Explore the vast range of titles available.

Nrf2, a transcription factor that regulates the response to oxidative stress, has been shown to rescue cone photoreceptors and slow vision loss in mouse models of retinal degeneration (rd). The retinal pigment epithelium (RPE) is damaged in these models, but whether it also could be rescued by Nrf2 has not been previously examined. We used an adeno-associated virus (AAV) with an RPE-specific (Best1) promoter to overexpress Nrf2 in the RPE of rd mice. Control rd mice showed disruption of the regular array of the RPE, as well as loss of RPE cells. Cones were lost in circumscribed regions within the cone photoreceptor layer. Overexpression of Nrf2 specifically in the RPE was sufficient to rescue the RPE, as well as the disruptions in the cone photoreceptor layer. Electron microscopy showed compromised apical microvilli in control rd mice but showed preserved microvilli in Best1-Nrf2-treated mice. The rd mice treated with Best1-Nrf2 had slightly better visual acuity. Transcriptome profiling showed that Nrf2 upregulates multiple oxidative defense pathways, reversing declines seen in the glutathione pathway in control rd mice. In summary, Nrf2 overexpression in the RPE preserves RPE morphology and survival in rd mice, and it is a potential therapeutic for diseases involving RPE degeneration, including age-related macular degeneration (AMD).

Anecdotal reports indicate that many animal shelters experienced increased adoption and foster care rates during the COVID-19 pandemic, yet peer-reviewed evidence is lacking. In this pilot survey of 14 animal shelters in the Northeastern United States, we aimed to investigate the impact of the COVID-19 pandemic on animal intakes, foster care and five outcome types and describe operational changes reported by shelters in response to COVID-19. Paired sample t-tests and Wilcoxon signed-rank tests were used to compare intake, adoption, euthanasia and foster care rates and numbers between March–June 2019 and 2020. The number of dogs and cats that entered shelters was significantly lower during the COVID-19 pandemic compared with the same months of 2019 (t = 3.41, p = 0.01, t = 2.69, p = 0.02). Although the overall rate of adoption and euthanasia did not differ, the numbers adopted and euthanized decreased significantly for both dogs and cats, reflecting the significantly decreased intake. We also found significant variability between shelters. During the pandemic, several shelters sought to expand their foster care networks through operational changes (n = 6) and statements made to the public (n = 7). However, the proportion of dogs and cats housed in foster care did not differ between March–June 2019 and 2020 in our sample. Our findings offer preliminary insights regarding the impact of a worldwide pandemic on the functioning of animal shelters.

Adeno-associated viral vectors (AAVs) have become popular for gene therapy, given their many advantages, including their reduced inflammatory profile compared with that of other viruses. However, even in areas of immune privilege such as the eye, AAV vectors are capable of eliciting host-cell responses. To investigate the effects of such responses on several ocular cell types, we tested multiple AAV genome structures and capsid types using subretinal injections in mice. Assays of morphology, inflammation, and physiology were performed. Pathological effects on photoreceptors and the retinal pigment epithelium (RPE) were observed. Müller glia and microglia were activated, and the proinflammatory cytokines TNF-α and IL-1β were up-regulated. There was a strong correlation between cisregulatory sequences and toxicity. AAVs with any one of three broadly active promoters, or an RPE-specific promoter, were toxic, while AAVs with four different photoreceptor-specific promoters were not toxic at the highest doses tested. There was little correlation between toxicity and transgene, capsid type, preparation method, or cellular contaminants within a preparation. The toxic effect was dose-dependent, with the RPE being more sensitive than photoreceptors. Our results suggest that ocular AAV toxicity is associated with certain AAV cis-regulatory sequences and/or their activity and that retinal damage occurs due to responses by the RPE and/or microglia. By applying multiple, sensitive assays of toxicity, AAV vectors can be designed so that they can be used safely at high dose, potentially providing greater therapeutic efficacy.

Human de novo genes can originate from neutral long non-coding RNA (lncRNA) loci and are evolutionarily significant in general, yet how and why this all-or-nothing transition to functionality happens remains unclear. Here, in 74 human/hominoid-specific de novo genes, we identified distinctive U1 elements and RNA splice-related sequences accounting for RNA nuclear export, differentiating mRNAs from lncRNAs, and driving the origin of de novo genes from lncRNA loci. The polymorphic sites facilitating the lncRNA–mRNA conversion through regulating nuclear export are selectively constrained, maintaining a boundary that differentiates mRNAs from lncRNAs. The functional new genes actively passing through it thus showed a mode of pre-adaptive origin, in that they acquire functions along with the achievement of their coding potential. As a proof of concept, we verified the regulations of splicing and U1 recognition on the nuclear export efficiency of one of these genes, the ENSG00000205704 , in human neural progenitor cells. Notably, knock-out or over-expression of this gene in human embryonic stem cells accelerates or delays the neuronal maturation of cortical organoids, respectively. The transgenic mice with ectopically expressed ENSG00000205704 showed enlarged brains with cortical expansion. We thus demonstrate the key roles of nuclear export in de novo gene origin. These newly originated genes should reflect the novel uniqueness of human brain development. Studying human-specific de novo genes originated from long non-coding RNA, the authors reveal molecular mechanisms that facilitate nuclear export of these young genes, and show experimental evidence for the role of one such gene in brain development.

Robust principal component analysis (RPCA) based methods via decomposition into low-rank plus sparse matrices offer a wide range of applications for image processing, video processing and 3D computer vision. Most of the time the observed imagery data is often arbitrarily corrupted by anything such as large sparse noise, small dense noise and other unknown fraction, which we call mixed noise in this paper. However, low rank matrix recovery by RPCA is born for the existence of large sparse noise, so its performance and applicability are limited in the presence of mixed noise. In this paper, a generalized robust principal component analysis with norm l 2 , 1 model is proposed to solve the problem of low-rank matrix recovery under mixed large sparse noise and small dense noise. The corrupted matrix is written as a combination that minimizes the nuclear norm, the 1-norm and the norm l 2 , 1 , which has high efficiency, flexibility and robustness for low rank matrix recovery from mixed noise. Then a novel and efficient algorithm called random permutation alternative direction of multiplier method is applied to solve the model. Experiments with simulations and real datasets demonstrate efficiency and robustness of this model and algorithm.

The Mueller Matrix Polar Decomposition method decomposes a Mueller matrix into a diattenuator, a retarder, and a depolarizer. Among these elements, the retarder, which plays a key role in medical and material characterization, is modelled as a circular retarder followed by a linear retarder when using this approach. However, this model may not accurately reflect the actual structure of the retarder in certain cases, as many practical retarders do not have a layered structure or consist of multiple (unknown) layers. Misinterpretation, therefore, may occur when the actual structure differs from the model. Here we circumvent this limitation by proposing to use a physically plausible parameter set that includes the axis orientation angle \\(\\phi\\), the degree of ellipticity \\(\\chi\\), and the elliptical retardance \\(\\rho\\). By working with this set of parameters, an overall characterization of a retarder is provided, encompassing its full optical response without making any assumptions about the structure of the material. In this study, experiments were carried out on liquid crystalline samples to validate the feasibility of our approach, demonstrating that the physically plausible parameter set adopted provides a useful tool for a broader range of applications in both biomedical imaging and optical material analysis.

在基于Ring-LWE体系的格密码算法中, 快速数论变换是加速多项式环乘法的常见方法, 但该方法对于系数域模数小于多项式长度的多项式环乘法不适用. 本文通过对多项式系数域构造扩域, 扩大系数域的阶数, 使小模数的多项式环乘法也能够使用快速数论变换来加速. 扩域上的有限域乘法会带来额外的计算开支, 但快速NTT变换的使用可以带来指数级的加速效果, 总体来说节省更多的计算复杂度. 常见的快速数论变换使用与快速傅里叶变换相似的折半定理, 进行基2的快速变换, 而系数域构造扩域后由于其阶数无法满足基2变换的条件, 本文通过将多项式长度进行质因子分解来推导复合基的快速数论变换, 最终为小模数多项式环乘法提供可观的加速效果.

目的：探讨羟基喜树碱联合顺铂和氟尿嘧啶结合同期放疗治疗晚期非小细胞肺癌的临床疗效和毒性反应。方法：羟基喜树碱6mg/m^2，静脉滴注第1～5天，顺铂30mg/m^2，静脉滴注第1～3天，氟尿嘧啶300mg/m^2，静脉滴注第1～5天，28天为一个周期，至少治疗2周期。放射治疗与化疗同期进行，原发灶总剂量DT50～70Gy／25～35次／5～9周，转移病灶30～60Gy/10～30次／2～8周。结果:全组共31例，完全缓解(CR)6例，部分缓解(PR)18例，总有效率为77．4％。中位生存期16．7个月，1、2年生存率分别为54．7％、30．2％，1、2年局部控制率分别为61％、40％。主要毒副反应是骨髓抑制和消化道反应，但均可耐受。结论:羟基喜树碱为主的联合化疗结合同期放疗是治疗晚期非小细胞肺癌的有效方法，能减轻症状，改善生存质量，延长生存期。