Characterization of host substrates of SARS-CoV-2 main protease

The main protease (Mpro) plays a crucial role in coronavirus, as it cleaves viral polyproteins and host cellular proteins to ensure successful replication. In this review, we discuss the preference in the recognition sequence of Mpro based on sequence-based studies and structural information and highlight the recent advances in computational and experimental approaches that have aided in discovering novel Mpro substrates. In addition, we provide an overview of the current understanding of Mpro host substrates and their implications for viral replication and pathogenesis. As Mpro has emerged as a promising target for the development of antiviral drugs, further insight into its substrate specificity may contribute to the design of specific inhibitors

Fluoroquinolone therapy for bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae

AbstractBackground/PurposeFor extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae infections, carbapenems are recommended as first line therapy, and clinical data on the therapeutic efficacy of fluoroquinolones (FQs) is limited. This study compares the efficacy of FQs and carbapenems for bloodstream infections caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae.MethodsBetween 2008 and 2010, adults with ESBL-producing E. coli or K. pneumoniae bacteremia at two medical centers were reviewed. Adults receiving definitive FQ or carbapenem therapy were compared in a propensity score-matched analysis, and 30-day mortality was the primary endpoint.ResultsA total of 299 patients were eligible. Patients receiving a FQ (n = 24), either ciprofloxacin or levofloxacin, had a lower 30-day mortality rate than those with carbapenem therapy (8.3%, 2/24 vs. 23.3%, 64/275; p = 0.12). Multivariate regression analysis revealed that a critical illness [Pitt bacteremia score ≥ 4 points; odds ratio (OR), 7.09; p < 0.001], rapidly fatal underlying disease (OR, 5.73; p < 0.001), and hospital-associated infection (OR, 2.57; p = 0.01) were independently associated with 30-day mortality. By contrast, FQ definitive therapy was a protective factor compared with carbapenems (OR, 0.18; p = 0.04). There were 72 matched cases with carbapenem therapy in a propensity score-matched analysis, and a difference in the 30-day mortality rate of two groups was noted (8.3% vs. 29.2%; p = 0.05).ConslusionFor ESBL-producing E. coli or K. pneumoniae bacteremia, ciprofloxacin or levofloxacin, if active in vitro, can be considered as a carbapenem-sparing alternative

A balanced homodyne detector for high-rate Gaussian-modulated coherent-state quantum key distribution

We discuss excess noise contributions of a practical balanced homodyne detector in Gaussian-modulated coherent-state (GMCS) quantum key distribution (QKD). We point out the key generated from the original realistic model of GMCS QKD may not be secure. In our refined realistic model, we take into account excess noise due to the finite bandwidth of the homodyne detector and the fluctuation of the local oscillator. A high speed balanced homodyne detector suitable for GMCS QKD in the telecommunication wavelength region is built and experimentally tested. The 3dB bandwidth of the balanced homodyne detector is found to be 104MHz and its electronic noise level is 13dB below the shot noise at a local oscillator level of 8.5*10^8 photon per pulse. The secure key rate of a GMCS QKD experiment with this homodyne detector is expected to reach Mbits/s over a few kilometers.Comment: 22 pages, 11 figure

Mitigating Routing Misbehavior Using Ant-Tabu-Based Routing Algorithm for Wireless Ad-Hoc

Summary Routing is a key factor in the design of modern communication networks, especially in wireless ad-hoc networks (WANs). In WANs, both selfish and malicious nodes are misbehaving nodes and cause severely routing and security problems. Selfish nodes may drop routing and data packets and malicious nodes may redirect the packets to another routing path or launch denial-of-service (DoS) attacks. In this paper, an efficient routing algorithm is proposed, Ant-Tabu-Based Routing Algorithm (ATBRA), to mitigate selfish problem and reduce routing overheads. In ATBRA, both the concepts of ant-based routing algorithm and Tabu search are applied. We compare the performance of the proposed scheme with that of DSR in terms of two performance metrics: successful delivery rate (SDR) and routing overhead (RO). By comparisons, we notice that the proposed algorithm outperforms DSR in all two categories. The simulation results also indicate that the proposed algorithm is more efficient than DSR

A Real-Time Pothole Detection Approach for Intelligent Transportation System

In recent years, fast economic growth and rapid technology advance have led to significant impact on the quality of traditional transport system. Intelligent transportation system (ITS), which aims to improve the transport system, has become more and more popular. Furthermore, improving the safety of traffic is an important issue of ITS, and the pothole on the road causes serious harm to drivers’ safety. Therefore, drivers’ safety may be improved with the establishment of real-time pothole detection system for sharing the pothole information. Moreover, using the mobile device to detect potholes has been more popular in recent years. This approach can detect potholes with lower cost in a comprehensive environment. This study proposes a pothole detection method based on the mobile sensing. The accelerometer data is normalized by Euler angle computation and is adopted in the pothole detection algorithm to obtain the pothole information. Moreover, the spatial interpolation method is used to reduce the location errors from global positioning system (GPS) data. In experiments, the results show that the proposed approach can precisely detect potholes without false-positives, and the higher accuracy is performed by the proposed approach. Therefore, the proposed real-time pothole detection approach can be used to improve the safety of traffic for ITS

Prognosis of Nasopharyngeal Carcinoma in the Elderly is Worse than in Younger Individuals–Experience of a Medical Institute

SummaryPurposeWe aimed to evaluate outcomes of the elderly (>65 years) by comparing with younger (<40 years) patients after treatments for nasopharyngeal carcinoma (NPC).Materials and methodsWe retrospectively obtained clinical data from charts for 23 older and 21 younger patients in whom NPC was diagnosed and who underwent curative managements during 2007 and 2011. Occurrence of local recurrence, distant metastasis, and death from any cause were recorded as endpoints. Cox proportional hazards regression was applied to determine age effects on survival risks after adjusting for the potential confounders.ResultsOlder patients more commonly received a diagnosis of chronic diseases than the younger patients (56.5% versus 23.8%, p = 0.036), whereas they were less likely to have received intensive treatments for NPC. After adjusting for medical history and neoadjuvant chemotherapy, older age was the only significant predictor in the study cohort for overall survival and progression-free survival. The adjusted hazard ratio (HR) for death from all causes in older patients was 6.3 (95% confidence interval [CI] = 1.3–30.2), and the adjusted HR for disease progression in older patients was 10.9 (95% CI = 2.3–50.6).ConclusionAging was the only independent prognostic risk factor in this study cohort. Medical history and treatment variations could not fully explain the difference in prognosis. Our results strengthen the need to ameliorate toxicities and improve supportive care for older patients with a diagnosis of NPC

Prevention and early management of carotid blowout syndrome for patients receiving head and neck salvage boron neutron capture therapy (BNCT)

Background/purpose The incidence rate of oral and pharyngeal cancers in Taiwan has increased gradually over the past few decades. The standard treatment strategy for oral and pharyngeal cancers includes surgery or radiotherapy, with concurrent chemotherapy in certain types of tumors. Unfortunately, in-field recurrence is sometimes inexorable. Furthermore, re-irradiation of the recurrence site may cause severe complications due to the tolerance of normal tissue to radiation therapy. One fatal complication is carotid blowout syndrome (CBS). Boron neutron capture therapy (BNCT) is a new modality of radiation therapy, which is also mentioned as targeted radiotherapy. It is a feasible treatment that has the potential to spare normal tissue from being damaged by irradiation while simultaneously treating the primary tumor. In this presentation, we will share our experience with BNCT in treating recurrent head and neck cancers, as well as the prevention and management of CBS. Materials and methods We evaluated 4 patients with head and neck cancers treated by BNCT in Taiwan. All patients had undergone surgery previously and had received postoperative concurrent chemoradiotherapy. Results The 4 patients in this study were diagnosed with head and neck malignancies. The median follow-up period after the first course of BNCT was 15.1 months. After BNCT, 2 patients developed impending CBS, and 1 of them died. The remaining 3 patients survived until the last date of follow-up. Conclusion Pre-BNCT carotid artery evaluation through computed tomography angiography and early intervention if necessary is crucial when treating patients with recurrent head and neck cancers by BNCT

The 3D-tomography of the nano-clusters formed by Fe-coating and annealing of diamond films for enhancing their surface electron field emitters

[[abstract]]The Fe-coating and H2-annealed processes markedly increased the conductivity and enhanced the surface electron field emission (s-EFE) properties for the diamondfilms. The enhancement on the s-EFE properties for the diamondfilms is presumably owing to the formation of nano-graphite clusters on the surface of the films via the Fe-to-diamond interaction. However, the extent of enhancement varied with the granular structure of the diamondfilms. For the microcrystalline (MCD)films, the s-EFE process can be turned on at (E0)MCD = 1.9 V/μm, achieving a large s-EFE current density of (Je)MCD = 315 μA/cm2 at an applied field of 8.8 V/μm. These s-EFE properties are markedly better than those for Fe-coated/annealed ultrananocrystalline diamond(UNCD)films with (E0)UNCD = 2.0 V/μm and (Je)UNCD = 120 μA/cm2. The transmission electron microscopy showed that the nano-graphite clusters formed an interconnected network for MCDfilms that facilitated the electron transport more markedly, as compared with the isolated nano-graphitic clusters formed at the surface of the UNCDfilms. Therefore, the Fe-coating/annealing processes improved the s-EFE properties for the MCDfilms more markedly than that for the UNCDfilms. The understanding on the distribution of the nano-clusters is of critical importance in elucidating the authentic factor that influences the s-EFE properties of the diamondfilms. Such an understanding is possible only through the 3D-tomographic investigations.[[journaltype]]國外[[ispeerreviewed]]Y[[booktype]]電子版[[countrycodes]]US