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Lead-free hybrid perovskites (LFHPs) have sparked considerable research interest in photocatalysis. This review introduces the surface engineering and photophysical behaviors of LFHPs for diverse solar-induced photocatalytic applications.

Antibiotic resistance represents a serious global health concern and has stimulated the development of antimicrobial nanomaterials to combat resistant bacteria. Protein-based nanoparticles combining characteristics of both proteins and nanoparticles offer advantages including high biocompatibility, attractive biodegradability, enhanced bioavailability and functional versatility. They have played an increasing role as promising candidates for broad applications ranging from biocatalysts and drug delivery to vaccine development to cancer therapeutics. However, their application as antibacterial biomaterials to address challenging antibiotic-resistance problems has not been explicitly pursued. Herein, we describe engineering protein-only nanoparticles against resistant Gram-positive bacteria. A self-assembling peptide (P

In this work, a novel acetamide-based deep eutectic solvent (DES) with Zn

Homogeneous photocatalysis has considerably contributed to green applications such as energy production and environmental decontamination. Currently, researchers mainly focus on the search for sustainable processes that can generate valuable chemical compounds with high selectivity and aid in the complete mineralization of hazardous compounds. Although homogeneous photocatalysts exhibit superior performance, their recovery after the reaction is difficult. The 3Rs process, i.e., recovery, recycling and reuse of photocatalysts respectively, is critical to make a photocatalytic process eco-friendly. Heterogenization of homogeneous photocatalysts is considered as an effective method to not only realize the recycling of homogeneous photocatalysts, but also enhance the overall photocatalytic activity. Conventional methods have employed synthetic materials for the heterogenization of homogeneous photocatalysts. Nevertheless, scientists have discovered that natural polymer sources can be alternatives due to their excellent chemical, mechanical, and electrical properties for applications under harsh reaction conditions. In this review, we have summarized state-of-the-art techniques employed for the heterogenization of homogeneous photocatalysts using various supporting materials in terms of design and preparation. First, we have organized these strategies into different categories, such as microporous encapsulation, dye-sensitized semiconductors, metal–organic framework (MOF) construction, carbon material fixation, synthetic polymer attachment and natural origin supports. To provide readers with deeper insights into this field, we have presented some fundamentals of homogeneous photocatalysis with respect to environmental applications and its heterogeneous strategies. Furthermore, we have discussed the performance of heterogeneous photocatalysts prepared from these methods, including photocatalytic performance, product selectivity and reusability. Finally, we have concluded with different aspects on the current challenges and new aspects in emerging technologies.

For the global energy demand and climate change challenges, seeking renewable, sustainable energy sources is of great significance. Photoelectrochemical (PEC) water splitting is one of the promising technologies for converting intermittent solar energy into storable hydrogen energy, to tackle these issues. As the core component in a PEC system, photoelectrodes have been modified by various strategies including nanostructuring, facet-engineering, elemental doping, and heterostructured engineering. Apart from these techniques, numerous effective post-synthetic treatments have also been used to facilely and powerfully boost the physicochemical properties of photoelectrodes, for the enhancement of their PEC performance. Among them, a number of post-treatments can selectively influence photoelectrode surface and subsurface areas, altering surface states that play crucial roles in the hydrogen/oxygen evolution reaction. In virtue of such post-treatments, we summarize recently reported post-synthetic treatments for enhanced PEC applications. Post-treatment methods are classified into three sections: chemical treatments, electrochemical and irradiation-based treatments, and post-annealing treatments. In the end, a summary and outlook section regarding the utilization of post-treatments for PEC applications have been provided. This review can provide inspiration for further studies about post-treatments, not only in the PEC water splitting field, but also in other aspects, such as electrolysis.

Gene therapies that chronically suppress vascular endothelial growth factor (VEGF) represent a new approach for managing retinal vascular leakage and neovascularization. However, constitutive suppression of VEGF in the eye may have deleterious side effects. Here, we developed a novel strategy to introduce Flt23k, a decoy receptor that binds intracellular VEGF, fused to the destabilizing domain (DD) of Escherichia coli dihydrofolate reductase (DHFR) into the retina. The expressed DHFR(DD)-Flt23k fusion protein is degraded unless "switched on" by administering a stabilizer; in this case, the antibiotic trimethoprim (TMP). Cells transfected with the DHFR(DD)-Flt23k construct expressed the fusion protein at levels correlated with the TMP dose. Stabilization of the DHFR(DD)-Flt23k fusion protein by TMP was able to inhibit intracellular VEGF in hypoxic cells. Intravitreal injection of self-complementary adeno-associated viral vector (scAAV)-DHFR(DD)-Flt23k and subsequent administration of TMP resulted in tunable suppression of ischemia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy (OIR). Hence, our study suggests a promising novel approach for the treatment of retinal neovascularization. Schematic diagram of the tunable system utilizing the DHFR(DD)-Flt23k approach to reduce VEGF secretion. a The schematic shows normal VEGF secretion. b Without the ligand TMP, the DHFR(DD)-Flt23k protein is destabilized and degraded by the proteasome. c In the presence of the ligand TMP, DHFR(DD)-Flt23k is stabilized and sequestered in the ER, thereby conditionally inhibiting VEGF. Green lines indicate the intracellular and extracellular distributions of VEGF. Blue lines indicate proteasomal degradation of the DHFR(DD)-Flt23k protein. Orange lines indicate the uptake of cell-permeable TMP. TMP, trimethoprim; VEGF, vascular endothelial growth factor; ER, endoplasmic reticulum.

Fibrosis is a pathological feature of chronic kidney disease and its progression correlates with declining renal function. Kidney fibrosis is driven by multiple profibrotic factors. This project examined the regulatory function of WNT1-inducible-signaling pathway protein 1 (WISP1) in the development of kidney fibrosis. Induction of WISP1 by transforming growth factor beta 1 (TGF-β1), and the role of WISP1 in TGF-β1/Smad signaling and fibrotic responses, was examined in multiple kidney cells. Kidney expression of WISP1 was examined in mouse models of unilateral ureter obstruction (UUO) and streptozotocin-induced diabetic nephropathy. WISP1 antibody was administered to UUO mice during the induction of kidney injury and the impact on kidney fibrosis was examined. WISP1 expression was upregulated in both mouse models. TGF-β1-induced expression of WISP1 and profibrotic genes in cultured kidney cells via TGF-βR1. Recombinant WISP1-induced expression of TGF-βR1 in kidney cells. Suppression of WISP1 by shRNA or neutralizing antibody reduced TGF-β1-mediated activation of Smad3, fibrotic gene expression, and fibroblast proliferation. Treatment with WISP1 antibody inhibited the development of kidney fibrosis in UUO mice. WISP1 mediates the profibrotic effects of TGF-β1 in kidney cells and in kidney disease. Pharmacological blockade of WISP1 exhibits potential as a novel therapy for inhibiting kidney fibrosis.

High-performance aqueous all-organic rechargeable batteries are promising candidates for cost-effective, safe, and environment-friendly next-generation energy storage devices. Herein, two organic copolymers with nanorod-like morphology (AN-TA, and AN-PA), composed of different tertiary amines, are synthesized as the cathode material for an aqueous proton battery. The individual copolymer electrodes possess the dominated diffusion-controlled electrode kinetics resulting from the proton insertion/de-insertion along with the surface-controlled processes in 2 M HCl and 2 M H

Gram-negative bacteria, mitochondria and chloroplasts contain β-barrel outer membrane proteins (OMPs). Most OMPs have a “β-signal” imprinted in the final β-strand. In Gram-negative bacteria, the β-barrel assembly machinery (BAM) complex recognize the β-signal for the folding and membrane insertion of the OMP. Here, we identified the “-5 signal”, a novel signal existing in the fifth β-strand from the C-terminus (-5 strand) responsible for the insertion step of the assembly process. We further identified the receptor for the -5 signal as BamD. BamD can recognize both β-signal and -5 signal, marshalling the OMP for assembly. There is sequence similarity in of both signals observed also in mitochondrial OMPs. Therefore, we propose the “-5 rule” repeating a similar sequence in the -5 and last strand, as a conserved feature of the OMP assembly process in bacteria and eukaryotes.

The incorporation of black phosphorus (BP) into methylammonium lead iodide (MAPbI3) perovskites has been investigated and optimized by a high throughput screening method using scanning photoelectrochemical microscopy (SPECM) to determine how the addition of BP affects its photoelectrochemical and photovoltaic properties. An optimum ratio of 2.0 mole% BP/MAPbI3 perovskite composite generates an increased photocurrent response compared to pristine MAPbI3 for 2 mM benzoquinone (BQ) reduction at −0.6 V vs Ag/AgNO3 on a spot array electrode under illumination. Due to the relatively high quantum yield of MAPbI3, time-resolved photoluminescence measurements have been conducted to investigate photophysical behaviors of BP/MAPbI3 composites. The optimal 2.0 mole% BP/MAPbI3 exhibits an increased electron-hole diffusion lifetime compared to the pristine MAPbI3 perovskite. Finally, we demonstrate the enhanced efficiency and stability of 2.0% BP/MAPbI3-based perovskite solar cells arising from impeded Pb0-defect generation and suppressed charge-carrier recombination.

Inflammation is a pathological feature of kidney injury and its progression correlates with the development of kidney fibrosis which can lead to kidney function impairment. This project investigated the regulatory function of WNT1-inducible signaling pathway protein 1 (WISP1) in kidney inflammation. Administration of recombinant WISP1 protein to healthy mice induced kidney inflammation (macrophage accrual and production of tumor necrosis factor α (TNF-α), CCL2 and IL-6), which could be prevented by inhibition of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB). Furthermore, inhibition of WISP1, by gene knockdown or neutralising antibody, could inhibit cultured macrophages producing inflammatory cytokines following stimulation with lipopolysaccharides (LPSs) and kidney fibroblasts proliferating in response to TNFα, which both involved NF-κB signaling. Kidney expression of WISP1 was found to be increased in mouse models of progressive kidney inflammation-unilateral ureter obstruction (UUO) and streptozotocin (STZ)-induced diabetic nephropathy (DN). Treatment of UUO mice with WISP1 antibody reduced the kidney inflammation in these mice. Therefore, pharmacological blockade of WISP1 exhibits potential as a novel therapy for inhibiting inflammation in kidney disease.

In this work, we have demonstrated the successful incorporation of selenium (Se)/tellurium (Te) into the covalently functionalized MoS2 (B-M) nanosheets as a host using a facile solvothermal method. The chalcogen-loaded composites (Se/Te@B-M-C) are characterized by various spectroscopic and microscopic analyses. These experiments prove that the amorphous Se/Te additive is homogeneously distributed over the MoS2 nanosheets with an expanded interlayer distance of ∼10 Å. The fabricated Li–S batteries composed of the Se/Te@B-M-C cathodes exhibit superior electrochemical performances when compared to that of the pristine chalcogens and bare host. The improved charge storage characteristics of these hybrids are attributed to the uniform distribution of chalcogens as the rate accelerators and the formation of a protective solid-electrolyte interphase layer over composites. The present study demonstrates that the structurally-engineered MoS2-based composites with evenly distributed amorphous Se (or Te) chalcogens as accelerators are potential candidates for next-generation high-performance lithium–sulfur batteries with high capacity and excellent cycle stability.

In Gram-negative bacteria, the β-barrel assembly machinery (BAM) complex catalyses the assembly of β-barrel proteins into the outer membrane, and is composed of five subunits: BamA, BamB, BamC, BamD and BamE. Once assembled, - β-barrel proteins can be involved in various functions including uptake of nutrients, export of toxins and mediating host-pathogen interactions, but the precise mechanism by which these ubiquitous and often essential β-barrel proteins are assembled is yet to be established. In order to determine the relative positions of BAM subunits in the membrane environment we reconstituted each subunit into a biomimetic membrane, characterizing their interaction and structural changes by Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) and neutron reflectometry. Our results suggested that the binding of BamE, or a BamDE dimer, to BamA induced conformational changes in the polypeptide transported-associated (POTRA) domains of BamA, but that BamB or BamD alone did not promote any such changes. As monitored by neutron reflectometry, addition of an unfolded substrate protein extended the length of POTRA domains further away from the membrane interface as part of the mechanism whereby the substrate protein was folded into the membrane.

Glaucoma, a major cause of irreversible blindness worldwide, is associated with elevated intraocular pressure (IOP) and progressive loss of retinal ganglion cells (RGCs) that undergo apoptosis. A mechanism for RGCs injury involves impairment of neurotrophic support and exogenous supply of neurotrophic factors has been shown to be beneficial. However, neurotrophic factors can have widespread effects on neuronal tissues, thus targeting neurotrophic support to injured neurons may be a better neuroprotective strategy. In this study, we have encapsulated LM22A-4, a small neurotrophic factor mimetic, into Annexin V-conjugated cubosomes (L4-ACs) for targeted delivery to injured RGCs in a model of acute IOP elevation, which is induced by acute IOP elevation. We have tested cubosomes formulations that encapsulate from 9% to 33% LM22A-4. Our data indicated that cubosomes encapsulating 9% and 17% LM22A-4 exhibited a mixture of Pn3m/Im3m cubic phase, whereas 23% and 33% showed a pure Im3m cubic phase. We found that 17% L4-ACs with Pn3m/Im3m symmetries showed better in-situ and in-vitro lipid membrane interactions than the 23% and 33% L4-ACs with Im3m symmetry. In vivo experiments showed that 17% L4-ACs targeted the posterior retina and the optic nerve head, which prevented RGCs loss and improved functional outcomes in a mouse model of acute IOP elevation. These results provide evidence that Annexin V-conjugated cubosomes-based LM22A-4 delivery may be a useful targeted approach to prevent the progression of RGCs loss in glaucoma. Statement of significance: Recent studies suggest that the therapy of effectively delivering neurotrophic factors to the injured retinal ganglion cells (RGCs) could promote the survival of RGCs in glaucoma. Our present work has for the first time used cubosomes as an active targeted delivery system and have successfully delivered a neuroprotective drug to the damaged RGCs in vivo. Our new cubosomal formulation can protect apoptotic cell death in vitro and in vivo, showing that cubosomes are a promising drug carrier system for ocular drug delivery and glaucoma treatment. We have further found that by controlling cubosomes in Pn3m phase we can facilitate delivery of neuroprotective drug through apoptotic membranes. This data, we believe, has important implications for future design and formulation of cubosomes for therapeutic applications.

Treatment of multidrug-resistant (MDR) bacterial infections increasingly relies on last-line antibiotics, such as polymyxins, with the urgent need for discovery of new antimicrobials. Nanotechnology-based antimicrobials have gained significant importance to prevent the catastrophic emergence of MDR over the past decade. In this study, phytantriol-based nanoparticles, named cubosomes, were prepared and examined in vitro by minimum inhibitory concentration (MIC) and time-kill assays against Gram-negative bacteria: Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Phytantriol-based cubosomes were highly bactericidal against polymyxin-resistant, lipopolysaccharide (LPS)-deficient A. baumannii strains. Small-angle neutron scattering (SANS) was employed to understand the structural changes in biomimetic membranes that replicate the composition of these LPS-deficient strains upon treatment with cubosomes. Additionally, to further understand the membrane-cubosome interface, neutron reflectivity (NR) was used to investigate the interaction of cubosomes with model bacterial membranes on a solid support. These results reveal that cubosomes might be a new strategy for combating LPS-deficient Gram-negative pathogens.

Gene therapies that chronically suppress vascular endothelial growth factor (VEGF) represent a new approach for managing retinal vascular leakage and neovascularization. However, constitutive suppression of VEGF in the eye may have deleterious side effects. Here, we developed a novel strategy to introduce Flt23k, a decoy receptor that binds intracellular VEGF, fused to the destabilizing domain (DD) of Escherichia coli dihydrofolate reductase (DHFR) into the retina. The expressed DHFR(DD)-Flt23k fusion protein is degraded unless "switched on" by administering a stabilizer; in this case, the antibiotic trimethoprim (TMP). Cells transfected with the DHFR(DD)-Flt23k construct expressed the fusion protein at levels correlated with the TMP dose. Stabilization of the DHFR(DD)-Flt23k fusion protein by TMP was able to inhibit intracellular VEGF in hypoxic cells. Intravitreal injection of self-complementary adeno-associated viral vector (scAAV)-DHFR(DD)-Flt23k and subsequent administration of TMP resulted in tunable suppression of ischemia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy (OIR). Hence, our study suggests a promising novel approach for the treatment of retinal neovascularization. Schematic diagram of the tunable system utilizing the DHFR(DD)-Flt23k approach to reduce VEGF secretion. a The schematic shows normal VEGF secretion. b Without the ligand TMP, the DHFR(DD)-Flt23k protein is destabilized and degraded by the proteasome. c In the presence of the ligand TMP, DHFR(DD)-Flt23k is stabilized and sequestered in the ER, thereby conditionally inhibiting VEGF. Green lines indicate the intracellular and extracellular distributions of VEGF. Blue lines indicate proteasomal degradation of the DHFR(DD)-Flt23k protein. Orange lines indicate the uptake of cell-permeable TMP. TMP, trimethoprim; VEGF, vascular endothelial growth factor; ER, endoplasmic reticulum.

Glaucoma, a major cause of irreversible blindness worldwide, is associated with elevated intraocular pressure (IOP) and progressive loss of retinal ganglion cells (RGCs) that undergo apoptosis. A mechanism for RGCs injury involves impairment of neurotrophic support and exogenous supply of neurotrophic factors has been shown to be beneficial. However, neurotrophic factors can have widespread effects on neuronal tissues, thus targeting neurotrophic support to injured neurons may be a better neuroprotective strategy. In this study, we have encapsulated LM22A-4, a small neurotrophic factor mimetic, into Annexin V-conjugated cubosomes (L4-ACs) for targeted delivery to injured RGCs in a model of glaucoma, which is induced by acute IOP elevation. We have tested cubosomes formulations that encapsulate from 9% to 33% LM22A-4. Our data indicated that cubosomes encapsulating 9% and 17% LM22A-4 exhibited a mixture of Pn3m/Im3m cubic phase, whereas 23% and 33% showed a pure Im3m cubic phase. We found that 17% L4-ACs with Pn3m/Im3m symmetries showed better in-situ and in-vitro lipid membrane interactions than the 23% and 33% L4-ACs with Im3m symmetry. In vivo experiments showed that 17% L4-ACs targeted the posterior retina and the optic nerve head, which prevented RGCs loss in a mouse model of acute IOP elevation. These results provide evidence that cubosomes-based LM22A-4 delivery may be a useful targeted approached to prevent the progression of RGCs loss in glaucoma.

Hybrid organic–inorganic halide perovskites have been extensively studied due to their remarkable optical and electronic features, such as high absorption coefficient, long exciton diffusion length, excellent carrier transport and low exciton binding energy, as well as a facile solution process for the fabrication of organic–inorganic halide perovskites. High-efficiency solar cells with methylammonium lead halide perovskites have been successfully achieved within just a few years. The high-quality perovskite films have made a significant impact on the fabrication of efficient and stable hybrid perovskite solar cells. Morphology engineering has been recognized as an effective way to obtain highly crystalline and pinhole-free perovskite films with optimized grain sizes. Here, we summarize several methodologies of morphology engineering, consisting of additive engineering, self-assembled monolayers (SAMs), solvent engineering, solvent annealing, thermal engineering, compositional engineering and humidity engineering. The highly crystallized perovskite layers prepared by using these techniques show a uniform surface morphology, resulting in enhanced photovoltaic efficiency and long-term stability of hybrid perovskite solar cells.

Polymyxins are last-line antibiotics against life-threatening multidrug-resistant Gram-negative bacteria. Unfortunately, polymyxin resistance is increasingly reported, leaving a total lack of therapies. Using lipidomics and transcriptomics, we discovered that polymyxin B induced lipid A deacylation via pagL in both polymyxin-resistant and -susceptible Pseudomonas aeruginosa. Our results demonstrated that the deacylation of lipid A is an "innate immunity" response to polymyxins and a key compensatory mechanism to the aminoarabinose modification to confer high-level polymyxin resistance in P. aeruginosa. Furthermore, cutting-edge neutron reflectometry studies revealed that an assembled outer membrane (OM) with the less hydrophobic penta-acylated lipid A decreased polymyxin B penetration, compared to the hexa-acylated form. Polymyxin analogues with enhanced hydrophobicity displayed superior penetration into the tail regions of the penta-acylated lipid A OM. Our findings reveal a previously undiscovered mechanism of polymyxin resistance, wherein polymyxin-induced lipid A remodeling affects the OM packing and hydrophobicity, perturbs polymyxin penetration, and thereby confers high-level resistance.

The composite of MoS2 and hollow carbon sphere (MoS2@HCS) is prepared via a glucose-assisted one pot synthesis. The composite consists of hierarchical spheres with a diameter of 0.5–4 μm and these hollow spheres are decorated with a number of curled and interlaced MoS2 nanosheets. After the composite is subject to the lithium intercalation, the MoS2 is converted from 2H to 1T phase. In this current work, the activities of 1T-MoS2@HCS toward photocatalytic hydrogen evolution and the reduction of I3− in dye-sensitized solar cells (DSCs) are systemically investigated. When evaluated as the photocatalyst for hydrogen evolution, the amount of evolved hydrogen over 1T-MoS2@HCS can reach 143 μmol in 2 h, being 3.6 times higher than as-synthesized 2H-MoS2@HCS. Additionally, the 1T-MoS2@HCS can be employed as the counter electrode (CE) material in DSCs. The DSCs based on 1T-MoS2@HCS CE possesses the power conversion efficiency of 8.94%, being higher than that with 2H-MoS2@HCS CE (8.16%) and comparable to that with Pt CE (8.87%). Our study demonstrates that 1T-MoS2@HCS has a great potential as an inexpensive alternative to Pt catalysts.

The regulatory role of a novel miRNA, miR-378, was determined in the development of fibrosis through repression of the MAPK1 pathway, miR-378 and fibrotic gene expression was examined in streptozotocin (STZ)-induced diabetic mice at 18 weeks or in unilateral ureteral obstruction (UUO) mice at 7 days. miR-378 transfection of proximal tubular epithelial cells, NRK52E and mesangial cells was assessed with/without endogenous miR-378 knockdown using the locked nucleic acid (LNA) inhibitor. NRK52E cells were co-transfected with the mothers against decapentaplegic homolog 3 (SMAD3) CAGA reporter and miR-378 in the presence of transforming growth factor-β (TGF-β1) was assessed. Quantitative polymerase chain reaction (qPCR) showed a significant reduction in miR-378 (P

In Gram–negative bacteria, the multi-protein β-barrel assembly machine (BAM) complex is a nanomachine playing a vital role in the process of assembling β-barrel proteins into the outer membrane (OM). The core component of this multiprotein complex, BamA, is an evolutionarily conserved protein that carries five polypeptide-transport-associated (POTRA) domains that project from the outer membrane. BamA is essential for chaperoning the insertion of proteins into the OM surface of bacterial cells. In this work, we have reconstituted a membrane containing BamA on a gold substrate and characterized structure of each component and movement in different situation at the nanoscale level using quartz-crystal microbalance with dissipation and neutron reflectometry (NR). The purified BamA in n-dodecyl β-D-maltoside (DDM) was first engineered onto a nickel-NTA (Nα, Nα-bis-(carboxymethyl)- l -lysine) modified gold surface followed by DDM removal and bilayer assembly. The system was then used to monitor the binding and insertion of a substrate membrane protein. The data shows the total reach of BamA was 120 A and the embedding of membrane had no effect on the BamA morphology. However, the addition of the substrate enabled the periplasmic POTRA domain of BamA to extend further away from the membrane surface. This dynamic behaviour of BamA POTRA domains is consistent with models invoking the gathering of transported substrates from the periplasmic space between the inner and outer membranes in bacterial cells. This study provides evidence that NR is a reliable tool for diverse investigations in the future, especially for applications in the field of membrane protein biogenesis.

Staphylococcus aureus is a notorious human bacterial pathogen with considerable capacity to develop antibiotic resistance. We have observed that human infections caused by highly drug-resistant S. aureus are more prolonged, complicated, and difficult to eradicate. Here we describe a metabolic adaptation strategy used by clinical S. aureus strains that leads to resistance to the last-line antibiotic, daptomycin, and simultaneously affects host innate immunity. This response was characterized by a change in anionic membrane phospholipid composition induced by point mutations in the phospholipid biosynthesis gene, cls2, encoding cardiolipin synthase. Single cls2 point mutations were sufficient for daptomycin resistance, antibiotic treatment failure, and persistent infection. These phenotypes were mediated by enhanced cardiolipin biosynthesis, leading to increased bacterial membrane cardiolipin and reduced phosphatidylglycerol. The changes in membrane phospholipid profile led to modifications in membrane structure that impaired daptomycin penetration and membrane disruption. The cls2 point mutations also allowed S. aureus to evade neutrophil chemotaxis, mediated by the reduction in bacterial membrane phosphatidylglycerol, a previously undescribed bacterial-driven chemoattractant. Together, these data illustrate a metabolic strategy used by S. aureus to circumvent antibiotic and immune attack and provide crucial insights into membrane-based therapeutic targeting of this troublesome pathogen.

Pseudomonas aeruginosa has been highlighted by the recent WHO Global Priority Pathogen List due to multidrug resistance. Without new antibiotics, polymyxins remain a last-line therapeutic option for this difficult-to-treat pathogen. The emergence of polymyxin resistance highlights the growing threat to our already very limited antibiotic armamentarium and the urgency to understand the exact mechanisms of polymyxin activity and resistance. Integration of the correlative metabolomics and transcriptomics results in the present study discovered that polymyxin treatment caused significant perturbations in the biosynthesis of lipids, lipopolysaccharide, and peptidoglycan, central carbon metabolism, and oxidative stress. Importantly, lipid A modifications were surprisingly rapid in response to polymyxin treatment at clinically relevant concentrations. This is the first study to reveal the dynamics of polymyxin-induced cellular responses at the systems level, which highlights that combination therapy should be considered to minimize resistance to the last-line polymyxins. The results also provide much-needed mechanistic information which potentially benefits the discovery of new-generation polymyxins., Polymyxins are a last-line therapy against multidrug-resistant Pseudomonas aeruginosa; however, resistance to polymyxins has been increasingly reported. Therefore, understanding the mechanisms of polymyxin activity and resistance is crucial for preserving their clinical usefulness. This study employed comparative metabolomics and transcriptomics to investigate the responses of polymyxin-susceptible P. aeruginosa PAK (polymyxin B MIC, 1 mg/liter) and its polymyxin-resistant pmrB mutant PAKpmrB6 (MIC, 16 mg/liter) to polymyxin B (4, 8, and 128 mg/liter) at 1, 4, and 24 h, respectively. Our results revealed that polymyxin B at 4 mg/liter induced different metabolic and transcriptomic responses between polymyxin-susceptible and -resistant P. aeruginosa. In strain PAK, polymyxin B significantly activated PmrAB and the mediated arn operon, leading to increased 4-amino-4-deoxy-L-arabinose (L-Ara4N) synthesis and the addition to lipid A. In contrast, polymyxin B did not increase lipid A modification in strain PAKpmrB6. Moreover, the syntheses of lipopolysaccharide and peptidoglycan were significantly decreased in strain PAK but increased in strain PAKpmrB6 due to polymyxin B treatment. In addition, 4 mg/liter polymyxin B significantly perturbed phospholipid and fatty acid levels and induced oxidative stress in strain PAK, but not in PAKpmrB6. Notably, the increased trehalose-6-phosphate levels indicate that polymyxin B potentially caused osmotic imbalance in both strains. Furthermore, 8 and 128 mg/liter polymyxin B significantly elevated lipoamino acid levels and decreased phospholipid levels but without dramatic changes in lipid A modification in wild-type and mutant strains, respectively. Overall, this systems study is the first to elucidate the complex and dynamic interactions of multiple cellular pathways associated with the polymyxin mode of action against P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa has been highlighted by the recent WHO Global Priority Pathogen List due to multidrug resistance. Without new antibiotics, polymyxins remain a last-line therapeutic option for this difficult-to-treat pathogen. The emergence of polymyxin resistance highlights the growing threat to our already very limited antibiotic armamentarium and the urgency to understand the exact mechanisms of polymyxin activity and resistance. Integration of the correlative metabolomics and transcriptomics results in the present study discovered that polymyxin treatment caused significant perturbations in the biosynthesis of lipids, lipopolysaccharide, and peptidoglycan, central carbon metabolism, and oxidative stress. Importantly, lipid A modifications were surprisingly rapid in response to polymyxin treatment at clinically relevant concentrations. This is the first study to reveal the dynamics of polymyxin-induced cellular responses at the systems level, which highlights that combination therapy should be considered to minimize resistance to the last-line polymyxins. The results also provide much-needed mechanistic information which potentially benefits the discovery of new-generation polymyxins.

Carbon-based conductive materials have been recognized as promising alternatives to noble metals as the electrode in optoelectronic devices. Herein, by utilizing energetic plasma ion implantation, Ni-doped TiN nanowire (NWs) modified graphitic carbon nanofibers (CNF) are designed and prepared as the candidates of the platinum (Pt) counter electrode for low-cost hybrid perovskite-based liquid-junction photoelectrochemical solar cells (LPSCs). Notably, the photoelectrochemical (PEC) response of p-Rb0.05FA0.95PbI3 based-LPSCs equipped with the Ni/TiN/CNF counter electrode is almost identical to that with a typical Pt counter electrode. From electrochemical investigations, i.e., electrochemical impedance spectroscopy (EIS), we observe that the CNF-based materials show a similar redox activity compared with the Pt counter electrode, indicating low charge-transfer resistance (Rct) and large capacitance (C). The LPSCs, with a configuration of p-Rb0.05FA0.95PbI3/BQ (2 mM), BQ − (2 mM)/Ni/TiN/CNF-based counter electrode, exhibit an open-circuit photovoltage of 1.00 V and a short-circuit current density of 7.02 mA/cm2 under 100 mW/cm2 irradiation. The overall optical-to-electrical energy conversion efficiency is 5.06%. The PEC solar cell shows good stability for 5 h under irradiation. The CNF-based counter electrode enables potential applications, including but not limited to PEC solar devices, dye-sensitized solar cells (DSSCs), solar fuel devices and hydrogen evolution reaction.

The advancement of microRNA (miRNA) therapies has been hampered by difficulties in delivering miRNA to the injured kidney in a robust and sustainable manner. Using bioluminescence imaging in mice with unilateral ureteral obstruction (UUO), we report that mesenchymal stem cells (MSCs), engineered to overexpress miRNA-let7c (miR-let7c-MSCs), selectively homed to damaged kidneys and upregulated miR-let7c gene expression, compared with nontargeting control (NTC)-MSCs. miR-let7c-MSC therapy attenuated kidney injury and significantly downregulated collagen IVα1, metalloproteinase-9, transforming growth factor (TGF)-β1, and TGF-β type 1 receptor (TGF-βR1) in UUO kidneys, compared with controls. In vitro analysis confirmed that the transfer of miR-let7c from miR-let7c-MSCs occurred via secreted exosomal uptake, visualized in NRK52E cells using cyc3-labeled pre-miRNA-transfected MSCs with/without the exosomal inhibitor, GW4869. The upregulated expression of fibrotic genes in NRK52E cells induced by TGF-β1 was repressed following the addition of isolated exosomes or indirect coculture of miR-let7c-MSCs, compared with NTC-MSCs. Furthermore, the cotransfection of NRK52E cells using the 3'UTR of TGF-βR1 confirmed that miR-let7c attenuates TGF-β1-driven TGF-βR1 gene expression. Taken together, the effective antifibrotic function of engineered MSCs is able to selectively transfer miR-let7c to damaged kidney cells and will pave the way for the use of MSCs for therapeutic delivery of miRNA targeted at kidney disease.

In this study, we demonstrate the formation of azo compounds on a composite of silver nanoparticles and graphene oxides (Ag@G) through a plasmon-assisted coupling reaction between different amine compounds. According to the time-dependent SERS experiments, 4-aminothiophenol (4ATP) molecules on Ag@G can be associated with external reactants such as 4-nitroaniline to form azo compounds when aided by the plasmons. Furthermore, the rate of the coupling reaction is dependent on the wavelength and the power of the excitation laser. It is noteworthy that the coupling reaction can only occur between two compounds containing amino groups in the presence of Ag nanoparticles. On the other hand, the NN double bond in the azo compound can be dissociated in a NaBH4 solution after 532 nm laser irradiation. The reduction of the azo compound results in the recovery of 4ATP molecules on Ag@G. Finally, we demonstrate that the plasmon-assisted coupling reaction allows for the immobilization of amine-terminated DNAs on 4ATP modified Ag@G. This DNA modified Ag@G can serve as the SERS substrate to sensitively detect its complementary DNA.