The ORF7a Protein of SARS-CoV-2 Initiates Autophagy and Limits Autophagosome-Lysosome Fusion via Degradation of SNAP29 To Promote Virus Replication

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1-mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the SNAP29 protein at aspartic acid residue 30 (D30), ultimately impairing complete autophagy. Importantly, SARS-CoV-2 infection-induced accumulated autophagosomes promote progeny virus production, whereby ORF7a downregulates SNAP29, ultimately resulting in failure of autophagosome fusion with lysosomes to promote viral replication. Taken together, our study reveals a mechanism by which SARS-CoV-2 utilizes the autophagic machinery to facilitate its own propagation via ORF7a.Abbreviations: 3-MA: 3-methyladenine; ACE2: angiotensin converting enzyme 2; ACTB/β-actin: actin beta; ATG7: autophagy related 7; Baf A1: bafilomycin A1; BECN1: beclin 1; CASP3: caspase 3; COVID-19: coronavirus disease 2019; GFP: green fluorescent protein; hpi: hour post-infection; hpt: hour post-transfection; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MERS: Middle East respiratory syndrome; MTOR: mechanistic target of rapamycin kinase; ORF: open reading frame; PARP: poly(ADP-ribose) polymerase; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; shRNAs: short hairpin RNAs; siRNA: small interfering RNA; SNAP29: synaptosome associated protein 29; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TCID50: tissue culture infectious dose; TEM: transmission electron microscopy; TUBB, tubulin, beta; ULK1: unc-51 like autophagy activating kinase 1

Feature Transformation Method for Wheel Hub Shape Based on Target Detection and Geometric Analysis

Extracting and transforming shape features has been an important research domain in wheel hub design. The study of wheel hub design based on shape semantics, brand planning, and structural optimization requires regression analysis by using shape features and the corresponding variables to guide wheel hub design through the correlation model. The practical role of feature transformation in design is determined by its effectiveness, accuracy, and convenience. This process, however, has generally been handled manually in previous studies, limiting the universality and comprehensiveness of research outcomes. With the development of artificial intelligence, the automation of this process has become possible, ushering in the era of big data research for feature extraction and transformation. Hence, this study proposes a wheel hub feature transformation method based on target detection and geometric analysis. This method implements feature transformation in the following automation steps: (1) wheel hub feature point detection based on the YOLO model; (2) wheel hub feature grouping based on morphological parameters and position parameters; (3) feature point grooming based on geometric relations; and (4) parameter construction and transformation based on morphological features. Thus, an automatic, bidirectional, and morphological mechanism for transforming the parameters of a wheel hub shape can be developed. With the proposed transformation model, parameters related to the wheel hub shape and features can be transformed quickly, and the generative design of the wheel hub can be conducted based on big data

A New Scheme for Keypoint Detection and Description

The keypoint detection and its description are two critical aspects of local keypoints matching which is vital in some computer vision and pattern recognition applications. This paper presents a new scale-invariant and rotation-invariant detector and descriptor, coined, respectively, DDoG and FBRK. At first the Hilbert curve scanning is applied to converting a two-dimensional (2D) digital image into a one-dimensional (1D) gray-level sequence. Then, based on the 1D image sequence, an approximation of DoG detector using second-order difference-of-Gaussian function is proposed. Finally, a new fast binary ratio-based keypoint descriptor is proposed. That is achieved by using the ratio-relationships of the keypoint pixel value with other pixel of values around the keypoint in scale space. Experimental results show that the proposed methods can be computed much faster and approximate or even outperform the existing methods with respect to performance

Manufacturer’s Encroachment and Carbon Emission Reduction Decisions Considering Cap-and-Trade Regulation and Consumers’ Low-Carbon Preference

Carbon emission reduction and achieving carbon neutrality has become an inevitable trend in the sustainable development era. We investigate the manufacturer’s encroachment and carbon emission reduction decisions considering government cap-and-trade regulations and consumers’ low-carbon preference. The equilibrium decisions for the four scenarios are analytically obtained and compared based using the Stackelberg game. A comparison with and without cap-and-trade regulation under two encroachment decisions regarding member’s profits and carbon emission reduction levels are conducted. It is shown that the encroachment decision is always advantageous for the manufacturer if the government decides not to implement cap-and-trade regulation, and the retailer always loses profit. Moreover, if the carbon quota is sufficient, cap-and-trade regulation benefits the manufacturer. Otherwise, the manufacturer’s encroachment decision depends on the appropriate initial unit amount of carbon emission and unit carbon price. The retailer’s profit may not always be hurt by the manufacturer’s encroachment with cap-and-trade regulation; unless the unit carbon price exceeds a certain threshold, a higher consumer’s low-carbon preference in the encroachment scenario reduces more carbon emissions than in the no-encroachment scenario for the manufacturer. Further, the rising platform commission rate causes the platform profit to increase first and then decrease; the platform profit will slightly decrease if both products become more substitutes

The Research on Cartoon Image Design And Application of Main Characters in The Legend of the White Snake

Cartoon images are one of the important carriers for the inheritance of folk literature and culture. We should pay attention to the positive role of cartoon images in the inheritance of intangible culture. So the study aims to design and develop cartoon images of main characters in the Legend of the White snake based on audience intention. So that the cartoon image can be endowed with historical and modern cultural connotations. In this way, it can play a role in inheriting intangible cultural heritage and enhance the cultural confidence. Through the combination of qualitative and quantitative method, it compared the main characters of the Legend of the White snake at home and abroad. After carrying out desk research on the historical background of the legend, we used the concept of participatory design to conduct a questionnaire survey on the preference of cartoon images and analyzed the problems of character design, carrier, communication, and etc. Finally, based on the audience's extraction and combination of design elements, the cartoon image of the main characters in the Legend of the White Snake was generated, which meets the perceptual needs of modern people. By making full use of the narrative function of cartoon images, the creatively designed cartoon images of the main characters in the Legend of the White Snake are deeply rooted in the hearts of the people. It can also raise public interest in the culture of the White Snake and arouse emotional resonance. In this way, it promotes the inheritance and development of the intangible cultural heritage, the White Snake, and provides a certain reference for the design of cartoon images of similar characters in folk literature

Digital experience design of qinhuai lantern based on user journey map

This research extends the design concepts and research methods of user journey maps to the field of intangible cultural heritage, and selects the typical lotus lantern material package in Qinhuai lanterns as an example to explore the digital experience design of lanterns. On-site research methods are used to understand users, define target users and build personas. AEIOU recording framework is used to record user behavior, analyze and reorganize user behavior with card classification, and summarize user behavior flow. The Likert Smiley Scale is used to ask children to evaluate specific behaviors, get emotional curves, and summarize design opportunities from the perspective of valley filling. Given the pain points in the experience of the target user children and the indirect user parents, the lotus lantern material package is digitally redesigned from four perspectives of materials, connection methods between materials, functions and storage to meet the users' emotional experience. This research method and process have certain reference significance for experience design research on the same type of intangible cultural heritages

The Overlooked Transformation Mechanisms of VLCFAs: Peroxisomal β-Oxidation

Beta-oxidation(β-oxidation) is an important metabolic process involving multiple steps by which fatty acid molecules are broken down to produce energy. The very long-chain fatty acids (VLCFAs), a type of fatty acid (FA), are usually highly toxic when free in vivo, and their oxidative metabolism depends on the peroxisomal β-oxidation. For a long time, although β-oxidation takes place in both mitochondria and peroxisomes, most studies have been keen to explore the mechanism of β-oxidation in mitochondria while ignoring the importance of peroxisomal β-oxidation. However, current studies indicate that it is hard to provide effective treatment for diseases caused by the disorder of peroxisomal β-oxidation, such as X-ALD, SCOX deficiency, and D-BP deficiency; thus, actions should be taken to solve this problem. Based on existing research results, this review will summarize the importance of peroxisomal β-oxidation and help further learning

The complete chloroplast genome of the extremely drought-resistant plant Primulina ophiopogoides

Primulina ophiopogoides is a perennial herb of Gesneriaceae distributed on the limestone rocks. Here, the complete chloroplast (cp) genome of P. ophiopogoides was assembled and characterized. The cp genome is in a total length of 152,718 bp with the typical quadripartite structure, containing 2 inverted repeats (IRs) of 25,472 bp separated by a large single-copy (LSC) region of 83,615 bp and a small single-copy (SSC) region of 18,159 bp. The whole cp genome of P. ophiopogoides contains 131 genes, including 86 protein-coding genes, 37 tRNAs genes, and 8 rRNAs. The phylogenetic analysis indicated that P. ophiopogoides displayed a closer kinship to Primulina linearifolia

Progress of m6A Methylation in Lipid Metabolism in Humans and Animals

N6-methyladenosine (m6A) methylation is a type of methylation modification discovered on RNA molecules, mainly on mRNAs, as well as on other RNAs. Similar to DNA methylation, m6A methylation regulates the post-transcriptional expression level of genes without altering their base sequences. It modulates gene expression mainly by affecting the binding of mRNAs to reader proteins, thereby regulating variable splicing, translation efficiency, and stability of mRNAs. Early in the research, the study of m6A-related biological functions was greatly hindered due to the lack of effective detection methods. As second-generation sequencing and bioinformatics develop, several methods have been available to detect and predict m6A methylation sites in recent years. Moreover, m6A methylation is also closely related to the development of lipid metabolism, as shown in current studies. Combined with recent research, this paper reviews the concept, detection, and prediction means of m6A methylation, especially the relationship between m6A and lipid metabolism, providing a new clue to enrich the molecular mechanism of lipid metabolism