...ischemic optic neuropathy (ION) was excluded. Fundus autofluorescence (FAF) of right eye showed multiple hyper-autofluorescent dots with corresponding ellipsoid zone (EZ) disruption on optical ...coherence tomography (OCT) (Figure 1A), which was consistent with Multiple Evanescent White Dot Syndrome (MEWDS). CONFLICT OF INTEREST STATEMENT All authors declare no conflict of interest.
In nature, almost every organism ages and has a limited lifespan. Aging has been explored by biologists to be an important mechanism for maintaining diversity. In a social animal colony, aging makes ...the old leader of the colony become weak, providing opportunities for the other individuals to challenge the leadership position. Inspired by this natural phenomenon, this paper transplants the aging mechanism to particle swarm optimization (PSO) and proposes a PSO with an aging leader and challengers (ALC-PSO). ALC-PSO is designed to overcome the problem of premature convergence without significantly impairing the fast-converging feature of PSO. It is characterized by assigning the leader of the swarm with a growing age and a lifespan, and allowing the other individuals to challenge the leadership when the leader becomes aged. The lifespan of the leader is adaptively tuned according to the leader's leading power. If a leader shows strong leading power, it lives longer to attract the swarm toward better positions. Otherwise, if a leader fails to improve the swarm and gets old, new particles emerge to challenge and claim the leadership, which brings in diversity. In this way, the concept "aging" in ALC-PSO actually serves as a challenging mechanism for promoting a suitable leader to lead the swarm. The algorithm is experimentally validated on 17 benchmark functions. Its high performance is confirmed by comparing with eight popular PSO variants.
Emerging studies show that long noncoding RNAs (lncRNAs) play important roles in carcinogenesis and cancer progression. The lncRNA ZEB1 antisense 1 (ZEB1-AS1) derives from the promoter region of ZEB1 ...and we still know little about its expressions, roles and mechanisms.
RACE was used to obtain the sequence of ZEB1-AS1. RNA interference was used to decrease ZEB1-AS1 expression. Adenovirus expression vector was used to increase ZEB1-AS1 expression. CHIP and RIP were used to detect the epigenetic mechanisms by which ZEB1-AS1 regulated ZEB1. CCK8 assay, wound healing assay and transwell assay were used to measure proliferation and migration of prostate cancer cells.
In this study, in prostate cancer cells, we found that RNAi-mediated downregulation of ZEB1-AS1 induced significant ZEB1 inhibition while artificial overexpression of ZEB1-AS1 rescued ZEB1 expression, which means that ZEB1-AS1 promotes ZEB1 expression. Also, ZEB1-AS1 indirectly inhibited miR200c, the well-known target of ZEB1, and upregulated miR200c's target BMI1. Mechanistically, ZEB1-AS1 bound and recruited histone methyltransferase MLL1 to the promoter region of ZEB1, induced H3K4me3 modification therein, and activated ZEB1 transcription. Biologically, ZEB1-AS1 promoted proliferation and migration of prostate cancer cells.
Collectively, ZEB1-AS1 functions as an oncogene in prostate cancer via epigenetically activating ZEB1 and indirectly regulating downstream molecules of ZEB1.
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare but lethal subtype of RCC. Little is known about the genomic profile of FH-deficient RCC, and the therapeutic options ...for advanced disease are limited. To this end, we performed a comprehensive genomics study to characterize the genomic and epigenomic features of FH-deficient RCC.
Integrated genomic, epigenomic, and molecular analyses were performed on 25 untreated primary FH-deficient RCCs. Complete clinicopathologic and follow-up data of these patients were recorded.
We identified that FH-deficient RCC manifested low somatic mutation burden (median 0.58 mutations per megabase), but with frequent somatic copy-number alterations. The majority of FH-deficient RCCs were characterized by a CpG sites island methylator phenotype, displaying concerted hypermethylation at numerous CpG sites in genes of transcription factors, tumor suppressors, and tumor hallmark pathways. However, a few cases (20%) with low metastatic potential showed relatively low DNA methylation levels, indicating the heterogeneity of methylation pattern in FH-deficient RCC. Moreover, FH-deficient RCC is potentially highly immunogenic, characterized by increased tumor T-cell infiltration but high expression of immune checkpoint molecules in tumors. Clinical data further demonstrated that patients receiving immune checkpoint blockade-based treatment achieved improved progression-free survival over those treated with antiangiogenic monotherapy (median, 13.3 vs. 5.1 months;
= 0.03).
These results reveal the genomic features and provide new insight into potential therapeutic strategies for FH-deficient RCC.
The interaction between soil and geotextile is essential for the performance of reinforced soil. This study reveals the microscopic mechanism of interface shear between sand and geotextile based on ...the discrete element method (DEM). The surface characteristics of geotextile are simulated by overlapped particles. The micromechanical parameters of sand, geotextile, and interface are calibrated effectively using laboratory test results. Three types of shear tests on the sand–geotextile interface are simulated; namely, interface direct shear test (IDST), double-sided interface shear test (D_IST), and interface direct shear test with periodic boundary (PBST). For IDST, the results show that the thickness of shear band is 2.4∼3.0 times the average particle diameter (D
50
); the contact force, percentage of sliding contact, and contact normal anisotropy inside the shear band are larger than those outside the shear band, whereas the coordination number is smaller inside the shear band. The mechanical response of D_IST is similar to that of IDST. However, D_IST has a shear band thickness of 3.0D
50
, and greater coordination number, percentage of sliding contact, and contact normal anisotropy. The results of PBST indicate that the peak stress and the shear band no longer appear without boundary constraint and the contact distribution is uniform.
TIM-3 (T cell immunoglobulin and mucin-domain containing protein 3) is a member of the TIM family of proteins that is preferentially expressed on Th1 polarized CD4+ and CD8+ T cells. Recent studies ...indicate that TIM-3 serves as a negative regulator of T cell function (i.e. T cell dependent immune responses, proliferation, tolerance, and exhaustion). Despite having no recognizable inhibitory signaling motifs, the intracellular tail of TIM-3 is apparently indispensable for function. Specifically, the conserved residues Y265/Y272 and surrounding amino acids appear to be critical for function. Mechanistically, several studies suggest that TIM-3 can associate with interleukin inducible T cell kinase (ITK), the Src kinases Fyn and Lck, and the p85 phosphatidylinositol 3-kinase (PI3K) adaptor protein to positively or negatively regulate IL-2 production via NF-κB/NFAT signaling pathways. To begin to address this discrepancy, we examined the effect of TIM-3 in two model systems. First, we generated several Jurkat T cell lines stably expressing human TIM-3 or murine CD28-ECD/human TIM-3 intracellular tail chimeras and examined the effects that TIM-3 exerts on T cell Receptor (TCR)-mediated activation, cytokine secretion, promoter activity, and protein kinase association. In this model, our results demonstrate that TIM-3 inhibits several TCR-mediated phenotypes: i) NF-kB/NFAT activation, ii) CD69 expression, and iii) suppression of IL-2 secretion. To confirm our Jurkat cell observations we developed a primary human CD8+ cell system that expresses endogenous levels of TIM-3. Upon TCR ligation, we observed the loss of NFAT reporter activity and IL-2 secretion, and identified the association of Src kinase Lck, and PLC-γ with TIM-3. Taken together, our results support the conclusion that TIM-3 is a negative regulator of TCR-function by attenuating activation signals mediated by CD3/CD28 co-stimulation.
•Psilocybin has a rapid, sizable, and long-term antidepressive effect for primary (major depression patients) and secondary depressive disorder (depressed cancer patients).•Within a certain range, ...the antidepressive effect of psilocybin decreases and then increases as the dose increases, with 30-35mg/70kg being the most effective dose.
Previous studies have shown that psilocybin has antidepressant effects. In the current study, we aim to explore the dose effects of psilocybin on primary (major depression patients) and secondary depression (depressed cancer patients).
Published studies concerning psilocybin for depression were retrieved. In accordance with PRISMA guidelines, 6 databases (PubMed, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov 2.3 and WanFang database) were searched for research studies published or still in progress from inception to 30 November, 2020, with language restricted to English and Chinese. Hedges’ g of Beck Depression Inventory (BDI) score changes was calculated as the primary outcome.
7 articles were finally included, with a total of 136 participants. In terms of efficacy, Hedges’ g was 1.289 (95%CI=1.020, 1.558, heterogeneity I2=50.995%, p<0.001). As psilocybin dose increases within a certain range, the antidepressive effect declines and then increases, with 30-35 mg/70 kg achieving the optimal therapeutic effect. Subgroup analysis suggested that the antidepressive effect of psilocybin was extremely significant at a relatively high dose (30-35mg/70kg: Hedges’ g=3.059, 95%CI=2.269, 3.849, p<0.001), long-term (>1month: Hedges’ g=1.123, 95%CI=0.861, 1.385, p<0.001) and when used in primary depression patients (Hedges’ g=2.190, 95%CI=1.423, 2.957, p<0.001).
Only a small number of studies can be identified of variable quality, thus our conclusions remain preliminary.
Our preliminary results have shown that psilocybin exerts a rapid effect in reducing depressive symptom on primary and secondary depression. The optimal dose of psilocybin may be 30-35mg/70kg or higher; future clinical trials are warranted for further evaluation on its effect.
Research is needed on the “institutionalization” of public relations as a strategic-management function. How and why public relations ought to be institutionalized certainly remains highly debatable. ...This study, thus, engages the current debate on the necessity and advantages of the institutionalization of public relation by taking on Chinese government crisis communication in the 2008 Sichuan earthquake as a test case.
This study employs both qualitative and quantitative methods, consisting largely of online and textual research, convenient and confidential telephone interviews, content analysis of government communication materials, and intercept surveys in Beijing (China's capital city) and Chengdu (the provincial capital of the Sichuan Province where the earthquake hits).
The study finds that the institutionalization of government public relations in China has visible results, especially, in the areas of crisis communication and management, as well as stakeholder-relationship building. Within the Chinese context, it suggests, “institutionalization” of the government public relations tends to render legitimacy to public relations practice and empower the practitioners by according PR practice a strategic function toward the achievement of public-institution effectiveness. Although a preliminary analysis, this study supports the argument on the necessity and advantages for PR practice becoming institutionalized.
There is considerable interest in understanding the effect of transposable elements (TEs) on embryonic development. Studies in humans and mice are limited by the difficulty of working with mammalian ...embryos, and by the relative scarcity of active TEs in these organisms. Zebrafish is an outstanding model for the study of vertebrate development and over half of its genome consists of diverse TEs. However, zebrafish TEs remain poorly characterized. Here we describe the demography and genomic distribution of zebrafish TEs and their expression throughout embryogenesis using bulk and single-cell RNA sequencing data. These results reveal a highly dynamic genomic ecosystem comprising nearly 2,000 distinct TE families, which vary in copy number by four orders of magnitude and span a wide range of ages. Longer retroelements tend to be retained in intergenic regions, whilst short interspersed nuclear elements (SINEs) and DNA transposons are more frequently found nearby or within genes. Locus-specific mapping of TE expression reveals extensive TE transcription during development. While two thirds of TE transcripts are likely driven by nearby gene promoters, we still observe stage and tissue-specific expression patterns in self-regulated TEs. Long terminal repeat (LTR) retroelements are most transcriptionally active immediately following zygotic genome activation, whereas DNA transposons are enriched amongst transcripts expressed in later stages of development. Single-cell analysis reveals several endogenous retroviruses expressed in specific somatic cell lineages. Overall, our study provides a valuable resource for using zebrafish as a model to study the impact of TEs on vertebrate development.
With the continuous development and innovation of information technology, virtual reality (VR) has become an important topic of education technology in recent years. VR is not only applied in many ...industries, but is also used by scholars for education applications as it enables students to have an immersive learning experience to enhance their learning effectiveness and motivation. Therefore, this study combined the spherical video-based virtual reality (SVVR) and a hands-on activity to help fifth-grade students learn natural geomorphological knowledge. The experimental group students used the hands-on approach to design a SVVR system to learn natural geomorphological knowledge; the control group used the conventional SVVR guiding system to learn. From the experimental results, there were non-significant differences in the learning achievement and learning motivation of students in the experimental and control groups. However, the students in the experimental group had better achievement on the in-depth knowledge test. In other words, the experimental group students needed to understand more about the learning content of natural geomorphological knowledge to design the VR system. Moreover, the hands-on approach cultivated their problem-solving and metacognitive skills.
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