Cr-Substituted SrCoO3-δ Perovskite with Abundant Oxygen Vacancies for High-Energy and Durable Low-Temperature Antifreezing Flexible Supercapacitor.

Developing high-performance electrodes for flexible antifreezing energy storage devices has been a significant challenge with the increasing demand for portable components. In this work, Cr-substituted SrCoO3-δ perovskites were first proposed as potential low-temperature supercapacitor electrode materials. The high-valence Cr6+ ([Ne]3s23p6) substitution favors a high-spin state of Co ions with enhanced electronic repulsion effect, ultimately forming a stable cubic structure with high conductivity. Accordingly, the modification strategies of SrCoO3 through the p6 configuration cation substitution have been improved. As a result, the asymmetric SrCo0.95Cr0.05O3-δ@CC//PPy@CC device exhibited a high energy density of 44.90 Wh kg-1 at 902.01 W kg-1 and maintained a 95.8% specific capacitance after 10,000 cycles, demonstrating an ultralong cyclic stability. The dramatically improved electrochemical performance was attributed to the stabilized crystal structure, increased oxygen vacancy, and accelerated oxygen diffusion rate. Furthermore, a quasi-solid-state supercapacitor with ethylene glycol (EG)-modified KOH/PVA organohydrogel electrolyte was developed through an advance in situ-integrated strategy. After bending at 180° for 1000 cycles, only a 9.7% capacity decay was observed. Even under -40 °C, the supercapacitor has a large energy density of 46.94 µWh cm-2. The present work represents the initial investigation into utilizing perovskite materials for antifreezing energy storage device, thereby confirming their potential application as low-temperature electronic components.

Cylindrospermopsin enhances the conjugative transfer of plasmid-mediated multi-antibiotic resistance genes through glutathione biosynthesis inhibition.

Cylindrospermopsin (CYN), a cyanobacterial toxin, has been detected in the global water environment. However, information concerning the potential environmental risk of CYN is limited, since the majority of previous studies have mainly focused on the adverse health effects of CYN through contaminated drinking water. The present study reported that CYN at environmentally relevant levels (0.1-100 µg/L) can significantly enhance the conjugative transfer of RP4 plasmid in Escherichia coli genera, wherein application of 10 µg/L of CYN led to maximum fold change of ∼6.5- fold at 16 h of exposure. Meanwhile, evaluation of underlying mechanisms revealed that environmental concentration of CYN exposure could increase oxidative stress in the bacterial cells, resulting in ROS overproduction. In turn, this led to an upregulation of antioxidant enzyme-related genes to avoid ROS attack. Further, inhibition of the synthesis of glutathione (GSH) was also detected, which led to the rapid depletion of GSH in cells and thus triggered the SOS response and promoted the conjugative transfer process. Increase in cell membrane permeability, upregulation of expression of genes related to pilus generation, ATP synthesis, and RP4 gene expression were also observed. These results highlight the potential impact on the spread of antimicrobial resistance in water environments.

Chlorite and bromate alter the conjugative transfer of antibiotic resistance genes: Co-regulation of oxidative stress and energy supply.

The widespread use of disinfectants during the global response to the 2019 coronavirus pandemic has increased the co-occurrence of disinfection byproducts (DBPs) and antibiotic resistance genes (ARGs). Although DBPs pose major threats to public health globally, there is limited knowledge regarding their biological effects on ARGs. This study aimed to investigate the effects of two inorganic DBPs (chlorite and bromate) on the conjugative transfer of RP4 plasmid among Escherichia coli strains at environmentally relevant concentrations. Interestingly, the frequency of conjugative transfer was initially inhibited when the exposure time to chlorite or bromate was less than 24 h. However, this inhibition transformed into promotion when the exposure time was extended to 36 h. Short exposures to chlorite or bromate were shown to impede the electron transport chain, resulting in an ATP shortage and subsequently inhibiting conjugative transfer. Consequently, this stimulates the overproduction of reactive oxygen species (ROS) and activation of the SOS response. Upon prolonged exposure, the resurgent energy supply promoted conjugative transfer. These findings offer novel and valuable insights into the effects of environmentally relevant concentrations of inorganic DBPs on the conjugative transfer of ARGs, thereby providing a theoretical basis for the management of DBPs.

Discovery of Phenylpyrazole Derivatives as a New Class of Selective Inhibitors of MCL-1 with Antitumor Activity.

MCL-1, an antiapoptotic member of the BCL-2 family, is dysregulated and overexpressed in various tumors. In tumors with MCL-1 overexpression, selective inhibitors of MCL-1 are expected to overcome the drug resistance caused by BCL-2 inhibitors currently used in clinical treatment. Here, we employed docking-based virtual screening to identify an active hit, LC126, with binding affinity around 10 µM for MCL-1 and BCL-2. Under the guidance of structure-based design, we obtained a few selective inhibitors of MCL-1 after three rounds of structural optimization. The representative compound GQN-B37-E exhibited binding affinity for MCL-1 at the submicromolar range (K i = 0.6 µM) without apparent binding to BCL-2 or BCL-XL. 15N-heteronuclear single-quantum coherence NMR spectra suggested that this compound binds to the BH3-domain-binding pocket in the MCL-1 surface. Cellular assays revealed that GQN-B37-Me, the precursor of GQN-B37-E, is effective particularly on leukemia cells (such as H929 and MV-4-11) to induce caspase-dependent apoptosis. Its interaction with MCL-1 in cells was confirmed by coimmunoprecipitation. Administration of GQN-B37-Me to MV-4-11 xenograft mice at 50 mg/kg every 2 days for 20 days led to 43% tumor growth inhibition. GQN-B37-Me also exhibited reasonable in vitro stability in GSH and liver microsomes from several species. This new class of MCL-1 inhibitor may have potential to be further developed into a preclinical candidate for treating leukemia.

The occurrence, ecological risk, and control of disinfection by-products from intensified wastewater disinfection during the COVID-19 pandemic.

Increased disinfection of wastewater to preserve its microbiological quality during the coronavirus infectious disease-2019 (COVID-19) pandemic have inevitably led to increased production of toxic disinfection by-products (DBPs). However, there is limited information on such DBPs (i.e., trihalomethanes, haloacetic acids, nitrosamines, and haloacetonitriles). This review focused on the upsurge of chlorine-based disinfectants (such as chlorine, chloramine and chlorine dioxide) in wastewater treatment plants (WWTPs) in the global response to COVID-19. The formation and distribution of DBPs in wastewater were then analyzed to understand the impacts of these large-scale usage of disinfectants in WWTPs. In addition, potential ecological risks associated with DBPs derived from wastewater disinfection and its receiving water bodies were summarized. Finally, various approaches for mitigating DBP levels in wastewater and suggestions for further research into the environmental risks of increased wastewater disinfection were provided. Overall, this study presented a comprehensive overview of the formation, distribution, potential ecological risks, and mitigating approaches of DBPs derived from wastewater disinfection that will facilitate appropriate wastewater disinfection techniques selection, potential ecological risk assessment, and removal approaches and regulations consideration.

Recent advances on bioactive baghdadite ceramic for bone tissue engineering applications: 20 years of research and innovation (a review).

Various artificial bone graft substitutes based on ceramics have been developed over the last 20 years. Among them, calcium-silicate-based ceramics, which are osteoconductive and can attach directly to biological organs, have received great attention for bone tissue engineering applications. However, the degradation rate of calcium-silicate and bone formation is often out of balance, resulting in stress shielding (osteopenia). A new strategy to improve the drawbacks of these ceramics is incorporating trace elements such as Zn, Mg, and Zr into their lattice structures, enhancing their physical and biological properties. Recently, baghdadite (Ca3ZrSi2O9) ceramic, one of the most appealing calcium-silicate-based ceramics, has demonstrated high bioactivity, biocompatibility, biodegradability, and cell interaction. Because of its physical, mechanical, and biological properties and ability to be shaped using various fabrication techniques, baghdadite has found high potential in various biomedical applications such as coatings, fillers, cement, scaffolds, and drug delivery systems. Undoubtedly, there is a high potential for this newly developed ceramic to contribute significantly to therapies to provide a tremendous clinical outcome. This review paper aims to summarize and discuss the most relevant studies performed on baghdadite-based ceramics and composites by focusing on their behavior in vivo and in vitro.

A putative colR(XC1049)-colS(XC1050) two-component signal transduction system in Xanthomonas campestris positively regulates hrpC and hrpE operons and is involved in virulence, the hypersensitive response and tolerance to various stresses.

The ColR-ColS two-component signal transduction system was originally characterized as a regulatory system involved in the capacity of root-colonizing biocontrol bacterium Pseudomonas fluorescens to colonize plant roots. There are three pairs of putative colR-colS two-component regulatory systems annotated in the phytopathogen Xanthomonas campestris pathovar campestris. Mutational studies revealed that one of them, named colR(XC1049) and colS(XC1050), is a global regulatory system involved in various cellular processes, including virulence, hypersensitive response and stress tolerance. Growth rate determination showed that, although the colR(XC1049) and colS(XC1050) mutants are not auxotrophic, colR(XC1049) and colS(XC1050) are required for the pathogen to proliferate well in standard media and host plants. Assays of beta-glucuronidase activities of plasmid-driven promoter-gusA reporters and/or semi-quantitative RT-PCR demonstrated that colR(XC1049) and colS(XC1050) positively regulate expression of hrpC and hrpE operons, and that expression of colR(XC1049) and colS(XC1050) is not controlled by key hrp regulators HrpG and HrpX.