The chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) controls cellular quiescence by hyperpolarizing the cell membrane during diapause in the crustacean Artemia

Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (V-mem) and quiescence. We found that V-mem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas V-mem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high V-mem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and up-regulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and V-mem in the Artemia model

A line search filter approach for the system of nonlinear equations

AbstractSome constrained optimization approaches have been recently proposed for the system of nonlinear equations (SNE). Filter approach with line search technique is employed to attack the system of nonlinear equations in this paper. The system of nonlinear equations is transformed into a constrained nonlinear programming problem at each step, which is then solved by line search strategy. Furthermore, at each step, some equations are treated as constraints while the others act as objective functions, and filter strategy is then utilized. In essence, constrained optimization methods combined with filter technique are utilized to cope with the system of nonlinear equations

硫酸氢氯吡格雷联合西洛他唑治疗糖尿病四肢并发症的临床疗效观察

Objective: To observe efficacy and safety of domestic clopidogrel cilostazol in treatment of diabetic limbs complications. Methods: 120 cases of diabetic patients with limb complications were randomly selected, including 60 cases of lower extremity arterial disease (PAD) and 60 patients with diabetic peripheral neuropathy (DPN) patients. According to the random number list, they were randomly divided into treatment group of 60 patients, DPN and PAD were given mecobalamin 0. 5mg / times , lipoic acid 500mg / d, alprostadil 10ug / d, DPN patients while giving epalrestat 50mg / times. The control group while giving cilostazol 0.1g, 2 times / d, plus clopidogrel treatment groups 150mg / d in the control group, based on continuous treatment for 8 weeks. Clinical evaluation of the two groups was made and conduction velocity of MNCV and SNCV was compared. Results: Analysis of DPN subgroup showed that the treatment group was efficient (73.4% vs 46.7%, P = 0.035), total efficiency (93.3% vs 73.3%, P = 0.038) were significantly higher, PAD subgroup analysis showed the efficiency of the treatment group was (70% vs 43.3%, P = 0.035), total efficiency (93.3% vs 73.3%, P = 0.038) were significantly higher. MNCV CKS nerve (54.3 ± 4.8 vs 50.5 ± 5.1) and the peroneal nerve (34.7 ± 3.2 vs 30.9 ± 3.4) conduction velocity improved more significantly. SNCV CKS nerve (43.4 ± 4.9 vs 38.2 ± 3.8) and the peroneal nerve (35.1 ± 5.6 vs 32.9 ± 5.4) conduction velocity, the treatment group improved significantly than the control group. PAD subgroup analysis, ABI degree of improvement (0.9 ± 0.3 vs 0.8 ± 0.3), dorsal blood flow (35.2±3.6 vs31.5±4.2), popliteal artery blood flow (64.2±5.6 vs 58.4±7.4) were better than the control group. Compared with clopidogrel, cilostazol did not increase in adverse events during treatment process. Conclusion: Clopidogrel cilostazol treatment of diabetic limb complications becomes safe and effective treatment of DPN and PAD, which can be used as a combination therapy.目的  观察国产氯吡格雷联合西洛他唑治疗糖尿病四肢并发症的有效性及安全性。方法  随机入选120例糖尿病四肢并发症患者，其中糖尿病周围神经病变（DPN）患者60例，下肢动脉病变（PAD）60例。按照随机数列表，随机分为治疗组60例，DPN及PAD均给予甲钴胺0. 5mg /次，硫辛酸500mg/d，前列地尔10ug/d，DPN患者同时给予依帕司他50mg /次。对照组同时给予西洛他唑0.1g，2次/d，治疗组在对照组基础上加上氯吡格雷首次600mg，后150mg/d连续7d，后改为75mg/d连续8周。评价两组的临床疗效及MNCV和SNCV传导速度。结果  DPN亚组分析显示，治疗组显效率（73.4% vs 46.7%, P=0.035）、总有效率（93.3% vs 73.3%，P=0.038）显著高于对照组，PAD亚组分析显示，治疗组显效率（70% vs 43.3%, P=0.035）、总有效率（93.3% vs 73.3%，P=0.038）显著高于对照组。MNCV中正中神经（54.3±4.8 vs 50.5±5.1）及腓总神经（34.7±3.2 vs 30.9±3.4）传导速度改善更为明显。SNCV中正中神经（43.4±4.9 vs 38.2±3.8）及腓总神经(35.1±5.6 vs 32.9±5.4)传导速度，治疗组改善亦较对照组更明显。PAD亚组分析显示，ABI改善程度（0.9±0.3 vs 0.8±0.3）、足背动脉血流速度（35.2±3.6 vs31.5±4.2），腘动脉血流量（64.2±5.6 vs 58.4±7.4）改善均优于对照组。治疗过程中氯吡格雷相比于西洛他唑并不增加不良事件。结论  氯吡格雷联合西洛他唑治疗糖尿病四肢并发症变安全、有效，可作为治疗DPN及PAD的联合治疗方案

Geometric density of states of electronic structures for local responses: Phase information from the amplitudes of STM measurement

Electronic band structures underlie the physical properties of crystalline materials, their geometrical exploration renovates the conventional cognition and brings about novel applications. Inspired by geometry phases, we introduce a geometric amplitude named as the geometric density of states (GDOS) dictated by the differential curvature of the constant-energy contour. The GDOS determines the amplitude of the real-space Green's function making it attain the ultimate expression with transparent physics. The local responses of crystalline materials are usually formulated by the real-space Green's function, so the relevant physics should be refreshed by GDOS. As an example of local responses, we suggest using scanning tunneling microscopy (STM) to characterize the surface states of three-dimensional topological insulator under an in-plane magnetic field. The GDOS favors the straightforward simulation of STM measurement without resorting to Fourier transform of the real-space measurement, and also excavates the unexplored potential of STM measurement to extract the phase information of wavefunction through its amplitude, i.e., the spin and curvature textures. Therefore, the proposed GDOS deepens the understanding of electronic band structures and is indispensable in local responses, and it should be universal for any periodic systems.Comment: 6 pages, 2 figure

Prediction of large esophageal varices in cirrhotic patients using classification and regression tree analysis

OBJECTIVES: Recent guidelines recommend that all cirrhotic patients should undergo endoscopic screening for esophageal varices. That identifying cirrhotic patients with esophageal varices by noninvasive predictors would allow for the restriction of the performance of endoscopy to patients with a high risk of having varices. This study aimed to develop a decision model based on classification and regression tree analysis for the prediction of large esophageal varices in cirrhotic patients. METHODS: 309 cirrhotic patients (training sample, 187 patients; test sample 122 patients) were included. Within the training sample, the classification and regression tree analysis was used to identify predictors and prediction model of large esophageal varices. The prediction model was then further evaluated in the test sample and different Child-Pugh classes. RESULTS: The prevalence of large esophageal varices in cirrhotic patients was 50.8%. A tree model that was consisted of spleen width, portal vein diameter and prothrombin time was developed by classification and regression tree analysis achieved a diagnostic accuracy of 84% for prediction of large esophageal varices. When reconstructed into two groups, the rate of varices was 83.2% for high-risk group and 15.2% for low-risk group. Accuracy of the tree model was maintained in the test sample and different Child-Pugh classes. CONCLUSIONS: A decision tree model that consists of spleen width, portal vein diameter and prothrombin time may be useful for prediction of large esophageal varices in cirrhotic patient