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We briefly discuss the history of cold atmospheric plasma (CAP) applications in dentistry. The reasons for seeking innovative solutions in dentistry are reported, highlighting results showing the potential of plasma along with some still-open questions. Finally, we suggest the next steps on the road from the laboratory to the dental chair.

Microglia adopt numerous fates with homeostatic microglia (HM) and a microglial neurodegenerative phenotype (MGnD) representing two opposite ends. A number of variants in genes selectively expressed in microglia are associated with an increased risk for neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Among these genes are progranulin ( GRN ) and the triggering receptor expressed on myeloid cells 2 ( TREM2 ). Both cause neurodegeneration by mechanisms involving loss of function. We have now isolated microglia from Grn −/− mice and compared their transcriptomes to those of Trem2 −/− mice . Surprisingly, while loss of Trem2 enhances the expression of genes associated with a homeostatic state, microglia derived from Grn −/− mice showed a reciprocal activation of the MGnD molecular signature and suppression of gene characteristic for HM. The opposite mRNA expression profiles are associated with divergent functional phenotypes. Although loss of TREM2 and progranulin resulted in opposite activation states and functional phenotypes of microglia, FDG (fluoro‐2‐deoxy‐ d ‐glucose)‐μPET of brain revealed reduced glucose metabolism in both conditions, suggesting that opposite microglial phenotypes result in similar wide spread brain dysfunction. Synopsis Microglia from Grn −/− & Trem2 −/− mice display opposite molecular signatures. While microglia are either locked in a hyperactivated or homeostatic state, Grn −/− & Trem2 −/− mice both show reduced glucose metabolism, suggesting that opposite microglial phenotypes result in similar brain dysfunction. First demonstration that microglia from both extremes of their functional stages cause brain wide dysfunctions. This study indicates that the therapeutic window for microglial modulation is rather narrow and care must be taken to balance microglial activity. Graphical Abstract Microglia from Grn −/− & Trem2 −/− mice display opposite molecular signatures. While microglia are either locked in a hyperactivated or homeostatic state, Grn −/− & Trem2 −/− mice both show reduced glucose metabolism, suggesting that opposite microglial phenotypes result in similar brain dysfunction.

Plant bacterial diseases are routinely managed with scheduled treatments based on heavy metal compounds or on antibiotics; to reduce the negative environmental impact due to the use of such chemical compounds, as pollution or selection of antibiotic resistant pathogens, the integrated control management is required. In the frame of a sustainable agriculture the use of bacterial antagonists, biological agents, plant defence response elicitors or resistant host plant genotypes are the most effective approaches. In this work, cold atmospheric pressure plasma (CAP) was applied to sterile distilled water, inducing the production of a hydrogen peroxide, nitrite and nitrate, and a pH reduction. In particular, an atmospheric pressure dielectric barrier discharge (DBD) has been used to produce plasma activated water (PAW), that was firstly assayed in in vitro experiments and then in planta through application at the root apparatus of tomato plants, against Xanthomonas vesicatoria (Xv), the etiological agent of bacterial leaf spot. Moreover, the transcription abundance of five genes related to the plant defense was investigated in response to PAW treatment. PAW did not show direct antimicrobial activity against Xv in in vitro experiments, but it enhanced the tomato plants defenses. It was effective in reducing the disease severity by giving relative protections of ca. 61, 51 and 38% when applied 1 h, 24 h and 6 days before the experimental inoculation, respectively. In addition, the experiments highlighted the pal gene involvement in response to the PAW treatments and against the pathogen; its transcription levels resulted significantly high from 1 to 48 h until their decrease 192 h after PAW application.

Nowadays, one of the main challenges is moving towards an eco-sustainable agriculture, able to preserve the food production through a reduced use of pesticides. Current global food sustenance by intensive agriculture is mainly based on economic crop monocultures and drastically reduces the biodiversity, increasing the yield losses due to the presence of biotic and abiotic stresses. A technology based on plasma activated water (PAW), characterized by the presence in liquid of reactive oxygen and nitrogen species, was tested to try to ensure yield stability also enhancing the plant resistance responses and to promote an eco-sustainable management of plant diseases. In PAW-treated micropropagated periwinkle shoots, periwinkle and grapevine plants, qRT-PCR and small RNAs high-throughput sequencing were used to analyse the differential expression of genes involved in the major plant defence pathways. The results indicate that PAW treatment enhances the plant defence responses and provide an encouraging framework for future applications in plant disease management programs.

Background Heterozygous loss-of-function mutations in the progranulin gene ( GRN ) lead to frontotemporal lobar degeneration (FTLD) while the complete loss of progranulin (PGRN) function results in neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Thus the growth factor-like protein PGRN may play an important role in lysosomal degradation. In line with a potential lysosomal function, PGRN is partially localized and processed in lysosomes. In the central nervous system (CNS), PGRN is like other lysosomal proteins highly expressed in microglia, further supporting an important role in protein degradation. We have previously reported that cathepsin (Cat) D is elevated in GRN -associated FTLD patients and Grn knockout mice. However, the primary mechanism that causes impaired protein degradation and elevated CatD levels upon PGRN deficiency in NCL and FTLD remains unclear. Methods mRNA expression analysis of selected lysosomal hydrolases, lysosomal membrane proteins and autophagy-related genes was performed by NanoString nCounter panel. Protein expression, maturation and in vitro activity of Cat D, B and L in mouse embryonic fibroblasts (MEF) and brains of Grn knockout mice were investigated. To selectively characterize microglial and non-microglial brain cells, an acutely isolated microglia fraction using MACS microbeads (Miltenyi Biotec) conjugated with CD11b antibody and a microglia-depleted fraction were analyzed for protein expression and maturation of selected cathepsins. Results We demonstrate that loss of PGRN results in enhanced expression, maturation and in vitro activity of Cat D, B and L in mouse embryonic fibroblasts and brain extracts of aged Grn knockout mice. Consistent with an overall enhanced expression and activity of lysosomal proteases in brain of Grn knockout mice, we observed an age-dependent transcriptional upregulation of certain lysosomal proteases. Thus, lysosomal dysfunction is not reflected by transcriptional downregulation of lysosomal proteases but rather by the upregulation of certain lysosomal proteases in an age-dependent manner. Surprisingly, cell specific analyses identified early lysosomal deficits in microglia before enhanced cathepsin levels could be detected in other brain cells, suggesting different functional consequences on lysosomal homeostasis in microglia and other brain cells upon lack of PGRN. Conclusions The present study uncovers early and selective lysosomal dysfunctions in Grn knockout microglia/macrophages. Dysregulated lysosomal homeostasis in microglia might trigger compensatory lysosomal changes in other brain cells.

Niemann-Pick type C disease (NPC) is a rare inherited neurodegenerative disorder characterized by an accumulation of intracellular cholesterol within late endosomes and lysosomes due to NPC1 or NPC2 dysfunction. In this work, we tested the hypothesis that retromer impairment may be involved in the pathogenesis of NPC and may contribute to increased amyloidogenic processing of APP and enhanced BACE1-mediated proteolysis observed in NPC disease. Using NPC1-null cells, primary mouse NPC1-deficient neurons and NPC1-deficient mice (BALB/cNctr-Npc1m1N), we show that retromer function is impaired in NPC. This is manifested by altered transport of the retromer core components Vps26, Vps35 and/or retromer receptor sorLA and by retromer accumulation in neuronal processes, such as within axonal swellings. Changes in retromer distribution in NPC1 mouse brains were observed already at the presymptomatic stage (at 4-weeks of age), indicating that the retromer defect occurs early in the course of NPC disease and may contribute to downstream pathological processes. Furthermore, we show that cholesterol depletion in NPC1-null cells and in NPC1 mouse brains reverts retromer dysfunction, suggesting that retromer impairment in NPC is mechanistically dependent on cholesterol accumulation. Thus, we characterized retromer dysfunction in NPC and propose that the rescue of retromer impairment may represent a novel therapeutic approach against NPC.

Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, the mechanisms of microbiome–brain interaction in AD were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as microbial metabolites which promote Aβ deposition. Germ-free (GF) AD mice exhibit a substantially reduced Aβ plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice increased the Aβ plaque load to levels of conventionally colonized (specific pathogen-free [SPF]) animals and SCFA supplementation to SPF mice even further exacerbated plaque load. This was accompanied by the pronounced alterations in microglial transcriptomic profile, including upregulation of ApoE. Despite increased microglial recruitment to Aβ plaques upon SCFA supplementation, microglia contained less intracellular Aβ. Taken together, our results demonstrate that microbiota-derived SCFA are critical mediators along the gut-brain axis which promote Aβ deposition likely via modulation of the microglial phenotype.

In industrialized countries, health care associated infections, the fourth leading cause of disease, are a major health issue. At least half of all cases of nosocomial infections are associated with medical devices. Antibacterial coatings arise as an important approach to restrict the nosocomial infection rate without side effects and the development of antibiotic resistance. Beside nosocomial infections, clot formation affects cardiovascular medical devices and central venous catheters implants. In order to reduce and prevent such infection, we develop a plasma-assisted process for the deposition of nanostructured functional coatings on flat substrates and mini catheters. Silver nanoparticles (Ag NPs) are synthesized exploiting in-flight plasma-droplet reactions and are embedded in an organic coating deposited through hexamethyldisiloxane (HMDSO) plasma assisted polymerization. Coating stability upon liquid immersion and ethylene oxide (EtO) sterilization is assessed through chemical and morphological analysis carried out by means of Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). In the perspective of future clinical application, an in vitro analysis of anti-biofilm effect has been done. Moreover, we employed a murine model of catheter-associated infection which further highlighted the performance of Ag nanostructured films in counteract biofilm formation. The anti-clot performances coupled by haemo- and cytocompatibility assays have also been performed.

Electrospun gelatin nanofibers attract great interest as a natural biomaterial for cartilage and tendon repair despite their high solubility in aqueous solution, which makes them also difficult to crosslink by means of chemical agents. In this work, we explore the efficiency of non-equilibrium atmospheric pressure plasma in stabilizing gelatin nanofibers. We demonstrate that plasma represents an innovative, easy and environmentally friendly approach to successfully crosslink gelatin electrospun mats directly in the solid state. Plasma treated gelatin mats display increased structural stability and excellent retention of fibrous morphology after immersion in aqueous solution. This method can be successfully applied to induce crosslinking both in pure gelatin and genipin-containing gelatin electrospun nanofibers, the latter requiring an even shorter plasma exposure time. A complete characterization of the crosslinked nanofibres, including mechanical properties, morphological observations, stability in physiological solution and structural modifications, has been carried out in order to get insights on the occurring reactions triggered by plasma.

The interaction of plasmas and liquid aerosols offers special advantages and opens new perspectives for plasma–liquid applications. The paper focuses on the key research challenges and potential of plasma-aerosol interaction at atmospheric pressure in several fields, outlining opportunities and benefits in terms of process tuning and throughputs. After a short overview of the recent achievements in plasma–liquid field, the possible application benefits from aerosol injection in combination with plasma discharge are listed and discussed. Since the nature of the chemicophysical plasma-droplet interactions is still unclear, a multidisciplinary approach is recommended to overcome the current lack of knowledge and to open the plasma communities to scientists from other fields, already active in biphasic systems diagnostic. In this perspective, a better understanding of the high chemical reactivity of gas–liquid reactions will bring new opportunities for plasma assisted in-situ and on-demand reactive species production and material processing.