In 15 participants with hemophilia A treated with a single infusion of AAV5 vector containing the factor VIII gene, 7 who received 6×10
13
vector genomes per kilogram had a median factor VIII level ...of 20 IU per deciliter, and 6 who received 4×10
13
vg per kilogram had a median level of 13 IU per deciliter. Factor VIII levels decreased in years 2 and 3 of follow-up, but the median annualized rate of bleeding events among these 13 participants remained zero.
The anthraquinone compound rhein is a natural agent in the traditional Chinese medicine rhubarb. Preclinical studies demonstrate that rhein has anticancer activity. Treatment of a variety of cancer ...cells with rhein may induce apoptosis. Here, we report that rhein induces atypical unfolded protein response in breast cancer MCF-7 cells and hepatoma HepG2 cells. Rhein induces CHOP expression, eIF2α phosphorylation and caspase cleavage, while it does not induce glucose-regulated protein 78 (GRP78) expression in both MCF-7 and HepG2 cells. Meanwhile, rhein inhibits thapsigargin-induced GRP78 expression and X box-binding protein 1 splicing. In addition, rhein inhibits Akt phosphorylation and stimulates FOXO transactivation activity. Rhein induces Bim expression in MCF-7 and HepG2 cells, which can be abrogated by FOXO3a knockdown. Knockdown of FOXO3a or Bim abrogates rhein-induced caspase cleavage and apoptosis. The chemical chaperone 4-phenylbutyrate acid antagonizes the induction of FOXO activation, Bim expression and caspase cleavage by rhein, indicating that protein misfolding may be involved in triggering these deleterious effects. We conclude that FOXO3a-mediated up-regulation of Bim is a key mechanism underlying rhein-induced cancer cells apoptosis.
This paper proposes a new 5D chaotic system with the flux-controlled memristor. The dynamics analysis of the new system can also demonstrate the hyperchaotic characteristics. The design and analysis ...of adaptive synchronization for the new memristor-based chaotic system and its slave system are carried out. Furthermore, the modularized circuit designs method is used in the new chaotic system circuit implementation. The Multisim simulation and the physical experiments are conducted, compared, and matched with each other which can demonstrate the existence of the attractor for the new system.
-harboring microorganisms facilitate mineralization of organic phosphorus (P), while their role in the regulation of soil P turnover under P-limited conditions in
plantations is poorly understood. ...The aim of the present study was to investigate the effects of stand age and season on soil P fractions and
-harboring microorganism communities in a chronosequence of Chinese
plantations including 3, 19, and 58 years. The soil P fractions (i.e., CaCl
-P, citrate-P, enzyme-P, and HCl-P) varied seasonally, with the higher values observed in the rainy season. The concentrations of the fractions were higher in old plantation (OP) soils and lower in young planation (YP) soils in both seasons. The OTU abundances were negatively correlated with total available P concentration, while were positively correlated with alkaline phosphomonoesterase (ALP) activity at 0-10 cm soil depth. The results indicate that
-harboring microorganisms have great potential to mineralize organic P under P-poor conditions and highlights those microorganisms are indicators of P bioavailability in
plantations.
The clipping distortion, which generated in the orthogonal frequency division multiplexing systems will have a serious impact on the bit error performance, can be mitigated by clipping distortion ...recovery techniques. In this paper, we propose a compressed sensing (CS) based signal assisted Clipping Distortion Recovery (saCDR). At the transmitter, we use the clipping position to generate an auxiliary signal to transmit sparse information. The proposed method solves the problem that it is difficult to obtain the sparsity K when the receiver uses orthogonal matching pursuit (OMP) for clipping distortion recovery. At the receiver, we propose the location-assisted OMP algorithm (laOMP), which greatly reduces the system complexity and can still ensure good recovery performance under severe clipping scenarios. Simulation results show that the proposed method can obtain good bit error rate performance under different channels.
High peak-to-average power ratio (PAPR) is a concern in orthogonal frequency division multiplexing (OFDM) systems. Hadamard based selected mapping (HSLM) which uses Hadamard code as the phase ...sequence in selected mapping (SLM) is an attractive technique to reduce PAPR. But it requires sending side information (SI) to the receiver for each data block, and this results in a reduction in bandwidth efficiency. In this paper, we proposed a modified PAPR reduction method called semi-Hadamard based selected mapping (semi-HSLM) to decouple the phase information matrix into a phase rotation matrix for PAPR reduction and a SI matrix for side information hiding. We proposed a semi-hadamard matrix generation method to generate the phase rotation matrix, and designed a cyclic shift matrix as the SI matrix. Compared with the traditional HSLM, the semi-HSLM saves half of the phase storage and achieves good PAPR reduction performance.
Deficiency of phenylalanine hydroxylase causes phenylketonuria (PKU) with elevated phenylalanine (Phe) levels and associated neuropsychiatric and neurocognitive symptoms. Pegvaliase (PEGylated ...phenylalanine ammonia lyase) is an investigational agent to lower plasma Phe in adults with PKU. This study aimed to characterize the long-term efficacy, safety, and immunogenicity of pegvaliase in adults with PKU.
PAL-003 is an ongoing, open-label, long-term extension study of the pegvaliase dose-finding parent phase 2 studies. Participants continued the dose of pegvaliase from one of three parent studies, with dose adjustments to achieve a plasma Phe concentration between 60 and 600 μmol/L.
Mean (standard deviation SD) plasma Phe at treatment-naïve baseline for 80 participants in the parent studies was 1302.4 (351.5) μmol/L. In the 68 participants who entered the extension study, plasma Phe decreased 58.9 (39)% from baseline, to 541.6 (515.5) μmol/L at Week 48 of treatment. Plasma Phe concentrations ≤120 μmol/L, ≤360 μmol/L, and ≤ 600 μmol/L were achieved by 78.7, 80.0, and 82.5% of participants, respectively. Mean (SD) protein intake at baseline was 69.4 (40.4) g/day (similar to the recommended intake for the unaffected population) and remained stable throughout the study. All participants experienced adverse events (AEs), which were limited to mild or moderate severity in most (88.8%); the most common AEs were injection-site reaction (72.5%), injection-site erythema (67.5%), headache (67.5%), and arthralgia (65.0%). The AE rate decreased from 58.3 events per person-year in the parent studies to 18.6 events per person-year in the extension study.
Pegvaliase treatment in adults with PKU produced meaningful and persistent reductions in mean plasma Phe concentration with a manageable safety profile for most subjects that continued with long-term treatment.
ClinicalTrials.gov , NCT00924703. Registered June 18, 2009, https://clinicaltrials.gov/ct2/show/NCT00924703.
Beauty tea with special flavor can be affected by the degree of leafhopper puncturing. The present research adopted widely targeted metabolomics to analyze the characteristic metabolites of fresh tea ...leaves and beauty tea with different degrees of leafhopper puncturing. Low-puncturing beauty tea (LPBT) exhibited a superior quality. Altogether, 95 and 65 differential metabolites, including tea polyphenols, saccharides, and lipids, were identified from fresh leaves and beauty tea, respectively. The partial least squares regression (PLSR) analysis results showed that isomaltulose, theaflavic acid, and ellagic acid, may be the characteristic metabolites that form the different taste outlines of beauty tea. Based on odor activity values (OAVs) and partial least squares discriminant analysis (PLS-DA), dihydrolinalool and cis-linalool oxide were identified as characteristic volatile components, which may be essential for the formation of the different aroma characteristic of beauty tea. The results provide a theoretical basis for selecting raw materials, performing quality research, and developing beauty tea industrially.
Elderly patients with intertrochanteric fractures exhibit post-traumatic hidden blood loss (HBL). This study aimed to evaluate the efficacy and safety of reducing post-traumatic HBL via early ...intravenous (IV) tranexamic acid (TXA) intervention in elderly patients with intertrochanteric fracture.
A prospective randomized controlled study was conducted with 125 patients (age ≥ 65 years, injury time ≤ 6 h) who presented with intertrochanteric fracture from September 2018 and September 2019. Patients in the TXA group (n = 63) received 1 g of IV TXA at admission, whereas those in the normal saline (NS) group (n = 62) received an equal volume of saline. Hemoglobin (Hgb) and hematocrit (Hct) were recorded at post-traumatic admission (PTA) and on post-traumatic days (PTDs) 1-3. HBL was calculated using the Gross formula. Lower extremity venous ultrasound was performed to detect venous thrombosis.
Hgb on PTDs 2 and 3 was statistically higher in the TXA group than in the NS group. Hct and HBL on PTDs 1-3 were significantly less in the TXA group compared to the NS group. Preoperative transfusion rate was significantly lower in the TXA group compared with the NS group. There was no difference between the two groups with regard to the rates of complications.
Early IV TXA intervention could reduce post-traumatic HBL and pre-operative transfusion rate in elderly patients with intertrochanteric fractures without increasing the risk of venous thrombosis.
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