Direct synthesis of carbamates, thiocarbamates, and ureas from Boc-protected amines: a sustainable and efficient approach.

In the quest for sustainable and efficient synthetic methodologies within medicinal chemistry, the synthesis of carbamates and their derivatives holds a pivotal role due to their widespread application in bioactive compounds. This investigation unveils a novel methodology for the straightforward transformation of Boc-protected amines into carbamates, thiocarbamates, and ureas, utilizing tert-butoxide lithium as the sole base. This approach effectively obviates the necessity for hazardous reagents and metal catalysts, presenting marked enhancements compared to traditional synthetic pathways. Notably, the method demonstrates facile scalability to gram-level production. This study contributes to the advancement of sustainable synthetic methodologies, offering a more benign and efficient alternative for the synthesis of key chemical intermediates with implications for broad pharmaceutical and agrochemical applications.

Network pharmacology and molecular docking-based investigation of monocyte locomotion inhibitory factor attenuates traumatic brain injury by regulating aquaporin 4 expression.

Traumatic brain injury (TBI) is a significant cause of disability and mortality worldwide, and effective treatment options are currently limited. Monocyte locomotion inhibitor factor (MLIF), a small molecular pentapeptide, has demonstrated a protective effect against cerebral ischemia. This study aimed to investigate the protective effects of MLIF on TBI and explore its underlying mechanism of action. In animal experiments, we observed that administration of MLIF after TBI reduced brain water content and improved brain edema, suggesting a certain degree of protection against TBI. By utilizing network pharmacology methodologies, we employed target screening techniques to identify the potential targets of MLIF in the context of TBI. As a result, we successfully enriched ten signaling pathways that are closely associated with TBI. Furthermore, using molecular docking techniques, we identified AQP4 as one of the top ten central genes discovered in this study. Eventually, our study demonstrated that MLIF exhibits anti-apoptotic properties and suppresses the expression of AQP4 protein, thus playing a protective role in traumatic brain injury. This conclusion was supported by TUNEL staining and the evaluation of Bcl-2, Bax, and AQP4 protein levels. These discoveries enhance our comprehension of the mechanisms by which MLIF exerts its protective effects and highlight its potential as a promising therapeutic intervention for TBI treatment.

I-C-F-6 attenuates chronic cerebral hypoperfusion-induced neurological injury in mice by modulating microglia polarization.

Chronic cerebral hypoperfusion (CCH) is the leading cause of chronic cerebral dysfunction syndrome with its complex pathological mechanisms involving cortical and hippocampal neuronal loss, white matter lesions, and neuroinflammation. I-C-F-6 is a septapeptide, which has anti-inflammatory and anti-fibrotic effects. This study aimed to evaluate the neuroprotective effect of I-C-F-6 in chronic cerebral hypoperfusion (CCH)-induced neurological injury. C57BL/6 J mice were subjected to bilateral common carotid artery stenosis (BCAS), and BV2 microglia cells were induced with oxygen-glucose deprivation (OGD). In vivo, mice were divided randomly into four groups: Sham, BCAS, GBE (30 mg/kg), and I-C-F-6 (0.5 mg/kg). In vitro, microglia were divided randomly into four groups: control, OGD, I-C-F-6 (25 µg/mL), and Shikonin (800 nmol/L). Through LFB, TUNEL, and NeuN staining, we found that I-C-F-6 was able to mitigate myelin pathology and reduce the number of apoptotic neurons. Furthermore, immunofluorescence staining revealed that I-C-F-6 was able to reduce microglia clustering and downregulate NF-κB p65. We also observed a significant downregulation of M1 phenotype microglia signature genes, such as TNF-α, iNOS, and upregulation of anti-inflammatory cytokines, such as Arg-1 and IL-10, indicating that I-C-F-6 may mainly reduce polarization towards the M1 phenotype in microglia. Notably, I-C-F-6 downregulated the expression of NF-κB signaling pathway-related proteins IKK-ß and NF-κB p65, as well as pro-inflammatory cytokines IL-1ß and iNOS. In conclusion, I-C-F-6 can improve neurological damage, alleviate neuroinflammation, and inhibit microglia polarization to the M1 phenotype via the NF-κB signaling pathway.

Cyclo (MQCNS) has the potential to treat ischemic stroke.

We previously found that monocyte locomotion inhibitory factor has a neuroprotective effect on ischemic brain injury during the acute phase of stroke. Therefore, we modified the structure of an anti-inflammatory monocyte locomotion inhibitory factor peptide to construct an active cyclic peptide-Cyclo (MQCNS) (LZ-3)-and investigated its effects on ischemic stroke. In this study, we established a rat model of ischemic stroke by occluding the middle cerebral artery and then administered LZ-3 (2 or 4 mg/kg) via the tail vein for 7 consecutive days. Our results showed that LZ-3 (2 or 4 mg/kg) substantially decreased infarct volume, reduced cortical nerve cell death, improved neurological function, reduced cortical and hippocampal injury, and decreased the levels of inflammatory factors in the blood and brain tissues. In a well-differentiated, oxygen-glucose deprivation/reoxygenation-induced BV2 cell model of post-stroke, LZ-3 (100 µM) inhibited the JAK1-STAT6 signaling pathway. LZ-3 regulated microglia/macrophage polarization from the M1 to the M2 type and inhibited microglia/macrophage phagocytosis and migration via the JAK1/STAT6 signaling pathway. To conclude, LZ-3 regulates microglial activation by inhibiting the JAK1/STAT6 signaling pathway and improves functional recovery post-stroke.

Network pharmacology and molecular docking-based analysis of protective mechanism of MLIF in ischemic stroke.

Objective: This study aimed to evaluate the potential mechanism by which Monocyte locomotion inhibitory factor (MLIF) improves the outcome of ischemic stroke (IS) inflammatory injury. Methods: Potential MLIF-related targets were predicted using Swiss TargetPrediction and PharmMapper, while IS-related targets were found from GeneCards, PharmGKB, and Therapeutic Target Database (TTD). After obtaining the intersection from these two datasets, the Search Tool for Retrieval of Interacting Genes/Protein (STRING11.0) database was used to analyze the protein-protein interaction (PPI) network of the intersection and candidate genes for MLIF treatment of IS. The candidate genes were imported into the Metascape database for Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The top 20 core genes and the "MLIF-target-pathway" network were mapped using the Cytoscape3.9.1. Using AutoDock Vina1.1.2, the molecular docking validation of the hub targets and MLIF was carried out. In the experimental part, transient middle cerebral artery occlusion (tMCAO) and oxygen and glucose deprivation (OGD) models were used to evaluate the protective efficacy of MLIF and the expression of inflammatory cytokines and the putative targets. Results: MLIF was expected to have an effect on 370 targets. When these targets were intersected with 1,289 targets for ischemic stroke, 119 candidate therapeutic targets were found. The key enriched pathways were PI3K-Akt signaling pathway and MAPK signaling pathway, etc. The GO analysis yielded 1,677 GO entries (P < 0.01), such as hormone stimulation, inflammatory response, etc. The top 20 core genes included AKT1, EGFR, IGF1, MAPK1, MAPK10, MAPK14, etc. The result of molecular docking demonstrated that MLIF had the strong binding capability to JNK (MAPK10). The in vitro and in vivo studies also confirmed that MLIF protected against IS by lowering JNK (MAPK10) and AP-1 levels and decreasing pro-inflammatory cytokines (IL-1, IL-6). Conclusion: MLIF may exert a cerebral protective effect by inhibiting the inflammatory response through suppressing the JNK/AP-1 signaling pathway.

Rapid Seismic Evaluation of Continuous Girder Bridges with Localized Plastic Hinges.

In seismic assessment of continuous girder bridges, plastic hinges form in bridge piers to dissipate seismic energy through nonlinear restoring forces. Considering temporal and spatial variations of ground motions, seismic evaluation of the bridges involves nonlinear stochastic vibration and expensive computation. This paper presents an approach to significantly increase the efficiency of seismic evaluation for continuous girder bridges with plastic hinges. The proposed approach converts nonlinear motion equations into quasi-linear state equations, solves the equations using an explicit time-domain dimension-reduced iterative method, and incorporates a stochastic sampling method to statistically analyze the seismic response of bridges under earthquake excitation. Taking a 3 × 30 m continuous girder bridge as an example, fiber beam-column elements are used to simulate the elastic-plastic components of the continuous girder bridge, and the elastic-plastic time history analysis of the continuous girder bridge under non-uniform seismic excitation is carried out. Results show that the computation time is only 5% of the time of the nonlinear time history approach while retaining the accuracy. This study advances the capability of rapid seismic assessment and design for bridges with localized nonlinear behaviors such as plastic hinges.

Lateral Vibration Control of Long-Span Small-Radius Curved Steel Box Girder Pedestrian Bridge with Distributed Multiple Tuned Mass Dampers.

Curved pedestrian bridges are important urban infrastructure with the desired adaptability to the landscape constraints and with aesthetic benefits. Pedestrian bridges feature thin cross-sections, which provide sufficient load capacities but lead to low natural frequencies that make the bridges susceptible to vibration under pedestrian excitation. This study investigates the lateral vibration of a curved bridge with a small radius down to 20 m, proposes an approach to mitigate the lateral vibration of bridges with large curvatures using distributed multiple tuned mass dampers (MTMD), and conducts in-situ bridge tests to evaluate the vibration mitigation performance. The lateral vibration was investigated through in-situ tests and finite element analysis as well as the code requirements. The key parameters of the distributed MTMD system were improved by strategically selecting the mass ratio, bandwidth, center frequency ratio, and damper number. The results showed that the curved bridge was subjected to significant lateral vibration due to the coupling of torque and moment, and the recommended design parameters for the studied bridge were derived, i.e., the total mass ratio is 0.02, bandwidth is 0.15, center frequency ratio is 1.0, and damper number is 3. The proposed approach effectively improves the deployment of MTMD for lateral vibration control of the curved bridge. The field tests showed that the vibration was reduced by up to 82% by using the proposed approach.

Assembling Alkaline-Responsive Chitosan@Giant Liposomes through an Ultrasound-Integrated Microfluidic Approach.

This paper presents the fabrication of an alkaline-responsive drug carrier, chitosan@giant liposome (CS-GL), by using an ultrasound-integrated microfluidic approach. On the microfluidic chip, water/oil/water droplets are first prepared and then move through an area of ultrasonic radiation to improve the regional saturation of organic solvent and accelerate its removal. At the same time, phospholipid molecules in the oil phase of the droplets are efficiently self-assembled into giant liposomes (GLs). Subsequently, microfluidic channels combined with an up-down separated structure can help in the fabrication and purification of the GLs. Due to the electrostatic interaction between the amino group of chitosan and the phosphate group of phospholipids, the GLs and chitosan are assembled into CS-GLs. The change of ζ potential after this operation indicates that chitosan is coated on the surface of GLs. The formed CS-GLs are monodispersed with a 54.1 ± 0.7 µm diameter and high drug encapsulation efficiency (∼96%), and the structural integrity can be kept without leakage of contents for more than a week in an acid medium (pH = 1.2). When this structure is placed in an aqueous solution of pH = 7.8, chitosan precipitates gradually and detaches from the GL, causing its rupture. The drug encapsulated in a single CS-GL can be rapidly released within 4 s, and 99.6% of the CS-GL carriers can complete the release within 10 min.

Identification of novel proteolytically inactive mutations in coronavirus 3C-like protease using a combined approach.

Coronaviruses (CoVs) infect humans and multiple other animal species, causing highly prevalent and severe diseases. 3C-like proteases (3CLpros) from CoVs (also called main proteases) are essential for viral replication and are also involved in polyprotein cleavage and immune regulation, making them attractive and effective targets for the development of antiviral drugs. Herein, the 3CLpro from the porcine epidemic diarrhea virus, an enteropathogenic CoV, was used as a model to identify novel crucial residues for enzyme activity. First, we established a rapid, sensitive, and efficient luciferase-based biosensor to monitor the activity of PDEV 3CLproin vivo. Using this luciferase biosensor, along with confirming the well-known catalytic residues (His41 and Cys144), we identified 4 novel proteolytically inactivated mutants of PDEV 3CLpro, which was also confirmed in mammalian cells by biochemical experiments. Our molecular dynamics (MD) simulations showed that the hydrogen bonding interactions occurring within and outside of the protease's active site and the dynamic fluctuations of the substrate, especially the van der Waals contacts, were drastically altered, a situation related to the loss of 3CLpro activity. These data suggest that changing the intermolecular dynamics in protein-substrate complexes eliminates the mechanism underlying the protease activity. The discovery of novel crucial residues for enzyme activity in the binding pocket could potentially provide more druggable sites for the design of protease inhibitors. In addition, our in-depth study of the dynamic substrate's envelope model using MD simulations is an approach that could augment the discovery of new inhibitors against 3CLpro in CoVs and other viral 3C proteases.-Zhou, J., Fang, L., Yang, Z., Xu, S., Lv, M., Sun, Z., Chen, J., Wang, D., Gao, J., Xiao, S. Identification of novel proteolytically inactive mutations in coronavirus 3C-like protease using a combined approach.

Transcriptome analysis of the effects of Cd and nanomaterial-loaded Cd on the liver in zebrafish.

The wide application of engineered nanoparticles to remove heavy metals in aquatic environments has raised concerns over nanomaterial-adsorbed heavy metal toxicity. To ensure safe use of nanomaterial-heavy metal composites, understanding their biological effects at the molecular level is crucial. In the present study, we used the Illumina HiSeq technology to study the transcriptome changes induced by Cd2+ and nano-manganese dioxide- or nano-hydroxyapatite-adsorbed CdCl2 composites (nMnO2-Cd, nHAP20-Cd, and nHAP40-Cd) in zebrafish liver cells. We identified 545 differentially expressed genes (DEGs), 33 of which were in common between the nMnO2-Cd, nHAP20-Cd, and nHAP40-Cd groups. The DEGs could be classified in four categories: hydrolases (enzymes involved in various physiological functions, including digestion, immune response, blood coagulation, and reproduction), biological binding (FMN-, actin- and metal ion-binding), metabolic enzymes (e.g., ceramidase, alpha-amylase, carboxylic ester hydrolase, and carboxypeptidase), and cell structure (cell surface, intermediate filament, and muscle myopen protein). The DEGs identified in this study are potentially useful markers to understand the physiological responses induced by Cd2+ and nano-Cd composites in zebrafish liver.

Oxidative stress and DNA damage in zebrafish liver due to hydroxyapatite nanoparticles-loaded cadmium.

This study investigated the acute and sub-acute toxicity responses in zebrafish following their exposure to hydroxyapatite-loaded cadmium nanoparticles (nHAP-Cd). The results indicate that cadmium chloride (Cd2+), 20 nm nHAP-Cd (nHAP20-Cd), and 40 nm nHAP-Cd (nHAP40-Cd) caused toxicity in zebrafish; the toxicity levels were in the following order: Cd2+ > nHAP20-Cd > nHAP40-Cd. Furthermore, nHAP-Cd showed level II grade of acute toxicity in zebrafish; the gradation was done on the guidelines of the Organization for Economic Co-operation and Development 203. We also found that Cd2+ ions and nHAP-Cd affected the malondialdehyde (MDA) levels and membrane permeability of zebrafish livers; these effects were compliant with the changes in antioxidant levels. The results of enzyme assays indicate the following notion: following the exposure of zebrafish to 0.12-0.93 mg/L nHAP-Cd, the activities of peroxidase, superoxide dismutase, and catalase enzymes increased significantly. Moreover, the content of anti-superoxide anion also increased substantially. This increasing trend of enzymatic activity was observed until the concentration of nHAP-Cd reached 1.86 mg/L nHAP-Cd. By increasing the concentration of both Cd2+ and nHAP-Cd, we found that levels of DNA damage had increased substantially in zebrafish liver; this effect was visualized by performing comet assay.

Toxic effects of nanomaterial-adsorbed cadmium on Daphnia magna.

Chemical immobilization technologies involving the use of chemical absorbents such as nanomaterials have been recommended for the remediation of Cd-contaminated water and soil. The impact of nanomaterials or nanomaterials coexisting with other contaminants on aquatic organisms has been reported, but information on the toxic effects of nanomaterial-adsorbed cadmium (Nano-Cd) on aquatic organisms is lacking. This study aimed to investigate the acute and sub-acute toxicity of Nano-Cd on Daphnia magna by using a method developed based on the standard Organisation for Economic Co-operation and Development (OECD) 202 guidelines. The toxicity of cadmium chloride (Cd2+), nano-manganese dioxide-cadmium (nMnO2-Cd), 20nm nano-hydroxyapatite-cadmium (nHAP20-Cd), and 40nm nano-hydroxyapatite-cadmium (nHAP40-Cd) to D. magna was in the following order: Cd2+> nMnO2-Cd > nHAP20-Cd > nHAP40-Cd. Further, nMnO2-Cd, nHAP20-Cd, and nHAP40-Cd showed acute toxicity to D. magna of level II grade according to the Commission of the European Communities and OECD standards. Exposure to low and medium, but not high, Nano-Cd concentrations increased the activities of peroxidase, superoxide dismutase, catalase, and anti-superoxide anion. Thus, Nano-Cd, particularly at high concentrations, could exert oxidative damage in D. magna. An increase in Cd2+ and Nano-Cd concentrations gradually increased the malondialdehyde content, indicating cell membrane damage caused by the production of excessive O2-. Thus, the use of nanomaterials after adsorption of Cd is associated with a potential risk to aquatic organisms.

Assessing activity of Hepatitis A virus 3C protease using a cyclized luciferase-based biosensor.

Hepatitis A is an acute infection caused by Hepatitis A virus (HAV), which is widely distributed throughout the world. The HAV 3C cysteine protease (3Cpro), an important nonstructural protein, is responsible for most cleavage within the viral polyprotein and is critical for the processes of viral replication. Our group has previously demonstrated that HAV 3Cpro cleaves human NF-κB essential modulator (NEMO), a kinase required in interferon signaling. Based on this finding, we generated four luciferase-based biosensors containing the NEMO sequence (PVLKAQ↓ADIYKA) that is cleaved by HAV 3Cpro and/or the Nostoc punctiforme DnaE intein, to monitor the activity of HAV 3Cpro in human embryonic kidney cells (HEK-293T). Western blotting showed that HAV 3Cpro recognized and cleaved the NEMO cleavage sequence incorporated in the four biosensors, whereas only one cyclized luciferase-based biosensor (233-DnaE-HAV, 233DH) showed a measurable and reliable increase in firefly luciferase activity, with very low background, in the presence of HAV 3Cpro. With this biosensor (233DH), we monitored HAV 3Cpro activity in HEK-293T cells, and tested it against a catalytically deficient mutant HAV 3Cpro and other virus-encoded proteases. The results showed that the activity of this luciferase biosensor is specifically dependent on HAV 3Cpro. Collectively, our data demonstrate that the luciferase biosensor developed here might provide a rapid, sensitive, and efficient evaluation of HAV 3Cpro activity, and should extend our better understanding of the biological relevance of HAV 3Cpro.

Porcine Deltacoronavirus nsp5 Antagonizes Type I Interferon Signaling by Cleaving STAT2.

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus. The first outbreak of PDCoV was announced from the United States in 2014, followed by reports in Asia. The nonstructural protein nsp5 is a 3C-like protease of coronavirus, and our previous study showed that PDCoV nsp5 inhibits type I interferon (IFN) production. In this study, we found that PDCoV nsp5 significantly inhibited IFN-stimulated response element (ISRE) promoter activity and transcription of IFN-stimulated genes (ISGs), suggesting that PDCoV nsp5 also suppresses IFN signaling. Detailed analysis showed that nsp5 cleaved signal transducer and activator of transcription 2 (STAT2) but not Janus kinase 1 (JAK1), tyrosine kinase 2 (TYK2), STAT1, and interferon regulatory factor 9 (IRF9), key molecules of the JAK-STAT pathway. STAT2 cleavage was dependent on the protease activity of nsp5. Interestingly, nsp5 cleaved STAT2 at two sites, glutamine 685 (Q685) and Q758, and similar cleavage was observed in PDCoV-infected cells. As expected, cleaved STAT2 impaired the ability to induce ISGs, demonstrating that STAT2 cleavage is an important mechanism utilized by PDCoV nsp5 to antagonize IFN signaling. We also discussed the substrate selection and binding mode of PDCoV nsp5 by homologous modeling of PDCoV nsp5 with the two cleaved peptide substrates. The results of our study demonstrate that PDCoV nsp5 antagonizes type I IFN signaling by cleaving STAT2 and provides structural insights for comprehending the cleavage mechanism of PDCoV nsp5, revealing a potential new function for PDCoV nsp5 in type I IFN signaling.IMPORTANCE The 3C-like protease encoded by nsp5 is a major protease of coronaviruses; thus, it is an attractive target for development of anticoronavirus drugs. Previous studies have revealed that the 3C-like protease of coronaviruses, including PDCoV and porcine epidemic diarrhea virus (PEDV), antagonizes type I IFN production by targeting the NF-κB essential modulator (NEMO). Here, for the first time, we demonstrate that overexpression of PDCoV nsp5 also antagonizes IFN signaling by cleaving STAT2, an essential component of transcription factor complex ISGF3, and that PDCoV infection reduces the levels of STAT2, which may affect the innate immune response.

Avoidance behavior of Eisenia fetida in oxytetracycline- and heavy metal-contaminated soils.

To determine the behavior of oxytetracycline (OTC) and heavy metals in soil, this study assessed the pollutant-induced avoidance behavior of earthworms (E. fetida) exposed to zinc (Zn2+), lead (Pb2+), and OTC in soil. The results showed a clear avoidance response within 48h of exposure to the highest concentrations of pollutants. Moreover, E. fetida was shown to be more sensitive to Zn2+ than to Pb2+ and OTC. Compared with OTC alone, the net response of earthworms increased in the OTC-Zn2+ and OTC-Pb2+ combined treatments, indicating a synergistic effect. Moreover, the net response (NR) of the earthworms was higher for OTC-Zn2+ than it was for OTC-Pb2+, possibly reflecting the differences in essential characteristics of Zn and Pb.

Salicylic acid mediates antioxidant defense system and ABA pathway related gene expression in Oryza sativa against quinclorac toxicity.

The auxin herbicide quinclorac is widely used for controlling weeds in transplanted and direct-seeded rice fields. However, its phytotoxic responses on rice are still unknown. Therefore, in the present investigation we studied the effects of different concentrations (0, 0.1 and 0.5g/L) of quinclorac herbicide on the physiological and biochemical changes of two rice cultivars (XS 134 and ZJ 88) and further analyzed the ameliorating role of salicylic acid (SA) on quinclorac toxicity in rice plants. The results revealed that exogenous application of SA significantly increased plant biomass and total chlorophyll contents in herbicide stressed plants. The lipid peroxidation and ROS (H2O2, O2(-.), (-)OH) production were significantly increased in roots and leaves of both rice cultivars under quinclorac stress, demonstrating an oxidative burst in rice plants. Whereas, application of SA significantly lowered ROS contents under quinclorac stress. Further, exogenous SA treatment significantly modulated antioxidant enzymes and enhanced GSH concentration in stress plants. Anatomical observations of leaf and root revealed that herbicide affected internal structures, while SA played a vital role in protection from toxic effects. Expression analysis of stress hormone ABA genes (OsABA8oxs, OsNCEDs) revealed that quinclorac application enhanced stress condition in cultivar ZJ 88, while SA treatment downregulated ABA genes more in cultivar XS 134, which correlated with the enhanced tolerance to quinclorac induced oxidative stress in this cultivar. The present study delineated that SA played a critical role under quinclorac stress in both rice cultivars by regulating antioxidant defense system, reducing ROS formation and preventing the degradation of internal cell organelles.

A dynamic interaction process between KaiA and KaiC is critical to the cyanobacterial circadian oscillator.

The core circadian oscillator of cyanobacteria consists of three proteins, KaiA, KaiB, and KaiC. This circadian oscillator could be functionally reconstituted in vitro with these three proteins, and therefore has been a very important model in circadian rhythm research. KaiA can bind to KaiC and then stimulate its phosphorylation, but their interaction mechanism remains elusive. In this study, we followed the "second-site suppressor" strategy to investigate the interaction mechanism of KaiA and KaiC. Using protein sequence analyses, we showed that there exist co-varying residues in the binding interface of KaiA and KaiC. The followed mutagenesis study verified that these residues are important to the functions of KaiA and KaiC, but their roles could not be fully explained by the reported complex structures of KaiA and KaiC derived peptides. Combining our data with previous reports, we suggested a dynamic interaction mechanism in KaiA-KaiC interaction, in which both KaiA and the intrinsically disordered tail of KaiC undergo significant structural changes through conformational selection and induced fit during the binding process. At last, we presented a mathematic model to support this hypothesis and explained the importance of this interaction mechanism for the KaiABC circadian oscillator.

Antibacterial activity of ruthenium(II) polypyridyl complex manipulated by membrane permeability and cell morphology.

This study investigates the antibacterial effects of the ruthenium(II) complex RuBP and the mechanism of RuBP action on bacteria. Results show that RuBP can inhibit the growth of Gram-positive bacteria, such as Staphylococcus aureus and Micrococcus tetragenus. Cellular uptake and laser confocal microscopic studies reveal the efficient uptake of RuBP by M. tetragenus cells. Scanning electron microscopic observations of the morphologies of M. tetragenus and S. aureus treated with RuBP further confirm that direct contact of both bacteria with RuBP can damage the cell membrane and membrane integrity, which may eventually induce growth inhibition and bacterial death. After RuBP treatment, the electrical conductivity of the bacterial suspensions increases. Spectroscopic studies and agarose gel electrophoresis indicate that intact DNA and RNA decrease or disappear in RuBP-treated bacterial cells, thus demonstrating that RuBP performs its antibacterial function by increasing the permeability of cell membranes. This study provides new insights for understanding the antibacterial actions of RuBP and designing metal complex antibiotics for other biomedical applications.