Dissection of molecular mechanisms of liver injury induced by microcystin-leucine arginine via single-cell RNA-sequencing.

The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern. Microcystin-leucine arginine (MC-LR) is a well-established toxin produced by cyanobacterial blooms, which is widely distributed in eutrophic waters. MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals. However, the underlying mechanisms of MC-LR-induced liver toxicity are unclear. Herein, we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice. We established the first single-cell atlas of mouse livers in response to MC-LR. Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treated with MC-LR are highly heterogeneous. Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3, which potentially contributed to hepatocyte apoptosis in response to MC-LR. Moreover, MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes. Furthermore, the MC-LR increased several subtypes of CD8+ T cells with highly expressed multiple cytokines and chemokines. Overall, apart from directly inducing hepatocytes apoptosis, MC-LR activated proinflammatory Kupffer cell and CD8+ T cells, and their interaction may constitute a hostile microenvironment that contributes to liver injury. Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.

Triphenyl phosphate (TPP) promotes hepatocyte toxicity via induction of endoplasmic reticulum stress and inhibition of autophagy flux.

Triphenyl phosphate (TPP), a commonly used organophosphate flame retardant, is frequently found in environmental and biota samples, indicating widespread human exposure. Recent studies have shown that TPP causes hepatotoxicity, but the underlying cellular mechanisms are not fully elucidated. Here, by using normal hepatocyte AML12 cells as a model, we showed that TPP induced apoptotic cell death. RNA sequencing analyses revealed that differentially expressed genes induced by TPP were related to endoplasmic reticulum (ER) stress and autophagy. Immunostaining and western blot results further confirmed that TPP activated ER stress. Interestingly, though TPP increased LC3-II, a canonical marker for autophagy, TPP inhibited autophagy flux rather than induced autophagy. Interestingly, TPP-induced ER stress facilitated autophagy flux inhibition and apoptosis. Furthermore, inhibition of autophagy aggravated, and activation of autophagy attenuated apoptosis induced by TPP. Collectively, these results uncovered that ER stress and autophagy flux inhibition were responsible for TPP-induced apoptosis in mouse hepatocytes. Thus, our foundlings provided novel insight into the potential mechanisms of TPP-induced hepatocyte toxicity.

MoS2 nanosheets grown on hollow carbon spheres as a strong polysulfide anchor for high performance lithium sulfur batteries.

Lithium sulfur batteries are expected to be one of the most promising energy storage systems due to their high energy density, low cost and environmental friendliness. However, the shuttle effect of lithium polysulfides severely hampers their practical application. The design of the sulfur cathode is one of the most important approaches to overcome the problem. In this work, MoS2 nanosheets have been successfully grown on the surface of hollow carbon spheres (HCS) to obtain MoS2@HCS nanocomposites with uniform morphology. The growth behavior of MoS2 nanosheets was also proved by adjusting the pore structure of HCS. With a sulfur loading of 74%, the MoS2@HCS/S cathode exhibits a high initial reversible capacity of 1419 mA h g-1 at a current density of 0.1 C and remains at 1010 mA h g-1 after 100 cycles. Even at 0.5 C, a capacity of 795 mA h g-1 can be retained after 600 cycles, corresponding to a capacity retention rate of 63.1%. By adjusting the concentration of the sulfur source, the relationship between different growth quantities of MoS2 and the cycling performance of the battery was also investigated. The excellent electrochemical performance of the MoS2@HCS/S cathode can be fully attributed to its physical and chemical double adsorption effect on lithium polysulfides, which has been confirmed through the visible adsorption and X-ray Photoelectron Spectroscopy (XPS) experiments. This work provides a simple design concept and method to synthesize a nanocomposite-based sulfur host for high performance lithium sulfur batteries.

Synthesis of Ti4O7/Ti3O5 Dual-Phase Nanofibers with Coherent Interface for Oxygen Reduction Reaction Electrocatalysts.

Electrocatalysts play an important role in oxygen reduction reaction (ORR) in promoting the reaction process. Although commercial Pt/C exhibits excellent performance in ORR, the low duration, high cost, and poor methanol tolerance seriously restrict its sustainable development and application. TinO2n-1 (3 ≤ n ≤ 10) is a series of titanium sub-oxide materials with excellent electrical conductivity, electrochemical activity, and stability, which have been widely applied in the field of energy storage and catalysis. Herein, we design and synthesize Ti4O7/Ti3O5 (T4/T3) dual-phase nanofibers with excellent ORR catalytic performance through hydrothermal growth, which is followed by a precisely controlled calcination process. The H2Ti3O7 precursor with uniform size can be first obtained by optimizing the hydrothermal growth parameters. By precisely controlling the amount of reducing agent, calcination temperature, and holding time, the T4/T3 dual-phase nanofibers with uniform morphology and coherent interfaces can be obtained. The orientation relationships between T4 and T3 are confirmed to be [ 001 ] T 3 / / [ 031 ] T 4 , ( 100 ) T 3 / / ( 92 6 ¯ ) T 4 , and ( 010 ) T 3 / / ( 1 2 ¯ 6 ) T 4 , respectively, based on comprehensive transmission electron microscopy (TEM) investigations. Furthermore, such dual-phase nanofibers exhibit the onset potential and half-wave potential of 0.90 V and 0.75 V as the ORR electrocatalysts in alkaline media, respectively, which illustrates the excellent ORR catalytic performance. The rotating ring-disk electrode (RRDE) experiment confirmed the electron transfer number of 3.0 for such catalysts, which indicates a mixture of two electron and four electron transfer reaction pathways. Moreover, the methanol tolerance and cycling stability of the catalysts are also investigated accordingly.

A Novel Dermaseptin Isolated from the Skin Secretion of Phyllomedusa tarsius and Its Cationicity-Enhanced Analogue Exhibiting Effective Antimicrobial and Anti-Proliferative Activities.

A novel dermaseptin peptide, dermaseptin-PT9 (DPT9), was isolated and identified from Phyllomedusa tarsius by the combination of molecular cloning and LC-MS analysis. Chemically synthesised DPT9 was broadly effective against the tested microorganisms through the disruption of cell membranes and showed weak haemolytic activity towards horse erythrocytes. It also exhibited anti-proliferative effect against various human cancer cells. Moreover, an analogue with enhanced cationicity, K8, 23-DPT9, in which Asp8 and Glu23 were substituted by lysine residues, had a markedly increased antimicrobial effect against all tested microorganisms and disrupted microbial cell membranes. This analogue also showed no haemolysis at its effective antimicrobial concentrations. In addition, K8, 23-DPT9 displayed an enhanced anti-proliferative effect against cancer cells, while displayed weak activity against the normal human cell line, HMEC-1.

Novel peptide dermaseptin-PS1 exhibits anticancer activity via induction of intrinsic apoptosis signalling.

Antimicrobial peptides (AMP) secreted by the granular glands of frog skin have been widely reported to exhibit strong bacteriostatic and bactericidal activities. Many of them have been documented with potent antiproliferative effects on multiple cancer cells, many studies also suggested that AMPs exert their functions via disrupting cell membranes. However, whether and how other cell death induction mechanism is involved in mammalian cancer cells has rarely been investigated. In this study, a novel AMP named Dermaseptin-PS1 was isolated and identified from Phyllomedusa sauvagei, it showed strong antimicrobial activities against three types of microorganisms. In vitro antiproliferative studies on human glioblastoma U-251 MG cells indicated that Dermaseptin-PS1 disrupted cell membranes at the concentrations of 10-5  M and above, while the cell membrane integrity was not affected when concentrations were decreased to 10-6  M or lower. Further examinations revealed that, at the relatively low concentration (10-6  M), Dermaseptin-PS1 induced apoptosis through mitochondrial-related signal pathway in U-251 MG cells. Thus, for the first time, we report a novel frog skin derived AMP with anticancer property by distinct mechanisms, which largely depends on its concentration. Together, our study provides new insights into the mechanism-illustrated drug design and the optimisation of dose control for cancer treatment in clinic.

High-Pressure Studies of 4-Acetamidobenzenesulfonyl Azide: Combined Raman Scattering, IR Absorption, and Synchrotron X-ray Diffraction Measurements.

We have reported the high-pressure behavior of 4-acetamidobenzenesulfonyl azide (C8H8N4O3S, 4-ABSA) by in situ Raman scattering, IR absorption, and synchrotron angle-dispersive X-ray diffraction (ADXRD) measurements in diamond anvil cells with the pressure up to ∼13 GPa at room temperature. All of the fundamental vibrational modes of 4-ABSA at ambient pressure were analyzed by combination of experimental measurements and theoretical calculations using the density functional theory method. Detailed Raman and IR spectroscopic analyses reveal two phase transitions in the pressure region of 0.8-2 and 4.2 GPa, respectively, which are confirmed by the changes in the ADXRD patterns. The first phase transition in the pressure region of 0.8-2 GPa is attributed to the ring distortion and the rotation of CH3 group, whereas the second phase transition at 4.2 GPa might be induced by the rearrangement of azide group and hydrogen bonds. The analyses of the N3 vibrational modes suggest that the bent azide group rotates progressively upon compression, which is ascribed to the compression of the unit cell along the b axis. This study is helpful to understand the behavior of azide group and structural evolution of 4-ABSA under high pressure.

A preliminary study of the oral microbiota in Chinese patients with Sjögren's syndrome.

OBJECTIVE: To investigate the oral microbiota in Sjögren's syndrome (SS) as opposed to that of healthy subjects. STUDY DESIGN: Ten patients with primary SS, [6 patients daily taking stable dosage of hydroxychloroquine (HC) and 4 patients taking hydroxychloroquine combined with Prednisone acetas (HC+PA)], along with 10 age-matched healthy controls were examined in regard of number of teeth, stimulated/unstimulated saliva secretion rate. Microflora on bilateral buccal mucosa was analyzed by high throughput sequencing. Statistical analyses were performed using the chi-square test, t test and Mann-Whitney U test. The Venn diagrams and Redundancy Analysis (RDA) were also used to evaluate effects of the disease and treatment on the bacterial community composition. RESULTS: The relative abundance of Proteobacteria in SS group was lower compared to controls (P=0.002). The total richness of genera for all groups was 339. The numbers of genera in SS group and in control group were 248 and 270, respectively. Some taxa with different prevalence and/or relative abundance were found between two groups. CONCLUSIONS: SS affects the oral microbiota and SS patients carry a different and less diverse microorganism community compared with healthy subjects. Prednisone acetas is an influence on the oral microbiome. This study provides a basic data on the oral flora in SS patients.