Zebrafish Mbd5 binds to RNA m5C and regulates histone deubiquitylation and gene expression in development metabolism and behavior.

Complex biological processes are regulated by both genetic and epigenetic programs. One class of epigenetic modifications is methylation. Evolutionarily conserved methyl-CpG-binding domain (MBD)-containing proteins are known as readers of DNA methylation. MBD5 is linked to multiple human diseases but its mechanism of action remains unclear. Here we report that the zebrafish Mbd5 does not bind to methylated DNA; but rather, it directly binds to 5-methylcytosine (m5C)-modified mRNAs and regulates embryonic development, erythrocyte differentiation, iron metabolism, and behavior. We further show that Mbd5 facilitates removal of the monoubiquitin mark at histone H2A-K119 through an interaction with the Polycomb repressive deubiquitinase (PR-DUB) complex in vivo. The direct target genes of Mbd5 are enriched with both RNA m5C and H2A-K119 ubiquitylation signals. Together, we propose that zebrafish MBD5 is an RNA m5C reader that potentially links RNA methylation to histone modification and in turn transcription regulation in vivo.

Antidepressants can induce mutation and enhance persistence toward multiple antibiotics.

Antibiotic resistance is an urgent threat to global health. Antidepressants are consumed in large quantities, with a similar pharmaceutical market share (4.8%) to antibiotics (5%). While antibiotics are acknowledged as the major driver of increasing antibiotic resistance, little attention is paid to the contribution of antidepressants in this process. Here, we demonstrate that antidepressants at clinically relevant concentrations induce resistance to multiple antibiotics, even following short periods of exposure. Antibiotic persistence was also enhanced. Phenotypic and genotypic analyses revealed the enhanced production of reactive oxygen species following exposure to antidepressants was directly associated with increased resistance. An enhanced stress signature response and stimulation of efflux pump expression were also associated with increased resistance and persistence. Mathematical modeling also predicted that antidepressants would accelerate the emergence of antibiotic-resistant bacteria, and persister cells would help to maintain the resistance. Overall, our findings highlight the antibiotic resistance risk caused by antidepressants.

Proteomics, Transcriptomics, and Phosphoproteomics Reveal the Mechanism of Talaroconvolutin-A Suppressing Bladder Cancer via Blocking Cell Cycle and Triggering Ferroptosis.

Talaroconvolutin-A (TalaA) is a compound from the endophytic fungus T. convolutispora of the Chinese herbal medicine Panax notoginseng. Whether TalaA exerts anticancer activity in bladder cancer remains unknown. Using CCK8 assay, EdU staining, crystal violet staining, flow cytometry, living/dead cell staining, and Western blotting, we studied the anticancer activity of TalaA in vitro. Moreover, we performed xenograft tumor implantation. The antitumor effects were evaluated through H&E and immunohistochemistry staining. Proteomics was conducted to detect changes in the protein profile; transcriptomics was performed to detect changes in mRNA abundance; phosphoproteomics was used to detect changes in protein phosphorylation. TalaA inhibited tumor cell proliferation, DNA replication, and colony formation in a dose-dependent manner in bladder cancer cells. The IC50 values of TalaA on SW780 and UM-UC-3 cells were 5.7 and 8.2 µM, respectively. TalaA (6.0 mg/kg) significantly repressed the growth of xenografted tumors and did not affect the body weight nor cause obvious hepatorenal toxicity. TalaA arrested the cell cycle by downregulating cyclinA2, cyclinB1, and AURKB and upregulating p21/CIP. TalaA also elevated intracellular reactive oxygen species and upregulated transferrin and heme oxygenase 1 to induce ferroptosis. Moreover, TalaA was able to bind to MAPKs (MAPK1, MAPK8, and MAPK14) to inhibit the phosphorylation of ∗SP∗ motif of transcription regulators. This study revealed that TalaA inhibited bladder cancer by arresting cell cycle to suppress proliferation and triggering ferroptosis to cause cell death. Conclusively, TalaA would be a potential candidate for treating bladder cancer by targeting MAPKs, suppressing the cell cycle, and inducing ferroptosis.

Ultralight Three-Layer Gradient-Structured MXene/ Reduced Graphene Oxide Composite Aerogels with Broadband Microwave Absorption and Dynamic Infrared Camouflage.

Infrared and radar detectors posed substantial challenges to weapon equipment and personnel due to their continuous surveillance and reconnaissance capabilities. Traditional single-band stealth devices are insufficient for dual-band detection in both infrared and microwave bands. To overcome this limitation, a gradient-structured MXene/reduced graphene oxide (rGO) composite aerogel (GMXrGA) is fabricated through a two-step bidirectional freeze casting process, followed by freeze-drying and thermal annealing. GMXrGA exhibits a distinct three-layered structure, with each layer playing a crucial role in microwave absorption. This deliberate design amplifies both the efficiency of microwave absorption and the material's effectiveness in dynamic infrared camouflage. GMXrGA displays an ultralow density of 5.2 mg∙cm-3 and demonstrates exceptional resistance to compression, enduring 200 cycles at a maximum strain of 80%. Moreover, it shows superior microwave absorption performance, with a minimum reflection loss (RLmin) of -60.1 dB at a broad effective absorption bandwidth (EAB) of 14.1 GHz (3.9-18.0 GHz). Additionally, the aerogel exhibits low thermal conductivity (≈26 mW∙m-1∙K-1) and displays dynamic infrared camouflage capabilities within the temperature range of 50-120 °C, achieving rapid concealment within 30 s. Consequently, they hold great potential for diverse applications, including intelligent buildings, wearable electronics, and weapon equipment.

Discovery of anticancer function of Febrifugine: Inhibition of cell proliferation, induction of apoptosis and suppression steroid synthesis in bladder cancer cells.

Bladder cancer is a prevalent malignancy affecting the urinary system, which presents a significant global health concern. Although there are many treatments for bladder cancer, identifying more effective drugs and methods remains an urgent problem. As a pivotal component of contemporary medical practice, traditional Chinese medicine (TCM) assumes a crucial role in the realm of anti-tumor therapy, especially with the identification of active ingredients and successful exploration of pharmacological effects. Febrifugine, identified as a quinazoline-type alkaloid compound extracted from the Cytidiaceae family plant Huangchangshan, exhibits heightened sensitivity to bladder cancer cells in comparison to control cells (non-cancer cells) group. The proliferation growth of bladder cancer cells T24 and SW780 was effectively inhibited by Febrifugine, and the IC50 was 0.02 and 0.018 µM respectively. Febrifugine inhibits cell proliferation by suppressing DNA synthesis and induces cell death by reducing steroidogenesis and promoting apoptosis. Combined with transcriptome analysis, Febrifugine was found to downregulate low density lipoprotein receptor-associated protein, lanosterol synthase, cholesterol biosynthesis second rate-limiting enzyme, 7-dehydrocholesterol reductase, flavin adenine dinucleotide dependent oxidoreductase and other factors to inhibit the production of intracellular steroids in bladder cancer T24 cells. The results of animal experiments showed that Febrifugine could inhibit tumor growth. In summary, the effect of Febrifugine on bladder cancer is mainly through reducing steroid production and apoptosis. Therefore, this study contributes to the elucidation of Febrifugine's potential as an inhibitor of bladder cancer and establishes a solid foundation for the future development of novel therapeutic agents targeting bladder cancer.

Coupling Nitrate-Dependent Anaerobic Ethane Degradation with Anaerobic Ammonium Oxidation.

The microbial oxidation of short-chain gaseous alkanes (SCGAs, consisting of ethane, propane, and butane) serves as an efficient sink to mitigate these gases' emission to the atmosphere, thus reducing their negative impacts on air quality and climate. "Candidatus Alkanivorans nitratireducens" are recently found to mediate nitrate-dependent anaerobic ethane oxidation (n-DAEO). In natural ecosystems, anaerobic ammonium-oxidizing (anammox) bacteria may consume nitrite generated from nitrate reduction by "Ca. A. nitratireducens", thereby alleviating the inhibition caused by nitrite accumulation on the metabolism of "Ca. A. nitratireducens". Here, we demonstrate the coupling of n-DAEO with anammox in a laboratory-scale model system to prevent nitrite accumulation. Our results suggest that a high concentration of ethane (6.9-7.9%) has acute inhibition on anammox activities, thus making the coupling process a significant challenge. By maintaining ethane concentrations within the range of 1.7-5.5%, stable ethane and ammonium oxidation, nitrate reduction, and dinitrogen gas generation without nitrite accumulation were finally achieved. After the accomplished coupling of n-DAEO with anammox, nitrate reduction rates increased by 8.1 times compared to the rate observed with n-DAEO alone. Microbial community profiling via 16S rRNA gene amplicon sequencing showed "Ca. A. nitratireducens" (6.6-12.9%) and anammox bacteria "Candidatus Kuenenia" (3.4-5.6%) were both dominant in the system, indicating they potentially form a syntrophic partnership to jointly contribute to nitrogen removal. Our findings offer insights into the cross-feeding interaction between "Ca. A. nitratireducens" and anammox bacteria in anoxic environments.

Methane-Driven Perchlorate Reduction by a Microbial Consortium.

The phenomenon of methane oxidation linked to perchlorate reduction has been reported in multiple studies; yet, the underlying microbial mechanisms remain unclear. Here, we enriched suspended cultures by performing methane-driven perchlorate reduction under oxygen-limiting conditions in a membrane bioreactor (MBR). Batch test results proved that perchlorate reduction was coupled to methane oxidation, in which acetate was predicted as the potential intermediate and oxygen played an essential role in activating methane. By combining DNA-based stable isotope probing incubation and high-throughput sequencing analyses of 16S rRNA gene and functional genes (pmoA, pcrA, and narG), we found that synergistic interactions between aerobic methanotrophs (Methylococcus and Methylocystis) and perchlorate-reducing bacteria (PRB; Denitratisoma and Dechloromonas) played active roles in mediating methane-driven perchlorate reduction. This partnership was further demonstrated by coculture experiments in which the aerobic methanotroph could produce acetate to support PRB to complete perchlorate reduction. Our findings advance the understanding of the methane-driven perchlorate reduction process and have implications for similar microbial consortia linking methane and chlorine biogeochemical cycles in natural environments.

Simultaneous Biogas Upgrading and Valuable Chemical Production Using Homoacetogens in a Membrane Biofilm Reactor.

Biogas produced from anaerobic digestion usually contains impurities, particularly with a high content of CO2 (15-60%), thus decreasing its caloric value and limiting its application as an energy source. H2-driven biogas upgrading using homoacetogens is a promising approach for upgrading biogas to biomethane and converting CO2 to acetate simultaneously. Herein, we developed a novel membrane biofilm reactor (MBfR) with H2 and biogas separately supplied via bubbleless hollow fiber membranes. The gas-permeable hollow fibers of the MBfR enabled high H2 and CO2 utilization efficiencies (∼98% and ∼97%, respectively) and achieved concurrent biomethane (∼94%) and acetate (∼450 mg/L/d) production. High-throughput 16S rRNA gene amplicon sequencing suggested that enriched microbial communities were dominated by Acetobacterium (38-48% relative abundance). In addition, reverse transcription quantitative PCR of the functional marker gene formyltetrahydrofolate synthetase showed that its expression level increased with increasing H2 and CO2 utilization efficiencies. These results indicate that Acetobacterium plays a key role in CO2 to acetate conversion. These findings are expected to facilitate energy-positive wastewater treatment and contribute to the development of a new solution to biogas upgrading.

Long-Term Field Application of a Plant Growth-Promoting Rhizobacterial Consortium Suppressed Root-Knot Disease by Shaping the Rhizosphere Microbiota.

Root-knot nematodes (Meloidogyne spp.) are one of the most economically important plant parasitic nematodes, infecting almost all cultivated plants and resulting in severe yield losses every year. Plant growth-promoting rhizobacteria (PGPR) have been extensively used to prevent and control root-knot diseases and increase yield. In this study, the effect of a consortium of three PGPR strains (Bacillus cereus AR156, B. subtilis SM21, and Serratia sp. XY21; hereafter "BBS") on root-knot disease of cucumber was evaluated. The application of BBS significantly reduced the severity of root-knot disease by 56 to 72%, increased yield by 36 to 55%, and improved fruit quality by 14 to 90% and soil properties by 1 to 90% relative to the control in the cucumber fields of the Nanjing suburb, Jiangsu Province, from 2015 to 2018. BBS altered the rhizosphere bacterial community. Compared with the control group, it significantly (false discovery rate, P < 0.05) increased the abundance of 14 bacterial genera that were negatively correlated with disease severity. Additionally, the redundancy analysis suggested that BBS-treated rhizosphere soil samples were dominated by disease-suppressive bacteria, including the genera Iamia, Kutzneria, Salinibacterium, Mycobacterium, Kribbella, Pseudonocardia, Sporichthya, Sphaerisporangium, Actinomadura, Flavisolibacter, Phenylobacterium, Bosea, Hyphomicrobium, Agrobacterium, Sphingomonas, and Nannocystis, which were positively related to total organic carbon, total nitrogen, total organic matter, dissolved organic carbon, [Formula: see text]-N, and available phosphorus contents. This suggests that BBS suppresses root-knot nematodes and improves the soil chemical properties of cucumber by altering the rhizosphere microbial community.

Spatio-Temporal Joint Optimization-Based Trajectory Planning Method for Autonomous Vehicles in Complex Urban Environments.

Providing safe, smooth, and efficient trajectories for autonomous vehicles has long been a question of great interest in the field of autopiloting. In dynamic and ever-changing urban environments, safe and efficient trajectory planning is fundamental to achieving autonomous driving. Nevertheless, the complexity of environments with multiple constraints poses challenges for trajectory planning. It is possible that behavior planners may not successfully obtain collision-free trajectories in complex urban environments. Herein, this paper introduces spatio-temporal joint optimization-based trajectory planning (SJOTP) with multi-constraints for complex urban environments. The behavior planner generates initial trajectory clusters based on the current state of the vehicle, and a topology-guided hybrid A* algorithm applied to an inflated map is utilized to address the risk of collisions between the initial trajectories and static obstacles. Taking into consideration obstacles, road surface adhesion coefficients, and vehicle dynamics constraints, multi-constraint multi-objective coordinated trajectory planning is conducted, using both differential-flatness vehicle models and point-mass vehicle models. Taking into consideration longitudinal and lateral coupling in trajectory optimization, a spatio-temporal joint optimization solver is used to obtain the optimal trajectory. The simulation verification was conducted on a multi-agent simulation platform. The results demonstrate that this methodology can obtain optimal trajectories safely and efficiently in complex urban environments.

Occurrence, transmission and risks assessment of pathogens in aquatic environments accessible to humans.

Pathogens are ubiquitously detected in various natural and engineered water systems, posing potential threats to public health. However, it remains unclear which human-accessible waters are hotspots for pathogens, how pathogens transmit to these waters, and what level of health risk associated with pathogens in these environments. This review collaboratively focuses and summarizes the contamination levels of pathogens on the 5 water systems accessible to humans (natural water, drinking water, recreational water, wastewater, and reclaimed water). Then, we showcase the pathways, influencing factors and simulation models of pathogens transmission and survival. Further, we compare the health risk levels of various pathogens through Quantitative Microbial Risk Assessment (QMRA), and assess the limitations of water-associated QMRA application. Pathogen levels in wastewater are consistently higher than in other water systems, with no significant variation for Cryptosporidium spp. among five water systems. Hydraulic conditions primarily govern the transmission of pathogens into human-accessible waters, while environmental factors such as temperature impact pathogens survival. The median and mean values of computed public health risk levels posed by pathogens consistently surpass safety thresholds, particularly in the context of recreational waters. Despite the highest pathogens levels found in wastewater, the calculated health risk is significantly lower than in other water systems. Except pathogens concentration, variables like the exposure mode, extent, and frequency are also crucial factors influencing the public health risk in water systems. This review shares valuable insights to the more accurate assessment and comprehensive management of public health risk in human-accessible water environments.

Rational Design of Orange-Red Emissive Carbon Dots for Tracing Lysosomal Viscosity Dynamics in Living Cells and Zebrafish.

Lysosomal viscosity is an essential microenvironment parameter in lysosomes, which is closely associated to the occurrence and development of various diseases, including cancer. Thus, accurately quantifying lysosomal viscosity changes is highly desirable for a better understanding of the dynamics and biological functions of lysosomes. In this study, lysosome self-targetable orange-red emissive carbon dots (OR-CDs) were rationally designed and developed for monitoring lysosomal viscosity fluctuations. The enhanced fluorescence of OR-CDs could be obviously observed as the viscosity increased from 1.07 to 950 cP. Moreover, the as-prepared OR-CDs could quickly enter cells for lysosome-targeting imaging and visualize viscosity variations in living cells and zebrafish. More importantly, by utilizing OR-CDs, we successfully achieved tracing the variations in lysosomal viscosity during the autophagy process. Additionally, as cancer cells possess high viscosity than normal cells, the OR-CDs have been effectively utilized for cancer imaging from cell, tissue, and organ to in vivo levels. It is expected that the developed OR-CDs not only provide a meaningful tool for visualizing investigations of lysosome viscosity-related diseases but also shed light on the development based on the nanomaterial for the clinical diagnosis of cancer.

Self-Templated Formation of Carbon Nanotubes Interpenetrating Ordered Microporous Carbon Nanospheres for High-Performance Li-S Batteries.

Lithium-sulfur (Li-S) batteries are known as a prospective new generation of battery systems owing to their high energy density, low cost, non-toxicity, and environmental friendliness. Nevertheless, several issues remain in the practical application of Li-S batteries, such as low sulfur usage, poor rate performance, and poor cycle stability. Ordered microporous carbon materials and carbon nanotubes (CNTs) can effectively limit the diffusion of polysulfides (LiPSs) and have high electrical conductivity, respectively. Here, inspired by the evaporation of zinc at high temperatures, we constructed CNTs interpenetrating ordered microporous carbon nanospheres (CNTs/OMC NSs) by high-temperature calcination and used them as a sulfur host material. With the benefit from the excellent electrical conductivity of CNTs and OMC achieving uniform sulfur dispersion and effectively limiting LiPS dissolution, the S@CNTs/OMC NS cathodes show outstanding cycling stability (initial discharge capacity of 879 mAh g-1 at 0.5 C, maintained at 629 mAh g-1 for 500 cycles) and excellent rate performance (521 mAh g-1 at 5.0 C). Furthermore, the current study can serve as a significant reference for the synthesis of CNTs that interpenetrate various materials.

Microbial Stratification Affects Conversions of Nitrogen and Methane in Biofilms Coupling Anammox and n-DAMO Processes.

A methane-based membrane biofilm reactor (MBfR) has a suitable configuration to incorporate anammox and nitrite/nitrate-dependent anaerobic methane oxidation (n-DAMO) processes because of its high gas-transfer efficiency and efficient biomass retention. In this study, the spatial distribution of microorganisms along with the biofilm depth in methane-based MBfRs was experimentally revealed, showing the dominance of anammox bacteria, n-DAMO bacteria, and n-DAMO archaea in the outer layer, middle layer, and inner layer of biofilms, respectively. The long-term and short-term experimental investigations in conjunction with mathematical modeling collectively revealed that microorganisms living in the outer layer of biofilms tend to use substrates from wastewater, while microorganisms inhabiting the inner layer of biofilms tend to use substrates originating from biofilm substratum. Specifically, anammox bacteria dominating the biofilm surface preferentially removed the nitrite provided from wastewater, while n-DAMO bacteria mostly utilized the nitrite generated from n-DAMO archaea as these two methane-related populations spatially clustered together inside the biofilm. Likewise, the methane supplied from the membrane was mostly consumed by n-DAMO archaea, while the dissolved methane in wastewater would be primarily utilized by n-DAMO bacteria. This study offers novel insights into the impacts of microbial stratification in biofilm systems, not only expanding the fundamental understanding of biofilms and microbial interactions therein but also providing a rationale for the potential applications of methane-based MBfRs in sewage treatment.

Nitrite Oxidation in Wastewater Treatment: Microbial Adaptation and Suppression Challenges.

Microbial nitrite oxidation is the primary pathway that generates nitrate in wastewater treatment systems and can be performed by a variety of microbes: namely, nitrite-oxidizing bacteria (NOB). Since NOB were first isolated 130 years ago, the understanding of the phylogenetical and physiological diversities of NOB has been gradually deepened. In recent endeavors of advanced biological nitrogen removal, NOB have been more considered as a troublesome disruptor, and strategies on NOB suppression often fail in practice after long-term operation due to the growth of specific NOB that are able to adapt to even harsh conditions. In line with a review of the history of currently known NOB genera, a phylogenetic tree is constructed to exhibit a wide range of NOB in different phyla. In addition, the growth behavior and metabolic performance of different NOB strains are summarized. These specific features of various NOB (e.g., high oxygen affinity of Nitrospira, tolerance to chemical inhibitors of Nitrobacter and Candidatus Nitrotoga, and preference to high temperature of Nitrolancea) highlight the differentiation of the NOB ecological niche in biological nitrogen processes and potentially support their adaptation to different suppression strategies (e.g., low dissolved oxygen, chemical treatment, and high temperature). This review implicates the acquired physiological characteristics of NOB to their emergence from a genomic and ecological perspective and emphasizes the importance of understanding physiological characterization and genomic information in future wastewater treatment studies.

Methane Oxidation Coupled to Selenate Reduction in a Membrane Bioreactor under Oxygen-Limiting Conditions.

Microbial methane oxidation coupled to a selenate reduction process has been proposed as a promising solution to treat contaminated water, yet the underlying microbial mechanisms are still unclear. In this study, a novel methane-based membrane bioreactor system integrating hollow fiber membranes for efficient gas delivery and ultrafiltration membranes for biomass retention was established to successfully enrich abundant suspended cultures able to perform methane-dependent selenate reduction under oxygen-limiting conditions. The microbial metabolic mechanisms were then systematically investigated through a combination of short-term batch tests, DNA-based stable isotope probing (SIP) microcosm incubation, and high-throughput sequencing analyses of 16S rRNA gene and functional genes (pmoA and narG). We confirmed that the methane-supported selenate reduction process was accomplished by a microbial consortia consisting of type-II aerobic methanotrophs and several heterotrophic selenate reducers. The mass balance and validation tests on possible intermediates suggested that methane was partially oxidized into acetate under oxygen-limiting conditions, which was consumed as a carbon source for selenate-reducing bacteria. High-throughput 16S rRNA gene sequencing, DNA-SIP incubation with 13CH4, and subsequent functional gene (pmoA and narG) sequencing results collectively proved that Methylocystis actively executed partial methane oxidation and Acidovorax and Denitratisoma were dominant selenate-reducing bacteria, thus forming a syntrophic partnership to drive selenate reduction. The findings not only advance our understanding of methane oxidation coupled to selenate reduction under oxygen-limiting conditions but also offer useful information on developing methane-based biotechnology for bioremediation of selenate-contaminated water.

Determining the Contribution of Micro/Nanoplastics to Antimicrobial Resistance: Challenges and Perspectives.

Microorganisms colonizing the surfaces of microplastics form a plastisphere in the environment, which captures miscellaneous substances. The plastisphere, owning to its inherently complex nature, may serve as a "Petri dish" for the development and dissemination of antibiotic resistance genes (ARGs), adding a layer of complexity in tackling the global challenge of both microplastics and ARGs. Increasing studies have drawn insights into the extent to which the proliferation of ARGs occurred in the presence of micro/nanoplastics, thereby increasing antimicrobial resistance (AMR). However, a comprehensive review is still lacking in consideration of the current increasingly scattered research focus and results. This review focuses on the spread of ARGs mediated by microplastics, especially on the challenges and perspectives on determining the contribution of microplastics to AMR. The plastisphere accumulates biotic and abiotic materials on the persistent surfaces, which, in turn, offers a preferred environment for gene exchange within and across the boundary of the plastisphere. Microplastics breaking down to smaller sizes, such as nanoscale, can possibly promote the horizontal gene transfer of ARGs as environmental stressors by inducing the overgeneration of reactive oxygen species. Additionally, we also discussed methods, especially quantitatively comparing ARG profiles among different environmental samples in this emerging field and the challenges that multidimensional parameters are in great necessity to systematically determine the antimicrobial dissemination risk in the plastisphere. Finally, based on the biological sequencing data, we offered a framework to assess the AMR risks of micro/nanoplastics and biocolonizable microparticles that leverage multidimensional AMR-associated messages, including the ARGs' abundance, mobility, and potential acquisition by pathogens.

The effectiveness and role of phages in the disruption and inactivation of clinical P. aeruginosa biofilms.

Biofilms of P. aeruginosa are known to be resilient forms of survival of this opportunistic pathogen, both within the host and in natural or engineered environments. This study investigated the role of phages in the disruption and inactivation of clinical P. aeruginosa biofilms by previously isolated phages. All seven tested clinical strains formed biofilms in 56-80 h. Four previously isolated phages were effective in disrupting the formed biofilms when applied at multiplicity of infection (MOI) of 10, where phage cocktails had equivalent or worse performance than single phages. Phage treatments reduced the biofilms' biomass (cells and extracellular matrix) by 57.6-88.5% after 72 h of incubation. Biofilm disruption led to the detachment of 74.5-80.4% of the cells. The phages were also able to kill the cells from the biofilms, reducing the living cell counts by approximately 40.5-62.0% after a single treatment. A fraction of 24-80% of these killed cells were also lysed due to phage action. This study showed that phages can have a relevant role in disrupting, inactivating, and destroying P. aeruginosa biofilms, which can be used in the development of treatment processes to complement or replace antibiotics and/or disinfectants.

Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model.

BACKGROUND: Porcine circovirus type 2 (PCV2) is one of the major pathogens commonly found in pigs, which causes immunosuppression and apoptosis. Vaccination and a single drug cannot totally prevent and treat PCV2 infection. Our previous in vitro study reported that the synergistic anti-PCV2 effect of Matrine and Osthole was better than that of Matrine or Osthole alone, This study was aimed to evaluate the synergistic anti-PCV2 effect as well as the underline molecular mechanism of Matrine and Osthole in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups namely control group, PCV2 infected, Matrine combined with Osthole high dose treatment (40 mg/kg + 12 mg/kg), medium dose treatment (20 mg/kg + 6 mg/kg), low dose treatment (10 mg/kg + 3 mg/kg), Matrine treatment (40 mg/kg), Osthole treatment (12 mg/kg) and Ribavirin positive control (40 mg/kg) groups. PCV2 was intraperitoneally (i.p.) injected in all mice except the control group. 5 days of post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for the next 5 consecutive days. RESULTS: The synergistic inhibitory effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly heigher than that of Matrine and Osthole alone. The expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax proteins were significantly reduced, while that of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological changes caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils. CONCLUSIONS: The synergistic anti-apoptotic effect of Matrine and Osthole was better than their alone effect, Both Matrine and Osthole had directly inhibited the expression of PCV2 Cap and the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provided a new insight to control PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.

Baicalin ameliorates high fat diet-induced nonalcoholic fatty liver disease in mice via adenosine monophosphate-activated protein kinase-mediated regulation of SREBP1/Nrf2/NF-κB signaling pathways.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease around the world, imposing severe threats on human health. Unfortunately, no clinically approved drugs are available for use as yet. Baicalin (BA) is reported to have hepatoprotective effects, and it is not clear whether BA can treat NAFLD and how. Here, a high-fat diet (HFD)-induced NAFLD mouse model was established to explore the protective roles and mechanisms of BA against HFD-induced NAFLD. Physiochemical results showed that BA exhibited significantly protective effects against HFD-induced NAFLD in mice. Liver transcriptomic analysis revealed that BA attenuated HFD-induced NAFLD via activating AMPK pathway, which was confirmed by the AMPK inhibitor Compound C. Additionally, the expression changes of AMPK downstream genes demonstrated that BA exerted ameliorative effects against NAFLD through AMPK-mediated inhibition of SREBP1 and NF-κB pathways, and activation of Nrf2 pathway. Taken together, our study reveals the protective roles of BA against HFD-caused NAFLD through AMPK-mediated modulation of SREBP1/Nrf2/NF-κB pathways, suggesting that BA has potential drug development implications. Most importantly, our study creates a paradigm through the combination of molecular biology and bioinformatics for further studies of action mechanisms of biomolecules combating diseases.