Characteristic Dermatoscopic Features of Hyperpigmented Macules on the Faces of Young Children.

The aim was to describe the characteristic dermatoscopic features of hyperpigmented macules on the faces of young children. Sixteen patients with typical clinical presentations of hyperpigmented macules on the faces of young children were included in this study. The lesions were evaluated using a dermatoscope. The clinical and dermatoscopic features were analyzed and summarized. There were 12 boys and 4 girls enrolled in the study. The hyperpigmented macules had an age of onset ranging from 1 to 18 months (mean, 6.12 months). The hyperpigmentation was distributed on the forehead and/or temple, as follows: forehead (n = 8 [50%]); temple (n = 3 [18.8%]); and both sites (n = 5 [31.2%]). Fifteen patients (93.7%) had pseudoreticular pigmentation, 1 patient (6.3%) had reticular pigment with pseudoreticular pigment, and 100% had erythema and linear/branching vessels. Light brown pseudoreticular pigment and linear vessels were shown to be the 2 major dermatoscopic manifestations of hyperpigmented macules on the faces of young children.

Association between individual resilience and depression or anxiety among general adult population during COVID-19: a systematic review.

BACKGROUND: The coronavirus disease (COVID-19) pandemic exacerbated depression and anxiety worldwide. Resilience is important to maintain mental health during uncertain times, but limited study has systematically reviewed its association with depression or anxiety with an emphasis on the general population. METHODS: We searched PubMed and Embase for quantitative or mixed-methods studies on the general adult population published between 1 January 2020 and 31 April 2022 (PROSPERO ID: CRD 42022340935). National Institute of the Health quality assessment tools was used to assess the risk of bias. We qualitatively synthesized findings by outcome and study design. RESULTS: A total of 2945 studies were screened and 35 studies were included in the narrative analysis (5 on depression, 9 on anxiety, and 21 on both). Overall, 21 studies identified statistically significant inverse associations between resilience and depression, while 24 studies found statistically significant inverse associations between resilience and anxiety. Eight studies reported no statistically significant relationships between resilience with depression or anxiety. CONCLUSIONS: Resilience was found to be inversely associated with depression and anxiety during the COVID-19 pandemic. The findings highlight the importance of resilience-enhancing intervention in migrating the global mental health burden from outbreaks of infectious diseases.

Metabolomics reveals that tris(1,3-dichloro-2-propyl)phosphate (TDCPP) causes disruption of membrane lipids in microalga Scenedesmus obliquus.

Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is one of the most widely used organophosphate ester flame retardants. The presence of TDCPP in surface waters and aquatic organisms have been reported worldwide, yet the ecological risk of TDCPP on microalgae is rarely studied. We investigated the biotransformation of TDCPP and its toxicity on the microalga Scenedesmus obliquus using an untargeted metabolomics approach. Exposure to TDCPP resulted in a dose-response decrease of micoalgal biomass. In the presence of microalgae, TDCPP concentration in the media decreased by 25.3-40.6% after 5 days. TDCPP metabolites were identified in the media including hydrolysis and hydroxyl-substituted dechlorination products. A dose-response separation of metabolic profiles of microalgae was observed, with effect seen at the lowest concentration of 10 µg/L tested, which is slightly higher than environmentally relevant concentrations. Differentiated metabolites identified include 52 lipids and 6 polar metabolites. Analysis of altered lipid pathways suggests that microalgal cells reinforce thylakoid membranes (function to protect photosynthesis) by compromising the integrity of plasma membrane (function to protect cellular substances) and extraplastidial cellular membranes. Changes in the polar metabolites might indicate osmotic stress and improved NO signaling after TDCPP exposure. Consistent with perturbation of membrane lipids, further experiment confirmed that exposure to 10 mg/L TDCPP resulted in significant (p < 0.01) plasma membrane damage. This study indicates biotransformation and the membrane damage toxicity mechanism of TDCPP on S. obliquus, demonstrating the usefulness of metabolomics for the toxicity mechanism elucidation of emerging pollutants.

A global metabolomic insight into the oxidative stress and membrane damage of copper oxide nanoparticles and microparticles on microalga Chlorella vulgaris.

To compare aquatic organisms' responses to the toxicity of copper oxide (CuO) nanoparticles (NPs) with those of CuO microparticles (MPs) and copper (Cu) ions, a global metabolomics approach was employed to investigate the changes of both polar and nonpolar metabolites in microalga Chlorella vulgaris after 5-day exposure to CuO NPs and MPs (1 and 10 mg/L), as well as the corresponding dissolved Cu ions (0.08 and 0.8 mg/L). Unchanged growth, slight reactive oxygen species production, and significant membrane damage (at 10 mg/L CuO particles) in C. vulgaris were demonstrated. A total of 75 differentiated metabolites were identified. Most metabolic pathways perturbed after CuO NPs exposure were shared by those after CuO MPs and Cu ions exposure, including accumulation of chlorophyll intermediates (max. 2.4-5.2 fold), membrane lipids remodeling for membrane protection (decrease of phosphatidylethanolamines (min. 0.6 fold) and phosphatidylcholines (min. 0.2-0.7 fold), as well as increase of phosphatidic acids (max. 1.5-2.9 fold), phosphatidylglycerols (max. 2.2-2.3 fold), monogalactosyldiacylglycerols (max. 1.2-1.4 fold), digalactosylmonoacylglycerols (max. 1.9-3.8 fold), diacylglycerols (max. 1.4 fold), lysophospholipids (max. 1.8-3.0 fold), and fatty acids (max. 3.0-6.2 fold)), perturbation of glutathione metabolism induced by oxidative stress, and accumulation of osmoregulants (max. 1.3-2.6 fold) to counteract osmotic stress. The only difference between metabolic responses to particles and those to ions was the accumulation of fatty acids oxidation products: particles caused higher fold changes (particles/ions ratio 1.9-3.0) at 1 mg/L and lower fold changes (particles/ions ratio 0.4-0.7) at 10 mg/L compared with ions. Compared with microparticles, there was no nanoparticle-specific pathway perturbed. These results confirm the predominant role of dissolved Cu ions on the toxicity of CuO NPs and MPs, and also reveal particle-specific toxicity from a metabolomics perspective.

Uptake and toxic effects of triphenyl phosphate on freshwater microalgae Chlorella vulgaris and Scenedesmus obliquus: Insights from untargeted metabolomics.

The flame retardant triphenyl phosphate (TPhP) has been widely detected in surface waters. Yet, little information is known regarding its impact on microalgae. We investigated the uptake and toxicity of TPhP on two freshwater microalgae Chlorella vulgaris (CV) and Scenedesmus obliquus (SO) after exposure to 10 µg/l-10 mg/l for 5 days. The presence of microalgae significantly enhanced TPhP degradation, with the final concentrations dropped to 5.5-35.1% of the original concentrations. Most of the medium TPhP were sorbed and transformed by microalgae in just one day. Growth of CV was inhibited in a concentration-dependent manner, whereas growth of SO were only inhibited significantly at 10 mg/l TPhP exposure. Mass spectrometry-based untargeted metabolomics revealed concentration- and species-dependent metabolic responses. Exposure to TPhP in CV resulted in enhanced respiration (increase of fumarate and malate) and osmoregulation (increase of sucrose and myo-inositol), synthesis of membrane lipids (accumulation of monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), decrease of lysoglycerolipids, fatty acids, and glyceryl-glucoside). Exposure to TPhP in SO resulted in enhanced osmoregulation (increase of valine, proline, and raffinose) and lipolysis (decrease of MGDG, accumulation of fatty acids, lysophospholipids, and glycerol phosphate). Although chlorophyll a and b contents did not change significantly, decrease of chlorophyll derivatives was observed in both CV and SO at high exposure concentrations. Further bioassays confirmed that CV exhibited enhanced membrane integrity and decreased cellular reactive oxygen species (ROS) possibly as a defense strategy, whereas SO showed disruption of membrane integrity and induction of ROS at 10 mg/l exposure. This study demonstrated the potential of microalgae to remove TPhP in water, and offered new insights for the risk assessment of TPhP on freshwater microalgae using metabolomics.

Untargeted metabolomics reveals transformation pathways and metabolic response of the earthworm Perionyx excavatus after exposure to triphenyl phosphate.

Triphenyl phosphate (TPHP) is one of the most highly utilized organophosphorus flame retardants, and has been frequently detected in various environmental matrices, including soil. So far, limited information is known regarding the potential toxicity of TPHP to the earthworm-soil ecosystem. We investigated the metabolism of TPHP and the perturbation of the endogenous metabolome in the earthworm, Perionyx excavatus, using gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole time-of-flight (LC-QTOF)-based untargeted metabolomics approach after acute exposure to TPHP for one and two days through a filter paper contact test, as well as after chronic exposure for 28 days in a soil microcosm experiment. TPHP showed low bioaccumulation potential in the earthworm-soil ecosystem at concentrations of 10 mg/kg and 50 mg/kg. Identified phase I metabolites include diphenyl phosphate, mono-hydroxylated and di-hydroxylated TPHP. Two groups of phase II metabolites, thiol conjugates (including mercaptolactic acid, cysteine, cysteinylglycine, and mercaptoethanol conjugates) and glucoside conjugates (including glucoside, glucoside-phosphate, and C14H19O10P conjugates), were putatively identified. Only acute TPHP exposure caused significant perturbations of the endogenous metabolome in earthworms, featuring fluctuations in amino acids, glucose, inosine and phospholipids. These results reveal novel phase II metabolism and toxicity of TPHP in P. excavatus.

Metabolism of tri-n-butyl phosphate in earthworm Perionyx excavatus.

Tri-n-butyl phosphate (TBP) is widely used in various industrial processes and has been detected in all environmental matrices. So far, little work has been done regarding the metabolism of TBP on terrestrial invertebrates. We investigated the metabolism of TBP in the earthworm, Perionyx excavatus, after acute exposure to TBP for one and two days in filter paper contact test, as well as after chronic exposure for 28 days in soil experiment. Biotransformation products were identified by using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, and by exploiting the information dependent acquisition in tandem mass spectrometry. TBP exhibited low accumulation in earthworm-soil ecosystem at 10 mg/kg and 50 mg/kg. The presence of earthworms significantly enhanced TBP degradation at 50 mg/kg in soil. Dibutyl phosphate and hydroxylated TBP were the major phase I metabolites. Three novel phase II metabolites were identified: ethanol dibutyl phosphate and its sulfate conjugate, and the phosphate conjugate of hydroxylated TBP. Hydroxylation and further phosphorylation dominated metabolism in chronic exposure. An extensive metabolic pathway of TBP in earthworm was proposed. This is the first report of TBP metabolism in terrestrial invertebrates and highlights the necessity to identify metabolites of contaminants when evaluating their bioaccumulation and toxicity.

Correlations in the elemental and metabolic profiles of the lichen Dirinaria picta after road traffic exposure.

Lichens can be used as cost-effective biomonitors of elements from road traffic in the urban environment. However, the nature of comprehensive interactions between hazardous heavy metals from road traffic and lichen metabolites remains unclear. In this study, elemental and metabolic profiles of the lichen Dirinaria picta after exposure to road traffic for 3 months in 9 sites of Singapore city were investigated. Concentrations of 34 elements reveal strong correlations among each other and a general increase with traffic exposure level. A variety of metabolites, i.e. sugar alcohols, sugars, amino acids, low-molecular mass organic acids, secondary metabolites and nucleosides, are identified through a multi-platform approach combining liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS), gas chromatography quadrupole mass spectrometry (GC-Q/MS) and 1H nuclear magnetic resonance (1H NMR). The total amount of the heavy metals Fe, Zn, Cu, Cd, Pb and Co can be significantly correlated with 21 metabolites positively and 9 metabolites negatively. These correlations reveal a heavy metal detoxification mechanism through ROS scavenging, osmoregulation and chelation with N atoms and sulfhydryl groups, as well as depletion of arabitol and inhibited synthesis of certain secondary metabolites such as quinones and steroids due to heavy metal stress. This study provides new insights into the metabolic toxicity and detoxification mechanisms in lichens under heavy metal exposure.

(1)H nuclear magnetic resonance-based metabolomics study of earthworm Perionyx excavatus in vermifiltration process.

In this study, (1)H nuclear magnetic resonance (NMR)-based metabolomics approach was used to characterize the metabolic response of the earthworm Perionyx excavatus in continuous vermifiltration for two months under hydraulic loading rates of 1m(3)m(-2)d(-1) (VF1) and 1.5m(3)m(-2)d(-1) (VF1.5). Both VF1 and VF1.5 showed higher removal of chemical oxygen demand and total nitrogen than the biofilter without earthworms. Principal component analysis of the NMR spectra of earthworm metabolites showed significant separations between those not subjected to wastewater filtration (control) and VF1 or VF1.5. Temporal variations of earthworm biomass, and the identified metabolites that are significantly different between control, VF1 and VF1.5 revealed that worms underwent increasing metabolic activity within 20days in VF1 and 14days in VF1.5, then decreasing metabolic activity. The use of NMR-based metabolomics in monitoring earthworm metabolism was demonstrated to be a novel approach in studying engineered vermifiltration systems.

CCL5, CXCL16, and CX3CL1 are associated with Henoch-Schonlein purpura.

Chemokines are involved in the pathogenesis of various vascular inflammations. However, information about chemokines in Henoch-Schonlein purpura (HSP) is limited. Herein, we investigated the serum CCL5, CXCL16, and CX3CL1 levels in HSP patients with controls and the ability of sera from HSP patients on chemokine production in human dermal microvascular endothelial cells. Enzyme-linked immunosorbent assay (ELISA) detected serum CCL5, CXCL16, and CX3CL1 levels in patients with HSP. Human dermal microvascular endothelial cell line (HMEC-1) was treated with sera from patients with HSP at different stages, patients with acute spontaneous urticaria, or controls. Serum levels of CCL5, CXCL16, and CX3CL1 were elevated in HSP patients at acute stage, which correlated with the severity of this disease. Sera from patients with active HSP markedly induced CCL5, CXCL16, and CX3CL1 production at both mRNA and protein levels. In addition, patients' sera-stimulated HMEC-1 supernatants enhanced HL-60 or THP-1 cells migration. Furthermore, patients' sera increased the phosphorylation of inhibitor of κB-α (IκBα) and phosphorylation of extracellular signal-regulated kinase (ERK)1/2 protein levels, upregulated the translocation of nuclear factor-κB (NF-κB) p65 to the nucleus. Taken together, we show firstly that CCL5, CXCL16, and CX3CL1 may be involved in the pathogenesis of HSP. Factors present in sera from patients with active HSP may act as an inducer of inflammatory response in HMEC-1 cells and contribute to chemokine production through NF-κB and ERK 1/2 pathways.

Peoniflorin suppresses tumor necrosis factor-α induced chemokine production in human dermal microvascular endothelial cells by blocking nuclear factor-κB and ERK pathway.

Peoniflorin (PF) extracted from the root of Paeonia lactiflora pall displays anti-inflammation and antioxidant properties in several animal models. Chemokines are vital for directing the movement of circulating leukocytes to the sites of inflammation and are involved in the pathogenesis of various inflammatory skin diseases. Herein, we investigated the effects and potential mechanisms of PF on tumor necrosis factor-α (TNF-α) induced chemokine production in human dermal microvascular endothelial cells. Human dermal microvascular endothelial cell line (HMEC-1) was treated by TNF-α with or without PF. PF markedly attenuated TNF-α-induced chemokines (including CCL2, CCL5, CCL20, CXCL8, CXCL16 and CX3CL1) mRNA expression in HMEC-1. PF also reduced the secretion of these chemokines in culture supernatants. In addition, endothelial activation in the presence of PF markedly blocked the chemotactic activities of TNF-α-stimulated HMEC-1 supernatant on promyelocytic leukemia cell line (HL-60) or the acute mature monocytic leukemia cell line (THP-1) cell migration. Furthermore, Western blot data revealed TNF-α upregulated phosphorylation of inhibitor of κB-α (IκBα) and phosphorylation of extracellular signal-regulated kinase (ERK)1/2, which was almost completely reversed by PF. Finally, PF inhibited nuclear factor-κB (NF-κB) nuclear translocation to the nucleus. Taken together, our data provide the first evidence that PF has an anti-inflammatory ability against TNF-α-induced chemokine production and leukocyte migration, which may be at least partly related to the inhibition of NF-κB and ERK pathway. PF may be a candidate medicine for the treatment of inflammatory skin diseases.