An In Vivo Assessment of a Novel Temperature Control Flexible Ureteroscope System for Monitoring and Controlling Intrarenal Temperature During Flexible Ureteroscopy.

OBJECTIVE: To evaluate the efficacy of a novel temperature control flexible ureteroscope system in the precise monitoring and control of intrarenal temperature during ureteroscopy. METHODS: We developed a novel temperature control flexible ureteroscope system (PT-Scope), including a temperature-monitoring ureteroscope and a irrigation-suction platform for temperature regulation. A porcine thermometry model was established to observe temperature changes under varying holmium laser powers (10, 20, 30W) and irrigation rates (0, 20, 50 ml/min), utilizing PCN thermometry and PT-Scope measurements, with subsequent evaluation of temperature variations at different distances from the laser fiber tip. A porcine kidney stone model was established while porcine were randomly assigned to two groups: In the temperature control group, PT-Scope was connected to the irrigation-suction platform with temperature regulation, while in the non-temperature control group without temperature regulation. Comparative analysis was performed to evaluate differences in intrarenal temperature between the two groups. RESULTS: Across various laser powers and irrigation rates, the temperature measurement capability of the PT-Scope was precise, demonstrating consistency with PCN temperature measurements. The temperature obtained from the PT-Scope reflect the temperature approximately 0.05 cm away from the fiber tip, whereas temperatures close to fiber tip were significantly higher. The peak temperature of the temperature control group vs non-temperature control group were 31.70±2.609℃and 44.37±3.318℃, respectively (p<0.01). The mean temperature of the temperature control group vs non-temperature control group was 27.40±2.107℃ vs 35.9±1.921℃(p <0.01). CONCLUSION: PT-Scope has demonstrated the capability to precisely monitor and control intrarenal temperature within a safe threshold.

Evaluating the role of DNA methyltransferases in trophoblast fusion and preeclampsia development: Insights from methylation-regulated genes.

The etiology of preeclampsia (PE), a complex and multifactorial condition, remains incompletely understood. DNA methylation, which is primarily regulated by three DNA methyltransferases (DNMTs), DNMT1, DNMT3A, and DNMT3B, plays a vital role in early embryonic development and trophectoderm differentiation. Yet, how DNMTs modulate trophoblast fusion and PE development remains unclear. In this study, we found that the DNMTs expression was downregulated during trophoblast cells fusion. Downregulation of DNMTs was observed during the reconstruction of the denuded syncytiotrophoblast (STB) layer of placental explants. Additionally, overexpression of DNMTs inhibited trophoblast fusion. Conversely, treatment with the DNA methylation inhibitor 5-aza-CdR decreased the expression of DNMTs and promoted trophoblast fusion. A combined analysis of DNA methylation data and gene transcriptome data obtained from the primary cytotrophoblasts (CTBs) fusion process identified 104 potential methylation-regulated differentially expressed genes (MeDEGs) with upregulated expression due to DNA demethylation, including CD59, TNFAIP3, SDC1, and CDK6. The transcription regulation region (TRR) of TNFAIP3 showed a hypomethylation with induction of 5-aza-CdR, which facilitated CREB recruitment and thereby participated in regulating trophoblast fusion. More importantly, clinical correlation analysis of PE showed that the abnormal increase in DNMTs may be involved in the development of PE. This study identified placental DNA methylation-regulated genes that may contribute to PE, offering a novel perspective on the role of epigenetics in trophoblast fusion and its implication in PE development.

Generating Synthetic Electronic Health Record Data Using Generative Adversarial Networks: Tutorial.

Synthetic electronic health record (EHR) data generation has been increasingly recognized as an important solution to expand the accessibility and maximize the value of private health data on a large scale. Recent advances in machine learning have facilitated more accurate modeling for complex and high-dimensional data, thereby greatly enhancing the data quality of synthetic EHR data. Among various approaches, generative adversarial networks (GANs) have become the main technical path in the literature due to their ability to capture the statistical characteristics of real data. However, there is a scarcity of detailed guidance within the domain regarding the development procedures of synthetic EHR data. The objective of this tutorial is to present a transparent and reproducible process for generating structured synthetic EHR data using a publicly accessible EHR data set as an example. We cover the topics of GAN architecture, EHR data types and representation, data preprocessing, GAN training, synthetic data generation and postprocessing, and data quality evaluation. We conclude this tutorial by discussing multiple important issues and future opportunities in this domain. The source code of the entire process has been made publicly available.

Cation-Modified Poly(vinyl alcohol) Film to Optimize the Bistability of Transparent Electrophoretic Display Based on Charge Adsorption Behavior in Nonpolar Solvent.

Electrophoretic displays (EPDs) utilize the electrophoretic particles in electronic ink (e-ink) to display different color states with bistability. Bistability of EPDs is achieved by placing colloidal particles in a highly viscous solvent to keep the distribution of colloidal particles stable without sustaining the external field, so it only consumes power when updating the image. The feature of low power consumption makes it suitable for applications such as advertising boards, price tags, etc. Apart from these applications, recent research on lateral-driving EPDs extends its applications to smart windows, privacy control, and so on. However, achieving bistability by simply increasing the viscosity of solvent is inefficient in the case of lateral driving operation. Therefore, it is deserving to have intensive study on the mechanism of bistability from other aspects. Herein, we propose a mechanism to investigate the charge adsorption behavior on the electrode to affect the bistability of particles, which is based on the "Stern layer adsorption/desorption" model. Based on the above mechanism, we further fabricated a hexadecyl trimethylammonium bromide (CTAB)/poly(vinyl alcohol) (PVA) composite film on the electrode to improve the bistability of lateral-driving EPD by reducing the diffusion current caused by unabsorbed charges. This developed lateral-driving EPD can significantly improve the bistability, which is enhanced from 40 s to 7 min, an increase by a factor of approximately 10. This work gives a way to consider the bistability of colloidal particles in nonpolar solvent.

Bibliometric analysis of research progress on tetramethylpyrazine and its effects on ischemia-reperfusion injury.

In recent decades, natural products have attracted worldwide attention and become one of the most important resources for pharmacological industries and medical sciences to identify novel drug candidates for disease treatment. Tetramethylpyrazine (TMP) is an alkaloid extracted from Ligusticum chuanxiong Hort., which has shown great therapeutic potential in cardiovascular and cerebrovascular diseases, liver and renal injury, as well as cancer. In this review, we analyzed 1270 papers published on the Web of Science Core Collection from 2002 to 2022 and found that TMP exerted significant protective effects on ischemia-reperfusion (I/R) injury that is the cause of pathological damages in a variety of conditions, such as ischemic stroke, myocardial infarction, acute kidney injury, and liver transplantation. TMP is limited in clinical applications to some extent due to its rapid metabolism, a short biological half-life and poor bioavailability. Obviously, the structural modification, administration methods and dosage forms of TMP need to be further investigated in order to improve its bioavailability. This review summarizes the clinical applications of TMP, elucidates its potential mechanisms in protecting I/R injury, provides strategies to improve bioavailability, which presents a comprehensive understanding of the important compound. Hopefully, the information and knowledge from this review can help researchers and physicians to better improve the applications of TMP in the clinic.

[Mechanism and compatibility efficacy of Astragali Radix-Chuanxiong Rhizoma drug pair in treating ischemic stroke based on network regulation].

Based on the association network of "drug pair-disease", the effect characteristics of Astragali Radix-Chuanxiong Rhizoma drug pair in the treatment of ischemic stroke(IS) with Qi deficiency and blood stasis and the matching mechanism of the two were explored. Through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction Database, the effective chemical components of the drug pair were screened, and the candidate targets were predicted. Databa-ses such as GeneCards, DrugBank, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD) were searched to obtain gene targets related to IS. Through STRING and Cytoscape 3.9.1 software, the protein-protein interaction(PPI) network was constructed by using the interaction information of disease syndrome-related genes and candidate targets of drug pairs, and the core targets were screened according to the network topological feature values. Based on the Metascape platform and DAVID database, the biomolecular interaction information was integrated to analyze the Kyoto Encyclopedia of Genes and Genomes(KEGG) and mine biological functions, so as to further explore the mechanism of action and compatibility characteristics of Astragali Radix-Chuan-xiong Rhizoma. The results showed that the candidate biological process was mainly involved in the regulation of functional modules such as immune, blood circulation, neurotransmitter, and oxidative stress, and it was enriched in lipid and atherosclerosis, calcium signaling pathway, and platelet activation. Astragali Radix and Chuanxiong Rhizoma have their own characteristics. Astragali Radix has a regulatory response to growth factors while maintaining the body's immune balance, while Chuanxiong Rhizoma mainly improves the circulatory system and participates in hormone metabolism, so as to indicate the compatibility mechanism of Astragali Radix-Chuanxiong Rhizoma drug pair for multi-target and multi-pathway synergistic treatment of IS. Through further experimental verification, it was found that the Astragali Radix-Chuanxiong Rhizoma drug pair could significantly down-regulate the expression of key targets including TLR4, NF-κB, IL-1ß, F2R, PLCß1, and MYLK. This study preliminarily reveals that the Astragali Radix-Chuanxiong Rhizoma drug pair may play the three replenishing effects of promoting blood circulation, benefiting Qi, and clearing collaterals by correcting immune di-sorders, blood circulation disorders, and inflammation, which provide support for the clinical research on the subsequent improvement of Qi deficiency and blood stasis in the treatment of IS and provide a new idea for the analysis of modern biological connotation of the compatibility of seven emotions of traditional Chinese medicine.

[Mechanism of tetramethylpyrazine intervention with ischemia-reperfusion rats based on Nrf2/HO-1/CXCR4 pathway through regulating neural stem cell migration].

This study aims to decipher the mechanism of tetramethylpyrazine(TMP) in regulating the migration of neural stem cells(NSCs) in the rat model of middle cerebral artery occlusion(MCAO) via the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)/C-X-C motif chemokine receptor 4(CXCR4) pathway. SD rats were randomized into sham, MCAO(model), and tetramethylpyrazine(TMP, 20 mg·kg~(-1) and 40 mg·kg~(-1)) groups. The neurological impairment was assessed by the modified neurological severity score(mNSS). The immunofluorescence assay was employed to detect the cells stained with both 5-bromodeoxyuridine(BrdU) and doublecortin(DCX) in the brain tissue. The effect of TMP on the migration of C17.2 cells was observed. Western blot was employed to determine the protein levels of Nrf2, HO-1, p62, NAD(P)H quinone oxidoreductase 1(NQO1), stromal cell-derived factor 1(SDF-1), and CXCR4 in the brain tissue and C17.2 cells. The results showed that after 7 days and 21 days of mode-ling, the mNSS and BrdU~+/DCX~+ cells were increased, and the expression of Nrf2 and CXCR4 in the brain tissue was up-regulated. Compared with the model group, TMP(40 mg·kg~(-1)) reduced the mNSS, increased the number of BrdU~+/DCX~+ cells, and up-regulated the expression of Nrf2, CXCR4, and SDF-1. In addition, TMP promoted the migration of C17.2 cells and up-regulated the expression of p62, Nrf2, HO-1, and NQO1 in a time-and dose-dependent manner. The expression was the highest at the time point of 12 h in the TMP(50 µg·mL~(-1)) group(P<0.01). In conclusion, TMP activates the Nrf2/HO-1/CXCR4 pathway to promote the migration of NSCs to the ischemic area, thus exerting the therapeutic effect on the ischemia-reperfusion injury. This study provides experimental support for the application of TMP in ischemic stroke.

[Mechanism of tetramethylpyrazine combined with neural stem cells transplantation on cerebral ischemia-reperfusion rats].

This study aimed to investigate the intervention effect of tetramethylpyrazine(TMP) combined with transplantation of neural stem cells(NSCs) on middle cerebral artery occlusion(MCAO) rat model and to explore the mechanism of TMP combined with NSCs transplantation on ischemic stroke based on the regulation of stem cell biological behavior. MCAO rats were randomly divided into a model group, a TMP group, an NSCs transplantation group, and a TMP combined with NSCs transplantation group according to neurological function scores. A sham group was set up at the same time. The neurological function score was used to evaluate the improvement of neurological function in MCAO rats after TMP combined with NSCs transplantation. The proliferation, migration, and differentiation of NSCs were evaluated by BrdU, BrdU/DCX, BrdU/NeuN, and BrdU/GFAP immunofluorescence labeling. The protein expression of stromal cell-derived factor 1(SDF-1), C-X-C motif chemokine receptor 4(CXCR4), as well as oxidative stress pathway proteins nuclear factor erythroid 2-related factor 2(Nrf2), Kelch-like ECH-associated protein 1(KEAP1), heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1) was detected by Western blot to study the migration mechanism of TMP combined with NSCs. The results showed that TMP combined with NSCs transplantation significantly improved the neurological function score in MCAO rats. Immunofluorescence staining showed a significant increase in the number of BrdU~+, BrdU~+/DCX~+, BrdU~+/NeuN~+, and BrdU~+/GFAP~+ cells in the TMP, NSCs transplantation, and combined treatment groups, with the combined treatment group showing the most significant increase. Further Western blot analysis revealed significantly elevated expression of CXCR4 protein in the TMP, NSCs transplantation, and combined treatment groups, along with up-regulated protein expression of Nrf2, HO-1, and NQO1, and decreased KEAP1 protein expression. This study showed that both TMP and NSCs transplantation can promote the recovery of neurological function by promoting the proliferation, migration, and differentiation of NSCs, and the effect of TMP combined with NSCs transplantation is superior. The mechanism of action may be related to the activation of the Nrf2/HO-1/CXCR4 pathway.

[Optimization and verification of conditions for induction of neutrophil extracellular traps in vitro].

This study aims to optimize the conditions for the formation of neutrophil extracellular traps(NETs) in vitro, so as to establish a relatively stable experimental research platform. Different conditions were compared, including commonly used laboratory animals(rats and mice) and a variety of cell sources(bone marrow neutrophils and peripheral blood neutrophils separated by percoll density gradient centrifugation). Different inducers like lipopolysaccharide(LPS) and phorbol 12-myristate 13-acetate(PMA) were used for induction in vitro. Myeloperoxidase(MPO)/citrullinated histone H3(CitH3)/DAPI immunofluorescence and cell free DNA(cf-DNA) content determination were used for comprehensive evaluation to screen the optimal conditions for the formation of NETs induced in vitro. Furthermore, the stability of the selected conditions for inducing the formation of NETs in vitro was evaluated by tetramethylpyrazine(TMP), an active component in Chinese herbal medicines. The results showed that coated poly-D-lysine(PDL) induced the formation of NETs in bone marrow neutrophils of mice to a certain extent. Both LPS and PMA significantly up-regulated the protein levels of MPO and CitH3 in mouse bone marrow neutrophils and elevated the cfDNA level in the supernatant of rat peripheral blood neutrophils. The cfDNA level in the PMA-induced group increased more significantly than that in the LPS-induced group(P<0.05). The results of immunofluorescence staining showed that the expression of MPO and CitH3 in mouse bone marrow neutrophils, rat bone marrow neutrophils, and rat peripheral blood neutrophils were significantly increased after PMA induction, especially in rat peripheral blood neutrophils. TMP significantly down-regulated the protein levels of MPO, CitH3, and neutrophil elastase(NE) in rat peripheral blood neutrophils induced by PMA. In conclusion, treating the peripheral blood neutrophils of rats with PMA is the optimal condition for inducing the formation of NETs in vitro. This study provides an optimal platform for in vitro studies based on NETs and a basis for studying the effects of traditional Chinese medicines targeting NETs.

[Mechanism of bulleyaconitine A in inhibiting bone destruction of rheumatoid arthritis via Src/PI3K/Akt signaling pathway].

Based on the sarcoma receptor coactivator(Src)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, the mechanism of action of bulleyaconitine A in the treatment of bone destruction of experimental rheumatoid arthritis(RA) was explored. Firstly, key targets of RA bone destruction were collected through GeneCards, PharmGKB, and OMIM databa-ses. Potential targets of bulleyaconitine A were collected using SwissTargetPrediction and PharmMapper databases. Next, intersection targets were obtained by the Venny 2.1.0 platform. Protein-protein interaction(PPI) network and topology analysis were managed by utilizing the STRING database and Cytoscape 3.8.0. Then, Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were conducted in the DAVID database. AutoDock Vina was applied to predict the molecular docking and binding ability of bulleyaconitine A with key targets. Finally, a receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model was established in vitro. Quantitative real-time polymerase chain reaction(qRT-PCR) was used to detect the mRNA expression levels of related targets, and immunofluorescence and Western blot were adopted to detect the protein expression level of key targets. It displayed that there was a total of 29 drug-disease targets, and Src was the core target of bulleyaconitine A in anti-RA bone destruction. Furthermore, KEGG enrichment analysis revealed that bulleyaconitine A may exert an anti-RA bone destruction effect by regulating the Src/PI3K/Akt signaling pathway. The molecular docking results showed that bulleyaconitine A had better bin-ding ability with Src, phosphatidylinositol-4,5-diphosphate 3-kinase(PIK3CA), and Akt1. The result of the experiment indicated that bulleyaconitine A not only dose-dependently inhibited the mRNA expression levels of osteoclast differentiation-related genes cathepsin K(CTSK) and matrix metalloproteinase-9(MMP-9)(P<0.01), but also significantly reduced the expression of p-c-Src, PI3K, as well as p-Akt in vitro osteoclasts(P<0.01). In summary, bulleyaconitine A may inhibit RA bone destruction by regulating the Src/PI3K/Akt signaling pathway. This study provides experimental support for the treatment of RA bone destruction with bulleyaconitine A and lays a foundation for the clinical application of bulleyaconitine A.

HMGB1 regulates autophagy of placental trophoblast through ERK signaling pathway.

OBJECTIVE: The purpose of this study is to investigate the role of high mobility group protein B1 (HMGB1) in placental development and fetal growth. METHODS: We employed the Cre-loxP recombination system to establish a placenta-specific HMGB1 knockout mouse model. Breeding HMGB1flox/flox mice with Elf5-Cre mice facilitated the knockout, leveraging Elf5 expression in extra-embryonic ectoderm, ectoplacental cone, and trophoblast giant cells at 12.5 days of embryonic development. The primary goal of this model was to elucidate the molecular mechanism of HMGB1 in placental development, assessing parameters such as placental weight, fetal weight, and bone development. Additionally, we utilized lentiviral interference and overexpression of HMGB1 in human trophoblast cells to further investigate HMGB1's functional role. RESULTS: Our findings indicate that HMGB1flox/floxElf5cre/+ mouse display fetal growth restriction (FGR), characterized by decreased placental and fetal weight and impaired bone development. And the absence of HMGB1 inhibits autophagosome formation, impairs lysosomal degradation, and disrupts autophagic flux. Depletion of HMGB1 in human trophoblast cells also suppresses cell viability, proliferation, migration, and invasion by inhibiting the ERK signaling pathway. Overexpression of HMGB1 observed the opposite phenotypes. CONCLUSIONS: HMGB1 participates in the regulation of autophagy through the ERK signaling pathway and affects placental development.

Antibacterial activity of cinnamon essential oil and its main component of cinnamaldehyde and the underlying mechanism.

Background: Plant essential oils have long been regarded as repositories of antimicrobial agents. In recent years, they have emerged as potential alternatives or supplements to antimicrobial drugs. Although literature reviews and previous studies have indicated that cinnamon essential oil (CIEO) and its major component, cinnamaldehyde (CID), possess potent antibacterial activities, their antibacterial mechanisms, especially the in vivo antibacterial mechanisms, remain elusive. Methods: In this study, we utilized the in vivo assessment system of Caenorhabditis elegans (C. elegans) to investigate the effects and mechanisms of high dose (100 mg/L) and low dose (10 mg/L) CIEO and CID in inhibiting Pseudomonas aeruginosa (P. aeruginosa). In addition, we also examined the in vitro antibacterial abilities of CIEO and CID against other common pathogens including P. aeruginosa and 4 other strains. Results: Our research revealed that both high (100 mg/L) and low doses (10 mg/L) of CIEO and CID treatment significantly alleviated the reduction in locomotion behavior, lifespan, and accumulation of P. aeruginosa in C. elegans infected with the bacteria. During P. aeruginosa infection, the transcriptional expression of antimicrobial peptide-related genes (lys-1 and lys-8) in C. elegans was upregulated with low-dose CIEO and CID treatment, while this trend was suppressed at high doses. Further investigation suggested that the PMK-1 mediated p38 signaling pathway may be involved in the regulation of CIEO and CID during nematode defense against P. aeruginosa infection. Furthermore, in vitro experimental results also revealed that CIEO and CID exhibit good antibacterial effects, which may be associated with their antioxidant properties. Conclusion: Our results indicated that low-dose CIEO and CID treatment could activate the p38 signaling pathway in C. elegans, thereby regulating antimicrobial peptides, and achieving antimicrobial effects. Meanwhile, high doses of CIEO and CID might directly participate in the internal antimicrobial processes of C. elegans. Our study provides research basis for the antibacterial properties of CIEO and CID both in vivo and in vitro.

Elucidating the role of MICAL1 in pan-cancer using integrated bioinformatics and experimental approaches.

Molecule interacting with CasL 1 (MICAL1) is a crucial protein involved in cell motility, axon guidance, cytoskeletal dynamics, and gene transcription. This pan-cancer study analyzed MICAL1 across 33 cancer types using bioinformatics and experiments. Dysregulated expression, diagnostic potential, and prognostic value were assessed. Associations with tumor characteristics, immune factors, and drug sensitivity were explored. Enrichment analysis revealed MICAL1's involvement in metastasis, angiogenesis, metabolism, and immune pathways. Functional experiments demonstrated its impact on renal carcinoma cells. These findings position MICAL1 as a potential biomarker and therapeutic target in specific cancers, warranting further investigation into its role in cancer pathogenesis.

NSD2 modulates Drp1-mediated mitochondrial fission in chronic renal allograft interstitial fibrosis by methylating STAT1.

Renal interstitial fibrosis/tubular atrophy (IF/TA) is a prominent pathological feature of chronic allograft dysfunction (CAD). Our previous study has demonstrated that epithelial-mesenchymal transition (EMT) plays a significant role in shaping the development of IF/TA. Nuclear SET domain (NSD2), a histone methyltransferase catalyzing methylation at lysine 36 of histone 3, is crucially involved in the development and progression of solid tumors. But its role in the development of renal allograft interstitial fibrosis has yet to be elucidated. Here, we characterize NSD2 as a crucial mediator in the mouse renal transplantation model in vivo and a model of tumor necrosis factor-α (TNF-α) stimulated-human renal tubular epithelial cells (HK-2) in vitro. Functionally, NSD2 knockdown inhibits EMT, dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in mice. Conversely, NSD2 overexpression exacerbates fibrosis-associated phenotypes and mitochondrial fission in tubular cells. Mechanistically, tubular NSD2 aggravated the Drp-1 mediated mitochondrial fission via STAT1/ERK/PI3K/Akt signaling pathway in TNF-α-induced epithelial cell models. Momentously, mass spectrometry (MS) Analysis and site-directed mutagenesis assays revealed that NSD2 interacted with and induced Mono-methylation of STAT1 on K173, leading to its phosphorylation, IMB1-dependent nuclear translocation and subsequent influence on TNF-α-induced EMT and mitochondrial fission in NSD2-dependent manner. Collectively, these findings shed light on the mechanisms and suggest that targeting NSD2 could be a promising therapeutic approach to enhance tubular cell survival and alleviate interstitial fibrosis in renal allografts during CAD.

Single-cell analysis extracted CAFs-related genes to established online app to predict clinical outcome and radiotherapy prognosis of prostate cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a significant role in regulating the clinical outcome and radiotherapy prognosis of prostate cancer (PCa). The aim of this study is to identify CAFs-related genes (CAFsRGs) using single-cell analysis and evaluate their potential for predicting the prognosis and radiotherapy prognosis in PCa. METHODS: We acquire transcriptome and single-cell RNA sequencing (scRNA-seq) results of PCa and normal adjacent tissues from The GEO and TCGA databases. The "MCPcounter" and "EPIC" R packages were used to assess the infiltration level of CAFs and examine their correlation with PCa prognosis. ScRNA-seq and differential gene expression analyses were used to extract CAFsRGs. We also applied COX and LASSO analysis to further construct a risk score (CAFsRS) to assess biochemical recurrence-free survival (BRFS) and radiotherapy prognosis of PCa. The predictive efficacy of CAFsRS was evaluated by ROC curves and subgroup analysis. Finally, we integrated the CAFsRS gene signature with relevant clinical features to develop a nomogram, enhancing the predictive accuracy. RESULTS: The abundance of CAFs is associated with a poor prognosis of PCa patients. ScRNA-seq and differential gene expression analysis revealed 323 CAFsRGs. After COX and LASSO analysis, we obtained seven CAFsRGs with prognostic significance (PTGS2, FKBP10, ENG, CDH11, COL5A1, COL5A2, and SRD5A2). Additionally, we established a risk score model based on the training set (n = 257). The ROC curve was used to confirm the performance of CAFsRS (The AUC values for 1, 3 and 5-year survival were determined to be 0.732, 0.773, and 0.775, respectively.). The testing set (n = 129), GSE70770 set (n = 199) and GSE116918 set (n = 248) revealed that the model exhibited exceptional predictive performance. This was also confirmed by clinical subgroup analysis. The violin plot demonstrated a statistically significant disparity in the CAFs infiltrations between the high-risk and low-risk groups of CAFsRS. Further analysis confirmed that both CAFsRS and T stage were independent prognostic factors for PCa. The nomogram was then established and its excellent predictive performance was demonstrated through calibration and ROC curves. Finally, we developed an online prognostic prediction app ( https://sysu-symh-cafsnomogram.streamlit.app/ ) to facilitate the practical application of the nomogram. CONCLUSIONS: The prognostic prediction risk score model we constructed could accurately predict BRFS and radiotherapy prognosis PCa, which can provide new ideas for clinicians to develop personalized PCa treatment and follow-up programs.

A nomogram for predicting the risk of preeclampsia in women with intrahepatic cholestasis of pregnancy based on prenatal monitoring time: a multicenter retrospective cohort study.

BACKGROUND AND AIMS: Intrahepatic cholestasis of pregnancy (ICP) is a special liver disease during pregnancy, characterized by abnormal bile acid metabolism. However, there is no consensus on how to group women with ICP based on the time of diagnosis worldwide. This study aimed to adopt a new grouping model of women with ICP, and the time from diagnosis to delivery was defined as the monitoring period. METHODS: This retrospective real-world data study was conducted across multiple centers and included 3172 women with ICP. The study first evaluated the significant difference in medication and nonmedication during different monitoring times. The least absolute shrinkage and selection operator (LASSO) model was then used to screen nine risk factors based on the predictors. The model's discrimination, clinical usefulness, and calibration were assessed using the area under the receiver operating characteristic (ROC) curve, decision curve, and calibration analysis. RESULTS: The incidence of preeclampsia risk in ICP patients without drug intervention increased with the extension of the monitoring period. However, the risk of preeclampsia decreased in ICP patients treated with ursodeoxycholic acid. A predictive nomogram and risk score model was developed based on nine risk factors. The area under the ROC curve of the nomogram was 0.765 [95% confidence interval (CI): 0.724-0.807] and 0.812 (95% CI: 0.736-0.889) for the validation cohort. CONCLUSIONS: This study found that a longer ICP monitoring period could lead to adverse pregnancy outcomes in the absence of drug intervention, especially preeclampsia. A predictive nomogram and risk score model was developed to better manage ICP patients, maintain pregnancy to term delivery, and minimize the risk of severe adverse maternal and fetal outcomes.

Active matrix driven electrophoretic display with in-plane switching layout and driving waveform for reflective and transparent modes.

In-plane switching electrophoretic display (IPS-EPD) is an emerging field of display technology which achieves particles moving horizontally through a lateral electric field. Compared to vertically driven electrophoretic display (V-EPD), IPS-EPD exhibits the feasibility of transparent display function. However, most of the previous research was hindered by long response time, low optical transmittance, or complex structures. In this paper, we have proposed a newly developed electrode layout and driving waveform for IPS-EPD, achieving a device with fast response time of 0.32 s, high transmittance of 58.07%, good transmittance-contrast ratio of 11.25, and simple structure, which show a significant improvement over other related research. Additionally, we elucidated the physical mechanism for the device through developing a particles motion simulation. Finally, we presented a prototype of an IPS-EPD with TFT panel, which exhibits excellent performance in various application scenarios, making it a possible application prospect in mobile phone cases, glasses, windows, and so on.

A comprehensive review of human trophoblast fusion models: recent developments and challenges.

As an essential component of the maternal-fetal interface, the placental syncytiotrophoblast layer contributes to a successful pregnancy by secreting hormones necessary for pregnancy, transporting nutrients, mediating gas exchange, balancing immune tolerance, and resisting pathogen infection. Notably, the deficiency in mononuclear trophoblast cells fusing into multinucleated syncytiotrophoblast has been linked to adverse pregnancy outcomes, such as preeclampsia, fetal growth restriction, preterm birth, and stillbirth. Despite the availability of many models for the study of trophoblast fusion, there exists a notable disparity from the ideal model, limiting the deeper exploration into the placental development. Here, we reviewed the existing models employed for the investigation of human trophoblast fusion from several aspects, including the development history, latest progress, advantages, disadvantages, scope of application, and challenges. The literature searched covers the monolayer cell lines, primary human trophoblast, placental explants, human trophoblast stem cells, human pluripotent stem cells, three-dimensional cell spheres, organoids, and placenta-on-a-chip from 1938 to 2023. These diverse models have significantly enhanced our comprehension of placental development regulation and the underlying mechanisms of placental-related disorders. Through this review, our objective is to provide readers with a thorough understanding of the existing trophoblast fusion models, making it easier to select most suitable models to address specific experimental requirements or scientific inquiries. Establishment and application of the existing human placental trophoblast fusion models.

miR-181d-5p, which is upregulated in fetal growth restriction placentas, inhibits trophoblast fusion via CREBRF.

PURPOSE: Fetal growth restriction (FGR) is a common complication characterized by impaired placental function and unfavorable pregnancy outcomes. This study aims to elucidate the expression pattern of miR-181d-5p in FGR placentas and explore its effects on trophoblast fusion. METHODS: The expression pattern of miR-181d-5p in human FGR placentas were evaluated using qRT-PCR. Western blot, qRT-PCR, and Immunofluorescence analysis were performed in a Forskolin (FSK)-induced BeWo cell fusion model following the transfection of miR-181d-5p mimic or inhibitor. Potential target genes for miR-181d-5p were identified by screening miRNA databases. The interaction between miR-181d-5p and Luman/CREB3 Recruitment Factor (CREBRF) was determined through a luciferase assay. Moreover, the effect of CREBRF on BeWo cell fusion was examined under hypoxic conditions. RESULTS: Aberrant up-regulation of miR-181d-5p and altered expression of trophoblast fusion makers, including glial cell missing 1 (GCM1), Syncytin1 (Syn1), and E-cadherin (ECAD), were found in human FGR placentas. A down-regulation of miR-181d-5p expression was observed in the FSK-induced BeWo cell fusion model. Transfection of the miR-181d-5p mimic resulted in the inhibition of BeWo cell fusion, characterized by a down-regulation of GCM1 and Syn1, accompanied by an up-regulation of ECAD. Conversely, the miR-181d-5p inhibitor promoted BeWo cell fusion. Furthermore, miR-181d-5p exhibited negative regulation of CREBRF, which was significantly down-regulated in the hypoxia-induced BeWo cell model. The overexpression of CREBRF was effectively ameliorated the impaired BeWo cell fusion induced by hypoxia. CONCLUSIONS: Our study demonstrated that miR-181d-5p, which is elevated in FGR placenta, inhibited the BeWo cell fusion through negatively regulating the expression of CREBRF.