Targeted aspect based multimodal sentiment analysis:an attention capsule extraction and multi-head fusion network

Multimodal sentiment analysis has currently identified its significance in a variety of domains. For the purpose of sentiment analysis, different aspects of distinguishing modalities, which correspond to one target, are processed and analyzed. In this work, we propose the targeted aspect-based multimodal sentiment analysis (TABMSA) for the first time. Furthermore, an attention capsule extraction and multi-head fusion network (EF-Net) on the task of TABMSA is devised. The multi-head attention (MHA) based network and the ResNet-152 are employed to deal with texts and images, respectively. The integration of MHA and capsule network aims to capture the interaction among the multimodal inputs. In addition to the targeted aspect, the information from the context and the image is also incorporated for sentiment delivered. We evaluate the proposed model on two manually annotated datasets. the experimental results demonstrate the effectiveness of our proposed model for this new task

Neddylation inhibitor MLN4924 suppresses cilia formation by modulating AKT1

Abstract The primary cilium is a microtubule-based sensory organelle. The molecular mechanism that regulates ciliary dynamics remains elusive. Here, we report an unexpected finding that MLN4924, a small molecule inhibitor of NEDD8-activating enzyme (NAE), blocks primary ciliary formation by inhibiting synthesis/assembly and promoting disassembly. This is mainly mediated by MLN4924-induced phosphorylation of AKT1 at Ser473 under serum-starved, ciliary-promoting conditions. Indeed, pharmaceutical inhibition (by MK2206) or genetic depletion (via siRNA) of AKT1 rescues MLN4924 effect, indicating its causal role. Interestingly, pAKT1-Ser473 activity regulates both ciliary synthesis/assembly and disassembly in a MLN4924 dependent manner, whereas pAKT-Thr308 determines the ciliary length in MLN4924-independent but VHL-dependent manner. Finally, MLN4924 inhibits mouse hair regrowth, a process requires ciliogenesis. Collectively, our study demonstrates an unexpected role of a neddylation inhibitor in regulation of ciliogenesis via AKT1, and provides a proof-of-concept for potential utility of MLN4924 in the treatment of human diseases associated with abnormal ciliogenesis.https://deepblue.lib.umich.edu/bitstream/2027.42/148214/1/13238_2019_Article_614.pd

Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway.

Background: Environmental and occupational exposure to arsenic is a major public health concern. Although it has been identified as a human carcinogen, the molecular mechanism underlying the arsenic-induced carcinogenesis is not well understood.Objectives: We aimed to determine the role and mechanisms of miRNAs in arsenic-induced tumor angiogenesis and tumor growth.Methods: We utilized an in vitro model in which human lung epithelial BEAS-2B cells were transformed through long-term exposure to arsenic. A human xenograft tumor model was established to assess tumor angiogenesis and tumor growth in vivo. Tube formation assay and chorioallantoic membranes assay were used to assess tumor angiogenesis.Results: We found that miR-199a-5p expression levels were more than 100-fold lower in arsenic-transformed cells than parental cells. Re-expression of miR-199a-5p impaired arsenic-induced angiogenesis and tumor growth through its direct targets HIF-1α and COX-2. We further showed that arsenic induced COX-2 expression through HIF-1 regulation at the transcriptional level. In addition, we demonstrated that reactive oxygen species are an upstream event of miR-199a-5p/ HIF-1α/COX-2 pathway in arsenic-induced carcinogenesis.Conclusion: The findings establish critical roles of miR-199a-5p and its downstream targets HIF-1/COX-2 in arsenic-induced tumor growth and angiogenesis.Citation: He J, Wang M, Jiang Y, Chen Q, Xu S, Xu Q, Jiang BH, Liu LZ. 2014. Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway. Environ Health Perspect 122:255-261; http://dx.doi.org/10.1289/ehp.1307545

Deformation mechanism of kink-step distorted coherent twin boundaries in copper nanowire

In the construction of nanotwinned (NT) copper, inherent kink-like steps are formed on growth twin boundaries (TBs). Such imperfections in TBs play a crucial role in the yielding mechanism and plastic deformation of NT copper. Here, we used the molecular dynamic (MD) method to examine the influence of kink-step characteristics in depth, including kink density and kink-step height, on mechanical behavior of copper nanowire (NW) in uniaxial tension. The results showed that the kink-step, a stress-concentrated region, is preferential in nucleating and emitting stress-induced partial dislocations. Mixed dislocation of hard mode I and II and hard mode II dislocation were nucleated from kink-step and surface atoms, respectively. Kink-step height and kink density substantially affected the yielding mechanism and plastic behavior, with the yielding stress functional-related to kink-step height. However, intense kink density (1 kink per 4.4 nm) encourages dislocation nucleation at kink-steps without any significant decline in tensile stress. Defective nanowires with low kink-step height or high kink density offered minimal resistance to kink migration, which has been identified as one of the primary mechanisms of plastic deformation. Defective NWs with refined TB spacing were also studied. A strain-hardening effect due to the refined TB spacing and dislocation pinning was observed for defective NWs. This study has implications for designing NT copper to obtain optimum mechanical performance.This research was undertaken with the assistance of resources from the National Computational Infrastructure (NCI), which is supported by the Australian Government. This work was supported by the Australian Research Council under Grant Nos. LP130101001

MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1.

The mechanism of cisplatin resistance in ovarian cancer is not clearly understood. In the present investigation, we found that the expression levels of miR-497 were reduced in chemotherapy-resistant ovarian cancer cells and tumor tissues due to hypermethylation of miR-497 promoter. Low miR-497 expression levels were associated with chemo-resistant phonotype of ovarian cancer. By analyzing the expression levels of miR-497, mTOR and p70S6K1 in a clinical gene-expression array dataset, we found that mTOR and p70S6K1, two proteins correlated to chemotherapy-resistance in multiple types of human cancers, were inversely correlated with miR-497 levels in ovarian cancer tissues. By using an orthotopic ovarian tumor model and a Tet-On inducible miR-497 expression system, our results demonstrated that overexpression of miR-497 sensitizes the resistant ovarian tumor to cisplatin treatment. Therefore, we suggest that miR-497 might be used as a therapeutic supplement to increase ovarian cancer treatment response to cisplatin

Image post-processing techniques of 64-slice CT in the diagnosis of external cardiac malformations

Abstract: Objective To discuss the value of Image post-processing techniques of 64-slice CT in the diagnosis of external cardiac malformations．Materials and methods Retrospective reviews of imaging data base were done which consisted of 59 patients with congenital cardiovascular malformations who presented to our hospital. The scanning data were carried on multiple planar reformation (MPR), maximum intensity projection (MIP) and volume rendering (VR) as needed. The operation results were taken as diagnostic standard to evaluate the diagnostic accuracy of 64-slice spiral CT. Results 69 external cardiac malformations (cardiovascular connection department and peripheral vascular malformations) were confirmed by operation in all 59 patients. 67 malformations correctly diagnosed and 2 malformations were incorrecty diagnos in 64-slice spiral CT. The accuracy in diagnosing cardiovascular connection department and peripheral vascular malformations were 97.10% (67/69). There was no significant difference in image scores compared with the three image post-processing techniques (P value were 0.612, 0.902 and 0.815, respectively). Conclusions 64-slice spiral CT may be used as a primary technique and as a substitute for the diagnosis imaging portion of cardiovascular connection and peripheral vascular malformations

A multicenter study of fetal chromosomal abnormalities in Chinese women of advanced maternal age

AbstractObjectiveThis study aimed to determine the rates of different fetal chromosomal abnormalities among women of advanced maternal age in China and to discuss the possible misdiagnosis risks of newer molecular techniques, for selection of appropriate prenatal screening and diagnostic technologies.Materials and MethodsSecond trimester amniocentesis and fetal karyotype results of 46,258 women were retrospectively reviewed. All women were ≥ 35 years old with singleton pregnancies. The rates of clinically significant chromosomal abnormalities (CSCAs), incidence of chromosomal abnormalities, and correlations with age were determined.ResultsFrom 2001 to 2010, the proportion of women of advanced maternal age undergoing prenatal diagnosis increased from 20% to 46%. The mean age was 37.4 years (range, 35–46 years). A total of 708 cases of CSCAs, with a rate of 1.53% were found. Trisomy 21 was the most common single chromosome abnormality and accounted for 55.9% of all CSCAs with an incidence of 0.86%. Trisomy 13, trisomy 18, and trisomy 21, the most common chromosome autosomal aneuploidies, accounted for 73.6% of all CSCAs, with a rate of 1.13%. As a group, the most common chromosomal aneuploidies (13/18/21/X/Y) accounted for 93.9% of all abnormalities, with a rate of 1.44%. The incidence of trisomy 21, trisomy 13/18/21 as a group, and 13/18/21/X/Y as a group was significantly greater in women aged 39 years and older (p < 0.001), but was not different between women aged 35 years, 36 years, 37 years, and 38 years.ConclusionThese findings may assist in genetic counseling of advanced maternal age pregnant women, and provide a basis for the selection of prenatal screening and diagnostic technologies

Real-world observations and impacts of Chinese herbal medicine for migraine: results of a registry-based cohort study

Background: Migraine is a prevalent, recurrent condition with substantial disease burden. Chinese herbal medicine (CHM) has been used frequently for migraine in controlled clinical settings. This study is to summarise the characteristics of patients who seek clinical care in a tertiary Chinese medicine hospital in China; to gather their preferences and values of using CHM; to explore the effect of CHM for migraine and its comorbidities in a real-world setting, and to collect first-hand expertise of clinicians’ practice pattern in prescribing CHM for migraine.Methods: This registry-based cohort study was prospectively conducted at Guangdong Provincial Hospital of Chinese Medicine from December 2020 to May 2022. Adult migraine patients seeking their initial anti-migraine clinical care at the hospital were consecutively recruited and followed up for 12 weeks. Practitioners specialised in headache management prescribed individualised treatments without research interference. Standardised case report forms were employed to gather information on patients’ preferences and perspective of seeking clinical care, as well as to assess participants’ migraine severity, comorbidities, and quality of life, at 4-weeks intervals. Various analytical methods were utilised based on the computed data.Results: In this study, we observed 248 participants. Of these, 73 received CHM treatment for 28 days or longer. Notably, these participants exhibited a greater disease severity, compared to those treated with CHM for less than 28 days. Of the 248 participants, 83.47% of them expected CHM would effectively reduce the severity of their migraine, around 50% expected effects for migraine-associated comorbidities, while 51.61% expressing concerns about potential side effects. CHM appeared to be effective in reducing monthly migraine days and pain intensity, improving patients’ quality of life, and potentially reducing comorbid anxiety, with a minimum of 28 days CHM treatment. Herbs such as gan cao, gui zhi, chuan xiong, fu ling, bai zhu, yan hu suo, etc. were frequently prescribed for migraine, based on patients’ specific symptoms.Conclusion: CHM appeared to be beneficial for migraine and comorbid anxiety in real-world clinical practice when used continuously for 28 days or more.Clinical Trial Registration:clinicaltrials.gov, identifier ChiCTR2000041003

The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer.

Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. The CAMK2N1 gene, cloned and characterized as an inhibitor of CaMKII (calcium/calmodulin-dependent protein kinase II), has been shown to affect tumorigenesis and tumor growth. However, it is still unknown whether CAMK2N1 plays a role in prostate cancer development. We first examined the protein and mRNA levels of CAMK2N1 and observed a significant decrease in human prostate cancers comparing to normal prostate tissues. Re-expression of CAMK2N1 in prostate cancer cells reduced cellular proliferation, arrested cells in G0/G1 phases, and induced apoptotic cell death accompanied by down-regulation of IGF-1, ErbB2, and VEGF downstream kinases PI3K/AKT, as well as the MEK/ERK-mediated signaling pathways. Conversely, knockdown of CAMK2N1 had a significant opposite effects on these phenotypes. Our analyses suggest that CAMK2N1 plays a tumor suppressive role in prostate cancer cells. Reduced CAMK2N1 expression correlates to human prostate cancer progression and predicts poor clinical outcome, indicating that CAMK2N1 may serve as a biomarker. The inhibition of tumor growth by expressing CAMK2N1 established a role of CAMK2N1 as a therapeutic target