Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the ...progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia.
Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression.
Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 51, 70 vs. 37 32, 41 years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 37.8, 38.6 vs. 37.5 37.0, 38.4°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 18, 48 vs. 24 16, 60 breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 14.3, 64.8 vs. 10.6 1.9, 33.1 mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio OR, 8.546; 95% confidence interval CI: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression.
Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, and C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.
Majorana bound states often occur at the end of a 1D topological superconductor. Validated by a new bulk invariant and an intuitive edge argument, we show the emergence of one Majorana Kramers pair ...at each corner of a square-shaped 2D topological insulator proximitized by an s_{±}-wave (e.g., Fe-based) superconductor. We obtain a phase diagram that addresses the relaxation of crystal symmetry and edge orientation. We propose two experimental realizations in candidate materials. Our scheme offers a higher-order and higher-temperature route for exploring non-Abelian quasiparticles.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Blockade of the protein–protein interaction between the transmembrane protein programmed cell death protein 1 (PD‐1) and its ligand PD‐L1 has emerged as a promising immunotherapy for treating ...cancers. Using the technology of mirror‐image phage display, we developed the first hydrolysis‐resistant D‐peptide antagonists to target the PD‐1/PD‐L1 pathway. The optimized compound DPPA‐1 could bind PD‐L1 at an affinity of 0.51 μM in vitro. A blockade assay at the cellular level and tumor‐bearing mice experiments indicated that DPPA‐1 could also effectively disrupt the PD‐1/PD‐L1 interaction in vivo. Thus D‐peptide antagonists may provide novel low‐molecular‐weight drug candidates for cancer immunotherapy.
Protein chemical synthesis and mirror‐image phage display were combined to develop a proteolysis‐resistant D‐peptide antagonist (DPPA‐1) which targets the immune checkpoint protein PD‐L1 (the ligand for PD‐1, the programmed cell death protein 1). DPPA‐1 was found to inhibit the PD‐1/PD‐L1 protein–protein interaction at the cellular level. IgV=immunoglobulin‐like variable.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health
. Despite intense research efforts, how, when and where ...new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing
of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China
. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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•Eu doping could enhance the SO2 resistance of Mn/TiO2 catalyst for SCR reaction.•The addition of Eu on Mn/TiO2 catalyst inhibited the formation of surface sulfate.•The SCR reaction ...(with SO2) over MnEu/TiO2 catalyst took place through L-H pathway.
Mn/TiO2 catalyst is a promising candidate for future utilization in low-temperature NH3-SCR reaction, but its bad resistance to SO2 is still a great challenge for practical application. In this study, Eu was successfully used as the additive to improve its resistance to SO2 under SCR conditions, while the pretreatment of Mn/TiO2 and MnEu/TiO2 catalyst by SO2 + O2 had a strong deactivation effect on them. In situ DRIFT study clarified that the deactivation of Mn/TiO2-S (SCR + SO2), Mn/TiO2-S (SO2 + O2) and MnEu/TiO2-S (SO2+O2) were mainly originated from the inhibited adsorption of NH3 and NOx species, as well as the formation of a large amount surface sulfate species on them, which had a strong blacking effect on the SCR reactions over the three catalysts via both E-R and L-H routes. After the addition of Eu, SCR reaction over MnEu/TiO2 catalyst with the existence of SO2 took place through L-H pathway, accompanied by the generation of less surface sulfate species, which brought about the excellent SO2 tolerance of MnEu/TiO2 catalyst under SCR conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We analyzed the number of circulating tumor cells (CTCs) and Epstein–Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The ...levels of CTCs and EBV DNA were measured at baseline and after first‐line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non‐mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first‐line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first‐line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first‐line chemotherapy was associated with significantly longer progression‐free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first‐line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first‐line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
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Endemic nasopharyngeal carcinoma (NPC) is associated with latent infection of the oncogenic Epstein‐Barr virus (EBV) and frequently metastasizes to distant lymph nodes and organs. Metastatic NPC is treated by serial administration of cytotoxic or targeted therapies and treatment response is generally assessed with serial imaging, which often fails to detect changes in tumor burden. Here, the authors show that the number of circulating tumor cells (CTCs) and EBV DNA levels before, after, and during first‐line chemotherapy are strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recently, we reported that some dairy cows could produce high amounts of milk with high amounts of protein (defined as milk protein yield MPY) when a population was raised under the same nutritional ...and management condition, a potential new trait that can be used to increase high-quality milk production. It is unknown to what extent the rumen microbiome and its metabolites, as well as the host metabolism, contribute to MPY. Here, analysis of rumen metagenomics and metabolomics, together with serum metabolomics was performed to identify potential regulatory mechanisms of MPY at both the rumen microbiome and host levels.
Metagenomics analysis revealed that several Prevotella species were significantly more abundant in the rumen of high-MPY cows, contributing to improved functions related to branched-chain amino acid biosynthesis. In addition, the rumen microbiome of high-MPY cows had lower relative abundances of organisms with methanogen and methanogenesis functions, suggesting that these cows may produce less methane. Metabolomics analysis revealed that the relative concentrations of rumen microbial metabolites (mainly amino acids, carboxylic acids, and fatty acids) and the absolute concentrations of volatile fatty acids were higher in the high-MPY cows. By associating the rumen microbiome with the rumen metabolome, we found that specific microbial taxa (mainly Prevotella species) were positively correlated with ruminal microbial metabolites, including the amino acids and carbohydrates involved in glutathione, phenylalanine, starch, sucrose, and galactose metabolism. To detect the interactions between the rumen microbiome and host metabolism, we associated the rumen microbiome with the host serum metabolome and found that Prevotella species may affect the host's metabolism of amino acids (including glycine, serine, threonine, alanine, aspartate, glutamate, cysteine, and methionine). Further analysis using the linear mixed effect model estimated contributions to the variation in MPY based on different omics and revealed that the rumen microbial composition, functions, and metabolites, and the serum metabolites contributed 17.81, 21.56, 29.76, and 26.78%, respectively, to the host MPY.
These findings provide a fundamental understanding of how the microbiome-dependent and host-dependent mechanisms contribute to varied individualized performance in the milk production quality of dairy cows under the same management condition. This fundamental information is vital for the development of potential manipulation strategies to improve milk quality and production through precision feeding. Video Abstract.
Oxidase‐mimicking nanozymes are more desirable than peroxidase‐mimicking ones since H2O2 can be omitted. However, only a few nanomaterials are known for oxidase‐like activities. In this work, we ...compared the activity of Mn2O3, Mn3O4 and MnO2 and found that Mn2O3 had the highest oxidase activity. Interestingly, the activity of Mn2O3 was even inhibited by H2O2. The oxidase‐like activity of Mn2O3 was not much affected by the presence of proteins such as bovine serum albumin (BSA), but the physisorption of antibodies to Mn2O3 was not strong enough to withstand the displacement by BSA. We then treated Mn2O3 with 3‐aminopropyltriethoxysilane to graft an amine group, which was used to conjugate antibodies using glutaraldehyde as a crosslinker. A one‐step indirect competitive ELISA (icELISA) was developed for the detection of isocarbophos, and an IC50 of 261.7 ng/mL was obtained, comparable with the results of the standard two‐step assay using horseradish peroxidase (HRP)‐labeled antibodies. This assay has the advantage of significant timesaving for rapid detection of large amounts of samples. This work has discovered a highly efficient oxidase‐mimicking nanozyme useful for various nano‐ and analytical applications.
Mn2O3 nanoparticles have the highest oxidase‐like activity among the tested metal oxides, but the activity is inhibited by H2O2. Mn3O4 behaves similarly, while the activity of MnO2 is enhanced by H2O2.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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Electromagnetic interference (EMI) shielding is critical in electronic applications. However, the currently available EMI shielding materials are restricted in customizability and ...application flexibility. Recent advances in manufacturing technologies have provided a unique path to achieve the custom creation of EMI shielding solutions. A successful example is additive manufacturing (AM), which has enabled high design freedom, efficient performance regulation, and multifunctionality simultaneously into fabricated shields, offering an opportunity to start a revolution in the field of EMI shielding. In this review, we summarize the latest advances in AM of EMI shielding materials, aiming to provide a deep understanding of the connection between raw materials, manufacturing methods, design considerations, and performances of the fabricated EMI shields. We first introduce the EMI shielding mechanism and available raw materials, subsequently focusing on the characteristics of representative AM methods and the as-created EMI shielding solutions. Based on the requirements to create application-oriented EMI shielding solutions, these methods are also critically compared. Thereafter, we present the state-of-the-art design considerations of EMI shields and examine the pivotal roles of AM in realizing the designs. We conclude by discussing future research directions, aiming at motivating the use of AM in the future developments of EMI shielding solutions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tunability and stability in the electrical properties of 2D semiconductors pave the way for their practical applications in logic devices. A robust layered indium selenide (InSe) field‐effect ...transistor (FET) with superior controlled stability is demonstrated by depositing an indium (In) doping layer. The optimized InSe FETs deliver an unprecedented high electron mobility up to 3700 cm2 V−1 s−1 at room temperature, which can be retained with 60% after 1 month. Further insight into the evolution of the position of the Fermi level and the microscopic device structure with different In thicknesses demonstrates an enhanced electron‐doping behavior at the In/InSe interface. Furthermore, the contact resistance is also improved through the In insertion between InSe and Au electrodes, which coincides with the analysis of the low‐frequency noise. The carrier fluctuation is attributed to the dominance of the phonon scattering events, which agrees with the observation of the temperature‐dependent mobility. Finally, the flexible functionalities of the logic‐circuit applications, for instance, inverter and not‐and (NAND)/not‐or (NOR) gates, are determined with these surface‐doping InSe FETs, which establish a paradigm for 2D‐based materials to overcome the bottleneck in the development of electronic devices.
A robust layered indium selenide (InSe) field‐effect transistor (FET) with superior high mobility (3700 cm2 V−1 s−1 at room temperature) is demonstrated by depositing an indium doping layer. With tunable carrier transport, the surface‐doped InSe FETs present flexible operations to realize various logic circuits, such as inverters and not‐or and not‐and gates.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK