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Feng Zhang,1,2 Xiangzhi Meng,2 Fang Lu,2 Aixian Liu,2 Hongyun Huang1,2 1Cell Therapy Center, Beijing Hongtianji Neuroscience Academy, 2Neurorehabilitation Center, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, People’s Republic of China Objective: To observe the result of olfactory ensheathing cell (OEC) transplantation in a patient with chronic sciatic nerve injury. Case report: A 53-year-old male patient with chronic (1 year) sciatic nerve injury on left side received OEC transplantation at the lesion site. He received follow-up assessment according to the American Spinal Injury Association standard at 10 days, 6 months, and 1 year after OEC therapy. The muscle strength of his left lower limb increased and numbness decreased during the early stage of cell therapy. His motor function improved with each evaluation. His limp walking gait recovered, and numbness sensation got nearly normal after 1 year of follow-up. There were no side effects. Conclusion: OEC transplantation may be an option for chronic peripheral (sciatic) nerve injury. Keywords: olfactory ensheathing cell transplantation, sciatic nerve injury, peripheral nerve injury, function improvement, neurorestoration

Alterations to the gut microbiota are associated with ulcerative colitis (UC), whereas restoration of normobiosis can effectively alleviate UC. l-Theanine has been shown to reshape the gut microbiota and regulate gut immunity. To investigate the mechanisms by which l-theanine alleviates UC, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice. In this study, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice to explore the mechanism by which l-theanine alleviates UC. By reducing inflammation in the colon, we demonstrated that l-theanine alleviates symptoms of UC. Meanwhile, l-theanine can improve the abundance of microbiota related to short-chain fatty acid, bile acid, and tryptophan production. Single-cell sequencing results indicated that l-theanine-mediated suppression of UC was associated with immune cell changes, especially regarding macrophages and T and B cells, and validated the immune cell responses to the gut microbiota. Further, flow cytometry results showed that the ability of dendritic cells, macrophages, and monocytes to present microbiota antigens to colonic T cells in an MHC-II-dependent manner was reduced after treating normal mouse fecal donors with l-theanine. These results demonstrate that l-theanine modulates colon adaptive and innate immunity by regulating the gut microbiota in an MHC-II-dependent manner, thereby alleviating UC.

Background: Disinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce., Methods: This study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures., Results: After adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = -1.29 %, 95 % CI: -2.49 %, -0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = -2.49 %, 95 % CI: -4.71 %, -0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships., Conclusion: Urinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mucositis is a pathological condition characterised by inflammation and ulceration of the mucous membranes lining the alimentary canal, particularly in the mouth (oral mucositis) and the gastrointestinal tract. It is a common side effect of cancer treatments, including chemotherapy and radiotherapy, and it is sometimes responsible for treatment interruptions. Preventing mucositis throughout the alimentary tract is therefore crucial. However, current interventions mainly target either oral or gastrointestinal side effects. This review aimed to investigate the use of systemically administered anti-inflammatory agents to prevent mucositis in cancer patients undergoing cancer treatment. PubMed, Ovid, Scopus, Web of Science, WHO ICTRP and ClinicalTrials.gov were screened to identify eligible randomised controlled trials (RCTs). The published literature on anti-inflammatory agents provides mixed evidence regarding the degree of efficacy in preventing/reducing the severity of mucositis in most anticancer treatments; however, sample size continued to be a significant limitation, alongside others discussed. Our review yielded a list of several anti-inflammatory agents that exhibit potential mucositis-preventive effects in cancer patients undergoing cancer treatment, which can be used to inform clinical practice.

Background: Disinfection byproducts (DBPs), the ubiquitous contaminants in drinking water, have been shown to impair renal function in experimental studies. However, epidemiological evidence is sparse., Objective: To investigate exposures to DBPs in associations with renal function among women., Methods: A total of 920 women from December 2018 to January 2020 were abstracted from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort study in Wuhan, China. Urine samples were gathered at baseline recruitment and analyzed for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. Serum uric acid (UA), creatinine, and estimated glomerular filtration rate (eGFR) were measured as indicators of renal function. Multivariate linear regression and restricted cubic spline (RCS) models were conducted to assess urinary DCAA and TCAA concentrations in associations with renal function indicators. Stratified analyses by age and body mass index (BMI) were also performed., Results: We found null evidence of urinary TCAA in associations with renal function indicators. However, elevated urinary DCAA tertiles were related to decreased eGFR (β = -1.78%, 95% CI: 3.21%, -0.36%, comparing the upper vs. lower tertile; P for trend = 0.01). This inverse association still existed when urinary DCAA concentration was treated as a continuous variable, and the dose-response relationship was linear based on the RCS model (P for overall association = 0.002 and P for non-linear associations = 0.44). In the stratified analyses, we found an association of urinary DCAA concentration with decreased UA level among women <30 years but an association with increased UA level among women ≥30 years (P for interaction = 0.04)., Conclusion: Urinary DCAA but not TCAA was associated with impaired renal function among women undergoing assisted reproductive technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Disinfection byproducts (DBPs) as ovarian toxicants have been documented in toxicological studies. However, no human studies have explored the effects of exposure to DBPs on diminished ovarian reserve (DOR)., Objective: To assess whether urinary biomarkers of exposure to drinking-water DBPs were associated with DOR risk., Methods: A total of 311 women undergoing assisted reproductive technology were diagnosed with DOR in the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. The cases were matched to the controls with normal ovarian reserve function by age in a ratio of 1:1. Urinary trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) were quantified as biomarkers of drinking-water DBP exposures. The conditional logistic regression and restricted cubic spline (RCS) were used to explore urinary biomarkers of drinking-water DBP exposures in associations with the risk of DOR., Results: Elevated urinary DCAA levels were associated with higher DOR risk [adjusted odds ratio (OR) = 1.87; 95 % confidence interval (CI): 1.16, 3.03 for the highest vs. lowest quartiles; P for trend = 0.016]. The association was confirmed in the RCS model, with a linear dose-response curve (P for overall association = 0.029 and P for non-linear association = 0.708). The subgroup analysis by age and body mass index (BMI) showed that urinary DCAA in association with DOR risk was observed among women ≥35 years old and leaner women (BMI < 24 kg/m 2 ), but the group differences were not statistically significant. Moreover, a U-shaped dose-response curve between urinary TCAA and DOR risk was estimated in the RCS model (P for overall association = 0.011 and P for non-linear association = 0.004)., Conclusions: Exposure to drinking-water DBPs may contribute to the risk of DOR among women undergoing assisted reproductive technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Toxicological studies have demonstrated that disinfection byproducts (DBPs), particularly haloacetic acids, cause testicular toxicity. However, evidence from human studies is sparse and inconclusive. This study included 1230 reproductive-aged men from the Tongji Reproductive and Environmental (TREE) cohort to investigate the associations between repeated measures of DBP exposures and semen parameters. Urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures and semen parameters in up to three samples from each man were assessed. The linear mixed effect models were applied to explore the associations between urinary biomarkers of DBP exposures and semen parameters. We found inverse associations of urinary DCAA with sperm count, progressive motility, and total motility (e.g., -14.86%; 95% CI: -19.33%, -10.15% in sperm total motility for the highest vs. lowest quartiles; all P for trends < 0.05). Moreover, urinary TCAA modeled as a continuous variable was negatively associated with sperm progressive motility and total motility, while the inverse associations across increasing urinary TCAA quartiles were seen among leaner men (BMI < 25 kg/m 2 ). Exposure to DBPs reflected by urinary DCAA and TCAA was inversely associated with sperm motility and such effects were more evident among leaner men., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce., Objective: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters., Methods: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored., Results: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m 2 ), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05)., Conclusion: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Decidualization is a process in which endometrial stromal fibroblasts differentiate into specialized secretory decidual cells and essential for the successful establishment of pregnancy. The underlying mechanism during decidualization still remains poorly defined. Because decidualization and fibroblast activation share similar characteristics, this study was to examine whether fibroblast activation is involved in decidualization. In our study, fibroblast activation-related markers are obviously detected in pregnant decidua and under in vitro decidualization. ACTIVIN A secreted under fibroblast activation promotes in vitro decidualization. We showed that arachidonic acid released from uterine luminal epithelium can induce fibroblast activation and decidualization through PGI 2 and its nuclear receptor PPARδ. Based on the significant difference of fibroblast activation-related markers between pregnant and pseudopregnant mice, we found that embryo-derived TNF promotes CPLA 2α phosphorylation and arachidonic acid release from luminal epithelium. Fibroblast activation is also detected under human in vitro decidualization. Similar arachidonic acid-PGI 2 -PPARδ-ACTIVIN A pathway is conserved in human endometrium. Collectively, our data indicate that embryo-derived TNF promotes CPLA 2α phosphorylation and arachidonic acid release from luminal epithelium to induce fibroblast activation and decidualization., Competing Interests: SC, WS, YL, ZY, YW, ML, YL, AL, YH, ZY No competing interests declared, (© 2023, Chen et al.)

The response of leaf functional traits can provide vital insight into the adaptive strategies of plants under global change. However, empirical knowledge on the acclimation of functional coordination between phenotypic plasticity and integration to increased nitrogen (N) deposition is still scarce. The variation of leaf functional traits of two dominant seedling species, Machilus gamblei and Neolitsea polycarpa, across four N deposition rates (0, 3, 6, and 12 kg N ha -1 yr -1 ), along with the relationship between leaf phenotypic plasticity and integration were investigated in a subtropical montane forest. We found that enhanced N deposition promoted the development of seedling traits toward the direction of resource acquisition, including improved leaf N content, specific leaf area and photosynthetic performance. Appropriate N deposition (≤6 kg N ha -1  yr -1 ) might induce the optimization of leaf functional traits to promote the capability and efficiency of nutrient use and photosynthesis in seedlings. However, excessive N deposition (12 kg N ha -1  yr -1 ) would result in detrimental effects on leaf morphological and physiological traits, thus inhibiting the efficiency in resource acquisition. A positive relationship occurred between leaf phenotypic plasticity and integration in both seedling species, implied that higher plasticity of leaf functional traits likely led to better integration with other traits under N deposition. Overall, our study emphasized that leaf functional traits could rapidly respond to changes in N resource, while the coordination between leaf phenotypic plasticity and integration can facilitate the adaptation of tree seedlings in coping with enhanced N deposition. Further studies are still needed on the role of leaf phenotypic plasticity and integration in plant fitness for predicting ecosystem functioning and forest dynamics, especially in the context of future high N deposition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

While the celebrated graph neural networks (GNNs) yield effective representations for individual nodes of a graph, there has been relatively less success in extending to the task of graph similarity learning. Recent work on graph similarity learning has considered either global-level graph-graph interactions or low-level node-node interactions, however, ignoring the rich cross-level interactions (e.g., between each node of one graph and the other whole graph). In this article, we propose a multilevel graph matching network (MGMN) framework for computing the graph similarity between any pair of graph-structured objects in an end-to-end fashion. In particular, the proposed MGMN consists of a node-graph matching network (NGMN) for effectively learning cross-level interactions between each node of one graph and the other whole graph, and a siamese GNN to learn global-level interactions between two input graphs. Furthermore, to compensate for the lack of standard benchmark datasets, we have created and collected a set of datasets for both the graph-graph classification and graph-graph regression tasks with different sizes in order to evaluate the effectiveness and robustness of our models. Comprehensive experiments demonstrate that MGMN consistently outperforms state-of-the-art baseline models on both the graph-graph classification and graph-graph regression tasks. Compared with previous work, multilevel graph matching network (MGMN) also exhibits stronger robustness as the sizes of the two input graphs increase.

Anomaly detection in multivariate time series is an important problem with applications in several domains. However, the key limitation of the approaches that have been proposed so far lies in the lack of a highly parallel model that can fuse temporal and spatial features. In this paper, we propose TDRT, a three-dimensional ResNet and transformer-based anomaly detection method. TDRT can automatically learn the multi-dimensional features of temporal-spatial data to improve the accuracy of anomaly detection. Using the TDRT method, we were able to obtain temporal-spatial correlations from multi-dimensional industrial control temporal-spatial data and quickly mine long-term dependencies. We compared the performance of five state-of-the-art algorithms on three datasets (SWaT, WADI, and BATADAL). TDRT achieves an average anomaly detection F1 score higher than 0.98 and a recall of 0.98, significantly outperforming five state-of-the-art anomaly detection methods.

Background and Purpose: Orthostatic hypotension (OH) is common in patients with Parkinson's disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD., Methods: This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET). According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively., Results: CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group ( p <0.05) at baseline. Logistic regression analysis indicated that peak load and ΔSBP during CPET had significant effects on OH ( p <0.05). Age, sex, peak load, and ΔSBP were used to construct the nomogram model (C-index=0.761). The prediction model had an AUC of 0.782 (95% confidence interval=0.649-0.889) and a specificity and sensitivity of 70.0% and 81.8%, respectively., Conclusions: This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Neurological Association.)

Endometrial decidualization plays a pivotal role during early pregnancy. Compromised decidualization has been tightly associated with recurrent implantation failure (RIF). Primary cilium is an antenna-like sensory organelle and acts as a signaling nexus to mediate Hh, Wnt, TGFβ, BMP, FGF, and Notch signaling. However, whether primary cilium is involved in human decidualization is still unknown. In this study, we found that primary cilia are present in human endometrial stromal cells. The ciliogenesis and cilia length are increased by progesterone during in vitro and in vivo decidualization. Primary cilia are abnormal in the endometrium of RIF patients. Based on data from both assembly and disassembly of primary cilia, it has been determined that primary cilium is essential to human decidualization. Trichoplein (TCHP)-Aurora A signaling mediates cilia disassembly during human in vitro decidualization. Mechanistically, primary cilium modulates human decidualization through PTEN-PI3K-AKT-FOXO1 signaling. Our study highlights primary cilium as a novel decidualization-related signaling pathway.

Ethnopharmacological Relevance: Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR)., Aim of the Study: Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action., Materials and Methods: HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose-induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3β (GSK3β), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting. Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2, and GSK3β., Results: DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3β, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3β signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3β; however, the binding force was relatively strong., Conclusions: DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3β pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Context: Spontaneous abortion (SA) is a common disorder in early pregnancy. Circular RNAs (circRNAs) have been reported to exert important regulatory effects on trophoblast function and embryo development., Objective: The aim of this study was to explore whether and how circRNAs regulate trophoblast function in SA during early pregnancy., Methods: Cell proliferation, 5-bromo-2-deoxyuridine (BrdU) staining, Transwell, immunofluorescence, Western blot, RNA pull-down, and dual luciferase reporter assays were performed to investigate the effect of circRNA cyclin B1 (circ-CCNB1) on trophoblast function in HTR-8/SVneo and JEG-3 cells., Results: An in vitro study demonstrated that upregulation of circ-CCNB1 significantly inhibited trophoblast proliferation and invasion compared with the controls using HTR-8/SVneo and JEG-3 cells, respectively. Moreover, miR-223 was downregulated in the villous tissues of patients with SA and was further predicted and shown to negatively interact with circ-CCNB1, which is involved in trophoblast proliferation and invasion. Using bioinformatics tools and subsequent RNA pull-down and dual luciferase assays, we found that miR-223 directly targets seven in absentia homolog-1 (SIAH1) and that upregulation of miR-223 decreased circ-CCNB1-induced SIAH1 expression levels in HTR-8/SVneo cells. Interestingly, upregulation of circ-CCNB1 suppressed trophoblast proliferation and invasion through inhibition of CCNB1 nuclear translocation induced by SIAH1. Downregulation of SIAH1 enhanced circ-CCNB1-suppressed CCNB1 nuclear protein expression in trophoblast cells., Conclusion: Circ-CCNB1 served as a modulator of trophoblast proliferation and invasion by sponging miR-223, thus forming a regulatory network of circ-CCNB1/miR-223/SIAH1 in modulating CCNB1 nuclear translocation, which enabled us to elucidate the molecular mechanisms involved in normal embryo implantation or in SA., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

In this paper, we propose a novel multi-user access in wireless optical communication based on the quantum detection of the coherent state. In this case, the coherent states are used as the signal carrier and a technique of quantum detection is applied to distinguish between signals from different users. To accomplish this task, two main quantum measurement methods are introduced; one is minimum error discrimination (MED), and the other is unambiguous state discrimination (USD). The theoretical derivation implies that the two methods can both distinguish between the signals from different users efficiently when the average photon number is large enough. Typically, the numerical result shows that in the two-user case, the channel capacity will approach the theoretical maximum limit when the average photon number is greater than 2.5 for MED and 5 for USD in the absence of noise. The MED gains more channel capacity than the USD at the same average photon number. However, the USD wins the error-correction scene with its free-error capability. Furthermore, the detection error probability and channel capacity for the USD with the thermal noise are examined. The result shows that increasing the signal average photon number can continue the USD's advantage of error-free detection even if in the presence of thermal noise. In addition, compared with non-orthogonal multiple access (NOMA), the bit error rate (BER) against signal-to-noise rate (SNR) performance of USD has been improved.

High maternal serum estradiol (E 2 ) levels in the first trimester of pregnancy are associated with a high incidence of low birth weight (LBW) and small for gestational age (SGA). This study aimed to investigate the effect of first-trimester high maternal serum E 2 levels on fetal growth and the underlying mechanisms in multiple pregnancies. Maternal serum E 2 levels of women at 8 weeks of gestation were measured. The expression levels of imprinted genes and DNMT1 were determined by RT-qPCR, and KvDMR1 methylation in embryo tissue, placenta, and newborn cord blood samples was examined by bisulfite sequencing PCR. The effect of E 2 on CDKN1C expression was investigated in HTR8 cells. The incidence of SGA was significantly higher in multiple pregnancies reduced to singleton than that in primary singleton pregnancies (11.4% vs. 2.9%) (P < 0.01) and multiple pregnancies reduced to twins than primary twins (38.5% vs. 27.3%) (P < 0.01). The maternal serum E 2 level at 8 weeks of gestation increased with the number of fetuses and was negatively correlated with offspring birth weight. CDKN1C and DNMT1 expression was significantly upregulated in embryo tissue, placenta, and cord blood from multiple pregnancies. Furthermore, there was a positive correlation between CDKN1C mRNA expression and KvDMR1 methylation levels. In HTR8 cells, DNMT1 mediated the estrogen-induced upregulation of CDKN1C, which might contribute to SGA. To minimize the risks of LBW and SGA, our findings suggest that abnormally high maternal serum E 2 levels should be avoided during the first trimester of multiple pregnancies from assisted reproductive technology (ART)., (© 2021. The Author(s).)

Decidualization is essential to the establishment of pregnancy in rodents and primates. Laminin A5 (encoding by Laminin α5 ) is a member of the laminin family, which is mainly expressed in the basement membranes. Although laminins regulate cellular phenotype maintenance, adhesion, migration, growth, and differentiation, the expression, function, and regulation of laminin A5 during early pregnancy are still unknown. Therefore, we investigated the expression and role of laminin A5 during mouse and human decidualization. Laminin A5 is highly expressed in mouse decidua and artificially induced deciduoma. Laminin A5 is significantly increased under in vitro decidualization. Laminin A5 knockdown significantly inhibits the expression of Prl8a2 , a marker for mouse decidualization. Progesterone stimulates the expression of laminin A5 in ovariectomized mouse uterus and cultured mouse stromal cells. We also show that progesterone regulates laminin A5 through the PKA-CREB-C/EBPβ pathway. Laminin A5 is also highly expressed in human pregnant decidua and cultured human endometrial stromal cells during in vitro decidualization. Laminin A5 knockdown by siRNA inhibits human in vitro decidualization. Collectively, our study reveals that laminin A5 may play a pivotal role during mouse and human decidualization via the PKA-CREB-C/EBPβ pathway.

High level of uric acid (UA) is the major origin of gout, and is highly associated with various pregnant complications, such as preeclampsia and gestational diabetes. However, UA's level and role in the very early stage of pregnancy has not been uncovered. This study aims to investigate the relevance of serum UA and decidualization, an essential process for the establishment and maintenance of pregnancy in women and mice during the early stage of pregnancy. In this study, we first proved that expression level of UA synthase xanthine dehydrogenase (XDH) is highly increased along with decidualization of endometrial stromal cells in both in vitro and in vivo models. Furthermore, serum and endometrial levels of UA are higher in mice with decidualized uterin horn and in vitro decidualized stromal cells. The existence of monosodium urate (MSU) crystal was also confirmed by immunostaining. Next, the roles of MSU on decidualization were explored by both in vitro and in vivo models. Our data shows MSU crystal but not UA enhances the decidualization response of endometrial stromal cells, via the upregulation of inflammatory genes such Ptgs2 and Il11 . inhibiting of Cox-2 activity abolishes MSU crystal induced higher expression of decidualization marker Prl8a2 . At last, in women, we observed enriched expression of XDH in decidua compare to non-decidualized endometrium, the serum level of UA is significantly increased in women in very early stage of pregnancy, and drop down after elective abortion. In summary, we observed an increased serum UA level in the early stage of women's pregnancy, and proved that the increased level of UA results from the expressed XDH in decidualizing endometrium of both human and mouse, leading to the formation of MSU crystal. MSU crystal can enhance the decidualization response via inflammatory pathways. Our study has uncovered the association between UA, MSU, and decidualization during the early stage of pregnancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Wu, Chen, Kang, Pan, Liu, Li, Yan, Liu, Huang, Yang and Su.)

Parkinson's disease (PD) can be classified into three motor-based subtypes: postural instability/gait difficulty (PIGD), tremor dominant (TD), and indeterminate. The neuropathophysiological mechanisms of the three motor subtypes are different, which may lead to different responses to therapy. Sixty-nine patients with idiopathic Parkinson's disease (Hoehn-Yahr stage ≤ 3) were screened from 436 patients with Parkinsonism recruited through outpatient services and the internet. According to the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) TD/PIGD ratio, the patients were divided into PIGD (TD/PIGD ≤ 0.09; n = 36), TD (TD/PIGD ≥1.15; n = 19), and indeterminate (TD/PIGD = 0.90-1.15; n = 14) groups. All patients received 2 weeks of multidisciplinary intensive rehabilitation treatment (MIRT) during hospitalization, as well as a remote home rehabilitation health education class. Compared with the scores at admission, all patients showed significant improvements in their MDS-UPDRS III score, walking ability, balance, and posture control at discharge. Moreover, the MDS-UPDRS III score improvement was greater in the PIGD group than in the TD group. The follow-up data, collected for 3 months after discharge, showed that overall symptom improvement in each group was maintained for 1-3 months. Furthermore, there were no significant differences in the duration or grade effects of symptom improvement among the three groups. These findings suggest that 2 weeks of MIRT is effective for improving motor performance in all three motor subtypes. Patients in the PIGD group had a better response after hospitalization than those in the TD group. This study was approved by the Institutional Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University of China (approval No. 2018bkky022) on May 7, 2018 and registered with the Chinese Clinical Trial Registry (registration No. ChiCTR1900020771) on January 19, 2019., Competing Interests: None

Objective: Efficient methods for assessing walking adaptability in individuals with Parkinson's disease (PD) are urgently needed. Therefore, this study aimed to assess C-Gait for detecting freezing of gait (FOG) in patients with early- to middle-stage PD., Method: People with PD (PWP) diagnosis (Hoehn and Yahr stages 1-3) were recruited from April 2019 to November 2019 in Beijing Rehabilitation Hospital. The participants performed six items of walking adaptability on an instrumented treadmill augmented with visual targets and obstacles (C-Mill). The patient's walking adaptability was evaluated by C-Gait assessment and traditional walking tests, and FOG-related indexes were collected as outcome measures. Two discriminant models were established by stepwise discriminant analysis; area under the receiver operating characteristic (ROC) curve (AUC) was used to validate the models., Result: In total, 53 patients were included in this study. Most C-Gait assessment items had no or low correlations with traditional walking tests. The obstacle avoidance ( r = -0.639, P = 0.003) and speed of adaptation ( r = -0.486, P = 0.035) items could lead to FOG with high sensitivity. In addition, the C-Gait assessment model (AUC = 0.755) had slightly better discrimination of freezers from non-freezers compared with traditional walking test models (AUC = 0.672); specifically, obstacle avoidance and speed of adaptation have uniquely discriminant potential., Conclusion: C-gait assessment could provide additional value to the traditional walking tests for PD. Gait adaptability assessment, as measured by C-Gait, may be able to help identify freezers in a PD population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Yan, Qi, Zhen, Liu, Wang, Liu, Wang, Liu, Fang, Su, Yan, Liu, Xi and Fang.)

Local renin-angiotensin system (RAS) in female reproductive system is involved in many physiological and pathological processes, such as follicular development, ovarian angiogenesis, ovarian, and endometrial cancer progress. However, studies on the functional relevance of RAS in human endometrium are limited, especially for renin-angiotensin-aldosterone system (RAAS). In this study, we defined the location of RAS components in human endometrium. We found that angiotensin II type-1 receptor (AT 1 R) and aldosterone synthase (CYP11B2), major components of RAAS, are specifically expressed in endometrial gland during mid-secretory phase. Aldosterone receptor, mineralocorticoid receptor (MR), is elevated in stroma in mid-secretory endometrium. In vitro, MR is also activated by aldosterone during decidualization. Activated MR initiates LKB1 expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. The impact of PDK4 on decidualization is independent on PDHE1α inactivation. Based on co-immunoprecipitation, PDK4 interacts with p-CREB to prevent its ubiquitination for facilitating decidualization via FOXO1. Restrain of MR activation interrupts LKB1/p-AMPK/PDK4/p-CREB/FOXO1 pathway induced by aldosterone, indicating that aldosterone action on decidualization is mainly dependent on MR stimulation. Aldosterone biosynthesized in endometrial gland during mid-secretory phase promotes decidualization via activating MR/LKB1/p-AMPK/PDK4/p-CREB/FOXO1 signaling pathway. This study provides the valuable information for understanding the underlying mechanism during decidualization.

Background: Although previous studies have reported the effectiveness of acupuncture combined mecobalamin (AM) in the treatment of elderly diabetic peripheral neuropathy (EDPN), no systematic study has assessed its effectiveness and safety. Thus, this study will evaluate the effectiveness and safety of AM for the treatment of patients with EDPN., Methods: Bibliographic electronic databases will be searched as follows: Cochrane Library, PUBMED, EMBASE, CINAHL, PsycINFO, WANGFANG, and China National Knowledge Infrastructure. All of them will be searched from each database initial to March 1, 2020 without language restrictions. All study selection, information extracted, and study quality evaluation will be performed by 2 independent authors. Any disagreements between 2 authors will be resolved by a third author via discussion. RevMan 5.3 software will be used for data pooling and meta-analysis performance if it is possible., Results: This study will provide synthesis of current evidence of AM for patients with EDPN through primary outcome of glycemic profile, and secondary of neuropathic pain intensity, plantar tactile sensitivity, sensory nerve conduction velocity and motor nerve conduction velocity, health-related quality of life, and adverse events., Conclusion: This study will provide helpful reference for the efficacy and safety of AM for the treatment of patients with EDPN to the clinicians and further studies.Study registration number: INPLASY202040094.

Small-molecule drug discovery can be hindered by the formation of aggregates that act as non-selective inhibitors of drug targets. Such aggregates appear as false positives in high-throughput screening campaigns and can bedevil structure-activity relationships during compound optimization. Protocols are described for resonant waveguide grating (RWG) and dynamic light scattering (DLS) as microplate-based high-throughput approaches to identify compound aggregation. Resonant waveguide grating and dynamic light scattering give equivalent results for the compound test set, as assessed with Bland-Altman analysis. © 2019 The Authors. Basic Protocol 1: Resonant waveguide grating (RWG) in 384-well or 1536-well plate format to detect compound aggregation Basic Protocol 2: Dynamic light scattering (DLS) in 384-well plate format to detect compound aggregation., (© 2020 The Authors.)

Background: Nurses frequently are caught between the demands of work and family. While studies have explored this issue among staff nurses, none have compared nurse leaders to staff nurses. This study compares work-family conflict (WFC) and family-work conflict (FWC) among staff, managerial, and executive nurses., Methods: In this survey design, 20% of registered nurses were randomly sampled across Florida with a 9% response rate. Survey questions included personal, professional, and work environment characteristics and perceptions of WFC/FWC. Analyses of variance tested the differences between- and within-group scores for WFC/FWC for staff, managerial, and executive nurses. Ordinary Least Squares regressions tested the relationships between personal, professional and work environment measures, focusing on the three different nursing roles, and WFC/FWC scores., Findings: Nurses experienced more WFC than FWC. Staff nurses experienced significantly less WFC than nurse managers and nurse executives (analysis of variance mean difference -0.881 and -2.693, respectively). Nonwhite nurses experienced more WFC and FWC than white nurses. Longer shift length predicted greater WFC. FWC was lower with paid leave for childbirth., Discussion: Higher WFC among nurse managers and executives may discourage nurses from taking on or staying in leadership roles. Efforts must be taken to decrease WFC/FWC among nurses in these roles., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The tunneling magnetoresistance micro-sensors (TMR) developed by magnetic multilayer material has many advantages, such as high sensitivity, high frequency response, and good reliability. It is widely used in military and civil fields. This work presents a high-performance interface circuit for TMR sensors. Because of the nonlinearity of signal conversion between sensitive structure and interface circuit in feedback loop and forward path, large harmonic distortion occurs in output signal spectrum, which greatly leads to the reduction of SNDR (signal noise distortion rate). In this paper, we analyzed the main source of harmonic distortion in closed-loop detection circuit and establish an accurate harmonic distortion model in TMR micro-sensors system. Some factors are considered, including non-linear gain of operational amplifier unit, effective gain bandwidth, conversion speed, nonlinearity of analog transmission gate, and nonlinearity of polycrystalline capacitance in high-order sigma-delta system. We optimized the CMOS switch and first-stage integrator in the switched-capacitor circuit. The harmonic distortion parameter is optimally designed in the TMR sensors system, aiming at the mismatch of misalignment of front-end system, non-linearity of quantizer, non-linearity of capacitor, and non-linearity of analog switch. The digital output is attained by the interface circuit based on a low-noise front-end interface circuit and a third-order sigma-delta modulator. The digital interface circuit is implemented by 0.35μm CMOS (complementary metal oxide semiconductor) technology. The high-performance digital TMR sensors system is implemented by double chip integration and the active interface circuit area is about 3.2 × 2 mm. The TMR sensors system consumes 20 mW at a single 5 V supply voltage. The TMR sensors system can achieve a linearity of 0.3% at full scale range (±10 5 nT) and a resolution of 0.25 nT/Hz 1/2 (@1Hz)., Competing Interests: The authors declare no conflict of interest.

Today's sensor networks need robustness, security and efficiency with a high level of assurance. Error correction is an effective communicational technique that plays a critical role in maintaining robustness in informational transmission. The general way to tackle this problem is by using forward error correction (FEC) between two communication parties. However, by applying zero-error coding one can assure information fidelity while signals are transmitted in sensor networks. In this study, we investigate zero-error coding via both classical and quantum channels, which consist of n obfuscated symbols such as Shannon's zero-error communication. As a contrast to the standard classical zero-error coding, which has a computational complexity of , a general approach is proposed herein to find zero-error codewords in the case of quantum channel. This method is based on a n-symbol obfuscation model and the matrix's linear transformation, whose complexity dramatically decreases to . According to a comparison with classical zero-error coding, the quantum zero-error capacity of the proposed method has obvious advantages over its classical counterpart, as the zero-error capacity equals the rank of the quantum coefficient matrix. In particular, the channel capacity can reach n when the rank of coefficient matrix is full in the n-symbol multilateral obfuscation quantum channel, which cannot be reached in the classical case. Considering previous methods such as low density parity check code (LDPC), our work can provide a means of error-free communication through some typical channels. Especially in the quantum case, zero-error coding can reach both a high coding efficiency and large channel capacity, which can improve the robustness of communication in sensor networks., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: 17β-Estradiol (E2) is a critical regulator of trophoblast function during pregnancy. Serum- and glucocorticoid-inducible kinase (SGK1) has been shown to regulate specific cellular targets downstream of E2. However, whether and how SGK1 directly mediates the regulatory effects of E2 on trophoblasts functions remain unknown., Methods: SGK1 expression in human villous samples and serum E2 levels were measured in women with early pregnancy loss (EPL) and healthy pregnant women. The effect of E2 on SGK1 regulation was assessed using luciferase reporter gene assay and Chromatin Immunoprecipitation assay. The mediation of regulatory effects of E2 by SGK1 on trophoblast functions including cell viability, invasion and related signaling molecules such as B cell leukemia/lymphoma 6, E-cadherin, matrix metalloproteinase 2, α-ENaC, vascular endothelial growth factor, and the phosphorylation status of FOXO1 and AKT were evaluated in HTR8/SVneo cells transfected with SGK1 knockdown plasmid with/without E2 treatment., Results: SGK1 protein levels in human villous samples and serum E2 levels were decreased in patients with EPL compared to controls. E2 (10 nM) increased SGK1 promoter activity directly through estrogen receptor. E2-activated SGK1 enhanced cell viability, invasion and downstream targets in trophoblast cells. SGK1 knockdown abrogated the above responses to E2 treatment., Conclusions: SGK1 mediates the effects of E2 on trophoblast viability and invasion, suggesting that SGK1 acts as a key node in regulating the cross-talk at the feto-maternal interface during the development of placenta and might be a potential therapeutic target for EPL., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

During pregnancy, a tremendous increase in fetoplacental angiogenesis is associated with elevated blood flow. Aberrant fetoplacental vascular function may lead to pregnancy complications including pre-eclampsia. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental endothelial function. G protein α subunit 14 (GNA14), a member of Gαq/11 subfamily is involved in mediating hypertensive diseases and tumor vascularization. However, little is known about roles of GNA14 in mediating the FGF2- and VEGFA-induced fetoplacental endothelial function. Using human umbilical vein endothelial cells (HUVECs) cultured under physiological chronic low oxygen (3% O 2 ) as a cell model, we show that transfecting cells with adenovirus carrying GNA14 complementary DNA (cDNA; Ad-GNA14) increases (p < 0.05) protein expression of GNA14. GNA14 overexpression blocks (p < 0.05) FGF2-stimulated endothelial migration, whereas it enhances (p < 0.05) endothelial monolayer integrity (maximum increase of ~35% over the control at 24 hr) in response to FGF2. In contrast, GNA14 overexpression does not significantly alter VEGFA-stimulated cell migration, VEGFA-weakened cell monolayer integrity, and intracellular Ca ++ mobilization in response to adenosine triphosphate (ATP), FGF2, and VEGFA. GNA14 overexpression does not alter either FGF2- or VEGFA-induced phosphorylation of ERK1/2. However, GNA14 overexpression time-dependently elevates (p < 0.05) phosphorylation of phospholipase C-β3 (PLCβ3) at S1105 in response to FGF2, but not VEGFA. These data suggest that GNA14 distinctively mediates fetoplacental endothelial cell migration and permeability in response to FGF2 and VEGFA, possibly in part by altering activation of PLCβ3 under physiological chronic low oxygen., (© 2018 Wiley Periodicals, Inc.)

Objective: Long non-coding RNA (lncRNA) is a significant member of the non-coding RNA family. New evidence has shown that it plays a pivotal role in the processes of tumor genesis and development. According to previous verification, the lncRNA Tubulin Alpha 4B (TUBA4B) is a tumor-associated molecule, but how TUBA4B expresses and functions in breast cancer is still not clear., Patients and Methods: We conducted this study to examine what expression and biological role TUBA4B plays in breast cancer. The expression of TUBA4B was measured in breast cancer samples and cell lines. CCK8 assays and transwell assays were used for evaluating the effects of TUBA4B on breast cancer cell proliferation and invasion. Luciferase reporter assays were used for identifying the direct target of TUBA4B., Results: According to the results, TUBA4B was largely downregulated in breast cancer samples and cell lines. The functional analysis demonstrated that breast cancer cells proliferation and invasion could be inhibited by overexpression of TUBA4B. The results of Luciferase reporter assays indicated that TUBA4B directly targeted miR-19, which could rescue the effects of TUBA4B on breast cancer cells., Conclusions: It is suggested that TUBA4B was downregulated in breast cancer and suppressed proliferation and invasion of breast cancer by targeting miR-19.

Introduction: Systematic documentation of chemotoxicities in outpatient clinics is challenging. Incorporating patient-reported outcome (PRO) measures in clinical workflows can be an efficient strategy to strengthen the assessment of symptomatic treatment toxicities in oncology clinical practice. We compared the adequateness, feasibility, and acceptability of toxicity documentation using systematic, prospective, application of the PRO Common Toxicity Criteria for Adverse Events (PRO-CTCAE) tool., Methods: At a comprehensive cancer center, data abstraction of electronic health record reviews elucidated current methods and degree of chemotoxicity documentation. Web-based 32-item PRO-CTCAE questionnaires, administered in ambulatory clinics of patients receiving chemotherapy, captured chemotoxicities and respective severities. Patient telephone surveys assessed whether healthcare providers had addressed chemotoxicities to the patients' satisfaction., Results: Over a broad demographic of 497 patients receiving chemotherapy, 90% (95% CI 84-96%) with significant chemotoxicities (n = 107) reported that their providers had discussed toxicities with them; of these, 70% received a therapy management change, while among the rest, 17% desired a change in management. Of patients surveyed, 91% (95% CI 82-99%) were satisfied with their current chemotoxicity management. Clinician chart documentation varied greatly; descriptors rather than numerical grading scales were typically used. Although 93% of patients were willing to complete the PRO survey, only 50% thought that it would be acceptable to complete this survey at routine clinic visits., Conclusion: Use of PRO-CTCAE in routine clinical practice promotes systematic evaluation of symptomatic toxicities and improves the clarity, consistency, and efficiency of clinician documentation; however, methods to improve patient willingness to complete this tool routinely are needed.

Galectin-1 is highly expressed in blastocysts and trophoblast giant cells during implantation, and dysregulated galectin-1 is associated with many pregnancy-related abnormalities. Elevated galectin-1 contributes to cancer cells invasion. Here, we found that galectin-1 is expressed in mouse oocytes, preimplantation embryos (all stages), and trophoblast stem (TS) cells. Peak levels of galectin-1 mRNA and protein were detected on day 4 and day 5 after the induction of TS cells differentiation. Overexpression of galectin-1 increased TS cells migration and invasion, whereas knockdown of galectin-1 attenuated these effects. Additionally, knockdown of galectin-1 in TS cells decreased the expression of matrix metalloproteinase (MMP) 2/9, ZEB-1, Snail, N-cadherin, TGF-β, Nodal, and phospho-Smad2/3, whereas the expression of E-cadherin was increased. In contrast, overexpression of galectin-1 in TS cells increased the expression of MMP2/9, ZEB-1, and N-cadherin, whereas the expression of E-cadherin was decreased. These findings suggest a potential role of galectin-1 in the differentiation of mouse TS cells., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Key Points: Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function. It is not known whether GNA11 mediates FGF2- and VEGFA-induced endothelial cell responses under physiological chronic low O 2 . In the present study, we show that knockdown of GNA11 significantly decreases FGF2- and VEGFA-induced fetoplacental endothelial cell migration but not proliferation and permeability. Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C-β3. The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2- and VEGFA-induced fetoplacental endothelial function., Abstract: During pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein α subunits q (GNAq) and 11 (GNA11) are two members of the Gα q/11 subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2- and VEGFA-induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O 2 (3% O 2 ), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P < 0.05) FGF2- and VEGFA-stimulated fetoplacental endothelial migration (by ∼36% and ∼50%, respectively) but not proliferation and permeability. GNA11 siRNA also elevated (P < 0.05) FGF2- and VEGFA-induced phosphorylation of phospholipase C-β3 (PLCβ3) at S537 in a time-dependent fashion but not mitogen-activated protein kinase 3/1 (ERK1/2) and v-akt murine thymoma viral oncogene homologue 1 (AKT1). These data suggest that GNA11 mediates FGF2- and VEGFA-stimulated fetoplacental endothelial cell migration partially via altering the activation of PLCβ3., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

It is well established that mRNAs encoding secretory or membrane-bound proteins are translated on the surface of the endoplasmic reticulum (ER). The extent to which mRNAs that encode cytosolic proteins associate with the ER, however, remains controversial. To address this question, we quantified the number of cytosolic protein-encoding mRNAs that co-localize with the ER using single-molecule RNA imaging in fixed and living cells. We found that a small but significant number of mRNAs that encode cytosolic proteins associate with the ER and show that this interaction is translation dependent. Furthermore, we demonstrate that cytosolic protein-encoding transcripts can remain on the ER with dwell times consistent with multiple rounds of translation and have higher ribosome occupancies than transcripts translated in the cytosol. These results advance our understanding of the diversity and dynamics of localized translation on the ER., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Context: Preeclampsia is a leading cause of fetal and maternal morbidity and mortality during pregnancy. Although the etiology of preeclampsia is unknown, preeclampsia offspring have increased risks of developing cardiovascular disorders in adulthood, implicating that preeclampsia programs fetal vasculature in utero., Objective: We hypothesize that preeclampsia alters expression profiles of endothelial microRNAs (miRNAs) in fetal endothelial cells and disturbs the vascular endothelial growth factor A (VEGFA)- and fibroblast growth factor 2 (FGF2)-induced endothelial function., Design and Setting: Unpassaged (P0) human umbilical vein endothelial cells (HUVECs) were isolated immediately after cesarean-section delivery from normotensive (NT) and preeclamptic (PE) pregnancies. Differentially expressed miRNAs between P0-HUVECs from NT and PE pregnancies were identified using a miRNA polymerase chain reaction (PCR) array and confirmed using reverse transcription quantitative PCR. To determine the function of these differentially expressed miRNAs, miRNAs of interest were knocked down in NT-HUVECs following by cell functional assays., Results: Sixteen miRNAs, including miR-29a/c-3p, were downregulated in P0-HUVECs from the PE group compared with the NT group. Bioinformatics analysis predicted the PI3K-v-akt murine thymoma viral oncogene homolog 1 (AKT) signaling pathway was dysregulated in P0-HUVECs from the PE group, which was associated with the miR-29a/c-3p downregulation. We further demonstrated that miR-29a/c-3p knockdown inhibited the VEGFA- and FGF2-induced endothelial migration as well as FGF2-induced AKT1 phosphorylation in HUVECs. However, miR-29a/c-3p knockdown did not alter the extracellular signal-regulated kinase 1/2 phosphorylation, cell proliferation, and endothelial monolayer integrity in response to VEGFA and FGF2 in HUVECs., Conclusions: Preeclampsia-downregulated miR-29a/c-3p may impair fetal endothelial function by disturbing the FGF2-activated PI3K-AKT signaling pathway, hence inhibiting endothelial cell migration., (Copyright © 2017 Endocrine Society)

A prevalent observation in high-throughput screening and drug discovery programs is the inhibition of protein function by small-molecule compound aggregation. Here, we present the X-ray structural description of aggregation-based inhibition of a protein-protein interaction involving tumor necrosis factor α (TNFα). An ordered conglomerate of an aggregating small-molecule inhibitor (JNJ525) induces a quaternary structure switch of TNFα that inhibits the protein-protein interaction between TNFα and TNFα receptors. SPD-304 may employ a similar mechanism of inhibition.

Aims: To identify the taxonomy of tobacco rhizosphere-isolated strain Lyc2 and investigate the mechanisms of the antifungal activities, focusing on antimicrobials gene clusters identification and function analysis., Methods and Results: Multilocus sequence typing and 16S rRNA analyses indicated that strain Lyc2 belongs to Burkholderia pyrrocinia. Bioassay results indicated strain Lyc2 showed significant antifungal activities against a broad range of plant and animal fungal pathogens and control efficacy on seedling damping off disease of cotton. A 55·2-kb gene cluster which was homologous to ocf gene clusters in Burkholderia contaminans MS14 was confirmed to be responsible for antifungal activities by random mutagenesis; HPLC was used to verify the production of antifungal compounds. Multiple antibiotic and secondary metabolized biosynthesis gene clusters predicated by antiSMASH revealed the broad spectrum of antimicrobials activities of the strain., Conclusions: Our results revealed the mechanisms of antifungal activities of strain Lyc2 and expand our knowledge about production of occidiofungin in the bacteria Burkholderia., Significance and Impact of the Study: Understanding the mechanisms of antifungal activities of strain Lyc2 has contributed to discovery of new antibiotics and expand our knowledge of production of occidiofungin in the bacteria Burkholderia., (© 2015 The Society for Applied Microbiology.)

Lung cancer is the leading cause of cancer-related mortality in both men and women worldwide. To identify novel factors that contribute to lung cancer pathogenesis, we analyzed a lung cancer database from The Cancer Genome Atlas and found that Krüppel-like Factor 4 (KLF4) expression is significantly lower in patients' lung cancer tissue than in normal lung tissue. In addition, we identified seven missense mutations in the KLF4 gene. KLF4 is a transcription factor that regulates cell proliferation and differentiation as well as the self-renewal of stem cells. To understand the role of KLF4 in the lung, we generated a tamoxifen-induced Klf4 knockout mouse model. We found that KLF4 inhibits lung cancer cell growth and that depletion of Klf4 altered the differentiation pattern in the developing lung. To understand how KLF4 functions during lung tumorigenesis, we generated the K-ras(LSL-G12D/+);Klf4(fl/fl) mouse model, and we used adenovirus-expressed Cre to induce K-ras activation and Klf4 depletion in the lung. Although Klf4 deletion alone or K-ras mutation alone can trigger lung tumor formation, Klf4 deletion combined with K-ras mutation significantly enhanced lung tumor formation. We also found that Klf4 deletion in conjunction with K-ras activation caused lung inflammation. To understand the mechanism whereby KLF4 is regulated during lung tumorigenesis, we analyzed KLF4 promoter methylation and the profiles of epigenetic factors. We found that Class I histone deacetylases (HDACs) are overexpressed in lung cancer and that HDAC inhibitors induced expression of KLF4 and inhibited proliferation of lung cancer cells, suggesting that KLF4 is probably repressed by histone acetylation and that HDACs are valuable drug targets for lung cancer treatment.

Although GHRH and GHRH-R are recognized as key factors in placental development, little is known about the mechanism(s) of the regulation in trophoblastic cells during placental development. The objective of this study is to determine the potential relationship between the expression levels of GHRH-R and the placental and JEG-3 cell function. Furthermore, we aim to investigate the downstream pathways of GHRH/GHRH-R axis in the control of the JEG-3 cell viability and apoptosis. In this study, we detected the expression pattern of GHRH-R in human chorionic villous tissues and JEG-3 cell. Then, we evaluated the effects of GHRH/GHRH-R and the downstream pathways by using GHRH antagonist (JMR-132) on JEG-3 cell. Our present study found the expressions of GHRH-R in placental villous tissues and JEG-3 cell, and the expression levels of GHRH-R was significantly lower in villous tissues of early pregnancy loss when compared to normal controls. JMR-132 inhibited cellular viability and induced apoptosis in JEG-3 cell in a time and dosedependent manners through activation of caspase-3, p38, and p53, as well as inhibition of phosphorylation of Akt. Interestingly, ER stress markers such as GRP78, ubiquitinated proteins and phospho-eIF2α were significantly increased in JEG-3 cell after being treated with JMR-132. Conversely, pretreated with salubrinal (a selective inhibition of protein phosphatase 1-mediated eIF2α dephosphorylation), JEG-3 cells were rescued from JMR-132-mediated cell growth inhibition, and abolished JMR-132-induced cleaved caspase-3, CHOP, phospho-p53, and ubiquitinated proteins accumulation. Knockdown of endogenous GHRH-R significantly abolished the JMR-132-induced cleaved caspase-3 and activation of p38. In conclusion, our results, for the first time, demonstrated the expression levels of GHRH-R were closely related to the placental function. Inhibition of GHRH-R by using GHRH antagonist in JEG-3 cell may reduce cell viability and induce apoptosis through inactivation of Akt and ER stress via phosphorylation of eIF2α. These observations have enriched our understanding on the function of GHRH/GHRH-R axis and the downstream pathways in the control of the placental development. The Most Important Aspect of the Paper: Our present study for the first time provided evidences that GHRH and GHRH-R loops involve in JEG-3 cell viability and apoptosis through Akt and eIF2α pathways.

Although one pathway for the post-translational targeting of tail-anchored proteins to the endoplasmic reticulum (ER) has been well defined, it is unclear whether additional pathways exist. Here, we provide evidence that a subset of mRNAs encoding tail-anchored proteins, including Sec61β and nesprin-2, is partially localized to the surface of the ER in mammalian cells. In particular, Sec61b mRNA can be targeted to, and later maintained on, the ER using both translation-dependent and -independent mechanisms. Our data suggests that this process is independent of p180 (also known as RRBP1), a known mRNA receptor on the ER, and the transmembrane domain recognition complex (TRC) pathway components, TRC40 (also known as ASNA1) and BAT3 (also known as BAG6). In addition, our data indicates that Sec61b mRNA might access translocon-bound ribosomes. Our results show that certain tail-anchored proteins are likely to be synthesized directly on the ER, and this facilitates their membrane insertion. Thus, it is clear that mammalian cells utilize multiple mechanisms to ensure efficient targeting of tail-anchored proteins to the surface of the ER., (© 2015. Published by The Company of Biologists Ltd.)

Lysobacter capsici strain X2-3 was isolated from the wheat rhizosphere in China and exhibits a remarkable capacity to inhibit the growth of multiple pathogens. Here, we report the draft genome sequence of L. capsici strain X2-3 in China., (Copyright © 2015 Yi et al.)

Purpose: To study the differences in protein expression profiles of follicular fluid (FF) between controlled ovarian hyperstimulation (COH) and natural ovulatory cycles., Methods: Twelve infertile women undergoing in vitro fertilization and embryo transfer (IVF-ET), with matched clinical information, were retrospectively recruited in the IVF center of our university hospital, including six undergoing COH and another six with natural cycles. FF was sampled from dominant follicles with mature oocytes. Protein expression profiles in each FF sample were analyzed respectively using two-dimensional gel electrophoresis. Differentially expressed proteins were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and validated by western blotting. Differentially expressed proteins were further analyzed using Ingenuity Pathway Analysis (IPA) software., Results: Two proteins were downregulated and 11 proteins were upregulated (change ≥1.5-fold, P < 0.05) in the COH group. We identified one down-egulated and seven upregulated proteins using MALDI-TOF MS. Four differentially expressed proteins, including transferrin, complement component C3 (C3), haptoglobin and alpha-1-antitrypsin (AAT), were further validated by rate nephelometry and western blotting analyses. The IPA analysis revealed a significant network involved in the humoral immune and inflammatory responses., Conclusions: The eight differentially expressed proteins were related to immune and inflammatory responses in the ovary. Our results provide new insights into the influence of COH on follicular (spp) development and IVF outcomes.

Aim: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinese patients with chronic hepatitis B (CHB)., Methods: A total of 325 Chinese patients with CHB were enrolled in this retrospective, hospital-based study. Patients with chronic hepatitis C (CHC), autoimmune hepatitis (AIH), or primary biliary cirrhosis (PBC) were included, with healthy donors acting as controls. A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay. The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies (ANA-H), smooth-muscle antibodies, anti-liver kidney microsome type 1, anti-liver cytosolic antigen type 1, and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rim-like, anti-mitochondrial antibodies-M2 (AMA-M2), anti-BPO (recombinant antigen targeted by AMA-M2), anti-Sp100, anti-promyelocytic leukemia protein (anti-PML), and anti-gp210. The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case. Anti-Ro52 antibodies were also tested., Results: The prevalence of any autoantibody in CHB amounted to 58.2%, which was similar to the 66.2% prevalence in CHC, significantly higher than the 6.7% in the healthy controls (P < 0.001), and lower than the 100% found in AIH and PBC (P = 0.004 and P < 0.001, respectively). There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients (11.1% vs 0%, P = 0.003; 12.6% vs 0%, P < 0.001, respectively). The prevalence and titer of AMA, anti-BPO, anti-PML, and anti-gp210 were higher in PBC than in those with CHB. Among the CHB patients, the prevalence of ANA, especially ANA-H, was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis. Thirty-eight cases of hepatocellular carcinoma (HCC) in CHB showed a significant difference compared with non-HCC patients in the prevalence of anti-PML (0% vs 12.5%, P = 0.013). Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC, and that it was strongly correlated with both compensated and decompensated cirrhosis. In contrast, the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis (18.5% vs 8.2%, P = 0.039). Moreover, the AIH profile was also closely associated with hepatitis B e-antigen positivity., Conclusion: ANA-H could be an indicator of early-stage CHB. Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.