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The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is incompletely understood. Here we demonstrate, using a combination of single cell and spatial RNA sequencing, IL-36 dependent amplification of IL-17A and TNF inflammatory responses in the absence of neutrophil proteases, which primarily occur within the supraspinous layer of the psoriatic epidermis. We further show that a subset of SFRP2 + fibroblasts in psoriasis contribute to amplification of the immune network through transition to a pro-inflammatory state. The SFRP2 + fibroblast communication network involves production of CCL13 , CCL19 and CXCL12 , connected by ligand-receptor interactions to other spatially proximate cell types: CCR2 + myeloid cells, CCR7 + LAMP3 + dendritic cells, and CXCR4 expressed on both CD8 + Tc17 cells and keratinocytes, respectively. The SFRP2 + fibroblasts also express cathepsin S, further amplifying inflammatory responses by activating IL-36G in keratinocytes. These data provide an in-depth view of psoriasis pathogenesis, which expands our understanding of the critical cellular participants to include inflammatory fibroblasts and their cellular interactions. Changes in Psoriasis and other inflammatory skin diseases during severity stages can be investigated using single cell and spatial transcriptomics. Here the authors compare different inflammatory skin diseases to emphasise differences in immune cells and inflammatory markers particularly keratinocytes and fibroblasts.

To explore the mechanism by which Astragalus membranaceus and Salvia miltiorrhiza (AS) regulates the “metabolic- transcriptional” co-expression network to improve Hypertensive renal damage (HRD). Spontaneously hypertensive rats (SHRs) were used to establish the model of HRD. The structure and function of the kidney were observed following AS intervention. We identified various metabolites in the kidneys using UHPLC-MS/MS and observed renal mRNA expression through RNA sequencing. The “metabolism-transcription” coexpression network was further constructed, and the target metabolites and target genes of AS were ultimately screened and validated. AS significantly reduced blood pressure, improved renal function and alleviated renal pathological damage in SHRs. A total of 596 target mRNAs of AS were identified. Of note, 254 of these mRNAs were expressed in 25 pathways that were closely related to metabolic processes. Additionally, the target metabolites of AS were determined, predominantly enriched in 8 pathways, including linoleic acid metabolism, cholesterol metabolism, choline metabolism in cancer, and the synthesis and degradation of ketone bodies, etc. In addition, the target metabolites and target mRNAs of AS were co-enriched in 3 specific pathways of linoleic acid metabolism, cholesterol metabolism, taurine and hypotaurine metabolism, involving 7 different metabolites and 18 differentially expressed (DE) mRNAs. The 7 metabolites exhibited high AUC prediction values, and the verification and sequencing results of the 4 genes were basically consistent. Conclusion The mechanisms by which AS improves HRD may be closely related to the regulation of linoleic acid metabolism, cholesterol metabolism and taurine and hypotaurine metabolism pathways as well as the relevant target genes.

Background Osteoporosis (OP) is a major and growing public health problem characterized by decreased bone mineral density and destroyed bone microarchitecture. Previous studies found that Lycium Chinense Mill (LC) has a potent role in inhibiting bone loss. Kukoamine A (KuA), a bioactive compound extract from LC was responsible for the anti-osteoporosis effect. This study aimed to investigate the anti-osteoporosis effect of KuA isolated from LC in treating OP and its potential molecular mechanism. Method In this study, network pharmacology and molecular docking were investigated firstly to find the active ingredients of LC such as KuA, and the target genes of OP by the TCMSP platform. The LC-OP-potential Target gene network was constructed by the STRING database and network maps were built by Cytoscape software. And then, the anti-osteoporotic effect of KuA in OVX-induced osteoporosis mice and MC3T3-E1 cell lines were investigated and the potential molecular mechanism including inflammation level, cell apoptosis, and oxidative stress was analyzed by dual-energy X-ray absorptiometry (DXA), micro-CT, ELISA, RT-PCR, and Western Blotting. Result A total of 22 active compounds were screened, and we found KuA was identified as the highest active ingredient. Glycogen Phosphorylase ( PYGM ) was the target gene associated with a maximum number of active ingredients of LC and regulated KuA. In vivo, KuA treatment significantly increased the bone mineral density and improve bone microarchitecture for example increased BV/TV, Tb.N and Tb.Th but reduced Tb.Sp in tibia and lumber 4. Furthermore, KuA increased mRNA expression of osteoblastic differentiation-related genes in OVX mice and protects against OVX-induced cell apoptosis, oxidative stress level and inflammation level. In vitro, KuA significantly improves osteogenic differentiation and mineralization in cells experiment. In addition, KuA also attenuated inflammation levels, cell apoptosis, and oxidative stress level. Conclusion The results suggest that KuA could protect against the development of OP in osteoblast cells and ovariectomized OP model mice and these found to provide a better understanding of the pharmacological activities of KuA again bone loss.

Skull stripping is a crucial preprocessing step in magnetic resonance imaging (MRI), where experts manually create brain masks. This labor-intensive process heavily relies on the annotator’s expertise, as automation faces challenges such as low tissue contrast, significant variations in image resolution, and blurred boundaries between the brain and surrounding tissues, particularly in rodents. In this study, we have developed a lightweight framework based on Swin-UNETR to automate the skull stripping process in MRI scans of mice and rats. The primary objective of this framework is to eliminate the need for preprocessing, reduce the workload, and provide an out-of-the-box solution capable of adapting to various MRI image resolutions. By employing a lightweight neural network, we aim to lower the performance requirements of the framework. To validate the effectiveness of our approach, we trained and evaluated the network using publicly available multi-center data, encompassing 1,037 rodents and 1,142 images from 89 centers, resulting in a preliminary mean Dice coefficient of 0.9914. The framework, data, and pre-trained models can be found on the following link: https://github.com/VitoLin21/Rodent-Skull-Stripping. •Released multi-center rodent MRI brain masks dataset.•RS2-Net is a lightweight framework based on modified Swin-UNETR.•Achieved state-of-the-art brain segmentation on various metrics.•Provides an user-friendly and performance-friendly rodent skull stripping tool.

The skin serves as the primary interface between our body and the external environment and acts as a barrier against entry of physical agents, chemicals, and microbes. Keratinocytes make up the main cellular constitute of the outermost layer of the skin, contributing to the formation of the epidermis, and they are crucial for maintaining the integrity of this barrier. Beyond serving as a physical barrier component, keratinocytes actively participate in maintaining tissue homeostasis, shaping, amplifying, and regulating immune responses in skin. Keratinocytes act as sentinels, continuously monitoring changes in the environment, and, through microbial sensing, stretch, or other physical stimuli, can initiate a broad range of inflammatory responses via secretion of various cytokines, chemokines, and growth factors. This diverse function of keratinocytes contributes to the highly variable clinical manifestation of skin immune responses. In this Review, we highlight the highly diverse functions of epidermal keratinocytes and their contribution to various immune-mediated skin diseases.

Systemic sclerosis (SSc) is a devastating autoimmune disease characterized by excessive production and accumulation of extracellular matrix, leading to fibrosis of skin and other internal organs. However, the main cellular participants in SSc skin fibrosis remain incompletely understood. Here using differentiation trajectories at a single cell level, we demonstrate a dual source of extracellular matrix deposition in SSc skin from both myofibroblasts and endothelial-to-mesenchymal-transitioning cells (EndoMT). We further define a central role of Hippo pathway effectors in differentiation and homeostasis of myofibroblast and EndoMT, respectively, and show that myofibroblasts and EndoMTs function as central communication hubs that drive key pro-fibrotic signaling pathways in SSc. Together, our data help characterize myofibroblast differentiation and EndoMT phenotypes in SSc skin, and hint that modulation of the Hippo pathway may contribute in reversing the pro-fibrotic phenotypes in myofibroblasts and EndoMTs. Systemic sclerosis (SSc) is an autoimmune disease causing skin fibrosis and organ inflammation. Here the authors generate and analyze SSc skin single cell RNA sequencing data to propose contributions from both myofibroblasts and endothelial-to-mesenchymal -transitioning cells (EndoMT) to skin fibrosis, and to implicate the involvement of Hippo signaling pathways.

A newly developed handheld device, the IC01 transpalpebral tonometer, was engineered to determine intraocular pressure (IOP) autonomously through upper eyelid palpation. This study aimed to evaluate the repeatability of the IC01 and to investigate its agreement with a non-contact tonometer (TOPCON CT-800). A comparative design was employed to analyze the agreement in IOP measurements between the innovative IC01 device and both the non-contact (TOPCON CT-800) and rebound (iCare IC200) tonometers, as well as its repeatability. Trained operators recorded measurements from 189 subjects at both the initial and one-month follow-up visits, adhering to a randomized sequence. IOP measurements from the IC01 showed no statistically significant difference from those obtained with the iCare IC200 or TOPCON CT-800. Repeatability, indicated by the intraclass correlation coefficient, averaged 0.77 for right eyes and 0.75 for left eyes. Furthermore, the mean IOP values at the one-month follow-up were 8.65 ± 4.15 mmHg for the right eye and 7.68 ± 2.61 mmHg. No sight-threatening adverse events occurred. Regarding patient preference among a subset of 69 respondents, 46.37% (n = 32) favored the IC01, compared to 17.39% (n = 12) for the TOPCON CT-800, while 36.23% (n = 25) expressed no preference. Gender did not show a significant correlation with outcomes. However, participants aged 50 years or younger demonstrated a greater preference for the IC01 (χ 2  = 5.68, P  = 0.012). The IC01 tonometer demonstrated clinical equivalence to established devices, showing superior repeatability and higher patient acceptance. Its distinctive practical advantages include the avoidance of corneal contact, operational independence from a clinician, and a design suitable for self-monitoring in a home environment.

Age related cataracts (ARC) represent the main reason for blindness globally. The lens epithelial cells (LECs) participate not only in the metabolism of many substances in the lens but also in maintaining lens transparency. This study used lipidomics to investigate the metabolic differences in LECs of ARC patients with different severity, aiming at identifying potential metabolic biomarkers of ARC. Patients diagnosed with ARC and underwent cataract surgery at Shanghai Tongren Hospital were selected to participate in this study, which were classified as mild ARC group and severe ARC group. During their cataract surgery, anterior lens capsules(LCs) containing LECs were obtained. The lipidomics of LECs were analyzed using the liquid chromatography‑mass spectrometry (LC-MS). Potential pathways of lipids were searched for using databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst platform. In LEC lipids, 26 lipids have been identified as potential biomarkers between mild ARC and severe ARC, with AUC values of 0.67–0.94. The pathway analysis results revealed that the Glycerophospholipid (GPL) metabolism was significantly influenced, indicating that these metabolic markers contribute significantly to regulating this pathway. The LEC metabolic spectrum demonstrates a proficient ability to differentiate between patients with varying levels of cataracts. Herein, we have successfully identified potential metabolic biomarkers and pathways that have proven to be valuable in enhancing our understanding of ARC pathogenesis. The finding has translational value for developing new cataract treatment methods in the future.

•The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus exhibit higher vulnerability to alterations induced by preterm birth.•The structural covariance (SC) between the thalamic and the insula show significant increase after preterm birth.•Preterm birth affects the development of the thalamus and has differential effects on its subregions. Acting as a central hub in regulating brain functions, the thalamus plays a pivotal role in controlling high-order brain functions. Considering the impact of preterm birth on infant brain development, traditional studies focused on the overall development of thalamus other than its subregions. In this study, we compared the volumetric growth and shape development of the thalamic hemispheres between the infants born preterm and full-term (Left volume: P = 0.027, Left normalized volume: P < 0.0001; Right volume: P = 0.070, Right normalized volume: P < 0.0001). The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus exhibit higher vulnerability to alterations induced by preterm birth. The structural covariance (SC) between the thickness of thalamus and insula in preterm infants (Left: corrected P = 0.0091, Right: corrected P = 0.0119) showed significant increase as compared to full-term controls. Current findings suggest that preterm birth affects the development of the thalamus and has differential effects on its subregions. The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus are more susceptible to the impacts of preterm birth.