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Airborne antibiotic-resistant bacteria (ARB) can critically impact human health. We performed resistome profiling of 283 personal airborne exposure samples from 15 participants spanning 890 days and 66 locations. We found a greater diversity and abundance of airborne bacteria community and antibiotic resistomes in spring than in winter, and temperature contributed largely to the difference. A total of 1123 bacterial genera were detected, with 16 genera dominating. Of which, 7/16 were annotated as major antibiotic resistance gene (ARG) hosts. The participants were exposed to a highly dynamic collection of ARGs, including 322 subtypes conferring resistance to 18 antibiotic classes dominated by multidrug, macrolide-lincosamide-streptogramin, β-lactam, and fosfomycin. Unlike the overall community-level bacteria exposure, an extremely high abundance of specific ARG subtypes, including lunA and qacG, were found in some samples. Staphylococcus was the predominant genus in the bacterial community, serving as a primary bacterial host for the ARGs. The annotation of ARG-carrying contigs indicated that humans and companion animals were major reservoirs for ARG-carrying Staphylococcus. This study contextualized airborne antibiotic resistomes in the precision medicine framework through longitudinal personal monitoring, which can have broad implications for human health., 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: The current treatments for adjacent two-segment cervical spondylotic myelopathy (CSM) include two-segment anterior cervical discectomy and fusion (ACDF) and single-segment anterior cervical corpectomy and fusion (ACCF). Long-term follow-up has demonstrated that both procedures have complications such as reduced cervical mobility, accelerated degeneration of adjacent segments and loosening of internal fixation screws. The purpose of this study is to demonstrate the feasibility, safety, and efficacy of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) via one vertebra with two bony channels for the treatment of adjacent two-segment CSM and to present our surgical experience., Methods: Anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) via one vertebra with two bony channels was performed for 12 patients with adjacent two-segment CSM with follow-up care for at least 12 months. The Visual analog scale (VAS) and the Japanese Orthopedic Association Score (JOA) were recorded, and modified Macnab criteria were used to evaluate the treatment excellence rate. Radiological examinations, including X-ray, computed tomography (CT) and magnetic resonance imaging (MRI), were used to evaluate spinal cord decompression, intervertebral stability and healing of the bony channel., Results: All 12 patients completed the operation successfully. No postoperative complications, such as dysphagia, Horner's syndrome, or laryngeal recurrent nerve palsy, were found. The postoperative VAS and JOA scores were significantly improved compared with those before surgery(P < 0.001). According to the modified Macnab criteria, the clinical outcome was excellent in 8 cases, good in 3 cases and fine in 1 case at the final follow-up and the excellent and good rate was 91.7%. Postoperative and follow-up imaging showed significant spinal cord decompression, well-healed bony channels and no cervical instability., Conclusions: This study is the first report of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord via one vertebra with two bony channels. This procedure has the advantages of less trauma, faster recovery, fewer complications and no need to implant internal fixators. This is a minimally invasive, feasible and safe surgical procedure for patients with adjacent two-segment CSM., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Nuclear magnetic resonance studies of many physiologically important proteins have long been impeded by the necessity to express such proteins in isotope-labeled form in higher eukaryotic cells and the concomitant high costs of providing isotope-labeled amino acids in the growth medium. Economical routes use isotope-labeled yeast or algae extracts but still require expensive isotope-labeled glutamine. Here, we have systematically quantified the effect of 15 N 2 -glutamine on the expression and isotope labeling of different proteins in insect cells. Sufficient levels of glutamine in the medium increase the protein expression by four to five times relative to deprived conditions. 1 H- 15 N nuclear magnetic resonance spectroscopy shows that the 15 N atoms from 15 N 2 -glutamine are scrambled with surprisingly high (60-70%) efficiency into the three amino acids alanine, aspartate, and glutamate. This phenomenon gives direct evidence that the high energy demand of insect cells during baculovirus infection and concomitant heterologous protein expression is predominantly satisfied by glutamine feeding the tricarboxylic acid cycle. To overcome the high costs of supplementing isotope-labeled glutamine, we have developed a robust method for the large-scale synthesis of 15 N 2 -glutamine and partially deuterated 15 N 2 -glutamine-α,β,β-d 3 from inexpensive precursors. An application is shown for the effective large-scale expression of the isotope-labeled β 1 -adrenergic receptor using the synthesized 15 N 2 -glutamine-α,β,β-d 3 ., Competing Interests: Conflict of interest The authors declare no conflict of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Uncovering an efficient and stable photocatalytic system for seawater splitting is a highly desirable but challenging goal. Herein, Cd 0.2 Zn 0.8 S@Silicalite-1 (CZS@S-1) composites, in which CZS is embedded in the hierarchical zeolite S-1, were prepared and show remarkably high activity, stability and salt resistance in seawater.

Background: To evaluate postoperative clinical outcomes and analyze influencing factors for patients with thymic epithelial tumors over 3 years after operation., Methods: Patients with thymic epithelial tumors (TETs) who underwent surgical treatment in the Department of Thoracic Surgery at Beijing Hospital from January 2011 to May 2019 were retrospectively enrolled in the study. Basic patient information, clinical, pathological, and perioperative data were collected. Patients were followed up by telephone interviews and outpatient records. Statistical analyses were performed using SPSS version 26.0., Results: A total of 242 patients (129 men, 113 women) with TETs were included in this study, of which 150 patients (62.0%) were combined with myasthenia gravis (MG) and 92 patients (38.0%) were not. 216 patients were successfully followed up and their complete information was available. The median follow-up period was 70.5 months (range, 2-137 months). The 3-year overall survival (OS) rate of the whole group was 93.9%, and the 5-year OS rate was 91.1%. The 3-year relapse-free survival (RFS) rate of the whole group was 92.2%, and the 5-year relapse-free survival rate was 89.8%. Multivariable COX regression analysis indicated that recurrence of thymoma was an independent risk factor for OS. Younger age, Masaoka-Koga stage III + IV, and TNM stage III + IV were independent risk factors for RFS. Multivariable COX regression analysis indicated that Masaoka-Koga staging III + IV, WHO type B + C were independent risk factors for postoperative improvement of MG. For patients with MG, the postoperative complete stable remission (CSR) rate was 30.5%. And the result of multivariable COX regression analysis showed that thymoma patients with MG with Osserman staging IIA + IIB + III + IV were not prone to achieving CSR. Compared with patients without MG, MG was more likely to develop in patients with WHO classification type B, and patients with myasthenia gravis were younger, with longer operative duration, and more likely to develop perioperative complications., Conclusions: The 5-year overall survival rate of patients with TETs was 91.1% in this study. Younger age and advanced stage were independent risk factors for RFS of patients with TETs, and recurrence of thymoma were independent risk factors for OS. In patients with MG, WHO classification type B and advanced stage were independent predictors of poor outcomes of MG treatment after thymectomy., (© 2023. The Author(s).)

Background: Disc herniation (DH) is a fragment of the disc nucleus that is pushed out of the annulus into the spinal canal due to a tear or rupture in the annulus. It is a common cause of lumbar and leg pains. Substantial advancements have been made to determine the cause of DH and to ensure accurate diagnosis, imaging, and treatment of this condition. Total endoscopic discectomy is an alternative surgical technique that is less invasive., Aim: To study the optimal approach for a total endoscopic discectomy and its influence on lumbar and leg function in DH patients., Methods: This prospective study enrolled 120 patients with lumbar DH who were treated in our hospital from February 2018 to January 2021. All patients were randomly divided into the following two groups: The observation group, comprising 62 patients who underwent surgery using the interlaminar approach, and the control group, comprising 58 patients who were operated through the foramina approach. The treatment effects, perioperative indicators, functional recovery, pain, and quality of life were compared between the two groups., Results: The treatment effect in the observation group (93.55%) was significantly better than that in the control group (77.59%). There was no difference in the operative time and intraoperative blood loss amount between the two groups ( P > 0.05). The hospitalization time of the observation group (4.34 ± 1.33 d) was significantly shorter than that of the control group (5.38 ± 1.57 days) ( P < 0.05). The Japanese Orthopaedic Association and Oswestry Disability Index scores decreased significantly in both groups after treatment, but the scores were lower in the observation group than in the control group. The visual analog scale scores of the lower back and legs of the two groups were significantly reduced after treatment, but scores were lower in the observation group (2.18 ± 0.88 in the lower back and 1.42 ± 0.50 in the leg) than in the control group (3.53 ± 0.50 in the lower back and 2.21 ± 0.52 in the leg). A short form of the Arthritis Impact Measurement Scales 2 measurement scale (AIMS2-SF) score and Barthel index of the lower back of the two groups increased significantly after treatment, with the observation group having a significantly higher AIMS2-SF score (95.16 ± 1.74) and Barthel index (97.29 ± 1.75) than the control group (84.95 ± 2.14 and 89.16 ± 2.71, respectively) ( P < 0.05)., Conclusion: Through total endoscopic discectomy with the interlaminar approach, the degree of pain in the waist and leg was reduced, and the lumbar function considerably recovered., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

NMR chemical shift changes can report on the functional dynamics of biomacromolecules in solution with sizes >1 MDa. However, their interpretation requires chemical shift assignments to individual nuclei, which for large molecules often can only be obtained by tedious point mutations that may interfere with function. We present here an efficient pseudocontact shift NMR method to assign biomacromolecules using bound antibodies tagged with lanthanoid DOTA chelators. The stability of the antibody allows positioning the DOTA tag at many surface sites, providing triangulation of the macromolecule nuclei at distances >60 Å. The method provides complete assignments of valine and tyrosine 1 H- 15 N resonances of the β 1 -adrenergic receptor in various functional forms. The detected chemical shift changes reveal strong forces exerted onto the backbone of transmembrane helix 3 during signal transmission, which are absorbed by its electronic structure. The assignment method is applicable to any soluble biomacromolecule for which suitable complementary binders exist.

Background: TGF-β superfamily signaling is indispensable for bone homeostasis. However, the global expression profiles of all the genes that make up this signaling module in bone and bone-related diseases have not yet been well characterized., Methods: Transcriptomic datasets from human bone marrows, bone marrow-derived mesenchymal stem cells (MSCs) and MSCs of primary osteoporotic patients were used for expression profile analyses. Protein treatments, gene quantification, reporter assay and signaling dissection in MSC lines were used to clarify the interactive regulations and feedback mechanisms between TGF-β superfamily ligands and antagonists. Ingenuity Pathway Analysis was used for network construction., Results: We identified TGFB1 in the ligand group that carries out SMAD2/3 signaling and BMP8A, BMP8B and BMP2 in the ligand group that conducts SMAD1/5/8 signaling have relatively high expression levels in normal bone marrows and MSCs. Among 16 antagonist genes, the dominantly expressed TGF-β superfamily ligands induced only NOG, GREM1 and GREM2 via different SMAD pathways in MSCs. These induced antagonist proteins further showed distinct antagonisms to the treated ligands and thus would make up complicated negative feedback networks in bone. We further identified TGF-β superfamily signaling is enriched in MSCs of primary osteoporosis. Enhanced expression of the genes mediating TGF-β-mediated SMAD3 signaling and the genes encoding TGF-β superfamily antagonists served as significant features to osteoporosis., Conclusion: Our data for the first time unveiled the transcription landscape of all the genes that make up TGF-β superfamily signaling module in bone. The feedback mechanisms and regulatory network prediction of antagonists provided novel hints to treat osteoporosis. Video Abstract., (© 2022. The Author(s).)

Currently, it is still a huge challenge to prepare high performance eco-friendly poly(lactic acid) (PLA) with high thermal stability, good processability, excellent crystallization behavior, good transparency and highly-efficient fire safety. In this paper, a novel bio-based nucleation agent N-(furan-2-ylmethyl)-P,P-diphenylphosphinic amide (FPPA) was prepared and used for the fabrication of fire safety PLA/FPPA composites. The chemical structure of FPPA was measured by FTIR, NMR and MS. Further, the crystallization behavior, thermal stability, fire safety and mechanical properties of PLA/FPPA composites were performed by TGA, DSC, polarization microscope, LOI, UL94, cone calorimeter, DMA and, SEM, Raman, GC-MS, and TGA-FTIR. The results showed that the multifunctional FPPA not only had a high thermal stability and was a good nucleation agent for PLA. Moreover, only loading of 3 wt% FPPA increased the LOI of PLA from 19.0 to 33.8 % with UL-94 V-0 classification. Furthermore, the heat release rate and total heat release values of PLA/3%FPPA composite reduced by 6.3 % and 15.3 % in cone-calorimeter test. Such high fire safety was mainly attributed to specific fire safety radicals due to thermal degradation of FPPA to interrupt composites burning in gas phase. Besides, transparency and mechanical properties were almost not changed because of low loading of FPPA in PLA. This multifunctional bio-based fire-retardant for PLA with good comprehensive performance promises broad application in engineering electronics, automobiles, 3D printing and construction materials., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objectives: Rates of chlamydia and gonorrhea among adolescents continue to rise. We aimed to evaluate if a universal testing program for chlamydia and gonorrhea improved testing rates in an urban general pediatric clinic and an urban family medicine clinic within a system of federally qualified health care centers and evaluated the feasibility, cost, and logistic challenges of expanding implementation across 28 primary care clinics within a federally qualified health care centers system., Methods: A universal testing quality improvement program for male and female patient 14 to 18 years old was implemented in a general pediatrics and family medicine clinic in Denver, Colorado. The intervention was evaluated by using a controlled pre-post quasi-experimental design. The difference in testing rates due to the intervention was assessed by using a difference-in-differences regression model weighted with the inverse probability of treatment., Results: In total, 15 541 pediatric encounters and 5420 family medicine encounters were included in the analyses. In pediatrics, the unadjusted testing rates increased from 32.0% to 66.7% in the intervention group and from 20.9% to 28.9% in the comparison group. For family medicine, the rates increased from 38.5% to 49.9% in the intervention group and decreased from 26.3% to 24.8% in the comparison group. The intervention resulted in an adjusted increase in screening rates of 25.2% ( P < .01) in pediatrics and 11.8% ( P < .01) in family medicine. The intervention was well received and cost neutral to the clinic., Conclusions: Universal testing for chlamydia and gonorrhea in primary care pediatrics and family medicine is a feasible approach to improving testing rates ., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Baicalin has been reported to have ameliorative effects on nerve-induced hypoxic ischemia injury; however, its role in the NLRP3 inflammasome-dependent inflammatory response during cerebral ischemia-reperfusion remains unclear. To investigate the molecular mechanisms involved in baicalin alleviating cerebral ischemia-reperfusion injury, we investigated the AMPK signaling pathway which regulates NLRP3 inflammasome activity. SD rats were treated with baicalin at doses of 100 mg/kg and 200 mg/kg, respectively, after middle cerebral artery occlusion at 2 h and reperfusion for 24 h (MCAO/R). MCAO/R treatment significantly increased cerebral infarct volume, changed the ultrastructure of nerve cells, and activated the NLRP3 inflammasome, manifesting as significantly increased expression of NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18. Our results demonstrated that baicalin treatment effectively reversed these phenomena in a dose-dependent manner. Additionally, inhibition of NLRP3 expression was found to promote the neuroprotective effects of baicalin on cortical neurons. Furthermore, baicalin remarkably increased the expression of p-AMPK following oxygen glucose deprivation/reperfusion (OGD/R). The expression of the NLRP3 inflammasome was also increased when the AMPK pathway was blocked by compound C. Taken together, our findings reveal that baicalin reduces the activity of the NLRP3 inflammasome and consequently inhibits cerebral ischemia-reperfusion injury through activation of the AMPK signaling pathway., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Medical records scoring is important in a health care system. Artificial intelligence (AI) with projection word embeddings has been validated in its performance disease coding tasks, which maintain the vocabulary diversity of open internet databases and the medical terminology understanding of electronic health records (EHRs). We considered that an AI-enhanced system might be also applied to automatically score medical records. This study aimed to develop a series of deep learning models (DLMs) and validated their performance in medical records scoring task. We also analyzed the practical value of the best model. We used the admission medical records from the Tri-Services General Hospital during January 2016 to May 2020, which were scored by our visiting staffs with different levels from different departments. The medical records were scored ranged 0 to 10. All samples were divided into a training set ( n = 74,959) and testing set ( n = 152,730) based on time, which were used to train and validate the DLMs, respectively. The mean absolute error (MAE) was used to evaluate each DLM performance. In original AI medical record scoring, the predicted score by BERT architecture is closer to the actual reviewer score than the projection word embedding and LSTM architecture. The original MAE is 0.84 ± 0.27 using the BERT model, and the MAE is 1.00 ± 0.32 using the LSTM model. Linear mixed model can be used to improve the model performance, and the adjusted predicted score was closer compared to the original score. However, the project word embedding with the LSTM model (0.66 ± 0.39) provided better performance compared to BERT (0.70 ± 0.33) after linear mixed model enhancement ( p < 0.001). In addition to comparing different architectures to score the medical records, this study further uses a mixed linear model to successfully adjust the AI medical record score to make it closer to the actual physician's score.

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infection rates continue to rise. Screening guidelines have largely focused on sexually active female individuals and men who have sex with men populations. Health care system testing and infection rates, particularly among heterosexual male individuals, are poorly understood. Our aim was to evaluate CT and GC testing and prevalence among 12- to 24-year-old patients in an urban federally qualified health center system., Methods: This retrospective study analyzed electronic health record data from 2017 to 2019 in a large system of federally qualified health centers in Denver, CO. Abstracted data included demographics, sexual activity, sexual orientation, and laboratory results. χ2 Tests were used to evaluate differences between groups., Results: Of the 44,021 patients included, 37.6% were tested, 15.0% were positive for CT, and 3.4% were positive for GC. Heterosexual male patients had a testing rate of 22.8% and positivity rates of CT and GC at 13.1% and 3.0%, respectively. Among tested patients documented as not sexually active, 7.5% were positive for CT. Multiple or reinfections were detected in 29% of patients., Conclusions: This study shows low testing rates and high rates of CT and GC infections among all patients, including heterosexual male patients and those documented as not sexually active. Improved screening of these populations in the primary care setting may be key to combating the sexually transmitted disease epidemic., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no conflicts of interest to disclose. H.M.F. received salary support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under Award Number K23HD099925. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (Copyright © 2020 American Sexually Transmitted Diseases Association. All rights reserved.)

Cumulus expansion is essential for ovulation and oocyte maturation in mammals. Previous studies suggest that this process requires certain cumulus expansion enabling factors, induced by LH surge, that activate SMAD signaling locally. However, their identities remain uncertain. Using a superovulated rat model, we showed that Bmp8 transcripts were abundant in cumulus cell-oocyte complexes (COCs) and their levels can be further induced during ovulation. By analyzing human COC-related transcriptomic datasets, BMP8 transcripts in cumulus cells were also found to be significantly elevated along with the maturation status and developmental competence of enclosed oocytes. In cultured rat COCs, treatment with recombinant BMP8A protein activated both SMAD1/5/8 and SMAD2/3 pathways; the resulting SMAD2/3 signaling induced COC expansion as well as the expression of COC expansion-related genes, whereas the resulting SMAD2/3 and SMAD1/5/8 activations were both required for protecting expanded cumulus cells from apoptosis. Taken together, our data demonstrated that addition of BMP8 protein in the in vitro rat COC cultures not only promotes cumulus expansion but also sustains survival of expanded cumulus cells via different SMAD downstreams. With these capabilities, BMP8 may have clinical applications to ameliorate the fertilizability and subsequent developmental competence of the enclosed oocytes when doing in vitro COC maturation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Tracheal stenosis is able to lead to airway obstruction., Objective: To evaluate the efficacy and safety profile of Montgomery T-tube implantation in patients with tracheal stenosis., Methods: Fifty-two patients with tracheal stenosis diagnosed between 2016 and 2019 were included in this retrospective cohort study. The patients were divided into observation group ( n  = 25 cases) and control group ( n  = 27). The therapeutic effect, arterial blood gas analysis, arterial oxygen partial pressure (PaO 2 ), arterial carbon dioxide partial pressure (PaCO 2 ), shortness of breath score, airway diameter change, dyspnea score, quality of life, and safety were compared between the two groups before and after treatment., Results: The therapeutic effect of the observation group gained better results than that of the control group (84.00% vs. 62.96%). One week after operation, the pH value, SaO 2 , PaCO 2 , shortness of breath score, airway diameter change, dyspnea score, life quality, and incidence of postoperative complications in the observation group exerted better results as compared to the control group., Conclusion: The implantation of Montgomery T-tube has effective function in terms of improving the symptoms of dyspnea and the life quality of patients with safety profile in patients harboring tracheal stenosis., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Feng-Jie Wu et al.)

Four types of middle-pressure chromatogram isolated gels are evaluated for adsorption or desorption characteristics of ginsenosides from Panax ginseng. Among them, SP207SS and SP2MGS were selected for dynamic investigations based on their static adsorption or desorption capacity of total ginsenoside. Their adsorption kinetics was better explained by pseudosecond-order model and isotherms were preferably fitted to Langmuir model. Dynamic breakthrough experiments indicated an optimum sample loading speed of 4 bed volume/h for either SP207SS or SP2MGS. Desorption speed was determined to be 2 bed volume/h according to desorption amount of total ginsenoside in their effluents. Eight ginsenosides were identified and quantified by high performance liquid chromatography-triple quadropole-mass spectrometry in total ginsenoside extract and different fractions during stepwise dynamic elution. For SP207SS, 27.62% of loaded ginsenosides was detected in 40% ethanol fraction, while 59.12% of them were found in 60% ethanol fraction. As on SP2MGS, the number went to 53.71 and 44.43%, respectively. Recovery rate of ginsenosides were calculated to 78.65% for SP207SS and 89.53% for SP2MGS, respectively. Intriguingly, content of Rg1 and Re in 40% ethanol fraction from SP207SS became 20.1 and 18.6 times higher than that in total ginsenoside extract by one-step elution, which could be leveraged for the facile enrichment of these two ginsenosides from natural sources., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

G protein-coupled receptors (GPCRs) use a series of conserved microswitches to transmit signals across the cell membrane via an allosteric network encompassing the ligand-binding site and the G protein-binding site. Crystal structures of GPCRs provide snapshots of their inactive and active states, but poorly describe the conformational dynamics of the allosteric network that underlies GPCR activation. Here, we analyzed the correlation between ligand binding and receptor conformation of the α 1A -adrenoreceptor, a GPCR that stimulates smooth muscle contraction in response to binding noradrenaline. NMR of [ 13 C ϵ H 3 ]methionine-labeled α 1A -adrenoreceptor variants, each exhibiting differing signaling capacities, revealed how different classes of ligands modulate the conformational equilibria of this receptor. [ 13 C ϵ H 3 ]Methionine residues near the microswitches exhibited distinct states that correlated with ligand efficacies, supporting a conformational selection mechanism. We propose that allosteric coupling among the microswitches controls the conformation of the α 1A -adrenoreceptor and underlies the mechanism of ligand modulation of GPCR signaling in cells., (© 2020 Wu et al.)

Objectives: The administration of androgen deprivation therapy (ADT) to patients with metastatic prostate cancer might be associated with some adverse effects such as anaemia; however, few studies have been performed in East Asian populations. This study aimed to investigate the association between ADT and iron-deficiency anaemia (IDA) among patients with prostate cancer in a population-based nationwide cohort., Design: Cohort study., Setting: Taiwan., Participants: Data for the cohort study were retrieved from the Taiwan National Health Insurance Research Database. Propensity score matching was used to select 7262 patients with prostate cancer who received ADT as the study group and 3631 patients who did not receive ADT as the control group., Primary and Secondary Outcome Measures: This study individually tracked patients over a 3-year study period and identified those who were subsequently diagnosed with IDA following the index date., Results: The incidence rates of IDA in the study and control groups were 1.66 (95% CI CI 1.45 to 1.86) and 1.01 per 100 person-years (95% CI 0.78 to 1.25), respectively. Furthermore, proportional Cox regression revealed an HR of 1.62 (95% CI 1.24 to 2.12) for IDA in the study group after adjusting for patients' age, monthly income, geographic location, residential urbanisation level and incidence of hyperlipidaemia, diabetes, hypertension, coronary heart disease, inflammatory bowel disease, other cancers and gastrointestinal bleeding., Conclusion: Compared with its non-use among patients with prostate cancer, ADT use was associated with a higher risk of IDA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bone morphogenetic proteins (BMPs) are known to play an indispensable role in preventing the precocious luteinization of granulosa cells within growing ovarian follicles. In this study, we found that the transcripts of BMP8 genes are enriched in the ovaries of humans and rodents. When analyzing transcriptomic datasets obtained from human mature granulosa cells, we further found that the BMP8 transcripts not only show the highest abundance among the searchable BMP-related ligands but also decrease significantly in women of advanced age or women with polycystic ovarian syndrome. The correlation between the BMP8 levels in granulosa cells and the decline in ovarian function in these subjects suggests that BMP8 protein may be involved in the regulation of granulosa cell function(s). Using a rat model, we demonstrated that human BMP8A protein activates the SMAD1/5/8 and the SMAD2/3 pathways simultaneously in both immature and mature granulosa cells. Furthermore, the expression of potential type I and type II receptors used by BMP8 in rat granulosa cells was characterized. We found that BMP8A treatment can significantly inhibit gonadotropin-induced progesterone production and steroidogenesis-related gene expression in granulosa cells. Pathway dissection using receptor inhibitors further revealed that such inhibitory effects occur specifically through the BMP8-activated SMAD1/5/8, but not SMAD2/3, pathway. Taken together, considering its abundance and possible functions in granulosa cells, we suggest that BMP8 may act as a novel luteinization inhibitor in growing follicles.

Objective: To analyze the features of chest CT imaging in adult patients with bronchiectasis and explore its correlation with clinical characteristics. Methods: From January 2010 to December 2017, patients with bronchiectasis diagnosed by chest high-resolution CT (HRCT) and aged at or above 18 years old in 5 general hospitals of Shandong province were included in the study. The correlations between the HRCT imaging features and etiology, clinical manifestations, lung function, sputum culture, prognosis and other characteristics were analyzed. Results: There were 410 bronchiectasis patients included in the study. The chest HRCT imaging of bronchiectasis were divided into three types, including columnar 46.8%, cystic 45.9% and varicose 7.3%, respectively. The HRCT imaging score was [6.0 (4.0, 7.0)]. In addition, the most common etiology of bronchiectasis was idiopathic (262, 69.3%). The proportion of idiopathic bronchiectasis in cystic bronchiectasis patients was significantly higher than that in columnar and varicose bronchiectasis (71.8% vs 58.3%, 50.0%; both P< 0.017). Compared with columnar bronchiectasis, patients with cystic bronchiectasis were more likely to suffer from clinical manifestations such as cough, dyspnea, fever and wet rales ( P< 0.017). Compared with patients with HRCT scores of 1 to 4, patients with scores ≥8 were more likely to suffer from cough, dyspnea, fever, wet rales and clubbing ( P< 0.017). The proportions of pulmonary ventilatory dysfunction were significantly greater in patients with cystic bronchiectasis and varicose bronchiectasis than columnar bronchiectasis (86.7%, 86.7% vs 51.0%; both P< 0.017). The HRCT scores were significantly negatively correlated with pulmonary function ( P< 0.001). The number of acute exacerbations, hospitalizations, and bronchiectasis severe index scores in patients with cystic bronchiectasis were significantly higher than those with columnar bronchiectasis ( P< 0.017). There was a significantly positive correlation between HRCT scores and the number of acute exacerbations, hospitalizations and the bronchiectasis severity index scores ( P< 0.001). The mortality of patients with cystic and varicose bronchiectasis was significantly higher than that of patients with columnar bronchiectasis (9.0%, 10.0% vs 2.1%; both P< 0.017). Compared with patients with HRCT scores of 1 to 4, patients with scores ≥8 had a higher mortality rate (15.9% vs 0.9%; P< 0.017). Conclusions: There is a correlation between HRCT findings and clinical manifestations in patients with bronchiectasis. The clinical manifestations, lung function and prognosis of patients with cystic bronchiectasis are worse than those of the columnar bronchiectasis; the higher the HRCT scores are, the worse the clinical manifestations, lung function and prognosis of the patients are.

Peritoneal dissemination is the most frequent metastatic route of ovarian cancer. However, due to the high heterogeneity in ovarian cancer, most conventional studies lack parental tumor controls relevant to metastases and, thus, it is difficult to trace the molecular changes of cancer cells along with the selection by the abdominal microenvironment. Here, we established an in vivo mouse peritoneal dissemination scheme that allowed us to select more aggressive sublines from parental ovarian cancer cells, including A2780 and SKOV-3. Microarray and gene profiling analyses indicated that autophagy-related genes were enriched in selected malignant sublines. Detection of LC3-II, p62 and autophagic puncta demonstrated that these malignant variants were more sensitive to autophagic induction when exposed to diverse stress conditions, such as high cell density, starvation and drug treatment. As compared with parental A2780, the selected variant acquired the ability to grow better under high-density stress; however, this effect was reversed by addition of autophagic inhibitors or knockdown of ATG5. When analyzing the clinical profiles of autophagy-related genes identified to be enriched in malignant A2780 variant, 73% of them had prognostic significance for the survival of ovarian cancer patients. Taken together, our findings indicate that an increase in autophagic potency among ovarian cancer cells is crucial for selection of metastatic colonies in the abdominal microenvironment. In addition, the derived autophagic gene profile can not only predict prognosis well but can also be potentially applied to precision medicine for identifying those ovarian cancer patients suitable for taking anti-autophagy cancer drugs., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Accumulating evidence suggests a role of bisphenol A (BPA) in non-alcoholic fatty liver disease (NAFLD), and its mechanism may be related to the up-regulation of lipogenic genes, but the mechanism of BPA induced lipogenic gene expression remains unknown. The aim of this study was to investigate the effects of perinatal exposure to BPA on NAFLD and its mechanisms. Pregnant Sprague-Dawley rats had access to drinking water containing 1 or 10 μg/ml BPA from gestational day 6 to post-natal day 21. For 5 weeks after weaning, offspring drank normal water without BPA. Body weight, lipid profile and the expression of genes or proteins involved in mTOR mediated lipid metabolism and autophagy, as well as inflammatory response were investigated in the 8-wk-old offspring of different genders. The results showed that body weight was increased only in females, however, males, and females from dams treated with BPA had significantly excess visceral adipose tissue, which was consistent with adipocyte hypertrophy. Elevated TG levels and up-regulation of lipogenic genes or proteins in liver, such as sterol regulatory element binding protein 1 (SREBP1), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS) were consistent with increased liver lipid droplets in offspring exposed to BPA. Compared with controls, the protein levels of InsR, p-IRS-1, IRS-1, TSC1, and TSC2 were decreased, p-PI3K, p-Akt (S473), p-Akt (T308), p-mTOR, and mTOR were increased, and the impaired autophagic degradation was evidenced by increased protein levels of p62, although the levels of p-ULK1, Beclin1, and LC3B proteins were increased in liver of BPA-exposed offspring. The levels of TLR4 and NF-κB proteins were also significantly increased, and ERα protein was significantly decreased in BPA-exposed offspring. Our findings indicate that perinatal exposure to BPA causes the development of NAFLD in both female and male offspring, which is associated with up-regulation of lipogenic genes, dysregulated autophagy and activated inflammatory response involving the PI3K/Akt/mTOR and TLR4/NF-κB pathways.

Objective: With the improvement of surgical operation, increasing incidence of secondary benign airway stenosis, as a complication of long-term tracheal intubation and tracheotomy, leads to significant increases in morbidity and mortality. Previous treatment of secondary benign airway stenosis was mainly based on surgical resection and reconstruction. There is an urgent need for new treatment methods except surgery, especially for those inoperable patients. Methods: This study retrospectively reviewed 20 patients who had treatments of secondary benign airway stenosis after tracheotomy with Montgomery T-tube. The clinical data including clinical features, efficacy, complications and prognosis were retrospectively evaluated. Results: Complete airway obstruction was 12/20, partial stenosis was 8/20, combined with airway granuloma and endoscopic granulation resection was 16/20, combined with scar stenosis and endoscopic balloon dilatation was 18/20. Plugging successfully was 19/20. Complications included mucous accumulation (20/20), secondary granulation tissue formation (13/20), subcutaneous soft tissue infection (1/20), and T-tube re-implantation (3/20). Conclusions: Montgomery T-tube implantation under rigid bronchoscopy is a safe, feasible and effective tracheal forming method with well tolerance for patients with benign airway stenosis. Secondary benign airway stenosis after tracheal intubation and tracheotomy is an indication of Montgomery T-tube implantation. Compared with the traditional tracheotomy, the advantage of Montgomery T-tube implantation is easy to make the patient phonate, significantly improving the quality of life of patients. T-tube implantation is safe, and the postoperative complications include mucous accumulation and formation of secondary T-tube granulation tissue.

The traditional Chinese herb Lonicerae Japonicae Flos has shown significant clinical benefits in the treatment of heart failure, but the mechanism remains unclear. As the main active ingredient found in the plasma after oral administration of Lonicerae Japonicae Flos, chlorogenic acid (CGA) has been reported to possess anti-inflammatory, anti-oxidant and anti-apoptosis function. We firstly confirmed the cardioprotective effects of CGA in transverse aortic constriction (TAC)-induced heart failure mouse model, through mitigating the TNF-α-induced toxicity. We further used TNF-α-induced cardiac injury in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to elucidate the underlying mechanisms. CGA pre-treatment could reverse TNF-α-induced cellular injuries, including improved cell viability, increased mitochondrial membrane potential and inhibited cardiomyocytes apoptosis. We then examined the NF-κB/p65 and major mitogen-activated protein kinases (MAPKs) signalling pathways involved in TNF-α-induced apoptosis of hiPSC-CMs. Importantly, CGA can directly inhibit NF-κB signal by suppressing the phosphorylation of NF-κB/p65. As for the MAPKs, CGA suppressed the activity of only c-Jun N-terminal kinase (JNK), but enhanced extracellular signal-regulated kinase1/2 (ERK1/2) and had no effect on p38. In summary, our study revealed that CGA has profound cardioprotective effects through inhibiting the activation of NF-κB and JNK pathway, providing a novel therapeutic alternative for prevention and treatment of heart failure., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

All of the objects in the real world are envisioned to be connected and/or represented, through an infrastructure layer, in the virtual world of the Internet, becoming Things with status information. Services are then using the available data from this Internet-of-Things (IoT) for various social and economical benefits which explain its extreme broad usage in very heterogeneous fields. Domain administrations of diverse areas of application developed and deployed their own IoT systems and services following disparate standards and architecture approaches that created a fragmentation of things, infrastructures and services in vertical IoT silos. Coordination and cooperation among IoT systems are the keys to build "smarter" IoT services boosting the benefits magnitude. This article analyses the technical trends of the future IoT world based on the current limitations of the IoT systems and the capability requirements. We propose a hyper-connected IoT framework in which "things" are connected to multiple interdependent services and describe how this framework enables the development of future applications. Moreover, we discuss the major limitations in today's IoT and highlight the required capabilities in the future. We illustrate this global vision with the help of two concrete instances of the hyper-connected IoT in smart cities and autonomous driving scenarios. Finally, we analyse the trends in the number of connected "things" and point out open issues and future challenges. The proposed hyper-connected IoT framework is meant to scale the benefits of IoT from local to global.

Death-associated protein kinase 2 (DAPK2) has indicated functional roles in cellular processes, including survival, apoptosis, and autophagy. This study is aimed to identify the effect of DAPK2 on oxidative damage and apoptosis of placental cells in hypertensive disorder complicating pregnancy (HDCP) through mTOR pathway. Microarray-based gene expression analysis was performed to predict the differentially expressed genes related to HDCP. To investigate the specific mechanism of DAPK2 in HDCP cells, placental microvascular endothelial cells were treated with mimic or siRNA of DAPK2 and mTOR to detect the expression of related genes, cell autophagy and apoptosis and oxidative damage. Finally, rats were modeled with HDCP to verify the cell experiment results. DAPK2 was downregulated in HDCP, and could activate mTOR. Besides, DAPK2 overexpression led to decreases in autophagy in HPVECs as well as apoptosis and oxidative damage in placental cells indicated by a substantial decrease in Beclin-1, LC3 II/LC3 I and Bax along with an increase in Bcl-2, 4EBP1 and p70S6K. It also ameliorates blood pressure elevation in HDCP rats. The study defined remission effect of DAPK2 on placental cell oxidative damage and apoptosis in HDCP via mTOR activation. Together, DAPK2 regulating mTOR pathway presents a promising therapy for HDCP treatment., (Copyright © 2018. Published by Elsevier B.V.)

Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. Accumulated studies have revealed that targeting protein for Xklp2 (TPX2) was tightly associated with the development and progression of OC. The present study further determined a novel mechanism of TPX2 in OC via the AKT signaling pathway. The differentially expressed genes were screened in GEO database for gene expression microarray of OC. Bioinformatics was used to analyze the key differentially expressed genes in OC. We prepared CD133/1+ OC stem cells. Then cells were treated with TPX2-1 siRNA and perifcsine to explore the correlation of TPX2 and the AKT signaling pathway. We determined the expression of TPX2, AKT, Pl3 K, PTEN, caspase-3, Bax and Bcl-2 in OC cells. Cell proliferation, migration, invasion, and apoptosis rate were respectively measured using MTT and EdU assays, Transwell assay, Scratch test, and flow cytometry. Xenograft tumor in nude mice was used to determine the effect of TPX2 in OC cells in vitro. Initially, TPX2 overexpression was observed in OC, and TPX2 mediated the effect of the AKT signaling pathway in OC. TPX2 knockdown decreased expression of AKT, Pl3 K, and Bcl-2, and the extent of AKT phosphorylation, but increased expression of PTEN, Caspase-3, and Bax. Furthermore, TPX2 knockdown suppressed OC cell proliferation, migration and invasion, but promoted OC cell apoptosis. Taken together, TPX2 silencing negatively regulates the AKT signaling pathway by which OC cell proliferation was inhibited yet cell apoptosis was accelerated, suggesting a potential therapeutic approach to OC., (© 2018 Wiley Periodicals, Inc.)

α 1A - and α 1B -adrenoceptors (α 1A -AR and α 1B -AR) are closely related G protein-coupled receptors (GPCRs) that modulate the cardiovascular and nervous systems in response to binding epinephrine and norepinephrine. The GPCR gene superfamily is made up of numerous subfamilies that, like α 1A -AR and α 1B -AR, are activated by the same endogenous agonists but may modulate different physiological processes. A major challenge in GPCR research and drug discovery is determining how compounds interact with receptors at the molecular level, especially to assist in the optimization of drug leads. Nuclear magnetic resonance spectroscopy (NMR) can provide great insight into ligand-binding epitopes, modes, and kinetics. Ideally, ligand-based NMR methods require purified, well-behaved protein samples. The instability of GPCRs upon purification in detergents, however, makes the application of NMR to study ligand binding challenging. Here, stabilized α 1A -AR and α 1B -AR variants were engineered using Cellular High-throughput Encapsulation, Solubilization, and Screening (CHESS), allowing the analysis of ligand binding with Saturation Transfer Difference NMR (STD NMR). STD NMR was used to map the binding epitopes of epinephrine and A-61603 to both receptors, revealing the molecular determinants for the selectivity of A-61603 for α 1A -AR over α 1B -AR. The use of stabilized GPCRs for ligand-observed NMR experiments will lead to a deeper understanding of binding processes and assist structure-based drug design.

This study aimed to examine the association of herpes zoster (HZ) with androgen deprivation therapy (ADT) use among patients with prostate cancer (PC), using a population-based data set. The study sample for this study was retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We selected 877 patients with PC who had received ADT as the study group, while 849 patients with PC who had not received ADT served as the comparison group. Each study patient was individually tracked for a 3-year period to discriminate those who subsequently received a diagnosis of HZ. Of the total 1,726 sampled patients, the incidence rate of HZ per 100 person-years was 1.80 (95% CI: 1.41-2.25) during the 3-year follow-up period. In particular, incidence rates of HZ per 100 person-years were 2.36 (95% CI: 1.75-3.13) and 1.24 (95% CI: 0.81-1.81), respectively, for patients with PC who had and those who had not received ADT. Furthermore, Cox proportional hazard regressions showed that the adjusted hazard ratio for an HZ attack during the 3-year follow-up period for patients with PC who had received ADT was 1.88 (95% CI: 1.13-3.11) than those who had not received ADT. We concluded that patients with PC who had received ADT had an increased risk of HZ., (© 2017 Blackwell Verlag GmbH.)

The interrelationships between ventilation rate, indoor air quality, and energy consumption in operation rooms at rest are yet to be understood. We investigate the effect of ventilation rate on indoor air quality indices and energy consumption in ORs at rest. The study investigates the air temperature, relative humidity, concentrations of carbon dioxide, particulate matter (PM), and airborne bacteria at different ventilation rates in operation rooms at rest of a medical center. The energy consumption and cost analysis of the heating, ventilating, and air conditioning (HVAC) system in the operation rooms at rest were also evaluated for all ventilation rates. No air-conditioned operation rooms had very highest PM and airborne bacterial concentrations in the operation areas. The bacterial concentration in the operation areas with 6-30 air changes per hour (ACH) was below the suggested level set by the United Kingdom (UK) for an empty operation room. A 70% of reduction in annual energy cost by reducing the ventilation rate from 30 to 6 ACH was found in the operation rooms at rest. Maintenance of operation rooms at ventilation rate of 6 ACH could save considerable amounts of energy and achieve the goal of air cleanliness.

Objective: Besides pulmonary arteriography, a number of imaging techniques, such as magnetic resonance imaging (MRI) and computed tomography (CT), were adopted in the detection of identifying pulmonary embolism (PE). However, the contrast of sensitivity and specificity in these methods was studied little in a statistical way. To compare the effects of MRI and CT, this study used a series of methods to analyze data in included researches., Methods: A comprehensive computer search was conducted through internet up to July 2016. The quality assessment was performed by the Quality Assessment Tool for Diagnostic Accuracy Studies, version 2 tool. The diagnostic value of comparison between MRI and CT was evaluated by using the pooled estimate of sensitivity, specificity, and summary receiver operating characteristic (SROC) curve. In addition, sensitivity analysis and bias analysis were applied to ensure the accuracy of the results., Results: Ten studies with 590 cases were involved in the study. Only 2 trials had high risk regarding bias while other trials were supposed to be at low risk of applicability. Heterogeneity existed in analysis of both CT and MRI. The pooled sensitivity of CT was 0.90 (95% CI: 0.85-0.93), pooled specificity was 0.88 (95% CI: 0.77 to 0.95), the pooled sensitivity of MRI was 0.92 (95% CI: 0.89-0.94), and pooled specificity was 0.91 (95% CI: 0.77-0.97). The Q index of sensitivity and specificity for CT and MRI were 71.38, 19.67, 47.14, and 12.35, respectively. The SROC curve area under the curve of CT and MRI were 0.94 (95% CI: 0.91-0.96) and 0.93 (95% CI: 0.91-0.95), respectively., Conclusion: This meta-analysis demonstrates that MRI has better sensitivity and specificity in detecting subsegmental artery PE. MRI is a relatively better detection technique for PE. This conclusion is consistent with many published researches., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Mutation in either of the genes encoding bone morphogenetic protein (BMP) 8A or 8B ( Bmp8a or Bmp8b ) causes postnatal depletion of spermatogonia in mice. We found that Bmp8a , but not Bmp8b , was expressed predominantly in the neonatal mouse spermatogonia. Although most BMPs induce activation of SMADs 1, 5, and 8 (SMAD1/5/8), but not SMADs 2 and 3 (SMAD2/3), we found that BMP8A induced signaling through both sets of transcription factors. In undifferentiated mouse spermatogonia, BMP8A activated SMAD1/5/8 through receptor complexes formed by ALK3 and either ACVR2A or BMPR2 and activated SMAD2/3 through receptor complexes formed by ALK5 and ACVR2A, ACVR2B, or TGFBR2. Signaling through SMAD2/3 promoted the proliferation of germ cells, whereas that through SMAD1/5/8 directed the subsequent differentiation of spermatogonia. BMP8A promoted spermatogenesis in cultured mouse testis explants, and the resulting spermatids were functionally competent for fertilization. These results suggest that the dual role of BMP8A in promoting proliferation and differentiation of spermatogonia may be exploited clinically to treat male infertility., (Copyright © 2017, American Association for the Advancement of Science.)

The objective was to assess the safety and outcome of cold snare technique used by flexible bronchoscopy in the treatment of airway benign neoplasms. The clinical data of 21 patients, who had airway benign neoplasm and were treated through the cold snare method in Sir Run Run Shaw Hospital, affiliated with the Zhejiang University, were retrospectively analyzed. The relief of the symptoms and occurrence of complications were observed and evaluated. All the tumors were benign and removed by cold snare. Postoperatively, we found that the treatment was completely effective in 12 patients, and there was a significant improvement in 7 patients and a moderate improvement in 2 patients, and no recurrence in follow-up visit. In conclusion, the cold snare technique is an economically feasible, safe, and effective method in the treatment of airway neoplasms.

In this study, we assessed whether the down-regulation of Yes-associated protein (YAP) is involved in the pathogenesis of extracellular matrix (ECM) mechanical stress-induced Stanford type A aortic dissection (STAAD). Human aortic samples were obtained from heart transplantation donors as normal controls and from STAAD patients undergoing surgical replacement of the ascending aorta. Decreased maximum aortic wall velocity, ECM disorders, increased VSMC apoptosis, and YAP down-regulation were identified in STAAD samples. In a mouse model of STAAD, YAP was down-regulated over time during the development of ECM damage, and increased VSMC apoptosis was also observed. YAP knockdown induced VSMC apoptosis under static conditions in vitro , and the change in mechanical stress induced YAP down-regulation and VSMC apoptosis. This study provides evidence that YAP down-regulation caused by the disruption of mechanical stress is associated with the development of STAAD via the induction of apoptosis in aortic VSMCs. As STAAD is among the most elusive and life-threatening vascular diseases, better understanding of the molecular pathogenesis of STAAD is critical to improve clinical outcome., Competing Interests: No conflicts of interest, financial or otherwise, are declared by the authors.

Objective: To examine the relationship between the use of androgen deprivation therapy (ADT) and the subsequent risk of falls in men with prostate cancer (PC) by employing a population-based dataset., Methods: We retrieved the study sample from the Taiwan Longitudinal Health Insurance Database 2005. We included 886 patients with PC who had received ADT as the study group, whereas 862 patients with PC who had not received ADT served as the comparison group. We then individually tracked each study patient for a 3-year period to identify those who subsequently received a diagnosis of a fall. We performed Cox proportional hazard regressions to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI) for a fall during the 3-year follow-up period between these 2 groups., Results: The incidence rates of falls per 1000 person-years were 13.37 (95% CI: 9.15~18.88) and 6.44 (95% CI: 3.61~10.63), respectively, for patients with PC who received ADT and those who did not receive ADT. Furthermore, the hazard ratio for a fall during the 3-year follow-up period for patients with PC who had received ADT was 1.95 (95% CI: 1.04~3.66, P = .037) compared to those who had not received ADT after censoring sampled patients who died during the 3-year follow-up period and adjusting for age, geographical location, monthly income, urbanization level, hypertension, diabetes, hyperlipidemia, coronary heart disease, Parkinson's disease, epilepsy, stroke, and mental illness., Conclusion: The present findings suggest that patients with PC who had received ADT had an increased risk of falls., (Copyright © 2016. Published by Elsevier Inc.)

Gonadotropin signaling plays an indispensable role in ovarian cancer progression. We previously have demonstrated that thyrostimulin and thyroid-stimulating hormone receptor (TSHR), the most ancient glycoprotein hormone and receptor pair that evolved much earlier than the gonadotropin systems, co-exist in the ovary. However, whether thyrostimulin-driven TSHR activation contributes to ovarian cancer progression in a similar way to gonadotropin receptors has never been explored. In this study, we first found that TSHR is expressed in both rat normal ovarian surface epithelium and human epithelial ovarian cancers (EOCs). Using human NIH:OVCAR-3 as a cell model, we demonstrated that thyrostimulin promotes EOC cell proliferation as strongly as gonadotropins. Thyrostimulin treatment not only activated adenylyl cyclase and the subsequent PKA, MEK-ERK1/2 and PI3K-AKT signal cascades, but also trans-activated EGFR signaling. Signaling dissection using diverse inhibitors indicated that EOC cell proliferation driven by thyrostimulin-TSHR signaling is PKA independent, but does require the involvement of the MEK-ERK and PI3K-AKT signal cascades, which are activated mainly via the trans-activation of EGFR. Thus, not only have we proved that this ancient glycoprotein hormone system is involved in NIH:OVCAR-3 cell proliferation for the first time, but also that it may possibly become a novel oncotarget when studying ovarian cancer.

Neuromedin U (NMU) was originally named based on its strong uterine contractile activity, but little is known regarding its signaling/functions in utero. We identified that NMU and one of its receptors, NMUR2, are not only present in normal uterine endometrium but also co-expressed in endometrial cancer tissues, where the NMU level is correlated with the malignant grades and survival of patients. Cell-based assays further confirmed that NMU signaling can promote cell motility and proliferation of endometrial cancer cells derived from grade II tumors. Activation of NMU pathway in these endometrial cancer cells is required in order to sustain expression of various adhesion molecules, such as CD44 and integrin alpha1, as well as production of their corresponding extracellular matrix ligands, hyaluronan and collagen IV; it also increased the activity of SRC and its downstream proteins RHOA and RAC1. Thus, it is concluded that NMU pathway positively controls the adhesion signaling-SRC-Rho GTPase axis in the tested endometrial cancer cells and that changes in cell motility and proliferation can occur when there is manipulation of NMU signaling in these cells either in vitro or in vivo. Intriguingly, this novel mechanism also explains how NMU signaling promotes the EGFR-driven and TGFβ receptor-driven mesenchymal transitions. Through the above axis, NMU signaling not only can promote malignancy of the tested endometrial cancer cells directly, but also helps these cells to become more sensitive to niche growth factors in their microenvironment.

Baicalin has been shown to provide the neuroprotective effect by alleviating cerebral ischemia injury. However, little's known about the underlying mechanism. Here, a cerebral artery occlusion (MACO)/reperfusion rat model and rat primary cortical neuron culture exposed to hydrogen peroxide (H2O2) were established to evaluate the effect of baicalin on ischemia-induced neuronal apoptosis. We found baicalin can significantly less neurological deficit and reduced infarct volume in vivo. And it efficiently inhibited neuronal apoptosis in vivo and vitro, which was especially characterized by the enhancing of transcription and expression of myeloid cell leukemia-1 (MCL-1) and B-cell lymphoma-2 (BCL-2) in a dose-dependent manner. Furthermore, Baicalin markedly increased myocardin-related transcription factor-A (MRTF-A) level either in ischemic hemisphere or in primary cortical neuron cultures, whiles the anti-apoptosis effect of baicalin was significantly inhibited by transfected with the small interfering RNA of MRTF-A (MRTF-A siRNA) in primary cortical neuron cultures. The luciferase assays also indicated baicalin enhanced the transactivity of MCL-1 and BCL-2 promoter by activating the key CArG box (CC [A/T] 6GG) element, which was reduced by MRTF-A siRNA, suggesting MRTF-A may participate the anti-apoptosis effect of baicalin, and MRTF-A was involved in the transcriptional activity of MCL-1 and BCL-2 that was induced by baicalin. LY294002 (phosphatidylinositol-3 kinase (PI3K) inhibitor) and PD98059 (extracellular signal regulates kinase-1/2 (ERK1/2) inhibitor) obviously reduced baicalin-induced MRTF-A expression and transactivity and expression of MCL-1 and BCL-2, which further abolished the anti-apoptotic effect of baicalin on neuronal apoptosis. Taken together, our data provided the evidence demonstrating the neuroprotective effect of baicalin partially due to MRTF-A-mediated transactivity and expression of MCL-1 and BCL-2 by triggering the CArG box, which might be controlled by the activation of PI3K and ERK1/2., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The high quality of induced pluripotent stem cells (iPSCs) has been determined to be high-grade chimeras that are competent for germline transmission, and viable mice can be generated through tetraploid complementation. Most of the high-quality iPSCs described to date have been male. Female iPSCs, especially fully pluripotent female iPSCs, are also essential for clinical applications and scientific research. Here, we show, for the first time, that a gender-mixed induction strategy could lead to a skewed sex ratio of iPSCs. After reprogramming, 50%, 70%, and 90% female initiating mouse embryonic fibroblasts at different male ratios resulted in 14.1 ± 6.8% (P < 0.05), 31.8 ± 5.4% (P < 0.05), and 80.1 ± 2.8% (P < 0.05) female iPSCs, respectively. Furthermore, these female iPSCs had pluripotent properties typical of embryonic stem cells. Importantly, these fully pluripotent female iPSCs could generate viable mice by tetraploid complementation. These findings indicate that high-quality female iPSCs could be derived effectively, and suggest that clinical application of female iPSCs is feasible., (© 2015 by the Society for the Study of Reproduction, Inc.)

Unlabelled: Preeclampsia (PE) is a pregnancy-specific syndrome that occurs in a previously normotensive woman. Some data suggested that the activation parameters of platelets in preeclampsia. The aim of this study is to determine whether the levels of GPIbα and GPIIb for patients with preeclampsia were enhanced after cesarean section. In this study, detecting levels of GPIbα and GPIIb by flow cytometry (FCM). The venous blood of 48 severe preeclampsia women, 16 mild preeclampsia and 22 normotensive women, were collected before operation and 72 hours after the operation. Blood samples were obtained also from 20 non-pregnant women., Results: The level of GPIbα of the normotensive pregnancy was lower than the control group, but there was no significance (P > 0.05). The level of GPIbα of the severe preeclampsia group was much lower than other groups (P < 0.01). In the severe preeclampsia group, the level of GPIbα of postoperative patients was higher than preoperative patients (P < 0.01). There was no significance of GPIIb levels between each group (P > 0.05). In conclusion, GPIbα was an important index of reflecting the change of severe preeclampsia. Detecting the levels of GPIbα plays an important role in observing the development of this disease and guiding clinical treatment.

Leucine-rich repeat containing G protein-coupled receptor 4 (LGR4) promotes the Wnt signaling through interaction with R-spondins or norrin. Using PCR amplification from rat ovarian cDNAs, we identified a naturally occurring Lgr4 splice variant encoding only the ectodomain of Lgr4, which was named Lgr4-ED. Lgr4-ED can be detected as a secreted protein in the extracts from rodent and bovine postnatal gonads, suggesting conservation of Lgr4-ED in mammals. Recombinant Lgr4-ED purified from the conditioned media of transfected 293T cells was found to dose-dependently inhibit the LGR4-mediated Wnt signaling induced by RSPO2 or norrin, suggesting that it is capable of ligand absorption and could have a potential role as an antagonist. Intraperitoneal injection of purified recombinant Lgr4-ED into newborn mice was found to significantly decrease the testicular expression of estrogen receptor alpha and aquaporin 1, which is similar to the phenotype found in Lgr4-null mice. Administration of recombinant Lgr4-ED to superovulated female rats can also decrease the expression of estrogen receptor alpha, aquaporin 1, LH receptor and other key steroidogenic genes as well as bring about the suppression of progesterone production. Thus, these findings suggest that endogenously expressed Lgr4-ED may act as an antagonist molecule and help to fine-tune the R-spondin/norrin-mediated Lgr4-Wnt signaling during gonadal development.

Controversy remains regarding the risk of bone abnormalities due to enzyme-inducing antiepileptic drugs (EIAEDs) and non-enzyme-inducing antiepileptic drugs (NEIAEDs). This case-control study aimed to investigate the possible association between osteoporosis and epilepsy disease and AEDs therapy using a population-based dataset in Taiwan. We first identified 48,102 cases, ≥ 18 years of age, who received a first-time diagnosis of osteoporosis, and then randomly selected 144,306 controls. We used conditional logistic regression analyses to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) to compare a previous diagnosis of epilepsy between cases and controls. We found that of the 192,408 sampled subjects, epilepsy was found in 117 (0.24%) cases and 240 (0.17%) controls (p<0.001). Cases were found to be more likely to have previously been diagnosed with epilepsy than controls (OR: 1.41, 95% CI: 1.11 ≈ 1.78, p<0.01), after taking confounders into consideration. Furthermore, we found that, compared to controls, the adjusted OR of cases in which enzyme-inducing AEDs had been prescribed was 2.06 (95% CI: 1.43 ≈ 2.95). A higher proportion of cases with prescribed NEIAED was also found (OR: 2.09, 95% CI: 1.49 ≈ 2.92) compared to controls. This study demonstrates that patients with osteoporosis were more likely to have epilepsy and receive EIAED or NEIAED treatment. For patients with epilepsy who take AEDs, attention should be paid to the adverse effects of osteoporosis.

Three polysaccharides, AAP, AVAP I, and AVAP II, were isolated from abalone Haliotis discus hannai Ino. The polysaccharides' compositions were analysed, and their effects on HepG2 cell proliferation were assessed. AVAP I had a greater growth-stimulatory effect than AAP or AVAP II. The oligosaccharide of AVAP I (Oli-AVAP I) exhibited the same growth effects, but rhamnose, the primary monosaccharide of AVAP I and Oli-AVAP I, did not exhibit this activity. Moreover, AVAP I dramatically reduced the mRNA levels of CDK6 and Cyclin E1 but significantly increased Cyclin B1, CDK1 and Cyclin F. Interestingly, AVAP I remained able to induce cell proliferation in a low serum concentration medium. AVAP I could therefore promote HepG2 cell proliferation by regulating gene expression and accelerating the cell cycle process. AVAP I may be useful as a serum supplement for stimulating the proliferation of mammalian cells. Our results offer a comprehensive method for utilising the abalone viscera, which is usually discarded as waste., (Copyright © 2014. Published by Elsevier B.V.)

The first step of biodegradation is the contact of microorganism and pollutants, in order to examine the influence of phenanthrene on Sphingomonas sp. GY2B's surface properties during its degrading process, the bacteria was cultivated at different conditions, and detected by flow cytometry combined with fluorescent dyes for its surface changes. The results indicated that, the membrane structure had been certainly damaged during the degrading process, leading to an increased membrane permeability. Moreover, the destruction of bacteria membrane integrity became more serious with a higher pollutant concentration. At the concentration of 300 mg x L(-1), the ratio of stained bacterial cells/unstained cells was 12.44 after cultured for 60 h, while at 100 mg x L(-1) and 1.2 mg x L(-1), the ratios were 1.95 and 1.11, respectively. The results of fourier transform infrared (FT-IR) absorbance spectroscopy detection, the discrimination of death, injured and intact cells, and Zeta potential detection further verified the bacterial cell surface permeability changes. Flow cytometry combined with fluorescent dye propidium iodide was used to monitor the changes of bacterial membrane integrity on single-cell level which exhibited a good potential for exploring the changes of bacterial surface properties during the degrading progress and more deeply for investigating the degradation mechanism.

Objectives: This study attempted to describe stressors, levels of stress, and coping strategies of 20-45-year-old Taiwanese patients undergoing chronic hemodialysis., Methods: A cross-sectional descriptive design was used. A convenience sample of 88 patients with a mean age of 38.55 years was recruited at six dialysis centers in southern Taiwan. Data were collected using the Hemodialysis Stressor Scale and the Jalowiec Coping Scale., Results: The results show that this group of patients had higher levels of stress than those reported in previous studies. The three most frequently reported stressors were limitations of liquids, limitations of food, and fatigue. The two most frequent coping methods were trying to find meaning in the situation and trying out different ways of solving problems to see which works the best. These patients had more physiological stressors than psychosocial stressors and used more problem-oriented coping strategies than affective-oriented ones. Additionally, the longer the patients had received hemodialysis, the lower stress level they had, and patients with jobs, with partners, or with children used significantly more coping strategies than those without jobs, partners, or children. Gender differences were not found in the total stress level or coping strategies of these patients, except that female patients had greater psychosocial stressors than male patients., Conclusions: The 20-45-year-old hemodialysis patients experienced considerable levels of stress and had a unique ranking order of stressors and coping strategies. These findings will provide healthcare professionals with detailed information to identify priority areas for future intervention development.