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NETosis, a regulated form of neutrophil death, is crucial for host defense against pathogens. However, the release of neutrophil extracellular traps (NETs) during NETosis can have detrimental effects on surrounding tissues and contribute to the pro-inflammatory response, in addition to their role in controlling microbes. Although it is well-established that the IL-23-Th17 axis plays a key role in the pathogenesis of psoriasis, emerging evidence suggests that psoriasis, as an autoinflammatory disease, is also associated with NETosis. The purpose of this review is to provide a comprehensive understanding of the mechanisms underlying NETosis in psoriasis. It will cover topics such as the formation of NETs, immune cells involved in NETosis, and potential biomarkers as prognostic/predicting factors in psoriasis. By analyzing the intricate relationship between NETosis and psoriasis, this review also aims to identify novel possibilities targeting NETosis for the treatment of psoriasis.

Background The potential effects of pre-pregnancy body mass (BMI) and gestational weight gain (GWG) on pregnancy outcomes remain unclear. Thus, we investigated socio-demographic characteristics that affect pre-pregnancy BMIs and GWG and the effects of pre-pregnancy BMI and GWG on Chinese maternal and infant complications. Methods 3172 women were enrolled in the Chinese Pregnant Women Cohort Study-Peking Union Medical College from July 25, 2017 to July 24, 2018, whose babies were delivered before December 31, 2018. Regression analysis was employed to evaluate the socio-demographic characteristics affecting pre-pregnancy BMI and GWG values and their effects on adverse maternal and infant complications. Results Multivariate logistic regression analysis revealed that age groups < 20 years (OR: 1.97), 25–30 years (OR: 1.66), 30–35 years (OR: 2.24), 35–40 years (OR: 3.90) and ≥ 40 years (OR: 3.33) as well as elementary school or education below (OR: 3.53), middle school (OR: 1.53), high school (OR: 1.40), and living in the north (OR: 1.37) were risk factors in maintaining a normal pre-pregnancy BMI. An age range of 30–35 years (OR: 0.76), living in the north (OR: 1.32) and race of ethnic minorities (OR: 1.51) were factors affecting GWG. Overweight (OR: 2.01) and inadequate GWG (OR: 1.60) were risk factors for gestational diabetes mellitus (GDM). Overweight (OR: 2.80) and obesity (OR: 5.42) were risk factors for gestational hypertension (GHp). Overweight (OR: 1.92), obesity (OR: 2.48) and excessive GWG (OR: 1.95) were risk factors for macrosomia. Overweight and excessive GWG were risk factors for a large gestational age (LGA) and inadequate GWG was a risk factor for low birth weights. Conclusions Overweight and obesity before pregnancy and an excessive GWG are associated with a greater risk of developing GDM, GHp, macrosomia and LGA. The control of body weight before and during the course of pregnancy is recommended to decrease adverse pregnancy outcomes, especially in pregnant women aged < 20 or > 25 years old educated below university and college levels, for ethnic minorities and those women who live in the north of China. Trial registration Registered at Clinical Trials ( NCT03403543 ), September 29, 2017.

Cadherin 17 (CDH17) is a cell adhesion glycoprotein essential for epithelial integrity. It is frequently overexpressed in various cancers, where it is associated with aggressive behaviour. While evidence indicates that CDH17 functions as an upstream regulator of Wnt/β-catenin signalling, findings are inconsistent across tumour types, limiting the assessment of CDH17 as a biomarker or therapeutic target for Wnt pathway in cancer. In this study, we systematically review and meta-analyse the relationship between CDH17 and Wnt/β-catenin signalling in human cancers and evaluate whether CDH17 modulation affects tumour behaviour through Wnt-related mechanisms. Our search of Medline, Web of Science and Scopus identified five studies examining CDH17 expression in the Wnt/β-catenin pathway in vitro and in vivo. All five studies identified CDH17 as a key driver of canonical Wnt signalling, directly influencing cancer progression in hepatocellular carcinoma (HCC), gastric cancer (GC), and colorectal cancer (CRC). Meta-analysis (MA) showed that CDH17 inhibition consistently reduced Wnt/β-catenin downstream T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) transcriptional activity (MD = −1.32, 95% CI: −1.64 to −0.99, p < 0.00001). Narrative synthesis found that CDH17 suppression decreased total and nuclear β-catenin, phosphorylated glycogen synthase kinase-3 beta (GSK-3β), and cyclin D1 while increasing tumour suppressors, retinoblastoma (Rb) and p53/p21. These changes were associated with reduced proliferation, colony formation, migration, invasion and cell cycle arrest. In vivo, CDH17 suppression resulted in 80–95% tumour growth suppression (Mean Difference (MD) = −96.67, 95% CI: [−144.35, −48.98], p < 0.0001), with immunohistochemistry confirming cytoplasmic β-catenin sequestration and lower cyclin D1 levels. Collectively, these findings show CDH17 as a critical upstream effector sustaining Wnt/β-catenin signalling, cancer progression, tumour proliferation, stem cell properties, and metastasis, and support CDH17 inhibition as a promising therapeutic target across multiple cancer types.

Genotoxic therapy triggers reactive oxygen species (ROS) production and oxidative tissue injury. S-nitrosylation is a selective and reversible posttranslational modification of protein thiols by nitric oxide (NO), and 5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for NO synthesis. However, the mechanism by which BH4 affects protein S-nitrosylation and ROS generation has not been determined. Here, we showed that ionizing radiation disrupted the structural integrity of BH4 and downregulated GTP cyclohydrolase I (GCH1), which is the rate-limiting enzyme in BH4 biosynthesis, resulting in deficiency in overall protein S-nitrosylation. GCH1-mediated BH4 synthesis significantly reduced radiation-induced ROS production and fueled the global protein S-nitrosylation that was disrupted by radiation. Likewise, GCH1 overexpression or the administration of exogenous BH4 protected against radiation-induced oxidative injury in vitro and in vivo. Conditional pulmonary Gch1 knockout in mice ( Gch1 fl/fl ; Sftpa1-Cre +/− mice) aggravated lung injury following irradiation, whereas Gch1 knock-in mice ( Gch1 lsl/lsl ; Sftpa1-Cre +/− mice) exhibited attenuated radiation-induced pulmonary toxicity. Mechanistically, lactate dehydrogenase (LDHA) mediated ROS generation downstream of the BH4/NO axis, as determined by iodoacetyl tandem mass tag (iodoTMT)-based protein quantification. Notably, S-nitrosylation of LDHA at Cys163 and Cys293 was regulated by BH4 availability and could restrict ROS generation. The loss of S-nitrosylation in LDHA after irradiation increased radiosensitivity. Overall, the results of the present study showed that GCH1-mediated BH4 biosynthesis played a key role in the ROS cascade and radiosensitivity through LDHA S-nitrosylation, identifying novel therapeutic strategies for the treatment of radiation-induced lung injury. Radiation-induced Lung Injury Mitigated by GCH1-Mediated ROS Regulation Radiation therapy for cancer can harm healthy tissues, causing swelling and oxidative stress (an imbalance between free radicals and antioxidants in your body). This research examined the part of a molecule named tetrahydrobiopterin (BH4) in this. The scientists discovered that radiation therapy decreases the amount of BH4 in the body, which then leads to a rise in harmful reactive oxygen species (ROS - molecules that can damage cells). However, when BH4 amounts were artificially boosted, this lowered ROS levels and shielded against radiation-caused harm. This implies that BH4 might be used as a treatment to guard against the damaging side effects of radiation therapy. More research is required to further investigate this potential in clinic. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Rolling bearings are crucial parts of primary mine fans. In order to guarantee the safety of coal mine production, primary mine fans commonly work during regular operation and are immediately shut down for repair in case of failure. This causes the sample imbalance phenomenon in fault diagnosis (FD), i.e., there are many more normal state samples than faulty ones, seriously affecting the precision of FD. Therefore, the current study presents an FD approach for the rolling bearings of primary mine fans under sample imbalance conditions via symmetrized dot pattern (SDP) images, denoising diffusion probabilistic models (DDPMs), the image generation method, and a convolutional neural network (CNN). First, the 1D bearing vibration signal was transformed into an SDP image with significant characteristics, and the DDPM was employed to create a generated image with similar feature distributions to the real fault image of the minority class. Then, the generated images were supplemented into the imbalanced dataset for data augmentation to balance the minority class samples with the majority ones. Finally, a CNN was utilized as a fault diagnosis model to identify and detect the rolling bearings’ operating conditions. In order to assess the efficiency of the presented method, experiments were performed using the regular rolling bearing dataset and primary mine fan rolling bearing data under actual operating situations. The experimental results indicate that the presented method can more efficiently fit the real image samples’ feature distribution and generate image samples with higher similarity than other commonly used methods. Moreover, the diagnostic precision of the FD model can be effectively enhanced by gradually expanding and enhancing the unbalanced dataset.

Umbilical cord blood (UCB) plays substantial roles in hematopoietic stem cell (HSC) transplantation and regenerative medicine. UCB is usually cryopreserved for years before use. It remains unclear whether and how cryopreservation affects UCB function. We constructed a single-cell transcriptomics profile of CD34+ hematopoietic stem and progenitor cells (HSPCs) and mononuclear cells (MNCs) from fresh and cryopreserved UCB stored for 1, 5, 10, and 19 years. Compared with fresh UCB, cryopreserved HSCs and multipotent progenitors (MPPs) exhibited more active cell-cycle and lower expression levels of HSC and multipotent progenitor signature genes. Hematopoietic reconstitution of cryopreserved HSPCs gradually decreased during the first 5 years but stabilized thereafter, aligning with the negative correlation between clinical neutrophil engraftment and cryopreservation duration of UCB. Cryopreserved HSPCs also showed reduced megakaryocyte generation. In contrast, cryopreserved NK cells and T cells maintained a capacity for cytokine production and cytotoxicity comparable to that of fresh cells. Mechanistically, cryopreserved HSPCs exhibited elevated ROS, reduced ATP synthesis, and abnormal mitochondrial distribution, which collectively led to attenuated hematopoietic reconstitution. These effects could be ameliorated by sulforaphane (SF). Together, we elucidate the negative effect of cryopreservation on UCB HSPCs and identify SF as a mitigation strategy, broadening the temporal window and scope for clinical applications of cryopreserved UCB.

Radiation-induced lung injury is a common complication of radiotherapy for lung cancer, breast cancer, esophageal cancer, and thymoma. This study aims to illustrate biomarkers of radiation-induced lung injury and its potential mechanism through the study of metabolomic alterations in serum of Sprague-Dawley rats with different radiation doses. Serum from 0, 10, or 20 Gy irradiated rats were collected and subjected to gas chromatography-mass spectrometry. The result showed that there were 23 dysregulated metabolites between the 10 Gy irradiation group and the 0 Gy control group, whereas 36 preferential metabolites were found between the 20 Gy irradiated rat serum and the control groups. Among them, there were 19 common differential metabolites in the 2 irradiation groups, including 3 downregulated (benzyl thiocyanate, carbazole, and N-formyl-L-methionine) and 16 upregulated metabolites. We further analyzed the metabolic pathways of different metabolites; the results showed that there were 3 significant enrichment pathways in the 10 Gy vs 0 Gy group and 7 significant enrichment pathways in the 20 Gy vs 0 Gy group. Among them, taurine and hypotaurine metabolism, riboflavin metabolism, and glyoxylate and dicarboxylate metabolism were the common metabolic enrichment pathways of the 10 Gy vs 0 Gy group and the 20 Gy vs 0 Gy group.

Background This study aims to explore the relationships between pre-pregnancy body mass index (BMI), gestational weight gain (GWG), rate of GWG during the second and third trimesters (GWG rate ) and birth weight among Chinese women. Methods Women were enrolled by 24 hospitals in 15 different provinces in mainland China from July 25th, 2017 to 26 November 2018. Pre-pregnancy BMI, GWG and GWG rate were calculated and divided in to different groups. The multinomial logistic regression model and restrictive cubic spline model were used to explore the relationships. Results Of the 3585 participants, women who were underweight, had insufficient GWG or GWG rate had 1.853-, 1850- or 1.524-fold higher risks for delivering small-for-gestational-age (SGA) infant compared with women who had normal BMI, sufficient GWG or GWG rate . Women who were overweight/obese, had excessive GWG or GWG rate had 1.996-, 1676- or 1.673-fold higher risks for delivering large-for-gestational-age (LGA) infant. The effects of GWG and GWG rate on birth weight varied by pre-pregnancy BMI statuses. Dose-response analysis demonstrated L-shaped and S-shaped relationships between pre-pregnancy BMI, GWG, GWG rate and neonatal birth weight. Conclusions Pre-pregnancy BMI, GWG or GWG rate were associated with neonatal birth weight among Chinese women. Both body weight before and during pregnancy should be maintained within the recommendations to prevent abnormal birth weight.

Autonomous artificial intelligence (AI) models for deciding treatment strategies are available but rarely applied prospectively in clinical settings. Here we present a prospective study of deploying daGOAT, an algorithm we have developed, as a conditional autonomous AI agent to prescribe a drug to prevent severe (grade 3−4) acute graft-versus-host disease (acute GvHD) following human leukocyte antigen (HLA)-mismatched haematopoietic cell transplantation (ClinicalTrials.gov, NCT05600855). During the enrollment period physicians invite 85% of eligible patients to participate and 88% of the invited patients agree. Among the 110 enrolled participants who receive HLA-haploidentical transplants, daGOAT predicts intermediate to high risk of severe acute GvHD in 57 participants between days +17 and +23 posttransplant and prescribes ruxolitinib in addition to the existing regimen to intensify immune suppression. The initial compliance with AI prescription is 98% (56/57), with dose and/or schedule deviating from the AI prescription within one month in a total of eight participants. In conclusion, we show that many physicians and patients are receptive to using conditional autonomous AI to prescribe a drug and that the decision for pharmaceutical intervention could be facilitated by autonomous AI. Autonomous artificial intelligence (AI) models to replace human decision-making in medical intervention need thorough testing. Here authors present the results of a clinical trial, NCT05600855, in which daGOAT, a conditional autonomous artificial intelligence agent successfully makes the decision whether to prescribe an immune suppressive drug to prevent severe acute graft-versus-host disease following HLA-mismatched haematopoietic cell transplantation.