Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020

Meconium peritonitis due to fetal appendiceal perforation: two case reports and a brief review of the literature

Abstract Background Meconium peritonitis is an infrequent congenital disease usually caused by perforation of the fetal digestive tract. Meconium peritonitis resulting from intrauterine appendiceal perforation has been rarely reported and is often overlooked during pregnancy. We herein report two cases of fetal appendiceal perforation. Case presentation Two neonates were found to have intestinal distension and gradually increasing ascites antenatally. After birth, diagnostic abdominal punctures revealed meconium peritonitis. Urgent surgery showed both neonates had developed gangrenous appendicitis in utero. Pathological examination supported the diagnosis of fetal appendiceal perforation in both neonates, and one also had deformity of cecal duplication. In the present report, we also review the presentation, diagnosis, pathology, management, and recent literature of fetal appendiceal perforation. Conclusion Meconium peritonitis due to fetal appendiceal perforation is extremely rare, and preoperative diagnosis is almost impossible. However, clinicians should be aware of abnormal gastrointestinal manifestations in the fetus during the antenatal examination. For neonates with severe meconium peritonitis, an early operation with careful intraoperative exploration is necessary

ACE: A Routing Algorithm Based on Autonomous Channel Scheduling for Bluetooth Mesh Network

The Internet of Things (IoT) interconnects massive cyber-physical devices (CPD) to provide various applications, such as smart home and smart building. Bluetooth Mesh is an emerging networking technology, which can be used to organize a massive network with Bluetooth Low Energy (BLE) devices. Managed-flooding protocol is used in Bluetooth Mesh to route the data packets. Although it is a highly desirable option when data transmission is urgent, it is inefficient in a larger and denser mesh network due to the collisions of broadcast data packets. In this paper, we introduce ACE: a Routing Algorithm based on Autonomous Channel Scheduling for Bluetooth Mesh Network. ACE relies on the existing Bluetooth Mesh messages to distribute routes without additional traffic overhead and conducts a beacon-aware routing update adaptively as the topology evolves. In ACE, BLE channel resources can be efficiently utilized by a channel scheduling scheme for each node locally and autonomously without any neighborly negotiation. We implement ACE on the nRF52840 from Nordic Semiconductor and evaluate its effectiveness on our testbed. Compared to the Bluetooth Mesh, our experiments proved that ACE could reduce the end-to-end latency by 16%, alleviate packets collisions issues, and increase the packet delivery ratio (PDR) by 30% under heavy traffic. Moreover, simulation results verified that ACE has better scalability when the size and density of networks become larger and denser

Vegetation Restoration with Mixed N2-Fixer Tree Species Alleviates Microbial C and N Limitation in Surface Soil Aggregates in South Subtropical Karst Area, China

Soil extracellular enzyme stoichiometry (EES) is the essential predictor in nutrient status and resource limitation of soil microorganisms, whose metabolism has a vital role in biogeochemical cycling and ecosystem function. However, little is known about how N2-fixer tree species with different planting patterns affect soil nutrient resources in terms of extracellular enzyme activity (EEA) or EES within aggregates in degraded karst ecosystems. In this study, we evaluated soil EEA and EES related to carbon (C), nitrogen (N), and phosphorus (P) cycles across two eight-year-old pure plantations of legume species [Dalbergia odorifera T. Chen (PD) and Acrocarpus fraxinifolius Wight ex Arn. (PA)] and a mixed plantation of the two tree species listed above (MP). Meanwhile, a nearby undisturbed shrubland was used as a control (CK). We concluded that the activities of C-, N-, and P-acquiring enzyme increased to different degrees in the N2-fixer tree species stands (particularly in MP) compared to CK in all aggregates. Compared to CK, MP significantly increased by 39.0%, 54.0%, 39.3%, and 24.8% in total C-acquiring EEA, 41.1%, 60.5%, 47.8%, and 12.5% in total N-acquiring EEA, and 100.4%, 79.7%, 69.2%, and 56.4% in total P-acquiring EEA within >2 mm, 1–2 mm, 0.25–1 mm, and <0.25 mm aggregates, respectively. Furthermore, the logarithmic transformed ratio of C-, N-, and P-acquiring enzyme activities was 1.20:1.08:1, which deviated from the global ratio (1:1:1). Vector analysis of EEA showed that the vector length (VL) within aggregates was significantly lower than that of CK in all stands of N2-fixer species except PD; while in all treatments, vector angle (VA) was <45° for all aggregate sizes, except in MP, where VA reached 45° for <0.25 mm aggregate. These indicated soil microbes were limited by C and N together. However, MP significantly alleviated microbial C and N limitation than CK (p < 0.05). There were obvious positive relationships between enzyme C:N, C:P, and N:P ratios. VL was markedly negatively linked to VA. EES was markedly related to most soil nutrients and microbial biomass stoichiometry ratios. Changes in soil EEA and EES were primarily driven by available phosphorus (AP), microbial biomass carbon (MBC), soil C:N and MBN:MBP ratios. Together, our results demonstrate the influences after introducing N2-fixer tree species (particularly MP) for vegetation recovery on soil microbial nutrient limitation and ecological processes in aggregate level and will contribute to the development of ecological restoration practices and fertility management in degraded karst ecosystems of southwest China

Annexin A2 could enhance multidrug resistance by regulating NF-κB signaling pathway in pediatric neuroblastoma

Abstract Background Chemotherapy is one of major therapeutic regimens for neuroblastoma (NB) in children. However, recurrence and metastasis associated with poor prognosis caused by acquired multidrug resistance remains a challenge. There is a great need to achieve new insight into the molecular mechanism of drug resistance in NB. The aim of this study is to identify novel drug sensitivity-related biomarkers as well as new therapeutic targets to overcome chemoresistance. Methods We proteome-wide quantitatively compared protein expression of two NB cell lines with different drug sensitivities, isolated from the same patient prior to and following chemotherapy. Annexin A2 (ANXA2) emerged as a key factor contributing to drug resistance in NB. Then, we assessed the correlation of ANXA2 expression and clinical characteristics using a tissue microarray. Further, the roles of ANXA2 in chemoresistance for NB and the underlying mechanisms were studied by using short hairpin RNA (shRNA) in vitro and vivo. Results First in total, over 6000 proteins were identified, and there were about 460 significantly regulated proteins which were up- or down-regulated by greater than two folds. We screened out ANXA2 which was upregulated by more than 12-fold in the chemoresistant NB cell line, and it might be involved in the drug resistance of NB. Then, using a tissue chip containing 42 clinical NB samples, we found that strong expression of ANXA2 was closely associated with advanced stage, greater number of chemotherapy cycles, tumor metastasis and poor prognosis. Following knockdown of ANXA2 in NB cell line SK-N-BE(2) using shRNA, we demonstrate enhanced drug sensitivity for doxorubicin (2.77-fold) and etoposide (7.87-fold) compared with control. Pro-apoptotic genes such as AIF and cleaved-PARP were upregulated. Inhibiting ANXA2 expression attenuated transcriptional activity of NF-κB via down-regulated nuclear translocation of subunit p50. Finally, simulated chemotherapy in a xenograft NB nude mouse model suggests that ANXA2 knockdown could improve clinical results in vivo. Conclusion Our profiling data provided a rich source for further study of the molecular mechanisms of acquired drug resistance in NB. Further study may determine the role of ANXA2 as a prognostic biomarker and a potential therapeutic target for patients with multidrug-resistant NB

CsPbBr3 Perovskite Nanocrystal Grown on MXene Nanosheets for Enhanced Photoelectric Detection and Photocatalytic CO2 Reduction.

All-inorganic CsPbX3 (X = Cl, Br or I) perovskite nanocrystals have attracted extensive interest recently due to their exceptional optoelectronic properties. In an effort to improve the charge separation and transfer following efficient exciton generation in such nanocrystals, novel functional nanocomposites were synthesized by the in situ growth of CsPbBr3 perovskite nanocrystals on two-dimensional MXene nanosheets. Efficient excited state charge transfer occurs between CsPbBr3 NCs and MXene nanosheets, as indicated by significant photoluminescence (PL) quenching and much shorter PL decay lifetimes compared with pure CsPbBr3 NCs. The as-obtained CsPbBr3/MXene nanocomposites demonstrated increased photocurrent generation in response to visible light and X-ray illumination, attesting to the potential application of these heterostructure nanocomposites for photoelectric detection. The efficient charge transfer also renders the CsPbBr3/MXene nanocomposite an active photocatalyst for the reduction of CO2 to CO and CH4. This work provides a guide for exploration of perovskite materials in next-generation optoelectronics, such as photoelectric detectors or photocatalyst

Magnetic field mapper based on rotating coils

This thesis presents a magnetic field mapper based on rotating coils. The requirements, the architecture, the conceptual design, and the prototype for straight magnets were shown. The proposed system is made up of a rotating coil transducer and a train-like system for longitudinal motion and positioning inside magnet bore. The mapper allows a localized measurement of magnetic fields and the variation of the harmonic multipole content in the magnet ends. The proof-of-principle demonstration and the experimental characterization of the rotating-coil transducer specifically conceived for mapping validated the main objective of satisfying the magnetic measurement needs of the next generation of compact accelerators

Additional file 6: Table S2. of Annexin A2 could enhance multidrug resistance by regulating NF-κB signaling pathway in pediatric neuroblastoma

Significantly regulated protein between priamry and resistant cell lines (p < 0.05 and fold of change > 2). (XLSX 98 kb