Comparison of stromal vascular fraction cell composition between Coleman fat and extracellular matrix/stromal vascular fraction gel.

As a mechanically condensed product of Coleman fat, extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) eliminates adipocytes, concentrates SVF cells, and improves fat graft retention. This study aims to compare SVF cell composition between Coleman fat and ECM/SVF-gel. Matched Coleman fat and ECM/SVF-gel of 28 healthy women were subjected to RNA-seq, followed by functional enrichment and cell-type-specific enrichment analyses, and deconvolution of SVF cell subsets, reconstructing SVF cell composition in the transcriptome level. ECM/SVF-gels had 9 upregulated and 73 downregulated differentially expressed genes (DEGs). Downregulated DEGs were mainly associated with inflammatory and immune responses, and enriched in fat macrophages. M2 macrophages, resting CD4+ memory T cells, M1 macrophages, resting mast cells, and M0 macrophages ranked in the top five most prevalent immune cells in the two groups. The proportions of the principal non-immune cells (e.g., adipose-derived stem cells, pericytes, preadipocytes, microvascular endothelial cells) had no statistical differences between the two groups. Our findings reveal ECM/SVF-gels share the same dominant immune cells beneficial to fat graft survival with Coleman fat, but exhibiting obvious losses of immune cells (especially macrophages), while non-immune cells necessary for adipose regeneration might have no significant loss in ECM/SVF-gels and their biological effects could be markedly enhanced by the ECM/SVF-gel's condensed nature.

Cohort profile of an early life observational cohort in China: Bone and MicroBiOme onset (BAMBOO) study.

PURPOSE: The Bone And MicroBiOme Onset (BAMBOO) study is an ongoing prospective observational cohort study conducted in Tianjin, China, aiming to determine age-appropriate trajectories for microbiome maturation and bone development and to identify the influence of dietary factors in the process. PARTICIPANTS: The recruitment started in September 2021 and was completed in February 2023. A total of 1380 subjects were recruited, 690 at birth (group 1) and 690 at 6 months of age (group 2). Groups 1 and 2 will be followed up for 12 months and 36 months, respectively. FINDINGS TO DATE: The age of the mothers was 31.1±3.7 (mean±SD), and the birth weight of infants was 3.3±0.5 kg with an incidence of caesarean section 50.4%. Food diary information of the first 100 subjects showed that 64 food items were introduced by 6 months. A pilot microbiome analysis revealed that at the species level, bacterial communities were composed of mostly Bacteroides dorei, Bacteroides vulgatus and Escherichia coli, which were consistent with that of previous reports. Feasibility assessments of breast milk vitamin D and human milk oligosaccharides were validated through certified reference measurements. The early data assessment showed a high reliability of the data generated from this study. FUTURE PLANS: Data collection will be completed in August 2025. Four stage-statistical analyses will be performed as the cohort reaches certain age thresholds before the final report. Analysis of BAMBOO data will be used to develop age-appropriate trajectories for microbiome maturation and bone development for children aged 0-3 years and investigate the contribution of dietary factors in the process. TRIAL REGISTRATION NUMBER: ChiCTR2100049972.

Integrative molecular and spatial analysis reveals evolutionary dynamics and tumor-immune interplay of in situ and invasive acral melanoma.

In acral melanoma (AM), progression from in situ (AMis) to invasive AM (iAM) leads to significantly reduced survival. However, evolutionary dynamics during this process remain elusive. Here, we report integrative molecular and spatial characterization of 147 AMs using genomics, bulk and single-cell transcriptomics, and spatial transcriptomics and proteomics. Vertical invasion from AMis to iAM displays an early and monoclonal seeding pattern. The subsequent regional expansion of iAM exhibits two distinct patterns, clonal expansion and subclonal diversification. Notably, molecular subtyping reveals an aggressive iAM subset featured with subclonal diversification, increased epithelial-mesenchymal transition (EMT), and spatial enrichment of APOE+/CD163+ macrophages. In vitro and ex vivo experiments further demonstrate that APOE+CD163+ macrophages promote tumor EMT via IGF1-IGF1R interaction. Adnexal involvement can predict AMis with higher invasive potential whereas APOE and CD163 serve as prognostic biomarkers for iAM. Altogether, our results provide implications for the early detection and treatment of AM.

Immature characteristics of the East Anatolian Fault Zone from SAR, GNSS and strong motion data of the 2023 Türkiye-Syria earthquake doublet.

On February 6, 2023, an Mw 7.9 earthquake occurred in the western section of the East Anatolia Fault Zone (EAFZ). It was subsequently followed by an Mw 7.7 earthquake on the northern branch of the EAFZ, known as the Sürgü Fault Zone. Coseismic deformation fields were derived for these earthquakes using joint evaluation of near-field strong motion data, Global Navigation Satellite System data, and Synthetic Aperture Radar datasets. The coseismic slip distribution model was determined through the joint kinematic finite fault inversion. The Mw 7.9 earthquake was a left-lateral strike-slip event, predominantly occurring at depths up to 20 km. The earthquake displayed three distinct asperities that correlate well with bends and stepovers along the EAFZ. The Mw 7.7 earthquake also exhibited left-lateral strike-slip characteristics, with a major asperity along the Çardak Fault featuring a maximum slip of approximately 9.5 m at depths between 0 and 24 km. The occurrence of this unanticipated large Mw 7.9 catastrophic seismic event on a fault with low-intermediate structural maturity is noteworthy. In the vicinity of immature faults with multiple jogs, stress tends to accumulate at barrier locations. When the accumulated stress near several adjacent barriers reaches a certain threshold, it may result in the transformation of multiple barriers into asperities, triggering cascading ruptures.

Characteristics of the oral microbiota in patients with primary Sjögren's syndrome.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is an autoimmune disease with unknown etiology that is considered to be related to environmental and genetic factors. The aim of this study was to clarify the oral microflora characteristics of pSS patients and to reveal the connection between oral bacterial composition and dental caries using a high-throughput sequencing technique. METHODS: Thirty-five pSS patients and 20 healthy controls were enrolled in this study. We collected saliva and plaque samples from pSS patients and saliva samples from healthy controls. We used 16S ribosomal DNA (16S rDNA) high-throughput sequencing targeting the V3-V4 hypervariable region to determine the composition and structure of the microbiota in the three sample sets. Finally, bioinformatics analyses, including the diversity of the microbiota, species differences, and functional prediction were performed. RESULTS: In the alpha diversity and beta diversity analysis, the Chao1 (P < 0.01), observed species (P < 0.01), and PD whole tree indices (P < 0.01) were significantly lower in the saliva and plaque samples of pSS patients than in the saliva samples of healthy controls, but the Shannon (P < 0.01) and Simpson indices (P < 0.01) were significantly higher in the healthy controls, and their total diversity significantly differed. In the main flora composition at the genus level (top 10), we identified Prevotella and Veillonella as more enriched in the saliva of pSS patients and Fusobacterium, Actinomyces, and Leptotrichia as more enriched in the plaque of pSS patients. Predictive functional analysis showed that the oral microbiota of pSS patients was related to translation, metabolism of cofactors and vitamins, and nucleotide metabolism. CONCLUSIONS: The oral microbial ecology of patients with pSS is dysregulated, resulting in a decrease in overall diversity. Prevotella and Veillonella may be related to pSS, while Fusobacterium, Actinomyces, and Leptotrichia may be related to dental caries in pSS patients. Key Points • This study revealed differences in the oral microbial composition of patients with pSS compared to healthy controls. • We included a plaque group of pSS patients to identify the microbiota related to pSS and dental caries. • Prevotella and Veillonella may contribute to pSS, and Fusobacterium, Actinomyces, and Leptotrichia are associated with dental caries in pSS patients.

A case report of a family with developmental arrest of human prokaryotic stage zygote.

To study the genetic variation leading to the arrest phenotype of pronuclear (PN) zygotes. We recruited a family characterized by recurrent PN arrest during in vitro fertilization (IVF) and intracytoplasmic sperm injection cycles (ICSI) and performed whole-exome sequencing for 2 individuals. The transcriptome profiles of PN-arrest zygotes were assessed by single-cell RNA sequencing analysis. The variants were then validated by PCR amplification and Sanger sequencing in the affected individuals and other family members. A family characterized by recurrent PN arrest during IVF and ICSI cycles were enrolled after giving written informed consent. Peripheral blood samples were taken for DNA extraction. Three PN-arrest zygotes from patient III-3 were used for single-cell RNA-seq as described. This phenotype was reproduced after multiple cycles of egg retrieval and after trying different fertilization methods and multiple ovulation regimens. The mutant genes of whole exon sequencing were screened and verified. The missense variant c. C1630T (p.R544W) in RGS12 was responsible for a phenotype characterized by paternal transmission. RGS12 controls Ca2+ oscillation, which is required for oocyte activation after fertilization. Single-cell transcriptome profiling of PN-arrest zygotes revealed defective established translation, RNA processing and cell cycle, which explained the failure of complete oocyte activation. Furthermore, we identified proximal genes involved in Ca2+ oscillation-cytostatic factor-anaphase-promoting complex (Ca2+ oscillation-CSF-APC) signaling, including upregulated CaMKII, ORAI1, CDC20, and CDH1 and downregulated EMI1 and BUB3. The findings indicate abnormal spontaneous Ca2+ oscillations leading to oocytes with prolonged low CSF level and high APC level, which resulted in defective nuclear envelope breakdown and DNA replication. We have identified an RGS12 variant as the potential cause of female infertility characterized by arrest at the PN stage during multiple IVF and ICSI.

Insulin resistance, combined with health-related lifestyles, psychological traits and adverse cardiometabolic profiles, is associated with cardiovascular diseases: findings from the BHMC study.

The triglyceride glucose (TyG) index is a reliable marker of insulin resistance; however, its combined impact with modifiable lifestyle risk factors and psychological traits on cardiovascular diseases (CVDs) remains unclear. The aim of this study was to explore the relationship between the TyG index, various behavioral factors, psychological traits, and CVDs. A total of 77 752 adults aged 18 and over from the baseline survey of the Beijing Health Management Cohort study were investigated. Associations of the TyG index, body roundness index (BRI), dietary habits, psychological traits, and sleep habits with CVDs were estimated using multivariable logistic regression models. Compared to the Q1 level, the Q4 level of the TyG index had an odds ratio (OR) and 95% confidence interval (CI) of 2.30 (1.98-2.68) for CVD risk in men and 2.12 (1.81-2.48) in women. Compared to a sleep duration of more than 7 hours, a sleep duration less than 5 hours had a 32% (8%-61%) higher risk in men and 22% (1%-48%) in women. The ORs (95% CIs) for fast eating compared to normal speed were 1.47 (1.23-1.76) in men and 1.17 (1.05-1.29) in women. Compared to individuals with a passive and depressed psychological trait, those who were positive and optimistic had a 47% (36%-56%) decreased risk in men and 43% (31%-53%) in women. In the age-stratified analysis, a higher BRI level showed a sex-differential effect on CVDs, which is potentially related to a lower risk of CVDs in elderly men. A high level of the TyG index combined with unhealthy lifestyle factors indicates a higher risk of CVDs, while maintaining a positive and optimistic psychological trait acts as a protective factor. These findings may be valuable for identifying high-risk populations for CVDs in community settings.

Whole-Exome Sequencing Reveals the Genomic Profile and IL6ST Variants as a Prognostic Biomarker of Paraneoplastic Pemphigus-Associated Unicentric Castleman Disease.

Unicentric Castleman disease (UCD) is a rare lymphoproliferative disorder. Paraneoplastic pemphigus (PNP) is a major complication associated with poor UCD prognosis. However, the genomic profiles and prognostic biomarkers of PNP-associated UCD remain unclear. In this study, we performed whole-exome sequencing analysis for 28 matched tumor-normal pairs and 9 tumor-only samples to define the genomic landscape of Chinese patients with PNP-associated UCD. An integrative analysis was performed to identify somatic variants, the mutational signatures, and key pathways in tumors. Besides, we analyzed the relationship among mutated genes, clinical characteristics, and prognosis. Sixty-one somatic mutant genes were identified in >1 patient with PNP-associated UCD. Specifically, IL6ST and PDGFRB were the most frequently mutated genes (32%), followed by DPP6 (18%) and MUC4 (18%). Signaling molecules and interactions, cellular processes, and signal transduction pathways were enriched. Furthermore, we found that poor overall survival was related to IL6ST variants (P = .02). Finally, we classified PNP-associated UCD into 4 genomic subgroups: IL6ST, PDGFRB, IL6ST-PDGFRB, and an unknown subgroup. In summary, we defined the molecular profile of PNP-associated UCD and identified a potential molecular biomarker for predicting prognosis, which may provide therapeutic targets for treating this severe disorder.

Whole genome sequencing identifies genetic variants associated with neurogenic inflammation in rosacea.

Rosacea is a chronic inflammatory skin disorder with high incidence rate. Although genetic predisposition to rosacea is suggested by existing evidence, the genetic basis remains largely unknown. Here we present the integrated results of whole genome sequencing (WGS) in 3 large rosacea families and whole exome sequencing (WES) in 49 additional validation families. We identify single rare deleterious variants of LRRC4, SH3PXD2A and SLC26A8 in large families, respectively. The relevance of SH3PXD2A, SLC26A8 and LRR family genes in rosacea predisposition is underscored by presence of additional variants in independent families. Gene ontology analysis suggests that these genes encode proteins taking part in neural synaptic processes and cell adhesion. In vitro functional analysis shows that mutations in LRRC4, SH3PXD2A and SLC26A8 induce the production of vasoactive neuropeptides in human neural cells. In a mouse model recapitulating a recurrent Lrrc4 mutation from human patients, we find rosacea-like skin inflammation, underpinned by excessive vasoactive intestinal peptide (VIP) release by peripheral neurons. These findings strongly support familial inheritance and neurogenic inflammation in rosacea development and provide mechanistic insight into the etiopathogenesis of the condition.

Large-scale sports events, sports gambling market and promotion risk management: Theoretical model and case analysis based on option hedging theory.

Large-scale sports events have become a good opportunity for major enterprises to promote due to their high social attention; however, they also force enterprises to confront the risks of uncertainty and extreme loss. During the 2018 Russia World Cup, Vatti Co., Ltd.'s promotion activity "If France Wins, Get a Full Refund" suffered double losses economically and reputationally due to France's victory and the company's failure to fulfill its promise. This paper uses option hedging theory, and the risk management tools to construct a risk management model. Case analysis and program improvement were carried out. The research results show that using the winning odds can effectively control the risks. Companies should determine their promotion plan based on sale returns and the maximum implicit income generated by promotional activities. The research paper opens a new field using derivative financial instruments to control corporate promotion risks.

Pancancer Analysis Revealed the Value of RAC2 in Immunotherapy and Cancer Stem Cell.

Objective: To investigate the oncogenic effect and clinical significance of RAC2 in pancarcinoma from the perspective of tumor immunity and cancer stem cell. Methods: After in-depth mining of TCGA, GEO, UCSC, and other databases, basic information of the RAC2 gene and its expression in tumor tissues as well as the relationship between RAC2 and tumor were analyzed based on survival, mutation, immune microenvironment, tumor stemness, and enrichment analysis on related pathways. Results: RAC2 mRNA expression was increased in most tumor tissues and was associated with their prognosis. Compared to normal tissues, the RAC2 mutation rate was higher in patients with skin melanoma, uterine sarcoma, and endometrial cancer. RAC2 had a strong relation with immune cell infiltration, immunomodulators, immunotherapy markers, cancer stem cell of THYM, and immune-related pathways. Conclusions: This study explored the potential importance of RAC2 in the prognosis, immunotherapy, and cancer stem cell of 33 cancers, laying the foundation for mechanistic experiments and its future application in clinical practice. However, the results using bioinformatics methods could be affected by the differences in patients across databases. Thus, the present results were preliminary and required further experimental validation.

COL1A1-PDGFB Fusion Gene Detection Through Bulk RNA-Seq and Transcriptomic Features of Dermatofibrosarcoma Protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with obscure origin and multidirectional differentiation. Application of RNA-Seq in the detection of COL1A1-PDGFB is still at early stages. OBJECTIVE: We aim to test the efficacy of fusion gene detection using bulk RNA-Seq in DFSPs, explore altered molecular pathways and biological processes for evidences of tumor origin and cell identity shift. MATERIALS AND METHODS: Dermatofibrosarcoma protuberans and normal dermis samples were acquired for RNA-Seq. Fusion gene detection was performed using STAR-Fusion. RNA-Seq 2G yielded differentially expressed genes. Altered pathways, key gene ontology terms, and similar cell/tissue types were identified with gene set enrichment analysis. xCell was used for cell types enrichment analysis. RESULTS: 28/30 CD34(+) cases were positive for COL1A1-PDGFB. 406 upregulated and 543 downregulated genes were determined. Among the top 10 upregulated genes, 6 had neural distribution, function, or disease correlation. The upregulated genes were related to synapse, trans-synaptic signaling, neural development, and extracellular matrix. Similarities between DFSP and nervous system components were highlighted, with fibroblast cellular abundancy increased during xCell analysis. CONCLUSION: Bulk RNA-Seq provided with high detection rate of COL1A1-PDGFB. Dermatofibrosarcoma protuberans showed fibroblastic activity and neural features, which validated DFSP's fibroblast origin and tendency of neural differentiation.

The Role of Extracellular Matrix in Wound Healing.

BACKGROUND: Extracellular matrix communicates with surrounding cells to maintain skin homeostasis and modulate multiple cellular processes including wound healing. OBJECTIVE: To elucidate the dynamic composition and potential roles of extracellular matrix in normal skin, wound healing process, and abnormal skin scarring. MATERIALS AND METHODS: Literature review was performed to identify relevant publications pertaining to the extracellular matrix deposition in normal skin and wound healing process, as well as in abnormal scars. RESULTS: A summary of the matrix components in normal skin is presented. Their primary roles in hemostasis, inflammation, proliferation, and remodeling phases of wound healing are briefly discussed. Identification of novel extracellular matrix in keloids is also provided. CONCLUSION: Abnormal scarring remains a challenging condition with unmet satisfactory treatments. Illumination of extracellular matrix composition and functions in wound healing process will allow for the development of targeted therapies in the future.

Extramammary Paget's disease involving the axilla: case series and literature review.

BACKGROUND: Axillary extramammary Paget's disease (EMPD) is a rare condition with only a few cases reported in the literature. METHODS: We performed a retrospective review and identified 16 cases of EMPD with axillary involvement. We summarized the clinical and histopathological characteristics, treatment, and prognosis, as well as reviewed the literature. RESULTS: Of the included patients, eight were male and eight were female with an average age of 63.9 years at diagnosis. Eleven patients presented with unilateral axillary lesions, two patients with bilateral axillary lesions, and three patients with both axillary and genital involvement. Four male patients had a history of secondary malignancies. Axillary EMPD exerted the typical histological and immunohistochemical features of Paget's disease. All except for one patient underwent Mohs micrographic surgery with a mean final margin of 1.3 cm, and the tumor was cleared 76.5% of the time with 1 cm margins. None of the patients developed recurrence or metastasis after surgery at a mean follow-up of 63.6 months. CONCLUSIONS: Axillary EMPD shares similar clinicopathological features with typical EMPD. Careful clinical and pathological examinations are mandatory to detect possible associated malignancies and to make a correct diagnosis. Axillary EMPD usually has a good prognosis. Due to the complete margin assessment and better recurrence rates for EMPD in general, Mohs micrographic surgery is the treatment of choice.

Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment.

Background: Anti-programmed cell death ligand-1 (anti-PD-L1) immunotherapy is often used for advanced urothelial carcinoma and melanoma, including amelanotic melanoma, a relatively rare subtype with little to no pigment in the tumor cells. However, cellular heterogeneity of amelanotic melanoma during or after anti-PD-L1 immunotherapy treatments has not been described. Purpose: To investigate cellular heterogeneity in acral amelanotic melanoma after immunotherapy exposure. Methods: We evaluated subtle visual changes of the melanoma by dermoscopy and performed a pathological examination to analyze the heterogeneity of microscopic morphological and immunohistochemistry changes. The cellular transcriptional heterogeneity and corresponding biological function profiles of the melanoma were determined by single-cell RNA sequencing (scRNA-seq). Results: The dermoscopic examination revealed black globules and scar-like depigmentation areas against a homogeneous red background. Pigmented and amelanotic melanoma cells were observed microscopically. The pigmented cells were large and contained melanin granules expressing Melan-A and HMB45; the amelanotic cells were small and did not express HMB45. Ki-67 immunohistochemical staining revealed that the pigmented melanoma cells had a higher proliferative ability than the amelanotic cells. scRNA-seq identified three cell clusters: amelanotic cell cluster 1, amelanotic cell cluster 2, and pigmented cell cluster. Furthermore, a pseudo-time trajectory analysis showed that amelanotic cell cluster 2 originated from amelanotic cell cluster 1 and transformed into the pigmented melanoma cell cluster. The expression pattern of melanin synthesis-related and lysosome-endosome-related genes in different cell clusters supported the cell cluster transformation results. Also, upregulated expression of cell cycle genes indicated that the pigmented melanoma cells had a high proliferative ability. Conclusion: Coexisting amelanotic and pigmented melanoma cells indicated cellular heterogeneity in an acral amelanotic melanoma from a patient who underwent immunotherapy treatment. Additionally, the pigmented melanoma cells acquired a higher proliferative ability than the amelanotic melanoma cells.

Application of logistic regression and machine learning methods for idiopathic inflammatory myopathies malignancy prediction.

OBJECTIVES: Malignancy is related to idiopathic inflammatory myopathies (IIM) and leads to a poor prognosis. Early prediction of malignancy is thought to improve the prognosis. However, predictive models have rarely been reported in IIM. Herein, we aimed to establish and use a machine learning (ML) algorithm to predict the possible risk factors for malignancy in IIM patients. METHODS: We retrospectively reviewed the medical records of 168 patients diagnosed with IIM in Shantou Central hospital, from 2013 to 2021. We randomly divided patients into two groups, the training sets (70%) for construction of the prediction model, and the validation sets (30%) for evaluation of model performance. We constructed six types of ML algorithms models and the AUC of ROC curves were used to describe the efficacy of the model. Finally, we set up a web version using the best prediction model to make it more generally available. RESULTS: According to the multi-variable regression analysis, three predictors were found to be the risk factors to establish the prediction model, including age, ALT<80U/L, and anti-TIF1-γ, and ILD was found to be a protective factor. Compared with five other ML algorithms models, the traditional algorithm logistic regression (LR) model was as good or better than the other models to predict malignancy in IIM. The AUC of the ROC using LR was 0.900 in the training set and 0.784 in the validation set. We selected the LR model as the final prediction model. Accordingly, a nomogram was constructed using the above four factors. A web version was built and can be visited on the website or acquired by scanning the QR code. CONCLUSIONS: The LR algorithm appears to be a good predictor of malignancy and may help clinicians screen, evaluate and follow up high-risk patients with IIM.

Transferring and Retaining of Different Polyaniline Nanofeatures via Electrophoretic Deposition for Enhanced Sensing Performance.

Nanofeatured polyaniline (PANI) electrodes have demonstrated impressive sensing performance due to the enhanced electrolyte diffusion and ion transport. However, the retaining of these nanostructures on substrates via electrophoretic deposition (EPD) faces an insurmountable challenge from the involved dedoping process. Here, camphorsulfonic acid is utilized with high steric effects to dope PANI (PANI-CSA) that can be directly used EPD without involving a dedoping process. Five different nanofeatures (sea cucumber-like, nanofiber, amorphous, nanotube, and nanorod) are synthesized, and they have been all successfully transferred onto indium tin oxide substrate in a formic acid/acetonitrile system, namely a morphology memory effect. The mechanism of retaining these nanofeatures is revealed, which is realized via the processes of dissolution of PANI-CSA, codoping and solvation, and reassembly of basic units into the original nanofeature. The enhanced protonation level by the codoping of formic acid and solvation of acetonitrile plays the key role in retaining these nanofeatures. This method is also applicable to transfer PANI/gold nanorod composites (PANI-CSA/AuNRs). The PANI-CSA/AuNRs electrode as an ascorbic acid sensor has shown an excellent sensing performance with a sensitivity up to 872.7 µA mm-1 cm-2 and a detection limit of as low as 0.18 × 10-6 m.

Transcriptomic Heterogeneity of Skin Across Different Anatomic Sites.

Multiomic studies, including RNA sequencing, single-cell RNA sequencing, and epigenomics, can provide insight into the connection between anatomically heterogeneous gene expression profile of the skin and dermatoses-predisposed sites, in which RNA sequencing is essential. Therefore, in this study, 159 skin samples collected mainly from discarded normal skin tissue during surgical treatment for benign skin tumors were used for RNA sequencing. On the basis of cluster analysis, the skin was divided into four regions, with each region showing specific physiological characteristics through differentially expressed gene analysis. The results showed that the head and neck region, perineum, and palmoplantar area were closely associated with lipid metabolism, hormone metabolism, blood circulation, and related neural regulation, respectively. Transcription factor enrichment indicated that different regions were associated with the development of adjacent tissues. Specifically, the head and neck region, trunk and extremities, perineum, and palmoplantar area were associated with the central nervous, axial, urogenital, and vascular systems, respectively. The results were imported into an open website (https://dermvis.github.io/) for retrieval. Our transcriptomic data elucidated that human skin exhibits transcriptomic heterogeneity reflecting physiological and developmental variation at different anatomic sites and provided guidance for further studies on skin development and dermatoses predisposed sites.

Pan-Cancer Analysis of TLE3 Revealed Its Value in Tumor Microenvironment and Prognosis.

Background: Transducin-like enhancer of split 3 (TLE3), a member of the TLE gene family, is related to tumor genesis and progression. However, whether TLE3 played a crucial role in the whole pan-cancer remained unknown. Methods: Comprehensive analysis of TCGA, GEO, and GTEx data with an online tool, and R language was performed to explore the relationship of TLE3 expression between prognosis, gene mutation, protein phosphorylation, DNA methylation, tumor microenvironment, and related pathways in 33 tumors. Results: TLE3 was high-expressed in most tumors, and TLE3 expression and the prognosis of some tumor types were significantly correlated. The level of TLE3 expression in 33 cancer types was closely associated with DNA methylation. High-level phosphorylation sites of Tle3, such as S267 and S217, may promote cancers. In terms of the tumor microenvironment, TLE3 affected a wide variety of cancers, especially PRAD and LIHC, and TLE3 may act on them via immune-related pathways. Conclusions: The current work provided the first comprehensive investigation of TLE3 in a pan-cancer study, highlighting the role of TLE3 in the tumor immune microenvironment, and also determined the potential of TLE3 as a prognostic, immunotherapy response, and diagnostic biomarker in many cancers. However, the present results were preliminary and required further validation as this study was based on bioinformatics analyses.