[Mechanism of Shenling Baizhu Powder on treatment of alcoholic liver disease by regulating TLR4/NLRP3 pathway].

This study aims to investigate the regulatory effects of Shenling Baizhu Powder(SBP) on cellular autophagy in alcoholic liver disease(ALD) and its intervention effect through the TLR4/NLRP3 pathway. A rat model of chronic ALD was established by gavage of spirits. An ALD cell model was established by stimulating BRL3A cells with alcohol. High-performance liquid chromatography(HPLC) was utilized for the compositional analysis of SBP. Liver tissue from ALD rats underwent hematoxylin-eosin(HE) and oil red O staining for pathological evaluation. Enzyme-linked immunosorbent assay(ELISA) was applied to quantify lipopolysaccharides(LPS), tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1ß), and interleukin-18(IL-18) levels. Quantitative reverse transcription polymerase chain reaction(qRT-PCR) was conducted to evaluate the mRNA expression of myeloid differentiation factor 88(MyD88) and Toll-like receptor 4(TLR4). The effect of different drugs on BRL3A cell proliferation activity was assessed through CCK-8 analysis. Western blot analysis was performed to examine the protein expression of NOD-like receptor pyrin domain-containing 3(NLRP3), nuclear factor-kappa B P65(NF-κB P65), phosphorylated nuclear factor-kappa B P65(p-P65), caspase-1, P62, Beclin1, and microtubule-associated protein 1 light chain 3(LC3Ⅱ). The results showed that SBP effectively ameliorated hepatic lipid accumulation, reduced liver function, mitigated hepatic tissue inflammation, and reduced levels of LPS, TNF-α, IL-1ß, and IL-18. Moreover, SBP exhibited the capacity to modulate hepatic autophagy induced by prolonged alcohol intake through the TLR4/NLRP3 signaling pathway. This modulation resulted in decreased expression of LC3Ⅱ and Beclin1, an elevation in P62 expression, and the promotion of autolysosome formation. These research findings imply that SBP can substantially enhance liver function and mitigate lipid irregularities in the context of chronic ALD. It achieves this by regulating excessive autophagic responses caused by prolonged spirit consumption, primarily through the inhibition of the TLR4/NLRP3 pathway.

An IGF1-expressing endometrial stromal cell population is associated with human decidualization.

BACKGROUND: Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and immunoprivileged matrix essential for blastocyst implantation and placental development. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure (RIF), and miscarriages. Despite the increasing number of genes reportedly associated with endometrial receptivity and decidualization, the cellular and molecular mechanisms triggering and underlying decidualization remain largely unknown. Here, we analyze single-cell transcriptional profiles of endometrial cells during the window of implantation and decidual cells of early pregnancy, to gains insights on the process of decidualization. RESULTS: We observed a unique IGF1+ stromal cell that may initiate decidualization by single-cell RNA sequencing. We found the IL1B+ stromal cells promote gland degeneration and decidua hemostasis. We defined a subset of NK cells for accelerating decidualization and extravillous trophoblast (EVT) invasion by AREG-IGF1 and AREG-CSF1 regulatory axe. Further analysis indicates that EVT promote decidualization possibly by multiply pathways. Additionally, a systematic repository of cell-cell communication for decidualization was developed. An aberrant ratio conversion of IGF1+ stromal cells to IGF1R+ stromal cells is observed in unexplained RIF patients. CONCLUSIONS: Overall, a unique subpopulation of IGF1+ stromal cell is involved in initiating decidualization. Our observations provide deeper insights into the molecular and cellular characterizations of decidualization, and a platform for further development of evaluation of decidualization degree and treatment for decidualization disorder-related diseases.

Frequency noise reduction of delay-coupled quantum cascade lasers.

This work theoretically investigates the frequency noise and spectral linewidth characteristics of mutually delay-coupled quantum cascade lasers, which are operated in the stable locking regime. We demonstrate that the mutual injection significantly reduces the frequency noise at proper coupling phases. However, the relative intensity noise is insensitive to the mutual injection. Influences of the pump current, the linewidth broadening factor, the coupling phase, and the delay time on the frequency noise are discussed as well. In addition, it is found that the appearance of multiple compound laser modes can deteriorate the frequency noise performance of the lasers.

Aberrant expression of five miRNAs in papillary thyroid carcinomas.

BACKGROUND: The miRNAs play critical roles in the progression of various tumors. Our study aimed to screen and identify miRNAs to investigate their diagnostic and prognostic value for papillary thyroid carcinoma (PTC). METHODS: miRNAs were evaluated in PTC (n = 30) tissues, A-PTC (n = 30), benign nodules (n = 35) and A-benign nodules (n = 35). The expression levels of five miRNAs were quantified using real-time, quantitative PCR. ROC analysis was used to evaluate the miRNA diagnostic value. RESULTS: The expression of miR-1296-5p, miR-1301-3p, and miR-532-5p was significantly downregulated (p = 0.0001, p = 0.0006, p = 0.0024, respectively), while miR-551b-3p and miR-455-3p were significantly upregulated in PTC tissues compared to A-PTC tissues (p = 0.0005, p = 0.0046, respectively). Interestingly, the expression of miR-1296-5p was downregulated, while miR-551b-3p and miR-455-3p were upregulated in the A-PTC group compared to the A-benign group. Moreover, the miR-1296-5p expression level was associated with tumor size, the number of foci and the TNM stage; the miR-455-3p expression level was correlated with patient age, tumor size, and TNM stage; and the miR-532-5p expression level was correlated with patient age, lymph node metastasis and TNM stage correspondingly. ROC analysis revealed that the AUCs for miR-1301-3p, miR-1296-5p, miR-455-3p, miR-532-5p, and miR-551b-3p were 0.773, 0.790, 0.783, 0.744, and 0.650, respectively. CONCLUSIONS: Our results indicated that miR-1296-5p, miR-1301-3p, miR-532-5p, miR-551b-3p, and miR-455-3p are aberrantly expressed in papillary thyroid carcinomas and correlated with clinicopathological features. ROC curve analysis indicated that these five miRNAs have a potential diagnostic value. Consequently, we speculate that the five altered miRNAs may serve as potential diagnostic and prognostic biomarkers for PTC.

miR-1301-3p suppresses tumor growth by downregulating PCNA in thyroid papillary cancer.

OBJECTIVE: Thyroid carcinoma is the most common endocrine tumor, and thyroid papillary carcinoma is the most common form. Although thyroid papillary carcinoma presents a good prognosis, some patients still exhibit recurrence or distant metastasis. miR-1301-3p has been found involved in the occurrence and development of some special tumors. Our study aims to investigate the miR-1301-3p expression in thyroid papillary carcinoma, to explore its biological function, and to provide a potential marker for diagnosis and treatment of thyroid papillary carcinoma. MATERIALS AND METHODS: The tissue samples from 70 patients with PTC (n = 35) and benign tumors (n = 35) were collected respectively. miR-1301-3p expression were detected by qPCR. Diagnostic value of miR-1301-3p was analyzed by ROC curve. CCK-8 assays and flow cytometry were performed to detect the effect of miR-1301-3p on TPC-1 function. PCNA expression of protein was detected by WB. RESULTS: Compared with the normal group, the expression of miR-1301-3p was obviously decreased in both benign group and PTC group. With the higher T and N grades, the lower expression of miR-1301-3p. ROC curve analysis showed that the diagnostic values of miR-1301-3p for benign tumor and PTC were 0.766 and 0.881, respectively. Vitro experiments showed that miR-1301-3p was decreased in TPC-1 cells, then, upregulated miR-1301-3p blocked the TPC-1 cell cycle in G1/S phase, and inhibited the proliferation. PCNA expression was significantly increased in TPC-1 cells and significantly decreased after upregulation of miR-1301-3p. CONCLUSION: The present study showed that the expression of miR-1301-3p in PTC was significantly decreased, which was related to T and N grade. Upregulation of miR-1301-3p could inhibit cell proliferation and cell migration. miR-1301-3p may serve as a potential biomarker for the early diagnosis and treatment of PTC.

Ischemic Preconditioning-Induced SOCS-1 Protects Rat Intestinal Ischemia Reperfusion Injury via Degradation of TRAF6.

BACKGROUND: The inflammatory immune response plays an important role in mesenteric ischemia and ischemia-reperfusion injury. Toll-like receptor 4 (TLR4) is a critical receptor in transduction of the inflammatory response and plays an important role in intestinal homeostasis. Tumor necrosis factor receptor-associated factor 6 (TRAF6), known as a key adaptor protein downstream of TLR4, is involved in the inflammatory response by activating multiple apoptotic signaling pathways. However, mechanisms of the suppressor of cytokine signaling-1 (SOCS-1) in regulating cell inflammation and apoptosis are still obscure. OBJECTIVES: To investigate the TLR4-TRAF6 signaling pathway in intestinal ischemia and reperfusion injury, as well as SOCS-1 expression after ischemic preconditioning in the rat intestine. METHODS: The small bowel ischemia, ischemia-reperfusion, and preconditioning models were induced using ligation of the superior mesenteric artery in male Sprague-Dawley rats; then, the mRNA and protein levels of TLR4, TRAF6, and SOCS-1 were analyzed using real-time PCR, Western blot, and immunohistochemistry, respectively. RESULTS: The expression of TLR4 and TRAF6 was gradually increased with increasing intestinal ischemia duration, but increased substantially after ischemia-reperfusion injury. After ischemic preconditioning, TLR4 and TRAF6 expressions decreased; however, expression of SOCS-1 and the TLR4-TRAF6 pathway inhibitor was increased. CONCLUSION: These data show that ischemic preconditioning may induce the activation of SOCS-1 to inhibit the TLR4-TRAF6 signaling pathway, thereby playing a protective role in ischemia-reperfusion injury.

[Intervention effects of Jiaotai pills on PCPA-induced insomnia in rats].

To elucidate the intervention effects of Jiaotai pills(JTP) on p-chlorophenylalanine (PCPA)-induced insomnia in rats and its underlying mechanism, the insomnia model was established by single intraperitoneal injection with PCPA in rats. The locomotor activity of rats was observed, and the levels of nerve growth factor(NGF) in hypothalamus, hippocampus, prefrontal cortex and serum of rats were determined by using ELISA. Moreover, a proton nuclear magnetic resonance(¹H-NMR)-based metabonomic approach was developed to profile insomnia-related metabolites in rat serum and hippocampus and analyze the intervention effects of JTP on changes in underlying biomarkers related to locomotor activity, NGF and insomnia. According to the results, JTP could significantly suppress the locomotor activity of insomnia rats, and increase the NGF levels in hypothalamus, hippocampus, prefrontal cortex and serum of rats with insomnia. The disturbed metabolic state associated with PCPA-induced insomnia in rat serum and hippocampus could be intervened by JTP. Meanwhile, six and five potential biomarkers related to insomnia in rat serum and hippocampus were reversed by administration of JTP. In conclusion, the current study demonstrated that JTP had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of NGF level and metabolism of amino acids, lipids and choline.

Endoplasmic reticulum stress may not be involved in intestinal epithelial cell apoptosis in experimental acute pancreatitis.

OBJECTIVES: To investigate whether endoplasmic reticulum (ER) stress is activated in the intestinal epithelium of acute pancreatitis (AP), and whether it is one of the inducing factors of the intestinal epithelial cell apoptosis in AP. METHODS: Twenty-four rats were randomly divided into two groups. AP was induced via retrograde injection of 3 % sodium taurocholate into the pancreatic duct. As a control group, rats received a sham operation. Forty-eight hours after the operation, the ultrastructural changes of ileal epithelial cells were investigated by transmission electron microscope. The protein expressions of GRP78, CHOP, caspase-12, and JNK in the ileal epithelium were determined by immunohistochemistry, and apoptosis was determined by TdT-mediated dUTP nick end labeling. The mRNA expressions of GRP78, CHOP, caspase-12, and JNK in the ileal epithelium were determined using quantitative RT-PCR. RESULTS: The ileal epithelium in rats with AP had significantly higher apoptotic cells compared with that of the control rats (P < 0.05). ER stress was activated in the ileal epithelium, which was characterized by dilated, irregular ER and upregulated expressions of GRP78 mRNA and protein. The mRNA and protein expressions of CHOP, caspase-12, and JNK in rats with AP were similar to that in the control rats (P > 0.05). CONCLUSIONS: ER stress is induced in intestinal epithelium during AP; however, ER stress is not likely to be involved in the apoptosis of the intestinal epithelium during AP.

Is radiofrequency ablation equal to surgical re-resection for recurrent hepatocellular carcinoma meeting the Milan criteria? A meta-analysis.

PURPOSE: To evaluate the clinical efficacy and safety of radiofrequency ablation (RFA) with surgical re-resection (SRR) in patients with postoperative recurrent hepatocellular carcinoma (RHCC) meeting the Milan criteria. METHODS: A literature search was performed to identify comparative studies addressing outcomes of both RFA and SRR for RHCC meeting the Milan criteria. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using either the fixed effects model or the random effects model. RESULTS: Five nonrandomized controlled trials were included in the analysis. These studies included a total of 543 patients: 243 treated with RFA and 300 treated with SRR. The SRR group had a better 3-year recurrence-free survival rate compared with RFA group (OR 0.44, 95%CI 0.25-0.77, p=0.004). However, there were no obvious differences between RFA and SRR group in overall survival (OS) rates, re-recurrence rate and OS rates with tumors ≤ 3cm. What's more, the RFA group had a safety advantage with less complications of Clavien classification grade II or higher compared with SRR group (OR 0.21, 95%CI 0.05-0.94, p=0.04). CONCLUSIONS: RFA seemed to be superior to SRR in the treatment of patients with RHCC meeting the Milan criteria on account of clinical safety. However, these findings have to be carefully interpreted due to the lower level of evidence.

Serum soluble ST2 is associated with ER-positive breast cancer.

BACKGROUND: ST2, a member of the interleukin (IL)-1receptor family, regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions. However, the role of ST2 signaling in tumor growth and metastasis of breast cancers has not been investigated. This study investigated the possible role of soluble ST2 (sST2) in breast cancer. METHODS: The serum levels of IL-33, sST2, and vascular endothelial growth factor (VEGF) in 150 breast cancer patients and 90 healthy women were measured by enzyme-linked immunosorbent assay. Estrogen receptor(ER), progesterone receptor, human epithelial receptor (HER)-2, and cell cycle regulated protein Ki-67 were measured. Clinical stage, tumor size, lymph node metastasis, and histological type were also recorded. RESULTS: The serum levels of sST2, IL-33, and VEGF were significantly higher in breast cancer patients than in the control group (P < 0.05, each). Serum sST2 levels in ER-positive breast cancer patients were significantly associated with age, histological type, clinical stage, tumor size, and Ki-67 status (P < 0.05, each). Moreover, the serum levels of IL-33 and sST2 in breast cancers significantly correlated with VEGF levels (IL-33: r = 0.375, P < 0.0001; sST2: r = 0.164, P = 0.045). Serum levels of sST2, IL-33, and VEGF decreased after modified radical mastectomy in ER-positive breast cancers. Serum levels of IL-33, sST2, and VEGF and clinicopathological factors were not significantly correlated with disease-free survival and overall survival of ER-positive breast cancer women during follow-up. CONCLUSION: Serum sST2 levels in ER-positive breast cancer patients are significantly associated with factors that indicate poor prognosis.

Mutations in the COPII vesicle component gene SEC24B are associated with human neural tube defects.

Neural tube defects (NTDs) are severe birth malformations that affect one in 1,000 live births. Recently, mutations in the planar cell polarity (PCP) pathway genes had been implicated in the pathogenesis of NTDs in both the mouse model and in human cohorts. Mouse models indicate that the homozygous disruption of Sec24b, which mediates the ER-to-Golgi transportation of the core PCP gene Vangl2 as a component of the COPII vesicle, will result in craniorachischisis. In this study, we found four rare missense heterozygous SEC24B mutations (p.Phe227Ser, p.Phe682Leu, p.Arg1248Gln, and p.Ala1251Gly) in NTDs cases that were absent in all controls. Among them, p.Phe227Ser and p.Phe682Leu affected its protein stability and physical interaction with VANGL2. Three variants (p.Phe227Ser, p.Arg1248Gln, and p.Ala1251Gly) were demonstrated to affect VANGL2 subcellular localization in cultured cells. Further functional analysis in the zebrafish including overexpression and dosage-dependent rescue study suggested that these four mutations all displayed loss-of-function effects compared with wild-type SEC24B. Our study demonstrated that functional mutations in SEC24B might contribute to the etiology of a subset of human NTDs and further expanded our knowledge of the role of PCP pathway-related genes in the pathogenesis of human NTDs.

Effects of particle size on the structure, cooking quality and anthocyanin diffusion of purple sweet potato noodles.

The effects of different particle sizes of purple sweet potato flour (PSPF) on the structure and quality of noodles and the diffusion kinetics of anthocyanins during cooking were studied. As the particle size of the PSPF decreased (from 269 to 66 µm), the adverse effects of the addition of PSPF on the quality of noodles were reduced. The smaller particle size of PSPF was beneficial for the secondary structure orderliness and the tighter microstructure of PSP noodles. The diffusion of anthocyanins in noodles to the soup during cooking could be fitted well with Fick's second law, and diffusion coefficients were in the range of 8.3248-14.0893 × 10-9 m2/s. The noodles with 15% 66 µm PSPF showed the best cooking properties, the highest sensory score, the highest anthocyanin retention ability and a compact and orderly microstructure. Thus, they could be considered as noodles rich in anthocyanins for commercial application.

Gestational palmitic acid suppresses embryonic GATA-binding protein 4 signaling and causes congenital heart disease.

Dysregulated maternal fatty acid metabolism increases the risk of congenital heart disease (CHD) in offspring with an unknown mechanism, and the effect of folic acid fortification in preventing CHD is controversial. Using gas chromatography coupled to either a flame ionization detector or mass spectrometer (GC-FID/MS) analysis, we find that the palmitic acid (PA) concentration increases significantly in serum samples of pregnant women bearing children with CHD. Feeding pregnant mice with PA increased CHD risk in offspring and cannot be rescued by folic acid supplementation. We further find that PA promotes methionyl-tRNA synthetase (MARS) expression and protein lysine homocysteinylation (K-Hcy) of GATA4 and results in GATA4 inhibition and abnormal heart development. Targeting K-Hcy modification by either genetic ablation of Mars or using N-acetyl-L-cysteine (NAC) decreases CHD onset in high-PA-diet-fed mice. In summary, our work links maternal malnutrition and MARS/K-Hcy with the onset of CHD and provides a potential strategy in preventing CHD by targeting K-Hcy other than folic acid supplementation.

Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease.

Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid-gestational age-the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case-control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.

Diagnosis of Ectopic Intrathyroidal Parathyroid Adenoma with Nodular Goiter by 18F Fluorocholine: A Case Report.

The occurrence of ectopic intrathyroidal parathyroid adenoma (EPTA) is very rare, which causes some difficulties in diagnosis and complicates treatment. In addition, the occurrence of EPTA with nodular goiter (NG) is rare, which makes diagnosis difficult and requires the assistance of clinical evidence, imaging data, and cytological examination results. Therefore, we present a patient with a final diagnosis of ETPA with NG.

A Practical Risk-Based Model for Early Warning of Seafarer Errors Using Integrated Bayesian Network and SPAR-H.

Unsafe crew acts (UCAs) related to human errors are the main contributors to maritime accidents. The prediction of unsafe crew acts will provide an early warning for maritime accidents, which is significant to shipping companies. However, there exist gaps between the prediction models developed by researchers and those adopted by practitioners in human risk analysis (HRA) of the maritime industry. In addition, most research regarding human factors of maritime safety has concentrated on hazard identification or accident analysis, but not on early warning of UCAs. This paper proposes a Bayesian network (BN) version of the Standardized Plant Analysis Risk-Human Reliability Analysis (SPAR-H) method to predict the probability of seafarers' unsafe acts. After the identification of performance-shaping factors (PSFs) that influence seafarers' unsafe acts during navigation, the developed prediction model, which integrates the practicability of SPAR-H and the forward and backward inference functions of BN, is adopted to evaluate the probabilistic risk of unsafe acts and PSFs. The model can also be used when the available information is insufficient. Case studies demonstrate the practicability of the model in quantitatively predicting unsafe crew acts. The method allows evaluating whether a seafarer is capable of fulfilling their responsibility and providing an early warning for decision-makers, thereby avoiding human errors and sequentially preventing maritime accidents. The method can also be considered as a starting point for applying the efforts of HRA researchers to the real world for practitioners.

Influence of the pendant groups on electrochemical water oxidation catalyzed by cobalt(II) triazolylpyridine complexes.

The development of low-cost catalysts for the water oxidation reaction (WOR) is important for solving the bottleneck issues in water splitting and benefits the widespread utilization of renewable energy sources. Herein, four cobalt(II) triazolylpyridine complexes, namely [Co(DTE)2(H2O)2](ClO4)2·CH3COCH3 (1), [Co(DTE)2Cl2]·2CH3OH (2) (DTE = (1-(2-acetoxymethyl)-4-(2-pyridyl)1,2,3-triazole), [Co(DTEL)2(CH3OH)2](ClO4)2 (3), and [Co(DTEL)2Cl2]·H2O (4) (DTEL = (1-(2-hydroxy)-4-(2-pyridyl)1,2,3-triazole), were synthesized and characterized. The crystal structures of 1-3 were determined by X-ray single crystal diffraction analysis. The electrocatalytic water oxidation by 1-4 was studied in 0.1 M NaOAc-HOAc solutions. Complexes 1-4 were single-site molecular catalysts for the WOR under near-neutral conditions. The overpotentials for the WOR were 440 mV and 480 mV. The faradaic efficiencies were 77-92%. The rate constants kcat were 0.21-0.96 s-1. The catalytic activities were affected by the pendant groups of DTE and DTEL. Complexes with DTE (1 and 2) showed better activities than those with DTEL (3 and 4). Moreover, complexes 1-4 adsorbed on indium-doped tin oxide (ITO) and glassy carbon electrode surfaces were active for the WOR. A mechanism was proposed for the WOR catalyzed by 1-4.

Psychosocial risk factors associated with esophageal cancer in Chinese cohort: A systematic review and meta-analysis.

ABSTRACT: Previous studies were controversial about the role of psychosocial factors in the pathogenesis of esophageal cancer (EC). This study aimed to systematically evaluate the effect size of psychosocial risk factors for EC in Chinese cohort.A literature search was conducted in both English and Chinese databases, and odds ratios (OR) with the corresponding 95% confidence intervals (CI) were pooled using a random-effects model.28 studies were identified with a total of 6951 EC cases and 7469 controls. The meta-analysis indicated a higher risk of EC among the individuals with psychological trauma (OR: 2.36, 95% CI: 1.71-3.26), Type A behavior (OR: 1.40, 95% CI: 1.17-1.67), depression (OR: 4.00, 95% CI: 2.44-6.55), melancholy (OR: 2.06, 95% CI: 1.32-3.20), always in sulks (OR: 2.49, 95% CI: 1.21-5.12), and irritable personality (OR: 2.13, 95% CI: 1.58-2.89). A lower EC risk was found in the individuals with good interpersonal relationship (OR: 0.35, 95% CI: 0.17-0.70) and outgoing personality (OR: 0.39, 95% CI: 0.19-0.78).This meta-analysis suggested a potential association between psychosocial factors and EC risk. For the individuals with psychosocial risk factors, physicians should pay more attention to EC screening.

Programmed Cell Death Ligand 1-Transfected Mouse Bone Marrow Mesenchymal Stem Cells as Targeted Therapy for Rheumatoid Arthritis.

Programmed cell death 1 ligand (PD-L1) and its receptor (PD-1) are key molecules for immunoregulation and immunotherapy. PD-L1 binding PD-1 is an effective way to regulate T or B cell immunity in autoimmune diseases such as rheumatoid arthritis (RA). In our study, we overexpressed PD-L1 by constructing a recombinant of PD-L1-lentiviral vector, which was subsequently used to transfect mouse bone marrow mesenchymal stem cells (MBMMSCs) and significantly suppressed the development of collagen-induced arthritis (CIA) in DBA/1j mice. In addition, PD-L1-transfected MBMMSCs (PD-L1-MBMMSCs) ameliorated joint damage, reduced proinflammatory cytokine expression, and inhibited T and B cell activation. Furthermore, PD-L1-MBMMSCs decreased the number of dendritic cells and increased the numbers of regulatory T cells and regulatory B cells in joints of CIA mice. In conclusion, our results provided a potential therapeutic strategy for RA treatment with PD-L1-MBMMSC-targeted therapy.

Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk.

Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.