Postbiotic of Pediococcus acidilactici GQ01, a Novel Probiotic Strain Isolated from Natural Fermented Wolfberry, Attenuates Hyperuricaemia in Mice through Modulating Uric Acid Metabolism and Gut Microbiota.

Hyperuricaemia (HUA) is a disorder of purine metabolism, which manifests itself as an increase in uric acid production and a decrease in uric acid excretion, as well as a change in the structure of the intestinal microbiota. Most of the drugs currently used to treat HUA have significant side effects, and it is essential to find a treatment for HUA that is free of side effects. In this study, a novel strain, Pediococcus acidilactici GQ01, was screened from natural fermented wolfberry. The effects of both live bacteria GQ01 and its heat-killed G1PB postbiotic on HUA were investigated. The results showed that both probiotic GQ01 and G1PB postbiotics could effectively decrease blood uric acid, creatinine, and urea nitrogen levels in the HUA mice model. P. acidilactici GQ01 was more effective in inhibiting ADA activity, while G1PB postbiotics was more effective in inhibiting XOD activity. Meanwhile, GQ01 and G1PB were able to ameliorate liver and kidney tissue injury, upregulate the expression of ABCG2 in kidney and XOD gene in liver, downregulate the protein expression of URAT1 and GLUT9 in kidney, and therefore reduce the value of blood uric acid by decreasing the uric acid reabsorption and increasing the excretion of uric acid. Additionally, both probiotics and postbiotics could regulate the intestinal microbiota structure of HUA mice, so as to bring the dysfunctional intestinal composition back to normal. Furthermore, P. acidilactici GQ01 and G1PB postbiotics can increase the levels of acetic acid, propionic acid, and butyric acid in the intestinal tract, improve the intestinal function, and maintain the healthy homeostatic state of the intestinal tract. In summary, P. acidilactici GQ01 and its G1PB postbiotics may be developed as functional food or drug materials capable of treating HUA.

Propionate alleviates itch in murine models of atopic dermatitis by modulating sensory TRP channels of dorsal root ganglion.

BACKGROUND: Itch is the most common symptom of atopic dermatitis (AD) and significantly decreases the quality of life. Skin microbiome is involved in AD pathogenesis, whereas its role in the regulation of itch remains elusive. In this study, we aimed to investigate the effects of skin microbial metabolite propionate on acute and chronic pruritus and to explore the mechanism. METHODS: Using various mouse models of itch, the roles of propionate were explored by behavioral tests and histopathology/immunofluorescent analysis. Primary-cultured dorsal root ganglion neurons and HEK293 cells expressing recombinant human TRP channels were utilized for in vitro calcium imaging/in vivo miniature two-photon imaging in combination with electrophysiology and molecular docking approaches for investigation of the mechanism. RESULTS: Propionate significantly alleviated itch and alloknesis in various mouse models of pruritus and AD and decreased the density of intraepidermal nerve fibers. Propionate reduced the responsiveness of dorsal root ganglion neurons to pruritogens in vitro, attenuated the hyper-excitability in sensory neurons in MC903-induced AD model, and inhibited capsaicin-evoked hTRPV1 currents (IC50 = 20.08 ± 1.11 µM) via interacting with the vanilloid binding site. Propionate also decreased the secretion of calcitonin gene-related peptide by nerves in MC903-induced AD mouse model, which further attenuated itch and skin inflammation. CONCLUSION: Our study revealed a protective effect of propionate against persistent itch through direct modulation of sensory TRP channels and neuropeptide production in neurons. Regulation of itch via the skin microbiome might be a novel strategy for the treatment of AD.

Causal associations between circulation ß-carotene and cardiovascular disease: A Mendelian randomization study.

The causal association between circulating ß-carotene concentrations and cardiovascular disease (CVD) remains controversial. We conducted a Mendelian randomization study to explore the effects of ß-carotene on various cardiovascular diseases, including myocardial infarction, atrial fibrillation, heart failure, and stroke. Three single nucleotide polymorphisms (SNPs) associated with the ß-carotene levels were obtained by searching published data and used as instrumental variables. Genetic association estimates for 4 CVDs (including myocardial infarction, atrial fibrillation, heart failure, and stroke) in the primary analysis, blood pressure and serum lipids (high-density lipoprotein [HDL] cholesterol, LDL cholesterol, and triglycerides) in the secondary analysis were obtained from large-scale genome-wide association studies (GWASs). We applied inverse variance-weighted as the primary analysis method, and 3 others were used to verify as sensitivity analysis. Genetically predicted circulating ß-carotene levels (natural log-transformed, µg/L) were positively associated with myocardial infarction (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.18, P = .011) after Bonferroni correction. No evidence supported the causal effect of ß-carotene on atrial fibrillation (OR 1.02, 95% CI 0.96-1.09, P = .464), heart failure (OR 1.07, 95% CI 0.97-1.19, P = .187), stroke (OR 1.03, 95% CI 0.93-1.15, P = .540), blood pressure (P > .372) and serum lipids (P > .239). Sensitivity analysis produced consistent results. This study provides evidence for a causal relationship between circulating ß-carotene and myocardial infarction. These findings have important implications for understanding the role of ß-carotene in CVD and may inform dietary recommendations and intervention strategies for preventing myocardial infarction.

A case of junctional epidermolysis bullosa intermediate with collagen XVII deficiency treated with dupilumab.

Inherited epidermolysis bullosa is a heterogeneous group of hereditary skin diseases characterized by skin (mucosa) fragility, which leads to blistering. Junctional epidermolysis bullosa is associated with mutations in genes expressing proteins of the dermo-epidermal junction. Dupilumab, an antibody that directly targets interleukin (IL)-4 receptor alpha, may be an effective treatment for dystrophic epidermolysis bullosa. We describe a case of junctional epidermolysis bullosa that improved with dupilumab.

A single-center, randomized, controlled study on the efficacy of niacinamide-containing body emollients combined with cleansing gel in the treatment of mild atopic dermatitis.

OBJECTIVE: To observe the effect of niacinamide-containing body emollients combined with a cleansing gel on the clinical symptoms of mild atopic dermatitis (AD) in adults. METHODS: From July 2022 to January 2023, adults with mild AD were enrolled at Huashan Hospital Affiliated to Fudan University using single-center, randomized and placebo-controlled methods. They were divided into three groups: the control group, treatment group 1 (T1) receiving niacinamide-containing body emollients alone, and treatment group 2 (T2) receiving emollients plus niacinamide-containing cleansing gel. All patients were orally administered 10 mg of ebastine tablets daily. AD severity (SCORAD score), peak pruritus numeric rating scale (PP-NRS), patient-oriented measure of eczema (POEM), dermatological quality of life index (DLQI) score, transepidermal water loss (TEWL), and stratum corneum water content (SCWC) were measured by the same dermatologist at days 0, 7, 14, and 28. RESULTS: A total of 122 patients were enrolled, including 38 in the control group, 42 in the T1 group and 42 in the T2 group. There were no obvious adverse reactions at the end of the study and the clinical scores and stratum corneum barrier of all the groups improved significantly relative to baseline. The SCORAD, PP-NRS, DLQI, TEWL and SCWC scores in T1 group (12.43 ± 3, 3.3 ± 0.9, 7.1 ± 2.33, 17.1 ± 9.12, 67.2 ± 21.46, seperately) and T2 group (11.17 ± 3.26, 3 ± 1.3, 6.5 ± 2.11, 16.3 ± 9.12, 69.4 ± 24.52, seperately) were significantly improved than the control group(15.1 ± 3.64, 4.3 ± 1.7, 9.5 ± 2.46, 21.2 ± 9.47, 52.7 ± 22.43, seperately) at the endpoint of the study, while compared the POEM scores, only T2 group showed the difference with control group (5.2 ± 1.4 vs. 6 ± 1.6). The epidermal barrier parameters of TEWL and SCWC in the T2 group (17.57 ± 5.24, 66.46 ± 21.38, seperately) were significantly better than that of the T1 (19.96 ± 4.45, 56.45 ± 20.48, seperately) and control group(21.89 ± 7.03, 51.56 ± 16.58, seperately) on the 14th day of follow-up. CONCLUSION: The use of niacinamide-containing body emollients can significantly improve the clinical symptoms, quality of life, and skin barrier function in patients with mild AD. The addition of niacinamide-containing cleansing gel can also affect the clinical efficacy at certain time points.

Inosine 5'- monophosphate derived umami taste intensity of beef determination by electrochemistry and chromatography.

The umami sensation contributes to beef taste and acceptability. Inosine 5'- monophosphate (IMP), the most abundant 5'-ribonucleotide in meat, is known to impart an umami taste without the undesired side effects commonly associated with glutamate. Nevertheless, the investigation of IMP's role in beef flavor has thus far been overlooked. Traditional methods for detecting IMP have relied on liquid chromatography coupled with ultraviolet spectroscopy or mass spectrometry techniques. However, these methods are not practical for production settings due to the complexity and resource demands of sophisticated laboratory techniques. Alternative methods like cyclic voltammetry might offer more practical solutions for rapidly detecting IMP. The objectives of this study were to evaluate the efficiency of using electrochemistry and chromatography on differentiating beef strips spiked with different IMP contents. The IMP threshold was 0.30 mM determined by a trained panel using the Best Estimates Threshold method. Beef strip steaks of USDA Prime, Choice, and Select were spiked at 0.30 and 0.60 mM of IMP, based on green weight and an estimated moisture content of 65%. In this study, differences in the IMP content of steaks were not detected by liquid chromatography-mass spectrometry. However, the cyclic voltammetry approach differentiated IMP concentrations at 0.50 mM or above in aqueous solutions and subsequentially meat extracts from the buffered blank solutions. In conclusion, cyclic voltammetry holds potential as a rapid and effective approach for detecting IMP in beef and other meat products, offering promising applications for future research.

Updated skin transcriptomic atlas depicted by reciprocal contribution of single-nucleus RNA sequencing and single-cell RNA sequencing.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of skin biology, but its utility is restricted by the requirement of fresh samples, inadequate dissociation-induced cell loss or death, and activation during tissue digestion. Single-nucleus RNA sequencing (snRNA-seq) can use frozen, hard-to-dissociate materials, which might be a promising method to circumvent the limitations of scRNA-seq for the skin tissue. OBJECTIVE: To profile skin cells using snRNA-seq in parallel with scRNA-seq. METHODS: We performed snRNA-seq in parallel with scRNA-seq for the bisected skin sample of one person and integrated previously published scRNA-seq data for analysis. We comparatively analyzed the differences in cell proportions and gene expression between the two methods. The differentiation trajectories of keratinocytes and fibroblasts were analyzed by Slingshot analysis. RESULTS: snRNA-seq was less susceptible to contamination from mitochondrial and ribosomal RNA, and exhibited a greater capacity to detect transcription factors. snRNA-seq identified more spatially and functionally relevant keratinocyte clusters that constitute cell trajectories with expected differentiation dynamics. Novel markers, e.g., LYPD3, EMP2, and CSTB, were revealed for different differentiation stages of keratinocytes, and NFIB and GRHL1 were identified as transcription factors involving in the proliferation and functional differentiation of keratinocytes. Fibroblasts were found in a state of activation in scRNA-seq. And scRNA-seq detected a greater number of immune cells. CONCLUSIONS: We generated an updated atlas of the skin transcriptome based on the reciprocal contribution of scRNA-seq and snRNA-seq.

Peripheral blood mononuclear cell- transcriptome signatures of atopic dermatitis and prediction for the efficacy of dupilumab.

BACKGROUND: Few studies have explored transcriptome of the peripheral blood mononuclear cells (PBMCs) of atopic dermatitis (AD). Parameters for prediction of the efficacy of dupilumab in AD remain obscure. OBJECTIVE: To explore transcriptome signature of the PBMCs from Chinese AD patients and the usage in predication for the efficacy of dupilumab. METHODS: A total of 56 moderate-to-severe adult AD patients were enrolled and followed up for 16 week-dupilumab treatment. PBMCs samples were collected at baseline and 16 weeks after dupilumab treatment. Thirty-five patients were subjected to RNA-sequencing. Weighted gene co-expression network analysis (WGCNA) was used to find genes for prediction of dupilumab efficacy, which was validated in the rest 21 AD patients. Another 30 healthy individuals were enrolled and subjected to RNA-sequencing as healthy controls. RESULTS: Upregulation of the T helper (Th) 2/Th22 pathway, Th17 antimicrobial genes, and natural T-regulatory cell abundance in the PBMCs of AD cases was observed, whereas TGF-ß signaling and NK-cell signaling were decreased. Dupilumab treatment reversed the increase in the expression of Th2 cytokine receptors. WGCNA identified two immune-related modules that were correlated significantly with the efficacy of dupilumab. Hub gene MAP2K3 and UBE2L3 of these two modules demonstrated potential predictive ability for efficacy in the RNA-sequencing group by Spearman correlation, ROC analysis, and regression analysis, which was further validated in additional 21 AD cases. CONCLUSION: We firstly revealed the molecular phenotype of PBMCs in Chinese patients with AD, and uncovered two molecules that might be useful for prediction of the efficacy of dupilumab.

Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans.

BACKGROUND: Metabolic biomarkers are reported to be associated with the risk of lung cancer (LC). However, the observed associations from epidemiological studies are either inconsistent or inconclusive. METHODS: The genetic summary data of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) and those of the LC and its histological subtypes were retrieved from previous GWASs. We performed two-sample Mendelian randomization (MR) and multivariable MR analyses to examine the associations between genetically predicted metabolic biomarkers and LC in East Asians and Europeans. RESULTS: In East Asians, the inverse-variance weighted (IVW) method suggests that LDL (odds ratio [OR] = 0.799, 95% CI 0.712-0.897), TC (OR = 0.713, 95% CI 0.638-0.797), and TG (OR = 0.702, 95% CI 0.613-0.804) were significantly associated with LC after correction for multiple testing. For the remaining three biomarkers, we did not detect significant association with LC by any MR method. Multivariable MR (MVMR) analysis yielded an OR of 0.958 (95% CI 0.748-1.172) for HDL, 0.839 (95% CI 0.738-0.931) for LDL, 0.942 (95% CI 0.742-1.133) for TC, 1.161 (95% CI 1.070-1.252) for TG, 1.079 (95% CI 0.851-1.219) for FPG, and 1.101 (95% CI 0.922-1.191) for HbA1c. In Europeans, the univariate MR analyses did not detect significant association between exposures and outcomes. However, in MVMR analysis integrating circulating lipids and lifestyle risk factors (smoking, alcohol drinking, and body mass index), we found that TG was positively associated with LC in Europeans (OR = 1.660, 95% CI 1.060-2.260). Subgroup and sensitivity analysis yielded similar results to the main analyses. CONCLUSIONS: Our study provides genetic evidence that circulating levels of LDL was negatively associated with LC in East Asians, whereas TG was positively associated with LC in both populations.

Deforming lanthanum trihydride for superionic conduction.

With strong reducibility and high redox potential, the hydride ion (H-) is a reactive hydrogen species and an energy carrier. Materials that conduct pure H- at ambient conditions will be enablers of advanced clean energy storage and electrochemical conversion technologies1,2. However, rare earth trihydrides, known for fast H migration, also exhibit detrimental electronic conductivity3-5. Here we show that by creating nanosized grains and defects in the lattice, the electronic conductivity of LaHx can be suppressed by more than five orders of magnitude. This transforms LaHx to a superionic conductor at -40 °C with a record high H- conductivity of 1.0 × 10-2 S cm-1 and a low diffusion barrier of 0.12 eV. A room-temperature all-solid-state hydride cell is demonstrated.

Massive Pelvic Hematoma After Atrial Septal Defect Closure Via Femoral Vein Cannulation.

We report a rare case of pelvic hematoma caused by iatrogenic external iliac artery hemorrhage following transfemoral venipuncture for atrial septal defect closure. By means of urgent femoral arteriography, bleeding in the branches of the external iliac artery was confirmed and occlusion of the bleeding branches was performed, thus avoiding the need for surgical laparotomy. The patient recovered well, and the hematoma significantly was reduced 2 months after surgery.

Cascade Synthesis of Benzotriazulene with Three Embedded Azulene Units and Large Stokes Shifts.

We report here the one-pot synthesis of benzo[1,2-a : 3,4-a' : 5,6-a'']triazulene (BTA), wherein three azulene units are embedded through a tandem reaction comprising two steps, Suzuki coupling and Knoevenagel condensation, between a readily available triborylated truxene precursor and 8-bromo-1-naphthaldehyde. Its nitration leads to a regioselective trinitrated product, namely, BTA-NO2 . Single-crystal X-ray crystallography revealed that the superstructure of BTA consists of a dimer stacked by two enantiomeric helicene conformers, while that of BTA-NO2 consists of an unprecedented π-tetramer stacked from two enantiomeric dimers, that is, four distinct helicene conformers. Both compounds show excellent stability and fluorescence with large Stokes shifts of up to 5100 cm-1 . In addition, BTA-NO2 exhibits a unique solvatochromic effect in different solvents and hydrogen-bonding-induced emission transfer in different ratios of THF/H2 O solutions.

Serum biomarker-based endotypes of atopic dermatitis in China and prediction for efficacy of dupilumab.

BACKGROUND: Atopic dermatitis (AD) is a highly heterogeneous disease clinically and biologically. Serum biomarkers have been utilized for endotype identification and have the potential to be predictors for treatment. OBJECTIVES: To explore the serum biomarker-based endotypes of Chinese patients with AD and to identify biomarkers for prediction of the efficacy of dupilumab. METHODS: Sera from 125 patients with moderate-to-severe AD and 60 normal controls (NC) were analysed for 24 cytokines/chemokines using the magnetic Luminex assay. After the patients received 16 weeks of dupilumab treatment, the efficacy was evaluated, and blood eosinophils, serum immunoglobulin (Ig) E and biomarkers were measured. RESULTS: Chinese patients with moderate-to-severe AD were characterized by T-helper (Th)2-dominant serum biomarkers that were mixed with differentially increased Th1-, Th17- and Th22-type cytokines/chemokines, and it was mainly Th2-type serum biomarkers that were positively correlated with disease severity and eosinophil counts. Adult (but not adolescent or elderly) patients with AD showed a consistent and more significant increase of biomarkers across different types of inflammation. The patients were grouped into two clusters by unsupervised k-means analysis, which were differentially associated with inflammation. Treatment with dupilumab decreased the levels of most cytokines/chemokines analysed. While there was no difference between the two clusters in the efficacy of dupilumab, baseline levels of CD25/soluble interleukin (sIL)-2Rα, IL-31 and IL-36ß were identified as predictive factors associated with the efficacy. CONCLUSIONS: Our study revealed two inflammation-related endotypes of Chinese patients with AD based on serum biomarkers. High levels of CD25/sIL-2Rα, IL-31 and IL-36ß might predict good efficacy of dupilumab treatment.

Cancer cells resistant to immune checkpoint blockade acquire interferon-associated epigenetic memory to sustain T cell dysfunction.

Prolonged interferon (IFN) signaling in cancer cells can promote resistance to immune checkpoint blockade (ICB). How cancer cells retain effects of prolonged IFN stimulation to coordinate resistance is unclear. We show that, across human and/or mouse tumors, immune dysfunction is associated with cancer cells acquiring epigenetic features of inflammatory memory. Here, inflammatory memory domains, many of which are initiated by chronic IFN-γ, are maintained by signal transducer and activator of transcription (STAT)1 and IFN regulatory factor (IRF)3 and link histone 3 lysine 4 monomethylation (H3K4me1)-marked chromatin accessibility to increased expression of a subset of IFN-stimulated genes (ISGs). These ISGs include the RNA sensor OAS1 that amplifies type I IFN (IFN-I) and immune inhibitory genes. Abrogating cancer cell IFN-I signaling restores anti-programmed cell death protein 1 (PD1) response by increasing IFN-γ in immune cells, promoting dendritic cell and CD8+ T cell interactions, and expanding T cells toward effector-like states rather than exhausted states. Thus, cancer cells acquire inflammatory memory to augment a subset of ISGs that promote and predict IFN-driven immune dysfunction.

Validation of diagnostic criteria for atopic dermatitis and proposal of novel diagnostic criteria for adult and elderly Chinese populations: a multicentre, prospective, clinical setting-based study.

BACKGROUND: A previous validation study showed a very low sensitivity and higher specificity associated with Hanifin and Rajka criteria (H&R) and the UK Working Party criteria (UKWP) in diagnosing AD vs. the Chinese criteria of atopic dermatitis (AD) for children (CCAD). However, their diagnostic efficacy in adult and elderly Chinese populations remains unknown. OBJECTIVES: To validate the diagnostic efficacy of three sets of AD criteria in adult and elderly Chinese populations in a hospital setting. METHODS: A total of 1034 patients (aged 19-95 years) from five university hospital dermatological clinics were recruited. Medical history, dermatological examination, AD diagnosis and evaluation of AD severity were done by dermatologists. Each patient was investigated by two dermatologist panels, one to establish a clinical diagnosis, and the other to identify and record the major or minor signs of H&R criteria, UKWP criteria and CCAD. Taking clinical diagnosis as the reference, the diagnostic efficacy of three sets of diagnostic criteria was evaluated. The χ2 test or rank sum test were used for between-groups comparisons. RESULTS: CCAD had a higher sensitivity (84.0%), especially among mild and moderate cases of AD (72.7% and 90.3%, respectively), than the H&R (58.0%; P < 0.001) and UKWP criteria (56.0%; P < 0.001) in diagnosing AD. The specificity of CCAD (92.7%) was slightly lower than the H&R (97.3%; P < 0.001) or UKWP criteria (97.4%; P < 0.001). The CCAD had the highest Youden index (0.77), accuracy rate (0.90) and Kappa value (0.76) of the three sets of diagnostic criteria. CONCLUSIONS: Consistent with results in a population of Chinese children, although the H&R and UKWP criteria had a high specificity for diagnosing AD, their low sensitivity limited their use in adult and elderly Chinese patients. Based on the high sensitivity and favourable diagnostic efficacy, the CCAD is proposed for AD diagnosis in adult and elderly Chinese populations, especially for cases of mild and moderate AD.

Detection of skin thickness and density in healthy Chinese people by using high-frequency ultrasound.

OBJECTIVES: Due to a recent development of high-frequency ultrasound (HFUS) systems, it is easier to realize high-resolution in vivo imaging of the biological tissues. The object of this study was to map the thickness and echo density of skin layers in healthy Chinese people and assess the influence of gender, age, and region on it. METHODS: A total of 189 volunteers (85 male, 104 female) with age range of 22-75-year old (mean age of 41.2-year old) were enrolled. The thickness and density of the epidermis and dermis layer were detected by high-frequency (22 or 75 MHz) ultrasonography at 13 different anatomical sites, including the forehead, cheeks, flexor and extensor forearms, flexor and extensor upper arms, inner and outer legs, inner and outer thighs, back, and abdomen. RESULTS: The thickness and density of epidermis/dermis between different anatomical sites were statistically significant (p < 0.05). The epidermis thickness of the face and trunk were less than that of the limbs, whereas the thicknesses of the dermis were on the contrary. The density of the epidermis/dermis of the face and trunk were less than that of the limbs. The thickness of dermis in most of the sites were higher in male than in female, and the density of epidermis and dermis in most of the sites were less in men than in women. The thicknesses/densities of dermis were lower in older age group in almost all sites, whereas only several sites reached statistical. The difference between the north and south regions showed the environment also influenced the thickness and density of the skin. CONCLUSION: HFUS provides a simple noninvasive method for evaluating the skin thickness and echo-density, which, reflecting intradermal structure, exhibit systematic regional variation. With the establishment of Chinese phenotypic database of skin thickness and density, it will be helpful for the skin disease assessment, skin surgery, and cosmetology technology.

Dysregulated lipidome of sebum in patients with atopic dermatitis.

BACKGROUND: Lipids are the major components of skin barrier, mainly produced by keratinocytes and sebaceous glands. Previous studies on barrier dysfunction of atopic dermatitis (AD) mainly focus on the lipids from keratinocytes, whereas the role of sebaceous gland-derived lipids in AD has long been underrecognized. METHODS: The sebum secreted on the skin surface of AD patients was measured using the Delfin Sebum Scale. Sebum was collected using Sebutape patches and subjected for liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis. Multivariate data analysis was applied to explore the relationship among the lipidome, clinical features, and sebaceous gland-related molecules. RESULTS: The amount of sebum secreted from sebaceous glands was decreased in AD patients and was negatively correlated with the barrier function and disease severity. LC-MS/MS revealed the lipidome of sebum, which clustered distinctly between AD patients and healthy individuals. Among the differential lipid subclasses, triglycerides (TG) were exclusively decreased in AD patients and correlated with disease severity. The first principal component scores of AD patients, which represented the main signature of the lipidome, were positively correlated with the SCORAD scores and were significantly different across the patient groups with differential clinical symptoms such as skin dryness and pruritus. Further analysis on the previously published transcriptome data revealed aberrant expression of lipid metabolism-related genes in non-lesional skin of AD patients, which was associated with skin inflammation and barrier dysfunction and mainly derived from inner root sheath keratinocytes and sebaceous gland cells. CONCLUSION: Atopic dermatitis patients demonstrated a deviated lipidome of sebum and aberrant lipid metabolism in sebaceous glands, indicating a possible role of lipids from sebaceous glands in the pathogenesis of AD.

Ixekizumab successfully treated severe pityriasis rubra pilaris after COVID-19 vaccination.

Pityriasis rubra pilaris is an inflammatory dermatologic disorder of unknown cause. We report a 67-year-old man with Pityriasis rubra pilaris might induced by COVID-19 vaccination. The patient developed the lesions after the first dose of vaccine and significantly aggravated after the second dose. He had poor effect and liver function impairment developed after acitretin used, but achieved satisfactory efficacy after replacement to ixekizumab, an interleukin-17A inhibitor.

Linear Nonalternant Isomers of Acenes Fusing Multiple Azulene Units.

A modular approach to azulene building blocks was developed starting from readily available aryl-substituted cyclopentadiene and ortho-haloaryl aldehyde by dehydration condensation followed by palladium-catalyzed C-H coupling. It facilitates the synthesis of four nonalternant isomers of pentacene and hexacene, namely, dibenzo[e,g]azulene, benzo[1,2-f : 5,4-f']diazulene, benzo[1,2-f : 4,5-f']diazulene, and naphtho[2,3-f : 6,7-f']diazulene, which exhibit narrow band gaps with high stability in addition to protonation-caused enhanced near-infrared fluorescence. We discovered that in these isomers, i) constitutional isomerism influences significantly their photoelectric properties and ii) the elongation of the conjugation system does not necessarily lead to a narrowing in the band gap. Due to the easy modifiability of the nonazulene building blocks, this strategy can be extended to modularly prepare numerous multiazulene-fused aromatics.