The challenges of developing neuromorphic vision systems inspired by the human eye come not only from how to recreate the flexibility, sophistication, and adaptability of animal systems, but also how ...to do so with computational efficiency and elegance. Similar to biological systems, these neuromorphic circuits integrate functions of image sensing, memory and processing into the device, and process continuous analog brightness signal in real-time. High-integration, flexibility and ultra-sensitivity are essential for practical artificial vision systems that attempt to emulate biological processing. Here, we present a flexible optoelectronic sensor array of 1024 pixels using a combination of carbon nanotubes and perovskite quantum dots as active materials for an efficient neuromorphic vision system. The device has an extraordinary sensitivity to light with a responsivity of 5.1 × 10
A/W and a specific detectivity of 2 × 10
Jones, and demonstrates neuromorphic reinforcement learning by training the sensor array with a weak light pulse of 1 μW/cm
.
Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase ...separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we identify that ~37% (36,941) of the genomes contain a specific trio-nucleotide polymorphism (GGG-to-AAC) in the coding sequence of N, which leads to the amino acid substitutions, R203K/G204R. Interestingly, N
exhibits a higher propensity to undergo LLPS and a greater effect on IFN inhibition. By screening the chemicals known to interfere with N-RNA binding in other viruses, we find that (-)-gallocatechin gallate (GCG), a polyphenol from green tea, disrupts the LLPS of N and inhibits SARS-CoV-2 replication. Thus, our study reveals that targeting N-RNA condensation with GCG could be a potential treatment for COVID-19.
Structural modulations have been recently found to cause some unusual physical properties, such as superconductivity or charge density waves; however, thus‐induced nonlinear optical properties are ...rare. We report herein two unprecedented incommensurately modulated nonlinear optical sulfides exhibiting phase matching behavior, A2SnS5 (A=Ba, Sr), with the (3+1)D superspace groups P21212(00γ)00s or P21(α0γ)0, featuring different modulations of the Sn2S7∞ belts. Remarkably, Ba2SnS5 exhibits an excellent second harmonic generation (SHG) of 1.1 times that of the benchmark compound AgGaS2 at 1570 nm and a very large laser‐induced damage threshold (LIDT) of 8×AgGaS2. Theoretical studies revealed that the structural modulations increase the distortions of the Sn/S building units by about 44 or 25 % in A2SnS5 (A=Ba, Sr), respectively, and enhance significantly the SHG compared with α‐Ba2SnSe5 without modulation. Besides, despite the smaller Eg, the A2SnS5 samples exhibit higher LIDTs owing to their smaller thermal expansion anisotropies (Ba2SnS5 (1.51)<Sr2SnS5 (2.08)<AgGaS2 (2.97)).
Two incommensurately modulated nonlinear optical sulfides, Ba2SnS5 and Sr2SnS5, exhibit phase matching behavior and large laser‐induced damage thresholds. The second harmonic generation of Ba2SnS5 at 1570 nm is 1.1‐fold stronger than that of AgGaS2 as it benefits from the positional and occupational modulations.
The class III deacetylase sirtuin 1 (SIRT1), a member of the sirtuin family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). Here we report that SIRT1 suppressed ...CRC metastasis in vitro and in vivo as a negative regulator for miR-15b-5p transcription. Mechanistically, SIRT1 impaired regulatory effects of activator protein (AP-1) on miR-15b-5p trans-activation through deacetylation of AP-1. Importantly, acyl-CoA oxidase 1 (ACOX1), a key enzyme of the fatty acid oxidation (FAO) pathway, was found as a direct target for miR-15b-5p. SIRT1 expression was positively correlated with ACOX1 expression in CRC cells and in xenografts. Moreover, ACOX1 overexpression attenuated the augmentation of migration and invasion of CRC cells by miR-15b-5p overexpression. In conclusion, our study demonstrated a functional role of the SIRT1/miR-15b-5p/ACOX1 axis in CRC metastasis and suggested a potential target for metastatic CRC therapy.
•SIRT1 is a tumor suppressor gene in colorectal cancer patients.•SIRT1 suppresses CRC metastasis by blocking miR-15b-5p transcription.•SIRT1 suppresses miR-15b-5p transcription by impairing the binding of AP-1 to its promoter.•SIRT1 inhibits CRC metastasis through SIRT1/miR-15b-5p/ACOX1 axis.
Cyclic GMP‐AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase‐activating protein‐(SH3 ...domain)–binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid‐phase condensation state. Using high‐resolution microscopy, we show that in resting cells, cGAS exhibits particle‐like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre‐condensed cGAS undergoes liquid–liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA‐induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA – but not RNA – treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.
Synopsis
Host cell encoded cGAS is a critical DNA sensor to detect invading pathogens. The stress‐granule protein G3BP1 engages cGAS in a primary condensation state to enable a rapid response to free DNA.
G3BP1 primes cGAS for its prompt activation.
G3BP1 engages cGAS in a primary condensation state.
DNA‐ but not RNA‐interaction leads to the dissociation of G3BP1 from cGAS.
Green tea compound epigallocatechin gallate (EGCG) inhibits G3BP1‐promoted cGAS phase condensation and activation.
Host cell encoded cGAS is a critical DNA sensor to detect invading pathogens. The stress‐granule protein G3BP1 engages cGAS in a primary condensation state to enable a rapid response to free DNA.
A covalent organic framework integrating naphthalenediimide and triphenylamine units (NT‐COF) is presented. Two‐dimensional porous nanosheets are packed with a high specific surface area of 1276 m2 ...g−1. Photo/electrochemical measurements reveal the ultrahigh efficient intramolecular charge transfer from the TPA to the NDI and the highly reversible electrochemical reaction in NT‐COF. There is a synergetic effect in NT‐COF between the reversible electrochemical reaction and intramolecular charge transfer with enhanced solar energy efficiency and an accelerated electrochemical reaction. This synergetic mechanism provides the key basis for direct solar‐to‐electrochemical energy conversion/storage. With the NT‐COF as the cathode materials, a solar Li‐ion battery is realized with decreased charge voltage (by 0.5 V), increased discharge voltage (by 0.5 V), and extra 38.7 % battery efficiency.
A covalent organic framework functionalized with triphenylamine and naphthalenediimide units was used as a cathode. It could synergize photoinduced charge transfer with reversible electrochemical (de)lithiation processes. This leads to decreased charge voltage (by 0.5 V), increased discharge voltage (by 0.5 V), and an extra 38.7 % battery efficiency under illumination.
A multiple-input-multiple-output dielectric resonator antenna with enhanced isolation is proposed in this letter for the future 5G millimeter (mm)-wave applications. Two rectangular dielectric ...resonators (DRs) are mounted on a substrate excited by rectangular microstrip-fed slots underneath DRs. Each DR has a metal strip printed on its upper surface moving the strongest part of the coupling field away from the exciting slot to improve the isolation between two antenna elements. The proposed antenna obtains a simulated impedance bandwidth (S11 ≤ -10 dB) from 27.25 to 28.59 GHz, which covers the 28 GHz band (27.5-28.35 GHz) allocated by the Federal Communications Commission for the 5G applications. A maximum improvement of 12 dB on the isolation over 27.5-28.35 GHz is achieved. The mechanism of the isolation improvement and the design procedure are given in this letter. A prototype is manufactured and measured as a validation of the proposed decoupling method.
Ubiquitination is a basic post-translational modification for cellular homeostasis, and members of the conjugating enzyme (E2) family are the key components of the ubiquitin-proteasome system. ...However, the role of E2 family in colorectal cancer (CRC) is largely unknown. Our study aimed to investigate the role of Ube2v1, one of the ubiquitin-conjugating E2 enzyme variant proteins (Ube2v) but without the conserved cysteine residue required for the catalytic activity of E2s, in CRC.
Immunohistochemistry and real-time RT-PCR were used to study the expressions of Ube2v1 at protein and mRNA levels in CRC, respectively. Western blotting and immunofluorescence, transmission electron microscopy, and in vivo rescue experiments were used to study the functional effects of Ube2v1 on autophagy and EMT program. Quantitative mass spectrometry, immunoprecipitation, ubiquitination assay, western blotting, and real-time RT-PCR were used to analyze the effects of Ube2v1 on histone H4 lysine 16 acetylation, interaction with Sirt1, ubiquitination of Sirt1, and autophagy-related gene expression.
Ube2v1 was elevated in CRC samples, and its increased expression was correlated with poorer survival of CRC patients. Ube2v1 promoted migration and invasion of CRC cells in vitro and tumor growth and metastasis of CRC cells in vivo. Interestingly, Ube2v1suppressed autophagy program and promoted epithelial mesenchymal transition (EMT) and metastasis of CRC cells in an autophagy-dependent pattern in vitro and in vivo. Moreover, both rapamycin and trehalose attenuated the enhanced Ube2v1-mediated lung metastasis by inducing the autophagy pathway in an orthotropic mouse xenograft model of lung metastasis. Mechanistically, Ube2v1 promoted Ubc13-mediated ubiquitination and degradation of Sirt1 and inhibited histone H4 lysine 16 acetylation, and finally epigenetically suppressed autophagy gene expression in CRC.
Our study functionally links Ube2v1, an E2 member in the ubiquitin-proteasome system, to autophagy program, thereby shedding light on developing Ube2v1 targeted therapy for CRC patients.
This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis ...of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up.
This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18–45 years, with intact cervix and 1–4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18–26 and 27–45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006.
Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2–100·0) against high-grade genital lesions (0 0% of 3310 participants in the vaccine group and 13 0·4% of 3302 participants in the control group) and 97·3% (89·9–99·7) against persistent infection (2 0·1% of 3262 participants in the vaccine group and 73 2·2% of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 7·2% of 3691 participants) and control groups (290 7·9% of 3681); none were considered related to vaccination.
The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention.
National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.
Materials exhibiting excitation wavelength‐dependent photoluminescence (Ex‐De PL) in the visible region have potential applications in bioimaging, optoelectronics and anti‐counterfeiting. Two ...multifunctional, chiral Au(NHC)2Au(CN)2 (NHC=(4R,5R)/(4S,5S)‐1,3‐dimethyl‐4,5‐diphenyl‐4,5‐dihydro‐imidazolin‐2‐ylidene) complex double salts display Ex‐De circularly polarized luminescence (CPL) in doped polymer films and in ground powder. Emission maxima can be dynamically tuned from 440 to 530 nm by changing the excitation wavelength. The continuously tunable photoluminescence is proposed to originate from multiple emissive excited states as a result of the existence of varied AuI⋅⋅⋅AuI distances in ground state. The steric properties of the NHC ligand are crucial to the tuning of AuI⋅⋅⋅AuI distances. An anti‐counterfeiting application using these two salts is demonstrated.
Ex‐De CPL: By modulating the strength of AuI⋅⋅⋅AuI and Coulombic interactions by adjusting steric hindrance of the ligand, together with the materials processing, the two chiral enantiomers of Au(NHC)2Au(CN)2 double salts in PMMA film or as ground powder exhibit mirror‐image excitation wavelength‐dependent photoluminescence (Ex‐De CPL).
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