Background Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. Methods A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA) -mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. Results The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 mmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC 50 ] of 0.98 mmol/L. The viral RNA yield in cells treated with 10 mmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] Â 10 À4 vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 mmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37 t = 2.42, P < 0.05) and viral replication ([6.18 ± 0.95] Â 10 À4 vs. 1.00 ± 0.43, t = 3.98, P < 0.05). Conclusions Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.Original Article * P < 0.01). Vero cells were transfected with 0.8, 4, and 20 nmol/L ACE2-specific siRNAs or NSC siRNA by using the RNAiMax transfection reagent. At 48 h p.t., the cells were infected with pangolin CoV at an MOI of approximately 10. At 24 h p.i., CoV-infected cells were lysed in lysis buffer, and the RNA levels of ACE2, CoV, and b-actin were determined by qRT-PCR.

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In a 51-year-old female patient with intraepidermal neutrophilic IgA dermatosis (IEN) type of IgA pemphigus, circulating IgA, but not IgG, autoantibodies were detected to bind to the cell surface of the whole epidermis, being much stronger in the upper epidermis. In the patient's skin a heavy intraepidermal IgA staining was observed throughout the whole epidermis, accompanied by a weak IgG and a more prominent C3 staining. IgA from the patient's serum showed no reactivity either with epidermal proteins by immunoblot analysis, or with COS 7 cells transiently transfected with mammalian cell expression constructs containing full length human Dsc1, Dsc2 and Dsc3. Our patient's IgA specifically reacted with conformational epitopes of human desmoglein (Dsg) 1 but not Dsg 3, when studied in a previously established, here for IgA antibody detection modified enzyme-linked immunoabsorbent assay (ELISA) of baculovirus expression system. The immunoreactivity against keratinocyte cell surface was completely removed from the serum of the patient by pre-incubation with recombinant Dsg1 baculoprotein. This finding indicates that the sera possess only IgA antibodies against the extracellular domain of Dsg1 baculoprotein, but no antibodies against components of keratinocyte cell surface other than Dsg1. This is the first case of IgA pemphigus where Dsg1 has been identified as the autoantigen.

In Bioelectrical impedance measurement, the impedance accuracy is a very important parameter. With the analysis of general Digital Phase Sensitive Detection (DPSD) algorithm and its error, this paper presents an improved DPSD algorithm. In this method, it firstly decomposes the orthogonal signals which have passed through the networks, and then sums (minus) the relevant signals to get the parameters amplitude and phase. By this way, it can avoid errors caused by filtering operation in general DPSD algorithm. At last, the paper gives a simulation which can be hardware-based achieved. The result proves the effectiveness and feasibility of this improved method.

The calculation methods of the city emergy yield ratio (EYR), environmental load rate (ELR) and city environmental efficiency index (CEI) are defined based on the emergy analysis of city social- economic- environment complex systems. The change trends of environmental efficiency indexes are studied which is from 2003 to 2009 year of Jiaxing city. The results show that the EYR takes on a slow growth trend, from 1.17 to 1.23. The ELR takes on a growth trend also, from 5.14 to 6.99. But, the EYR average annual growth rate is only 0.66 percent which is much lower than the inflation of ELR, whose rate is 5.13 percent. In general, the CEI has a downward trend, from 0.23 to 0.18. Industrial restructuring in Jiaxing has achieved a considerable success. The study results show that, however, the environment has a high pressure still from the social economic development. The task of industrial restructuring has a long road to walk.

Hangzhou urban agglomeration (HzUA) plays a decisive role in Zhejiang province and even in the Changjiang delta. Whose core is Hangzhou, the main body is Hangzhou district and Huzhou, Jiaxing, Shaoxing city is the vice center. It is an important subject to evaluate sustainability of the HzUA quantitatively.The article constructs the city ecological efficiency index (CEI) with the emergy analysis theory, analyzes quantitatively the resources supply and environmental capacity of the HzUA. The case study shows that the CEIs of the four major cities are all not high, among 0.15-0.19. Especially, the CEI of Jiaxing is the minimum, although whose renewable natural resources of unit area is the maximum. It is worth attention. To realize the HzUA steady, harmonious and healthy development, two aspects measures must be adopted, namely, adjust industrial structure and strengthen environmental protection.

Contrast sensitivity measurement is widely used in clinical ophthalmology to evaluate visual function of the human eye, and of great significance for early diagnosis and identification of ophthalmic diseases. On the basis of contrast sensitivity definition, current measurement method was analyzed. By analyzing the existing principles and shortcomings of the human eye contrast sensitivity methods, a new method for generating observation targets of contrast sensitivity was proposed. By using double optical path design idea with integrating sphere and self-developed brightness adjustment systems, two beams of uniform light with specific luminance could be produced. With subsequent reuse of the optical path, accurate measurement of eye contrast sensitivity could be achieved, and calibration of contrast sensitivity tester widely used in clinical practice could be solved by developing assistant transfer tools. Moreover, output parameters of this method could be precisely adjusted according to the need as a result it ccould achieve real-time control and calibration. The research result has set the foundation for future establishment of visual threshold measuring device which is especially suitable for scientific and experimental research in clinical ophthalmology and metrology.

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