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Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health 1 . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 – 10 . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96–98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013–2016, predominantly in horseshoe bats ( Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth. Analysis of viral samples from deceased piglets shows that a bat coronavirus was responsible for an outbreak of fatal disease in China and highlights the importance of the identification of coronavirus diversity and distribution in bats in order to mitigate future outbreaks of disease.

Klebsiella pneumoniae found in the normal flora of the human oral and intestinal tract mainly causes hospital-acquired infections but can also cause community-acquired infections. To date, most clinical trials of vaccines against K. pneumoniae have ended in failure. Furthermore, no single conserved protein has been identified as an antigen candidate to accelerate vaccine development. In this study, we identified five outer membrane proteins of K. pneumoniae , namely, Kpn_Omp001, Kpn_Omp002, Kpn_Omp003, Kpn_Omp004, and Kpn_Omp005, by using reliable second-generation proteomics and bioinformatics. Mice vaccinated with these five KOMPs elicited significantly higher antigen-specific IgG, IgG1, and IgG2a. However, only Kpn_Omp001, Kpn_Omp002, and Kpn_Omp005 were able to induce a protective immune response with two K. pneumoniae infection models. These protective effects were accompanied by the involvement of different immune responses induced by KOMPs, which included KOMPs-specific IFN-γ-, IL4-, and IL17A-mediated immune responses. These findings indicate that Kpn_Omp001, Kpn_Omp002, and Kpn_Omp005 are three potential Th1, Th2, and Th17 candidate antigens, which could be developed into multivalent and serotype-independent vaccines against K. pneumoniae infection.

Hepatocellular carcinoma (HCC) remains challenging due to the lack of efficient therapy. Promoting degradation of certain cancer drivers has become an innovative therapy. The nuclear transcription factor sine oculis homeobox 1 (SIX1) is a key driver for the progression of HCC. Here, we explored the molecular mechanisms of ubiquitination of SIX1 and whether targeting SIX1 degradation might represent a potential strategy for HCC therapy. Through detecting the ubiquitination level of SIX1 in clinical HCC tissues and analyzing TCGA and GEPIA databases, we found that ubiquitin specific peptidase 1 (USP1), a deubiquitinating enzyme, contributed to the lower ubiquitination and high protein level of SIX1 in HCC tissues. In HepG2 and Hep3B cells, activation of EGFR-AKT signaling pathway promoted the expression of USP1 and the stability of its substrates, including SIX1 and ribosomal protein S16 (RPS16). In contrast, suppression of EGFR with gefitinib or knockdown of USP1 restrained EGF-elevated levels of SIX1 and RPS16. We further revealed that SNS-023 (formerly known as BMS-387032) induced degradation of SIX1 and RPS16, whereas this process was reversed by reactivation of EGFR-AKT pathway or overexpression of USP1. Consequently, inactivation of the EGFR-AKT-USP1 axis with SNS-032 led to cell cycle arrest, apoptosis, and suppression of cell proliferation and migration in HCC. Moreover, we showed that sorafenib combined with SNS-032 or gefitinib synergistically inhibited the growth of Hep3B xenografts in vivo. Overall, we identify that both SIX1 and RPS16 are crucial substrates for the EGFR-AKT-USP1 axis-driven growth of HCC, suggesting a potential anti-HCC strategy from a novel perspective.

Organic nonvolatile transistor memories (ONVMs) using a hybrid spiro [fluorene-9,7′-dibenzo [c, h] acridine]-5′-one (SFDBAO)/polystyrene (PS) film as bulk-heterojunction-like tunneling and trapping elements were fabricated. From the characterization of the 10% SFDBAO/PS based on ONVM, a sterically hindered small-molecule SFDBAO with rigid orthogonal configuration and a donor–acceptor (D-A) structure as a molecular-scale charge storage element demonstrated significantly higher charge trapping ability than other small-molecule materials such as C60 and Alq3. The ONVM based on 10% SFDBAO/PS presents ambipolar memory behaviors with a wide memory window (146 V), a fast-switching speed (20 ms), an excellent retention time (over 5 × 104 s), and stable reversibility (36 cycles without any noticeable decay). By applying different gate voltages, the above ONVM shows reliable four-level data storage characteristics. The investigation demonstrates that the strategical bulk-heterojunction-like tunneling and trapping elements composed of small-molecule materials and polymers exhibit promising potential for high-performance ambipolar ONVMs.

Purpose To design and investigate a novel technique of percutaneous posterior transdiscal oblique screw fixation with lateral interbody fusion. Methods CT scans of 45 patients were collected and imported into Mimics software for three-dimensional (3D) reconstruction. Cylinders were drawn to simulate the trajectory of the oblique screw. Six measurements were obtained for each unit to design a right size cage: a the distance between the intersection of the simulated trajectory of the screw with the inferior border of the upper vertebra and its anteroinferior corner; b the distance between the intersection of the simulated trajectory of the screw with the superior border of the inferior vertebra and its anterosuperior corner; h the height of the intervertebral space; θ the angle between simulated trajectory of screw and the upper endplate of inferior vertebra; uw: the width of the inferior endplate of upper vertebra; iw: the width of upper endplate of inferior vertebra. Three intact adult fresh-frozen cadaveric specimens were obtained, percutaneous posterior transdiscal oblique screw fixation was performed under X-ray apparatus, and interbody cage was implanted by assistance with special self-retaining retractor system and endoscope. Results According to the results of data measured from 3D images, trapezoid shape interbody cages with suitable size were designed. Percutaneous posterior oblique screw fixation with lateral interbody fusion was performed on three cadaveric specimens successfully. Conclusion Using specially designed trapezoid shape interbody cages, assisted by intra-operative image intensification and endoscope, it is feasible to perform percutaneous posterior transdiscal oblique screw fixation with lateral interbody fusion technique.

MQTT protocol is a publish/subscribe message protocol based on TCP/IP protocol. It has the characteristics of low power consumption, scalability, openness and simplicity. HTTP protocol is an open and low-cost request/reply message protocol based on TCP/IP protocol. It is the main protocol of Internet communication, but it is not suitable for the environment of computing, processing and bandwidth limited. In this paper, a simplified wireless sensor network node was designed based on MQTT protocol. The node was designed to use the Arduino development environment and use the WiFi for networking. It has the characteristics of simple structure, low power consumption and so on. The design can be widely used in smart home, environmental monitoring and medical applications, and is the main contents of the Internet of things (IoT).

To investigate the Fe^2＋ effects on root tips in rice plant, experiments were carried out using border cells in vitro. The border cells were pre-planted in aeroponic culture and detached from root tips. Most border cells have a long elliptical shape. The number and the viability of border cells in situ reached the maxima of 1600 and 97.5%, respectively, at 20---25 mm root length. This mortality was more pronounced at the first 1-12 h exposure to 250 mg/L Fe^2＋ than at the last 12-36 h. After 36 h, the cell viability exposed to 250 mg/L Fe^2＋ decreased to nought, whereas it was 46.5% at 0 mg/L Fe^2＋. Increased Fe^2＋ dosage stimulated the death of detached border cells from rice cultivars. After 4 h Fe^2＋ treatment, the cell viabilities were _〉80% at 0 and 50 mg/L Fe^2＋ treatment and were 〈62% at 150, 250 and 350 mg/L Fe^2＋ treatment; The viability of border cells decreased by 10% when the Fe^2＋ concentration increased by 100 mg/L. After 24 h Fe^2＋ treatment, the viabilities of border cells at all the Fe^2＋ levels were 〈65%; The viability of border cells decreased by 20% when the Fee＋ concentration increased by 100 mg/L. The decreased viabilities of border cells indicated that Fe^2＋ dosage and treatment time would cause deadly effect on the border cells. The increased cell death could protect the root tips from toxic harm. Therefore, it may protect root from the damage caused by harmful iron toxicity.

A multi-residue method using gas chromatography (GC) and gas chromatography!mass spectrometry (GC/MS) was developed for the determination of severalorganochlorine pesticides in three crude drugs: Astragali Radix (黃耆), ZizyphiSativae Fructus (大棗), and Zingiberis Rhizoma (乾薑). The pesticides including ｖ-BHC, β-BHC, γ-BHC, δ-BHC, 2,4'-DDE, 4,4'-DDE, 2,4'-DDT and 4,4'-DDT weredetermined using a modified extraction and refining procedure, separated by acapillary column DB-1, 0.25 μm, 0.25 mm * 30 M), observed with an electron capturedetector (ECD). amid confirmed by GC/MS if necessary. The precision and accuracy weresatisfactory. Calibration graphs of eight pesticides were constructed in the rangeof 0.25-2.0 - μg/ml and their correlation coefficients (r) were in the range of0.995-0.998. - Recovery studies were performed at the 1.0 ppm spike level of eachpesticide in these three crude drugs. Recovery rates were 66.4-98.0% for AstragaliRadix. 36.7-86.9% for Zizyphi Sativae Fructus, and 31.1-109.7% for Zingiberis Rhi