Optical and EPR Detection of a Triplet Ground State Phenyl Nitrenium Ion.

Nitrenium ions are important reactive intermediates participating in the synthetic chemistry and biological processes. Little is known about triplet phenyl nitrenium ions regarding their reactivity, lifetimes, spectroscopic features, and electronic configurations, and no ground state triplet nitrenium ion has been directly detected. In this work, m-pyrrolidinyl-phenyl hydrazine hydrochloride (1) is synthesized as the photoprecursor to photochemically generate the corresponding m-pyrrolidinyl-phenyl nitrenium ion (2), which is computed to adopt a π, π* triplet ground state. A combination of femtosecond (fs) and nanosecond (ns) transient absorption (TA) spectroscopy, cryogenic continuous-wave electronic paramagnetic resonance (CW-EPR) spectroscopy, computational analysis, and photoproduct studies was performed to elucidate the photolysis pathway of 1 and offers the first direct experimental detection of a ground state triplet phenyl nitrenium ion. Upon photoexcitation, 1 forms S1, where bond heterolysis occurs and the NH3 leaving group is extruded in 1.8 ps, generating a vibrationally hot, spin-conserving closed-shell singlet phenyl nitrenium ion (12) that undergoes vibrational cooling in 19 ps. Subsequent intersystem crossing takes place in 0.5 ns, yielding the ground state triplet phenyl nitrenium ion (32), with a lifetime of 0.8 µs. Unlike electrophilic singlet phenyl nitrenium ions, which react rapidly with nucleophiles, this triplet phenyl nitrenium reacts through sequential H atom abstractions, resulting in the eventual formation of the reduced m-pyrrolidinyl-aniline as the predominant stable photoproduct. Supporting the triplet ground state, continuous irradiation of 1 in a glassy matrix at 80 K in an EPR spectrometer forms a paramagnetic triplet species, consistent with a triplet nitrenium ion.

Identification of the role of DAB2 and CXCL8 in uterine spiral artery remodeling in early-onset preeclampsia.

Aberrant remodeling of uterine spiral arteries (SPA) is strongly associated with the pathogenesis of early-onset preeclampsia (EOPE). However, the complexities of SPA transformation remain inadequately understood. We conducted a single-cell RNA sequencing analysis of whole placental tissues derived from patients with EOPE and their corresponding controls, identified DAB2 as a key gene of interest and explored the mechanism underlying the communication between Extravillous trophoblast cells (EVTs) and decidual vascular smooth muscle cells (dVSMC) through cell models and a placenta-decidua coculture (PDC) model in vitro. DAB2 enhanced the motility and viability of HTR-8/SVneo cells. After exposure to conditioned medium (CM) from HTR-8/SVneoshNC cells, hVSMCs exhibited a rounded morphology, indicative of dedifferentiation, while CM-HTR-8/SVneoshDAB2 cells displayed a spindle-like morphology. Furthermore, the PDC model demonstrated that CM-HTR-8/SVneoshDAB2 was less conducive to vascular remodeling. Further in-depth mechanistic investigations revealed that C-X-C motif chemokine ligand 8 (CXCL8, also known as IL8) is a pivotal regulator governing the dedifferentiation of dVSMC. DAB2 expression in EVTs is critical for orchestrating the phenotypic transition and motility of dVSMC. These processes may be intricately linked to the CXCL8/PI3K/AKT pathway, underscoring its central role in intricate SPA remodeling.

Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion.

Rare gene variants have been found to play a role in complex disorders. Preeclampsia, and especially early-onset preeclampsia, has a strong genetic link. However, the role of rare variants in the offspring of mothers with preeclampsia remains unclear. In this study, whole-exome sequencing (WES) was used to identify rare pathogenic variants in two families with early-onset preeclampsia. Two heterozygous rare variants in CCDC7, c.625C>T (p.R209C) and c.1015C>T (p.R339X), were detected in two families and were cosegregated in the offspring of preeclamptic pregnancies. We examined the spatiotemporal expression pattern of CCDC7 in human placental villi and the effects of CCDC7 on migration and invasion of trophoblast cells JEG-3. The quantitative real-time PCR and Western blot results showed that the expression of CCDC7 in placental villi was the lowest during the first trimester and increased as the pregnancy progressed. The CCDC7 p.R339X variant showed a decrease in mRNA and protein expressions. Loss-of-function assays showed that knockdown of CCDC7 suppressed the migration and invasion of JEG-3 cells. In conclusion, CCDC7 is a potential susceptibility gene for preeclampsia, which is key for the migration and invasion of trophoblast cells. Rare variants of preeclampsia in offspring may play a crucial role in the pathogenesis of preeclampsia and require further research.

A sonographic endometrial thickness <7 mm in women undergoing in vitro fertilization increases the risk of placenta accreta spectrum.

BACKGROUND: The prevalence of placenta accreta spectrum, a potentially life-threatening condition, has exhibited a significant global rise in recent decades. Effective screening methods and early identification strategies for placenta accreta spectrum could enable early treatment and improved outcomes. Endometrial thickness plays a crucial role in successful embryo implantation and favorable pregnancy outcomes. Extensive research has been conducted on the impact of endometrial thickness on assisted reproductive technology cycles, specifically in terms of pregnancy rates, live birth rates, and pregnancy loss rates. However, limited knowledge exists regarding the influence of endometrial thickness on placenta accreta spectrum. OBJECTIVE: This study aimed to evaluate the association between preimplantation endometrial thickness and the occurrence of placenta accreta spectrum in women undergoing assisted reproductive technology cycles. STUDY DESIGN: A total of 4637 women who had not undergone previous cesarean delivery and who conceived by in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment and subsequently delivered at the Third Affiliated Hospital of Guangzhou Medical University between January 2008 and December 2020 were included in this study. To explore the relationship between endometrial thickness and placenta accreta spectrum, we used smooth curve fitting, threshold effect, and saturation effect analysis. Multivariate logistic regression analysis was performed to evaluate the independent association between endometrial thickness and placenta accreta spectrum while adjusting for potential confounding factors. Propensity score matching was performed to reduce the influence of bias and unmeasured confounders. Furthermore, we used causal mediation effect analysis to investigate the mediating role of endometrial thickness in the relationship between gravidity and ovarian stimulation protocol and the occurrence of placenta accreta spectrum. RESULTS: Among the 4637 women included in this study, pregnancies with placenta accreta spectrum (159; 3.4%) had significantly thinner endometrial thickness (non-placenta accreta spectrum, 10.08±2.04 mm vs placenta accreta spectrum, 8.88±2.21 mm; P<.001) during the last ultrasound before embryo transfer. By using smooth curve fitting, it was found that changes in endometrial thickness had a significant effect on the incidence of placenta accreta spectrum up to a thickness of 10.9 mm, beyond which the effect plateaued. Then, the endometrial thickness was divided into the following 4 groups: ≤7, >7 to ≤10.9, >10.9 to ≤13, and >13 mm. The absolute rates of placenta accreta spectrum in each group were 11.91%, 3.73%, 1.35%, and 2.54%, respectively. Compared with women with an endometrial thickness from 10.9 to 13 mm, the odds of placenta accreta spectrum increased from an adjusted odds ratio of 2.27 (95% confidence interval, 1.33-3.86) for endometrial thickness from 7 to 10.9 mm to an adjusted odds ratio of 7.15 (95% confidence interval, 3.73-13.71) for endometrial thickness <7 mm after adjusting for potential confounding factors. Placenta previa remained as an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 11.80; 95% confidence interval, 7.65-18.19). Moreover, endometrial thickness <7 mm was still an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 3.91; 95% confidence interval, 1.57-9.73) in the matched cohort after PSM. Causal mediation analysis revealed that approximately 63.9% of the total effect of gravidity and 18.6% of the total effect of ovarian stimulation protocol on placenta accreta spectrum were mediated by endometrial thickness. CONCLUSION: The findings of our study indicate that thin endometrial thickness is an independent risk factor for placenta accreta spectrum in women without previous cesarean delivery undergoing assisted reproductive technology treatment. The clinical significance of this risk factor is slightly lower than that of placenta previa. Furthermore, our results demonstrate that endometrial thickness plays a significant mediating role in the relationship between gravidity or ovarian stimulation protocol and placenta accreta spectrum.

Thymidine Phosphorylase Promotes the Formation of Abdominal Aortic Aneurysm in Mice Fed a Western Diet.

Aims: The precise molecular drivers of abdominal aortic aneurysm (AAA) remain unclear. Thymidine phosphorylase (TYMP) contributes to increased platelet activation, thrombosis, and inflammation, all of which are key factors in AAA development. Additionally, TYMP suppresses the proliferation of vascular smooth muscle cells (VSMCs), which are central to the development and progression of AAA. We hypothesize that TYMP plays a key role in AAA development. Methods and Results: We conducted a histological study using human AAA samples and normal abdominal aortas, revealing heightened levels of TYMP in human AAA vessel walls. To validate this observation, we utilized an Ang II perfusion-induced AAA model in wild-type C57BL/6J (WT) and Tymp-/- mice, feeding them a Western diet (TD.88137) starting from 4 weeks of age. We found that Tymp-/- mice were protected from Ang II perfusion-induced AAA formation. Furthermore, by using TYMP-expressing VSMCs as well as primarily cultured VSMCs from WT and Tymp-/- mice, we elucidated the essential role of TYMP in regulating MMP2 expression and activation. TYMP deficiency or inhibition by tipiracil, a selective TYMP inhibitor, led to reduced MMP2 production, release, and activation in VSMCs. Additionally, TYMP was found to promote pro-inflammatory cytokine expression systemically, and its absence attenuates TNF-α-stimulated activation of MMP2 and AKT. By co-culturing VSMCs and platelets, we observed that TYMP-deficient platelets had a reduced inhibitory effect on VSMC proliferation compared to WT platelets. Moreover, TYMP appeared to enhance the expression of activated TGFß1 in cultured VSMCs in vitro and in human AAA vessel walls in vivo. TYMP also boosted the activation of thrombospondin-1 type 1 repeat domain-enhanced TGFß1 signaling, resulting in increased connective tissue growth factor production. Conclusion: Our findings collectively demonstrated that TYMP serves as a novel regulatory force in vascular biology, exerting influence over VSMC functionality and inflammatory responses that promote the development of AAA.

Transcriptome Analysis of Compensatory Growth and Meat Quality Alteration after Varied Restricted Feeding Conditions in Beef Cattle.

Compensatory growth (CG) is a physiological response that accelerates growth following a period of nutrient limitation, with the potential to improve growth efficiency and meat quality in cattle. However, the underlying molecular mechanisms remain poorly understood. In this study, 60 Huaxi cattle were divided into one ad libitum feeding (ALF) group and two restricted feeding groups (75% restricted, RF75; 50% restricted, RF50) undergoing a short-term restriction period followed by evaluation of CG. Detailed comparisons of growth performance during the experimental period, as well as carcass and meat quality traits, were conducted, complemented by a comprehensive transcriptome analysis of the longissimus dorsi muscle using differential expression analysis, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and weighted correlation network analysis (WGCNA). The results showed that irrespective of the restriction degree, the restricted animals exhibited CG, achieving final body weights comparable to the ALF group. Compensating animals showed differences in meat quality traits, such as pH, cooking loss, and fat content, compared to the ALF group. Transcriptomic analysis revealed 57 genes and 31 pathways differentially regulated during CG, covering immune response, acid-lipid metabolism, and protein synthesis. Notably, complement-coagulation-fibrinolytic system synergy was identified as potentially responsible for meat quality optimization in RF75. This study provides novel and valuable genetic insights into the regulatory mechanisms of CG in beef cattle.

Transient Absorption Spectroscopic Investigation of the Photocyclization-Deprotection Reaction of 3',5'-Dimethoxybenzoin Fluoride.

The 3',5'-dimethoxybenzoin (DMB) system has been widely investigated as a photoremovable protecting group (PRPG) for the elimination of various functional groups and has been applied in many fields. The photolysis of DMB fluoride leads to a highly efficient photocyclization-deprotection reaction, resulting in a high yield of 3',5'-dimethoxybenzofuran (DMBF) in a MeCN solution, while there is a competitive reaction that produces DMB in an aqueous solution. The yield of DMB increased as the volume ratio of water increased. To understand the solvent effect of the photolysis of selected DMB-based compounds, a combination of femtosecond to nanosecond transient absorption spectroscopies (fs-TA and ns-TA), nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) and quantum chemical calculation was employed to study the photophysical and photochemical reaction mechanisms of DMB fluoride in different solutions. Facilitated by the bichromophoric nature of DMB fluoride with electron-donating and -withdrawing chromophores, the cyclized intermediates could be found in a pure MeCN solution. The deprotection of a cyclic biradical intermediate results in the simultaneous formation of DMBF and a cyclic cation species. On the other hand, in aqueous solution, fs-TA experiments revealed that α-keto cations could be observed after excitation directly, which could easily produce the DMB through the addition of a hydroxyl within 8.7 ps. This work provides comprehensive photo-deactivation mechanisms of DMB fluoride in MeCN and aqueous conditions and provides critical insights regarding the biomedical application of DMB-based PRPG compounds.

Comparing the severity of second preeclampsia with first preeclampsia: a multicenter retrospective longitudinal cohort study.

OBJECTIVE: Compare the clinical severity of second preeclampsia with the first preeclampsia. METHODS: This retrospective longitudinal cohort study was conducted in three teaching hospitals in Guangzhou, where there were a total of 296 405 deliveries between 2010 and 2021. Two consecutive singleton deliveries complicated with preeclampsia were included. Clinical features, laboratory results within 1 week before delivery, and maternal and neonatal outcomes of both deliveries were collected. Univariate analyses were made using paired Wilcoxon tests and McNemar tests. Multivariable logistic regression and generalized linear models were performed to assess the association of adverse maternal and neonatal outcomes with second preeclampsia. RESULTS: A total of 151 women were included in the study. The mean maternal age was 28 and 33 years for the first and second deliveries, respectively. The proportion of preventive acetylsalicylic acid use was 4.6% for the first delivery and 15.2% for the second delivery. No significant differences were observed in terms of blood pressure on admission, gestational weeks of admission and delivery, application of perinatal antihypertensive agents, rates of preterm delivery, and severe features between the two occurrences. However, the rates of heart disease, edema, and admission to the ICU were lower, and hospital stays were shorter in the second preeclampsia compared with the first preeclampsia. Sensitivity analysis conducted among women who did not use preventive acetylsalicylic acid yielded similar results. After adjusting for potential confounding variables, the occurrence of second preeclampsia was associated with significantly decreased risks of heart disease, edema, complications, and admission to the NICU, with odds ratios ranging between 0.157 and 0.336. CONCLUSION: Contrary to expectations, the second preeclampsia did not exhibit worse manifestations or outcomes to the first occurrence. In fact, some clinical features and outcomes appeared to be better in the second preeclampsia.

In situ growth of ZIF-67 to construct core-shell mosaic structural composites for efficient extraction of benzoylurea insecticides.

A novel mosaic structure Silica@C/Co@ZIF-67 composite was synthesized by successfully embedding Co nanoparticles on the surface of silica spheres with the help of thermoplastic polyethyleneimine by carbon-reduction. The ZIF-67 half-shell layer structure was synthesized by the in-situ growth of ZIF-67 on the surface of silica spheres through the coordination of 2-methylimidazole with Co metal nodes. The composite was used as a magnetic solid-phase extraction adsorbent combined with high performance liquid chromatography-ultraviolet detector (HPLC-UV) for the extraction and determination of benzoylurea insecticides (BUs) in vegetables and tea. Based on the presence of π-π, hydrophobic and hydrogen bonding interactions between Silica@C/Co@ZIF-67 and BUs, the BUs were rapidly captured by the composites resulting in high adsorption performance. Under the optimal extraction parameters, the linear ranges were 0.3-200 µg L-1 for diflubenzuron, 0.6-200 µg L-1 for chlorbenzuron, and 1.0-200 µg L-1 for triflumuron, teflubenzuron, and flufenoxuron, with correlation coefficients (R2) greater than 0.9991. The limits of detection (LODs) of the method were 0.1-0.3 µg L-1, and the relative standard deviations (RSDs) were 1.2-3.0% for intra-day and 2.6-4.6% for inter-day. In the spiked recovery experiments of vegetables and tea, the recoveries of the five kinds of BUs ranged from 75.8 to 112.9%. In addition, after 10 repetitions using Silica@C/Co@ZIF-67, the recoveries of the five kinds of BUs were still as high as 78.4 to 83.9%.

Malachite green: a long-buried water-soluble AIEgen with near-infrared fluorescence for living cell nucleus staining.

Fluorescent imaging probes are crucial for exploring nucleus-related cellular events in live cells. Ideal probes should be photostable, small-sized, highly contrasted, and low in background. Here, we discovered that malachite green is a water-soluble near-infrared luminogen with aggregation-induced emission properties. Importantly, it can be used for living cell nucleus staining in a wash-free manner.

Enhancing effluent quality prediction in wastewater treatment plants through the integration of factor analysis and machine learning.

Precisely predicting the concentration of nitrogen-based pollutants from the wastewater treatment plants (WWTPs) remains a challenging yet crucial task for optimizing operational adjustments in WWTPs. In this study, an integrated approach using factor analysis (FA) and machine learning (ML) models was employed to accurately predict effluent total nitrogen (Ntoteff) and nitrate nitrogen (NO3-Neff) concentrations of the WWTP. The input values for the ML models were honed through FA to optimize factors, thereby significantly enhancing the ML prediction accuracy. The prediction model achieved a highest coefficient of determination (R2) of 97.43 % (Ntoteff) and 99.38 % (NO3-Neff), demonstrating satisfactory generalization ability for predictions up to three days ahead (R2 >80 %). Moreover, the interpretability analysis identified that the denitrification factor, the pollutant load factor, and the meteorological factor were significant. The model framework proposed in this study provides a valuable reference for optimizing the operation and management of wastewater treatment.

Development, validation, and clinical utility of a risk prediction model for recurrent preeclampsia.

OBJECTIVES: We aim to establish a predictive model for recurrent preeclampsia. METHODS: A retrospective review of medical records from three hospitals between 2010 and 2021 was conducted. The study included women who had two consecutive singleton deliveries at the same hospital, with the first delivery complicated by preeclampsia. A multivariable logistic regression model was constructed using a training cohort, and subsequently cross-validated and tested using an independent cohort. The model's performance was assessed in terms of discrimination and calibration, and its clinical utility was evaluated using decision curve analysis (DCA). RESULTS: Among 296 405 deliveries, 694 women met the inclusion criteria, with 151 (21.8%) experiencing recurrent preeclampsia. The predictive model incorporated 10 risk factors from previous preeclampsia, including gestational weeks with elevated blood pressure, gestational diabetes mellitus (GDM), pericardial effusion, heart failure, limb edema, serum creatinine, white blood cell count, low platelet counts within one week before delivery, SBP on the first postpartum day, and postpartum antihypertensive use. Additionally, one risk factor from the index pregnancy was included, which was antihypertensive use before 20 weeks. The model demonstrated better discrimination, calibration, and a net benefit across a wide range of recurrent preeclampsia risk thresholds. Furthermore, the model has been translated into a clinical risk calculator, enabling clinicians to calculate individualized risks of recurrent preeclampsia. CONCLUSION: Our study demonstrates that a predictive tool utilizing routine clinical and laboratory factors can accurately estimate the risk of recurrent preeclampsia. This predictive model has the potential to facilitate shared decision-making by providing personalized and risk-stratified care.

RNF125, transcriptionally regulated by NFATC2, alleviates osteoarthritis via inhibiting the Wnt/ß-catenin signaling pathway through degrading TRIM14.

Osteoarthritis (OA) is a chronic joint disease characterized by the progressive degradation of articular cartilage. In this study, as determined by histological staining, the cartilage surface of the OA rats was damaged, defective and broken, and chondrocytes and proteoglycan were reduced. While moderate physical exercise showed protective effects on the cartilage. Besides, RNA-seq was performed to select a target protein and RNF125 (an E3 ubiquitin ligase) was decreased in the cartilage tissues of OA rats and increased after physiological exercise. However, the precise role of RNF125 in OA is still unknown. This work aimed to investigate the involvement and underlying mechanism of RNF125 in OA pathogenesis. Our results defined that adenovirus-mediated overexpression of RNF125 inhibited the degradation of extracellular matrix of chondrocytes induced by IL-1ß, as revealed by increased chondrocyte viability, upregulated COL2A1 and ACAN levels, and downregulated MMP1, MMP13 and ADAMTS5 levels, which was abrogated by NR4A2 knockdown. In vivo, RNF125 relieved OA, manifested as reduced cartilage injury and increased chondrocytes. Mechanically, NFATC2 bound to the RNF125 promoter and directly regulated RNF125 transcription, as illustrated by luciferase reporter, Ch-IP and DNA pull-down assays. Furthermore, RNF125 overexpression inhibited the nuclear translocation of ß-catenin, thus suppressing activation of the Wnt/ß-catenin signaling pathway. Also, RNF125 as E3 ubiquitin ligase led to the ubiquitination and degradation of TRIM14 protein, and TRIM14 overexpression efficiently reversed the effects of RNF125 overexpression on OA progression. Totally, this study provides new insights into OA pathogenesis regulated by RNF125. RNF125 may be a novel biomarker for OA therapy.

Homology Identification and Cross-Contamination Analysis: A Method for Evaluating the Quality of Biological Samples Stored in a Biobank Using the Advanta Sample ID Genotyping Panel.

Biological samples are important resources for scientific research. These samples are stored in biobanks over years until needed, and some of them can never be retrieved if they are improperly stored, causing them to be wasted. Thus, they are priceless, and they should be used correctly and effectively. Sample quality substantially affects biomedical research results. However, sample misidentification or mix-up is common. It is necessary to establish quality standards for sample identification. In this study, we used the Advanta Sample ID genotyping panel to detect homology identification and cross-contamination. We compared the single-nucleotide polymorphism (SNP) typing results of two different samples and calculated the similarity score of homologous sample pairs and nonhomologous sample pairs. Through analysis, we obtained a similarity score cutoff point of 0.8620, which was an effective way to distinguish homology and nonhomology. Cross-contamination was detected in two sets of mixtures (STD8:STD6 and jj3:1-P) mixed at a series of special ratios. Sensitivity was dependent on the sample characteristics and mixing ratios. Finally, we assessed the effect of sample degradation degree on SNP genotyping and found that degraded samples with a minimal DNA integrity number of 1.9 had complete genotyping results. On the whole, this study shows that the Sample ID panel is reliable for homology identification and cross-contamination analysis. Moreover, this technology has promising further applications in biological sample quality control.

Pre-analytical effects on whole transcriptome and targeted RNA sequencing analysis in cytology: The effects of prolonged time in storage of effusion specimens prior to preservation.

OBJECTIVES: To investigate the pre-analytics of the molecular testing of cytology specimens, we studied the effects of time in refrigerator storage (4°C) of malignant effusions on RNA sequencing (RNAseq) results. METHODS: Ten effusion specimens were stored in a refrigerator (4°C) for different durations (day 0, 1, 4, and 7). All specimens were prepared as cytospins fixed in either Carnoy's solution or 95% ethanol (EtOH) and in an RNA preservative for a fresh frozen (FF) high-quality reference. Whole transcriptome (wt) and targeted (t)RNAseq of two multigene expression signatures were performed. We then compared transcript expression levels (including mutant allele fraction) according to pre-analytical variables using a concordance correlation coefficient (CCC) and a mixed effect model. RESULTS: Sequencing results were mostly stable over increasing time in storage. Cytospins fixed in Carnoy's solution were more concordant with FF samples than cytospins fixed in 95% EtOH at all timepoints. This finding was consistent for both wtRNAseq (averages: day 0 CCC = 0.98 vs 0.91; day 7 CCC = 0.88 vs 0.78) and tRNAseq methods (averages: day 0 CCC = 0.98 vs 0.81; day 7 CCC = 0.98 vs 0.90). Cytospins fixed in Carnoy's solution did not show significant changes in expression over timepoints or between expression signatures, whereas 95% EtOH did. CONCLUSION: RNAseq can be accurately performed on effusion specimens after prolonged refrigerator storage. RNA extracted from scraped cytospin slides fixed in Carnoy's solution was marginally superior to 95% EtOH fixation, but either method had comparable analytic performance to high-quality FF RNA samples.

Generating Functional Multicellular Organoids from Human Placenta Villi.

The interaction between trophoblasts, stroma cells, and immune cells at the maternal-fetal interface constitutes the functional units of the placenta, which is crucial for successful pregnancy outcomes. However, the investigation of this intricate interplay is restricted due to the absence of efficient experimental models. To address this challenge, a robust, reliable methodology for generating placenta villi organoids (PVOs) from early, late, or diseased pregnancies using air-liquid surface culture is developed. PVOs contain cytotrophoblasts that can self-renew and differentiate directly, along with stromal elements that retain native immune cells. Analysis of scRNA sequencing and WES data reveals that PVOs faithfully recapitulate the cellular components and genetic alterations of the corresponding source tissue. Additionally, PVOs derived from patients with preeclampsia exhibit specific pathological features such as inflammation, antiangiogenic imbalance, and decreased syncytin expression. The PVO-based propagation of primary placenta villi should enable a deeper investigation of placenta development and exploration of the underlying pathogenesis and therapeutics of placenta-originated diseases.

Evaluation of Clinical Diagnostic and Prognostic Value of Preoperative Serum Carcinoembryonic Antigen, CA19-9, and CA24-2 for Colorectal Cancer.

Objective: To investigate the clinical diagnostic and prognostic value of preoperative serum tumor markers in patients with colorectal cancer (CRC). Methods: From September 2013 to September 2016, we enrolled 980 patients diagnosed with CRC and 870 healthy subjects from The Affiliated Cancer Hospital of Shanxi Medical University. Patients were grouped and compared in accordance with tumor stage, tumor location, lymph node metastasis, distant metastasis, histological type, depth of invasion, growth type, and other factors. Serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 24-2 (CA24-2) concentrations in patient peripheral blood were measured, and the diagnostic value of the tumor markers in diagnosing CRC was assessed by receiver operating characteristic analysis. Results: The sensitivity of serum tumor markers in combination was significantly higher than serum tumor markers detected individually. CA19-9 levels were significantly correlated with CA24-2 levels (r = 0.884; P < .001) in patients with CRC. The preoperative CEA, CA19-9, and CA24-2 levels in patients with colon cancer were significantly higher than in patients with rectum cancer (all P < .001). The CA19-9 and CA24-2 levels were significantly higher in patients with lymph node metastasis than without (both P < .001). In addition, the CEA, CA19-9, and CA24-2 levels in patients with distant metastasis were significantly higher than those in patients without metastasis (all P < .001). Stratified analysis showed that CEA, CA19-9, and CA24-2 levels were significantly correlated with TNM staging (P < .05). With regard to the depth of tumor invasion, CEA, CA19-9, and CA24-2 levels in tumors outside the serosa were significantly higher than those in other tumor types (P < .05). In terms of diagnostic performance, CEA had a sensitivity of 0.52 and a specificity of 0.98, CA19-9 had a sensitivity of 0.35 and a specificity of 0.91, and CA24-2 had a sensitivity of 0.46 and a specificity of 0.95. Conclusion: The detection of serum tumor markers CEA, CA19-9, and CA24-2 is a good method for supporting diagnosis, making treatment decisions, judging therapeutic effect, and predicting prognosis when managing patients with CRC.

JAZF1 safeguards human endometrial stromal cells survival and decidualization by repressing the transcription of G0S2.

Decidualization of human endometrial stromal cells (hESCs) is essential for the maintenance of pregnancy, which depends on the fine-tuned regulation of hESCs survival, and its perturbation contributes to pregnancy loss. However, the underlying mechanisms responsible for functional deficits in decidua from recurrent spontaneous abortion (RSA) patients have not been elucidated. Here, we observed that JAZF1 was significantly downregulated in stromal cells from RSA decidua. JAZF1 depletion in hESCs resulted in defective decidualization and cell death through apoptosis. Further experiments uncovered G0S2 as a important driver of hESCs apoptosis and decidualization, whose transcription was repressed by JAZF1 via interaction with G0S2 activator Purß. Moreover, the pattern of low JAZF1, high G0S2 and excessive apoptosis in decidua were consistently observed in RSA patients. Collectively, our findings demonstrate that JAZF1 governs hESCs survival and decidualization by repressing G0S2 transcription via restricting the activity of Purß, and highlight the clinical implications of these mechanisms in the pathology of RSA.

Two-Step Synthesis of B2 N2 -Doped Polycyclic Aromatic Hydrocarbon Containing Pentagonal and Heptagonal Rings with Long-Lived Delayed Fluorescence.

Pentagon-heptagon embedded polycyclic aromatic hydrocarbons (PAHs) have aroused increasing attention in recent years due to their unique physicochemical properties. Here, for the first time, this report demonstrates a facile method for the synthesis of a novel B2 N2 -doped PAH (BN-2) containing two pairs of pentagonal and heptagonal rings in only two steps. In the solid state of BN-2, two different conformations, including saddle-shaped and up-down geometries, are observed. Through a combined spectroscopic and calculation study, the excited-state dynamics of BN-2 is well-investigated in this current work. The resultant pentagon-heptagon embedded B2 N2 -doped BN-2 displays both prompt fluorescence and long-lived delayed fluorescence components at room temperature, with the triplet excited-state lifetime in the microsecond time region (τ = 19 µs). The triplet-triplet annihilation is assigned as the mechanism for the observed long-lived delayed fluorescence. Computational analyses attributed this observation to the small energy separation between the singlet and triplet excited states, facilitating the intersystem crossing (ISC) process which is further validated by the ultrafast spectroscopic measurements.