Motor neuron degeneration resulting from the aggregation of the androgen receptor with an expanded polyglutamine tract (AR-polyQ) has been linked to the development of spinal and bulbar muscular ...atrophy (SBMA or Kennedy disease). Here we report that adding 5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one (ASC-J9) disrupts the interaction between AR and its coregulators, and also increases cell survival by decreasing AR-polyQ nuclear aggregation and increasing AR-polyQ degradation in cultured cells. Intraperitoneal injection of ASC-J9 into AR-polyQ transgenic SBMA mice markedly improved disease symptoms, as seen by a reduction in muscular atrophy. Notably, unlike previous approaches in which surgical or chemical castration was used to reduce SBMA symptoms, ASC-J9 treatment ameliorated SBMA symptoms by decreasing AR-97Q aggregation and increasing VEGF164 expression with little change of serum testosterone. Moreover, mice treated with ASC-J9 retained normal sexual function and fertility. Collectively, our results point to a better therapeutic and preventative approach to treating SBMA, by disrupting the interaction between AR and AR coregulators.
Although nearly all countries in the world have taken active measures to mitigate the greenhouse effect, which is the primary cause of extreme climate change, the electric motor accounts for 40–50% ...of the total global electricity consumption, thus becoming the primary appliance requiring high-efficiency standards. In this report, a survey is conducted on high-efficiency motor promotion cases in Taiwan and developed countries. Furthermore, a comparison of the policy, technology, regulatory, and trend aspects is summarized. We conclude that the research and technical development of DC brushless motors is the most popular program in the motor industry, and permanent magnet synchronous motors are essentially the most welcome product in the market. The corresponding R&D items include the optimization of the motor design, electromagnetic enhancement of silicon steel sheets, promotion of the advantages of the permanent magnetic field, modification of the wire-winding technology, and improvements in the electronic control technology. Described at the end of this report, the suggested policies for the development of high-efficiency motors are applicable to Taiwan as well as other countries. The energy saving and carbon reduction issues as well as the approach of the high-energy price era have led to the rapid development and popularization of high-efficiency motors.
Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new ...tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.
3D object recognition in cluttered scenes is a rapidly growing research area. Based on the used types of features, 3D object recognition methods can broadly be divided into two categories-global or ...local feature based methods. Intensive research has been done on local surface feature based methods as they are more robust to occlusion and clutter which are frequently present in a real-world scene. This paper presents a comprehensive survey of existing local surface feature based 3D object recognition methods. These methods generally comprise three phases: 3D keypoint detection, local surface feature description, and surface matching. This paper covers an extensive literature survey of each phase of the process. It also enlists a number of popular and contemporary databases together with their relevant attributes.
Integral membrane proteins of the divalent anion/Na⁺ symporter (DASS) family are conserved from bacteria to humans. DASS proteins typically mediate the coupled uptake of Na⁺ ions and dicarboxylate, ...tricarboxylate, or sulfate. Since the substrates for DASS include key intermediates and regulators of energy metabolism, alterations of DASS function profoundly affect fat storage, energy expenditure and life span. Furthermore, loss-of-function mutations in a human DASS have been associated with neonatal epileptic encephalopathy. More recently, human DASS has also been implicated in the development of liver cancers. Therefore, human DASS proteins are potentially promising pharmacological targets for battling obesity, diabetes, kidney stone, fatty liver, as well as other metabolic and neurological disorders. Despite its clinical relevance, the mechanism by which DASS proteins recognize and transport anionic substrates remains unclear. Recently, the crystal structures of a bacterial DASS and its humanized variant have been published. This article reviews the mechanistic implications of these structures and suggests future work to better understand how the function of DASS can be modulated for potential therapeutic benefit.
Aim: To investigate the effects of ROS scavenger N-acetylcysteine (NAC) on angiotensin II (Ang II)-mediated renal fibrosis in vivo and in vitro. Methods: Mice were subjected to unilateral ureteral ...obstruction (UUO), and then treated with vehicle or NAC (250 mg/kg, ip) for 7 days. Histological changes of the obstructed kidneys were observed with Masson's trichrome staining. ROS levels were detected with DHE staining. The expression of relevant proteins in the obstructed kidneys was assessed using Western blotting assays. Cultured rat renal fibroblast NRK-49F cells were used for in vitro experiments. Results: In the obstructed kidneys, Ang II levels were significantly elevated, and collagen I was accumulated in the interstitial spaces. Furthermore, ROS production and the expression of p47 (a key subunit of NADPH oxidase complexes) were increased in a time- dependent manner; the expression of fibronectin, α-SMA and TGF-β were upregulated. Administration of NAC significantly alleviated the fibrotic responses in the obstructed kidneys. In cultured NRK-49F cells, treatment with Ang II (0.001-10 pmol/L) increased the expression of fibronectin, collagen I, α-SMA and TGF-β in dose-dependent and time-dependent manners. Ang II also increased ROS production and the phosphorylation of Smad3. Pretreatment with NAC (5 pmol/L) blocked Ang II-induced oxidative stress and ECM production in the cells. Conclusion" In mouse obstructed kidneys, the fibrotic responses result from Ang II upregulation can be alleviated by the ROS scavenger N-acetylcysteine.
Prime editing is a novel and universal CRISPR/Cas-derived precision genome-editing technology that has been recently developed. However, low efficiency of prime editing has been shown in transgenic ...rice lines. We hypothesize that enhancing pegRNA expression could improve prime-editing efficiency. In this report, we describe two strategies for enhancing pegRNA expression. We construct a prime editing vector harboring two pegRNA variants for W542L and S621I double mutations in ZmALS1 and ZmALS2. Compared with previous reports in rice, we achieve much higher prime-editing efficiency in maize. Our results are inspiring and provide a direction for the optimization of plant prime editors.
Research activities relating to data envelopment analysis (DEA) have grown at a fast rate recently. Exactly what activities have been carrying the research momentum forward is a question of ...particular interest to the research community. The purpose of this study is to find these research activities, or research fronts, in DEA. A research front refers to a coherent topic or issue addressed by a group of research articles in recent years. The large amount of DEA literature makes it difficult to use any traditional qualitative methodology to sort out the matter. Thus, this study applies a network clustering method to group the literature through a citation network established from the DEA literature over the period 2000 to 2014. The keywords of the articles in each discovered group help pinpoint its research focus. The four research fronts identified are “bootstrapping and two-stage analysis”, “undesirable factors”, “cross-efficiency and ranking”, and “network DEA, dynamic DEA, and SBM”. Each research front is then examined with key-route main path analysis to uncover the elements in its core. In addition to presenting the research fronts, this study also updates the main paths and author statistics of DEA development since its inception and compares them with those reported in a previous study.
•This study presents research fronts in DEA in the period 2000-2014.•These research fronts include two-stage analysis, undesirable factors, cross-efficiency, and network DEA.•The growth of the network DEA subarea shows a surge in the period 2008-2012.•This study also updates the main paths and author statistics of DEA development since its inception.
LncRNAs have been recognized as significant regulators in various diseases including neuropathic pain. Although the lncRNA NEAT1 has been reported to be involved in multiple cancers, its biological ...functions in neuropathic pain still remain unknown. In our present study, a chronic constriction injury (CCI) rat model was established and we found that NEAT1 was greatly upregulated in the spinal cord tissues of CCI rats. Knockdown of NEAT1 can repress neuropathic pain behaviors including mechanical and thermal hyperalgesia. In addition, NEAT1 downregulation inhibited neuroinflammation via inhibiting IL‐6, IL‐1β, and tumor necrosis factor (TNF)‐α in CCI rats. We also observed that miR‐381 was decreased significantly in CCI rats. By using bioinformatics analysis, miR‐381 was predicted to be a microRNA target of NEAT1, which indicated a negative correlation between miR‐381 and NEAT1. Inhibition of NEAT1 can induce miR‐381 expression in CCI rats, which indicated a negative correlation between NEAT1 and miR‐381. HMGB1, as a downstream target gene of miR‐381 was observed to be dramatically increased in CCI rats. miR‐381 can modulate HMGB1 expression negatively and meanwhile, NEAT1 was able to regulate HMGB1 through sponging miR‐381. Downregulation of HMGB1 can inhibit neuropathic pain behaviors which can be reversed by miR‐381 inhibitors. Taken these together, it was indicated that NEAT1 can induce neuropathic pain development in CCI rats via regulating miR‐381/HMGB1 axis.
We found that knockdown of NEAT1 can alleviate neuropathic pain by increasing miR‐381 and inhibiting neuro‐inflammation in CCI rats. For another, NEAT1 can modulate HMGB1 by sponging miR‐381 in neuropathic pain. Our findings indicated that NEAT1 can serve as a treatment target in neuropathic pain.
Current influenza vaccines only confer protection against homologous viruses. We synthesized pulmonary surfactant (PS)-biomimetic liposomes encapsulating 2',3'-cyclic guanosine ...monophosphate-adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING (stimulator of interferon genes). The adjuvant (PS-GAMP) vigorously augmented influenza vaccine-induced humoral and CD8
T cell immune responses in mice by simulating the early phase of viral infection without concomitant excess inflammation. Two days after intranasal immunization with PS-GAMP-adjuvanted H1N1 vaccine, strong cross-protection was elicited against distant H1N1 and heterosubtypic H3N2, H5N1, and H7N9 viruses for at least 6 months while maintaining lung-resident memory CD8
T cells. Adjuvanticity was then validated in ferrets. When alveolar epithelial cells (AECs) lacked
or gap junctions were blocked, PS-GAMP-mediated adjuvanticity was substantially abrogated in vivo. Thus, AECs play a pivotal role in configuring heterosubtypic immunity.