Collectively, our results demonstrate that piezo1 might be involved in CCH-induced cognitive impairment and BBB damage, which may be at least partially mediated through regulation of NLRP3 inflammasome.

Effects of atrazine and curcumin exposure on TCMK-1 cells: Oxidative damage, pyroptosis and cell cycle arrest.

Atrazine (ATR), a commonly used herbicide, is highly bioaccumulative and toxic, posing a threat to a wide range of organisms. Curcumin has strong antioxidant properties. However, it is unclear whether curcumin counteracts cellular pyroptosis as well as cell cycle arrest induced by ATR exposure. Therefore, we conducted a study using TCMK-1 cells and established cell models by adding 139 µmol/L ATR and 20 µmol/L curcumin. The results showed that ATR exposure produced excessive reactive oxygen species (ROS), reduced activities of enzymes such as GSH-PX, SOD and Total Antioxidant Capacity, markedly increased the content of H2O2, disrupted the antioxidant system, activated Caspase-1, and the expression levels of the pyroptosis-related genes NLRP3, GSDMD, ASC, Caspase-1, IL-1ß and IL-18 were increased. The simultaneous excess of ROS led to DNA damage, activation of P53 led to elevated expression levels of P53 and P21, as a consequence, the expression levels of cyclinE, CDK2 and CDK4 were reduced. These results suggest that Cur can modulate ATR exposure-induced pyroptosis as well as cell cycle arrest in TCMK-1 cells by governing oxidative stress.

Electro-catalytic adsorption mechanism of acetonitrile in water using a ME-ACFs system.

Acetonitrile wastewater is difficult to treat due to its high salinity and toxicity to microorganisms. In this paper, a micro electro-activated carbon fiber coupled system (ME-ACF) was established to treat simulated acetonitrile wastewater. In the 200 ml system, the concentration of acetonitrile adsorbed by ACF was 91.3 mg/L, while that of acetonitrile adsorbed by ME-ACF was 150.6 mg/L, and the removal efficiency was increased by 65 % in comparison. The activated carbon fibers before and after the reaction were subjected to a series of characterization, and it was found that the SABET decreased from 1393.48 m2/g to 1114.93 m2/g and 900.23 m2/g, respectively, but the oxygen on the surface of the activated carbon fibers was increased, and the effect of the micro electrolytic system on the activated carbon fibers was then analyzed. The possible reasons for the formation of acetic acid contained in the products were also discussed using DFT simulations. The removal mechanism of acetonitrile by ME-ACF was considered to be electrically enhanced adsorption and electro-catalytic hydrolysis.

Selenium alleviates lead-induced CIK cells pyroptosis and inflammation through IRAK1/TAK1/IKK pathway.

The toxic heavy metal lead is widely found in rivers and soils as an environmental pollutant, posing a threat to the health of aquatic organisms. Selenium is an essential trace element and a powerful antioxidant that has been shown to have anti-inflammatory and antioxidant properties as well as alleviating heavy metal poisoning. Many studies have shown that lead poisoning produces inflammatory responses and damage to the kidneys of a wide range of animals, but the effects on cellular pyroptosis and immune function and selenium antagonism in CIK cells are not clear. In this study, 500 µM Pb and 20 nM Se were applied to grass carp kidney cells, and the results showed that Pb exposure to CIK cells resulted in oxidative stress, activation of the IRAK1/TAK1/IKK pathway, up-regulation of the expression of cellular pyroptosis markers GSDMD and NLRP3, and cellular pyroptosis of CIK cells, as well as up-regulation of IL-1ß and IL-18, and the generation of cellular inflammatory response. In contrast, Se treatment significantly reduced the ROS level, the expression of cellular pyroptosis markers GSDMD, NLRP3 and inflammatory element IL-1ß and IL-18. Taken together, Se alleviated cellular pyroptosis and immune dysfunction caused by Pb exposure through oxidative stress and activation of the IRAK1/TAK1/IKK pathway. This study complements the harmful effects of the heavy metal Pb on fish and the real-life application of selenium in the healthy culture of fish as a reference will be provided.

One-pot synthesis of dynamically cross-linked polymers for serum-resistant nucleic acid delivery.

Cationic polymers used for nucleic acid delivery often suffer from complicated syntheses, undesired intracellular cargo release and low serum stability. Herein, a series of ternary polymers were synthesized via facile green chemistry to achieve efficient plasmid DNA and mRNA delivery in serum. During the one-pot synthesis of the ternary polymer, acetylphenylboric acid (APBA), polyphenol and low-molecular weight polyethyleneimine (PEI 1.8k) were dynamically cross-linked with each other due to formation of an imine between PEI 1.8k and APBA and formation of a boronate ester between APBA and polyphenol. Series of polyphenols, including ellagic acid (EA), epigallocatechin gallate (EGCG), nordihydroguaiaretic acid (NDGA), rutin (RT) and rosmarinic acid (RA), and APBA molecules, including 2-acetylphenylboric acid (2-APBA), 3-acetylphenylboric acid (3-APBA) and 4-acetylphenylboric acid (4-APBA), were screened and the best-performing ternary polymer, 2-PEI-RT, constructed from RT and 2-APBA, was identified. The ternary polymer featured efficient DNA condensation to favor cellular internalization, and the acidic environment in endolysosomes triggered effective degradation of the polymer to promote cargo release. Thus, 2-PEI-RT showed robust plasmid DNA transfection efficiencies in various tumor cells in serum, outperforming the commercial reagent PEI 25k by 1-3 orders of magnitude. Moreover, 2-PEI-RT mediated efficient cytosolic delivery of Cas9-mRNA/sgRNA to enable pronounced CRISPR-Cas9 genome editing in vitro. Such a facile and robust platform holds great potential for non-viral nucleic acid delivery and gene therapy.

Understanding changing public transit travel patterns of urban visitors during COVID-19: A multi-stage study.

COVID-19 has caused huge disruptions to urban travel and mobility. As a critical transportation mode in cities, public transit was hit hardest. In this study, we analyze public transit usage of urban visitors with a nearly two-year smart card dataset collected in Jeju, South Korea - a major tourism city in the Asia Pacific. The dataset captures transit usage behavior of millions of domestic visitors who traveled to Jeju between January 1, 2019 and September 30, 2020. By identifying a few key pandemic stages based on COVID-19 timeline, we employ ridge regression models to investigate the impact of pandemic severity on transit ridership. We then derive a set of mobility indicators - from perspectives of trip frequency, spatial diversity, and travel range - to quantify how individual visitors used the transit system during their stay in Jeju. By further employing time series decomposition, we extract the trend component for each mobility indicator to study long-term dynamics of visitors' mobility behavior. According to the regression analysis, the pandemic had a dampening effect on public transit ridership. The overall ridership was jointly affected by national and local pandemic situations. The time series decomposition result reveals a long-term decay of individual transit usage, hinting that visitors in Jeju tended to use the transit system more conservatively as the pandemic endured. The study provides critical insights into urban visitors' transit usage behavior during the pandemic and sheds light on how to restore tourism, public transit usage, and overall urban vibrancy with some policy suggestions.

Antiviral Activity of Benzoheterocyclic Compounds from Soil-Derived Streptomyces jiujiangensis NBERC-24992

Pseudorabies virus (PRV) is a pathogen that causes Aujeszky's disease (AD) in animals, leading to huge economic losses to swine farms. In order to discover anti-PRV compounds, we studied the extracts of the strain Streptomyces jiujiangensis NBERC-24992, which showed significant anti-PRV activity. Eight benzoheterocyclic secondary metabolites, including three new compounds (1-3, virantmycins D-G) and five known compounds (4-8, virantmycin, A-503451 D, A-503451 D acetylate, A-503451 A, and A-503451 B), were isolated from the broth of NBERC-24992. The structures of the new compounds were identified by using extensive spectroscopic data, including mass spectrometry (MS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD). Compound 1 was found to be a novel heterocyclic compound with a tricyclic skeleton from natural product. All compounds were tested for antiviral activity, and 4 (virantmycin) showed an excellent effect against PRV and was better than ribavirin and acyclovir. Our study revealed that chlorine atom and tetrahydroquinoline skeleton were important active moiety for antiviral activity. Virantmycin could be a suitable leading compound for an antiviral drug against PRV.

Impact of the COVID-19 pandemic on travel behavior: A case study of domestic inbound travelers in Jeju, Korea.

This study analyzes a large-scale navigation dataset that captures travel activities of domestic inbound visitors in Jeju, Korea in the first nine months of 2020. A collection of regression models are introduced to quantify the dynamic effects of local and national COVID-19 indicators on their travel behavior. Results suggest that behavior of inbound travelers was jointly affected by pandemic severity locally and remotely. The daily number of new cases in Jeju has a greater impact on reducing travel activities than the national-level daily new cases of COVID-19. The impacts of the pandemic did not diminish over time but produced heterogeneous effects on travels with different trip purposes. Our findings reveal the persistence of COVID-19's effects on travel behavior and the variability in travelers' responses across tourism activities with different levels of perceived health risks. The implications for crisis management and recovery strategies are also discussed.

Secondary metabolites of Alternaria: A comprehensive review of chemical diversity and pharmacological properties.

Fungi are considered to be one of the wealthiest sources of bio-metabolites that can be employed for yielding novel biomedical agents. Alternaria, including parasitic, saprophytic, and endophytic species, is a kind of dark fungi that can produce a broad array of secondary metabolites (SMs) widely distributed in many ecosystems. These are categorized into polyketides, nitrogen-containing compounds, quinones, terpenes, and others based on the unique structural features of the metabolites. New natural products derived from Alternaria exhibit excellent bioactivities characterized by antibacterial, antitumor, antioxidative, phytotoxic, and enzyme inhibitory properties. Thus, the bio-metabolites of Alternaria species are significantly meaningful for pharmaceutical, industrial, biotechnological, and medicinal applications. To update the catalog of secondary metabolites synthesized by Alternaria fungi, 216 newly described metabolites isolated from Alternaria fungi were summarized with their diverse chemical structures, pharmacological activity, and possible biosynthetic pathway. In addition, possible insights, avenues, and challenges for future research and development of Alternaria are discussed.