Role of L-Arginine on the Expression of Coagulation Factor VIII Gene.

Objective: To explore the key sites in which L-arginine affects the expression of human coagulation factor VIII gene, and to create new drug targets for the treatment of hemophilia. Methods: A total of 5 human FVIII genes (A1, A2, A3, C1 and C2) with B domain deletion were transfected into human umbilical vein endothelial cells (HUVECs) as promoters. Run-on assay and ELISA analysis were performed to observe the driving effect of each domain gene on chloramphenicol acetyl transferase (CAT) gene transcription and expression, and the effect of L-arginine on each promoter. Results: In co-culture with L-arginine, transcriptional expression of the CAT gene was not detected in the PCAT3-Basic group (negative control without promoters), PA3-CAT3-Enhancer group or PC1-CAT3-Enhancer group. The transcriptional expression of CAT gene in the PCAT3-Control group (positive control with promoters) and PA1-CAT3-Enhancer group was unchanged compared with the non-L-arginine intervention, while the transcriptional expression of CAT gene in the PA2-CAT3-Enhancer group was significantly enhanced. Conclusions: A1 and A2 domain genes had promoter function and could initiate the transcription and expression of CAT gene, but A3, C1 and C2 domain genes could not. Moreover, L-arginine can significantly enhance transcription and expression of human coagulation factor VIII via A2 domain.

Investigation on abnormal gene loci of a Chinese pedigree with hereditary combined deficiency of blood coagulation factor XI, XII, and protein S.

OBJECTIVE: In order to clarify the interaction mechanism, the phenotype and abnormal gene loci of FXI, FXII, and PS were investigated in this study. METHODS: Chinese pedigree with hereditary combined deficiency of coagulation factor (F) XI, FXII, and PS was enrolled in our study. Activated partial thromboplastin time (APTT), partial thromboplastin time (PT), FXI:C, FXII:C, and protein S (PS):C were determined using the one-stage coagulation method. FXI:antigen (Ag), FXII:Ag, and PS:Ag were detected using enzyme-linked immunosorbent assay (ELISA). Exons and introns of the FXI, FXII, and PS genes were amplified by polymerase chain reaction (PCR), and gene sequencing results were analyzed using Chromas software. RESULTS: A deletion of two bases located in introns A-149 and-150 within the FXI gene of the proband, his father, wife, and both sons. A missense variant in exon 14 (GGT â†’ AGT, Gly542Ser) within FXII of the proband, his parents, and both sons. Four variants in exon 4 within the PS gene of all members of the pedigree: GTT â†’ GTG (Val46Val), CGC â†’ CTC (Arg49Leu), CGT â†’ CAT (Arg60His), and CAG â†’ TAG (Gln61stop). CONCLUSIONS: None of the pedigree members showed a tendency for bleeding or thrombosis. Therefore, we speculated that the lack of coagulation factors counteracted the lack of PS, restoring the balance between the coagulation and anticoagulation systems. Another possible explanation is that these defects individually have only partial penetrance.

From Supramolecular Species to Self-Templated Porous Carbon and Metal-Doped Carbon for Oxygen Reduction Reaction Catalysts.

The preparation of carbon materials usually involves the decomposition of precursors and the reorganization of the as-generated fragments. However, the cleavage of bonds and the simultaneous formation of new bonds at nearly the same positions prevents effective yet precise fabrication. Herein, a supramolecular precursor, cucurbit[6]uril, that contains multiple bonds with distinct bond strengths is proposed to decouple the twin problem of simultaneous bond cleavage and formation, allowing multistage transformations to hierarchical porous carbon and metal-doped carbon in a single yet effective pyrolysis step without the need of a template or additional purification. As a proof-of-concept, the Fe-doped carbon electrocatalysts realized a Pt/C-like half-wave potential of 0.869 V vs. RHE and small Tafel slope of 51.3 mV dec-1 in oxygen reduction reaction.

Activating Inert Metallic Compounds for High-Rate Lithium-Sulfur Batteries Through In Situ Etching of Extrinsic Metal.

Surface reactions constitute the foundation of various energy conversion/storage technologies, such as the lithium-sulfur (Li-S) batteries. To expedite surface reactions for high-rate battery applications demands in-depth understanding of reaction kinetics and rational catalyst design. Now an in situ extrinsic-metal etching strategy is used to activate an inert monometal nitride of hexagonal Ni3 N through iron-incorporated cubic Ni3 FeN. In situ etched Ni3 FeN regulates polysulfide-involving surface reactions at high rates. Electron microscopy was used to unveil the mechanism of in situ catalyst transformation. The Li-S batteries modified with Ni3 FeN exhibited superb rate capability, remarkable cycling stability at a high sulfur loading of 4.8 mg cm-2 , and lean-electrolyte operability. This work opens up the exploration of multimetallic alloys and compounds as kinetic regulators for high-rate Li-S batteries and also elucidates catalytic surface reactions and the role of defect chemistry.

Enhanced Electrochemical Kinetics on Conductive Polar Mediators for Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries have been recognized as promising substitutes for current energy-storage technologies owing to their exceptional advantage in energy density. The main challenge in developing highly efficient and long-life Li-S batteries is simultaneously suppressing the shuttle effect and improving the redox kinetics. Polar host materials have desirable chemisorptive properties to localize the mobile polysulfide intermediates; however, the role of their electrical conductivity in the redox kinetics of subsequent electrochemical reactions is not fully understood. Conductive polar titanium carbides (TiC) are shown to increase the intrinsic activity towards liquid-liquid polysulfide interconversion and liquid-solid precipitation of lithium sulfides more than non-polar carbon and semiconducting titanium dioxides. The enhanced electrochemical kinetics on a polar conductor guided the design of novel hybrid host materials of TiC nanoparticles grown within a porous graphene framework (TiC@G). With a high sulfur loading of 3.5 mg cm-2 , the TiC@G/sulfur composite cathode exhibited a substantially enhanced electrochemical performance.

Role of Ca2+, Calnexin and Calreticulin in Platelet from Adult Patients with Chronic Immune Thrombocytopenic Purpura.

BACKGROUND: Adult chronic immune thrombocytopenia (chronic ITP) is a common autoimmune hemorrhagic disease characterized by decreased platelet production and increased platelet destruction, leading to thrombocytopenia. In this study, Ca2+, calnexin (CNX) and calreticulin (CRT) within platelets from adult patients with chronic ITP were investigated. METHODS: Platelets were isolated from blood specimen collected from 20 adult patients with chronic ITP and 20 healthy volunteers. Ca2+, CNX and CRT were determined by flow cytometry, and the results were analyzed with EXPO32 ADC software. RESULTS: Flow cytometry showed the expressions of Ca2+ (74.19±19.40% vs 22.79±10.47%) was elevated (P<0.05). However, CNX (15.10±7.32% vs 41.79±14.45%) and CRT (25.11±12.66% vs 38.58±12.02%) were decreased markedly in platelets from adult patients with chronic ITP (P<0.05 compared with healthy volunteers). CONCLUSION: Based on enhanced expression of Ca2+ and attenuated expression of CNX and CRT in patients with chronic ITP, Ca2+ concentration and its associated down-regulated proteins may be important regulatory signals in the pathogenesis of chronic ITP.

[Changes of light response indicators and its impact factors of Larix principis-rupprechtii on Saihanba Forest Farm, China.] / å¡žç½•ååŽåŒ—è½å¶æ¾é’ˆå¶å ‰å“åº”æŒ‡æ ‡å˜åŒ–è§„å¾‹åŠå ¶å½±å“å› ç´ .

We examined the differences of maximum light use efficiency (LUEmax), most effective light intensity (PARe), light compensation point (LCP) and light saturation point (LSP) in diffe-rent vertical positions and different phenological periods of tree crown in Larix principis-rupprechtii plantation in Saihanba Mechanical Forest Farm of Hebei Province. We analyzed the main influencing factors for all the variables. The results showed that LUEmax increased with the increasing crown depth, and that PARe, LCP and LSP decreased with the increasing crown depth. Such a result indicated that upper crown had higher utilization efficiency to strong light and that the lower crown was more efficient to adapt to weak light environment. During the leaf development in the growth period, the LUEmax approximately increased except in July, while the changes of other photosynthe-tic-light factors showed a tendency of unimodal curve. Environmental factors were significantly correlated with the indices of light response, mainly due to the stress reaction of leaf stomata to surrounding environment. Understanding the spatial and seasonal changes of the photosynthetic-light indicators was important for formulating scientific management measures, optimizing stand structure, improving local microenvironment and maximizing forest productivity.

[Prediction of crown leaf mass per area for young Larix olgensis plantation]. / äººå·¥é•¿ç™½è½å¶æ¾å¹¼é¾„æž—æ ‘å† æ¯”å¶é‡.

Leaf mass per area (LMA) is an important parameter in the construction of the ecosystem process models. Accurate prediction of the dynamic validation of canopy LMA is of significance to improve the accuracy of ecosystem process models. We conducted vertical whorl-by-whorl sampling and analyzed LMA in different seasons for Larix olgensis plantation in Maoershan in Shangzhi, Heilongjiang Province, China. We analyzed the vertical and developmental variations of LMA and their main effective factors, established the dynamic prediction model of LMA for young L. olgensis plantation. The results showed that the LMA decreased with the increases of relative depth into crown (RDINC) in the vertical direction of the crown. The range of LMA in the vertical direction after leaf expanded was significantly larger than that during leaf expanding. During the different development periods of leaves, LMAs increased first and then remained stable, and this trend gra-dually weakened with the increases of crown depth. The Ra2 values were lower than 0.6 when RDINC or DOY were used as the single variable to model LMA, but were increased by 0.19 when both of them being used, and the model performed well in validation (ME=0.54 g·m-2, MAE=5.74 g·m-2). LMA varied across different crown whorls and different leaf development periods. The LMA model constructed with RDINC and DOY could well describe the vertical and temporal variations of LMA. The simulation of crown LMA provided a basis for clarifying crown development and a foundation for the establishment of ecological process model.

The diagnostic profile of rare acute myelomegakaryoblastic leukemia.

Acute myelomagakaryocytic leukemia is a diagnostic and therapeutic challenge owing to its heterogeneity and overlapping features with other types of acute leukemia. In order to build a diagnostic profile, we analyzed the biological, clinical and hematologic characteristics of acute myelomagakaryocytic leukemia. We found that, in three patients diagnosed with acute myelomagakaryocytic leukemia, there were two types of leukemia cells. One type was myeloblastic with positive peroxidase (POX) stainig and the expression of antigens CD13 and CD33. The other type was megakaryoblastic with negative POX staining and the expression of antigens CD36, CD41, CD42a and CD61. Three patients displayed the same cytogenetic abnormality, a (9: 22) translocation. Among the three patients with RT-PCR, two patients displayed BCR-ABL fusion gene amplification and one patient showed a previously undescribed OTT-MAL fusion gene amplification.

Apoptosis in platelets from adult patients with chronic idiopathic thrombocytopenic purpura.

Adult chronic idiopathic thrombocytopenic purpura (cITP) is a chronic and usually life-long haemorrhagic disorder in which enhanced platelet destruction and weakened platelet production lead to thrombocytopenia. Platelets were isolated from blood samples collected from 40 adult patients with cITP and 40 healthy volunteers. Mitochondrial membrane potential (ΔΨm) and plasma membrane phosphatidylserine externalization were determined by flow cytometry, and activation of caspase-3 and expressions of Bax, Bak and Bcl-xL were analysed by western blotting. Flow cytometry showed increased mitochondrial depolarization and lower ΔΨm in platelets from adult patients with cITP. In addition, plasma membrane phosphatidylserine externalization was observed on platelets from adult patients with cITP, but rarely from healthy volunteers. Western blot analysis of platelet proteins revealed that, in adult cITP patients, caspase-3 was activated, which cleaved gelsolin and to release a 47-kDa fragment. Moreover, the expressions of Bax and Bak were elevated, and Bcl-xL was decreased markedly in platelets from adult patients with cITP. Our findings reveal, based on loss of mitochondrial membrane potential (Δψm), phosphatidylserine exposure, caspase-3 activation, enhanced expression of Bax and Bak, and attenuated expression of Bcl-xL, that platelet death in the pathogenesis of thrombocytopenia in chronic ITP in adults is apoptotic.