Ozone therapy for skin diseases: Cellular and molecular mechanisms.

Ozone is a highly reactive oxidant molecule consisting of triatomic oxygen atoms. Ozone therapy can be achieved using ozonated hydrotherapy, ozonated oil, ozone autohemotherapy, and other innovative dosage forms of ozone products. Ozone is frequently used as a complementary therapy for various cutaneous diseases, including infectious skin diseases, wound healing, eczema, dermatitis, psoriasis, axillary osmidrosis, diabetic foot, and pressure ulcers. In addition, several studies have reported the superior potential of ozone therapy for improving skin and gut microbiomes, as well as antitumour and antiaging treatment. Ozone therapy is an emerging treatment strategy that acts via complex mechanisms, including antioxidant effects, immunomodulatory capacity, and modulation of local microcirculation. Studies assessing the mechanism of ozone have gradually expanded in recent years. This review article aims to summarise and explore the possible molecular biological mechanisms of ozone in cutaneous diseases and provide compelling theoretical evidence for the application of ozone in cutaneous diseases.

Ozonated oil alleviates dinitrochlorobenzene-induced allergic contact dermatitis via inhibiting the FcεRI/Syk signaling pathway. / 医用臭氧油通过抑制FcεRI/Syk信号通路缓解DNCB诱导的变应性接触性皮炎（英文）.

OBJECTIVES: Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms. METHODS: Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions. RESULTS: Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1ß, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1ß, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05). CONCLUSIONS: Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.

Influence of urban spatial and socioeconomic parameters on PM2.5 at subdistrict level: A land use regression study in Shenzhen, China.

The intraurban distribution of PM2.5 concentration is influenced by various spatial, socioeconomic, and meteorological parameters. This study investigated the influence of 37 parameters on monthly average PM2.5 concentration at the subdistrict level with Pearson correlation analysis and land-use regression (LUR) using data from a subdistrict-level air pollution monitoring network in Shenzhen, China. Performance of LUR models is evaluated with leave-one-out-cross-validation (LOOCV) and holdout cross-validation (holdout CV). Pearson correlation analysis revealed that Normalized Difference Built-up Index, artificial land fraction, land surface temperature, and point-of-interest (POI) numbers of factories and industrial parks are significantly positively correlated with monthly average PM2.5 concentrations, while Normalized Difference Vegetation Index and Green View Factor show significant negative correlations. For the sparse national stations, robust LUR modelling may rely on a priori assumptions in direction of influence during the predictor selection process. The month-by-month spatial regression shows that RF models for both national stations and all stations show significantly inflated mean values of R2 compared with cross-validation results. For MLR models, inflation of both R2 and R2CV was detected when using only national stations and may indicate the restricted ability to predict spatial distribution of PM2.5 levels. Inflated within-sample R2 also exist in the spatiotemporal LUR models developed with only national stations, although not as significant as spatial LUR models. Our results suggest that a denser subdistrict level air pollutant monitoring network may improve the accuracy and robustness in intraurban spatial/spatiotemporal prediction of PM2.5 concentrations.

Scrotal Dowling-Degos disease caused by a novel frameshift variant in gamma-secretase subunit presenile enhancer gene.

We reported a Chinese pedigree with scrotal Dowling-Degos disease and evaluated the phenotypic and genotypic characteristics. In affected cases, pigmented macules were identified on the scrotum. The rashes increased, and the colour deepened progressively. No pain or pruritus were noticed, and no other skin folds were involved. Skin histopathology showed characteristic features of Dowling-Degos disease. A heterozygous PSENEN frameshift variant c.292delC（p.L98Wfs*47） was identified in affected cases. The variant was not found in dbSNP, 1000 Genomes project database and the ExAC Browser. The p.L98 and adjacent amino acids are highly conserved among species. Our cases expand the phenotypic and genotypic spectrum of PSENEN-related Dowling-Degos disease.

Water-energy-vegetation nexus explain global geographical variation in surface urban heat island intensity.

Surface urban heat island (SUHI) is a key climate risk associated with urbanization. Previous case studies have suggested that precipitation (water), radiation (energy), and vegetation have important effects on urban warming, but there is a lack of research that combines these factors to explain the global geographic variation in SUHI intensity (SUHII). Here, we utilize remotely sensed and gridded datasets to propose a new water-energy-vegetation nexus concept that explains the global geographic variation of SUHII across four climate zones and seven major regions. We found that SUHII and its frequency increase from arid zones (0.36 ± 0.15 °C) to humid zones (2.28 ± 0.10 °C), but become weaker in the extreme humid zones (2.18 ± 0.15 °C). We revealed that from semi-arid/humid to humid zones, high precipitation is often coupled with high incoming solar radiation. The increased solar radiation can directly enhance the energy in the area, leading to higher SUHII and its frequency. Although solar radiation is high in arid zones (mainly in West, Central, and South Asia), water limitation leads to sparse natural vegetation, suppressing the cooling effect in rural areas and resulting in lower SUHII. In extreme humid regions (mainly in tropical areas), incoming solar radiation tends to flatten out, which, coupled with increased vegetation as hydrothermal conditions become more favorable, leads to more latent heat and reduces the intensity of SUHI. Overall, this study offers empirical evidence that the water-energy-vegetation nexus highly explains the global geographic variation of SUHII. The results can be used by urban planners seeking optimal SUHI mitigation strategies and for climate change modeling work.

Evaluation of in vivo reflectance confocal microscopy in the diagnosis of extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that most commonly affects the apocrine glands of older men and women. Because it is associated with other cancers, early diagnosis and evaluation are needed. This study is to evaluate the value of reflectance confocal microscopy (RCM) in diagnosing EMPD. A total of 73 patients with clinically suspicious diagnosis of EMPD were enrolled in this study, and the RCM device imaged their lesions. Moreover, 67 patients underwent skin biopsies to confirm the diagnosis. We retrospectively analyzed the results of RCM and histological diagnosis and then evaluated the RCM value of biopsy-confirmed lesions. Based on the RCM image analysis, 54 of 73 (74.0%) patients were diagnosed with EMPD. Of all 67 biopsied lesions, 52 (77.6%) were EMPD. Then, we analyzed the RCM characteristics of 52 cases of biopsy-confirmed EMPD, compared their RCM image characteristics of three different lesions of EMPD, and further concluded the key points of EMPD under RCM microscopy based on the 52 EMPD cases. Finally, we focused on the differential diagnosis of EMPD from other skin diseases. RCM showed great diagnostic value in diagnosing EMPD.