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1.
Thorac Cancer ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31901156

RESUMO

BACKGROUND: TP73 antisense RNA 1 (TP73-AS1) is a long noncoding RNA which has been shown to be involved in the progression of multiple malignant tumors. Previous studies have demonstrated the oncogenic role of TP73-AS1 in breast cancer. However, its molecular mechanism remains largely unknown in breast tumorigenesis. METHODS: Expression of TP63-AS1, miRNA-125a-3p (miR-125a) and metadherin (MTDH) was detected by real-time quantitative PCR and western blotting. The malignancy was evaluated by cell counting kit 8 (CCK-8), transwell assays, flow cytometry and western blotting. The target binding was confirmed by dual luciferase reporter assay. Xenograft tumor model was performed to detect tumor growth in vivo. RESULTS: Expression of TP73-AS1 was higher in breast cancer tissues and cell lines. Biologically, its knockdown could promote cell apoptosis rate, and inhibit proliferative capacity, migration and invasion ability in HCC-70 and MB231 cells, accompanied with higher cleaved caspase 3 level and lower Ki67, N-cadherin and Vimentin level. Moreover, TP73-AS1 downregulation restrained the tumor growth of HCC-70 cells in vivo. Mechanically, TP73-AS1 functioned as a molecular "sponge" for miR-125a to modulate MTDH, a downstream target of miR-125a. Intriguingly, both miR-125a overexpression and MTDH silencing exerted a tumor-suppressive effect in the malignant progression of HCC-70 and MB231 cells, which was counteracted by TP73-AS1 upregulation and miR-125a downregulation, respectively. CONCLUSION: Knockdown of TP73-AS1 inhibited cell proliferation, migration and invasion, but facilitated apoptosis in breast cancer cells in vitro through targeting miR-125a and upregulating MTDH, suggesting a novel TP73-AS1/miR-125a/MTDH pathway in the malignant progression of breast cancer.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31831452

RESUMO

In this article, the event-triggered-based adaptive neural network control problem is studied for a class of nonlinear time-delay systems with nonstrict-feedback structures and unknown control directions. First, a compensation system is introduced to handle the input delay and an observer is also designed to estimate the unmeasurable states. Then, by employing the neural networks and the variable separation approach, the adaptive backstepping method is applied to control the nonlinear systems with nonstrict-feedback structures. By codesigning the adaptive controller and the triggering mechanism, the input-to-state stability (ISS) assumption with respect to the measurement error is removed. Finally, it is shown that the proposed event-triggered adaptive controller can ensure the semiglobal boundedness of all the states in the closed-loop systems.

3.
J Arthroplasty ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31784362

RESUMO

BACKGROUND: A number of articles have been published reporting on the clinical outcomes of various acetabular reconstructions for the management of chronic pelvic discontinuity (PD). However, no systematic review of the literature has been published to date comparing the outcome and complications of different approaches to reconstruction. METHODS: The US National Library of Medicine (PubMed/MEDLINE) and EMBASE were queried for publications from January 1980 to January 2019 using keywords pertinent to total hip arthroplasty, PD, acetabular dissociation, clinical or functional outcomes, and revision total hip arthroplasty or postoperative complications. RESULTS: Overall, 18 articles were included in this analysis (569 cases with chronic PD). The overall survival rate of the acetabular components used for the treatment of chronic PD was 84.7% (482 of 569 cases) at mid-term follow-up, whereas the most common reasons for revision were aseptic loosening (54 of 569 hips; 9.5%), dislocations (45 of 569 hips; 7.9%), periprosthetic joint infection (30 of 569 hips; 5.3%), and periprosthetic fractures (11 of 569 hips; 1.9%). Both pelvic distraction technique (combined with highly porous shells) and custom triflanges resulted in less than 5% failure rates (96.2% and 95.8%, respectively) at final follow-up. Also, highly effective in the treatment of PD were cup-cages and highly porous shells with and/or without augments with 92% survivorship free of revision for aseptic loosening for both reconstruction methods. Inferior outcomes were reported for conventional cementless shells combined with acetabular plates (72.7%) as well as ilioischial cages and reconstruction rings (66.7% and 60.6% survivorship, respectively). CONCLUSION: The current literature contains moderate quality evidence in support of the use of custom triflange implants and pelvic distraction techniques for the treatment of chronic PD, with a less than 5% all-cause revision rate and low complication rates at mean mid-term follow-up. Cup-cages and highly porous shells with or without augments could also be considered for the treatment of PD because both resulted in greater than 90% survival rates. Finally, there is still no consensus regarding the impact of different types of acetabular reconstruction methods on optimizing the healing potential of PD, and further studies are required in this area to better understand the influence of PD healing on construct survivorship and functional outcomes with each reconstruction method.

4.
Light Sci Appl ; 8: 98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31700618

RESUMO

Intelligence at either the material or metamaterial level is a goal that researchers have been pursuing. From passive to active, metasurfaces have been developed to be programmable to dynamically and arbitrarily manipulate electromagnetic (EM) wavefields. However, the programmable metasurfaces require manual control to switch among different functionalities. Here, we put forth a smart metasurface that has self-adaptively reprogrammable functionalities without human participation. The smart metasurface is capable of sensing ambient environments by integrating an additional sensor(s) and can adaptively adjust its EM operational functionality through an unmanned sensing feedback system. As an illustrative example, we experimentally develop a motion-sensitive smart metasurface integrated with a three-axis gyroscope, which can adjust self-adaptively the EM radiation beams via different rotations of the metasurface. We develop an online feedback algorithm as the control software to make the smart metasurface achieve single-beam and multibeam steering and other dynamic reactions adaptively. The proposed metasurface is extendable to other physical sensors to detect the humidity, temperature, illuminating light, and so on. Our strategy will open up a new avenue for future unmanned devices that are consistent with the ambient environment.

5.
J Hazard Mater ; : 121659, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31776080

RESUMO

Although in-vivo exposure of PM2.5 has been suggested to initiate a disorder on vascular permeability, the effects and related mechanism has not been well defined. In this work, an obvious increase on vascular permeability has been confirmed in vivo by vein injection of PM2.5 into Balb/c mouse. Human umbilical vein vascular endothelial cells and the consisted ex-vivo vascular endothelium were used as model to investigate the effects of PM2.5 on the vascular permeability and the underlying molecular mechanism. Upon PM2.5 exposure, the vascular endothelial growth factor receptor 2 on cell membrane phosphorylates and activates the downstream mitogen-activated protein kinase (MAPK)/ERK signaling. The adherens junction protein VE-cadherin sheds and the intercellular junction opens, damaging the integrity of vascular endothelium via paracellular pathway. Besides, PM2.5 induces the intracellular reactive oxygen species (ROS) production and triggers the oxidative stress including activity decrease of superoxide dismutase, lactate dehydrogenase release and permeability increase of cell membrane. Taken together, the paracellular and transcellular permeability enhancement jointly contributes to the significant increase of endothelium permeability and thus vascular permeability upon PM2.5 exposure. This work provides an insight into molecular mechanism of PM2.5 associated cardiovascular disease and offered a real-time screening method for the health risk of PM2.5.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31776607

RESUMO

L-Theanine is a unique non-protein amino acid found in tea plants that has been shown to possess numerous functional properties relevant to food science and human nutrition. L-Theanine has been commercially developed as a valuable additive for use in food and beverages, and its market is expected to expand substantially if the production cost can be lowered. Although the enzymatic approach holds considerable potential for use in L-theanine production, demand exists for developing more tractable methods (than those currently available) that can be implemented under mild conditions and will reduce operational procedures and cost. Here, we sought to engineer fermentative production of L-theanine in Corynebacterium glutamicum, an industrially safe host. For L-theanine synthesis, we used γ-glutamylmethylamide synthetase (GMAS), which catalyzes the ATP-dependent ligation of L-glutamate and ethylamine. First, distinct GMASs were expressed in C. glutamicum wild-type ATCC 13032 strain and GDK-9, an L-glutamate overproducing strain, to produce L-theanine upon ethylamine addition to the hosts. Second, the L-glutamate exporter in host cells was disrupted, which markedly increased the L-theanine titer in GDK-9 cells and almost eliminated the accumulation of L-glutamate in the culture medium. Third, a chromosomally gmasMm-integrated L-alanine producer was constructed and used, attempting to synthesize ethylamine endogenously by expressing plant-derived L-serine/L-alanine decarboxylases; however, these enzymes showed no L-alanine decarboxylase activity under our experimental conditions. The optimal engineered strain that we ultimately created produced ~ 42 g/L L-theanine, with a yield of 19.6%, in a 5-L fermentor. This is the first report of fermentative production of L-theanine achieved using ethylamine supplementation.

7.
Am J Chin Med ; 47(7): 1541-1569, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31752524

RESUMO

Corilagin is a polyphenol that can be extracted from many medicinal plants and shows multiple pharmacological effects. We aimed to investigate the role of corilagin on miR-21-regulated hepatic fibrosis, especially miR-21-regulated TGF-ß1/Smad signaling pathway, in hepatic stellate LX2 cell line and Sprague-Dawley rats. The mRNA or protein levels of miR-21, Smad7, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), collagen type I alpha 1 (COL1A1), Smad2, Smad3, Smad2/3, p-Smad2, p-Smad3, p-Smad2/3, and transforming growth factor-ß1 (TGF-ß1) in LX2 cells and liver tissues were determined. Furthermore, gain-of and loss-of function of miR-21 in miR-21-regulated TGF-ß1/Smad signaling pathway were analyzed in LX2 cells. Liver tissues and serum were collected for pathological analysis, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Corilagin treatment reduced mRNA or protein levels of miR-21, CTGF, α-SMA, TIMP-1, TGF-ß1, COL1A1, p-Smad2, p-Smad3, and p-Smad2/3 both in vitro and in vivo. While corilagin increased mRNA and protein levels of Smad7 and MMP-9. After gain-of and loss-of function of miR-21, the downstream effectors of miR-21-regulated TGF-ß1/Smad signaling pathway in LX2 cells changed accordingly, and the changes were inhibited by corilagin. Simultaneously, administration of corilagin not only ameliorated pathological manifestation of liver fibrosis but also reduced levels of α-SMA and COL1A1 in liver tissues and TGF-ß1, ALT levels in serum. Corilagin is able to potentially prevent liver fibrosis by blocking the miR-21-regulated TGF-ß1/Smad signaling pathway in LX2 cells and CCl4-induced liver fibrosis rats, which may provide a novel therapeutic strategy for liver fibrosis.

8.
Fish Physiol Biochem ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624991

RESUMO

Osmoregulation mechanism underlying acclimation of migratory fish to different salinities has been a classical research topic for decades. In this study, the roughskin sculpin (Trachidermus fasciatus) were subjected to two different acute osmotic treatments (one extreme acute and one acute treatment, i.e., E-acute and acute group). Comparisons of branchial enzyme activity, as well as the time-course expression profiling of sirt1, hsf1, and hsp70 were performed to reveal changes at the physiological and molecular levels. As a result, the branchial Na+/K+-ATPase activity was significantly inhibited and the caspase 3/7 relating to apoptosis was significantly induced in the E-acute group; no significant difference of branchial enzyme activity was detected in the acute group. These results suggested that T. fasciatus could keep stable physiological levels when experiencing the acute salinity change but not under extreme osmotic stress. Significant variations of sirt1, hsf1, and hsp70 expression were determined in the four target tissues (gill, intestine, kidney, and liver). Similar profiling was detected between the time-course expression of sirt1 and hsf1, suggesting their association in the osmoregulation process. Tissue-specific gene expression patterns in all the three target genes showed that each tissue possesses its own gene expression pattern in response to salinity changes. The overall different expression profiling of sirt1, hsf1, and hsp70 under the extreme acute and acute osmotic treatments might respectively represent the molecular regulation of stress response and acclimation. The findings make it possible to provide more reliable data to decipher the mechanism of osmoregulation in migratory fish.

9.
Mol Hum Reprod ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31633178

RESUMO

Male 'blind sterile' mice with the causative TBC1 domain family member 20 (TBC1D20) deficiency are infertile with excessive germ cell apoptosis and spermatogenesis arrest at the spermatid stage. Sertoli cells are characterised as 'nurse cells' essential for normal spermatogenesis, but the role and corresponding molecular mechanisms of TBC1D20 deficiency in Sertoli cells of mice are not clear to date. In the present study, the histopathology of the testis and Sertoli cell proliferation and apoptosis were determined, and the corresponding molecular mechanisms were investigated by western blotting. Our data showed the TBC1D20 exhibits a testis-abundant expression pattern, and its expression level is positively associated with spermatogenesis. TBC1D20 is assembled in the Golgi and endoplasmic reticulum and is widely expressed by various germ cell subtypes and Sertoli cells. TBC1D20 deficiency in Sertoli cells led to an excessive apoptosis ratio and G1/S arrest. The increased apoptosis of TBC1D20-deficient Sertoli cell resulted from caspase-12 activation. TBC1D20-deficient Sertoli cells had an abnormal Golgi-endoplasmic reticulum structure, which led to endoplasmic reticulum stress, resulting in cell cycle arrest and excessive apoptosis. It suggested that TBC1D20 deficiency triggers irreversible endoplasmic reticulum stress resulting in G1/S arrest and excessive apoptosis in TBC1D20-deficient Sertoli cells, and TBC1D20 deficiency in Sertoli cells may also contribute to the infertility phenotype in 'blind sterile' male mice.

10.
BMC Genomics ; 20(1): 760, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640558

RESUMO

BACKGROUND: Transcription factors act as important regulators of transcription networks. Basic leucine zipper (bZIP) transcription factors have been shown to be involved in multiple biological processes in plants. However, no information is available for the bZIP family in Cleistogenes songorica, which is an important xerophytic and allotetraploid grass in desert grasslands. RESULTS: In this study, 86 CsbZIPs were identified in the allotetraploid C. songorica genome. For location analysis, CsbZIPs were distributed evenly across two subgenomes of C. songorica. Phylogenetic tree analysis among three species indicated that CsbZIPs were evolutionarily more closely related to OsbZIPs than AtbZIPs. Syntenic and phylogenetic analyses confirmed that the CsbZIPs were mainly expanded by whole-genome duplication events. Furthermore, it was determined that rice and C. songorica might have undergone purified selection during their long evolutionary history by calculating the Ks values and Ka/Ks ratios of orthologous gene pairs. By analysing the expression patterns of CsbZIPs in different tissues and under abiotic stresses, 21 CsbZIP genes were differentially expressed between chasmogamous (CH) and cleistogamous (CL) flowers, including two FLOWERING LOCUS D (FD) genes. In shoots and roots, 79.1 and 87.2% of the CsbZIP genes, respectively, displayed transcript changes under at least one stress treatment, such as heat, cold, drought and salt. Strikingly, 17 common CsbZIP genes showed differential expression under stress response and during CL flowering. Co-expression network, GO annotation and real-time quantitative reverse transcription PCR (qRT-PCR) analyses revealed a close relationship between CL flowering-associated genes and abiotic stress-related genes. CONCLUSIONS: BZIP TFs were comprehensively analysed and identified in allotetraploid C. songorica. Our results provide insights into the evolutionary history of the bZIP family in C. songorica and provide abiotic stress-responsive and CL-associated candidate CsbZIP genes for potential applications in the genetic improvement of plants.

11.
Bioengineered ; 10(1): 561-573, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31648597

RESUMO

Currently, the mechanism of temperature-sensitive production of glutamate in Corynebacterium glutamicum has not been clarified. We first found the murA and murB genes were potentially related to temperature-sensitive secretion of glutamate, which were not existed in a temperature-sensitive mutant. When replenishing murA or/and murB in the mutant, the temperature sensitivity was weakened. While, their knockout in a wild-type strain resulted in temperature-sensitive secretion of glutamate. Peptidoglycan analysis showed that deletion of murA and murB decreased the peptidoglycan synthesis. Comparative metabolomics analysis suggested that the variation in cell wall structure resulted in decreased overall cellular metabolism but increased carbon flow to glutamate synthesis, which was a typical metabolism pattern in industrial temperature-sensitive producing strains. This study clarifies the mechanism between murA and murB deletion and the temperature-sensitive secretion of glutamate in C. glutamcium, and provides a reference for the metabolic engineering of cell wall to obtain increased bioproduction of chemicals.

12.
Oncol Lett ; 18(4): 4194-4202, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31579421

RESUMO

Interaction between endoplasmic reticulum (ER) stress and oxidative stress contributes to the occurrence and development of various types of cancer. The X-box-binding protein 1 (XBP1), which is an important transcription factor in ER stress-related pathways, has also been reported to serve a protective role against oxidative stress. However, the role of XBP1 in serous ovarian cancer (SOC) remains elusive. The aim of the present study was to explore the biological function of XBP1 in SOC cells under normal or oxidative stress conditions. The expression of XBP1 was downregulated in the SOC cell lines A2780 and HO8910 by lentivirus-mediated short hairpin RNA (shRNA). Cell proliferative ability was evaluated by cell colony formation and viability assays. The sensitivity of ovarian cancer cells to oxidative stress was evaluated using cell survival rate and apoptotic rate, determined by the Cell Counting Kit-8 assay and flow cytometry, respectively. Reactive oxygen species (ROS) levels were measured by flow cytometry and cell immunofluorescence using a dichlorodihydrofluorescein diacetate probe. The mRNA and protein expression levels were detected by fluorescence quantitative polymerase chain reaction and western blot analysis, respectively. The results demonstrated that XBP1 was overexpressed in SOC compared with normal ovarian epithelial cells, and that downregulation of XBP1 significantly reduced cell proliferative ability. In addition, the downregulation of XBP1 significantly enhanced the sensitivity of SOC cells to H2O2 by increasing the intracellular ROS levels. The phosphorylation level of the mitogen-activated protein kinase (MAPK) p38 decreased in the cells of the XBP1-knockdown group. These results indicated that XBP1 may serve a protective role against oxidative stress in SOC cells, and the underlying molecular mechanism may be associated with the downregulation of phosphorylated p38. Therefore, targeting XBP1 may act synergistically with ROS inducers in the treatment of SOC.

13.
Light Sci Appl ; 8: 97, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31645938

RESUMO

There is an increasing need to remotely monitor people in daily life using radio-frequency probe signals. However, conventional systems can hardly be deployed in real-world settings since they typically require objects to either deliberately cooperate or carry a wireless active device or identification tag. To accomplish complicated successive tasks using a single device in real time, we propose the simultaneous use of a smart metasurface imager and recognizer, empowered by a network of artificial neural networks (ANNs) for adaptively controlling data flow. Here, three ANNs are employed in an integrated hierarchy, transforming measured microwave data into images of the whole human body, classifying specifically designated spots (hand and chest) within the whole image, and recognizing human hand signs instantly at a Wi-Fi frequency of 2.4 GHz. Instantaneous in situ full-scene imaging and adaptive recognition of hand signs and vital signs of multiple non-cooperative people were experimentally demonstrated. We also show that the proposed intelligent metasurface system works well even when it is passively excited by stray Wi-Fi signals that ubiquitously exist in our daily lives. The reported strategy could open up a new avenue for future smart cities, smart homes, human-device interaction interfaces, health monitoring, and safety screening free of visual privacy issues.

15.
J Exp Clin Cancer Res ; 38(1): 402, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519193

RESUMO

BACKGROUND: Dihydroartemisinin (DHA) has been shown to exert anticancer activity through iron-dependent reactive oxygen species (ROS) generation, which is similar to ferroptosis, a novel form of cell death. However, whether DHA causes ferroptosis in glioma cells and the potential regulatory mechanisms remain unclear. METHODS: Effects of DHA on the proliferation, cell death, ROS and lipid ROS generation as well as reduced gluthione consumption were assessed in glioma cells with or without ferroptosis inhibitor. The biological mechanisms by which glioma cells attenuate the pro-ferroptotic effects of DHA were assessed using molecular methods. RESULTS: DHA induced ferroptosis in glioma cells, as characterized by iron-dependent cell death accompanied with ROS generation and lipid peroxidation. However, DHA treatment simultaneously activated a feedback pathway of ferroptosis by increasing the expression of heat shock protein family A (Hsp70) member 5 (HSPA5). Mechanistically, DHA caused endoplasmic reticulum (ER) stress in glioma cells, which resulted in the induction of HSPA5 expression by protein kinase R-like ER kinase (PERK)-upregulated activating transcription factor 4 (ATF4). Subsequent HSPA5 upregulation increased the expression and activity of glutathione peroxidase 4 (GPX4), which neutralized DHA-induced lipid peroxidation and thus protected glioma cells from ferroptosis. Inhibition of the PERK-ATF4-HSPA5-GPX4 pathway using siRNA or small molecules increased DHA sensitivity of glioma cells by increasing ferroptosis both in vitro and in vivo. CONCLUSIONS: Collectively, these data suggested that ferroptosis might be a novel anticancer mechanism of DHA in glioma and HSPA5 may serve as a negative regulator of DHA-induced ferroptosis. Therefore, inhibiting the negative feedback pathway would be a promising therapeutic strategy to strengthen the anti-glioma activity of DHA.

16.
Cell Biochem Funct ; 37(8): 591-597, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31512281

RESUMO

Cervical cancer is still a serious threat to women's health and life safety worldwide, and new treatment strategies are urgently needed. Accumulating evidences also imply that long non-coding RNAs (lncRNAs) are involved in a wide range of cellular processes, such as cell proliferation, apoptosis, and cell cycle. We found that the expression of lncOGFRP1 in cervical cancer tissues was significantly higher than that in normal cervical tissues (P < .05). Further, CCK8 detection found when lncOGFRP1 was silenced, the proliferation of cells was inhibited. After depleting lncOGFRP1, the proportion of apoptosis cells in C33A (3.71 ± 0.38% VS 11.98 ± 1.26%, P < .05) and SiHa (0.69 ± 0.06% VS 11.06 ± 1.03%, P < .05) cells increased significantly, and cell cycle was arrested in S phase. On the other hand, migration detection found the migration of cells also was hindered when lncOGFRP1 level was reduced. And the depletion of lncOGFRP1 inhibited the expression of ß-catenin, Vimentin, N-cadherin, and SNAIL and promoted the expression of E-cadherin. In summary, we first discovered the high expression of lncOGFRP1 in cervical cancer and revealed that silencing lncOGFRP1 inhibits the proliferation and migration of cervical carcinoma cells. SIGNIFICANCE OF THE STUDY: We first discovered the high expression of lncOGFRP1 in cervical cancer and revealed that silencing lncOGFRP1 inhibits the proliferation and migration of cervical carcinoma cells. These results help to better understand the pathogenesis and development of cervical cancer and provide insight to develop better diagnosis and treatment strategies.

17.
JCI Insight ; 4(18)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31534052

RESUMO

Hereditary renal cystic diseases are characterized by defects in primary cilia of renal tubular epithelial cells and abnormality of tubular epithelium, which ultimately result in the development of renal cysts. However, the mechanism leading from abnormality of the tubular epithelium to cystogenesis is not well understood. In this report, we demonstrate a critical role for Robo2 in regulating epithelial development, including ciliogenesis, polarization, and differentiation. We found that Robo2 deficiency results in cystic kidneys, and the cyst cells showed defective cilia and polarity defects in tubular epithelium. The cyst cells, less than terminally differentiated, continue to proliferate. We further established that Robo2 works with p53 as well as polarity and ciliary proteins (Par3, PKCς, ZO-2, and Claudin-2) to regulate these processes. Robo2 binds to Baiap2 (also known as IRSp53) through the IRSp53/MIM homology domain in renal epithelial cells. This binding allows Robo2 to phosphorylate MDM2 at Ser166 via Baiap2 and maintain p53 homeostasis. Disruption of the Robo2-Baiap2 complex causes MDM2 to be subjected to dephosphorylation, leading to a high level of active p53, and initiated p53-mediated cellular senescence via p21 and decreased the expression of ZO-1, ZO-2, PKCς, Par3, and Claudin-2 proteins, resulting in defects in epithelial development, including ciliogenesis, polarization, and differentiation. Importantly, double knockout of Robo2 and p53 rescued all the epithelial defects in kidneys compared with those in Robo2-knockout kidneys. Taken together, the present results demonstrate that Robo2 deficiency causes renal cystic disease, which is largely dependent on defective Robo2-Baiap2 integrated signaling in kidneys.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31541312

RESUMO

Evolution is a powerful tool for the breeding of microorganisms, while the connection between the changes of intracellular metabolism and different evolution directions is still unclear, which once clarified, will greatly expand the application of evolutionary engineering. We aim to clarify the correlation between metabolism changes and evolution directions in two Corynebacterium glutamicum strains for L-valine and L-leucine overproducing originated from the same parental strain by repeated random mutagenesis and selection. GC-MS metabolomics was performed to identify and quantify intracellular metabolites of the evolved and wild-type C. glutamicum strains. Time-series comparison of the fermentation processes was performed. The metabolism differences of three strains mainly exist in central carbon metabolism and the stress-resisting modes. C. glutamicum XV developed an overall "pyruvate-saving" mode for L-valine synthesis, and adopted a trehalose accumulating strategy to resist environmental stresses. C. glutamicum CP depended on an enhanced "pyruvate-producing" mode, together with certain "pyruvate-saving" strategies, for efficient L-leucine synthesis, and accumulated proline, my-inositol, and inositol as the stress-resisting measure. These elaborate regulation strategies could be used in future metabolic engineering, making evolution more informative and applicable.

19.
Research (Wash D C) ; 2019: 2584509, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31549052

RESUMO

In modern wireless communications, digital information is firstly converted to analog signal by a digital-analog convertor, which is then mixed to high-frequency microwave to be transmitted through a series of devices including modulator, mixer, amplifier, filter, and antenna and is finally received by terminals via a reversed process. Although the wireless communication systems have evolved significantly over the past thirty years, the basic architecture has not been challenged. Here, we propose a method to transmit digital information directly via programmable coding metasurface. Since the coding metasurface is composed of '0' and '1' digital units with opposite phase responses, the digital information can be directly modulated to the metasurface with certain coding sequences and sent to space under the illumination of feeding antenna. The information, being modulated in radiation patterns of the metasurface, can be correctly received by multiple receivers distributed in different locations. This method provides a completely new architecture for wireless communications without using complicated digital-analog convertor and a series of active/passive microwave devices. We build up a prototype to validate the new architecture experimentally, which may find promising applications where information security is highly demanded.

20.
Food Chem ; 301: 125302, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31387034

RESUMO

The autolysis of sea cucumber is caused by depolymerisation of collagen fibres and unfolding of fibrils. In order to highlight the role of collagenase in sea cucumber autolysis, collagen fibres from sea cucumber were hydrolysed with collagenase type I. Electron microscopy (EM) results indicated the collagenase caused partial depolymerisation of collagen fibres into fibrils due to the fracture of proteoglycan interfibrillar bridges, as well as uncoiling of collagen fibrils. Chemical analysis and SDS-PAGE both indicated collagenase induced a time-dependent release of glycosaminoglycans (GAGs) and soluble proteins, which further demonstrated the degradation of proteoglycan interfibrillar bridges. Collagenase also degraded collagens by releasing soluble hydroxyproline (Hpy), with the dissolution rate of Hyp reaching 11.11% after 72 h. Fourier transform infrared analysis showed that collagenase caused the reduction of intermolecular interactions and structural order of collagen. Hence, collagenase participated in the autolysis of sea cucumber by deteriorating both macromolecular and monomeric collagens.


Assuntos
Colágeno/química , Colagenases/química , Stichopus/química , Animais , Autólise , Colágeno/metabolismo , Colagenases/metabolismo , Eletroforese em Gel de Poliacrilamida , Glicosaminoglicanos/metabolismo , Hidrólise , Hidroxiprolina/metabolismo , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Proteoglicanas/química , Proteoglicanas/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Stichopus/anatomia & histologia
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