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Recently, ionic conductive hydrogels have been developed in the field of energy-storage devices owing to their unique properties, such as high ionic conductivity, mechanical flexibility, liquid-leakage-free operation, and stability.

Human T-cell leukemia virus 1 (HTLV-1) causes adult T-cell leukemia (ATL), but the mechanism underlying its initiation remains elusive. In this study, ORP4L was expressed in ATL cells but not in normal T-cells. ORP4L ablation completely blocked T-cell leukemogenesis induced by the HTLV-1 oncoprotein Tax in mice, whereas engineering ORP4L expression in T-cells resulted in T-cell leukemia in mice, suggesting the oncogenic properties and prerequisite of ORP4L promote the initiation of T-cell leukemogenesis. For molecular insight, we found that loss of miR-31 caused by HTLV-1 induced ORP4L expression in T-cells. ORP4L interacts with PI3Kδ to promote PI(3,4,5)P3 generation, contributing to AKT hyperactivation; NF-κB–dependent, p53 inactivation-induced pro-oncogene expression; and T-cell leukemogenesis. Consistently, ORP4L ablation eliminates human ATL cells in patient-derived xenograft ATL models. These results reveal a plausible mechanism of T-cell deterioration by HTLV-1 that can be therapeutically targeted.

The persistent challenge in Zn-ion batteries is the decomposition of coordinated water around Zn2+-induced side reactions and dendrite growth on Zn anode, leading to short lifespans. This situation is even worse in fiber-shaped Zn-ion batteries (FZIBs). Their curved and complex surface structure makes it even challenging to stabilize Zn anode via existing strategies. Herein, we address this dilemma via cost-effective citrate anion (Cit3−) additives which work as a tridentate chelating agent to regulate electrolytes on the molecular level. Synchrotron X-ray absorption fine structure analyses reveal that Cit3− manipulates the solvation shell of Zn2+ by forming [ZnCit(H2O)3]− chelate complexes. Combining with density functional theory calculation, for the first time, we demonstrate that Cit3− facilitates dehydration in [ZnCit(H2O)3]−, passivates remaining coordinated water via mitigating H O bond (H2O) elongation by 77.7%, suppresses Zn2+ transfer kinetics, homogenizes Zn2+ distribution at interfaces, enabling ∼500% extended lifespan. Based on this, we developed high-performance FZIBs by coupling Zn/carbon fiber anodes with highly conductive polypyrrole/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate fiber (∼3700 S cm−1) cathodes. Further mechanism study suggests that polypyrrole provides extra charge storage capacity by accommodating dual ions, i.e., Zn2+ and SO42−. The obtained quasi-solid-state FZIB possesses excellent performance for practical applications.

Polymer hydrogel electrolytes combine the advantages of solvent-free solid electrolytes and liquid electrolytes, with a specific ion migration rate, excellent flexibility and safety. However, the critical limitation to the application...

The treatment of bacterial infections is becoming increasingly challenging with the emergence of antimicrobial resistance. Thus, the development of antimicrobials with novel mechanisms of action is much needed. Previously, we designed several cationic main-chain imidazolium compounds and identified the polyimidazolium PIM1 as a potent antibacterial against a wide panel of multidrug-resistant nosocomial pathogens, and it had relatively low toxicity against mammalian epithelial cells. However, little is known about the mechanism of action of PIM1. Using an oligomeric version of PIM1 with precisely six repeating units (OIM1-6) to control for consistency, we showed that OIM1-6 relies on an intact membrane potential for entry into the bacterial cytoplasm, as resistant mutants to OIM1-6 have mutations in their electron transport chains. These mutants demonstrate reduced uptake of the compound, which can be circumvented through the addition of a sub-MIC dose of colistin. Once taken up intracellularly, OIM1-6 exerts double-stranded DNA breaks. Its potency and ability to kill represents a promising class of drugs that can be combined with membrane-penetrating drugs to potentiate activity and hedge against the rise of resistant mutants. In summary, we discovered that cationic antimicrobial OIM1-6 exhibits an antimicrobial property that is dissimilar to the conventional cationic antimicrobial compounds. Its killing mechanism does not involve membrane disruption but instead depends on the membrane potential for uptake into bacterial cells so that it can exert its antibacterial effect intracellularly. Ministry of Education (MOE) Nanyang Technological University National Supercomputing Centre (NSCC) Singapore Published version This study was supported by the Ministry of Education, Singapore, under its MOE AcRF Tier 3 Award of MOE2018-T3-1-003. M.Y. acknowledges the support of the MOE Ph.D. scholarship under the MOE AcRF Tier 3 Award (MOE2018-T3-1-003). C.H.K. acknowledges the support of an NTU Ph.D. scholarship. Y.M. acknowledges the support of the Singapore MOE Tier 1 Grant RG27/21 and the Singapore National Supercomputing Center (NSCC).

Publisher Copyright: © 2022, The Author(s). Lipid remodeling is crucial for malignant cell transformation and tumorigenesis, but the precise molecular processes involved and direct evidences for these in vivo remain elusive. Here, we report that oxysterol-binding protein (OSBP)-related protein 4 L (ORP4L) is expressed in adult T-cell leukemia (ATL) cells but not normal T-cells. In ORP4L knock-in T-cells, ORP4L dimerizes with OSBP to control the shuttling of OSBP between the Golgi apparatus and the plasma membrane (PM) as an exchanger of phosphatidylinositol 4-phosphate [PI(4)P]/cholesterol. The PI(4)P arriving at the PM via this transport machinery replenishes phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2] and phosphatidylinositol (3,4,5) trisphosphate [PI(3,4,5)P-3] biosynthesis, thus contributing to PI3K/AKT hyperactivation and T-cell deterioration in vitro and in vivo. Disruption of ORP4L and OSBP dimerization disables PI(4)P transport and T-cell leukemogenesis. In summary, we identify a non-vesicular lipid transport machinery between Golgi and PM maintaining the oncogenic signaling competence initiating T-cell deterioration and leukemogenesis. The oxysterol-binding protein-related protein 4 (ORP4L) is expressed in T-cell acute lymphoblastic leukemia and is required for leukemogenesis. Here the authors show that ORP4L orchestrates the transport of the phospholipid PI(4)P from Golgi to the plasma membrane, contributing to PI3K/AKT hyperactivation and T-cell leukemogenesis.

Antimicrobial resistance is a global threat. In addition to the emergence of resistance to last resort drugs, bacteria escape antibiotics killing by forming complex biofilms. Strategies to tackle antibiotic resistance as well as biofilms are urgently needed. Wall teichoic acid (WTA), a generic anionic glycopolymer present on the cell surface of many Gram-positive bacteria, has been proposed as a possible therapeutic target, but its druggability remains to be demonstrated. Here we report a cationic glycosylated block co-β-peptide that binds to WTA. By doing so, the co-β-peptide not only inhibits biofilm formation, it also disperses preformed biofilms in several Gram-positive bacteria and resensitizes methicillin-resistant Staphylococcus aureus to oxacillin. The cationic block of the co-β-peptide physically interacts with the anionic WTA within the cell envelope, whereas the glycosylated block forms a nonfouling corona around the bacteria. This reduces physical interaction between bacteria-substrate and bacteria-biofilm matrix, leading to biofilm inhibition and dispersal. The WTA-targeting co-β-peptide is a promising lead for the future development of broad-spectrum anti-biofilm strategies against Gram-positive bacteria. Ministry of Education (MOE) Nanyang Technological University Accepted version This research is supported by the Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 3 (Grants MOE2013-T3-1-002 and MOE2018-T3-1-003) and Nanyang Technological University

Natural nacre built up with a brick-and-mortar architecture, exhibiting extraordinary strength and toughness, provides an inspiration to construct high-performance multifunctional films for flexible energy storage and portable electrical devices. In the present work, a nacre-mimetic graphene-based film (CNT@PANI/rGO/TA) is fabricated following this idea, wherein electroactive biomass tannin (TA) serves as glue, accompanied by the “mortar” polyaniline wrapped carbon nanotubes (CNT@PANI), to stick the reduced graphene oxide (rGO) “bricks” together. Benefiting from the thin layer of PANI on CNTs, the CNT@PANI nanowires intercalate into the rGO interlayers thus interlocking the nanosheets, and resulting in a well-defined porous multilayered structure. The obtained CNT@PANI/rGO/TA film exhibits both high mechanical strength (174.6 MPa) and toughness (9.17 MJ m−3). Meanwhile, the all-solid-state flexible supercapacitor assembled with CNT@PANI/rGO/TA demonstrates a high capacitance of 548.6 F cm−3 and an outstanding rate performance of 70.5% from 1 A g−1 to 50 A g−1. Even at −40 °C, the specific capacitance of the supercapacitor is up to 454.9 F cm−3, approximately 83% of the capacitance delivered at room temperature. The strategy of using electroactive biomass as glue to construct a nacre-mimetic graphene-based film with high strength, toughness and energy storage performance is proved to be straightforward and effective.

To endow high mechanical strength and thermal stability aramid nanofibers (ANF) with novel functionality will lead to great applications. Herein, a strategy to generate covalent bonds among components towards obtaining uniform ANF/reduced holey graphene oxide (ANF/rHGO) and ANF/rHGO/polyaniline (ANF/rHGO/PANI) hydrogels with high mechanical properties is proposed through solvent exchange gelation and subsequent hydrothermal treatment. The as-prepared ANF/rHGO and ANF/rHGO/PANI hydrogels demonstrate excellent recoverability at high compressive strength of 20.2 and 13.8 kPa with a strain of 34.4% and 30.6%, respectively, compared to a recoverability of 92.5% at a strain of ∼20% for ANF hydrogels. Moreover, ANF/rHGO and ANF/rHGO/PANI aerogels possess fast and high oil absorption capacity of 38.9–64.1 g g−1 and 24.5–44.0 g g−1, respectively. ANF/rHGO and ANF/rHGO/PANI films obtained after vacuum-drying exhibit a high tensile strength of 121.4 and 95.5 MPa, respectively. Additionally, ANF/rHGO/PANI thin films present good selective absorption of visible light by controlling the doping level of PANI. ANF/rHGO/PANI aerogel films prepared by freeze-drying are assembled into flexible solid-state symmetric supercapacitors and deliver a favorable specific capacitance of 200 F g−1, a desirable capacitance retention of 98.9% after 2500 mechanical bending cycles and an approximately 100% capacitance retention even after keeping tensile force for 15 h. The as-prepared hydrogels, aerogels and derived films with such excellent performances are promising for applications in oil pollution removal, optical filters and flexible load-bearing energy storage devices.

Fast tool servo (FTS) machining is a highly efficient approach to generate optical freeform surfaces and microstructures, where submicrometric form accuracy and nanometric surface finish are often required. The on-machine surface measurement (OMSM) is an enabling technology to improve the metrology efficiency and machining accuracy of FTS. However, the integration of the OMSM with FTS on an ultra-precision machine is a huge challenge due to the complexity of data processing and synchronization. In this paper, a dedicated controller is in-house developed with data processing algorithms for the integration. The effectiveness of the proposed method is demonstrated through the successful fabrication and measurement of a freeform lens array.

In this letter, amorphous silicon nitride (Si3N4) film grown by inductively coupled plasma chemical vapor deposition (ICPCVD) method is used as the photosensitive layer of deep ultraviolet (DUV) detection, whose thickness and roughness are 200 nm and 0.92 nm, respectively. The transverse symmetrical photoconductive detector with interdigital electrodes spacing of $4~\mu \text{m}$ is fabricated by photolithography, exhibiting ultrahigh photo-to-dark current ratio (PDCR) more than 105, fast fall speed of 127 ms and also a satisfying responsivity of 1.09 mA/W. This work lays a foundation for further researches on Si3N4 in photonics and electronics.

Wearable supercapacitors, as one of the most important power supplies for wearable electronics, require excellent flexibility and deformability and a structure that is not easily delaminated. In th...

There are many holes and oxygen groups in reduced graphene oxide (rGO), which influences its conductivity, packing density, mechanical performance, thermal properties, and optical absorption. To co...

Phospholipase C (PLC) isoforms play central roles in signaling cascades by cleaving PIP2 into the second messengers IP3 and DAG. In this study, to our knowledge, we uncover that ORP5L interacts physically with PLCγ1 in T cells, extracts PIP2 from the plasma membrane via its ORD domain (OSBP-related domain), presents it to PLCγ1 (enabling IP3 generation), and eventually maintains intracellular Ca2+ homeostasis. Through this mechanism, ORP5L promotes T cell proliferation in a Ca2+-activated NFAT2-dependent manner. To our knowledge, our study uncovers a new key function of ORP5L as a critical cofactor for PLCγ1 catalysis and its crucial role in human T cell proliferation.

The preparation of graphene-based aerogels with excellent mechanical strength, elasticity, and compressibility is still a challenge. Herein, we demonstrate a robust, elastic, and lightweight graphene/aramid nanofiber/polyaniline nanotube (rGO/ANF/PANIT) aerogel that is prepared by mixing graphene oxide (GO), ANF, and PANIT dispersions, followed by thermal treatment at 90 °C, freeze-drying, and a low-temperature annealing process. The PANIT bonds the graphene sheets tightly, benefitting the formation of composite gels. The ANF tightly interconnects the graphene sheets and further reinforces the composite network framework significantly, hence endowing rGO/ANF/PANIT composite aerogels with robust mechanical property. The prepared aerogels present a low density of ∼12 mg cm

The development of a novel preparation strategy for 3D porous network structures with an aligned channel or wall is always in challenge. Herein, a 3D porous network composed of an aligned graphene-based wall is fabricated by a confined self-assembly strategy in which holey reduced graphene oxide (HrGO)/lignin sulfonate (Lig) composites are orientedly anchored on the framework of the Lig/single-wall carbon nanotube (Lig/SWCNT) hydrogel by vacuum-assisted filtration accompanied with confined self-assembly and followed with hydrothermal treatment. After freeze drying, the obtained ultralight Lig/SWCNT/HrGO

Leukemia stem cells (LSCs) propagate leukemia and are responsible for the high frequency of relapse of treated patients. The ability to target LSCs remains elusive, indicating a need to understand the underlying mechanism of LSC formation. Here, we report that miR-31-5p is reduced or undetectable in human LSCs compared to hematopoietic stem progenitor cells (HSPCs). Inhibition of miR-31-5p in HSPCs promotes the expression of its target gene FIH , encoding FIH [factor inhibiting hypoxia-inducing factor 1α (HIF-1α)], to suppress HIF-1α signaling. Increased FIH resulted in a switch from glycolysis to oxidative phosphorylation (OXPHOS) as the predominant mode of energy metabolism and increased the abundance of the oncometabolite fumarate. Increased fumarate promoted the conversion of HSPCs to LSCs and initiated myeloid leukemia-like disease in NOD-Prkdc scid IL2rg tm1 /Bcgen (B-NDG) mice. We further demonstrated that miR-31-5p inhibited long- and short-term hematopoietic stem cells with a high frequency of LSCs. In combination with the chemotherapeutic agent Ara-C (cytosine arabinoside), restoration of miR-31-5p using G7 poly (amidoamine) nanosized dendriplex encapsulating miR-31-5p eliminated LSCs and inhibited acute myeloid leukemia (AML) progression in patient-derived xenograft mouse models. These results demonstrated a mechanism of HSC malignant transformation through altered energy metabolism and provided a potential therapeutic strategy to treat patients with AML.

Correction for ‘Polymers as advanced antibacterial and antibiofilm agents for direct and combination therapies’ by Zhangyong Si et al., Chem. Sci., 2022, 13, 345–364, https://doi.org/10.1039/D1SC05835E.

Monoclinic gallium oxide ( β-Ga2O3) has attracted much attention from the fields of optoelectronic and electronic devices owing to the properties of wide bandgap, great breakdown field strength, as well as the economic advantages of low-cost growth of large-size single crystals. Here, the basic photophysical properties including absorption (free-carrier absorption and band-edge absorption) and reflection (phonon polaritons and exciton polaritons) of differently doped β-Ga2O3 with diverse carrier concentrations are studied in detail. The unpolarized reflection spectra of differently doped β-Ga2O3 crystals are well fitted based on the non-polarized reflection model. Besides, according to analysis, the longitudinal–transverse splitting energy of β-Ga2O3 direct excitons is estimated to be as high as 100 meV, reflecting the strong interaction between light and excitons. It is hoped that this work can provide beneficial reference for a comprehensive understanding on the spectral physical characteristics of β-Ga2O3, so as to deepen and expand the basic recognition of this material in the aspect of photophysical properties.

The freeform surfaces including both the aspherical and prismatic concave/convex have been widely utilized in optical, electronical, and biomedical areas. Most recently, it is reported that grinding with structured wheels provides new possibility to generate patterns on hard and brittle materials. This paper reports the latest research progress on micro-grooving glass ceramic using laser structured bronze bond diamond grinding wheels. A nanosecond pulse laser is firstly integrated into an ultra-precision machine tool and used for the in-line conditioning of super abrasive grinding wheels, i.e. truing, dressing, and profiling/texturing. Meanwhile, an offset compensation method, considering the shifting depth of focus (DoF) at different laser irradiation position, is proposed to accurately generate various profiles on the periphery of the grinding wheels. Three types of patterns (riblets, grooves, and pillars) are successfully fabricated on the ceramic substrate using the laser textured grinding wheels. The results indicate that the integrated laser system offers high flexibility and accuracy in shaping super abrasive grinding wheels, and the grinding using textured grinding wheels provide a promising solution to generate functional structures on hard and brittle materials.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of drug-resistant infections. Its propensity to develop biofilms makes it especially resistant to conventional antibiotics. We present a novel nanoparticle (NP) system made from biocompatible F-127 surfactant, tannic acid (TA), and biguanide-based polymetformin (PMET) (termed FTP NPs), which can kill MRSA biofilm bacteria effectively in vitro and in vivo and which has excellent biocompatibility. FTP NPs exhibit biofilm bactericidal activity—ability to kill bacteria both inside and outside biofilm—significantly better than many antimicrobial peptides or polymers. At low concentrations (8–32 μg/mL) in vitro, FTP NPs outperformed PMET with ∼100-fold (∼2 log10) greater reduction of MRSA USA300 biofilm bacterial cell counts, which we attribute to the antifouling property of the hydrophilic poly(ethylene glycol) contributed by F-127. Further, in an in vivo murine excisional wound model, FTP NPs achieved 1.8 log10 reduction of biofilm-associated MRSA USA300 bacteria, which significantly outperformed vancomycin (0.8 log10 reduction). Moreover, in vitro cytotoxicity tests showed that FTP NPs have less toxicity than PMET toward mammalian cells, and in vivo intravenous injection of FTP NPs at 10 mg/kg showed no acute toxicity to mice with negligible body weight loss and no significant perturbation of blood biomarkers. These biguanide-based FTP NPs are a promising approach to therapy of MRSA infections. ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) Accepted version

To improve machining capability of diamond turning of hierarchical structured surfaces, fast-tool-servo (FTS) turning using a sharp point diamond cutting tool (tool tip width

Oxysterol-binding protein–related protein (ORP) 4L acts as a scaffold protein assembling CD3-e, G-αq/11, and PLC-β3 into a complex at the plasma membrane that mediates inositol (1,4,5)-trisphosphat...

Single metal-organic coordination polymers have limited functions as precursors for porous carbon electrode materials. The construction of bimetallic organic coordination polymers can effectively utilize the advantages of each single metal-organic coordination polymer to improve the performance of the derived carbon materials. Herein, High performance nitrogen-doped porous carbon (BCFe–Ni) have been produced by directly carbonizing bimetallic organic coordination polymers formed by 4,4′-bipyridine (BPD) reaction with FeCl3 and NiCl2. The BCFe–Ni exhibits high nitrogen content (12.66 at%), large specific surface area (1049.51 m2 g−1) and hierarchical porous structure, which contributes to an excellent gravimetric specific gravity of 320.5 F g−1 and 108% of specific capacitance retention after 10000 cycles. The BCFe–Ni assembled symmetrical supercapacitor shows an energy density of 18.3 W h kg−1 at a power density of 350 W kg−1. It is expected that the as-prepared N-doped porous carbon derived from bimetallic-organic coordination polymer is a promising electrode material for high performance energy storage devices. Keywords: Bimetallic-organic coordination polymers, N-doped porous carbon, High specific surface area, Supercapacitors

Driven by the ever increasing demand in function integration, more and more next generation high value-added products, such as head-up displays, solar concentrators and intra-ocular-lens, etc., are designed to possess freeform (i.e., non-rotational symmetric) surfaces. The toolpath, composed of high density of short linear and circular segments, is generally used in computer numerical control (CNC) systems to machine those products. However, the discontinuity between toolpath segments leads to high-frequency fluctuation of feedrate and acceleration, which will decrease the machining efficiency and product surface finish. Driven by the ever-increasing need for high-speed high-precision machining of those products, many novel toolpath interpolation and smoothing approaches have been proposed in both academia and industry, aiming to alleviate the issues caused by the conventional toolpath representation and interpolation methods. This paper provides a comprehensive review of the state-of-the-art toolpath interpolation and smoothing approaches with systematic classifications. The advantages and disadvantages of these approaches are discussed. Possible future research directions are also offered.

Summary: Leukemia stem cells (LSCs) are a rare subpopulation of abnormal hematopoietic stem cells (HSCs) that propagates leukemia and are responsible for the high frequency of relapse in therapies. Detailed insights into LSCs’ survival will facilitate the identification of targets for therapeutic approaches. Here, we develop an inhibitor, LYZ-81, which targets ORP4L with high affinity and specificity and selectively eradicates LCSs in vitro and in vivo. ORP4L is expressed in LSCs but not in normal HSCs and is essential for LSC bioenergetics and survival. It extracts PIP2 from the plasma membrane and presents it to PLCβ3, enabling IP3 generation and subsequent Ca2+-dependent bioenergetics. LYZ-81 binds ORP4L competitively with PIP2 and blocks PIP2 hydrolysis, resulting in defective Ca2+ signaling. The results provide evidence that LSCs can be eradicated through the inhibition of ORP4L by LYZ-81, which may serve as a starting point of drug development for the elimination of LSCs to eventually cure leukemia. : Zhong et al. report that abnormal expression of ORP4L is essential for leukemia stem cell survival; it enables IP3 generation by extracting and presenting PIP2 from the plasma membrane to PLCβ3 for hydrolysis. The compound LYZ-81, which blocks this process via targeting ORP4L, selectively eradicates leukemia stem cells. Keywords: leukemia stem cell, OSBP-related protein 4L, PIP2 hydrolysis, Ca2+ signaling, energy metabolism, therapy

Two dimensional MXenes with fascinating characteristics of high electrical conductivity, high density and electroactivity show promising applications in various fields. However, the direct applications of MXenes have been limited due to their inferior mechanical properties and easy restacking. Herein, a kind of nacre-like composite film constructed with Ti3C2Tx, cellulose nanofiber (HCNF) and sodium lignosulfonate (Lig) obtained through the hydrothermal process, named Ti3C2Tx/HCNF@Lig, has been successfully synthesized. The hydrothermal cellulose nanofiber (HCNF) film shows an enhanced mechanical strength (114 MPa) compared to that of the CNF film (95 MPa). Wood-inspired HCNF@Lig composite films present an enhanced mechanical tensile strength of up to 133 MPa. Nacre-like deformable Ti3C2Tx/HCNF@Lig(3@1) composite films exhibit high conductivity (up to 1.75 × 105 S m−1) and mechanical properties (up to 258 MPa). The electrodes of Ti3C2Tx/HCNF@Lig(3@1)97/3 composite film assembled flexible solid-state supercapacitors possess an excellent volumetric specific capacitance of 748.96 F cm−3. The corresponding deformable supercapacitors show an excellent energy density of 16.2 W h L−1 and outstanding electrochemical cycling stability. The as-prepared nacre-like Ti3C2Tx/HCNF@Lig composite films with high mechanical properties and electrochemical performance are expected to be practically applied in flexible/wearable energy storage devices.

Significance We designed and synthesized antimicrobial compounds effective in killing pan-drug-resistant bacterial pathogens. These compounds have a large therapeutic window due to their low mammalian cell toxicity. A lead compound showed efficacy in treating murine model S. aureus and P. aeruginosa infections. In the case of the obligate respiratory bacterium P. aeruginosa we were unable to evolve strains resistant to these compounds. This paper points toward the potential of this type of compound to deal with the current threat of pan-resistant pathogens., For a myriad of different reasons most antimicrobial peptides (AMPs) have failed to reach clinical application. Different AMPs have different shortcomings including but not limited to toxicity issues, potency, limited spectrum of activity, or reduced activity in situ. We synthesized several cationic peptide mimics, main-chain cationic polyimidazoliums (PIMs), and discovered that, although select PIMs show little acute mammalian cell toxicity, they are potent broad-spectrum antibiotics with activity against even pan-antibiotic-resistant gram-positive and gram-negative bacteria, and mycobacteria. We selected PIM1, a particularly potent PIM, for mechanistic studies. Our experiments indicate PIM1 binds bacterial cell membranes by hydrophobic and electrostatic interactions, enters cells, and ultimately kills bacteria. Unlike cationic AMPs, such as colistin (CST), PIM1 does not permeabilize cell membranes. We show that a membrane electric potential is required for PIM1 activity. In laboratory evolution experiments with the gram-positive Staphylococcus aureus we obtained PIM1-resistant isolates most of which had menaquinone mutations, and we found that a site-directed menaquinone mutation also conferred PIM1 resistance. In similar experiments with the gram-negative pathogen Pseudomonas aeruginosa, PIM1-resistant mutants did not emerge. Although PIM1 was efficacious as a topical agent, intraperitoneal administration of PIM1 in mice showed some toxicity. We synthesized a PIM1 derivative, PIM1D, which is less hydrophobic than PIM1. PIM1D did not show evidence of toxicity but retained antibacterial activity and showed efficacy in murine sepsis infections. Our evidence indicates the PIMs have potential as candidates for development of new drugs for treatment of pan-resistant bacterial infections.

Flexible all-solid-state supercapacitors (ASSSs) are excellent energy storage devices for portable/wearable electronics, although the development of an excellent comprehensive performance film electrode for the extraordinary flexible ASSSs still faces a great challenge. Here, bendable, foldable and anti-exfoliative Ti3C2Tx MXene-based films utilized as supercapacitor electrodes are reported. Polyaniline/Ti3C2Tx composites (i-PANI@Ti3C2Tx) were prepared by in situ oxidant-free polymerization of aniline on Ti3C2Tx nanosheets with p-phenylenediamine (PPD) as an initiator. Lignosulfonate (Lig) and Ti3C2Tx were constructed into a compact composite (Lig@Ti3C2Tx) film based on the hydrogen bonds formed between Lig and Ti3C2Tx. The Lig@Ti3C2Tx/i-PANI@Ti3C2Tx(5/5) hybrid film was produced by vacuum-assisted filtration of the mixed two composite dispersions. The as-prepared films can be arbitrarily deformed (such as bending and folding). They show high tensile strength and vertical-plane (the plane of film) tensile strength with 33.2 and 0.28 MPa for the i-PANI@Ti3C2Tx film, 75.4 and 0.77 MPa for the Lig@Ti3C2Tx film, and 53.7 and 0.58 MPa for the Lig@Ti3C2Tx/i-PANI@Ti3C2Tx(5/5) film (those of Ti3C2Tx film are 17.4 and 0.21 MPa), respectively. The enhanced vertical-plane tensile strength of the as-prepared composite films indicates that the large binding force generated between the Ti3C2Tx nanosheets can effectively prevent the exfoliation of films. The electrodes of the as-prepared i-PANI@Ti3C2Tx, Lig@Ti3C2Tx and Lig@Ti3C2Tx/i-PANI@Ti3C2Tx(5/5) films assembled into symmetric flexible ASSSs can deliver excellent specific capacitances of 310 F g-1 (∼1001 F cm-3), 271 F g-1 (∼881 F cm-3) and 295 F g-1 (∼959 F cm-3), respectively. In addition, the corresponding supercapacitors exhibit ultrahigh energy densities of 34.8, 30.6 and 33.3 W h L-1, respectively. It is expected that the as-prepared MXene-based films can be applied in various fields, such as electromagnetic-interference shielding and batteries. Furthermore, the as-prepared flexible ASSSs can be practically used as a wearable energy storage device.

Recently, natural biomass has been widely explored as a precursor to prepare carbon materials due to its abundant, low-cost, and renewable character. Herein, a series of high-performance heteroatom...

Carbon cloth (CC) is widely used as a freestanding substrate for energy storage devices, due to its high conductivity, special porous network, and good mechanical flexibility. However, it is still challenging to fully utilize the space of CC to achieve a high mass loading of electroactive materials and ultimately fulfill high electrochemical performance. Herein, a new strategy is proposed to fill the gaps and voids in CC with a functionalized graphene hydrogel (FGH) through one-step hydrothermal treatment of oxidized CC submerged in a mixture of graphene oxide and p-phenylenediamine. The as-prepared FGH/functionalized CC is then adopted as a scaffold to load a lignosulfonate/polyaniline (Lig/PANI) hydrogel via in situ polymerization of aniline in the presence of lignosulfonate, and thereby an integrated textile (Lig/PANI/FGH/FCC) is obtained. The symmetric supercapacitor assembled with Lig/PANI/FGH/FCC electrodes and 1 M H2SO4 electrolyte shows a superior areal capacitance of 1223 mF cm−2 and an energy density of 169.9 μW h cm−2 at 2 mA cm−2. Moreover, the assembled flexible all-solid-state supercapacitor presents competitive energy density (160.6 μW h cm−2 at 1000 μW cm−2) and excellent flexibility. This design of anchoring a hierarchical porous conductive network in a macroscopic macropore framework paves a new avenue towards high mass loading and low interfacial resistance in macroporous material-based electrodes for high-performance energy storage devices.

Electroactive and conductive hydrogels with porous network structure, super hydrophilicity, mechanical flexibility and biocompatibility are prominent electrode materials for flexible/wearable supercapacitors. In this work, novel PPy hydrogels (m-PPy) with crystalline core–shell structure have been facilely fabricated with assistance of 2-methylimidazole via one-step oxidative polymerization. The m-PPy hydrogels exhibit significantly improved recoverable compressive strength of up to 26.7 kPa at 50% strain and remarkable maximum compressive strength of up to 265 kPa, due to effective energy dissipation by nanocrystalline shells. The m-PPy3:3 exhibits high specific capacitance of 536 F g−1 and corresponding symmetric supercapacitor possesses superior areal specific capacitance of 603 mF cm−2, good rate capability and superb areal energy density of 53.6 μWh cm−2. Particularly, m-PPy3:3 based flexible supercapacitor presents remarkable flexibility and mechanical stability, which can sustain 10,000 bending cycles without severe degradation of electrochemical performance.

Developing high nitrogen content carbon-based electrode materials with high volumetric specific capacitance and high energy density has attracted considerable attentions for practical applications of supercapacitors. Herein, N-doped porous carbon/multi-walled carbon nanotubes (NPCMT) with high nitrogen content is prepared by directly pyrolyzing metal-organic coordination polymer (MOCP) composite, which was formed by the reaction of 4,4′-bipyridine (BPD), FeCl3 and multi-walled carbon nanotubes. The as-prepared NPCMT exhibits a hierarchical pore structure with high specific surface area (862.5 m2 g−1) and high N-doped content (10.71 at.%). Benefited from these unique properties, NPCMT presents high gravimetric specific capacitance of 295.2 F g−1, high volumetric specific capacitance of 312.9 F cm−3 and excellent cycle stability. Moreover, the assembled symmetric supercapacitors possess superior energy density of 18.82 W h kg−1. The combination of MOCP and multiwall nanotubes points toward a prominent direction to develop N-doped porous carbon electrode materials for high performances supercapacitors.

Nitrogen-doped hierarchical porous carbons are prepared by hydrothermal crosslinking reaction and KOH activation using sodium lignosulfonate as carbon precursor, 1,6-hexanediamine as crosslinking agent and nitrogen source. As-prepared nitrogen-doped hierarchical porous carbon possesses a high specific surface area (1867.4 m2 g−1), moderate nitrogen-doped content (3.6 at.%) and presents a superior three-dimensional hierarchical porous structure with rich micropores, favorable mesopores and interconnected macropores. The nitrogen-doped hierarchical porous carbon electrode performs high specific capacitance (440 F g-1 at 0.5 A g−1) and excellent cycle stability (94.8% of its initial capacitance after 3000 cycles at 20 A g−1) in a three-electrode workstation using 6 M KOH electrolyte, while it shows a superior rate capability (80.4% from 331 F g-1 at 1 A g−1 to 266 F g-1 at 20 A g−1) in 1 M H2SO4. Furthermore, the nitrogen-doped hierarchical porous carbon assembled supercapacitor delivers a high specific capacitance (370 F g-1 at 0.5 A g−1) and remarkable energy density (18.5 Wh kg−1 at a power density of 300 W kg−1, 10.4 Wh kg−1 at high power density of 12 kW kg−1) in 6 M KOH electrolyte. The as-prepared nitrogen-doped hierarchical porous carbon with outstanding electrochemical performance is promising for applications in sustainable energy-storage devices.

Electroactive hydrogels have been considered as flexible solid-state supercapacitor electrode materials. Herein, a novel strategy has been proposed to directly prepare polyaniline (PANI) hydrogels from soluble PANI dispersion by self-crosslinking of molecules during the hydrothermal process. The PANI hydrogel single-electrode shows high specific capacitance (325 F g−1) and superior rate capability. To achieve more excellent electrochemical performance, the graphene/PANI hydrogel (GPH7) is prepared using graphene oxide (GO) and soluble PANI dispersion. However, a slightly enhanced specific capacitance (375 F g−1) is achieved for the GPH7 single-electrode, due to the strong interactions between GO and PANI molecules. It is of particular interest that the incorporation of m-phenylenediamine (mPD) into the GO and PANI system could protect the inherent conjugated structure of PANI, and thereby the as-prepared N-doped graphene/PANI hydrogels (GMPH7) show significantly improved specific capacitance (514.3 F g−1). Moreover, the assembled flexible solid-state supercapacitors based on the PANI hydrogel, GPH7 and GMPH7 exhibit excellent areal specific capacitance (484, 519.2 and 584.7 mF cm−2, respectively), approximately 100% capacitance retention after 2000 mechanical bending cycles and favorable energy density (42.96, 60.9 and 81.28 μW h cm−2, respectively). Such hydrogel assembled supercapacitors with robust capacitive behavior and outstanding flexibility are promising for applications in flexible and wearable electronics.

To extend the applications of supercapacitors, it is important and challenging to develop structural/stiff supercapacitors with excellent mechanical and electrochemical performance. In this work, high performance double-crosslinked network functionalized graphene/polyaniline stiff hydrogels (DN-PGH/PANIPA) have been successfully synthesized by polymerization of aniline in a confined functionalized graphene (PGH) hydrogel framework. A unique polyaniline (PANI) morphology with a combination of nanodot protrusions and nanofibers is obtained, where nanodot protrusions are tightly anchored to graphene walls and nanofiber crosslinked graphene sheets. The as-prepared DN-PGH/PANIPA hydrogel, consisting of a continuous conductive closely combined double-crosslinked network and PANI nanofibers, together with a high crystallization degree of the PANI structure, is both stiff and mechanically robust with a high tensile strength of 1.39 MPa at a small ruptured elongation of 0.42%. Meanwhile, the DN-PGH/PANIPA stiff hydrogels are assembled into symmetric supercapacitors and achieve a superior areal specific capacitance of 3488.3 mF cm−2 and a volumetric specific capacitance of 872 F cm−3, remarkable rate capability, and excellent cycling stability, resulting in a notable energy density of 155 μW h cm−2 at 200 μW cm−2 and an outstanding power density of 20 015 μW cm−2 at 67.5 μW h cm−2. This novel double-crosslinked network design strategy establishes a promising approach towards the development of other stiff electrode materials as high performance structural supercapacitors.

Peptidoglycan is the core component of the bacterial cell wall, which makes it an attractive target for the development of bacterial targeting agents. Intercepting its enzymatic assembly with synthetic substrates allows for labeling and engineering of live bacterial cells. Over the past two decades, small-molecule-based labeling agents, such as antibiotics, d-amino acids or monosaccharides have been developed for probing biological processes in bacteria. Herein, peptidoglycan oligomers, substrates for transglycosylation, are prepared for the first time using a top-down approach, which starts from chitosan as a cheap feedstock. A high efficiency of labeling has been observed in all bacterial strains tested using micromolar substrates. In contrast, uptake into mammalian cells was barely observable. Additional mechanistic studies support a hypothesis of bacteria-specific metabolic labeling rather than non-specific binding to the bacterial surface. Eventually, its practicality in bacterial targeting capability is demonstrated in resistant strain detection and in vivo infection models., Peptidoglycan oligomers have been derived from chitosan, using a top-down bio-hybrid strategy, as highly bacteria-specific substrates.

Oxysterol-binding protein-related protein (ORP) 4L acts as a scaffold protein assembling CD3-ε, G-α

The challenge of maintaining good surface quality under high operational frequencies in freeform machining invokes the need for a deterministic error analysis approach and a quantitative understanding on how structural design affects the positioning errors. This paper proposes a novel stiff-support positioning system with a systematic error analysis approach which reveals the contributions of disturbances on the tool positioning errors. The new design reduces the structural complexity and enables the detailed modelling of the closed loop system. Stochastic disturbances are analysed in the frequency domain while the non-stochastic disturbances are simulated in the time domain. The predicted following error spectrum agrees with the measured spectrum across the frequency range and this approach is justified. The real tool positioning error, which is free from sensor noise, is revealed for the first time. The influences of moving mass under various bandwidth settings have been studied both theoretically and experimentally. It is found that a larger moving mass helps combating disturbances except the sensor noises. The influences of cutting force are modelled and experimentally verified in the micro lens array cutting experiments. The origins of the form errors of the lenslet are discussed based on the error analysis model.

To combat the increasing risk of infection by pathogenic bacteria, the new generation of antimicrobial agents is expected to exhibit nonmetabolic killing mechanisms, high potency and biocompatibility. In this work, cysteine-terminated antimicrobial peptide (AMP) was employed directly as a reducing ligand to synthesize AMP-coated gold nanoclusters (Au NCs), bypassing the use of other reagents which might interfere with the efficacy of the resulting NCs. In addition to the use of a biocompatible Au core, the primary amines of AMP coating were functionalized with anionic citraconyl moieties to further reduce cytotoxicity. The citraconyl amides could autocleave to re-expose the cationic amines at low pH. As a result, the AMP-coated Au NCs with citraconyl protection were stable and cytocompatible under physiological conditions as determined by fluorescamine, hemolytic, cytotoxicity, and in vivo toxicology studies, but would switch into a cationic bactericidal mode in an acidic environment commonly encountered at bacterial infection sites. Furthermore, the AMP-coated Au NCs system exhibited bacterial binding and photoluminescence features as determined by flow cytometry and confocal microscopy, which were useful for the detection and imaging of bacterial contamination. The AMP-coated Au NCs with citraconyl moieties therefore represent a "smart" design of pH-responsive antimicrobial agents that can serve multiple functions of bacterial detection, bacterial imaging, and anti-infection therapy.

Phospholipase C (PLC) isoforms play central roles in signaling cascades by cleaving PIP

Tannic acid (TA) is a natural polyphenolic biomass, which shows high electro-activity and can be considered for supercapacitor applications. However, the negligible electronic conductivity of TA hinders its direct use as an electrode. In order to achieve the electrochemical activity of TA, herein, a three-dimensional porous TA/graphene composite (TAG) is prepared by mixing TA with graphene oxide (GO) via hydrothermal assembly, and various structural composites are realized by adding metal ions into the system before hydrothermal treatment. Metal ions can chelate with TA molecules and coordinate with GO via electrostatic interactions. As a result, a uniform and well-defined three-dimensional porous network (TAGNi), a regularly arranged scale-like microstructure (TAGCu) and a flower-like structure (TAGFe) are achieved by introducing Ni2+, Cu2+ and Fe3+, respectively. The as-prepared TAG, TAGNi, TAGCu and TAGFe electrodes exhibit a high specific capacitance of 373.6, 412.4, 460.4 and 429.4 F g-1 at 1 A g-1, respectively, and excellent cycling stability. The TAG, TAGNi, TAGCu and TAGFe assembled symmetric supercapacitors display a favorable energy density of 14.76, 16.76, 19.13 and 17.6 W h kg-1 at 300 W kg-1, respectively. The morphology-tunable TA/graphene composites with excellent electrochemical performance are promising for renewable energy storage device applications.