LAS0811: From Combinatorial Chemistry to Activation of Antioxidant Response Element

The antioxidant response element (ARE) and its transcription factor, nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), are potential targets for cancer chemoprevention. We sought to screen small molecules synthesized with combinatorial chemistry for activation of ARE. By high-throughput screening of 9400 small molecules from 10 combinatorial chemical libraries using HepG2 cells with an ARE-driven reporter, we have identified a novel small molecule, 1,2-dimethoxy-4,5-dinitrobenzene (LAS0811), as an activator of the ARE. LAS0811 upregulated the activity of NAD(P)H:quinone oxidoreductase 1 (NQO1), a representative antioxidative enzyme regulated by ARE. It enhanced production of an endogenous reducing agent, glutathione (GSH). In addition, LAS0811 induced expression of heme oxygenase 1 (HO1), which is an ARE-regulated enzyme with anti-inflammatory activity. Furthermore, LAS0811 reduced cell death due to the cytotoxic stress of a strong oxidant, t-butyl hydroperoxide (t-BOOH). Mechanistically, LAS0811 upregulated the expression of Nrf2 and promoted its translocation into the nuclei leading to subsequent ARE activation. Taken together, LAS0811 is a novel activator of the ARE and its associated detoxifying genes and, thus, a potential agent for cancer chemoprevention

Chaotic Non-Orthogonal Matrix-Based Encryption for Secure OFDM-PONs

We propose and experimentally demonstrate a novel encryption scheme to enhance the physical layer security in broad-cast passive optical networks (PONs). We exploit, for the first time, a new dimension using non-orthogonality for encryption. Different from the conventional masking of data, the proposed chaotic non-orthogonal matrix (CNOM) can also dynamically scramble the number of subcarriers in an orthogonal frequency division multi-plexing (OFDM) signal while maintaining the same bandwidth to further deceive potential eavesdroppers. By simultaneously using faster-than-Nyquist signaling and redundant precoding, the proposed scheme can achieve the compromise between spectral efficiency (SE) and resilience against system impairments, while increasing the overall key space. We then carry out a proof-of-concept experiment to verify the feasibility of the proposed CNOM-based encryption. Results showed that the transmission performance could be improved in addition to the security enhancement

Decentralized Multi-Floor Exploration by a Swarm of Miniature Robots Teaming with Wall-Climbing Units

In this paper, we consider the problem of collectively exploring unknown and dynamic environments with a decentralized heterogeneous multi-robot system consisting of multiple units of two variants of a miniature robot. The first variant-a wheeled ground unit-is at the core of a swarm of floor-mapping robots exhibiting scalability, robustness and flexibility. These properties are systematically tested and quantitatively evaluated in unstructured and dynamic environments, in the absence of any supporting infrastructure. The results of repeated sets of experiments show a consistent performance for all three features, as well as the possibility to inject units into the system while it is operating. Several units of the second variant-a wheg-based wall-climbing unit-are used to support the swarm of mapping robots when simultaneously exploring multiple floors by expanding the distributed communication channel necessary for the coordinated behavior among platforms. Although the occupancy-grid maps obtained can be large, they are fully distributed. Not a single robotic unit possesses the overall map, which is not required by our cooperative path-planning strategy.Comment: Accepted for publication in IEEE-MRS 2019, Rutgers University, New Brunswick (NJ), US

The national and subnational prevalence of cataract and cataract blindness in China:a systematic review and meta-analysis

Background: Cataract is the second leading cause of visual impairment and the first of blindness globally. However, for the most populous country, China, much remains to be understood about the scale of cataract and cataract blindness. We aimed to investigate the prevalence of cataract and cataract blindness in China at both the national and subnational levels, with projections till 2050. Methods: In this systematic review and meta-analysis, China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM-SinoMed), PubMed, Embase, and Medline were searched using a comprehensive search strategy to identify all relevant articles on the prevalence of cataract or cataract blindness in Chinese population published from January 1990 onwards. We fitted a multilevel mixed-effects meta-regression model to estimate the prevalence of cataract, and a random-effects meta-analysis model to pool the overall prevalence of cataract blindness. The United Nations Population Division (UNPD) data were used to estimate and project the number of people with cataract and cataract blindness from 1990 to 2050. According to different demographic and geographic features in the six geographic regions in China, the national numbers of people with cataract in the years 2000 and 2010 were distributed to each region. Results: In males, the prevalence of any cataract (including post-surgical cases) ranged from 6.71% (95% CI = 5.06-8.83) in people aged 45-49 years to 73.01% (95% CI = 65.78-79.2) in elderly aged 85-89 years. In females, the prevalence of any cataract increased from 8.39% (95% CI = 6.36-10.98) in individuals aged 45-49 years to 77.51% (95% CI = 71.00-82.90) in those aged 85-89 years. For age-related cataract (ARC, including post-surgical cases), in males, the prevalence rates ranged from 3.23% (95% CI = 1.51-6.80) in adults aged 45-49 years to 65.78% (95% CI = 46.72-80.82) in those aged 85-89 years. The prevalence of ARC in females was 4.72% (95% CI = 2.22-9.76) in the 45-49 years age group and 74.03% (95% CI = 56.53-86.21) in the 85-89 years age group. The pooled prevalence rate of cataract blindness (including post-surgical cases) by best corrected visual acuity (BCVA)<0.05 among middle-aged and older Chinese was 2.30% (95% CI = 1.72-3.07), and those of cataract blindness by BCVA<0.10 and cataract blindness by presenting visual acuity (PVA)<0.10 were 2.56% (95% CI = 1.94-3.38) and 4.51% (95% CI = 3.53-5.75) respectively. In people aged 45-89 years, the number of any cataract cases was 50.75 million (95% CI = 42.17-60.37) in 1990 and 111.74 million (95% CI = 92.94-132.84) in 2015, and that of ARC rose from 35.77 million (95% CI = 19.81-59.55) in 1990 to 79.04 million (95% CI = 44.14-130.85) in 2015. By 2050, it is projected that the number of people (45-89 years of age) affected by any cataract will be 240.83 million (95% CI = 206.07-277.35), and that of those with ARC will be 187.26 million (95% CI = 113.17-281.23). During 2000 and 2010, South Central China consistently owed the most cases of any cataract, whereas Northwest China the least. Conclusions: The prevalence of cataract and cataract blindness in China was unmasked. In the coming decades, cataract and cataract blindness will continue to be a leading public-health issue in China due to the ageing population. Future work should be prioritized to the promotion of high-quality epidemiological studies on cataract

Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism

<p>Abstract</p> <p>Background</p> <p>Two active compounds, baicalein and its glycoside baicalin were found in the dried root of <it>Scutellaria baicalensis </it>Georgi, and reported to be neuroprotective <it>in vitro </it>and <it>in vivo</it>. This study aims to evaluate the protective effects of baicalein on the rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to parkinsonism.</p> <p>Methods</p> <p>Cell viability and cytotoxicity were determined by MTT assay. The degree of nuclear apoptosis was evaluated with a fluorescent DNA-binding probe Hoechst 33258. The production of reactive oxidative species (ROS) and loss of mitochondrial membrane potential (ΔΨm) were determined by fluorescent staining with DCFH-DA and Rhodanmine 123, respectively. The expression of Bax, Bcl-2, cleaved caspase-3 and phosphorylated ERK1/2 was determined by the Western blots.</p> <p>Results</p> <p>Baicalein significantly increased viability and decreased rotenone-induced death of SH-SY5Y cells in a dose-dependent manner. Pre- and subsequent co-treatment with baicalein preserved the cell morphology and attenuated the nuclear apoptotic characteristics triggered by rotenone. Baicalein antagonized rotenone-induced overproduction of ROS, loss of ΔΨm, the increased expression of Bax, cleaved caspase-3 and phosphorylated ERK1/2 and the decreased expression of Bcl-2.</p> <p>Conclusion</p> <p>The antioxidative effect, mitochondrial protection and modulation of anti-and pro-apoptotic proteins are related to the neuroprotective effects of baicalein against rotenone induced cell death in SH-SY5Y cells.</p

An improved method for the rescue of of recombinant Newcastle disease virus

Reverse genetics has been used to generate recombinant Newcastle disease virus with enhanced immunogenic properties for vaccine development. The system, which involves co-transfecting the viral antigenomic plasmid with three helper plasmids into a T7 RNA polymerase-expressing cell to produce viral progenies, poses a great challenge. We have modified the standard transfection method to improve the transfection efficiency of the plasmids, resulting in a higher titer of virus progeny production. Two transfection reagents (i.e., lipofectamine and polyethylenimine) were used to compare the transfection efficiency of the four plasmids. The virus progenies produced were quantitated with flow cytometry analysis of the infectious virus unit. The modified transfection method increased the titer of virus progenies compared with that of the standard transfection method

Prevalence of epilepsy in China between 1990 and 2015:A systematic review and meta-analysis

Background: Epilepsy is a major neurological disorder that affects approximately 65 million people worldwide. Globally, the burden of epilepsy is not evenly distributed, with more than 80% of sufferers residing in low- and middle-income countries. This study estimates the burden of epilepsy in mainland China from 1990 to 2015 and explores the variations of burden by age and gender. Methods: We conducted a systematic review of the peer-reviewed literature from 1990 to 2015 using Chinese and English academic databases (CNKI, WanFang, VIP and PubMed) to identify population- based prospective studies on the prevalence of epilepsy in mainland Chinese. Multilevel mixed-effects logistic regression was used to estimate the prevalence of lifetime epilepsy (LTE), and restricted cubic regression splines were applied to model the functional forms of the non-linear effects of age and LTE prevalence. Random-effects meta-analysis was used to obtain the pooled prevalence of 1-year active epilepsy (AE), 2-year AE and 5-year AE separately. To estimate the number of people with LTE and AE in the years 1990, 2000, and 2015, LTE and AE prevalence were multiplied by the total population of mainland China of the corresponding year. Findings:Analyses were conducted using 39 prevalence studies that met the inclusion criteria and comprised 77 separate data points (37 on LTE, 16 on 1-year AE, 12 on 2-year AE and 12 on 5-year AE). In 1990, the prevalence of LTE ranged from 1.31‰ (95% CI = 0.85- 2.00) in the 0-4 age group to 2.42‰ (95% confidence interval CI = 1.60-3.65) in the 30-34 age group. By 2015, the LTE prevalence had increased to 4.57‰ (95% CI = 2.52-8.27) in the 0-4 group and 8.43‰ (95% CI = 4.71-15.04) in the 30-34 group. Over the 25-year period, the overall prevalence of LTE had steadily increased by 259%, from 1.99‰ (95% CI = 1.31-3.02) in 1990 to 7.15‰ (95% CI = 3.98-12.82) in 2015. The rates of increase were similar across the whole age spectrum, fluctuating around 250%. Between 1990 and 2015, the total number of people with LTE in mainland China increased by 328%, from 2.30 million (95% CI = 1.51-3.49) in 1990 to 9.84 million (95% CI = 5.48-17.64) in 2015. The pooled 1-year, 2-year, and 5-year AE prevalence were 3.79‰ (95% CI = 3.31-4.34), 4.08‰ (95% CI = 3.41-4.89) and 4.19‰ (95% CI = 3.42-5.15). Conclusions The burden of LTE in China has increased substantially between 1990 and 2015, with the prevalence of LTE having more than doubled and the number of people with LTE more than tripled. The large amount of AE cases in China calls for optimal management and treatment. More high-quality epidemiological studies on LTE and AE prevalence are still neede