Antimicrobial and Antiviral Nanofibers Halt Co-Infection Spread via Nuclease-Mimicry and Photocatalysis.

The escalating spread of drug-resistant bacteria and viruses is a grave concern for global health. Nucleic acids dominate the drug-resistance and transmission of pathogenic microbes. Here, imidazolium-type poly(ionic liquid)/porphyrin (PIL-P) based electrospun nanofibrous membrane and its cerium (IV) ion complex (PIL-P-Ce) are developed. The obtained PIL-P-Ce membrane exhibits high and stable efficiency in eradicating various microorganisms (bacteria, fungi, and viruses) and decomposing microbial antibiotic resistance genes and viral nucleic acids under light. The nuclease-mimetic and photocatalytic mechanisms of the PIL-P-Ce are elucidated. Co-infection wound models in mice with methicillin-resistant S. aureus and hepatitis B virus demonstrate that PIL-P-Ce integrate the triple effects of cationic polymer, photocatalysis, and nuclease-mimetic activities. As revealed by proteomic analysis, PIL-P-Ce shows minimal phototoxicity to normal tissues. Hence, PIL-P-Ce has potential as a "green" wound dressing to curb the spread of drug-resistant bacteria and viruses in clinical settings.

The inhibitory role of microRNA-141-3p in human cutaneous melanoma growth and metastasis through the fibroblast growth factor 13-mediated mitogen-activated protein kinase axis.

Human cutaneous melanoma (CM) is a highly invasive malignancy arising from melanocytes, and accompanied by ever-increasing incidence and mortality rates worldwide. Interestingly, microRNAs (miRNAs) possess the ability to regulate CM cell biological functions, resulting in the aggressive progression of CM. Nevertheless, a comprehensive understanding of the underlying mechanism remains elusive. Accordingly, the current study sought to elicit the functional role of miR-141-3p in human CM cells in association with fibroblast growth factor 13 (FGF13) and the MAPK pathway. First, miR-141-3p expression patterns were detected in human CM tissues and cell lines, in addition to the validation of the targeting relationship between miR-141-3p and FGF13. Subsequently, loss- and gain-of-function studies of miR-141-3p were performed to elucidate the functional role of miR-141-3p in the malignant features of CM cells. Intriguingly, our findings revealed that FGF13 was highly expressed, whereas miR-141-3p was poorly expressed in the CM tissues and cells. Further analysis highlighted FGF13 as a target gene of miR-141-3p. Meanwhile, overexpression of miR-141-3p inhibited the proliferative, invasive, and migratory abilities of CM cells, while enhancing their apoptosis accompanied by downregulation of FGF13 and the MAPK pathway-related genes. Collectively, our findings highlighted the inhibitory effects of miR-141-3p on CM cell malignant properties via disruption of the FGF13-dependent MAPK pathway, suggesting a potential target for treating human CM.

Antimicrobial poly(ionic liquid)-induced bacterial nanotube formation and drug-resistance spread.

Bacterial nanotubes are tubular membranous structures bulging from the cell surface that can connect neighboring bacteria for the exchange of intercellular substances. However, little is known about the formation and function of bacterial nanotubes under the stress of antimicrobial materials. Herein, an imidazolium-type cationic poly(ionic liquid) (PIL) and corresponding PIL membranes with antimicrobial properties were synthesized. The effects of these cationic polymers on the formation of bacterial nanotubes between Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) or Vibrio fischeri (V. fischeri), followed by intraspecies and interspecies exchange of antibiotic resistance genes (ARGs) were investigated. The results showed that bacteria tend to produce more nanotubes accompanied by drug-resistance trade, which can even make the ARGs of pathogens spread to the environmental microbes of V. fischeri. Given the unique antimicrobial sustainability toward bacteria after they acquire ARGs via bacterial nanotubes, antimicrobial PILs demonstrate bright prospects in the battle against resistant bacteria.

Enhanced photocatalytic and antibacterial activity of acridinium-grafted g-C3N4 with broad-spectrum light absorption for antimicrobial photocatalytic therapy.

As a metal-free polymeric photocatalyst, graphitic carbon nitride (g-C3N4) has attracted great attention owing to its high stability and low toxicity. However, g-C3N4 suffers from low light harvesting ability which limits its applications in antimicrobial photocatalytic therapy (APCT). Herein, acridinium (ADN)-grafted g-C3N4 (ADN@g-C3N4) nanosheets are prepared via covalent grafting of ADN to g-C3N4. The obtained ADN@g-C3N4 exhibits a narrow optical band gap (2.12 eV) and a wide optical absorption spectrum (intensity a.u. > 0.30) ranging from ultraviolet to near-infrared region. Moreover, ADN@g-C3N4 would produce reactive oxygen species (ROS) under light irradiation to exert effective sterilization and biofilm elimination activities against both gram-negative and gram-positive bacteria. Molecular dynamics simulation reveals that the ADN@g-C3N4 may move toward, tile and insert the bacterial lipid bilayer membrane through strong van der Waals and electrostatic interaction, decreasing the order parameter of the lipid while increasing the conducive of ROS migration, inducing ADN@g-C3N4 with improved antimicrobial and antibiofilm performance. Moreover, ADN@g-C3N4 could efficiently eradicate oral biofilm on artificial teeth surfaces. This work may provide a broad-spectrum light-induced photocatalytic therapy for preventing and treating dental plaque diseases and artificial teeth-related infections, showing potential applications for intractable biofilm treatment applications. An acridinium-grafted g-C3N4 (ADN@g-C3N4) with a narrow band gap and broad-spectrum light absorption was synthesized. The narrow optical band gap and improved electrostatic interaction with bacterial lipid bilayer membrane of ADN@g-C3N4 strengthened the ROS generation and facilitated the diffusion of ROS to bacteria surface, leading to enhanced photocatalytic and antibacterial activity against bacteria and corresponding biofilm under light irradiation. STATEMENT OF SIGNIFICANCE: An acridinium-grafted g-C3N4 (ADN@g-C3N4) with a narrow band gap and broad-spectrum light absorption was developed as an antimicrobial photocatalytic therapy agent. The ADN@g-C3N4 exhibited enhanced photocatalytic and antibacterial activity against bacteria and corresponding biofilm under light irradiation, showing potential applications for intractable biofilm treatment.

A Novel Missense Variant of HOXD13 Caused Atypical Synpolydactyly by Impairing the Downstream Gene Expression and Literature Review for Genotype-Phenotype Correlations.

Synpolydactyly (SPD) is a hereditary congenital limb malformation with distinct syndactyly designated as SPD1, SPD2, and SPD3. SPD1 is caused by mutations of HOXD13, which is a homeobox transcription factor crucial for limb development. More than 143 SPD patients have been reported to carry HOXD13 mutations, but there is a lack of genotype-phenotype correlation. We report a novel missense mutation of c. 925A > T (p.I309F) in an individual with atypical synpolydactyly inherited from her father with mild clinodactyly and three other different alanine insertion mutations in HOXD13 identified by whole exome sequencing (WES) in 12 Chinese SPD families. Unlike polyalanine extension, which tends to form α-helix and causes protein aggregation in the cytoplasm as shown by molecular simulation and immunofluorescence, the c. 925A > T mutation impairs downstream transcription of EPHA7. We compiled literature findings and analyzed genotype-phenotype features in 173 SPD individuals of 53 families, including 12 newly identified families. Among the HOXD13-related individuals, mutations were distributed in three regions: polyalanine, homeobox, and non-homeobox. Polyalanine extension was the most common variant (45%), followed by missense mutations (32%) mostly in the homeobox compared with the loss-of-function (LOF) variants more likely in non-homeobox. Furthermore, a more severe degree and classic SPD were associated with polyalanine mutations although missense variants were associated with brachydactyly and syndactyly in hands and feet and LOF variants with clinodactyly in hands. Our study broadens the HOXD13 mutation spectrum and reveals the profile of three different variants and their severity of SPD, the genotype-phenotype correlation related to the HOXD13 mutation site provides clinical insight, including for genetic counseling.

Highly Integrated Cell-Imprinted Biomimetic Interface for All-in-One Diagnosis of Heterogeneous Circulating Tumor Cells.

Single-cell capture and in situ analysis of circulating tumor cells (CTCs) in blood are of great significance for early cancer diagnosis, prognosis, and individualized treatment. However, designing an all-in-one platform that enables not only efficiently specific isolation of CTCs but also in situ analysis of heterogeneity and drug screening is challenging. Here, a cell-imprinted alginate hydrogel (CIAH) interface with all-in-one functions was developed for the capture, in situ analysis, and drug-response study at a single-cell level. Based on the equivalent morphology and "specific odor" left by template cells and supplemented by natural antibody, the CIAH interface exhibited outstanding performance in isolating CTCs from samples suffering from cancers. Beyond capture, the CIAH interface was also able to serve as a high-throughput platform for subpopulation analysis and drug response of heterogeneous CTCs. We demonstrated that the highly integrated multifunctional CIAH interface is a promising new tool for single-cell profiling of phenotypic heterogeneity and guiding of personalized anticancer therapy.

Activating PIK3CA mutation promotes adipogenesis of adipose-derived stem cells in macrodactyly via up-regulation of E2F1.

Macrodactyly is a congenital malformation characterized by enlargement of bone and soft tissues in limbs, typically with excessive accumulation of adipose tissues. Although gain-of-function mutation of PIK3CA has been identified in macrodactyly, the mechanism of PIK3CA mutation in adipose accumulation is poorly understood. In this study, we found that adipocytes from macrodactyly were more hypertrophic than those observed in polydactyly. PIK3CA (H1047R) activating mutation and enhanced activity of PI3K/AKT pathway were detected in macrodactylous adipose-derived stem cells (Mac-ADSCs). Compared to polydactyly-derived ADSCs (Pol-ADSCs), Mac-ADSCs had higher potential in adipogenic differentiation. Knockdown of PIK3CA or inhibition by BYL-719, a potent inhibitor of PIK3CA, impaired adipogenesis of Mac-ADSCs in vitro. In vivo study, either transient treatment of ADSCs or intragastrical gavage with BYL-719 inhibited the adipose formation in patient-derived xenograft (PDX). Furthermore, RNA-seq revealed that E2F1 was up-regulated in Mac-ADSCs and its knockdown blocked the PIK3CA-promoted adipogenesis. Our findings demonstrated that PIK3CA activating mutation promoted adipogenesis of ADSCs in macrodactyly, and that this effect was exerted by the up-regulation of E2F1. This study revealed a possible mechanism for adipose accumulation in macrodactyly and suggested BYL-719 as a potential therapeutic agent for macrodactyly treatment.

Active pharmaceutical ingredient poly(ionic liquid)-based microneedles for the treatment of skin acne infection.

As an inflammatory skin disease of pilosebaceous follicles, Propionibacterium acnes (P. acnes) can aggravate local inflammatory responses and forms acne lesions. However, due to the skin barrier, various transdermal measures other than antibiotic creams are necessary. Microneedle (MN) patches are emerging platforms for the transdermal delivery of various therapeutics since it can effectively create transport pathways in the epidermis. Herein, we develop an active pharmaceutical ingredient poly(ionic liquid) (API PIL)-based MN patches containing salicylic acid (SA). The PIL-based MNs are simply prepared through photo-crosslinking of an imidazolium-type ionic liquid (IL) monomer in MN micro-molds, and following by anion exchange with salicylic acid anions (SA-). The fabricated SA-loaded PIL-MNs exhibited therapeutic efficiency in the topical treatment of P. acnes infection in vitro and in vivo. These active pharmaceutical ingredient PIL-based MNs can improve acne treatment, demonstrating potential applications for skin diseases. STATEMENT OF SIGNIFICANCE: Microneedle (MN) patches can be used as platforms for transdermal delivery of various therapeutics to treat bacterial infection. Here, a facile strategy was developed to synthesize active pharmaceutical ingredient poly(ionic liquid)-based microneedle patches by anion-exchange with salicylic acid anion (SA-). The fabricated SA-loaded PIL-MNs are active on not only anti-bacteria but also anti-inflammation in P. acnes treated mice, and may have potential applications for skin acne infection.

Activating PIK3CA mutation promotes osteogenesis of bone marrow mesenchymal stem cells in macrodactyly.

Macrodactyly is a disabling congenital disease characterized by overgrowth of soft tissues and bones, which leads to finger enlargement and joint deformity. The mechanism of bone overgrowth in macrodactyly was rarely understood. In our study bone manifestations of three macrodactyly patients were analyzed by micro-CT. PIK3CA mutation was detected by next-generation sequencing (NGS) of a tumor gene-panel. The PI3K/AKT/mTOR pathway activation and target genes were analyzed. The osteogenic potential of macrodactyly-derived bone marrow mesenchymal stem cells (MAC-BMSCs) was compared with polydactyly-derived bone marrow mesenchymal stem cells (PD-BMSCs). PIK3CA inhibitors were tested for proliferation and osteogenesis potential of MAC-BMSCs. Activating PIK3CA mutations and activation of PI3K/AKT/mTOR pathway were detected in all MAC-BMSCs. MAC-BMSCs had enhanced osteogenesis potential compared with PD-BMSCs. PIK3CA knockdown by shRNA or BYL719 treatment significantly reduced osteogenic differentiation capacity of MAC-BMSCs. RNA-Seq and qRT-PCR revealed the upregulation of distal-less homeobox 5 (DLX5) in MAC-BMSCs compared with PD-BMSCs. The osteogenic potential of MAC-BMSCs was inhibited by DLX5 knockdown, indicating that DLX5 is a downstream target of PIK3CA activation-mediated osteogenesis. This study revealed that osteogenic differentiation in MAC-BMSCs is enhanced by PIK3CA activation mutation through PI3K/AKT/mTOR signaling pathway and can be reversed by PIK3CA knockdown or drug inhibition.

Histone H4K20 Demethylation by Two hHR23 Proteins.

Histone methyl groups can be removed by demethylases. Although LSD1 and JmjC domain-containing proteins have been identified as histone demethylases, enzymes for many histone methylation states or sites are still unknown. Here, we perform a screening of a cDNA library containing 2,500 nuclear proteins and identify hHR23A as a histone H4K20 demethylase. Overexpression of hHR23A reduces the levels of H4K20me1/2/3 in cells. In vitro, hHR23A specifically demethylates H4K20me1/2/3 and generates formaldehyde. The enzymatic activity requires Fe(II) and α-ketoglutarate as cofactors and the UBA domains of hHR23A. hHR23B, a protein homologous to hHR23A, also demethylates H4K20me1/2/3 in vitro and in vivo. We further demonstrate that hHR23A/B activate the transcription of coding genes by demethylating H4K20me1 and the transcription of repetitive elements by demethylating H4K20me3. Nuclear magnetic resonance (NMR) analyses demonstrate that an HxxxE motif in the UBA1 domain is crucial for iron binding and demethylase activity. Thus, we identify two hHR23 proteins as histone demethylases.

Inhibition of Sphingosine Kinase 1 Attenuates Sepsis-induced Microvascular Leakage via Inhibiting Macrophage NLRP3 Inflammasome Activation in Mice.

BACKGROUND: Sepsis is the overwhelming inflammatory response to infection, in which nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome plays a crucial role. Shingosine-1-phosphate is reported to evoke NLRP3 inflammasome activation. Sphingosine kinase 1 (SphK1) is the major kinase that catalyzes bioactive lipid shingosine-1-phosphate formation and its role in sepsis remains uncertain. The authors hypothesize that SphK1 elicits NLRP3 inflammasome activation and exacerbates sepsis. METHODS: Peripheral blood mononuclear cells were isolated from septic patients and healthy volunteers to measure messenger RNA (mRNA) expression. In mice, sepsis was induced by cecal ligation and puncture. Bone marrow-derived macrophages were prepared from C57BL/6J wild-type, Casp1, Nlrp3 and SphK1 mice. PF-543 was used as the specific inhibitor of SphK1. Mortality, peripheral perfusion, lung Evan's blue dye index, lung wet/dry ratio, lung injury score, lung myeloperoxidase activity, NLRP3 activation, and function of endothelial adherens junction were measured. RESULTS: SphK1 mRNA expression was higher in cells from septic patients versus healthy volunteers (septic patients vs. healthy volunteers: 50.9 ± 57.0 fold change vs. 1.2 ± 0.1 fold change, P < 0.0001) and was positively correlated with IL-1ß mRNA expression in these cells (r = 0.537, P = 0.012) and negatively correlated with PaO2/FIO2 ratios (r = 0.516, P = 0.017). In mice that had undergone cecal ligation and puncture, the 5-day mortality was 30% in PF-543-treated group and 80% in control group (n = 10 per group, P = 0.028). Compared with controls, PF-543-treated mice demonstrated improved peripheral perfusion and alleviated extravascular Evan's blue dye effusion (control vs. PF-543: 25.5 ± 3.2 ng/g vs. 18.2 ± 1.4 ng/g, P < 0.001), lower lung wet/dry ratio (control vs. PF-543: 8.0 ± 0.2 vs. 7.1 ± 0.4, P < 0.0001), descending lung injury score, and weaker lung myeloperoxidase activity. Inhibition of SphK1 suppressed caspase-1 maturation and interleukin-1ß release through repressing NLRP3 inflammasome activation, and subsequently stabilized vascular endothelial cadherin through suppressing interleukin-1ß-evoked Src-mediated phosphorylation of vascular endothelial cadherin. CONCLUSIONS: SphK1 plays a crucial role in NLRP3 inflammasome activation and contributes to lung injury and mortality in mice polymicrobial sepsis.

Fluorescent Imidazolium-Type Poly(ionic liquid)s for Bacterial Imaging and Biofilm Inhibition.

Fluorescent imidazolium-type poly(ionic liquid)s (PIL)s were synthesized by anion exchange of bromide (Br-) in poly(3-butyl-1-vinylimidazolium bromide) (PIL-Br) with a fluorescent anion, namely, 3-(4-(1,2,2-triphenylvinyl)phenoxy)propane-1-sulfonate (TPESO3-). Such an anion exchange provided antibacterial PILs with aggregation-induced emission (AIE) properties that simultaneously kill and image bacteria. These fluorescence and antibacterial properties could be regulated by controlling the Br-/TPESO3- ratio. The fluorescence intensity increases as this ratio increases, while the antibacterial property exhibits an opposite trend. Moreover, the AIE-type PILs are useful for fluorescently imaging dead bacteria (macroscopically and microscopically) and could effectively inhibit biofilm growth. This study provided a convenient method to obtain fluorescent PILs with adjustable antibacterial and imaging properties.

Aggregation-induced emission-based ionic liquids for bacterial killing, imaging, cell labeling, and bacterial detection in blood cells.

A series of aggregation-induced emission (AIE)-based imidazolium-type ionic liquids (ILs) were designed and synthesized for bacterial killing and imaging, cell labeling, and bacterial detection in blood cells. The AIE-based ILs showed antibacterial activities against both Escherichia coli and Staphylococcus aureus. The carbon chain length of substitution at the N3 position of the imidazolium cations highly affects the antibacterial properties of ILs. Owing to their AIE characteristics, the ILs could selectively capture fluorescence image of dead bacteria while killing the bacteria. The fluorescence intensity varied with the concentration of bacteria, indicating that AIE-based ILs has potential as an antibacterial material and an efficient probe for bacterial viability assay. In addition, the synthesized AIE-based ILs exhibit relatively low cytotoxicity and hemolysis rate and therefore potential for cell labeling, as well as bacterial detection in blood cells. STATEMENT OF SIGNIFICANCE: Bacteria are ubiquitous, especially the pathogenic bacteria, which pose a serious threat to human health. There is an urgent need for materials with efficient antibacterial properties and biocompatibility and without causing drug resistance. In this work, we synthesized a series of aggregation-induced emission (AIE)-doped imidazolium type ionic liquids (ILs) with multifunction potential of bacterial killing and imaging, cell labeling, and detection of bacteria from blood cells. The synthesized AIE-based ILs can image dead bacteria at the same time of killing these bacteria, which can avoid the fluorescent dyeing process. Simultaneously, the fluorescent imaging of dead bacteria can be distinguished by the naked eye, and the fluorescence intensity from the AIE-based ILs varied with the concentration of bacteria. In addition, the AIE-based ILs exhibit relatively low cytotoxicity and hemolysis rate and therefore potential for cell labeling as well as detection of bacteria from red blood cell suspension.

Antibacterial Amino Acid-Based Poly(ionic liquid) Membranes: Effects of Chirality, Chemical Bonding Type, and Application for MRSA Skin Infections.

Bacteria induced infection remains a serious medical hazard to humans. Antibacterial polymeric materials, which can kill or inhibit bacteria by disrupting cell membranes, inhibiting certain enzymes, or interfering with the transcription or synthesis of DNA or RNA, have been applied to reduce or inhibit microbial drug resistance. Herein, amino acid-based ionic liquids (ILs) and poly(ionic liquid) (PIL) membranes were synthesized and used as antibacterial materials to treat skin wounds infected by methicillin-resistant Staphylococcus aureus (MRSA). The effects of chirality (D- or L-enantiomers) and chemical bonding (ionic or covalent) of the amino acid groups attached to the IL (or PIL) on antibacterial properties were investigated. Both the ILs and PIL membranes containing D-enantiomeric amino acid groups exhibited higher antibacterial activities compared with those containing L-enantiomeric amino acids. In addition, the ionically-bonded PIL membranes showed higher antibacterial activities than the corresponding covalently-bonded polymeric membranes. These results indicate that both the chirality and chemical bonding type of amino acid groups affect the antimicrobial activity of the PIL membranes. Additionally, the amino acid-based PIL membranes accelerated the wound-healing process, alleviated local tissue inflammation, and reduced the influence of bacteria on vital organs (liver and spleen) in MRSA-infected mouse models, demonstrating the potential applications for antimicrobial wound dressing.

Integrated Endotoxin Adsorption and Antibacterial Properties of Cationic Polyurethane Foams for Wound Healing.

Gram-negative bacteria, containing toxic proinflammatory and pyrogenic substances [endotoxin or lipopolysaccharide (LPS)], can lead to infection and associated serious diseases, such as sepsis and septic shock. Development of antimicrobial materials with intrinsically endotoxin adsorption activity can prevent the release of bacterial toxic components while killing bacteria. Herein, a series of imidazolium-type polyurethane (PU) foams with antimicrobial properties were synthesized. The content effects of cationic moieties on the antimicrobial activities against Gram-negative Escherichia coli and Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus as well as the endotoxin adsorption property were investigated. The obtained PU foams show slightly higher efficiency against two Gram-negative strains than for Gram-positive one and high absorbability of LPS. A wound healing test using P. aeruginosa and its isolated LPS-treated mice as the models further demonstrated that imidazolium-type PU foams combine both antibacterial and endotoxin adsorption properties and may have a potential application as an antimicrobial wound dressing in a clinical setting.

Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner.

Symplekin is a multifunctional protein that localizes to both tight junctions and the nucleus in polarized epithelial cells, with confirmed roles in mRNA maturation, transcriptional modulation and tight-junction assembly. However, the mechanisms governing its subcellular distribution and related functions remain unclear. In this study, we found that symplekin primarily localizes to the nuclei of cultured dedifferentiated colorectal cancer cells, and nuclear symplekin showed higher phosphorylation and binding affinity with YBX3 than its membrane fraction. Moreover, the accumulation of nuclear symplekin promoted cell proliferation and dedifferentiation as well as ß-catenin transactivation in vitro. Nuclear symplekin acts as a transcriptional co-activator for the expression of many cell cycle-related genes. Furthermore, extracellular signal-regulated kinase (ERK) phosphorylated symplekin at T1257 to facilitate its nuclear accumulation upon epidermal growth factor (EGF) stimulation. Meanwhile, reduction of total symplekin also induced certain epithelial-mesenchymal transition features in HT-29 cells. Taken together, our results confirm the coordinated roles of symplekin in cell junctions and gene transcription, which are related to its subcellular localization. The significance of nuclear symplekin in tumorigenesis is also highlighted, and ERK-dependent phosphorylation represents a mechanism for its subcellular sorting.

Polyanionic Antimicrobial Membranes: An Experimental and Theoretical Study.

Polycationic polymers have been widely used as antimicrobial materials because of their broad spectrum activity and potential use as new antibiotics. Herein, we report the synthesis of polyanionic antimicrobial membranes by in situ photo-cross-linking of a sulfate based anionic monomer, followed by cation-exchange with organic (quaternary ammonium or imidazolium) or metal (Ag+, Cu2+, Fe3+, Zn2+, Na+, K+) cations. The resultant polyanionic membranes show high and broad spectrum antibacterial activities against both bacteria (Escherichia coli, Staphylococcus aureus) and fungi (Candida albicans ). In addition, the polyanionic antimicrobial membranes efficiently inhibited the formation of biofilms by SC5314 and its crk1 gene deleted (Δcrk1) C. albicans strains. Furthermore, the synthesized polyanionic membranes exhibit good blood compatibility, low cytotoxicity and long-term antibacterial stability, demonstrating safe antimicrobial materials in the application of healthcare.

Zinc Ion Coordinated Poly(Ionic Liquid) Antimicrobial Membranes for Wound Healing.

Herein, a series of quaternary ammonium (Qa) or imidazolium (Im) cation-based poly(ionic liquid) (PIL) membranes and their corresponding zinc ion coordinated PIL membranes were synthesized. The effects of chemical structure, including organic cations, alkyl side chain of substitution, and zinc atoms on the antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Candida albicans were investigated. The Zn-containing PIL membranes show higher antibacterial activities compared to those of pristine PIL membranes due to the synergistic attributes of both organic cations (Qa or Im) and zinc atoms. A wound healing test using methicillin-resistant S. aureus infected mouse as the model further demonstrated that zinc ion coordinated PIL membranes were antibacterially active, biologically safe, and may have potential application as an antimicrobial wound dressing in a clinical setting.

Synthesis of Pyrrolidinium-Type Poly(ionic liquid) Membranes for Antibacterial Applications.

Pyrrolidinium-type small molecule ionic liquids (ILs), poly(ionic liquid) (PIL) homopolymers, and their corresponding PIL membranes were synthesized and used for antibacterial applications. The influences of substitutions at the N position of pyrrolidinium cation on the antimicrobial activities against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were studied by minimum inhibitory concentration (MIC). The antibacterial efficiency of both the small molecule ILs and PIL homopolymers increased with the increase of the alkyl chain length of substitutions. Furthermore, PIL homopolymers show relatively lower MIC values, indicating better antimicrobial activities than those of the corresponding small molecule ILs. However, the antibacterial properties of the PIL membranes are contrary to corresponding ILs and PIL homopolymers, which reduce with the increase of alkyl chain length. Furthermore, the resultant PIL membranes show excellent hemocompatibility and low cytotoxicity toward human cells, demonstrating clinical feasibility in topical applications.

Identification of long noncoding RNAs for the detection of early stage lung squamous cell carcinoma by microarray analysis.

The aberrant expressions of long noncoding RNAs have been reported in numerous cancers, which have facilitated the cancer diagnosis. However, the expression profile of lncRNAs in early stage lung squamous cell carcinoma has not been well discussed. The present study aimed to examine the expression profile of lncRNAs in early stage lung squamous cell carcinoma and identify lncRNA biomarkers for diagnosis. Through high-throughput lncRNA microarray, we screened thousands of aberrantly expressed lncRNAs and mRNAs in early stage lung squamous cell carcinoma tissues compared to their corresponding adjacent nontumorous tissues. Bioinformatics analyses were used to investigate the functions of aberrantly expressed mRNAs and their associated lncRNAs. After that, in order to identify lncRNA biomarkers for early detection, candidate lncRNA biomarkers were selected based on our established filtering pipeline and validated by real-time quantitative polymerase chain reaction on a total of 63 pairs of tumor samples. Five lncRNAs were finally identified which were able to distinguish early stage tumor and normal samples with high sensitivity (92%) and specificity (83%). These results imply that lncRNAs may be powerful biomarker for early diagnosis.