Enterovirus 71 induces pyroptosis of human neuroblastoma SH-SY5Y cells through miR-146a/ CXCR4 axis.

Enterovirus 71 (EV71) is a predominant causative pathogen of hand-foot-and-mouth disease (HFMD) in children. Compared with other HFMD-associated viruses, EV71 tends to induce more severe neurological complications and even death. However, the detailed mechanism of EV71 causes nervous system disorder is still unclear. In this study, we found that EV71 induced the GSDMD/NLRP3-mediated pyroptosis of SH-SY5Y cells through up-regulated miR-146a. Through bioinformatic analysis, we identified C-X-C chemokine receptor type 4 (CXCR4) as the potential target of miR-146a. We noticed that the expression of CXCR4 was regulated by miR-146a during EV71 infection. Moreover, our results show that over-expression of CXCR4 attenuated EV71-induced pyroptosis of SY-SY5Y cells. These results reveal a previously unrecognized mechanism in which EV71 induces nervous system cells damage through regulating miR-146a/CXCR4 mediated pyroptosis.

First Report of Anthracnose Caused by Colletotrichum boninense on Spotted laurel in China.

Spotted laurel (Aucuba japonica 'Variegata') is an evergreen shrub native to China, Korea and Japan, prized for its foliage of green and golden yellow mottled foliage (Fang and Hu 1990). In November 2020, about 50% of spotted laurel in Jiangxi Academy of Forestry (28°44'10''N, 115°49'1.62"E) at Jiangxi province were observed to have anthracnose-like symptoms. The typical symptoms were tended to coalesce to form initially dark brown specks on the leaves, which developed to nearly circular spots of the diameter no more than 1.2 cm and might join to large irregular spots. The spots were grayish white at the center, purple brown at the border and surrounded by a yellow halo. To isolate and identify the pathogen, 15 leaves with typical symptoms were sampled. Isolation and morphological analysis were performed following the method of Ding et al. (2021). Among 40 fungal isolates, 33 showed the same morphological characters. The colony on PDA was umbonate pink-gray in the center surrounding by white margin, the reverse was greyish-cream. The average mycelial growth rate was ca. 0.8 mm per day at 25±1°C on PDA. The conidia were hyaline, aseptate, straight, apex round and base round, mean ± SD = 16.50±3.75 µm × 7.50±2.50 µm. For further confirmation of the identity, six genes, including ITS, GAPDH, ACT, TUB2, CAL and CHS-1 (Damm et al. 2012) were amplified and sequenced. The sequences of rDNA-ITS, GAPDH, ACT, TUB2, CAL and CHS-1 of 1SJ5 were deposited in GenBank as: OM988385, ON009367-ON009371. Phylogenetic analysis based on the above six genes showed that isolates formed a single clade with the strains of Colletotrichum boninense. Pathogenicity tests of isolate 1SJ5 were carried out on the leaves in the field. The mycelial plugs of isolate 1SJ5 were applied on punctured leaves of A. japonica using a sterile needle in field. Inoculation with only a PDA plug served as controls. 14 -21 days, symptoms like those observed in the field, developed on the inoculated plants but not on the controls. The fungus was re-isolated from the margins of the leaf spots and identified by morphological and molecular characters. C. boninense has been reported as causing anthracnose on a broad range of hosts including strawberry (Bi et al. 2017), Eucalyptus robusta (Zhang and Zhu 2018), Alcantarea imperialis (Meneses et al. 2019), and so on. To our knowledge, this is the first report of leaf anthracnose on A. japonica caused by C. boninense in China and our findings will be useful for its management.

Monitoring of viral myocarditis injury using an energy-confined upconversion nanoparticle and nature-inspired biochip combined CRISPR/Cas12a-powered biosensor.

The early diagnosis and timely intervention of viral myocarditis urgently require a noninvasive detection approach. Therefore, we present a CRISPR/Cas12a-powered biosensor that integrates an exceptionally efficient upconversion luminescent resonance energy transfer (LRET) with a nature-inspired biochip to determine a golden-standard cardiac biomarker (cardiac troponin I). First, a unique sandwich-structured energy-confined upconversion nanoparticle (acting as the energy donor) is synthesized to dramatically reinforce the LRET's ability. Such a structural improvement endows a relatively high quenching efficiency (as much as 93.8%) toward the surface acceptors and enhances the working adaption in complicated biological media. Moreover, a three-dimensional photonic crystal fabricated using a self-assembly of nanospheres is employed to construct a biochip interface, under which the upconversion luminescence is prominently boosted to approximately 27-fold to achieve signal amplification. Finally, the newly developed luminescence sensing method exhibits remarkable assay performance after introducing these attempts into a dual-aptamer-regulated CRISPR/Cas12a system to transduce the target. More importantly, this biosensor can primarily be a quite useful tracer tool to allow dynamic monitoring of the entire myocardial injury process in a coxsackievirus B3 infected mouse model, paving an attractive venue for medical diagnostic techniques.

[Non-coding RNAs in viral myocarditis].

Viral myocarditis (VMC) is a disease characterized by inflammation of myocardial cells caused by viral infection. Since the pathogenesis mechanism of VMC has not been fully elucidated, the diagnosis and treatment of this disease remains extremely challenging. Non-coding RNAs (ncRNAs) are a class of RNAs that do not encode proteins. An increasing number of studies have shown that ncRNAs are involved in regulating the occurrence and development of VMC, thus providing potential new targets for the treatment and diagnosis of VMC. This review summarizes the possible roles of ncRNAs in the pathogenesis and diagnosis of VMC revealed recently.

Effect of irradiation of silicon photodiode arrays for ITER radial x-ray camera investigated by measuring response and current-voltage characteristics.

The response and current-voltage (I-V) characteristics of irradiated and non-irradiated silicon photodiode arrays (SPDAs) for use in the International Thermonuclear Experimental Reactor camera are measured and compared. Irradiation experiments are carried out using a uranium-zirconium hydride pulsed reactor. The total equivalent 1 MeV neutron fluence with energy above 0.01 MeV is ∼9.89 × 1013 n cm-2. The output signal of the irradiated SPDA (XD2) shows a nonlinear trend during the irradiation experiment. The final signal is about 5.6% of the original one in the visible light region. Tests on the Experimental Advanced Superconducting Tokamak (EAST) show that the XD2 signal is 70%-80% of that of a non-irradiated SPDA (XD3). This indicates that irradiated SPDAs can still observe plasma radiation after exposure to 9.89 × 1013 n cm-2 neutron fluence. However, because the neutron fluence of external camera detectors will reach 1.4 × 1016 n cm-2 in D-T phase, the SPDAs might become unusable at some point. The responsivity ratio of irradiated and non-irradiated SPDAs is about 4%-20% from 7 to 13 keV. The degradation of responsivity is related to the energy level. After irradiation, the reversed dark current rises from 0.1 to 10 nA to a level of around 1 µA. In terms of tests of XD2 on EAST, zero bias is a good working condition for irradiated SPDAs.

Efficient Synthesis of Hydroxytyrosol from l-3,4-Dihydroxyphenylalanine Using Engineered Escherichia coli Whole Cells.

Hydroxytyrosol is a high-value-added compound with a variety of biological and pharmacological activities. In this study, a whole-cell catalytic method for the synthesis of hydroxytyrosol was developed: aromatic amino acid aminotransferase (TyrB), l-glutamate dehydrogenase (GDH), α-keto acid decarboxylase (PmKDC), and aldehyde reductase (YahK) were co-expressed in Escherichia coli to catalyze the synthesis of hydroxytyrosol from l-3,4-dihydroxyphenylalanine (l-DOPA). The plasmids with different copy numbers were used to balance the expression of the four enzymes, and the most appropriate strain (pRSF- yahK- tyrB and pCDF- gdh- Pmkdc) was identified. After determination of the optimum temperature (35 °C) and pH (7.5) for whole-cell catalysis, the yield of hydroxytyrosol reached 36.33 mM (5.59 g/L) and the space-time yield reached 0.70 g L-1 h-1.

Integrated waste load allocation for river water pollution control under uncertainty: a case study of Tuojiang River, China.

This paper presents a bi-level optimization waste load allocation programming model under a fuzzy random environment to assist integrated river pollution control. Taking account of the leader-follower decision-making in the water function zones framework, the proposed approach examines the decision making feedback relationships and conflict coordination between the river basin authority and the regional Environmental Protection Agency (EPA) based on the Stackelberg-Nash equilibrium strategy. In the pollution control system, the river basin authority, as the leader, allocates equitable emissions rights to different subareas, and the then subarea EPA, as the followers, reallocates the limited resources to various functional zones to minimize pollution costs. This research also considers the uncertainty in the water pollution management, and the uncertain input information is expressed as fuzzy random variables. The proposed methodological approach is then applied to Tuojiang River in China and the bi-level linear programming model solutions are achieved using the Karush-Kuhn-Tucker condition. Based on the waste load allocation scheme results and various scenario analyses and discussion, some operational policies are proposed to assist decision makers (DMs) cope with waste load allocation problem for integrated river pollution control for the overall benefits.

Waste load equilibrium allocation: a soft path for coping with deteriorating water systems.

Waste load allocation is always regarded as another efficient approach comparing with the technology-based approach to improve the water quality. This paper proposes a bi-level multi-objective optimization model for optimally allocating the waste load of a river basin incorporating some concerns (i) the allocation equity from the regional authority, (ii) maximal benefits from the subareas along the river, and (iii) the Stackelberg-Nash-Cournot equilibrium strategy between the upper and lower decision makers. Especially, a novel Gini coefficient for measuring the load allocation equity is defined by considering the economic level and waste water quantity. The applicability and effectiveness of the proposed model is demonstrated through a practical case based on the Tuojiang River, which is a typical basin with diversified industrial waste discharges in western China. Some operational suggestions are developed to assist the decision makers' cope with deteriorating water systems.