The outbreak of 2019 coronavirus disease (COVID-19) has been a challenge for hospital laboratories because of the huge number of samples that must be tested for the presence of the causative ...pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Simple and rapid immunodiagnostic methods are urgently needed to identify positive cases. Here we report the development of a rapid and sensitive lateral flow immunoassay (LFIA) that uses lanthanide-doped polysterene nanoparticles (LNPs) to detect anti-SARV-CoV-2 IgG in human serum. A recombinant nucleocapsid phosphoprotein of SARS-CoV-2 was dispensed onto a nitrocellulose membrane to capture specific IgG. Mouse anti-human IgG antibody was labeled with self-assembled LNPs that served as a fluorescent reporter. A 100-μL aliquot of serum samples (1:1000 dilution) was used for this assay and the whole detection process took 10 min. The results of the validation experiment met the requirements for clinical diagnostic reagents. A value of 0.0666 was defined as the cutoff value by assaying 51 normal samples. We tested 7 samples that were positive by reverse-transcription (RT-)PCR and 12 that were negative but clinically suspicious for the presence of anti-SARS-CoV-2 IgG. One of the negative samples was determined to be SARS-CoV-2 IgG positive, while the results for the other samples were consistent with those obtained by RT-PCR. Thus, this assay can achieve rapid and sensitive detection of anti-SARS-CoV-2 IgG in human serum and allow positive identification in suspicious cases; it can also be useful for monitoring the progression COVID-19 and evaluating patients’ response to treatment.
An efficient and scalable approach is described for the total synthesis of the marine natural product Et‐743 and its derivative lubinectedin, which are valuable antitumor compounds. The method ...delivers 1.6 % overall yield in 26 total steps from Cbz‐protected (S)‐tyrosine. It features the use of a common advanced intermediate to create the right and left parts of these compounds, and a light‐mediated remote C−H bond activation to assemble a benzo1,3dioxole‐containing intermediate.
A game of two halves: An efficient and scalable approach is described for the total synthesis of the complex antitumor agents Et‐743 and lurbinectedin. The method delivers 1.6 % overall yield in 26 total steps from Cbz‐protected (S)‐tyrosine. It features the use of a common advanced intermediate to create the right and left parts of these compounds, and a light‐mediated remote C−H bond activation to assemble a benzo1,3dioxole‐containing intermediate.
Microcharcoal morphology, which changes with biofuel type in the wildfire, can be used as an index for wildfire history and vegetation evolution. Here, five loess sites across the Chinese Loess ...Plateau were used to establish the biofuel history of the region during the Holocene based on microcharcoal morphological records. The results suggested that consistently increasing grass biofuel dominated the mid‐Holocene (∼7,500–3,000 yr BP), and the grassland or steppe expanded in the same interval. Since the climate conditions with simultaneous high precipitation and temperature of the mid‐Holocene are the most recent paleoclimate analog for future warming, we argue that the humid and warm conditions expected under future global warming on the Loess Plateau might lead to an increase in the grass rather than trees.
Plain Language Summary
As the product of the incomplete combustion of plants, microcharcoal has been widely used as a wildfire indicator, though microcharcoal morphology has received little attention. Studies have recognized that microcharcoal morphology can indicate the biofuel type (grass or wood) burnt in wildfires and thus can be used as an ideal index in wildfire history and vegetation evolution research. Here, we shed new light on biofuel history based on this established relationship. We compiled 425 microcharcoal records from five sites across the Chinese Loess Plateau and combined the data with compiled pollen records to establish the vegetation history during the Holocene. The results suggest that grassland or steppe was prevalent during the mid‐Holocene, consistent with the synthesized herb pollen records, biome reconstruction, and high precipitation and temperature. Because the climate conditions of the mid‐Holocene are the most recent paleoclimate analog for future warming, we infer that the humid and warm conditions expected under future global warming may promote the expansion of grass vegetation on the Loess Plateau. The insights may reveal the vulnerability of the restoration achievements dominated by plantations today. In addition, we highlight the potential of the more easily preserved microcharcoal to explore vegetation history in future work.
Key Points
Microcharcoal morphological history reveals that grassland or steppe dominated the mid‐Holocene on the Chinese Loess Plateau
The humid and warm conditions under future global warming on the Chinese Loess Plateau might lead to prevalent grass rather than trees
Evidence suggests that more native grassland or steppe should be considered in future restoration programs on the Loess Plateau
In sequential recommendation, it is critical to accurately capture the user's intention with limited session information. Previous work concentrates on modeling a single relationship existing between ...items in an ongoing session, e.g., sequential dependency or graph structures. They lack the exploration of constituent semantic properties of user intention and also lack effective mechanisms binding important features to deduce user intention accurately. In this paper, we present a novel intention detection-enhanced sequential recommendation model, named DASR, which can capture both sequential dependencies and user intent components. We innovatively introduce slot attention to bind the low-level local features extracted by CNN and design multiple rounds of competitive iteration mechanisms to refine the high-level representation of user intent continuously. Finally, these high-level features cooperate with the global dependencies captured by self-attention to achieve sequential recommendations. Extensive experiments are carried out on three benchmark datasets, the experimental results show that DASR outperforms the state-of-the-art baseline methods up to 6.91%, and 4.73% on Recall@20, and MRR@20, respectively.
Hierarchical ZnS structures with different sizes have been successfully prepared by a facile one-step method. By modulating the experimental parameters, we were able to fabricate hierarchical zinc ...sulfide (wurtzite) assembled structures with average sizes of 30, 200, and 400 nm on a large scale. Systematic experiments were carried out to investigate the factors such as the amounts of the reagents (thiourea and sodium hydroxide), which have great influence on the morphologies and sizes of the products. In addition, studies of the photocatalytic properties by exposure to UV light irradiation demonstrated that the as-obtained ZnS structures show potential photocatalytic activity. Therefore, the preparation and properties studies of different ZnS structures will offer great opportunities to explore the dependence of a material's properties on the morphology and size and find many interesting applications in the optoelectronic devices.
Continuous Cenozoic deposits have accumulated in the Tarim Basin, northwestern China, and are crucial to investigating the aridification history of the Asian interior, which has long been thought to ...be linked with the growth of the Tibetan Plateau, retreat of the Para-Tethys Sea and global cooling. However, less and poor climatic records from the region hinder our understanding of the questions above. Here we report continuous lithologic (sedimentary color) and geochemical (CaCO3 and salt ions) records from precisely dated late Miocene–early Pleistocene sedimentary sequence from western Tarim Basin, NW China. They indicate that arid climate had prevailed within the basin at latest at ca. 5.7Ma and gradually increased in degree until ca. 3.7Ma. Between ca. 3.7 and 2.1Ma, a hydrologic event occurred, which supplied more water from the Tien Shan. After ca. 2.1Ma the climate in the basin turned to hyper arid. We attribute the stepwise drying of the Asian inland since ca. 5.7Ma to the late Miocene–Pliocene episodic uplift of the Tibetan Plateau, Pamir and the Tien Shan and the connection of the Pamir with the Tien Shan in remote response to the collision of India with Asia.
Continuous lithologic (sedimentary color) and geochemical (CaCO3 and salt ions) records from precisely dated late Miocene–early Pleistocene sedimentary sequence from western Tarim Basin indicate that arid climate had prevailed within the Tarim Basin at latest at ca. 5.7Ma. Between ca. 3.7 and 2.1Ma, a hydrologic event occurred, which supplied more water from the Tien Shan. After 2.1Ma the climate in the basin turned to hyper arid.
The late Miocene–Pliocene episodic rapid uplift of the Tibetan Plateau and the Kunlun Shan, the fast northward movement and rise of the Pamir, and close of the Alay valley between the Pamir and Tien Shan are likely the major forcing mechanisms driving the stepwise drying of the Asian inland since ca. 5.7Ma. Display omitted
•High quality late Mio-Pleistocene geochemical proxies from central Asia.•Drying of Asian inland since 5.7Ma, followed by a humid event at 3.7-2.1Ma.•A further aridification proceeded in the Asian inland since ca. 2.1Ma•The rapid uplift of the Tibetan Plateau and Pamir might be driving forces
Late Cenozoic sediments in the Linxia Basin of China, on the northeastern Tibetan Plateau, bear abundant fossils of the Hipparion fauna. From late Miocene times, these sections record a history of ...aridification in the Asian Interior, the evolution of the east Asian monsoon, and multiple uplifts of the Tibetan Plateau. In this paper, a new detailed magnetostratigraphic study of a sedimentary sequence from the Duikang (DK) section containing the Hipparion fauna is presented, to better understand interconnected ecologic and environmental changes. The 90-m-thick section reveals nine normal and nine reversed zones that span from chron. C5n.2n to chron. C3Ar or from chron. C4n.2n to chron. C2Ar, yielding magnetostratigraphic ages of ~8.1 Ma - 3.7 Ma for the studied section and 5.3 Ma for the Hipparion fauna-bearing bed. Combined with all the previous magnetostratigraphic ages of the fauna-bearing sediments in the Linxia Basin, Hipparion can be distinguished as mainly having lived during five periods: Phase I (11.5 Ma), Phase II (8.2 Ma), Phase III (6.3 Ma), Phase IV (~5.3 Ma) and Phase V (2.5 Ma). Based on comparison of climate records in the Linxia Basin with aridification records from surrounding regions and global cooling during the late Cenozoic, we suggest that the evolution of Hipparion from the Linxia Basin was mainly driven by continuous global cooling and tectonic uplift of the northeastern Tibetan Plateau since the late Miocene.
•Depositional age of the DK section in the Linxia Basin is between 8.1 Ma and 3.7 Ma.•Hipparion lived during five different periods (11.5, 8.2, 6.3, 5.3 and 2.5 Ma).•Linxia Basin experienced the stepwise aridification since the late Miocene.
An organosilane-based strategy has been used to accomplish the convergent total synthesis of (-)-exiguolide. The key steps involve: (1) geminal bis(silyl) Prins cyclization to construct the A ring; ...(2) silicon-protected RCM reaction to construct the 20-membered macrocycle; and (3) Hiyama-Denmark cross-coupling of vinylsilane with vinyliodide to install the triene side chain.
A member of the Janus kinase (JAK) family, Tyrosine Kinase 2 (TYK2), is crucial in mediating various cytokine-signaling pathways such as interleukin-23 (IL23), interleukin-12 (IL12) and type I ...Interferons (IFN) which contribute to autoimmune disorders (e.g., psoriasis, lupus, and inflammatory bowel disease). Thus, TYK2 represents an attractive target to develop small-molecule therapeutics for the treatment of cytokine-driven inflammatory diseases. Selective inhibition of TYK2 over other JAK isoforms is critical to achieve a favorable therapeutic index in the development of TYK2 inhibitors. However, designing small molecule inhibitors to target the adenosine triphosphate (ATP) binding site of TYK2 kinase has been challenging due to the substantial structural homology of the JAK family catalytic domains. Here, we employed an approach to target the JAK homology 2 (JH2) pseudokinase regulatory domain of the TYK2 protein. We developed a series of small-molecule TYK2 pseudokinase ligands, which suppress the TYK2 catalytic activity through allosteric regulation. The TYK2 pseudokinase-binding small molecules in this study simultaneously achieve high affinity-binding for the TYK2 JH2 domain while also affording significantly reduced affinity for the TYK2 JAK homology 1 (JH1) kinase domain. These TYK2 JH2 selective molecules, although possessing little effect on suppressing the catalytic activity of the isolated TYK2 JH1 catalytic domain in the kinase assays, can still significantly block the TYK2-mediated receptor-stimulated pathways by binding to the TYK2 JH2 domain and allosterically regulating the TYK2 JH1 kinase. These compounds are potent towards human T-cell lines and primary immune cells as well as in human whole-blood specimens. Moreover, TYK2 JH2-binding ligands exhibit remarkable selectivity of TYK2 over JAK isoforms not only biochemically but also in a panel of receptor-stimulated JAK1/JAK2/JAK3-driven cellular functional assays. In addition, the TYK2 JH2-targeting ligands also demonstrate high selectivity in a multi-kinase screening panel. The data in the current study underscores that the TYK2 JH2 pseudokinase is a promising therapeutic target for achieving a high degree of biological selectivity. Meanwhile, targeting the JH2 domain represents an appealing strategy for the development of clinically well-tolerated TYK2 inhibitors that would have superior efficacy and a favorable safety profile compared to the existing Janus kinase inhibitors against autoimmune diseases.
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