Electronic structure of the strongly correlated electron system plutonium hexaboride: A study from single-particle approximations and many-body calculations.

The electronic structure of the strongly correlated electron system plutonium hexaboride is studied by using single-particle approximations and a many-body approach. Imaginary components of impurity Green's functions show that 5fj=5/2 and 5fj=7/2 manifolds are in conducting and insulating regimes, respectively. Quasi-particle weights and their ratio suggest that the intermediate coupling mechanism is applicable for Pu 5f electrons, and PuB6 might be in the orbital-selective localized state. The weighted summation of occupation probabilities yields the interconfiguration fluctuation and average occupation number of 5f electrons n5f ~ 5.101. The interplay of 5f-5f correlation, spin-orbit coupling, Hund's exchange interaction, many-body transition of 5f configurations, and final state effects might be responsible for the quasiparticle multiplets in electronic spectrum functions. Prominent characters in the density of state, such as the coexistence of atomic multiplet peaks in the vicinity of the Fermi level and broad Hubbard bands in the high-lying regime, suggest that PuB6 could be identified as a Racah material. Finally, the quasiparticle band structure is also presented.

Commonality and diversity in tRNA substrate recognition in t6A biogenesis by eukaryotic KEOPSs.

N 6-Threonylcarbamoyladenosine (t6A) is a universal and pivotal tRNA modification. KEOPS in eukaryotes participates in its biogenesis, whose mutations are connected with Galloway-Mowat syndrome. However, the tRNA substrate selection mechanism by KEOPS and t6A modification function in mammalian cells remain unclear. Here, we confirmed that all ANN-decoding human cytoplasmic tRNAs harbor a t6A moiety. Using t6A modification systems from various eukaryotes, we proposed the possible coevolution of position 33 of initiator tRNAMet and modification enzymes. The role of the universal CCA end in t6A biogenesis varied among species. However, all KEOPSs critically depended on C32 and two base pairs in the D-stem. Knockdown of the catalytic subunit OSGEP in HEK293T cells had no effect on the steady-state abundance of cytoplasmic tRNAs but selectively inhibited tRNAIle aminoacylation. Combined with in vitro aminoacylation assays, we revealed that t6A functions as a tRNAIle isoacceptor-specific positive determinant for human cytoplasmic isoleucyl-tRNA synthetase (IARS1). t6A deficiency had divergent effects on decoding efficiency at ANN codons and promoted +1 frameshifting. Altogether, our results shed light on the tRNA recognition mechanism, revealing both commonality and diversity in substrate recognition by eukaryotic KEOPSs, and elucidated the critical role of t6A in tRNAIle aminoacylation and codon decoding in human cells.

Molecular basis for human mitochondrial tRNA m3C modification by alternatively spliced METTL8.

METTL8 has recently been identified as the methyltransferase catalyzing 3-methylcytidine biogenesis at position 32 (m3C32) of mitochondrial tRNAs. METTL8 also potentially participates in mRNA methylation and R-loop biogenesis. How METTL8 plays multiple roles in distinct cell compartments and catalyzes mitochondrial tRNA m3C formation remain unclear. Here, we discovered that alternative mRNA splicing generated several isoforms of METTL8. One isoform (METTL8-Iso1) was targeted to mitochondria via an N-terminal pre-sequence, while another one (METTL8-Iso4) mainly localized to the nucleolus. METTL8-Iso1-mediated m3C32 modification of human mitochondrial tRNAThr (hmtRNAThr) was not reliant on t6A modification at A37 (t6A37), while that of hmtRNASer(UCN) critically depended on i6A modification at A37 (i6A37). We clarified the hmtRNAThr substrate recognition mechanism, which was obviously different from that of hmtRNASer(UCN), in terms of requiring a G35 determinant. Moreover, SARS2 (mitochondrial seryl-tRNA synthetase) interacted with METTL8-Iso1 in an RNA-independent manner and modestly accelerated m3C modification activity. We further elucidated how nonsubstrate tRNAs in human mitochondria were efficiently discriminated by METTL8-Iso1. In summary, our results established the expression pattern of METTL8, clarified the molecular basis for m3C32 modification by METTL8-Iso1 and provided the rationale for the involvement of METTL8 in tRNA modification, mRNA methylation or R-loop biogenesis.

Electron correlation and relativistic effects on the electronic properties of a plutonium and americium mixed oxide (PuAmO4): from single-particle approximation to dynamical mean-field theory.

First-principles calculations were performed on a plutonium and americium mixed oxide (PuAmO4), aiming at revealing the effects of electron correlation, Pu/Am 5f-conduction electrons' hybridization, and relativity on its electronic properties. The many-body calculation suggests that the spin-orbit-coupling (SOC)-splitting of j = 5/2 and j = 7/2 manifolds are both in the weakly and moderately correlated states, respectively, implying that the jj coupling scheme is more appropriate for Pu/Am 5f electrons. The density of states, 5f occupation numbers, and Green's functions all suggest that both Pu and Am 5f electrons exhibit the coexistence of the localized and delocalized states. The admixture of 5fn atomic configurations, Pu/Am 5f-conduction electrons' hybridization, and dual characteristics of 5f electrons yield average occupation numbers of 5f electrons n5f = 4.78 and 5.86 for Pu and Am ions, respectively. Within the DFT+DMFT calculation, the weighted-summation-derived occupation numbers in terms of 5f4/5f5/5f6 and 5f5/5f6 configurations for Pu and Am 5f electrons, respectively, are in reasonable agreement with those of other DFT-based calculations.

Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6.

tRNAs harbor the most diverse posttranscriptional modifications. The 3-methylcytidine (m3C) is widely distributed at position C32 (m3C32) of eukaryotic tRNAThr and tRNASer species. m3C32 is decorated by the single methyltransferase Trm140 in budding yeasts; however, two (Trm140 and Trm141 in fission yeasts) or three enzymes (METTL2A, METTL2B and METTL6 in mammals) are involved in its biogenesis. The rationale for the existence of multiple m3C32 methyltransferases and their substrate discrimination mechanism is hitherto unknown. Here, we revealed that both METTL2A and METTL2B are expressed in vivo. We purified human METTL2A, METTL2B, and METTL6 to high homogeneity. We successfully reconstituted m3C32 modification activity for tRNAThr by METT2A and for tRNASer(GCU) by METTL6, assisted by seryl-tRNA synthetase (SerRS) in vitro. Compared with METTL2A, METTL2B exhibited dramatically lower activity in vitro. Both G35 and t6A at position 37 (t6A37) are necessary but insufficient prerequisites for tRNAThr m3C32 formation, while the anticodon loop and the long variable arm, but not t6A37, are key determinants for tRNASer(GCU) m3C32 biogenesis, likely being recognized synergistically by METTL6 and SerRS, respectively. Finally, we proposed a mutually exclusive substrate selection model to ensure correct discrimination among multiple tRNAs by multiple m3C32 methyltransferases.

Speech silence character as a diagnostic biomarker of early cognitive decline and its functional mechanism: a multicenter cross-sectional cohort study.

BACKGROUND: Language deficits frequently occur during the prodromal stages of Alzheimer's disease (AD). However, the characteristics of linguistic impairment and its underlying mechanism(s) remain to be explored for the early diagnosis of AD. METHODS: The percentage of silence duration (PSD) of 324 subjects was analyzed, including patients with AD, amnestic mild cognitive impairment (aMCI), and normal controls (NC) recruited from the China multi-center cohort, and the diagnostic efficiency was replicated from the Pitt center cohort. Furthermore, the specific language network involved in the fragmented speech was analyzed using task-based functional magnetic resonance. RESULTS: In the China cohort, PSD increased significantly in aMCI and AD patients. The area under the curve of the receiver operating characteristic curves is 0.74, 0.84, and 0.80 in the classification of NC/aMCI, NC/AD, and NC/aMCI+AD. In the Pitt center cohort, PSD was verified as a reliable diagnosis biomarker to differentiate mild AD patients from NC. Next, in response to fluency tasks, clusters in the bilateral inferior frontal gyrus, precentral gyrus, left inferior temporal gyrus, and inferior parietal lobule deactivated markedly in the aMCI/AD group (cluster-level P < 0.05, family-wise error (FWE) corrected). In the patient group (AD+aMCI), higher activation level of the right pars triangularis was associated with higher PSD in in both semantic and phonemic tasks. CONCLUSIONS: PSD is a reliable diagnostic biomarker for the early stage of AD and aMCI. At as early as aMCI phase, the brain response to fluency tasks was inhibited markedly, partly explaining why PSD was elevated simultaneously.

The impacts of health insurance and resource on the burden of Alzheimer's disease and related dementias in the world population.

INTRODUCTION: The increasing prevalence of Alzheimer's disease and related dementias (ADRD) presents both a burden and an opportunity for intervention. This study aims to estimate the impacts of health insurance and resources on the burden attributed to ADRD. METHOD: Data were mainly collected from global databases for ADRD. Analysis of variance, Pearson correlation, random-effects, and fixed-effects model analyses were used in this study. RESULTS: Although the current medical expenditures were increasing and out of pocket (OOP) expenditures were declining generally in various countries, the collected global data showed an increased burden of ADRD on patients both physically and economically. Furthermore, health resources were negatively associated with disability-adjusted life years (DALY), death, and years of life lost (YLL), but were otherwise positively associated with years of life lived with disability (YLD). DISCUSSION: Effective measures should be considered to cope with the rising burden. Meanwhile, there is an urgent call for constructive and sustainable rational plans and global collaboration. HIGHLIGHTS: We explored how health insurance and resources affect Alzheimer's disease and related dementias (ADRD)-related burden. Health insurance and resources were imbalanced among four income level groups. Health insurance and resources may decrease the total ADRD burden primarily from a reduction in death-related burden. Health insurance and resources may increase disability-related burden.

Expression, regulation and clinical significance of B7-H3 on neutrophils in human gastric cancer.

Neutrophils are conspicuous components of gastric cancer (GC) tumors, increasing with tumor progression and poor patient survival. However, the phenotype, regulation and clinical relevance of neutrophils in human GC are presently unknown. Most intratumoral neutrophils showed an activated CD54+ phenotype and expressed high level B7-H3. Tumor tissue culture supernatants from GC patients induced the expression of CD54 and B7-H3 on neutrophils in time-dependent and dose-dependent manners. Locally enriched CD54+ neutrophils and B7-H3+ neutrophils positively correlated with increased granulocyte-macrophage colony stimulating factor (GM-CSF) detection ex vivo; and in vitro GM-CSF induced the expression of CD54 and B7-H3 on neutrophils in both time-dependent and dose-dependent manners. Furthermore, GC tumor-derived GM-CSF activated neutrophils and induced neutrophil B7-H3 expression via JAK-STAT3 signaling pathway activation. Finally, intratumoral B7-H3+ neutrophils increased with tumor progression and independently predicted reduced overall survival. Collectively, these results suggest B7-H3+ neutrophils to be potential biomarkers in GC.

Discovery of aryl sulfonamide-selective Nav1.7 inhibitors with a highly hydrophobic ethanoanthracene core.

Nav1.7 channels are mainly distributed in the peripheral nervous system. Blockade of Nav1.7 channels with small-molecule inhibitors in humans might provide pain relief without affecting the central nervous system. Based on the facts that many reported Nav1.7-selective inhibitors contain aryl sulfonamide fragments, as well as a tricyclic antidepressant, maprotiline, has been found to inhibit Nav1.7 channels, we designed and synthesized a series of compounds with ethanoanthracene and aryl sulfonamide moieties. Their inhibitory activity on sodium channels were detected with electrophysiological techniques. We found that compound 10o potently inhibited Nav1.7 channels stably expressed in HEK293 cells (IC50 = 0.64 ± 0.30 nmol/L) and displayed a high Nav1.7/Nav1.5 selectivity. In mouse small-sized dorsal root ganglion neurons, compound 10o (10, 100 nmol/L) dose-dependently decreased the sodium currents and dramatically suppressed depolarizing current-elicited neuronal discharge. Preliminary in vivo experiments showed that compound 10o possessed good analgesic activity: in a mouse visceral pain model, administration of compound 10o (30-100 mg/kg, i.p.) effectively and dose-dependently suppressed acetic acid-induced writhing.

Nanoscale Proteinosomes Fabricated by Self-Assembly of a Supramolecular Protein-Polymer Conjugate.

Proteinosomes are a type of protein-based spherical capsules, which have potential applications in drug delivery, cell imaging, gene expression, and biocatalysis. In this research, a novel approach to the fabrication of proteinosomes entirely composed of protein molecules based on self-assembly of a supramolecular protein-polymer conjugate is proposed. A supramolecular protein-polymer conjugate was prepared by mixing ßCD-modified bovine serum albumin (BSA) and adamantane-terminated poly(N-isopropylamide) (Ad-PNIPAM) in aqueous solution. The BSA-PNIPAM bioconjugate self-assembled into micelles with PNIPAM cores and BSA coronae at a temperature above the lower critical solution temperature (LCST) of PNIPAM. After cross-linking of BSA in the coronae, and followed by addition of excess ßCD, PNIPAM chains were cleaved from the micellar structures, and nanoscale proteinosomes were prepared. The dual-responsive proteinosomes dissociated in the presence of trypsin or glutathione.

Exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of ERK signal pathway.

Bisphenol A (BPA) is an estrogenic environmental toxin widely used in the production of plastics and ubiquitous human exposure to this chemical has been proposed to be a potential risk to human health. Exposure to BPA can negatively impact sperm quality. However, the mechanism remains largely unknown. The objectives of this study were to assess the role of BPA on sperm quality and explore the possible mechanisms. The Wistar male rats (aged 28 days) were administered BPA by oral gavage for 28 days at dose of 50, 100 and 200 mg/kg/day; meanwhile, the negative control with corn oil (0 mg/kg/day BPA) and positive control with E2 at the dose of 100 µg/kg/day. The sperm density, sperm activity and sperm survival rate were analyzed byCASA system, and the sperm abnormality rate was analyzed by improved Papanicolaou stained. The protein expression levels of Src/p-Src, ERK1/2, p-ERK1/2 and CREB/p-CREB were detected by Western bolt. The results showed that the body weight gain, testes weight, testis coefficient, sperm density, sperm activity, sperm survival rate and protein expression levels of p-ERK1, p-ERK2 and p-CREB decreased, but the sperm abnormality rate increased with increasing BPA concentrations. There were positive correlations between sperm density, sperm activity and sperm survival rate with protein expression levels of p-ERK1, p-ERK2 and p-CREB, and negative correlations between sperm abnormality rate with the protein expression levels of p-ERK1, p-ERK2 and p-CREB. Results from the structural equation model demonstrated that BPA retained a significant negative effect to p-ERK, whereas p-ERK retained a significant positive effect to sperm quality and acted as the mediate variable. This study provides a novel insight regarding the potential role of p-ERK1 and p-ERK2 protein kinase on reproductive toxicity of BPA. The adverse effects of BPA on adult male sperm quality may be through the induction of the disruption of ERK signal pathway. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms.

Improving the stability of perovskite nanocrystals via SiO2 coating and their applications.

Lead halide perovskite nanocrystals (LHP NCs) with outstanding optical properties have been regarded as promising alternatives to traditional phosphors for lighting and next-generation display technology. However, the practical applications of LHP NCs are seriously hindered by their poor stability upon exposure to moisture, oxygen, light, and heat. Hence, various strategies have been proposed to solve this issue. In this review, we have focused our attention on improving the stability of LHP NCs via SiO2 coating because it has the advantages of simple operation, less toxicity, and easy repetition. SiO2 coating is classified into four types: (a) in situ hydrolytic coating, (b) mesoporous silica loading, (c) mediated anchoring, and (d) double coating. The potential applications of SiO2-coated LHP NCs in the field of optoelectronics, biology, and catalysis are presented to elucidate the reliability and availability of SiO2 coating. Finally, the future development and challenges in the preparation of SiO2-coated LHP NCs are analyzed in order to promote the commercialization process of LHP NC-related commodities.

Molecular dynamics (MD) study to predict performances of a novel hexanitrohexaazaisowurtzitane/1,4-dinitroimidazole (CL-20/1,4-DNI) energetic cocrystal under different temperatures.

CONTEXT: To estimate the influence of temperature on properties of 2,4,6,8,10,12-hexanitro- 2,4,6,8,10,12-hexaazaisowurtzitane/1,4-dinitroimidazole (CL-20/1,4-DNI) cocrystal explosive, the supercell crystal of CL-20/1,4-DNI cocrystal model was established. The mechanical properties, sensitivity, and stability of cocrystal model under different temperatures (T = 225 K, 250 K, 275 K, 300 K, 325 K, 350 K) were predicted. Results show that mechanical parameters, including bulk modulus, tensile modulus and shear modulus are the lowest when temperature is 300 K, while Cauchy pressure is the highest, indicating that CL-20/1,4-DNI cocrystal model has better mechanical properties at 300 K. Cohesive energy density (CED) and its components energies decrease monotonically with the increase of temperature, illustrating that the CL-20 and 1,4-DNI molecules are activated and the safety of cocrystal explosive is worsened with the increase of temperature. Cocrystal model has relatively higher binding energy when the temperature is 300 K, implying that the CL-20/1,4-DNI cocrystal explosive is more stable under this condition. METHODS: The CL-20/1,4-DNI cocrystal model was optimized and the properties were predicted through molecular dynamics (MD) method. The MD simulation was performed with COMPASS force field and the ensemble was set as NPT, external pressure was set as 0.0001 GPa.

Palladium-Catalyzed Hiyama-Type Coupling of Thianthrenium and Phenoxathiinium Salts.

Here, we demonstrate palladium-catalyzed Hiyama-type cross-coupling reactions of aryl thianthrenium or phenoxathiinium salts. By employing stable and inexpensive organosilanes, the arylation, alkenylation, and alkynylation were realized in high efficiency using commercially available Pd(tBu3P)2 as the catalyst, thus providing a reliable method for preparation of biaryls, styrenes, and aryl acetylenes with a broad functional group tolerance under mild conditions. Given the accessibility of aryl thianthrenium or phenoxathiinium salts from simple arenes in a remarkable regioselective fashion, this protocol also provides an attractive approach for the late-stage modification of complex bioactive scaffolds.

Multifunctional chitosan-based lanthanide luminescent hydrogel with stretchability, adhesion, self-healing, color tunability and antibacterial ability.

Lanthanide luminescent hydrogels have broad application prospects in various fields. However, most of lanthanide hydrogels possess relatively simple functions, which is not conducive to practical applications. Therefore, it is becoming increasingly urgent to develop multifunctional hydrogels. Herein, a multifunctional chitosan-based lanthanide luminescent hydrogel with ultra-stretchability, multi-adhesion, excellent self-healing, emission color tunability, and good antibacterial ability was prepared by a simple one-step free radical polymerization. In this work, our designed lanthanide complexes [Ln(4-VDPA)3] contain three reaction sites, which can be copolymerized with N-[tris(hydroxymethyl) methyl] acrylamide (THMA), acrylamide (AM), and diacryloyl poly(ethylene glycol) (DPEG) to form the first chemical crosslinking network, while hydroxypropyltrimethyl ammonium chloride chitosan (HACC) interacts with the hydroxyl and amino groups derived from the chemical crosslinking network through hydrogen bonds to form the second physical crosslinking network. The structure of the double network as well as the dynamic hydrogen bond and lanthanide coordination endow the hydrogel with excellent stretchability, adhesion and self-healing properties. Moreover, the introduction of lanthanide complexes and chitosan makes the hydrogel exhibit outstanding luminescence and antibacterial performances. This research not only realizes the simple synthesis of multifunctional luminescent hydrogels, but also provides a new idea for the fabrication of biomass-based hydrogels as intelligent and sustainable materials.

Advances in the techniques for the prediction of microRNA targets.

MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules that play important roles in a variety of normal and diseased biological processes by post-transcriptionally regulating the expression of target genes. They can bind to target messenger RNA (mRNA) transcripts of protein-coding genes and negatively control their translation or cause mRNA degradation. miRNAs have been found to actively regulate a variety of cellular processes, including cell proliferation, death, and metabolism. Therefore, their study is crucial for the better understanding of cellular functions in eukaryotes. To better understand the mechanisms of miRNA: mRNA interaction and their cellular functions, it is important to identify the miRNA targets accurately. In this paper, we provide a brief review for the advances in the animal miRNA target prediction methods and available resources to facilitate further study of miRNAs and their functions.

Role of GSK-3ß in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats.

This study investigated the role of glycogen synthase kinase-3ß (GSK-3ß) in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride (LiCl, 100 mg/kg) and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-3ß was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Morris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3ß was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflurane anesthesia increased mRNA levels of TNF-α, IL-1ß and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiCl, a non-selective inhibitor of GSK-3ß. Additionally, we discovered that LiCl alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-3ß in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-κB p65 (Lys310). In conclusion, these results suggested that GSK-3ß is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.

Designing and property prediction of a novel three-component CL-20/HMX/TNAD energetic cocrystal explosive by MD method.

CONTEXT: Cocrystallization technology can effectively regulate crystal structure, alter packing mode, and improve physicochemical performances of energetic materials at molecule level. CL-20/HMX cocrystal explosive has high energy density than HMX, but it also exhibits high mechanical sensitivity. To decrease the sensitivity and improve the properties of CL-20/HMX energetic cocrystal, the three-component energetic cocrystal CL-20/HMX/TNAD was designed. The properties of CL-20, CL-20/HMX, and CL-20/HMX/TNAD cocrystal models were predicted. The results show that CL-20/HMX/TNAD cocrystal models have better mechanical properties than CL-20/HMX cocrystal model, implying that the mechanical properties can be effectively improved. The binding energy of CL-20/HMX/TNAD cocrystal models is higher than CL-20/HMX cocrystal model, indicating that the three-component energetic cocrystal is more stable, and the cocrystal model with the ratio 3:4:1 is predicted to be the most stable phase. CL-20/HMX/TNAD cocrystal models have higher value of trigger bond energy than pure CL-20 and CL-20/HMX cocrystal models, meaning that the three-component energetic cocrystal is more insensitive. The crystal density and detonation parameters of CL-20/HMX and CL-20/HMX/TNAD cocrystal models are lower than CL-20, illustrating that the energy density is declined. The CL-20/HMX/TNAD cocrystal has higher energy density than RDX and can be regarded as a potential high energy explosive. METHODS: This paper was performed with molecular dynamics (MD) method with the software of Materials Studio 7.0 under COMPASS force field. The MD simulation was performed under isothermal-isobaric (NPT) ensemble, the temperature and pressure was 295 K and 0.0001 GPa, respectively.

Multicolor, injectable BSA-based lanthanide luminescent hydrogels with biodegradability.

Protein hydrogels have attracted increasing attention because of their excellent biodegradability and biocompatibility, but frequently suffer from the single structures and functions. As a combination of luminescent materials and biomaterials, multifunctional protein luminescent hydrogels can exhibit wider applications in various fields. Herein, we report a novel, multicolor tunable, injectable, and biodegradable protein-based lanthanide luminescent hydrogel. In this work, urea was utilized to denature BSA to expose disulfide bonds, and tris(2-carboxyethyl)phosphine (TCEP) was employed to break the disulfide bonds in BSA to generate free thiols. A part of free thiols in BSA rearranged into disulfide bonds to form a crosslinked network. In addition, lanthanide complexes (Ln(4-VDPA)3), containing multiple active reaction sites, could react with the remaining thiols in BSA to form the second crosslinked network. The whole process avoids the use of nonenvironmentally friendly photoinitiators and free radical initiators. The rheological properties and structure of hydrogels were investigated, and the luminescent performances of hydrogels were studied in detail. Finally, the injectability and biodegradability of hydrogels were verified. This work will provide a feasible strategy for the design and fabrication of multifunctional protein luminescent hydrogels, which may have further applications in biomedicine, optoelectronics, and information technology.

Synthesis and biological evaluation of ruthenium complexes containing phenylseleny against Gram-positive bacterial infection by damage membrane integrity and avoid drug-resistance.

Compounds modified with selenium atom as potential antibacterial agents have been exploited to combat the nondrug-resistant bacterial infection. In this study, we designed and synthesized four ruthenium complexes retouching of selenium-ether. Fortunately, those four ruthenium complexes shown excellent antibacterial bioactive (MIC: 1.56-6.25 µg/mL) against Staphylococcus aureus (S. aureus), and the most active complex Ru(II)-4 could kill S. aureus by targeting the membrane integrity and avoid the bacteria to evolve drug resistance. Moreover, Ru(II)-4 was found to significantly inhibit the formation of biofilms and biofilm eradicate capacity. In toxicity experiments, Ru(II)-4 exhibited poor hemolysis and low mammalian toxicity. To illustrate the antibacterial mechanism: we conducted scanning electron microscope (SEM), fluorescent staining, membrane rupture and DNA leakage assays. Those results demonstrated that Ru(II)-4 could destroy the integrity of bacterial cell membrane. Furthermore, both G. mellonella wax worms infection model and mouse skin infection model were established to evaluate the antibacterial activity of Ru(II)-4 in vivo, the results indicated that Ru(II)-4 was a potential candidate for combating S. aureus infections, and almost non-toxic to mouse tissue. Thus, all the results indicated that introducing selenium-atom into ruthenium compounds were a promising strategy for developing interesting antibacterial agents.