University of Science and Technology of China

Liu Q., Jiang Y., Jin K., Qin J., Xu J., Li W., Xiong J., Liu J., Xiao Z., Sun K., Yang S., Zhang X., Ding L.

Wang J., Sun K., Cheng T., Jiang B., Deng C., Zhao Y., Liu D., Mu Y., Tan M., Wang X., Liu W., Xiao B.

High-resolution representations are essential for position-sensitive vision problems, such as human pose estimation, semantic segmentation, and object detection. Existing state-of-the-art frameworks first encode the input image as a low-resolution representation through a subnetwork that is formed by connecting high-to-low resolution convolutions in series (e.g., ResNet, VGGNet), and then recover the high-resolution representation from the encoded low-resolution representation. Instead, our proposed network, named as High-Resolution Network (HRNet), maintains high-resolution representations through the whole process. There are two key characteristics: (i) Connect the high-to-low resolution convolution streams in parallel and (ii) repeatedly exchange the information across resolutions. The benefit is that the resulting representation is semantically richer and spatially more precise. We show the superiority of the proposed HRNet in a wide range of applications, including human pose estimation, semantic segmentation, and object detection, suggesting that the HRNet is a stronger backbone for computer vision problems. All the codes are available at https://github.com/HRNet .

Wang Q., Zhang Y., Wu L., Niu S., Song C., Zhang Z., Lu G., Qiao C., Hu Y., Yuen K., Wang Q., Zhou H., Yan J., Qi J.

Summary The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.

Klionsky D.J., Abdel-Aziz A.K., Abdelfatah S., Abdellatif M., Abdoli A., Abel S., Abeliovich H., Abildgaard M.H., Abudu Y.P., Acevedo-Arozena A., Adamopoulos I.E., Adeli K., Adolph T.E., Adornetto A., Aflaki E., et. al.

ABSTRACT In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Xu X., Han M., Li T., Sun W., Wang D., Fu B., Zhou Y., Zheng X., Yang Y., Li X., Zhang X., Pan A., Wei H.

Significance In patients with coronavirus disease 2019, a large number of T lymphocytes and mononuclear macrophages are activated, producing cytokines such as interleukin-6 (IL-6), which bind to the IL-6 receptor on the target cells, causing the cytokine storm and severe inflammatory responses in lungs and other tissues and organs. Tocilizumab, as a recombinant humanized anti-human IL-6 receptor monoclonal antibody, can bind to the IL-6 receptor with high affinity, thus preventing IL-6 itself from binding to its receptor, rendering it incapable of immune damage to target cells, and alleviating the inflammatory responses. After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.

Wu F., Maier J., Yu Y.

This review article summarizes the current trends and provides guidelines towards next-generation rechargeable lithium and lithium-ion battery chemistries.

Zhong H., Wang H., Deng Y., Chen M., Peng L., Luo Y., Qin J., Wu D., Ding X., Hu Y., Hu P., Yang X., Zhang W., Li H., Li Y., et. al.

A light approach to quantum advantage Quantum computational advantage or supremacy is a long-anticipated milestone toward practical quantum computers. Recent work claimed to have reached this point, but subsequent work managed to speed up the classical simulation and pointed toward a sample size–dependent loophole. Quantum computational advantage, rather than being a one-shot experimental proof, will be the result of a long-term competition between quantum devices and classical simulation. Zhong et al. sent 50 indistinguishable single-mode squeezed states into a 100-mode ultralow-loss interferometer and sampled the output using 100 high-efficiency single-photon detectors. By obtaining up to 76-photon coincidence, yielding a state space dimension of about 1030, they measured a sampling rate that is about 1014-fold faster than using state-of-the-art classical simulation strategies and supercomputers. Science, this issue p. 1460 Quantum computational advantage is demonstrated using boson sampling with photons. Quantum computers promise to perform certain tasks that are believed to be intractable to classical computers. Boson sampling is such a task and is considered a strong candidate to demonstrate the quantum computational advantage. We performed Gaussian boson sampling by sending 50 indistinguishable single-mode squeezed states into a 100-mode ultralow-loss interferometer with full connectivity and random matrix—the whole optical setup is phase-locked—and sampling the output using 100 high-efficiency single-photon detectors. The obtained samples were validated against plausible hypotheses exploiting thermal states, distinguishable photons, and uniform distribution. The photonic quantum computer, Jiuzhang, generates up to 76 output photon clicks, which yields an output state-space dimension of 1030 and a sampling rate that is faster than using the state-of-the-art simulation strategy and supercomputers by a factor of ~1014.

Liu Y., Yang Y., Zhang C., Huang F., Wang F., Yuan J., Wang Z., Li J., Li J., Feng C., Zhang Z., Wang L., Peng L., Chen L., Qin Y., et. al.

The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.

Zheng M., Gao Y., Wang G., Song G., Liu S., Sun D., Xu Y., Tian Z.

In December 2019, a novel coronavirus was first reported in Wuhan, China. It was named by the World Health Organization as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is responsible for coronavirus disease 2019 (COVID-19). Up to 28 February 2020, 79,394 cases have been confirmed according to China’s National Health Commission. Outside China, the virus has spread rapidly to over 36 countries and territories. Cytotoxic lymphocytes such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are necessary for the control of viral infection, and the functional exhaustion of cytotoxic lymphocytes is correlated with disease progression. However, whether the cytotoxic lymphocytes in patients infected with SARS-CoV-2 become functionally exhausted has not been reported. We showed that the total number of NK and CD8 T cells was decreased markedly in patients with SARS-CoV-2 infection. The function of NK and CD8 T cells was exhausted with the increased expression of NKG2A in COVID-19 patients. Importantly, in patients convalescing after therapy, the number of NK and CD8 T cells was restored with reduced expression of NKG2A. These results suggest that the functional exhaustion of cytotoxic lymphocytes is associated with SRAS-CoV-2 infection. Hence, SARS-CoV-2 infection may break down antiviral immunity at an early stage. SARS-CoV-2 has been identified as a genus β-coronavirus, and it shares 79.5% sequence homology with SARS-CoV. In our cohort of 68 COVID-19 patients admitted to The First Affiliated Hospital (Hefei) and Fuyang Hospital (Fuyang), both of which are part of Anhui Medical University in China, there were 55 cases of mild disease (MD) and 13 cases of severe disease (SD). Patients were aged 11–84 years, and the median age of patients was 47.13 years. The percentage of male patients was 52.94%. Consistent with previous studies, many patients had fever (80.88%), cough (73.53%), and sputum (32.36%) upon admission. The prevalence of other symptoms (e.g., headache, diarrhea) was relatively low (Supplementary Table 1). The clinical features of patients infected with SARS-CoV-2 was consistent with those reported by Chen and colleagues. Upon admission, the neutrophil count was remarkably higher in SD patients than in MD cases, whereas the lymphocyte count was significantly lower in SD cases than in MD cases. The concentration of total bilirubin, D-dimer, and lactate dehydrogenase in blood was higher in SD patients than that in MD patients. Levels of alanine aminotransferase and aspartate aminotransferase were slightly higher in SD cases than those in MD cases. Levels of albumin and hemoglobin were lower in SD patients than those in MD patients (Supplementary Table 2). Specifically, T cell and CD8 T cell counts were decreased significantly in MD and SD patients compared with those in healthy controls (HCs). The number of T cells and CD8 T cells was significantly lower in SD patients than that in MD cases. The counts of NK cells were reduced remarkably in SD patients compared with those in MD cases and HCs (Fig. 1a). As an inhibitory receptor, NKG2A has been demonstrated to induce NK cell exhaustion in chronic viral infections. Notably, NKG2A expression on NK and CD8 T cells results in functional exhaustion of NK and CD8 T cells. In patients infected with SARSCoV-2, NKG2A expression was increased significantly on NK and CD8 T cells compared with that in HCs (Fig. 1b). Next, to identify the role of NKG2A on the function of NK and CD8 T cells, levels of CD107a, interferon (IFN)-γ, interleukin (IL)-2, granzyme B, and tumor necrosis factor (TNF)-α were measured through staining of intracellular cytokines. We found lower percentages of CD107a NK, IFN-γ NK, IL-2 NK, and TNF-α NK cells and mean fluorescence intensity (MFI) of granzyme B NK cells in COVID-19 patients than those in HCs. Consistent with these findings, COVID-19 patients also showed decreased percentages of CD107a CD8, IFN-γCD8, and IL-2CD8 T cells and MFI of granzyme BCD8 T cells, compared with those in HCs (Fig. 1c). Taken together, these results suggest the functional exhaustion of cytotoxic lymphocytes in COVID-19 patients. Hence, SARS-CoV-2 may break down antiviral immunity at an early stage. In our setting, ~94.12% of patients were administered antiviral therapy (Kaletra®). Chloroquine phosphate was used in 7.35% of patients, and the proportion of patients treated with IFN was 64.71%. In addition, 48.53% patients received antibiotic treatment (Supplementary Table 3). Comparison of the total number of cytotoxic lymphocytes (including CTLs and NK cells) after therapy was carried out. The total number of T cells and NK cells recovered in the convalescent period in four of the five patients, and the total count of CTLs was restored in the convalescent period in three of the five patients (Fig. 1d). Hence, efficacious therapy was accompanied by an increased number of T cells, CTLs, and NK cells. Importantly, the percentage of NKG2A NK cells was decreased in the convalescent period compared with that before treatment among five patients. Similarly, five patients showed a decreased percentage of NKG2A CTLs in the convalescent period (Fig. 1e).

Yu Z., Duan Y., Feng X., Yu X., Gao M., Yu S.

Hydrogen economy has emerged as a very promising alternative to the current hydrocarbon economy, which involves the process of harvesting renewable energy to split water into hydrogen and oxygen and then further utilization of clean hydrogen fuel. The production of hydrogen by water electrolysis is an essential prerequisite of the hydrogen economy with zero carbon emission. Among various water electrolysis technologies, alkaline water splitting has been commercialized for more than 100 years, representing the most mature and economic technology. Here, the historic development of water electrolysis is overviewed, and several critical electrochemical parameters are discussed. After that, advanced nonprecious metal electrocatalysts that emerged recently for negotiating the alkaline oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are discussed, including transition metal oxides, (oxy)hydroxides, chalcogenides, phosphides, and nitrides for the OER, as well as transition metal alloys, chalcogenides, phosphides, and carbides for the HER. In this section, particular attention is paid to the catalyst synthesis, activity and stability challenges, performance improvement, and industry-relevant developments. Some recent works about scaled-up catalyst synthesis, novel electrode designs, and alkaline seawater electrolysis are also spotlighted. Finally, an outlook on future challenges and opportunities for alkaline water splitting is offered, and potential future directions are speculated.