Proteasome activator 28A: A clinical biomarker and pharmaceutical target in acute cerebral infarction therapy

Purpose: To determine the dynamic changes in serum levels of PA28α in patients with acute cerebral infarction (ACI), and to investigate its correlation with infarct size and neurological deficit of the disease. Methods: A total of 100 ACI patients and 100 healthy volunteers were recruited from The First Affiliated Hospital of Xinxiang Medical University as case and control groups, respectively. Their serum levels of PA28α were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The potential of PA28α in predicting the incidence of ACI was assessed by plotting ROC curves. Multivariate logistic regression analysis was conducted to investigate the risk factors of ACI. In addition, an ACI model in rats was established, and ACI rats were classified into 1, 3, 5, 7 and 14 day subgroups based on the duration post-ACI. Rats in the sham group served as control. Results: Serum level of PA28α was significantly higher in ACI patients than in controls. Moreover, the serum level of PA28α at admission was positively correlated to the NIHSS score and infarct volume of ACI patients. The level of PA28α in ACI rats gradually increased post-ACI, reaching a peak on day 7. The number of apoptotic brain cells in ACI rats gradually decreased after ACI. In addition, PA28α level was negatively correlated to the number of apoptotic brain cells in ACI rats (R2 = 0.5148, p < 0.001). Conclusion: The serum level of PA28α is elevated in ACI patients, and is positively correlated to infarct volume and neurological deficit of the disease. The dynamic change in brain cell apoptosis post-ACI is negatively correlated to the serum level of PA28α. These findings may provide theoretical basis for the diagnosis and treatment of ACI

Development of a human-size magnetic particle imaging device for sentinel lymph node biopsy of breast cancer

In this study, a novel human-size handheld magnetic particle imaging (MPI) system was developed for the high-precision detection of sentinel lymph nodes for breast cancer. The system consisted of a highly sensitive home-made MPI detection probe, a set of concentric coils pair for spatialization, a solenoid coil for uniform excitation at 8 [email protected] mT, and a full mirrored coil set positioned far away from the scanning area. The mirrored coils formed an extremely effective differential pickup structure which suppressed the system noise as high as 100 dB. The different combination of the inner and outer gradient current made the field free point (FFP) move in the Z direction with a uniform intensity of 0.54T/m, while the scanning in the XY direction was implemented mechanically. The third-harmonic signal of the Superparamagnetic Iron Oxide Nanoparticles (SPIONs) at the FFP was detected and then reconstructed synchronously with the current changes. Experiment results showed that the tomographic detection limit was 30 mm in the Z direction, and the sensitivity was about 10 μg Fe SPIONs at 40 mm distance with a spatial resolution of about 5 mm. In the rat experiment, 54 μg intramuscular injected SPIONs were detected successfully in the sentinel lymph node, in which the tracer content was about 1.2% total injected Fe. Additionally, the effective detection time window was confirmed from 4 to 6 min after injection. Relevant clinical ethics are already in the application process. Large mammalian SLNB MPI experiments and 3D preoperative SLNB imaging will be performed in the future

Enhanced multiclass SVM with thresholding fusion for speech-based emotion classification

As an essential approach to understanding human interactions, emotion classification is a vital component of behavioral studies as well as being important in the design of context-aware systems. Recent studies have shown that speech contains rich information about emotion, and numerous speech-based emotion classification methods have been proposed. However, the classification performance is still short of what is desired for the algorithms to be used in real systems. We present an emotion classification system using several one-against-all support vector machines with a thresholding fusion mechanism to combine the individual outputs, which provides the functionality to effectively increase the emotion classification accuracy at the expense of rejecting some samples as unclassified. Results show that the proposed system outperforms three state-of-the-art methods and that the thresholding fusion mechanism can effectively improve the emotion classification, which is important for applications that require very high accuracy but do not require that all samples be classified. We evaluate the system performance for several challenging scenarios including speaker-independent tests, tests on noisy speech signals, and tests using non-professional acted recordings, in order to demonstrate the performance of the system and the effectiveness of the thresholding fusion mechanism in real scenarios.Peer ReviewedPreprin

Nanomedicines for Overcoming Cancer Drug Resistance

Clinically, cancer drug resistance to chemotherapy, targeted therapy or immunotherapy remains the main impediment towards curative cancer therapy, which leads directly to treatment failure along with extended hospital stays, increased medical costs and high mortality. Therefore, increasing attention has been paid to nanotechnology-based delivery systems for overcoming drug resistance in cancer. In this respect, novel tumor-targeting nanomedicines offer fairly effective therapeutic strategies for surmounting the various limitations of chemotherapy, targeted therapy and immunotherapy, enabling more precise cancer treatment, more convenient monitoring of treatment agents, as well as surmounting cancer drug resistance, including multidrug resistance (MDR). Nanotechnology-based delivery systems, including liposomes, polymer micelles, nanoparticles (NPs), and DNA nanostructures, enable a large number of properly designed therapeutic nanomedicines. In this paper, we review the different mechanisms of cancer drug resistance to chemotherapy, targeted therapy and immunotherapy, and discuss the latest developments in nanomedicines for overcoming cancer drug resistance

Halogen–Metal Exchange on Bromoheterocyclics with Substituents Containing an Acidic Proton via Formation of a Magnesium Intermediate

A selective and practical bromine–metal exchange on bromoheterocyclics bearing substituents with an acidic proton under non-cryogenic conditions was developed by a simple modification of an existing protocol. Our protocol of using a combination of i-PrMgCl and n-BuLi has not only solved the problem of intermolecular quenching that often occurred when using alkyl lithium alone as the reagent for halogen–lithium exchange, but also offered a highly selective method for performing bromo–metal exchange on dibrominated arene compounds through chelation effect

Structural Characterization of Polysaccharides from Dendrobium officinale and Their Effects on Apoptosis of HeLa Cell Line

Dendrobium officinale is a widely used medicinal plant in China with numerous bio-activities. However, the main structure and anti-tumor activity of the polysaccharides from this plant have not been investigated. In this study, we elucidated the main structure of polysaccharides purified with DEAE and Sephadex G-25 from Dendrobium officinale grown under different planting conditions. In addition, the anti-tumor activity was tested via MTT assays. The results showed that the polysaccharides of Dendrobium officinale grown under different conditions were almost the same, with slight differences in the branched chain; both polysaccharide fractions consisted of (1→4)-linked mannose and (1→4)-linked glucose, with an O-acetyl group in the mannose. After degradation, the polysaccharide fractions from wild plants showed significant anti-proliferation activity in HeLa cells. The fractions F1 and F3 induced apoptosis by up-regulating the expression of ERK, JNK, and p38. We concluded that polysaccharides from Dendrobium officinale planted in the wild exhibit significant anti-tumor effects only after being degraded to smaller molecular weight species. The planting mode is a significant factor in the pharmacological activity of Dendrobium officinale. We advise that the planting conditions for Dendrobium officinale should be changed

Nitrite oxidizing bacteria (NOB) contained in influent deteriorate mainstream NOB suppression by sidestream inactivation

Sidestream sludge treatment approaches have been developed in recent years to achieve mainstream nitrite shunt or partial nitritation, where NOB are selectively inactivated by biocidal factors such as free nitrous acid (FNA) or free ammonium (FA) in a sidestream reactor. The existence of NOB in raw wastewater has been increasingly realized and could pose critical challenge to stable NOB suppressions in those systems. This study, for the first time, evaluated the impact of influent NOB on the NOB suppressions in a mainstream nitrite shunt system achieved through sidestream sludge treatment. An over 500-day sequential batch reactor operation with six experimental phases rigorously demonstrated the negative effects of influent NOB on mainstream NOB control. Continuously seeding of NOB contained in influent stimulated NOB community shifts, leading to different extents of ineffective NOB suppression. The role of primary wastewater treatment in NOB removal from raw wastewater was also investigated. Results suggest primary settling and High Rate Activated Sludge system could remove a large part of NOB contained in raw wastewater. Primary treatment for raw wastewater is necessary for ensuring stable mainstream NOB suppressions

Rebar corrosion and its interaction with concrete degradation in reinforced concrete sewers

Concrete corrosion, as a major issue in sewer management, has attracted considerable research. In comparison, the corrosion of reinforcing steel bar (rebar) is not well understood. Particularly, fundamental knowledge of rebar corrosion and its interactions with concrete corrosion/cracking is largely lacking. This study investigated rebar corrosion and concrete degradation using reinforced concrete coupons exposed in a pilot sewer system. The physical-chemical corrosion characteristics were investigated in local regions; the nature of rebar rusts was analyzed using the advanced mineral analytical techniques, including Scanning Electron Microscope (SEM), Energy Dispersive X-ray Spectroscopy (EDS) and X-ray Diffraction (XRD); further, the interactions between rebar corrosion and concrete corrosion/cracking were elucidated by characterizing the microstructure and element distribution in interfacial areas using Mineral Liberation Analysis (MLA). The rebar corrosion products were found to be iron oxides, oxyhydroxides, chlorides, sulfides and sulfates. The predominant rebar corrosion reactions varied with exposure time and the development of concrete corrosion. When concrete corrosion reached rebar surface, the cracking of the concrete cover was influenced by multiple effects, including the macro-cracking induced by the corrosion products expansion, and the micro-cracking accelerated by the dissolution, diffusion and deposition of Fe derived from rebar rusts at the concrete corrosion front. A conceptual model elucidating rebar corrosion and the complex interactions between rebar corrosion and concrete degradation is proposed to support the development of corrosion prevention and refurbishment strategies for reinforced concrete sewers