Quantitative proteomics revealed the transition of ergosterol biosynthesis and drug transporters processes during the development of fungal fluconazole resistance.

Fungal infections and antifungal resistance are the increasing global public health concerns. Mechanisms of fungal resistance include alterations in drug-target interactions, detoxification by high expression of drug efflux transporters, and permeability barriers associated with biofilms. However, the systematic panorama and dynamic changes of the relevant biological processes of fungal drug resistance acquisition remain limited. In this study, we developed a yeast model of resistance to prolonged fluconazole treatment and utilized the isobaric labels TMT (tandem mass tag)-based quantitative proteomics to analyze the proteome composition and changes in native, short-time fluconazole stimulated and drug-resistant strains. The proteome exhibited significant dynamic range at the beginning of treatment but returned to normal condition upon acquisition drug resistance. The sterol pathway responded strongly under a short time of fluconazole treatment, with increased transcript levels of most enzymes facilitating greater protein expression. With the drug resistance acquisition, the sterol pathway returned to normal state, while the expression of efflux pump proteins increased obviously on the transcription level. Finally, multiple efflux pump proteins showed high expression in drug-resistant strain. Thus, families of sterol pathway and efflux pump proteins, which are closely associated with drug resistance mechanisms, may play different roles at different nodes in the process of drug resistance acquisition. Our findings uncover the relatively important role of efflux pump proteins in the acquisition of fluconazole resistance and highlight its potential as the vital antifungal targets.

A Novel Conductive Antibacterial Nanocomposite Hydrogel Dressing for Healing of Severely Infected Wounds.

Wound infections are serious medical complications that can endanger human health. Latest researches show that conductive composite materials may make endogenous/exogenous electrical stimulation more effective, guide/comb cell migration to the wound, and subsequently promote wound healing. To accelerate infected wound healing, a novel medical silver nanoparticle-doped conductive polymer-based hydrogel system (Ag NPs/CPH) dressing with good conductivity, biocompatibility, and mechanical and antibacterial properties was fabricated. For the hydrogel dressing, Ag NPs/CPH, polyvinyl alcohol (PVA), and gelatin were used as the host matrix materials, and phytic acid (PA) was used as the cross-linking agent to introduce conductive polyaniline into the matrix, with antibacterial Ag NPs loaded via impregnation. After a series of analyses, the material containing 5 wt% of PVA by concentration, 1.5 wt% gelatin, 600 µL of AN reactive volume, and 600 µL of PA reactive volume was chosen for Ag NPs/CPH preparation. XPS and FTIR analysis had been further used to characterize the composition of the prepared Ag NPs/CPH. The test on the swelling property showed that the hydrogels had abundant pores with good water absorption (≈140% within 12 h). They can be loaded and continuously release Ag NPs. Thus, the prepared Ag NPs/CPH showed excellent antibacterial property with increasing duration of immersion of Ag NPs. Additionally, to evaluate in vivo safety, CCK-8 experiments of HaCat, LO2 and 293T cells were treated with different concentrations of the Ag NPs/CPH hydrogel soaking solution. The experimental results showed the Ag NPs/CPH had no significant inhibitory effect on any of the cells. Finally, an innovative infection and inflammation model was designed to evaluate the prepared Ag NPs/CPH hydrogel dressing for the treatment of severely infected wounds. The results showed that even when infected with bacteria for long periods of time (more than 20 h), the proposed conductive antibacterial hydrogel could treat severely infected wounds.

A Novel Temperature-Dependent Hydrogel Emulsion with Sol/Gel Reversible Phase Transition Behavior Based on Polystyrene-co-poly(N-isopropylacrylamide)/Poly(N-isopropylacrylamide) Core-Shell Nanoparticle.

As a kind of temperature-responsive hydrogel, polystyrene-co-poly(N-isopropylacrylamide)/poly(N-isopropylacrylamide) (PS-co-PNIPAM/PNIPAM) core-shell nanoparticles prepared by two-step copolymerization are widely studied and used because of their specific structures and properties. Unlike most reports about the steady stability of PS-co-PNIPAM/PNIPAM core-shell nanoparticle hydrogel emulsion, in this work, the PS-co-PNIPAM/PNIPAM core-shell nanoparticle hydrogel emulsion (symbolized as PS/PNIPAM hydrogel emulsion), which is prepared after the second step of synthesis and without washing out a large number of PNIPAM polymer segments, shows a reversible temperature-dependent sol-gel transition characteristic during the temperature range of 34-80 °C. The PS/PNIPAM hydrogel emulsion is a normal solution at room temperature, and it changes from a sol to a gel statue when the temperature approaches up to low critical solution temperature (LCST). As the temperature continues to increase, the gel (core-shell nanoparticles as the crosslinkers and the linear PNIPAM chain as the 3D gel network) of the PS/PNIPAM hydrogel emulsion gradually shrinks and drains linearly. Compared with most crosslinked hydrogels, the hydrogel here can be arbitrarily changed in shape according to use needs, which is convenient for use, transportation, and storage. Here a new route is provided for the preparation of a PS/PNIPAM core-shell hydrogel nanoparticle system, as well as a new supramolecular crosslinking sol-gel system for application in biomedical materials, sensors, biological separation, drug release, macromolecular adsorption, and purification.

Transparent Conductive Supramolecular Hydrogels with Stimuli-Responsive Properties for On-Demand Dissolvable Diabetic Foot Wound Dressings.

Diabetic foot ulcers (DFU) remain a very considerable health care burden, and their treatment is difficult. Hydrogel-based wound dressings are appealing to provide an optimal environment for wound repair. However, the currently available hydrogel dressings still need surgical or mechanical debridement from the wound, causing reinjury of the newly formed tissues, wound infection, delayed healing time, and personal suffering. Additionally, to meet people's increasing demand, hydrogel wound dressings with improved performance and multifunctionality are urgently required. Here, a new multifunctional supramolecular hydrogel for on-demand dissolvable diabetic foot wound dressings is designed and constructed. Based on multihydrogen bonds between hydrophilic polymers, the resultant supramolecular hydrogels present controlled and excellent properties, such as good transparency, antibacterial ability, conductive, and self-healing properties. Thus, the supramolecular hydrogels improve the new tissue formation and provide a significant therapeutic effect on DFU by inducing angiogenesis, enhancing collagen deposition, preventing bacterial infection, and controlling wound infection. Remarkably, the resultant hydrogels also exhibit stimuli-responsive ability, which renders its capability to be dissolved on-demand, allowing for a facile DFU dressing removal. This multifunctional supramolecular hydrogel may provide a novel concept in the design of on-demand dissolvable wound dressings.

Enhanced dielectric deposition on single-layer MoS2 with low damage using remote N2 plasma treatment.

Using remote N2 plasma treatment to promote dielectric deposition on the dangling-bond free MoS2 is explored for the first time. The N2 plasma induced damages are systematically studied by the defect-sensitive acoustic-phonon Raman of single-layer MoS2, with samples undergoing O2 plasma treatment as a comparison. O2 plasma treatment causes defects in MoS2 mainly by oxidizing MoS2 along the already defective sites (most likely the flake edges), which results in the layer oxidation of MoS2. In contrast, N2 plasma causes defects in MoS2 mainly by straining and mechanically distorting the MoS2 layers first. Owing to the relatively strong MoS2-substrate interaction and chemical inertness of MoS2 in N2 plasma, single-layer MoS2 shows great stability in N2 plasma and only stable point defects are introduced after long-duration N2 plasma exposure. Considering the enormous vulnerability of single-layer MoS2 in O2 plasma and the excellent stability of single-layer MoS2 in N2 plasma, the remote N2 plasma treatment shows great advantage as surface functionalization to promote dielectric deposition on single-layer MoS2.

Improved Gate Dielectric Deposition and Enhanced Electrical Stability for Single-Layer MoS2 MOSFET with an AlN Interfacial Layer.

Transistors based on MoS2 and other TMDs have been widely studied. The dangling-bond free surface of MoS2 has made the deposition of high-quality high-k dielectrics on MoS2 a challenge. The resulted transistors often suffer from the threshold voltage instability induced by the high density traps near MoS2/dielectric interface or inside the gate dielectric, which is detrimental for the practical applications of MoS2 metal-oxide-semiconductor field-effect transistor (MOSFET). In this work, by using AlN deposited by plasma enhanced atomic layer deposition (PEALD) as an interfacial layer, top-gate dielectrics as thin as 6 nm for single-layer MoS2 transistors are demonstrated. The AlN interfacial layer not only promotes the conformal deposition of high-quality Al2O3 on the dangling-bond free MoS2, but also greatly enhances the electrical stability of the MoS2 transistors. Very small hysteresis (ΔVth) is observed even at large gate biases and high temperatures. The transistor also exhibits a low level of flicker noise, which clearly originates from the Hooge mobility fluctuation instead of the carrier number fluctuation. The observed superior electrical stability of MoS2 transistor is attributed to the low border trap density of the AlN interfacial layer, as well as the small gate leakage and high dielectric strength of AlN/Al2O3 dielectric stack.