29 research outputs found
GTC: Guided Training of CTC Towards Efficient and Accurate Scene Text Recognition
Connectionist Temporal Classification (CTC) and attention mechanism are two
main approaches used in recent scene text recognition works. Compared with
attention-based methods, CTC decoder has a much shorter inference time, yet a
lower accuracy. To design an efficient and effective model, we propose the
guided training of CTC (GTC), where CTC model learns a better alignment and
feature representations from a more powerful attentional guidance. With the
benefit of guided training, CTC model achieves robust and accurate prediction
for both regular and irregular scene text while maintaining a fast inference
speed. Moreover, to further leverage the potential of CTC decoder, a graph
convolutional network (GCN) is proposed to learn the local correlations of
extracted features. Extensive experiments on standard benchmarks demonstrate
that our end-to-end model achieves a new state-of-the-art for regular and
irregular scene text recognition and needs 6 times shorter inference time than
attentionbased methods.Comment: Accepted by AAAI 202
Peiminine Inhibits Glioblastoma in Vitro and in Vivo Through Cell Cycle Arrest and Autophagic Flux Blocking
Background/Aims: Glioblastoma multiforme (GBM) is the most devastating and widespread primary central nervous system tumour in adults, with poor survival rate and high mortality rates. Existing treatments do not provide substantial benefits to patients; therefore, novel treatment strategies are required. Peiminine, a natural bioactive compound extracted from the traditional Chinese medicine Fritillaria thunbergii, has many pharmacological effects, especially anticancer activities. However, its anticancer effects on GBM and the underlying mechanism have not been demonstrated. This study was conducted to investigate the potential antitumour effects of peiminine in human GBM cells and to explore the related molecular signalling mechanisms in vitro and in vivo Methods: Cell viability and proliferation were detected with MTT and colony formation assays. Morphological changes associated with autophagy were assessed by transmission electron microscopy (TEM). The cell cycle rate was measured by flow cytometry. To detect changes in related genes and signalling pathways in vitro and in vivo, RNA-seq, Western blotting and immunohistochemical analyses were employed. Results: Peiminine significantly inhibited the proliferation and colony formation of GBM cells and resulted in changes in many tumour-related genes and transcriptional products. The potential anti-GBM role of peiminine might involve cell cycle arrest and autophagic flux blocking via changes in expression of the cyclin D1/CDK network, p62 and LC3. Changes in Changes in flow cytometry results and TEM findings were also observed. Molecular alterations included downregulation of the expression of not only phospho-Akt and phospho-GSK3ÎČ but also phospho-AMPK and phospho-ULK1. Furthermore, overexpression of AKT and inhibition of AKT reversed and augmented peiminine-induced cell cycle arrest in GBM cells, respectively. The cellular activation of AMPK reversed the changes in the levels of protein markers of autophagic flux. These results demonstrated that peiminine mediates cell cycle arrest by suppressing AktGSk3ÎČ signalling and blocks autophagic flux by depressing AMPK-ULK1 signalling in GBM cells. Finally, peiminine inhibited the growth of U251 gliomas in vivo. Conclusion: Peiminine inhibits glioblastoma in vitro and in vivo via arresting the cell cycle and blocking autophagic flux, suggesting new avenues for GBM therapy
Control of anterior GRadient 2 (AGR2) dimerization links endoplasmic reticulum proteostasis to inflammation
International audienceAnterior gradient 2 (AGR2) is a dimeric protein disulfide isomerase family member involved in the regulation of protein quality control in the endoplasmic reticulum (ER). Mouse AGR2 deletion increases intestinal inflammation and promotes the development of inflammatory bowel disease (IBD). Although these biological effects are well established, the underlying molecular mechanisms of AGR2 function toward inflammation remain poorly defined. Here, using a protein-protein interaction screen to identify cellular regulators of AGR2 dimerization, we unveiled specific enhancers, including TMED2, and inhibitors of AGR2 dimerization, that control AGR2 functions. We demonstrate that modulation of AGR2 dimer formation, whether enhancing or inhibiting the process, yields pro-inflammatory phenotypes, through either autophagy-dependent processes or secretion of AGR2, respectively. We also demonstrate that in IBD and specifically in Crohn's disease, the levels of AGR2 dimerization modulators are selectively deregulated, and this correlates with severity of disease. Our study demonstrates that AGR2 dimers act as sensors of ER homeostasis which are disrupted upon ER stress and promote the secretion of AGR2 monomers. The latter might represent systemic alarm signals for pro-inflammatory responses
Role of TMED2 in murine labyrinth layer development and non-alcoholic fatty liver disease
TMED2 belongs to the transmembrane emp24 domain (TMED) protein family, which is the key protein in the early transport of transmembrane and secretory proteins between the Endoplasmic Reticulum (ER) and the Golgi apparatus. Tmed2 was expressed in the allantois and the chorion, two pre-placental tissues, and homozygous mutation of Tmed2 (a 99J mouse line) resulted in abnormal chorioallantoic fusion and failure of placental labyrinth formation. Expression of genes associated with spongiotrophoblast, Tpbpα, and syncytiotrophoblast, Gcm1, differentiation was reduced in Tmed2 null (Tmed299J/99J) placenta, and all Tmed299J/99J embryos died by mid-gestation. In situ hybridization using a Tmed2 probe revealed a tissue and temporal specific pattern of Tmed2 expression in the embryo. Furthermore, Tmed2 was highly expressed in the liver bud at embryonic day (E)9.5. Thus, we hypothesized that Tmed2 exhibits a tissue-specific role in the chorion for normal chorioallantoic fusion and that disrupted TMED2 levels could result in perturbed function in the liver. We established a novel ex vivo culture model of pre-placental tissues of chorion and allantois, which recapitulated events associated with early placental labyrinth layer development. Then, we investigated the tissue-specific requirement for Tmed2 using this ex vivo model. Recombinants of Tmed299J/99J and wildtype pre-placental tissues suggested that Tmed2 is required in the chorion for mixing of allantoic and chorionic cells. Tmed2 mutant allantoic cells could mix with wild type chorionic cells, but Tmed2 was found to be required in the allantois for proliferation. Although homozygous mutation in Tmed2 led to embryonic lethality, Tmed2 heterozygous mice (Tmed299J/+) were viable and fertile. Histological and molecular analysis using livers from Tmed299J/+ mice revealed a requirement for TMED2 in liver health. We showed that Tmed299J/+mice had decreased levels of TMED2 and TMED10, dilated endoplasmic reticulum membrane, and increased phosphorylation of an ER stress marker, eIF2α, and activation of the Unfolded Protein Response (UPR). Increased expression of sterol regulatory element binding protein (Srebp) 1a and 2 at the newborn stage and increased incidence of non-alcoholic fatty liver disease (NAFLD) were also found in Tmed299J/+ mice. Our data established Tmed299J/+ mice as a novel mouse model for NAFLD and suggests a novel role for TMED2 in liver health.TMED2 fait partie de la famille de protĂ©ines TMED (transmembrane emp24 domain). Celles-ci jouent un rĂŽle dans le transport membranaire ainsi que dans la sĂ©crĂ©tion des protĂ©ines entre le rĂ©ticulum endoplasmique (RE) et lâappareil de Golgi. Le gĂšne Tmed2 est exprimĂ© dans les tissus prĂ©-placentaires de la souris, soit lâallantoĂŻde et le chorion. De plus, une mutation homozygote de Tmed2 (la lignĂ©e murine 99J), provoque une fusion anormale de ces deux tissus, empĂȘchant la formation de la rĂ©gion du labyrinthe du placenta. Lâexpression des gĂšnes associĂ©s Ă la diffĂ©renciation des spongiotrophoblastes, Tpbpα, et des syncytiotrophoblastes, Gcm1, est diminuĂ©e dans les placenta Tmed299J/99J. De plus, les embryons mutants Tmed299J/99J meurent Ă la mi-gestation. Des donnĂ©es provenant dâhybridation in situ montrent un patron dâexpression de Tmed2 tissu et temps spĂ©cifique chez lâembryon murin. De maniĂšre intĂ©ressante, une forte expression de Tmed2 a Ă©tĂ© observĂ©e dans le bourgeon hĂ©patique. Notre hypothĂšse est que 1) Tmed2 joue un rĂŽle spĂ©cifique dans le chorion, crucial Ă la fusion chorio-allantoĂŻde et que 2) son inhibition partielle perturbe la fonction hĂ©patique. Pour tester notre premiĂšre hypothĂšse, nous avons mis au point un systĂšme de culture ex vivo du chorion et de lâallantoĂŻde murin, qui rĂ©capitule la formation de la couche placentaire du labyrinthe. En utilisant des tissus prĂ©-placentaires de la souris mutante Tmed299J/99J ou de type sauvage dans ce systĂšme ex vivo, nous avons pu Ă©valuer le rĂŽle de Tmed2 exprimĂ© exclusivement dans le chorion ou lâallantoĂŻde dans la formation de la rĂ©gion du labyrinthe. Ainsi, nous avons dĂ©terminĂ© que Tmed2 est requis dans le chorion pour quâil y ait un mĂ©lange des deux types de tissus. Dâun autre cĂŽtĂ©, les cellules allantoĂŻdes Tmed299J/99J pouvaient se mĂ©langer aux cellules du chorion de type sauvage mais une diminution de leur prolifĂ©ration a Ă©tĂ© observĂ©e. MalgrĂ© la mort au stade embryonnaire des souris Tmed299J/99J, les souris hĂ©tĂ©rozygotes quant Ă elles sont viables et fertiles. Des analyses histologiques et molĂ©culaires des foies de souris Tmed299J/+ ont rĂ©vĂ©lĂ©es une augmentation de lâincidence de NAFLD (Non-Alcoholic Fatty Liver Disease). De plus, nous avons dĂ©montrĂ© une diminution significative de lâexpression gĂ©nique et protĂ©ique de TMED2 et TMED10, une dilatation de la membrane du rĂ©ticulum endoplasmique (RE), une augmentation de la phosphorylation dâun marqueur de stress du RE, eIF2ïĄ, lâactivation du UPR (unfolded protein response) et finalement, une augmentation des facteurs de transcription Srebp 1a et 2 (Sterol regulatory element binding protein). Pris dans leur ensemble, nos travaux mettent de lâavant un nouveau modĂšle murin pour Ă©tudier NAFLD et suggĂšrent un nouveau rĂŽle de TMED2 dans le fonctionnement hĂ©patique
Sustainable composites with ultrahigh energy absorption from beverage cans and polyurethane foam
Crashworthiness analysis of novel cactus-inspired multi-cell structures under axial crushing
This study introduces an innovative cactus-inspired bionic tube (CBT) designed for enhanced energy absorption, drawing inspiration from the ribbed structure of cacti. Validation is achieved through quasi-static crushing experiments, confirming the numerical model's accuracy. Numerical simulations investigate critical factors, including structural mass, wall thickness, loading velocity, and cross-sectional configuration, revealing that proper cross-section design can boost the specific energy absorption (SEA) of the original CBT by 15.84 %. Additionally, a theoretical model is developed to forecast the mean crushing force of CBTs. Comparative analysis demonstrates the superior crashworthiness of CBTs over contemporary bionic and widely adopted multicell structures with the same mass, achieving a remarkable SEA of 11.44 J/gâexceeding maximum and minimum SEA values of these structures by 28.3 % and 127.9 %, respectively. This research significantly contributes to advancing the development of high-performance bionic energy-absorbing structures for crash applications
The Effect of Dietary Supplementation with Zinc Amino Acids on Immunity, Antioxidant Capacity, and Gut Microbiota Composition in Calves
The aim of this study was to investigate the effect of dietary supplementation with zinc (Zn) amino acids at different concentrations on immunity, antioxidant capacity, and gut microbiota composition in calves. Twenty-four one-month-old healthy Angus calves of comparable body weight were randomly divided into three groups (four males and four females in each group) based on the amount of Zn supplementation added to the feed the animals received: group A, 40 mg/kg DM; group B, 80 mg/kg DM; and group C, 120 mg/kg DM. The experiment ended when calves reached three months of age (weaning period). The increase in dietary Zn amino acid content promoted the growth of calves, and the average daily weight gain increased by 36.58% (p p p p p p Firmicutes and Bacteroidota, whereas the dominant genera were Unclassified-Lachnospiraceae and Ruminococcus. Linear discriminant analysis showed that the relative abundance of Bacteroides in the gut microbiota of calves in group B was higher than that in group A, and the relative abundance of Prevotellaceae-UCG-003 was higher compared to that in experimental group C. Thus, dietary supplementation of 80 mg/kg of Zn amino acids to calves could improve the immune function and antioxidant capacity, as well as enrich and regulate the equilibrium of gut microbiota, thus promoting the healthy growth of calves
Expression of lipid biosynthesis regulators-SREBPs in wildtype and <i>Tmed2</i><sup><i>99J/+</i></sup> livers.
<p>A). <i>Srebp1α</i> level was increased in <i>Tmed2</i><sup><i>99J/+</i></sup> increased in P5 <i>Tmed2</i><sup><i>99J/+</i></sup> mice compared to age-matched wildtype controls. B). <i>Srebp1c</i> level was comparable in <i>Tmed2</i><sup><i>99J/+</i></sup> and age-matched wildtype control mice at all stages. C). <i>Srebp2</i> level was increased in P5 <i>Tmed2</i><sup><i>99J/+</i></sup> mice compared to age-matched wildtype controls. D). Levels of activated SREBP1C was comparable in <i>Tmed2</i><sup><i>99J/+</i></sup> and age-matched wildtype control at 1â2 and 3â6 months. E). Levels of activated SREBP2 was comparable in <i>Tmed2</i><sup><i>99J/+</i></sup> and age-matched wildtype control at 1â2 and 3â6 months. F). Representative images of Western blot showing expression of full SREBP1C, cleaved SREBP1C (active form), SREBP2, and total protein loading control. 3 animals of each genotype were analyzed per age group. WT = wildtype. *P<0.05 by t-test.</p
Representative images of liver samples stained with Oil Red O and Sudan Black B.
<p>A). wildtype liver with score of 1 had no Oil Red O staining. B). <i>Tmed2</i><sup><i>99J/+</i></sup> liver with score of 5 had intense Oil Red O staining. C). Same wildtype sample as in A had no Sudan Black B staining. D). Same <i>Tmed2</i><sup><i>99J/+</i></sup> sample as in B had intense Sudan Black B staining. Scale bar = 50um. WT = Wildtype, n = 4 for each genotype.</p
TMED2 level in livers of wildtype and <i>Tmed2</i><sup><i>99J/+</i></sup> mice at P5, 1â2 months and 3â6 months.
<p>A. RT-qPCR shows no difference in <i>Tmed2</i> in livers. B. Western blot analysis showed significantly reduced TMED2 in livers of P5 <i>Tmed2</i><sup><i>99J/+</i></sup>mice compared to wildtype littermates C. Representative images of Western blot showing expression of TMED2 and ÎČ-ACTIN, used as a loading control. D. Reduced TMED2 in livers of 1â2 months and 3â6 months <i>Tmed2</i><sup><i>99J/+</i></sup>mice compared to age-matched wildtype. E. Representative images of Western blot showing expression of TMED2 and total protein used as loading control. 3 animals of each genotype were analyzed per age group. **P<0.01 by t-test. WT = wildtype.</p