Base excision repair of the N-(2-deoxy-d-erythro-pentofuranosyl)-urea lesion by the hNEIL1 glycosylase.

The N-(2-deoxy-d-erythro-pentofuranosyl)-urea DNA lesion forms following hydrolytic fragmentation of cis-5R,6S- and trans-5R,6R-dihydroxy-5,6-dihydrothymidine (thymine glycol, Tg) or from oxidation of 7,8-dihydro-8-oxo-deoxyguanosine (8-oxodG) and subsequent hydrolysis. It interconverts between α and ß deoxyribose anomers. Synthetic oligodeoxynucleotides containing this adduct are efficiently incised by unedited (K242) and edited (R242) forms of the hNEIL1 glycosylase. The structure of a complex between the active site unedited mutant CΔ100 P2G hNEIL1 (K242) glycosylase and double-stranded (ds) DNA containing a urea lesion reveals a pre-cleavage intermediate, in which the Gly2 N-terminal amine forms a conjugate with the deoxyribose C1' of the lesion, with the urea moiety remaining intact. This structure supports a proposed catalytic mechanism in which Glu3-mediated protonation of O4' facilitates attack at deoxyribose C1'. The deoxyribose is in the ring-opened configuration with the O4' oxygen protonated. The electron density of Lys242 suggests the 'residue 242-in conformation' associated with catalysis. This complex likely arises because the proton transfer steps involving Glu6 and Lys242 are hindered due to Glu6-mediated H-bonding with the Gly2 and the urea lesion. Consistent with crystallographic data, biochemical analyses show that the CΔ100 P2G hNEIL1 (K242) glycosylase exhibits a residual activity against urea-containing dsDNA.

Indole induces anxiety-like behaviour in mice mediated by brainstem locus coeruleus activation.

The gut microbiota produces metabolites that enrich the host metabolome and play a part in host physiology, including brain functions. Yet the biological mediators of this gut-brain signal transduction remain largely unknown. In this study, the possible role of the gut microbiota metabolite indole, originating from tryptophan, was investigated. Oral administration of indole to simulate microbial overproduction of this compound in the gut consistently led to impaired locomotion and anxiety-like behaviour in both C3H/HeN and C57BL/6 J mice. By employing c-Fos protein expression mapping in mice, we observed a noticeable increase in brain activation within the dorsal motor nucleus of the vagus nerve (DMX) and the locus coeruleus (LC) regions in a dose-dependent manner. Further immune co-labelling experiments elucidated that the primary cells activated within the LC were tyrosine hydroxylase positive. To delve deeper into the mechanistic aspects, we conducted chemogenetic activation experiments on LC norepinephrine neurons with two doses of clozapine N-oxide (CNO). Low dose of CNO at 0.5 mg/kg induced no change in locomotion but anxiety-like behaviour, while high dose of CNO at 2 mg/kg resulted in locomotion impairment and anxiety-like behaviour. These findings support the neuroactive roles of indole in mediating gut-brain communication. It also highlights the LC as a novel hub in the gut-brain axis, encouraging further investigations.

Macrophage migration inhibitory factor mediates skin aging via CD74: Insights from single-cell and bulk RNA sequencing data.

Cell-cell communication is crucial for regulating signaling and cellular function. However, the precise cellular and molecular changes remain poorly understood in skin aging. Based on single-cell and bulk RNA data, we explored the role of cell-cell ligand-receptor interaction in skin aging. We found that the macrophage migration inhibitory factor (MIF)/CD74 ligand-receptor complex was significantly upregulatedin aged skin, showing the predominant paracrine effect of keratinocytes on fibroblasts. Enrichment analysis and in vitro experiment revealed a close association of the activation of the MIF/CD74 with inflammatory pathways and immune response. Mechanistically, MIF/CD74 could significantly inhibit PPARγ protein, which thus significantly increased the degree of fibroblast senescence, and significantly up-regulated the expression of senescence-associated secretory phenotype (SASP) factors and FOS gene. Therefore, our study reveals that MIF/CD74 inhibits the activation of the PPAR signaling pathway, subsequently inducing the production of SASP factors and the upregulation of FOS expression, ultimately accelerating fibroblast senescence.

A Highly Sensitive and Selective Fluorescent Sensor for Folic Acid Detection Based on D-penicillamine Stabilized Ag/Cu Alloy Nanoclusters.

In this work, a highly sensitive and selective method for detecting folic acid (FA) was developed using D-penicillamine (DPA) stabilized Ag/Cu alloy nanoclusters (DPA@Ag/Cu NCs). The yellow emission of DPA@Ag/Cu NCs was found to be quenched upon the addition of FA to the system. The fluorescence intensity quenching value demonstrated a linear relationship with FA concentrations ranging from 0.01 to 1200 µM, with a limit of detection (LOD) of 5.3 nM. Furthermore, the detection mechanism was investigated through various characterization analyses, including high resolution transmission electron microscopy, fluorescence spectra, ultraviolet-visible absorption spectra, and fluorescence lifetime. The results indicated that the fluorescence quenching induced by FA was a result of electron transfer from FA to the ligands of DPA@Ag/Cu NCs. The selectivity of the FA sensor was also evaluated, showing that common amino acids and inorganic ions had minimal impact on the detection of FA. Moreover, the standard addition method was successfully applied to detect FA in human serum, chewable tablets and FA tablets with promising results. The use of DPA@Ag/Cu NCs demonstrates significant potential for detecting FA in complex biological samples.

Queen bee gut microbiota extends honeybee lifespan by inhibiting insulin signaling.

Queen and worker bees are natural models for aging research, as their lifespans vary considerably independent of genetic variation. Investigating the reasons why queens live longer than workers is of great significance for research on the universal processes of aging in animals. The gut microbiome has received attention as a vital regulator of host health, while its precise role in honeybee aging needs further investigation. The effects and mechanisms behind the relationship between gut microbiota and worker lifespan were measured by transplanting queen bee gut bacteria (QG) and worker bee gut bacteria (WG) into microbiota-free (MF) workers. The transplantation of QG to MF bees significantly extended the workers' lifespans compared with MF and WG bees. Untargeted metabolomics identified 49 lifespan-related differential metabolites, and Kyoto Encyclopedia of Genes and Genomes analysis of these revealed three lifespan-related metabolic pathways: insulin/insulin-like growth factor signaling, immune, and ketone body metabolism pathways. Further verification showed that QG inhibited the expression of insulin-like peptides (ILPs), and the expression of ILPs was lower in natural queens than in natural workers. QG transplantation also stimulated the expression of antioxidant genes and lowered oxidative damage products in natural queen bees. However, gut microbiota transplantation failed to mimic the immune properties and ketone body metabolism profiles of natural queens and workers. Concisely, QG could increase the antioxidant capacity to extend lifespan by inhibiting insulin signaling. These findings may help determine the mechanisms behind queen longevity and provide further insights into the role of gut symbionts. IMPORTANCE: Queen and worker bees share the same genetic background but have vastly different lifespans. The gut microbiome regulates host health, suggesting that differences in lifespan between queen and worker bees could be related to gut bacteria. Herein, we used an innovative method to transplant gut microbiota from adult queen or worker bees to microbiota-free bees. The transplantation of queen gut microbiota to microbiota-free bees extended their lifespan. Insulin/insulin-like growth factor signaling, a highly conserved metabolic pathway related to lifespan, displayed identical expression profiles in natural queen bees and microbiota-free bees transplanted with queen microbiota. This finding significantly expands our understanding of the relationships between intestinal bacteria, host health, and the biology of aging.

Immune interplay from circulation to local lesion in pemphigus pathogenesis.

Pemphigus, a potentially lethal autoimmune skin disease, is mediated by desmoglein-specific antibodies, manifesting cutaneous and mucosal blisters and erosions. The interaction between multiple immune counterparts contributes to the progress of pemphigus. Currently, the emergence of bioinformatic analysis enables investigators to gain a global picture of the pemphigus immune network, based on the exhaustive pedigree annotation of multiple subsets. T helper subsets dominate the landscape as mentioned previously, and innate immune cells have been involved as well. Of particular interests is which phenotype of T cells orchestrates the autoimmune process and chronic inflammation in a certain condition. In this review, the circulatory and peripheral immune cells and cytokine components constituting the immune microenvironment are separately discussed to provide a perspective on pemphigus pathogenesis, with particular reference to insights provided by the bioinformation technique.

The genetic landscape of germline DDX41 variants predisposing to myeloid neoplasms.

Germline DDX41 variants are the most common mutations predisposing to acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) in adults, but the causal variant (CV) landscape and clinical spectrum of hematologic malignancies (HMs) remain unexplored. Here, we analyzed the genomic profiles of 176 patients with HM carrying 82 distinct presumably germline DDX41 variants among a group of 9821 unrelated patients. Using our proposed DDX41-specific variant classification, we identified features distinguishing 116 patients with HM with CV from 60 patients with HM with variant of uncertain significance (VUS): an older age (median 69 years), male predominance (74% in CV vs 60% in VUS, P = .03), frequent concurrent somatic DDX41 variants (79% in CV vs 5% in VUS, P < .0001), a lower somatic mutation burden (1.4 ± 0.1 in CV vs 2.9 ± 0.04 in VUS, P = .012), near exclusion of canonical recurrent genetic abnormalities including mutations in NPM1, CEBPA, and FLT3 in AML, and favorable overall survival (OS) in patients with AML/MDS. This superior OS was determined independent of blast count, abnormal karyotypes, and concurrent variants, including TP53 in patients with AML/MDS, regardless of patient's sex, age, or specific germline CV, suggesting that germline DDX41 variants define a distinct clinical entity. Furthermore, unrelated patients with myeloproliferative neoplasm and B-cell lymphoma were linked by DDX41 CV, thus expanding the known disease spectrum. This study outlines the CV landscape, expands the phenotypic spectrum in unrelated DDX41-mutated patients, and underscores the urgent need for gene-specific diagnostic and clinical management guidelines.

A novel small-molecule PCSK9 inhibitor E28362 ameliorates hyperlipidemia and atherosclerosis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 µM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fraction in both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 µM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg-1·d-1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE-/- mice (20, 60 mg·kg-1·d-1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg-1·d-1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en face aortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.

Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy.

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

Unilateral levator avulsion increases the risk of de novo stress urinary incontinence after cystocele repair.

INTRODUCTION: Patients without concurrent baseline stress urinary incontinence (SUI) can develop de novo SUI after transvaginal mesh surgery (TVM) for cystocele repair. Surgeons should be aware of de novo SUI risk factors after TVM. METHODS: A total of 1124 women who were underwent TVM surgeries were recruited and assessed for eligibility from January 1, 2012 to April 30, 2021. All data related to patients and surgeries was collected, which included general conditions, clinical examination, surgery records, and follow-up results. Patients were divided into three groups according to follow-up results and data were compared with each group. The relative risk (RR) of de novo SUI with levator avulsion was also calculated. RESULTS: Three hundred thirty-six patients were included in this study. They were divided into no complication group (n = 249), de novo SUI group (n = 68), and other complications group (n = 19). It seemed elder or obese women had a higher risk of de novo SUI after TVM (p < 0.05). In de novo SUI group, incidence of levator avulsion before surgery were higher than the other two groups (p = 0.001). TVM can significantly change a prolapse to point Aa and Ba on POP-Q quantification system (p < 0.05). RR ratios of de novo SUI with unilateral avulsion group is 2.60 (95% confidence interval [CI] 1.39-4.87), and 2.58 (95%CI 0.82-8.15) for bilateral group. CONCLUSION: Unilateral levator avulsion, instead of bilateral levator avulsion, is a risk factor of de novo SUI after cystocele repair surgery.

Identification of the cytochrome P450 gene AccCYP6A13 in Apis cerana cerana and its response to environmental stress.

Cytochrome P450 plays a crucial role in regulating insect growth, development, and resisting a variety of stresses. Insect metamorphosis and response to external stress are altered by deleting CYP450 genes. In this study, we identified and analyzed a novel gene of CYP450 family, AccCYP6A13, from Apis cerana cerana, and explored its role in the response of Apis cerana cerana to adverse external stressors. It was found that the expression of AccCYP6A13 was spatiotemporal specificity. The expression level increased with age and reached its highest value in the adult stage. The primarily expressiong location were legs, brain, and epidermis of honeybees. Stress conditions can affect the expression of AccCYP6A13 depending on treatment times. RNA interference experiments have shown that knocking down AccCYP6A13 reduces antioxidant activity and deactivates detoxification enzymes, resulting in oxidative damage accumulation and a decline in detoxification capability in bees, as well as inhibiting numerous antioxidant genes. Additionally, knockdown of the AccCYP6A13 gene in Apis cerana cerana resulted in increased sensitivity to pesticides and increased mortality when treated with neonicotinoid pesticides such as thiamethoxam. AccCYP6A13 overexpression in a prokaryotic system further confirmed its role in resistance to oxidative stress. To summarize, AccCYP6A13 may play an essential role in the normal development and response to environmental stress in Apis cerana cerana. Furthermore, this study contributed to the theoretical understanding of bee resistance biology.

Automated radiosynthesis of [18 F]CETO, a PET radiotracer for imaging adrenal glands, on Synthra RNplus.

Primary aldosteronism (PA) is the leading secondary cause of hypertension. Determining whether one (unilateral) or both (bilateral) adrenal glands are the source of PA in a patient remains challenging, and yet it is a critical step in the decision whether to recommend potentially curative surgery (adrenalectomy) or lifelong medical therapy (typically requiring multiple drugs). Recently, we have developed a fluorine-18 radiopharmaceutical [18 F]CETO to permit greater access to PA molecular imaging. Herein, we report an automated synthesis of this radiotracer. To manufacture the radiopharmaceutical routinely for clinical PET studies, we implemented an automated radiosynthesis method on a Synthra RNplus© synthesiser for which Cl-tosyletomidate was used as the precursor for radiolabelling via nucleophilic [18 F]fluorination. [18 F]CETO was produced with 35 ± 1% (n = 7), decay corrected and 25 ± 4% (n = 7) non-decay corrected radiochemical yield with molar activities ranging from 150 to 400 GBq/µmol. The GMP compliant manufacturing process produces a sterile formulated [18 F]CETO injectable solution for human use as demonstrated by the results of quality control. Automation of the radiosynthesis of [18 F]CETO should facilitate uptake by other adrenal centres and increase access to molecular imaging in PA.

The evolutionary patterns of barley pericentromeric chromosome regions, as shaped by linkage disequilibrium and domestication.

The distribution of recombination events along large cereal chromosomes is uneven and is generally restricted to gene-rich telomeric ends. To understand how the lack of recombination affects diversity in the large pericentromeric regions, we analysed deep exome capture data from a final panel of 815 Hordeum vulgare (barley) cultivars, landraces and wild barleys, sampled from across their eco-geographical ranges. We defined and compared variant data across the pericentromeric and non-pericentromeric regions, observing a clear partitioning of diversity both within and between chromosomes and germplasm groups. Dramatically reduced diversity was found in the pericentromeres of both cultivars and landraces when compared with wild barley. We observed a mixture of completely and partially differentiated single-nucleotide polymorphisms (SNPs) between domesticated and wild gene pools, suggesting that domesticated gene pools were derived from multiple wild ancestors. Patterns of genome-wide linkage disequilibrium, haplotype block size and number, and variant frequency within blocks showed clear contrasts among individual chromosomes and between cultivars and wild barleys. Although most cultivar chromosomes shared a single major pericentromeric haplotype, chromosome 7H clearly differentiated the two-row and six-row types associated with different geographical origins. Within the pericentromeric regions we identified 22 387 non-synonymous SNPs, 92 of which were fixed for alternative alleles in cultivar versus wild accessions. Surprisingly, only 29 SNPs found exclusively in the cultivars were predicted to be 'highly deleterious'. Overall, our data reveal an unconventional pericentromeric genetic landscape among distinct barley gene pools, with different evolutionary processes driving domestication and diversification.

UVB promotes melanogenesis by regulating METTL3.

Ultraviolet (UV) radiation is the primary exogenous inducer of skin pigmentation, although the mechanism has not been fully elucidated. N6-methyladenosine (m6 A) modification is one of the key epigenetic form of gene regulation that affects multiple biological processes. The aim of this study was to explore the role and underlying mechanisms of m6 A modification in UVB-induced melanogenesis. Low-dose UVB increased global m6 A modification in melanocytes (MCs) and MNT1 melanoma cell line. The GEPIA database predicted that methyltransferase METTL3 is positively correlated with the melanogenic transcription factor MITF in the sun-exposed skin tissues. After METTL3 respectively overexpressed and knocked down in the MNT1, the melanin content and melanogenesis-related genes were significantly upregulated after overexpression of METTL3, especially with UVB irradiation, and downregulated after METTL3 knockdown. METTL3 levels were also higher in melanocytic nevi with high melanin content. METTL3 overexpression and knockdown also altered the protein level of YAP1. SRAMP analysis predicted four high-potential m6 A modification sites on YAP1 mRNA, of which three were confirmed by methylated RNA immunoprecipitation. Inhibition of YAP1 expression can partially reverse melanogenesis induced by overexpression of METTL3. In conclusion, UVB irradiation promotes global m6 A modification in MCs and upregulates METTL3, which increases the expression level of YAP1 through m6 A modification, thereby activating the co-transcription factor TEAD1 and promoting melanogenesis.

Core root-associated prokaryotic community and its relationship to host traits across wheat varieties.

The root-associated microbiomes play important roles in plant growth. However, it is largely unknown how wheat variety evolutionary relatedness shapes each subcommunity in the root microbiome and, in turn, how these microbes affect wheat yield and quality. Here we studied the prokaryotic communities associated with the rhizosphere and root endosphere in 95 wheat varieties at regreening and heading stages. The results indicated that the less diverse but abundant core prokaryotic taxa occurred among all varieties. Among these core taxa, we identified 49 and 108 heritable amplicon sequence variants, whose variations in relative abundances across the root endosphere and rhizosphere samples were significantly affected by wheat variety. The significant correlations between phylogenetic distance of wheat varieties and prokaryotic community dissimilarity were only observed in non-core and abundant subcommunities in the endosphere samples. Again, wheat yield was only significantly associated with root endosphere microbiota at the heading stage. Additionally, wheat yield could be predicted using the total abundance of 94 prokaryotic taxa as an indicator. Our results demonstrated that the prokaryotic communities in the root endosphere had higher correlations with wheat yield and quality than those in the rhizosphere; thus, managing root endosphere microbiota, especially core taxa, through agronomic practices and crop breeding, is important for promoting wheat yield and quality.

miR-342-5p targets CTNNBIP1 to promote enterovirus 71 replication.

OBJECTIVE: The aim of this research was to explore the role of miR-342-5p in EV71 replication. METHODS: Peritoneal injection of EV71 (107 TCID50/mL) at 50, 100, and 150 µL was conducted to infect 12-day-old suckling mice (n = 10 per group), and clinical scores and survival rates were recorded during a 6-day trial duration and followed by transcriptome sequencing of collected spinal cord tissues. The differential miRNAs and target genes of the infected and uninfected EV71 mice were analyzed. The miR-342 and CTNNBIP1 binding sites were detected using a dual luciferase reporter assay. Cell viability was detected by CCK-8. RT-qPCR, Western blot, immunofluorescence, and immunohistochemistry assays were conducted to detect VP1 protein levels. RESULTS: Transcriptome sequencing analyses know that the Wnt pathway played a role in EV71 infection, and the CTNNBIP1 gene in this pathway was the target gene of miR-342-5p. Whether in HMC3 cells or in the spinal cord tissue from the suckling mice, high levels of miR-342-5p markedly promoted EV71 VP1 mRNA and protein expression, elevated TNF-α, IL-6, and IL-10 levels, and inhibited IFN-ß levels. In addition, highly expressed miR-342-5p destroyed neuronal structure in spinal cord tissues and reduced the number of glial cells. Highly expressed CTNNBIP1 blocked the promotion of miR-342-5p in EV71 replication, and inhibited TNF-α, IL-6, and IL-10 levels, whereas elevated IFN-ß levels. This mechanism is that miR-342-5p can target the CTNNBIP1 3' UTR region, inhibit its expression and reduce its binding to CTNNB1, thus enhancing the interaction between CTNNB1 and TCF4 and activating the Wnt pathway-mediated type I interferon response. CONCLUSION: In nerve cells and tissues, the overexpression of miR-342-5p promoted the replication of EV71 and attenuated the innate immune response to antiviral disease via Wnt/CTNNB1 signaling pathway.

Characteristics and pathogenesis of Koebner phenomenon.

The Koebner phenomenon, also known as isomorphic reaction, refers to the development of secondary lesions with the same clinical manifestations and histopathological characteristics as the primary lesions in normal skin after trauma or other stimuli. The triggering factors of Koebner phenomenon include physical trauma, chemical stimulation, mechanical stress, iatrogenic stimulation and pathogenic infection. Vitiligo, psoriasis and lichen planus are considered true Koebner phenomenon. Recent studies have shown that immunological disorders, oxidative stress, defective melanocyte adhesion and growth factor deficiency are the main pathological mechanisms of vitiligo Koebner phenomenon. In psoriasis, triggers may drive skin inflammation to induce a psoriatic phenotype through multiple signalling pathways and thereby cause Koebner phenomenon in susceptible individuals. Significantly, keratinocytes mediate the occurrence of Koebner phenomenon in psoriasis through mechano-induced signalling pathways after sensing mechanical signals and explains the high frequency of psoriasis lesions on the extensor side of the elbow and knee joints. On the contrary, TRPA1-driven mechano-transduction, autoimmunity and actinic damage are the underlying mechanisms of Koebner phenomenon in lichen planus. In this review, we have summarized the current understanding of the characteristics and pathogenesis of Koebner phenomenon.

High-Pressure Coupling Reactions to Produce a Spherical Bulk RexN/Fe3N Composite.

We report a novel high-pressure coupling (HPC) reaction that couples the nitridation of Re with high-pressure solid-state metathesis (HPSSM) of Fe3N to produce a spherical bulk RexN/Fe3N composite. Compared with conventional methods, upon coupling of the HPSSM reactions, the synthetic pressure for Re nitridation was successfully reduced from 13 to 10 GPa (for Re3N) and from 20 to 15 GPa (for Re2N). The product RexN species would be surrounded by product Fe3N, resulting in a spherical bulk RexN/Fe3N composite (x = 2 or 3). The composite exhibits a soft magnetic behavior, and the content of nitrogen in RexN (x = 2 or 3) was controlled by adjusting the P-T conditions. The HPC reaction establishes a new approach for the bulk synthesis of 5d transition metal nitride.

Disease Awareness and Treatment Preferences in Vitiligo: A Cross-sectional Study in China.

In China, there is a lack of data regarding the awareness and treatment preferences among patients with vitiligo and their families. To address this gap, a cross-sectional questionnaire-based study was conducted to investigate disease awareness and treatment preferences in Chinese patients with vitiligo. The study also evaluated willingness to pay, using 2 standardized items, and assessed quality of life, using the Dermatology Life Quality Index (DLQI) score. Data from 307 patients with vitiligo (59.3% women, mean age 28.98 years, range 2-73 years) were analysed. Of these patients, 44.7% had insufficient knowledge of vitiligo, particularly those from rural areas or with low levels of education. Mean DLQI total score was 4.86 (5.24 for women and 4.30 for men). Among the most accepted treatments were topical drugs, phototherapy, and systemic therapy. Patients were relatively conservative about the duration and cost of treatment, with only 27.7% willing to pay more than 10,000 Chinese yuan renminbi (CNY) for complete disease remission. High level of education, high income, skin lesions in specific areas, and skin transplantation therapy predicted higher willingness to pay. Insufficient knowledge was associated with a higher burden of disease. In order to reduce the disease burden and improve treatment adherence it is crucial to enhance disease awareness and take into account patient preferences.

Vascular wall microenvironment: exosomes secreted by adventitial fibroblasts induced vascular calcification.

Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment.