Development and external validation of a prognostic model for occult atrial fibrillation in patients with ischemic stroke

ObjectiveCurrently, the risk of occult atrial fibrillation (AF) could not be predicted in patients with acute ischemic stroke (AIS) using a simple scoring system. Therefore, in this study, we developed and externally validated a nomogram to predict occult AF in patients with AIS.MethodsIn this study, we prospectively conducted a development cohort study with data collected at our stroke center from July 2017 to February 2018, and an external validation cohort from March 2019 to December 2019.ResultsFollow-up data were collected from 177 participants (56.5% older than 65 years, 29.4% female) for generating the nomogram model. Multivariate logistic regression analysis was performed with AF as the dependent variable indicated that age >65 years, heart rate >100, C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP) >270, hemorrhagic transformation (HT) as independent variables for predicting the development of AF, and a nomogram was generated based on these factors. The area under the receiver operating characteristic curve (AUC-ROC) for the model was 0.937, the C-index was 0.926, and the AUC-ROC for the validation cohort was 0.913.ConclusionTo our knowledge, this is the first nomogram developed and externally validated in a stroke center cohort for individualized prediction of risk of developing AIS in patients with occult AF. This nomogram could provide valuable information for the screening of occult AF after a stroke

Development of novel polymeric nanoagents and their potential in cancer diagnosis and therapy runing title: Polymeric nanoagents for cancer theranostics

Cancer has been one of the leading factors of death around the world. Cancer patients usually have low 5-year survival rates and poor life quality requiring substantial improvement. In clinic, the presenting diagnostic strategies lack sensitivity with only a small proportion of patients can be accurately identified. For diagnosed patients, most of them are at the advanced stages thus being delayed to receive treatment. Therefore, it is eager to investigate and develop highly effective and accurate techniques for cancer early diagnosis and individualized therapy. Various nanoplatforms are emerging as imaging agents and drug carriers for cancer theranostics recently. Novel polymeric nanoagents, as a potent exemplar, have extraordinary merits, such as good stability, high biosafety and high drug loading efficacy, showing the great prospect for cancer early diagnosis and precise treatment. Herein, we review the recent advances in novel polymeric nanoagents and elucidate their synthesis procedures. We further introduce the applications of novel polymeric nanoagents in cancer diagnosis, treatment, and theranostics, as well as associated challenges and prospects in this field

Predicting land use changes in northern China using logistic regression, cellular automata, and a Markov model

Abstract(#br)Land use changes are complex processes affected by both natural and human-induced driving factors. This research is focused on simulating land use changes in southern Shenyang in northern China using an integration of logistic regression, cellular automata, and a Markov model and the use of fine resolution land use data to assess potential environmental impacts and provide a scientific basis for environmental management. A set of environmental and socio-economic driving factors was used to generate transition potential maps for land use change simulations in 2010 and 2020 using logistic regression. An average relative operating characteristic value of 0.824 was obtained, indicating the validity of the logistic regression model. The logistic–cellular automata (CA)–Markov model..

Morphological Study of the Alimentary Canal and Malpighian Tubules in the Adult of the Pollen Beetle Meligethes (Odonthogethes) chinensis (Coleoptera: Nitidulidae: Meligethinae)

Meligethinae has entirely become strictly anthophagous, also being called "pollen beetles", with all members (similar to 700 species) of this subfamily using pollen and other floral parts as food resources for their larvae and adults. In this study, we used light, fluorescence, and scanning electron microscopy (LM, FM, and SEM) to explore the fine morphological structure of the alimentary canal and Malpighian tubules of Meligethes (Odonthogethes) chinensis, a common Chinese pollen beetle associated with flowers of Rosaceae. The results show that the alimentary canal of M. (O.) chinensis is divided into three parts of foregut, midgut, and hindgut. The foregut is the shortest part and has no crop; the midgut is the widest part with numerous blunt-fingered gastric ceca; the front of the hindgut folds in a circle and then extends back to the anus. Six Malpighian tubules are attached to the colon to form a cryptonephridial system. We also provide a schematic color picture of the alimentary canal and Malpighian tubules in the hemocoelic cavity of the dissected M. (O.) chinensis. This study is the first to systematically study the general morphology of the alimentary canal and Malpighian tubules of Meligethinae, which can provide important support for subsequent anatomical and physiological studies of anthophagous beetles.Meligethes (Odonthogethes) chinensis is a highly specialized species of Nitidulidae in China that takes pollen as its main food source, and its main host plant is Rubus idaeus L. (Rosaceae). In this study, the structural morphology of the alimentary canal and Malpighian tubules of adult M. (O.) chinensis was observed under light, fluorescence, and scanning electron microscopy. The alimentary canal of adult M. (O.) chinensis is divided into foregut, midgut, and hindgut. The foregut is the shortest and consists of the pharynx, esophagus, proventriculus, and cardiac valve. The midgut is a straight, distended, cylindrical, thin-walled tube. Numerous blunt-fingered gastric ceca are distributed irregularly throughout the midgut. The hindgut is subdivided into the ileum, colon, and rectum. The ileum is coiled. The colon gradually enlarges posteriorly. The rectum is thickly muscled and followed by a membranous structure. The openings of proximal Malpighian tubules are evenly inserted into the junction of the midgut and hindgut, and distal Malpighian tubules are evenly attached to the colon to form a cryptonephridial system. In this study, we also compare the structure and infer the function of the alimentary canal and Malpighian tubules among beetles, as well as discuss the evolutionary and taxonomical implications

OR-030 Influences of Four Weeks Intermittent Hypoxic Training on Aerobic Ability of High-Level Race Walking Athletes

Objective Altitude training is an important training method for endurance athletes to improve aerobic capacity. Endurance athletes take advantage of the dual stimulation of hypoxia in the altitude environment and hypoxic during training to improve their exercise capacity and physiological function. However, due to the high stimulation of altitude training, the difficulty of recovery and other characteristics, and with the appearance of hypoxic installation, a series of new training methods have been developed.  The advantage of IHT is that it can be combined with routine training, and the training altitude and training plan can be adjusted according to the actual situation. Studies in recent years have shown that IHT has some advantages in achieving better athletic performance: (1) IHT can prevent athletes from having sleep disorders and dehydration, which are typical symptoms of prolonged exposure to high altitude environments; (2) The recovery after IHT training is performed under normoxic conditions, which can prevent the athletes from the harmful effects of prolonged hypoxia, and shorten the recovery time after training; and (3) the time spent apart from training under hypoxic conditions may be used for normal training activity.  The study intended to develop a appropriate four-week IHT plan, which would be integrated into the training of five high-level race walking athletes in the winter training and with the plain training period, full attention to the combination of special training，hoping to achieve better training effect. At the same time, through the test of aerobic capacity-related indicators, explored the influences of four-weeks IHT on specific ability of high-level race walking athletes. This study will be of great significance to guide the race walking training in the future. Methods Five high-level male race walking athletes(20.6±2.5 y,175±7.7 cm,57.4±9.1 kg) provided informed consent to participate in this study. They would be conducted to four weeks of routine training and four weeks of IHT training. IHT was performed for four weeks, three times a week, about three hours each, in a hypoxic laboratory at an altitude of 2500 m and an oxygen concentration of about 15.3%. Each week, athletes would  do aerobic walk training (10 km~15 km,85%AT), intermittent walking training (2 km*5~2 km*6,90-100%AT) and special endurance walking training (16 km~20 km,80%AT). The training programs for routine training and hypoxic training were all consistent. Blood test and treadmill incremental load test were performed before and after the two trainings. In the blood test, the functional indexes such as RBC, Hb, Hct, CK and BU were recorded. In the incremental load test of treadmill, the initial speed was 9 km/h, added 1 km/h every 3 minutes, and HR, BLA, VO2were recorded indicators of aerobic capacity. During the routine and hypoxic training, the athletes wore heart rate monitors and oxygen saturation meters throughout the course of training and recorded the heart rates and oxygen saturations before and after training.  Statistical analyses were undertaken using the SPSS software (Version 20). All test results were presented as mean ± SD, and the mean of relevant indicators before and after hypoxic training were analyzed using the paired sample T-test, as p <0.05, with significant difference, as p <0.01, with significant significance differences. Results There was no significant difference in blood lactate and maximal oxygen uptake in post-routine training compared with pre-routine training, and heart rate was significantly different (p<0.01); post-IHT compared to pre-IHT, there was a significant difference in the heart rate and oxygen uptake (P<0.05), but the difference in blood lactate was not significant (P>0.05). Before and after the two trainings, there were no significant differences in blood parameters such as CK, BU, RBC, Hb, and Ferri (P>0.05). After routine training, the maximum speed increased from 13.2±0.64km/h to 13.4±0.55km/h, and the maximum heart rate of anaerobic threshold decreased from 194.7±10.17 beats/min to 188.6±12.18 beats/min. During the intermittent hypoxia training, the oxygen saturation in the quiet state and after training gradually increased. Among them, the maximum heart rate of anaerobic threshold decreased from 188.6±12.18 beats/min to 182.8±8.35 beats/min, and the maximum walking speed increased from 13.4±0.55 km/h to 13.8±1.1 km/h. After intermittent hypoxia training, HRAT and %HRmaxincreased, while HRmaxdecreased. The increase in HRAT and %HRmaxindicated that the proportion of aerobic energy supply had increased in incremental loads. The decrease in HRmaxindicated that the athletes' heart and lung function had improved after training. VO2maxis one of the major determinants of endurance exercise capacity. It reflects the ability of the body to ingest, transport and utilize oxygen. It is a good index for evaluating cardiopulmonary function and aerobic endurance of athletes. The anaerobic threshold（AT）refers to the body in the process of incremental loads, means the critical point from the aerobic energy supply to anaerobic energy supply. Evaluation of the body's aerobic capacity is not only dependent on VO2max, but also closely related to AT. VO2maxmainly reflects the cardiopulmonary function and skeletal muscle metabolism, while AT can reflect the utilization of VO2maxwhen lactic acid begins to accumulate, which can reflect the utilization of oxygen by skeletal muscle. Zhang compared the anaerobic threshold ventilation and heart rate anaerobic threshold, pointed out that the test condition of the ventilation anaerobic threshold is demanding, it is difficult to achieve in general, and use of heart rate monitoring training is simple and easy to operate. Ham's Study also pointed out that lactic acid anaerobic threshold requires blood, ventilation anaerobic threshold requires expensive equipment and manpower, and heart rate anaerobic threshold to estimate anaerobic threshold is more appropriate. The point at which heart rate begins to increase non-linearly is usually called the anaerobic threshold heart rate (HRAT). In this experiment, the results of HRAT, anaerobic thresholds / maximum heart rate (% HRmax) were analyzed. After hypoxic training, HRAT% HRmaxincreased, while HRmaxdecreased. Increases in HRAT and % HRmax, indicated that there is an increase in the proportion of aerobic energy supplied during incremental loads. The drop in HRmaxindicated that athletes improved cardiorespiratory fitness after training. After four weeks of routine and hypoxic training, RBC, Hb, Hct decreased. Wilber mentioned in his article, there was no relevant research that RBC production-related transferrin receptor, RBC volume, Hct quality had increased. Park conducted a meta-analysis of eight sports of elite athletes and found that hypoxic training for more than three weeks, three times per week, and one hour each can improve blood oxygen delivery and aerobic capacity, reflected in RBC, Hb and other related indicators. Levine’ related studies have shown that hypoxic training exercise performance improvement is not the role of hematological mechanisms, but the skeletal muscle mitochondria, capillary fiber ratio, the changes in fiber cross-sectional area. The reason for this may be related to the duration of hypoxic exposure in the experimental protocol and the training intensity stimulating RBC production had not been reached or the body was still in an adaptive state. Increasing the duration of hypoxic exposure may result in an increase in RBC levels. In addition, because of individual differences, each athlete has his/her own range of the best parameters of blood cells, even if the relevant indicators are not high, but can complete the corresponding training plans. Besides of individual differences, it is also possible to reduce blood cell parameters during periods of intensive training due to excessive body exhaustion, as long as proper adjustment is made before the competition, a athlete can still be in the best condition.  Conclusions After 4 weeks of IHT, the heart rate anaerobic threshold of high-level race walking athletes has been increased, indicating that aerobic energy ratio has been increased and aerobic capacity has been improved. After 4 weeks of IHT, the RBC, Hb and other hematological indicators of high-level walking athletes do not improve

Loss of PDZK1 expression activates PI3K/AKT signaling via PTEN phosphorylation in gastric cancer

Phosphorylation of PTEN plays an important role in carcinogenesis and progression of gastric cancer. However, the underlying mechanism of PTEN phosphorylation regulation remains largely elusive. In the present study, PDZK1 was identified as a novel binding protein of PTEN by association of PTEN through its carboxyl terminus and PDZ domains of PDZK1. By direct interaction with PTEN, PDZK1 inhibited the phosphorylation of PTEN at S380/T382/T383 cluster and further enhanced the capacity of PTEN to suppress PI3K/AKT activation. PDZK1 suppressed gastric cancer cell proliferation by diminishing PI3K/AKT activation via inhibition of PTEN phosphorylation in vitro and in vivo. The expression of PDZK1 was frequently downregulated in gastric cancer specimens and correlated with progression and poor prognosis of gastric cancer patients. Downregulation of PDZK1 was associated with PTEN inactivation, AKT signaling and cell proliferation activation in clinical specimens. Thus, low levels of PDZK1 in gastric cancer specimens lead to increase proliferation of gastric cancer cells via phosphorylation of PTEN at the S380/T382/T383 cluster and constitutively activation of PI3K/AKT signaling, which results in poor prognosis of gastric cancer patients

Thermodynamic assessments of the Er-Sb and Sb-Tm systems

通讯作者：E-mail address: [email protected] (X.J. Liu).By using the calculation of phase diagrams (CALPHAD) method, thermodynamic assessments of the Er-Sb and Sb-Tm systems were carried out based on the available experimental data including thermodynamic properties and phase equilibria. The Gibbs free energies of the liquid, hcp, and rhombohedral phases in the Er-Sb and Sb-Tm systems were modeled by the substitutional solution model with the Redlich-Kister formula, and the intermetallic compounds (Er(5)Sb(3), alpha ErSb, beta ErSb, ErSb(2), Sb(2)Tm, alpha SbTm, beta SbTrn, alpha Sb(3)Tm(5), and beta Sb(3)Tm(5) phases) in these two binary systems were described by the sublattice model. An agreement between the present calculated results and experimental data was obtained.National Natural Science Foundation of China 51031003 Ministry of Education of China 707037 Ministry of Science and Technology of China 2009DFA52170 2009AA03Z101 Doctoral Foundation of Qingdao University of Science and Technolog

Breast cancer-derived K172N, D301V mutations abolish Na+/H+ exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling

AbstractNa+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein known to interact with a number of cancer-related proteins. nherf1 Mutations (K172N and D301V) were recently identified in breast cancer cells. To investigate the functional properties of NHERF1, wild-type and cancer-derived nherf1 mutations were stably expressed in SKMES-1 cells respectively. NHERF1-wt overexpression suppressed the cellular malignant phenotypes, including proliferation, migration, and invasion. nherf1 Mutations (K172N and D301V) caused complete or partial loss of NHERF1 functions by affecting the PTEN/NHERF1/PDGFRβ complex formation, inactivating NHERF1 inhibition of PDGF-induced AKT and ERK activation, and attenuating the tumor-suppressor effects of NHERF1-wt. These results further demonstrated the functional consequences of breast cancer-derived nherf1 mutations (K172N and D301V), and suggested the causal role of NHERF1 in tumor development and progression

HBV infection-induced liver cirrhosis development in dual-humanized mice with human bone mesenchymal stem cell transplantation

疾病动物模型是现代医学发展的基石，尤其是重大、突发传染病暴发时，适宜的疾病动物模型可为及时发现病原体、制定防控策略提供强大保障，原创的疾病动物模型已成为衡量一个国家生物医药科研水平的标志。我校夏宁邵教授团队和浙江大学附属第一医院李君教授团队历经5年的协同攻关，终于建立了国际上首个高度模拟人类乙肝病毒（HBV）自然感染诱发的慢乙肝肝硬化小鼠模型。厦门大学公共卫生学院袁伦志博士生、浙江大学医学院附属第一医院江静博士和厦门大学公共卫生学院刘旋博士生为该论文共同第一作者。厦门大学夏宁邵教授、浙江大学附属第一医院李君教授和厦门大学程通副教授为该论文共同通讯作者。【Abstract】Objective： Developing a small animal model that accurately delineates the natural history of hepatitis B virus (HBV) infection and immunopathophysiology is necessary to clarify the mechanisms of host-virus interactions and to identify intervention strategies for HBV-related liver diseases. This study aimed to develop an HBV-induced chronic hepatitis and cirrhosis mouse model through transplantation of human bone marrow mesenchymal stem cells (hBMSCs). Design： Transplantation of hBMSCs into Fah -/- Rag2 -/- IL-2Rγc -/- SCID (FRGS) mice with fulminant hepatic failure (FHF) induced by hamster-anti-mouse CD95 antibody JO2 generated a liver and immune cell dual-humanized (hBMSC-FRGS) mouse. The generated hBMSC-FRGS mice were subjected to assessments of sustained viremia, specific immune and inflammatory responses and liver pathophysiological injury to characterize the progression of chronic hepatitis and cirrhosis after HBV infection. Results： The implantation of hBMSCs rescued FHF mice, as demonstrated by robust proliferation and transdifferentiation of functional human hepatocytes and multiple immune cell lineages, including B cells, T cells, NK cells, dendritic cells (DCs) and immune cell lineages, including B cells, T cells, NK cells, dendritic cells (DCs) and viremia and specific immune and inflammatory responses and showed progression to chronic hepatitis and liver cirrhosis at a frequency of 55% after 54 weeks. Conclusion： This new humanized mouse model recapitulates the liver cirrhosis induced by human HBV infection, thus providing research opportunities for understanding viral immune pathophysiology and testing antiviral therapies in vivo.this work was supported by the national Science and technology Major Project (grant nos. 2017ZX10304402, 2017ZX10203201 and 2018ZX09711003-005-003), the national natural Science Foundation of china(grant nos. 81672023, 81571818 and 81771996), the Scientific research Foundation of the State Key laboratory of Molecular Vaccinology and Molecular Diagnostics (grant no 2016ZY005), Zhejiang Province and State's Key Project of the research and Development Plan of china (grant nos 2017c01026 and 2016YFc1101304/3).该研究获得了传染病防治国家科技重大专项、新药创制国家科技重大专项和国家自然科学基金的资助