Occurrence and potential risks of pharmaceutical contamination in global Estuaries: A critical review and analysis.

Input of pollutants to estuaries is one of the major threats to marine biodiversity and fishery resources, and pharmaceuticals are one of the most important contaminants of emerging concern in aquatic ecosystems. To synthesize pharmaceutical pollution levels in estuaries over the past 20 years from a global perspective, this review identified 3229 individual environmental occurrence data for 239 pharmaceuticals across 91 global estuaries distributed in 26 countries. The highest cumulative weighted average concentration level (WACL) of all detected pharmaceuticals in estuarine water was observed in Africa (145,461.86 ng/L), with 30 pharmaceuticals reported. North America (24,316.39 ng/L) was ranked second in terms of WACL, followed by South America (20,784.13 ng/L), Asia (5958.38 ng/L), Europe (4691.23 ng/L), and Oceania (2916.32 ng/L). Carbamazepine, diclofenac, and paracetamol were detected in all continents. A total of 41 functional categories of pharmaceuticals were identified, and analgesics, antibiotics, and stimulants were amongst the most ubiquitous groups in estuaries worldwide. Although many pharmaceuticals were observed to present lower than or equal to moderate ecological risk, 34 pharmaceuticals were identified with high or very high ecological risks in at least one continent. Pharmaceutical pollution in estuaries was positively correlated with regional unemployment and poverty ratios, but negatively correlated with life expectancy and GDP per capita. There are some limitations that may affect this synthesis, such as comparability of the sampling and pretreatment methodology, differences in the target pharmaceuticals for monitoring, and potentially limited number and diversity of estuaries covered, which prompt us to standardize methods for monitoring these pharmaceutical contaminants in future global studies.

Fungibility, accessibility and clinical utility of remote electronic fetal monitoring in improving maternal emotional status compared with traditional method: A multicenter prospective cohort analysis.

OBJECTIVE: Supported by remote signal processing techniques and wireless communication technology, remote electronic fetal monitoring (REFM) has emerged as a promising alternative to traditional electronic fetal monitoring (TEFM) in clinical practice. The aim of this study was to evaluate the comparability, accessibility, and clinical utility of REFM in contrast to TEFM. METHODS: This was a multicenter prospective cohort study. A cohort of 2900 pregnant women were enrolled from three medical centers between June 1, 2021 and June 31, 2022. Among them, 800 utilized REFM, with 760 of them completing the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) assessments using the devices for 1 month. The control group comprised 2100 pregnant women who did not use REFM. Additionally, 80 pregnant women concurrently employed both REFM and TEFM, and their respective curve coincidence rates were determined through curve fitting. Primary outcomes encompassed pregnancy outcomes in both groups, average curve coincidence rates between REFM and TEFM, as well as SDS and SAS scores. RESULTS: Among the 760 pregnant women who completed SAS and SDS assessments, their average SAS scores before and after 1 month of REFM usage were 43.09 ± 8.04 and 41.58 ± 6.59, respectively. Concurrently, the average SDS scores before and after 1 month of REFM usage were 45.45 ± 9.60 and 44.80 ± 9.17, respectively. A statistically significant decrease was observed in SAS scores (P = 0.005), whereas no significant difference was noted in SDS scores (P = 0.340). Furthermore, a statistically significant difference in the rate of adverse pregnancy outcomes (neonatal asphyxia) emerged between the two groups, those who employed REFM and those who did not (P = 0.021). In the subset of 80 pregnant women employing both REFM and TEFM, all 80 results showed precise congruence between the two methods. The average coincidence rate was determined to be 79.45% ± 12.64%. CONCLUSION: REFM contributes to improved pregnancy outcomes and exhibits a high level of concordance with TEFM, thereby accurately reflecting the quality of fetal heart monitoring. Additionally, REFM effectively mitigates pregnant women's anxiety. Thus, REFM demonstrates comparability, accessibility, and clinical utility.

Causal associations between intermediate very-low-density lipoprotein cholesterol-to-total lipids ratio and peptic ulcer: A bidirectional Mendelian randomization study.

BACKGROUND: Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-low-density lipoprotein (VLDL) and the occurrence of peptic ulcers (PU). However, the precise causal relationship between these factors remains ambiguous. Consequently, this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer. AIM: To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein (VLDL) association with PU via genetic methods, guiding future clinical research. METHODS: Genome-wide association study (GWAS) datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project (https://gwas.mrcieu.ac.uk). For the forward Mendelian randomization (MR) analysis, 72 single nucleotide polymorphisms (SNPs) were identified as instrumental variables. These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL, with peptic ulcer as the outcome variable. Conversely, for the inverse MR analysis, no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome. All MR analyses utilized inverse variance weighted (IVW) as the primary analytical method. Additionally, weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects. Egger regression was used as a supplementary method to evaluate potential directional pleiotropy. Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing. RESULTS: The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer (IVW: OR = 2.557, 95%CI = 1.274-5.132, P = 0.008). However, no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis. CONCLUSION: In conclusion, our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers. However, further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.

A Novel Heterozygous Intronic FBN1 Variant Contributes to Aberrant RNA Splicing in Marfan Syndrome.

BACKGROUND: Marfan syndrome (MFS) is a complex genetic systemic connective tissue disorder. It is well known that genetic factors play a critical role in the progression of MFS, with nearly all cases attributed to variants in the FBN1 gene. METHODS: We investigated a Chinese family with MFS spanning two generations. Whole exome sequencing, in silico analysis, minigene constructs, transfection, RT-PCR, and protein secondary structure analysis were used to analyze the genotype of the proband and his father. RESULTS: The main clinical manifestations of the proband and his father were subluxation of the left lens and high myopia with pectus deformity. Whole exome sequencing identified a novel single nucleotide variant (SNV) in the FBN1 gene at a non-canonical splice site, c.443-3C>G. This variant resulted in two abnormal mRNA transcripts, leading to a frameshift and an in-frame insertion. Further in vitro experiments indicated that the c.443-3C>G variant in FBN1 was pathogenic and functionally harmful. CONCLUSION: This research identified a novel intronic pathogenic FBN1: c.443-3C>G gene variant, which led to two different aberrant splicing effects. Further functional analysis expands the variant spectrum and provides a strong indication and sufficient basis for preimplantation genetic testing for monogenic disease (PGT-M).

Exosomes derived from gastric cancer cells promote phenotypic transformation of hepatic stellate cells and affect the malignant behavior of gastric cancer cells.

OBJECTIVE: This study aimed to evaluate the effect of exosomes derived from gastric cancer cells on the phenotypic transformation of hepatic stellate cells (HSCs) and the effect of HSC activation on the malignant behavior of gastric cancer cells, including its molecular mechanism. METHODS: Exosomes derived from the human gastric adenocarcinoma cell line AGS were extracted and purified by polymer precipitation and ultrafiltration, respectively. The exosomes' morphologic characteristics were observed using transmission electron microscopy, particle size was determined through nanoparticle-tracking analysis, and marker proteins were detected using western blotting. Exosome uptake by LX-2 HSCs was observed through fluorescence-based tracing. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the messenger RNA (mRNA) expression of alpha-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). Using functional assays, the effects of LX-2 HSC activation on the biological behavior of malignant gastric cancer cells were evaluated. The effects of LX-2 HSC activation on the protein expression of epithelial-mesenchymal transition (EMT)-related genes and ß-catenin were evaluated via western blotting. RESULTS: The extracted particles conformed to the definitions of exosomes and were thus considered gastric cancer cell-derived exosomes. Fluorescence-based tracing successfully demonstrated that exosomes were enriched in LX-2 HSCs. RT-qPCR revealed that the mRNA expression of the cancer-associated fibroblast markers α-SMA and FAP was significantly increased. LX-2 HSC activation considerably enhanced gastric cancer cell proliferation, invasion, and migration. Western blotting showed that the expression of the EMT-related epithelial marker E-cadherin was significantly downregulated, whereas the expression of interstitial markers (N-cadherin and vimentin) and ß-catenin was remarkably upregulated in gastric cancer cells. CONCLUSION: Exosomes derived from gastric cancer cells promoted phenotypic transformation of HSCs and activated HSCs to become tumor-associated fibroblasts. Gastric cancer cell-derived cells significantly enhanced gastric cancer cell proliferation, invasion, and migration after HSC activation, which may promote EMT of gastric cancer cells through the Wnt/ß-catenin pathway.

DualNetGO: a dual network model for protein function prediction via effective feature selection.

MOTIVATION: Protein-protein interaction (PPI) networks are crucial for automatically annotating protein functions. As multiple PPI networks exist for the same set of proteins that capture properties from different aspects, it is a challenging task to effectively utilize these heterogeneous networks. Recently, several deep learning models have combined PPI networks from all evidence, or concatenated all graph embeddings for protein function prediction. However, the lack of a judicious selection procedure prevents the effective harness of information from different PPI networks, as these networks vary in densities, structures, and noise levels. Consequently, combining protein features indiscriminately could increase the noise level, leading to decreased model performance. RESULTS: We develop DualNetGO, a dual-network model comprised of a Classifier and a Selector, to predict protein functions by effectively selecting features from different sources including graph embeddings of PPI networks, protein domain, and subcellular location information. Evaluation of DualNetGO on human and mouse datasets in comparison with other network-based models shows at least 4.5%, 6.2%, and 14.2% improvement on Fmax in BP, MF, and CC gene ontology categories, respectively, for human, and 3.3%, 10.6%, and 7.7% improvement on Fmax for mouse. We demonstrate the generalization capability of our model by training and testing on the CAFA3 data, and show its versatility by incorporating Esm2 embeddings. We further show that our model is insensitive to the choice of graph embedding method and is time- and memory-saving. These results demonstrate that combining a subset of features including PPI networks and protein attributes selected by our model is more effective in utilizing PPI network information than only using one kind of or concatenating graph embeddings from all kinds of PPI networks. AVAILABILITY AND IMPLEMENTATION: The source code of DualNetGO and some of the experiment data are available at: https://github.com/georgedashen/DualNetGO.

Aggravating Pollution of Emerging Aryl Organophosphate Esters in Urban Estuarine Sediments of South China.

Emerging aryl organophosphate esters (aryl-OPEs) have been employed as substitutes for organohalogen flame retardants in recent years; however, their environmental occurrence and associated impacts in urban estuarine sediments have not been adequately investigated, impeding regulatory decision-making. Herein, field-based investigations and modeling based on surface sediment and sediment core analysis were employed to uncover the historical pollution and current environmental impacts of aryl-OPEs in the Pearl River Estuary, South China. Our results revealed a substantial increase in aryl-OPE emission, particularly emerging aryl-OPEs, through sediment transport to the estuary since the 2000s. The emerging aryl-OPEs comprised 83% of the total annual input in the past decade, with an average annual input of 155,000 g. Additionally, the emerging-to-traditional aryl-OPE concentration ratios increased with decreasing distance from the shore, peaking in the highly urbanized riverine outlets. These findings indicate that inventories of emerging aryl-OPEs are likely increasing in estuarine sediments and their emissions are surpassing those of traditional aryl-OPEs. Our risk-based priority screening approach indicates that some emerging aryl-OPEs, particularly bisphenol A bis(diphenyl phosphate), can pose a higher environmental risk than traditional aryl-OPEs in estuarine sediments. Overall, our study highlights the importance of recognizing the environmental impacts of emerging aryl-OPEs.

Role of ADP ribosylation factor guanylate kinase 1 in the malignant biological behavior of gastric cancer.

Aim: This study aims to investigate the influence of ASAP1 (ADP ribosylation factor guanylate kinase 1) on the malignant behavior of gastric cancer (GC) cells and to elucidate the potential molecular mechanisms involved in cancer development and progression. Methods: We assessed the impact of ASAP1 overexpression and knockdown on GC cell malignancy using CCK8, colony formation, flow cytometry (Annexin V/propidium iodide), Transwell migration, invasion, and scratch assays. Western blot analysis was used to assess the effects of ASAP1 on angiogenesis, matrix metalloproteinases (MMPs), apoptotic proteins, epithelial-mesenchymal transition (EMT)-related proteins, as well as AKT and p-AKT. The influence of ASAP1 knockdown was also evaluated in nude mice bearing BGC823 cell-derived tumors. Results: Our findings revealed that ASAP1 was significantly overexpressed in GC cells, enhancing their proliferation, invasion, and migration, while reducing apoptosis. Conversely, ASAP1 knockdown reversed these effects, markedly increasing the expression of cleaved-caspase 3 (Casp3), PARP, and the epithelial marker E-cadherin, and significantly decreasing MMP2, MMP9, VEGFA, and mesenchymal markers such as N-cadherin and vimentin. Additionally, it reduced AKT, and p-AKT levels (P < 0.01). Tumor growth in nude mice was suppressed following ASAP1 knockdown. Conclusion: The overexpression of ASAP1 significantly promotes malignant behaviors in GC cells, whereas its knockdown diminishes these effects. This modulation is potentially through the downregulation of VEGFA, leading to reduced angiogenesis, Cleaved-Casp3 and Cleaved-PARP overexpression, and a decrease in MMPs, EMT, AKT, and p-AKT activity.

Effector MoSDT1 enhances Magnaporthe oryzae virulence and plays a dual role in regulating rice defense.

C2H2 zinc effectors are a class of pathogen proteins that play a dual role in plant-pathogen interactions, promoting pathogenicity and enhancing plant defense. In our previous research, we identified Magnaporthe oryzae Systemic Defense Trigger 1 (MoSDT1) as a C2H2 zinc effector that activates rice (Oryza sativa) defense when overexpressed in rice. However, its regulatory roles in pathogenicity and defense require further investigation. In this study, we generated an MoSDT1 overexpressing strain and 2 knockout strains of M. oryzae to assess the impact of MoSDT1 on pathogenicity, rice defense, and phenotypic characteristics. Our analyses revealed that MoSDT1 substantially influenced vegetative growth, conidia size, and conidiation, and was crucial for the virulence of M. oryzae while suppressing rice defense. MoSDT1 localized to the nucleus and cytoplasm of rice, either dependent or independent of M. oryzae delivery. Through RNA-seq, scRNA-seq, and ChIP-seq, we identified that MoSDT1 modulates rice defense by regulating the phosphorylation and ubiquitination of various rice signaling proteins, including transcription factors, transcription repressors, kinases, phosphatases, and the ubiquitin system. These findings provide valuable insights into the regulatory mechanisms of C2H2 zinc finger effector proteins and offer important foundational information for utilizing their target genes in disease resistance breeding and the design of targets for disease management.

G-quadruplex structures in FGFR3 promoter negatively regulate its gene expression and DNA replication.

FGFR3 activating mutations and abnormal expression are linked to tumor development. However, the current state of research on FGFR3 gene expression regulation is relatively insufficient. In this study, we have reported that the FGFR3 promoter's positive strand contains several G-tracts and most likely forms a G-quadruplex (G4) structure. Circular dichroism investigations revealed that oligonucleotides from this region exhibit G-quadruplex-like molar ellipticity. We further validated the G4 structure of the FGFR3 promoter using biochemical and cellular molecular biology techniques. The G-quadruplex mutation enhanced the transcriptional activity of the FGFR3 promoter and DNA replication, suggesting that the G4 structure inhibits its expression. Furthermore, we conducted a preliminary screen for helicases associated with FGFR3 expression and explored their regulatory effects on FGFR3 gene transcription. Subsequently, we investigated the effect of curcumin on the stability of the G4 structure of the FGFR3 promoter and its regulatory effect on FGFR3 expression.

Development of a prognostic risk model of uveal melanoma based on N7-methylguanosine-related regulators.

BACKGROUND: Uveal melanoma (UVM) stands as the predominant type of primary intraocular malignancy among adults. The clinical significance of N7-methylguanosine (m7G), a prevalent RNA modifications, in UVM remains unclear. METHODS: Primary information from 80 UVM patients were analyzed as the training set, incorporating clinical information, mutation annotations and mRNA expression obtained from The Cancer Genome Atlas (TCGA) website. The validation set was carried out using Gene Expression Omnibus (GEO) database GSE22138 and GSE84976. Kaplan-Meier and Cox regression of univariate analyses were subjected to identify m7G-related regulators as prognostic genes. RESULT: A prognostic risk model comprising EIF4E2, NUDT16, SNUPN and WDR4 was established through Cox regression of LASSO. Evaluation of the model's predictability for UVM patients' prognosis by Receiver Operating Characteristic (ROC) curves in the training set, demonstrated excellent performance Area Under the Curve (AUC) > 0.75. The high-risk prognosis within the TCGA cohort exhibit a notable worse outcome. Additionally, an independent correlation between the risk score and overall survival (OS) among UVM patients were identified. External validation of this model was carried out using the validation sets (GSE22138 and GSE84976). Immune-related analysis revealed that patients with high score of m7G-related risk model exhibited elevated level of immune infiltration and immune checkpoint gene expression. CONCLUSION: We have developed a risk prediction model based on four m7G-related regulators, facilitating effective estimate UVM patients' survival by clinicians. Our findings shed novel light on essential role of m7G-related regulators in UVM and suggest potential novel targets for the diagnosis, prognosis and therapy of UVM.

Development and validation of a nomogram for predicting placenta accreta spectrum in pregnancies with one previous cesarean delivery.

OBJECTIVE: This study aimed to develop and validate a prenatal nomogram to predict the risk of placenta accreta spectrum (PAS) in women with one previous cesarean delivery. METHODS: This retrospective study enrolled 5157 pregnant women with one previous cesarean delivery in China from January 2021 to January 2023. The nomogram was developed from a training cohort of 3612 pregnant women and tested on a validation cohort of 1545 pregnant women. Multivariate regression analysis was performed using the minimum value of the Akaike information criterion to select prognostic factors that can be included in the nomogram. We evaluated the nomogram by the area under the receiver operating characteristic (ROC) curve, calibration curves, and the decision curve analysis (DCA). RESULTS: PAS occurred in 199 (5.51%) and 80 (5.18%) patients in the training and validation cohorts, respectively. Backward stepwise algorithms in the multivariable logistic regression model determined abortion, hypertensive disorders complicating pregnancy, fetal position, and placenta previa as relevant PAS predictors. The area under the ROC curve for the nomogram was 0.770 (95% confidence interval [CI] 0.733-0.807) and 0.791 (95% CI 0.730-0.853) for the training and validation cohorts, respectively. The calibration curves indicated that the nomogram's prediction probability was consistent with the actual probability. The DCA curve revealed that the nomogram has potential clinical benefit. CONCLUSION: A prenatal nomogram was developed for PAS in our study, which helped obstetricians determine potential patients with PAS and make sufficient preoperative preparation to reduce maternal and neonatal complications.

Associations among neighborhood walkability, metal exposure, and sex steroid hormone levels: Results from Hangzhou Birth Cohort Study â ¡.

BACKGROUND: Neighborhood walkability may influence maternal-fetal exposure to environmental hazards and maternal-fetal health (e.g., fetal growth restriction, reproductive toxicity). However, few studies have explored the association between neighborhood walkability and hormones in pregnant women. METHODS: We included 533 pregnant women from the Hangzhou Birth Cohort Study II (HBCS-II) with testosterone (TTE) and estradiol (E2) measured for analysis. Neighborhood walkability was evaluated by calculating a walkability index based on geo-coded addresses. Placental metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). TTE and E2 levels in umbilical cord blood were measured using chemiluminescence microparticle immunoassay (CMIA). Linear regression model was used to estimate the relationship between the walkability index, placental metals, and sex steroid hormones. Effect modification was also assessed to estimate the effect of placental metals on the associations of neighborhood walkability with TTE and E2. RESULTS: Neighborhood walkability was significantly linked to increased E2 levels (P trend=0.023). Compared with participants at the first quintile (Q1) of walkability index, those at the third quintiles (Q3) had lower chromium (Cr) levels (ß = -0.212, 95% CI = -0.421 to -0.003). Arsenic (As), cobalt (Co), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), tin (Sn), and vanadium (V) were linked to decreased TTE levels, and cadmium (Cd) was linked to increased TTE levels. No metal was significantly associated with E2 levels in trend analysis. In the analysis of effect modification, the associations of neighborhood walkability with TTE and E2 were significantly modified by Mn (P = 0.005) and Cu (P = 0.049) respectively. CONCLUSION: Neighborhood walkability could be a favorable factor for E2 production during pregnancy, which may be inhibited by maternal exposure to heavy metals.

Separation, identification, and fingerprinting of antioxidant components in persimmon (Diospyros kaki) leaves by offline two-dimensional liquid chromatography with electrochemical detection and tandem mass spectrometry.

In this work, the antioxidant components in persimmon (Diospyros kaki) leaves were separated by offline two-dimensional liquid chromatography-electrochemical detection (LC×LC-ECD) and identified by LC-tandem mass spectrometry (LC-MS/MS). A total of 33 antioxidants, mainly proanthocyanidins, and glycosides of kaempferol and quercetin, were identified. The antioxidant assays demonstrated that the fractions collected from the first-dimension LC (1D-LC) possessed considerable radical scavenging capabilities, with correlation coefficients of peak area versus radical scavenging capability of 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) being 0.9335 and 0.9116, respectively. The fingerprinting showed that 37 peaks were present in all samples. The major antioxidant components of persimmon leaves were the glycosides of kaempferol and quercetin. Finally, fourteen antioxidants were quantitatively assessed. Offline LC×LC provided high peak capacity and separation; ECD enabled specific screening and detection of antioxidant components; and MS/MS provided excellent identification capability. In this study, the combination of the three approaches was utilized to screen for antioxidant components in persimmon leaves, with satisfactory findings. In conclusion, this technique is an effective means for rapid analysis of antioxidant components and quality control of medicinal plants, achieving rapid separation of congeners and facilitating more accurate qualitative and quantitative analyses.

Iguratimod suppresses plasma cell differentiation and ameliorates experimental Sjögren's syndrome in mice by promoting TEC kinase degradation.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg-1·d-1) or hydroxychloroquine (50 mg·kg-1·d-1) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg-1·d-1) was more effective than hydroxychloroquine (50 mg·kg-1·d-1). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option.

Preterm birth, a consequence of immune deviation mediated hyperinflammation.

Preterm birth represents a multifaceted syndrome with intricacies still present in our comprehension of its etiology. In the context of a semi-allograft, the prosperity from implantation to pregnancy to delivery hinges on the establishment of a favorable maternal-fetal immune microenvironment and a successful trilogy of immune activation, immune tolerance and then immune activation transitions. The occurrence of spontaneous preterm birth could be related to abnormalities within the immune trilogy, stemming from deviation in maternal and fetal immunity. These immune deviations, characterized by insufficient immune tolerance and early immune activation, ultimately culminated in an unsustainable pregnancy. In this review, we accentuated the role of both innate and adaptive immune reason in promoting spontaneous preterm birth, reviewed the risk of preterm birth from vaginal microbiome mediated by immune changes and the potential of vaginal microbiomes and metabolites as a new predictive marker, and discuss the changes in the role of progesterone and its interaction with immune cells in a preterm birth population. Our objective was to contribute to the growing body of knowledge in the field, shedding light on the immunologic reason of spontaneous preterm birth and effective biomarkers for early prediction, providing a roadmap for forthcoming investigations.

Role and mechanism of NCAPD3 in promoting malignant behaviors in gastric cancer.

Background: Gastric cancer (GC) is one of the major malignancies threatening human lives and health. Non-SMC condensin II complex subunit D3 (NCAPD3) plays a crucial role in the occurrence of many diseases. However, its role in GC remains unexplored. Materials and Methods: The Cancer Genome Atlas (TCGA) database, clinical samples, and cell lines were used to analyze NCAPD3 expression in GC. NCAPD3 was overexpressed and inhibited by lentiviral vectors and the CRISPR/Cas9 system, respectively. The biological functions of NCAPD3 were investigated in vitro and in vivo. Gene microarray, Gene set enrichment analysis (GSEA) and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms. Results: NCAPD3 was highly expressed in GC and was associated with a poor prognosis. NCAPD3 upregulation significantly promoted the malignant biological behaviors of gastric cancer cell, while NCAPD3 inhibition exerted a opposite effect. NCAPD3 loss can directly inhibit CCND1 and ESR1 expression to downregulate the expression of downstream targets CDK6 and IRS1 and inhibit the proliferation of gastric cancer cells. Moreover, NCAPD3 loss activates IRF7 and DDIT3 to regulate apoptosis in gastric cancer cells. Conclusion: Our study revealed that NCAPD3 silencing attenuates malignant phenotypes of GC and that it is a potential target for GC treatment.

Targeting JUNB to modulate M2 macrophage polarization in preeclampsia.

Preeclampsia (PE) is a complex disorder affecting pregnant women, leading to significant maternal and fetal morbidity and mortality. Understanding the cellular dynamics and molecular mechanisms underlying PE is crucial for developing effective therapeutic strategies. This study utilized single-cell RNA sequencing (scRNA-seq) to delineate the cellular landscape of the placenta in PE, identifying 11 distinct cell subpopulations, with macrophages playing a pivotal role in mediating cell-cell communication. Specifically, the transcription factor JUNB was found to be a key gene in macrophages from PE samples, influencing the interaction between macrophages and both epithelial and endothelial cells. Functional experiments indicated that interference with JUNB expression promoted macrophage polarization towards an M2 phenotype, which facilitated trophoblast invasion, migration, and angiogenesis. Mechanistically, JUNB regulated the MIIP/PI3K/AKT pathway, as evidenced by gene expression analysis following JUNB knockdown. The study further demonstrated that targeting JUNB could activate the PI3K/AKT pathway by transcriptionally activating MIIP, thus promoting M2 polarization and potentially delaying the onset of PE. These findings present new insights into the pathogenesis of PE and suggest a novel therapeutic approach by modulating macrophage polarization.