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About a hundred years ago, the Russian biologist A. Gurwitsch, based on experiments with onion plants by measuring their growth rate, hypothesized that plants emit a weak electromagnetic field that somehow influences cell growth. This interesting observation remained fundamentally ignored by the scientific community; only in the 1950s the electromagnetic emission from some plants was measured using a photomultiplier used in single counting mode. Later, in the 1980s, several groups around the world started extensive work to understand the origin and role of this ultraweak emission, now called biophotons, coming from living organisms. Biophotons are an endogenous very small production of photons in the visible energy range in and from cells and organisms, and this emission is characteristic of living organisms. Today, there is no doubt that biophotons exist, this emission has been measured by many groups and for many different living organisms, from humans to bacteria. However, the origin of biophotons and whether organisms use them to exchange information is not yet well understood; no model proposed to date is capable of reproducing and interpreting the great variety of experimental data coming from the many different living systems measured so far. In this brief review, we present our experimental work on the biophotons coming from germinating seeds, the main experimental results, and some new methods we are using to analyze the data to open the door for interpretative models of this phenomenon clarifying its function in the regulation and communication between cells and living organisms. We also discuss ideas on how to increase the signal-to-noise ratio of the measured signal to open up new experimental possibilities that allow the measurement and the characterization of currently unmeasurable quantities.

We hypothesize that the injection of JP4-039, a mitochondria-targeted nitroxide, prior to irradiation of the mouse retina may decrease apoptosis and reduce neutrophil and macrophage migration into the retina. In our study, we aimed to examine the effects of JP4-039 in the mouse retina using fluorescent microscopy, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and flow cytometry. Forty-five mice and one eye per mouse were used. In Group 1, fluorescent microscopy was used to determine retinal uptake of 10 µL (0.004 mg/µL) of intravitreally injected BODIPY-labeled JP4-039 at 0, 15, and 60 min after injection. In Group 2, the TUNEL assay was performed to investigate the rate of apoptosis after irradiation in addition to JP4-039 injection, compared to controls. In Group 3, flow cytometry was used to determine the extent of inflammatory cell migration into the retina after irradiation in addition to JP4-039 injection, compared to controls. Maximal retinal uptake of JP4-039 was 15 min after intravitreal injection (p < 0.0001). JP4-039-treated eyes had lower levels of retinal apoptosis (35.8 ± 2.5%) than irradiated controls (49.0 ± 2.7%; p = 0.0066) and demonstrated reduced migration of N1 cells (30.7 ± 11.7% vs. 77.7 ± 5.3% controls; p = 0.004) and M1 cells (76.6 ± 4.2 vs. 88.1 ± 3.7% controls, p = 0.04). Pretreatment with intravitreally injected JP4-039 reduced apoptosis and inflammatory cell migration in the irradiated mouse retina, marking the first confirmed effect of this molecule in retinal tissue. Further studies may allow for safety profiling and potential use for patients with radiation retinopathy.

Abstract Biologics are almost exclusively administered systemically, but localized delivery is preferable as it minimizes off-target exposure and allows more aggressive treatments. Topical application of biologics to epithelia is generally ineffective because most are covered with fluids and biologics are washed out too quickly to have significant therapeutic effects. Here we explore the idea that attaching a binding domain can serve as an “anchor” to extend the residency time of biologics on wet epithelia, allowing their effective use even with infrequent applications. We use topical application to the ocular surface as a challenging test since foreign substances are washed out especially efficiently by tear flow and blinking. Our results demonstrate that conjugation of antibodies to wheat germ agglutinin, which binds GlcNAc and sialic acid that are ubiquitously present in tissues, increases their half-life 350-fold upon application to the ocular surface in a mouse model of dry eye, a common and onerous disease in humans. Importantly, antibodies to IL-17A, IL-23, and IL-1β conjugated to the agglutinin reduces manifestations of dry eye, even when applied just once daily. In contrast, unconjugated antibodies are ineffective. Attaching an anchor to biologics is a simple means to overcome washout and to extend their therapeutic use.

Resident macrophages are distributed across all tissues and are highly heterogeneous due to adaptation to different tissue-specific environments. The resident macrophages of the sensory ganglia (sensory neuron-associated macrophages, sNAMs) are in close contact with the cell body of primary sensory neurons and might play physiological and pathophysiological roles. After peripheral nerve injury, there is an increase in the population of macrophages in the sensory ganglia, which have been implicated in different conditions, including neuropathic pain development. However, it is still under debate whether macrophage accumulation in the sensory ganglia after peripheral nerve injury is due to the local proliferation of resident macrophages or a result of blood monocyte infiltration. Here, we confirmed that the number of macrophages increased in the sensory ganglia after the spared nerve injury (SNI) model in mice. Using different approaches, we found that the increase in the number of macrophages in the sensory ganglia after SNI is a consequence of the proliferation of resident CX3CR1+ macrophages, which participate in the development of neuropathic pain, but not due to infiltration of peripheral blood monocytes. These proliferating macrophages are the source of pro-inflammatory cytokines such as TNF and IL-1b. In addition, we found that CX3CR1 signaling is involved in the sNAMs proliferation and neuropathic pain development after peripheral nerve injury. In summary, these results indicated that peripheral nerve injury leads to sNAMs proliferation in the sensory ganglia in a CX3CR1-dependent manner accounting for neuropathic pain development. In conclusion, sNAMs proliferation could be modulated to change pathophysiological conditions such as chronic neuropathic pain.

How cells control gene expression is a fundamental question. The relative contribution of protein-level and RNA-level regulation to this process remains unclear. Here, we perform a proteogenomic analysis of tumors and untransformed cells containing somatic copy number alterations (SCNAs). By revealing how cells regulate RNA and protein abundances of genes with SCNAs, we provide insights into the rules of gene regulation. Protein complex genes have a strong protein-level regulation while non-complex genes have a strong RNA-level regulation. Notable exceptions are plasma membrane protein complex genes, which show a weak protein-level regulation and a stronger RNA-level regulation. Strikingly, we find a strong negative association between the degree of RNA-level and protein-level regulation across genes and cellular pathways. Moreover, genes participating in the same pathway show a similar degree of RNA- and protein-level regulation. Pathways including translation, splicing, RNA processing, and mitochondrial function show a stronger protein-level regulation while cell adhesion and migration pathways show a stronger RNA-level regulation. These results suggest that the evolution of gene regulation is shaped by functional constraints and that many cellular pathways tend to evolve one predominant mechanism of gene regulation at the protein level or at the RNA level.

New technologies are facing the market to overcome high energy costs and efficiency regulations. Among these, the use of ozone in domestic appliances has been recently proposed for a cold-water sanitizing system for clothes or even a no-water cycle to refresh clothes. Ozone is a contaminant in indoor environments and its toxicity is mainly due to the strong oxidizing action on cellular components that can reduce lung function and increase respiratory symptoms. This study illustrates a risk assessment for ozone emissions released from new domestic clothes washer/dryer during normal operation and in the case of a failure. Indoor ozone concentrations were measured, and a mass-balance model was applied, considering ozone released from the appliance during the no-water cycle and the outdoor ozone contribution. Monte Carlo analysis was used to derive the probability of exceeding the air quality standards established by the main international organizations for the protection of human health. This study indicated the most suitable ozone generator and the best refresh cycle to minimize health risks. This method can be generally used to assess the potential health risk for the indoor environment, due to the release of harmful emissions from household appliances.

The hyperinflammatory phase represents the main cause for the clinical worsening of acute respiratory distress syndrome (ARDS) in Coronavirus disease 2019 (COVID-19), leading to the hypothesis that steroid therapy could be a mainstream treatment in COVID-19 patients. This is an observational study including all consecutive patients admitted to two Italian University Hospitals for COVID-19 from March 2020 to December 2021. The aim of this study was to describe clinical characteristics and outcome parameters of hospitalized COVID-19 patients treated with dexamethasone 6 mg once daily (standard-dose group) or methylprednisolone 40 mg twice daily (high-dose group). The primary outcome was the impact of these different steroid treatments on 30-day mortality. During the study period, 990 patients were evaluated: 695 (70.2%) receiving standard dosage of dexamethasone and 295 (29.8%) receiving a high dose of methylprednisolone. Cox regression analysis showed that chronic obstructive pulmonary disease (HR 1.98, CI95% 1.34–9.81, p = 0.002), chronic kidney disease (HR 5.21, CI95% 1.48–22.23, p = 0.001), oncologic disease (HR 2.81, CI95% 1.45–19.8, p = 0.005) and high-flow nasal cannula, continuous positive airway pressure or non-invasive ventilation oxygen therapy (HR 61.1, CI95% 5.12–511.1, p < 0.001) were independently associated with 30-day mortality; conversely, high-dose steroid therapy was associated with survival (HR 0.42, CI95% 0.38–0.86, p = 0.002) at 30 days. Kaplan–Meier curves for 30-day survival displayed a statistically significant better survival rate in patients treated with high-dose steroid therapy (p = 0.018). The results of this study highlighted that the use of high-dose methylprednisolone, compared to dexamethasone 6 mg once daily, in hospitalized patients with COVID-19 may be associated with a significant reduction in mortality.

Currently used techniques for intraoperative assessment of tumor resection margins are time-consuming and laborious and, more importantly, lack specificity. Moreover, pathological diagnosis during surgery does not often give a clear outcome. Recent advances in mass spectrometry (MS) and instrumentation have made it possible to obtain detailed molecular information from tissue specimens in real-time, with minimal sample pre-treatment. Probe Electro Spray Ionization MS (PESI-MS), combined with artificial intelligence (AI), has demonstrated its effectiveness in distinguishing liver cancer tissues from healthy tissues in a large Italian population group. As the MS profile can reflect the patient’s ethnicity, dietary habits, or particular operating room procedures, the AI algorithm must be well trained to distinguish different groups. We used a large dataset composed of liver tumor and healthy specimens, from the Italian and Japanese populations, to develop a versatile algorithm free from ethnic bias. The system can classify tissues with discrepancies

Commercially available UV-adsorbent TiO2 nanoparticles were used to assist laser/desorption ionization in the course of matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Titanium nano-powders proved extremely stable and efficient for small molecule ionization, with negligible background noise in the low mass region (m/z < 500 Da). Validation steps were carried out, assessing detection limits and comparing the results to those of the established DESI/Orbitrap technique. The new analytical method was used to reveal the molecular distribution of endogenous (lipids) and exogenous (analgesics and antipyretics) compounds in latent finger marks (LFMs). The detection limits of endogenous fatty acids and small molecules such as caffeine were in the range of fmol/mm2 on LFMs. The technique separated overlapping latent finger marks, exploiting the differences in lipid expression of human skin. Finally, the method was used to prove contact between skin and objects contaminated by different substances, such as credit cards and paper clips, with chemical images that maintain the shape of the objects on the LFM.

Bitumen-related production sites are facing increasing difficulties with nearby residents due to odor emissions. This parameter is still not regulated for these plants and little is known about the emissions that these plants have put into the atmosphere with the technologies available today. In this study, emission data from 47 Italian production plants were collected and analyzed to assess which values could describe the current situation in Italy. The results of the analysis showed that emissions are very variable, with odor concentration values between 200 to 37,000 ouE/m3, but data have a normal distribution. The mean value of the stack odor concentration was found to be 2424 ouE/m3. It was also possible to calculate emission factors of the plants, such as odor emission rate (OER), which represents the quantity of odor emitted per unit of time, and is expressed in odor units per second (ouE∙s−1) and odor emission factor (OEF) per ton of product, expressed in ouE/t. The values obtained were 7.1 × 104 ouE/s and 1.4 × 106 ouE/t. respectively. These data could provide a starting point for the definition of shared values among various stakeholders for the definition of regional guidelines for the emissions of these plants, in order to adjust available technologies towards emission parameters that are protective of the surrounding environment.

ApreciseKUre is a multi-purpose digital platform facilitating data collection, integration and analysis for patients affected by Alkaptonuria (AKU), an ultra-rare autosomal recessive genetic disease. It includes genetic, biochemical, histopathological, clinical, therapeutic resources and quality of life scores that can be shared among registered researchers and clinicians in order to create a Precision Medicine Ecosystem (PME). The combination of machine learning application to analyse and re-interpret data available in the ApreciseKUre shows the potential direct benefits to achieve patient stratification and the consequent tailoring of care and treatments to a specific subgroup of patients. In this study, we have developed a tool able to investigate the most suitable treatment for AKU patients in accordance with their Quality of Life scores, which indicates changes in health status before/after the assumption of a specific class of drugs. This fact highlights the necessity of development of patient databases for rare diseases, like ApreciseKUre. We believe this is not limited to the study of AKU, but it represents a proof of principle study that could be applied to other rare diseases, allowing data management, analysis, and interpretation.

Polyamines (PAs) are essential metabolites in plants performing multiple functions during growth and development. Copper-containing amine oxidases (CuAOs) catalyse the catabolism of PAs and in Arabidopsis thaliana are encoded by a gene family. Two mutants of one gene family member, AtCuAOδ, showed delayed seed germination, leaf emergence, and flowering time. The height of the primary inflorescence shoot was reduced, and developmental leaf senescence was delayed. Siliques were significantly longer in mutant lines and contained more seeds. The phenotype of AtCuAOδ over-expressors was less affected. Before flowering, there was a significant increase in putrescine in AtCuAOδ mutant leaves compared to wild type (WT), while after flowering both spermidine and spermine concentrations were significantly higher than in WT leaves. The expression of GA (gibberellic acid) biosynthetic genes was repressed and the content of GA1, GA7, GA8, GA9, and GA20 was reduced in the mutants. The inhibitor of copper-containing amine oxidases, aminoguanidine hydrochloride, mimicked the effect of AtCuAOδ mutation on WT seed germination. Delayed germination, reduced shoot height, and delayed flowering in the mutants were rescued by GA3 treatment. These data strongly suggest AtCuAOδ is an important gene regulating PA homeostasis, and that a perturbation of PAs affects plant development through a reduction in GA biosynthesis.

This study was designed to investigate the levels of acetaldehyde residues in polyethylene terephthalate bottled water and its significance in terms of consumer health. We analyzed 104 samples collected throughout Italy, so as to be representative of the national market. Parameters such as CO2 level, shelf life, weight of the empty bottle and distance from the production sites to the point of sale were also collected. Although the levels of acetaldehyde complied with the limits established by Italian legislation, they varied widely, with concentrations ranging from 0.41 to 76.2 µg/L. An assessment of safety for human health, using the margin of exposure approach, showed that the amount of acetaldehyde in bottled water is unlikely to be of any safety concern for human health. The acetaldehyde residues were mainly due to CO2 levels which influence solubility of acetaldehyde in water. They are also related to the size of the bottle and the distance from the store, but not to the shelf life, at least for 40 days. The findings suggest some good practices for a better product from the point of view of public health, like polymer quality and limitation of transport distances.

RNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and false negatives. To ameliorate these issues, we combined information from the existing HDF screens together with new screens performed with multiple orthologous RNAi reagents (MORR). In addition to being traditionally validated, the MORR screens and the historical HDF screens were quantitatively integrated by the adaptation of an established analysis program, RIGER, for the collective interpretation of each gene’s phenotypic significance. False positives were addressed by the removal of poorly expressed candidates through gene expression filtering, as well as with GESS, which identifies off-target effects. This workflow produced a quantitatively integrated network of genes that modulate HIV-1 replication. We further investigated the roles of GOLGI49, SEC13, and COG in HIV-1 replication. Collectively, the MORR-RIGER method minimized the caveats of RNAi screening and improved our understanding of HIV-1–host cell interactions.

The Internet of Things (IoT) will bring together billions of devices, denoted as Smart Objects (SOs), in an Internet-like architecture. Typically, SOs are embedded devices with severe constraints in terms of processing capabilities, available memory (RAM/ROM), and energy consumption. SOs tend to be deployed in environments in which the human intervention is not suitable or needs to be minimized (e.g., smart city maintenance). They must adapt to the surrounding environment by self-configuring: to this end, several mechanisms have been proposed (e.g., UPnP, ZeroConf, etc.). In this paper, we focus on IEEE 802.15.4 networks with IPv6 over Low-Power Wireless Personal Area Network (6LoWPAN) adaptation layer, where IPv6 Routing Protocol for Low-Power and Lossy Networks (RPL) is the routing protocol of choice. In this context, we propose a lightweight RPL-based mechanism to Resource Discovery (RD) and Service Discovery (SD), denoted as DiRPL. In particular, DiRPL exploits the RPL handshake to detect new nodes in the network; resources are then simply discovered with a Constrained Application Protocol (CoAP) request and can thus be published in a local resource directory. A very attractive feature of the proposed DiRPL approach is that it builds on well-defined and well-known standard protocols. The performance of the proposed system is investigated with WisMote nodes deployed inside the Cooja simulator, running the Contiki operating system. Practical application scenarios to large-scale smart city monitoring, such as smart lighting and large-scale water consumption monitoring, are investigated.

Myelomeningocele (MMC) is a neural tube defect that often causes spinal cord injury at the thoracolumbar region, as well as sensory and motor paralysis in the lower limbs. This leads to continuous use of a wheelchair and, consequently, a sedentary lifestyle, predisposition to muscle weakness, cardiovascular and respiratory disorders, obesity, and structural alterations in the spine. We assessed the respiratory function and shoulder strength of MMC participants who were wheelchair-users and had no respiratory complaints and compared them to healthy children and adolescents. MMC (n=10) and healthy (n=25) participants of both genders with a mean age of 12.45 years (SD=2.1) were assessed for weight, height, respiratory performance, and isometric peak for shoulder flexors, extensors, abductors, and adductors, using an isokinetic dynamometer. Medullary lesion, functional levels, and abnormal curvatures of the spine were assessed for MMC participants. The level of spinal cord injury for the majority of the MMC participants was high lumbar and they had scoliosis. MMC showed lower values for forced vital capacity, forced expiratory volume at the first second, forced expiratory flow (25–75%), maximal voluntary ventilation, and isometric peak for shoulder flexors and adductors compared to healthy participants. This indicated a decreased vital capacity, respiratory muscle endurance, and shoulder muscle strength.