Heavy monsoon rainfall ravaged a large swath of East Asia in summer 2020. Severe flooding of the Yangtze River displaced millions of residents in the midst of a historic public health crisis. This ...extreme rainy season was not anticipated from El Niño conditions. Using observations and model experiments, we show that the record strong Indian Ocean Dipole event in 2019 is an important contributor to the extreme Yangtze flooding of 2020. This Indian Ocean mode and a weak El Niño in the Pacific excite downwelling oceanic Rossby waves that propagate slowly westward south of the equator. At a mooring in the Southwest Indian Ocean, the thermocline deepens by a record 70 m in late 2019. The deepened thermocline helps sustain the Indian Ocean warming through the 2020 summer. The Indian Ocean warming forces an anomalous anticyclone in the lower troposphere over the Indo-Northwest Pacific region and intensifies the upper-level westerly jet over East Asia, leading to heavy summer rainfall in the Yangtze Basin. These coupled ocean-atmosphere processes beyond the equatorial Pacific provide predictability. Indeed, dynamic models initialized with observed ocean state predicted the heavy summer rainfall in the Yangtze Basin as early as April 2020.
The L-type amino acid transporter 1 (LAT1; also known as SLC7A5) catalyses the cross-membrane flux of large neutral amino acids in a sodium- and pH-independent manner
. LAT1, an antiporter of the ...amino acid-polyamine-organocation superfamily, also catalyses the permeation of thyroid hormones, pharmaceutical drugs, and hormone precursors such as L-3,4-dihydroxyphenylalanine across membranes
. Overexpression of LAT1 has been observed in a wide range of tumour cells, and it is thus a potential target for anti-cancer drugs
. LAT1 forms a heteromeric amino acid transporter complex with 4F2 cell-surface antigen heavy chain (4F2hc; also known as SLC3A2)-a type II membrane glycoprotein that is essential for the stability of LAT1 and for its localization to the plasma membrane
. Despite extensive cell-based characterization of the LAT1-4F2hc complex and structural determination of its homologues in bacteria, the interactions between LAT1 and 4F2hc and the working mechanism of the complex remain largely unknown
. Here we report the cryo-electron microscopy structures of human LAT1-4F2hc alone and in complex with the inhibitor 2-amino-2-norbornanecarboxylic acid at resolutions of 3.3 Å and 3.5 Å, respectively. LAT1 exhibits an inward open conformation. Besides a disulfide bond association, LAT1 also interacts extensively with 4F2hc on the extracellular side, within the membrane, and on the intracellular side. Biochemical analysis reveals that 4F2hc is essential for the transport activity of the complex. Together, our characterizations shed light on the architecture of the LAT1-4F2hc complex, and provide insights into its function and the mechanisms through which it might be associated with disease.
Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome-coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious ...coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo-electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B
AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B
AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.
This paper focuses on the rural promotion of fruit and vegetable agricultural technology and proposes a network flow optimization model based on linear programming for the diffusion of fruit and ...vegetable agricultural technology. Based on the Bass model, it describes the process of natural growth of network users and the word-of-mouth effect among them. Fruit and vegetable agricultural technology diffusion in real social networks is fitted and predicted by the social network information dissemination model, and the network flow problem of fruit and vegetable agricultural technology promotion is optimized using linear programming equations. Based on this basis, the algorithm designed in this paper and the effect of rural promotion of fruit and vegetable agricultural technology are analyzed with relevant data. The results show that the coefficient of the variable of the number of promotion times in the behavior of agrotechnology promotion is 0.064, which has a significant positive effect on the evaluation of the rural promotion performance of fruit and vegetable agricultural technology, indicating that increasing the number of agricultural technology training and enriching the content of agricultural technology promotion will help to improve the evaluation of the rural promotion performance of fruit and vegetable agricultural technology by farmers. The network flow optimization model constructed in this paper can enable farmers to master more modern fruit and vegetable agricultural technology to meet the needs of modern production of fruit and vegetable agriculture so as to improve the level of local fruit and vegetable agricultural development.
A hepta-band coupled-fed loop antenna for LTE/WWAN unbroken metal-rimmed smartphone applications is proposed. The unbroken metal rim is designed as a part of the loop antenna radiation structure, ...which is also composed of a system ground, a coupled-fed U-shaped microstrip line, and an L-shaped microstrip line. The feeding and L-shaped microstrip lines are located on an ungrounded area of 72 × 8 mm 2 along the top short edge of the system ground plane on an FR4 substrate. The operating band of the antenna is widened by the matching circuit elements on the feeding line. Combining multiple resonant modes generated by the coupling loop, the proposed antenna can operate on two wide operating bands of 824-960 and 1710-2690 MHz. The detailed working principles of the proposed antenna are described. Good antenna radiation characteristics are obtained. Both experimental and simulation results are presented and discussed.
This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues ...and tumor‐associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2‐polarized macrophage‐derived exosomes (M2‐exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2‐exo reverses the promotional effect of M2‐exo on cell proliferation in CDDP‐treated GC cells and homograft tumor growth in CDDP‐treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4‐1 (NEDD4‐1)‐mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2‐exo enhances the CDDP sensitivity of GC cells treated with M2‐exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM‐derived exosomes.
SYNOPSIS
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
LncRNA CRNDE is enriched in TAMs of GC patients.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes in vitro.
CRNDE facilitates NEDD4‐1‐mediated PTEN ubiquitination in GC cells.
Exosomal transfer of LncRNA CRNDE is linked to cisplatin resistance in GC cells caused by reduced PTEN levels.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
Accurate and rapid diagnosis of COVID-19 suspected cases plays a crucial role in timely quarantine and medical treatment. Developing a deep learning-based model for automatic COVID-19 diagnosis on ...chest CT is helpful to counter the outbreak of SARS-CoV-2. A weakly-supervised deep learning framework was developed using 3D CT volumes for COVID-19 classification and lesion localization. For each patient, the lung region was segmented using a pre-trained UNet; then the segmented 3D lung region was fed into a 3D deep neural network to predict the probability of COVID-19 infectious; the COVID-19 lesions are localized by combining the activation regions in the classification network and the unsupervised connected components. 499 CT volumes were used for training and 131 CT volumes were used for testing. Our algorithm obtained 0.959 ROC AUC and 0.976 PR AUC. When using a probability threshold of 0.5 to classify COVID-positive and COVID-negative, the algorithm obtained an accuracy of 0.901, a positive predictive value of 0.840 and a very high negative predictive value of 0.982. The algorithm took only 1.93 seconds to process a single patient's CT volume using a dedicated GPU. Our weakly-supervised deep learning model can accurately predict the COVID-19 infectious probability and discover lesion regions in chest CT without the need for annotating the lesions for training. The easily-trained and high-performance deep learning algorithm provides a fast way to identify COVID-19 patients, which is beneficial to control the outbreak of SARS-CoV-2. The developed deep learning software is available at https://github.com/sydney0zq/covid-19-detection .
Multi-task learning (MTL) methods have shown promising performance by learning multiple relevant tasks simultaneously, which exploits to share useful information across relevant tasks. Among various ...MTL methods, clustered multi-task learning (CMTL) assumes that all tasks can be clustered into groups and attempts to learn the underlying cluster structure from the training data. In this paper, we present a new approach for CMTL, called flexible clustered multi-task (FCMTL), in which the cluster structure is learned by identifying representative tasks. The new approach allows an arbitrary task to be described by multiple representative tasks, effectively soft-assigning a task to multiple clusters with different weights. Unlike existing counterpart, the proposed approach is more flexible in that (a) it does not require clusters to be disjoint, (b) tasks within one particular cluster do not have to share information to the same extent, and (c) the number of clusters is automatically inferred from data. Computationally, the proposed approach is formulated as a row-sparsity pursuit problem. We validate the proposed FCMTL on both synthetic and real-world data sets, and empirical results demonstrate that it outperforms many existing MTL methods.
Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its abilities to overcome critical limitations including low tissue‐penetration depth and ...phototoxicity in photodynamic therapy. Herein, the design of a new type of sonosensitizer is revealed, namely, ultrasmall oxygen‐deficient bimetallic oxide MnWOX nanoparticles, for multimodal imaging‐guided enhanced SDT against cancer. As‐made MnWOX nanoparticles with poly(ethylene glycol) (PEG) modification show high physiological stability and biocompatibility. Interestingly, such MnWOX‐PEG nanoparticles exhibit highly efficient US‐triggered production of 1O2 and •OH, higher than that of previously reported sonosensitizers (e.g., protoporphyrin IX and titanium dioxide), because the oxygen‐deficient structure of MnWOX serves as an electron trap site to prevent electron–hole recombination. The glutathione depletion capability of MnWOX‐PEG can also further favor SDT‐triggered cancer cell killing. With efficient tumor homing as illustrated by computer tomography and magnetic resonance imaging, MnWOX‐PEG enables effective destruction of mouse tumors under US stimulation. After accomplishing its therapeutic functions, MnWOX‐PEG can be metabolized by the mouse body without any long‐term toxicity. Herein, a new type of sono‐sensitizing agent with high SDT efficacy, multimodal imaging functions, and rapid clearance is presented, an agent which is promising for noninvasive SDT cancer treatment.
A new type of sonodynamic therapy (SDT) agent based on ultrasmall oxygen‐deficient bimetallic oxide MnWOX nanoparticles, which exhibit much higher sono‐sensitization efficiency compared with conventional SDT agents, as well as glutathione depletion capability to further favor SDT. Furthermore, their multimodal imaging functions and rapid renal clearance make them promising theranostic agents for imaging‐guided SDT.
Voltage-gated sodium (Na
) channels are responsible for the initiation and propagation of action potentials. They are associated with a variety of channelopathies and are targeted by multiple ...pharmaceutical drugs and natural toxins. Here, we report the cryogenic electron microscopy structure of a putative Na
channel from American cockroach (designated Na
PaS) at 3.8 angstrom resolution. The voltage-sensing domains (VSDs) of the four repeats exhibit distinct conformations. The entrance to the asymmetric selectivity filter vestibule is guarded by heavily glycosylated and disulfide bond-stabilized extracellular loops. On the cytoplasmic side, a conserved amino-terminal domain is placed below VSD
, and a carboxy-terminal domain binds to the III-IV linker. The structure of Na
PaS establishes an important foundation for understanding function and disease mechanism of Na
and related voltage-gated calcium channels.
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