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1.
J Dairy Sci ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32113772

RESUMO

Breast milk is the main source of nutrition for infants; it contains considerable microflora that can be transmitted to the infant endogenously or by breastfeeding, and it plays an important role in the maturation and development of the immune system. In this study, we isolated and identified lactic acid bacteria (LAB) from human colostrum, and screened 2 strains with probiotic potential. The LAB isolated from 40 human colostrum samples belonged to 5 genera: Lactobacillus, Bifidobacterium, Streptococcus, Enterococcus, and Staphylococcus. We also isolated Propionibacterium and Actinomyces. We identified a total of 197 strains of LAB derived from human colostrum based on their morphology and 16S rRNA sequence, among them 8 strains of Bifidobacterium and 10 strains of Lactobacillus, including 3 Bifidobacterium species and 4 Lactobacillus species. The physiological and biochemical characteristics of strains with good probiotic characteristics were evaluated. The tolerances of some of the Bifidobacterium and Lactobacillus strains to gastrointestinal fluid and bile salts were evaluated in vitro, using the probiotic strains Bifidobacterium lactis BB12 and Lactobacillus rhamnosus GG as controls. Among them, B. lactis Probio-M8 and L. rhamnosus Probio-M9 showed survival rates of 97.25 and 78.33% after digestion for 11 h in artificial gastrointestinal juice, and they exhibited growth delays of 0.95 and 1.87 h, respectively, in 0.3% bile salts. These two strains have the potential for application as probiotics and will facilitate functional studies of probiotics in breast milk and the development of human milk-derived probiotics.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32159326

RESUMO

Polarization-sensitive photodetectors are highly desirable for high-performance optical signal capture and stray light shielding in order to enhance the capability for detection and identification of targets in dark, haze, and other complex environments. Usually, filters and polarizers are utilized for conventional devices to achieve polarization-sensitive detection. Herein, to simplify the optical system, a two-dimensional self-powered polarization-sensitive photodetector is fabricated based on a stacked GeSe/MoS2 van der Waals (vdW) heterojunction which facilitates efficient separation and transportation of the photogenerated carriers because of type-II band alignment. Accordingly, a high-performance self-powered photodetector is achieved with merits of a very large on-off ratio photocurrent at zero bias of currently 104 and a high responsivity (Rλ) of 105 mA/W with an external quantum efficiency of 24.2%. Furthermore, a broad spectral photoresponse is extended from 380 to 1064 nm owing to the high absorption coefficient in a wide spectral region. One of the key benefits from these highly anisotropic orthorhombic structures of layered GeSe is self-powered polarization-sensitive detection with a peak/valley ratio of up to 2.95. This is realized irradiating with a 532 nm wavelength laser with which a maximum photoresponsivity of up to 590 mA/W is reached when the input polarization is parallel to the armchair direction. This work provides a facile route to fabricate self-powered polarization-sensitive photodetectors from GeSe/MoS2 vdW heterojunctions for integrated optoelectronic devices.

3.
J Membr Biol ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170353

RESUMO

KCNQ2 channel is one of the important members of potassium voltage-gated channel. KCNQ2 is closely related to neuronal excitatory diseases including epilepsy and neuropathic pain, and also acts as a drug target of the anti-epileptic drug, retigabine (RTG). In the past few decades, RTG has shown strong efficacy in the treatment of refractory epilepsy but has been withdrawn from clinical use due to its multiple adverse effects in clinical phase III trials. To overcome the drawbacks of RTG, several RTG analogues have been developed with different activation potency to KCNQ2. However, the detailed molecular mechanism by which these RTG analogues regulate KCNQ2 channel remains obscure. In this study, we used molecular simulations to analyse the interaction mode between the RTG analogues and KCNQ2, and to determine their molecular mechanism of action. Our data show that the van der Waals interactions, hydrophobic interactions, hydrogen bond, halogen bond, and π-π stacking work together to maintain the binding stability of the drugs in the binding pocket. On an atomic scale, the amide group in the carbamate and the amino group in the 2-aminophenyl moiety of RTG and RL648_81 are identified as key interaction sites. Our finding provides insight into the molecular mechanism by which KCNQ2 channels are regulated by RTG analogues. It also provides direct theoretical support for optimizing design of the KCNQ2 channel openers in the future, which will help treat refractory epilepsy caused by nerve excitability.

4.
Cells ; 9(3)2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32210151

RESUMO

Non-invasive electrical stimulation (ES) is increasingly applied to improve vision in untreatable eye conditions, such as retinitis pigmentosa and age-related macular degeneration. Our previous study suggested that ES promoted retinal function and the proliferation of progenitor-like glial cells in mice with inherited photoreceptor degeneration; however, the underlying mechanism remains obscure. Müller cells (MCs) are thought to be dormant residential progenitor cells that possess a high potential for retinal neuron repair and functional plasticity. Here, we showed that ES with a ramp waveform of 20 Hz and 300 µA of current was effective at inducing mouse MC proliferation and enhancing their expression of progenitor cell markers, such as Crx (cone-rod homeobox) and Wnt7, as well as their production of trophic factors, including ciliary neurotrophic factor. RNA sequencing revealed that calcium signaling pathway activation was a key event, with a false discovery rate of 5.33 × 10-8 (p = 1.78 × 10-10) in ES-mediated gene profiling changes. Moreover, the calcium channel blocker, nifedipine, abolished the observed effects of ES on MC proliferation and progenitor cell gene induction, supporting a central role of ES-induced Ca2+ signaling in the MC changes. Our results suggest that low-current ES may present a convenient tool for manipulating MC behavior toward neuroregeneration and repair.

5.
Microb Pathog ; 143: 104109, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32171710

RESUMO

Acute lung injury (ALI) is considered as an uncontrolled inflammatory response that can leads to acute respiratory distress syndrome (ARDS), which limits the therapeutic strategies. Ginsenosides Rb1 (Rb1), an active ingredient obtained from Panax ginseng, possesses a broad range of pharmacological and medicinal properties, comprising the anti-inflammatory, anti-oxidant, and anti-tumor activities. Therefore, the purpose of the present study was to investigate the protective effects of Rb1 against S. aureus-induced (ALI) through regulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial-mediated apoptotic pathways in mice (in-vivo), and RAW264.7 cells (in-vitro). For that purpose, forty Kunming mice were randomly assigned into four treatment groups; (1) Control group (phosphate buffer saline (PBS); (2) S. aureus group; (3) S. aureus + Rb1 (20 mg/kg) group; and (4) Rb1 (20 mg/kg) group. The 20 µg/mL dose of Rb1 was used in RAW264.7 cells. In the present study, we found that Rb1 treatment reduced ALI-induced oxidative stress via suppressing the accumulation of malondialdehyde (MDA) and myeloperoxidase (MPO) and increase the antioxidant enzyme activities of superoxidase dismutase 1 (SOD1), Catalase (CAT), and glutathione peroxidase 1 (Gpx1). Similarly, Rb1 markedly increased messenger RNA (mRNA) expression of antioxidant genes (SOD1, CAT and Gpx1) in comparison with ALI group. The histopathological results showed that Rb1 treatment ameliorated ALI-induced hemorrhages, hyperemia, perivascular edema and neutrophilic infiltration in the lungs of mice. Furthermore, Rb1 enhanced the antioxidant defense system through activating the Nrf2 signaling pathway. Our findings showed that Rb1 treated group significantly up-regulated mRNA and protein expression of Nrf2 and its downstream associated genes down-regulated by ALI in vivo and in vitro. Moreover, ALI significantly increased the both mRNA and protein expression of mitochondrial-apoptosis-related genes (Bax, caspase-3, caspase-9, cytochrome c and p53), while decreased the Bcl-2. In addition, Rb1 therapy significantly reversed the mRNA and protein expression of these mitochondrial-apoptosis-related genes, as compared to the ALI group in vivo and in vitro. Taken together, Rb1 alleviates ALI-induced oxidative injury and apoptosis by modulating the Nrf2 and mitochondrial signaling pathways in the lungs of mice.

6.
J Cell Physiol ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32003008

RESUMO

Acute lung injury (ALI), characterized by increased excessive pulmonary inflammation, is a pervasive inflammatory disease with clinically high incidence. MicroRNA (miRNAs) have been associated with the progression of multiple diseases and are regarded as novel regulators of inflammation. However, it remains largely unknown whether the miRNAs-mediated regulatory mechanism has an effect on lipopolysaccharide (LPS)-induced inflammation in ALI. We discovered that miR-182 distinctly lessened expression in the lung tissue of mice with ALI and macrophages stimulated by LPS. We also found that overexpression of miR-182 significantly cut down the secretion of inflammatory cytokines, while this change was reversed by inhibition of miR-182. In addition, miR-182 suppressed the activation of NF-κB by targeting TLR4 expression. And it was confirmed that miR-182 directly regulated TLR4 expression at the posttranscriptional level by binding to the 3'-UTR of TLR4. Together, these data suggested that inhibition of TLR4 expression assuaged LPS-stimulated inflammation through negative feedback regulation of miR-182.

7.
Sensors (Basel) ; 20(3)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023983

RESUMO

In airborne passive bistatic radar (PBR), the reference channel toward the opportunity illuminator is applied to receive the direct-path signal as the reference signal. In the actual scenario, the reference signal is contaminated by the multipath signals easily. Unlike the multipath signal in traditional ground PBR system, the multipath signal in the airborne PBR owns not only the time delay but also the Doppler frequency. The contaminated reference signal can cause the spatial-temporal clutter spectrum to expand and the false targets to appear. The performance of target detection is impacted severely. However, the existing blind equalization algorithm is unavailable for the contaminated reference signal in airborne PBR. In this paper, the modified blind equalization algorithm is proposed to suppress the needless multipath signal and restore the pure reference signal. Aiming at the Doppler frequency of multipath signal, the high-order moment information and the cyclostationarity of source signal are exploited to construct the new cost function for the phase constraint, and the complex value back propagation (BP) neural network is exploited to solve the constraint optimization problem for the better convergence. In final, the simulation experiments are conducted to prove the feasibility and superiority of proposed algorithm.

8.
Biotechnol Adv ; : 107534, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32088327

RESUMO

Messenger RNA (mRNA)-based therapeutics hold the potential to cause a major revolution in the pharmaceutical industry because they can be used for precise and individualized therapy, and enable patients to produce therapeutic proteins in their own bodies without struggling with the comprehensive manufacturing issues associated with recombinant proteins. Compared with the current therapeutics, the production of mRNA is much cost-effective, faster and more flexible because it can be easily produced by in vitro transcription, and the process is independent of mRNA sequence. Moreover, mRNA vaccines allow people to develop personalized medications based on sequencing results and/or personalized conditions rapidly. Along with the great potential from bench to bedside, technical obstacles facing mRNA pharmaceuticals are also obvious. The stability, immunogenicity, translation efficiency, and delivery are all pivotal issues need to be addressed. In the recently published research results, these issues are gradually being overcome by state-of-the-art development technologies. In this review, we describe the structural properties and modification technologies of mRNA, summarize the latest advances in developing mRNA delivery systems, review the preclinical and clinical applications, and put forward our views on the prospect and challenges of developing mRNA into a new class of drug.

9.
J Healthc Eng ; 2020: 1506250, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104556

RESUMO

Discussed in this paper is the tip-over stability analysis of a pelvic support walking robot. To improve the activities of daily living (ADL) in hemiplegic patients, a pelvic support walking robot is proposed to help patients facilitating their rehabilitation. During the gait training with the robot, the abnormal man-machine interaction forces may lead to the tip-over of the robot, which is not beneficial to the rehabilitation process. A new method is proposed to predict the possibility of tipping over and evaluate the stability of the robot based on statics model, dynamics model, and zero-moment point (ZMP) theory. Through the interaction forces and moments analysis with static case, the safe point (ZMP) is studied, and the influence factors of force/moment are analyzed by dynamics case. An optimization algorithm based on the genetic algorithm (GA) is proposed to reduce the risk of tipping over. The simulation results show that the optimization algorithm can keep the robot from tipping over when the interaction forces exceed the safety threshold.

10.
Onco Targets Ther ; 13: 1365-1374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110038

RESUMO

Aim: Traditional non-invasive diagnostic markers for gastric cancer (GC) exhibit insufficient sensitivity and specificity. Circulating exosomes are clinically useful non-invasive biomarkers for tumor diagnosis. In addition to their potential role in cancer biology, circulating long non-coding RNAs (lncRNAs) are a new class of promising cancer biomarkers. In the present study, we aimed to identify lncRNAs in circulating exosomes with potential as biomarkers for GC detection. Methods: We compared the expression of CEBPA-AS1 between GC cells and gastric epithelial cells. The biological function of exosomal CEBPA-AS1 was determined by cell phenotype experiments and rescue assays. We also compared the expression of CEBPA-AS1 in cancerous tissue from GC patients and corresponding adjacent normal tissues, as well as the expression of CEBPA-AS1 in plasma exosomes of GC patients and healthy controls. Diagnostic accuracy was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). Results: CEBPA-AS1 was highly expressed in both GC cells and in exosomes secreted by GC cells. In addition, CEBPA-AS1-containing exosomes secreted by GC cells could promote cell proliferation and inhibit apoptosis, thereby inducing the malignant behavior of GC cells. The level of CEBPA-AS1 was also significantly increased in tissues and plasma exosomes of GC patients. Stability tests showed that most plasma CEBPA-AS1 was encased in exosomes, thus avoiding degradation by RNases. We evaluated the diagnostic accuracy of exosome-derived CEBPA-AS1. The AUC value of CEBPA-AS1 in discriminating GC patients from healthy controls was 0.824, which was higher than the diagnostic accuracy of other traditional tumor biomarkers. Conclusion: CEBPA-AS1-containing exosomes secreted from GC cells could promote cell proliferation, inhibit apoptosis, and induce GC progression, indicating that exosomal CEBPA-AS1 is involved in cell-to-cell communication in GC carcinogenesis. Exosomal CEBPA-AS1 is a promising new biomarker for clinical diagnosis of GC.

11.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(1): 129-135, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32096386

RESUMO

In order to stimulate the patients' active participation in the process of robot-assisted rehabilitation training of stroke patients, the rehabilitation robots should provide assistant torque to patients according to their rehabilitation needs. This paper proposed an assist-as-needed control strategy for wrist rehabilitation robots. Firstly, the ability evaluation rules were formulated and the patient's ability was evaluated according to the rules. Then the controller was designed. Based on the evaluation results, the controller can calculate the assistant torque needed by the patient to complete the rehabilitation training task and send commands to motor. Finally, the motor is controlled to output the commanded value, which assists the patient to complete the rehabilitation training task. The control strategy was implemented to the wrist function rehabilitation robot, which could achieve the training effect of assist-as-needed and could avoid the surge of assistance torque. In addition, therapists can adjust multiple parameters in the ability evaluation rules online to customize the difficulty of tasks for patients with different rehabilitation status. The method proposed in this paper does not rely on the information from force sensor, which reduces development costs and is easy to implement.


Assuntos
Robótica , Reabilitação do Acidente Vascular Cerebral/instrumentação , Punho/fisiologia , Humanos , Modalidades de Fisioterapia
12.
Pharmacol Res ; 155: 104721, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32097750

RESUMO

TMEM16A plays critical roles in physiological process and may serve as drug targets for diverse diseases. Recently, TMEM16A has started to be regarded as potential primary lung adenocarcinoma targets. Here, we identified that arctigenin, a natural compound, is a novel TMEM16A inhibitor, and it can suppress lung adenocarcinoma growth through inhibiting TMEM16A both in vitro and in vivo. Our data also showed that the IC50 of actigenin to TMEM16A whole-cell current was 19.29 ± 4.69 µM, and the putative binding sites of arctigenin in TMEM16A were R515 and R535. Arctigenin concentration-dependently inhibited the proliferation and migration of LA795, however, the inhibition effect can be abolished by knockdown of the endogenous TMEM16A with shRNA. Further, we injected arctigenin on xenograft mouse model which exhibited significant antitumor activity with no adverse effect. At last, western blotting results showed the mechanism of arctigenin inhibiting lung adenocarcinoma was through inhibiting MAPK pathway. In summary, TMEM16A is a novel drug target for lung adenocarcinoma treatment. Arctigenin can be used as a lead compound for the development of lung adenocarcinoma therapy drugs.

13.
Phys Med Biol ; 65(5): 055010, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31935699

RESUMO

The 3D/2D registration of pre-operative computed tomography angiography (CTA) and intra-operative x-ray angiography (XRA) images in vascular intervention is imperative for guiding surgical instruments and reducing the dosage of toxic contrast agents. In this study, 3D/2D vascular registration is formulated as a search tree problem on the basis of the topological continuity of vessels and the fact that matching can be decomposed into continuous states. In each node of the tree, a closed-solution of 3D/2D transformation is used to obtain the registration results based on the dense correspondences of vessel points, and the results of matching and registration are calculated and recorded. Then, a hand-crafted score that quantifies the qualities of matching and registration of vessels is used, and the remaining problem focuses on finding the highest score in the search tree. An improved heuristic tree search strategy is also proposed to find the best registration. The proposed method is evaluated and compared with four state-of-the-art methods. Experiments on simulated data demonstrate that our method is insensitive to initial pose and robust to noise and deformation. It outperforms other methods in terms of registering real model data and clinical coronary data. In the 3D/2D registration of uninitialized and initialized coronary arteries, the average registration errors are 1.85 and 1.79 mm, respectively. Given that the proposed method is independent of the initial pose, it can be used to navigate vascular intervention for clinical practice.

14.
Scand J Gastroenterol ; 55(2): 193-201, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31976783

RESUMO

Objective: The benefit of adjuvant therapy (AT) remains controversial in stage IB gastric cancer (GC). This study aimed to offer a reference for the rational indications of AT.Methods: We retrospectively included 1216 stage IB GC who experienced curative surgery from the SEER database between 2004 and 2015. These patients were allocated into two groups: Group AT and Group surgery alone (Group SA). We established a nomogram to predict OS and then divided whole cohort into low-risk and high-risk groups based on the OS predicted by the nomogram.Results: Six variables, which were significantly related with OS of entire patients after matched, were incorporated in the nomogram. These variables were age, examined lymph nodes, tumor site, marital, family income and stage IB. The C-index of the model was 0.637 and the calibration curve showed that the anticipated values were in accordance with the actual values. The decision curve demonstrated that the optimal clinical impact was achieved when the threshold possibility was 0-56%. Then, the entire cohort was separated into low-risk (≤159 points) as well as high-risk (>159 points) groups based on the projected 5-year OS of recursive partitioning analysis. Group SA revealed a significantly poorer OS than Group AT for high-risk patients (p < .001); on the other hand, there was a comparable OS for low-risk patients (p = .361).Conclusions: We have developed an effective, intuitional and applied prognostic tool to clinical decision-making. For stage IB GC after surgical resection, AT was only recommended for high-risk patients. However, AT may be dispensable for low-risk patients.

15.
Int J Clin Oncol ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894433

RESUMO

BACKGROUND: Gastric cancer (GC) is the most common and aggressive cancer of the digestive system and poses a serious threat to human health. Since genes do not work alone, our aim was to elucidate the potential network of mRNAs and noncoding RNAs (ncRNAs) in this study. METHODS: Transcriptome data of GC were obtained from TCGA. R and Perl were used to obtain the differentially expressed RNAs and construct a competing endogenous RNA (ceRNA) regulatory network. To investigate the biological functions of differentially expressed RNAs, loss-of-function and gain-of-function experiments were performed. Real-time PCR (RT-qPCR), western blot analysis, dual-luciferase reporter assays and fluorescence in situ hybridization were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs). RESULTS: Based on TCGA data and bioinformatics analysis, we identified the LINC00163/miR-183/A-Kinase Anchoring Protein 12 (AKAP12) axis. We observed that AKAP12 was weakly expressed in GC and suppressed invasion and metastasis in GC cells, which could be abolished by miR-183. In addition, LINC00163 can be used as a ceRNA to inhibit the expression of miR-183, thus enhancing the anticancer effect of AKAP12. CONCLUSION: Our results demonstrated that weak LINC00163 expression in GC can sponge miR-183 to promote AKAP12. We established that the LINC00163/miR-183/AKAP12 axis plays an important role in GC invasion and metastasis and may be a potential biomarker and target for GC treatment.

16.
J Cell Physiol ; 235(5): 4766-4777, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31674024

RESUMO

Endometritis is an inflammatory change in the structure of the endometrium due to various causes and is a common cause of infertility. Studies have confirmed that microRNAs (miRNAs) play a key regulatory role in various inflammatory diseases. However, the miRNA-mediated mechanism of endometrial inflammation induced by lipopolysaccharides (LPS) remains unclear. In this study, real-time quantitative polymerase chain reaction, Western blot analysis, immunofluorescence and Rac family small GTPase 1 (Rac1) interference were used to reveal the overexpression of miR-488 in the LPS-induced bovine uterus, and the effect of protein kinase B κ-light chain enhancement of the nuclear factor-activated B cells (AKT/NF-κB) pathway in intimal epithelial cells. The results showed that the expression of inflammatory cytokines such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α in the experimental group was significantly lower than that in the control group when miR-488 was overexpressed. Similar results were observed in the expression levels of p-AKT, p-IKK, and p-p65 proteins. In addition, the dual-luciferase reporter system confirmed that miRNA-488 may directly target the 3'-untranslated region of Rac1. In turn, the expression of Rac1 was inhibited. Moreover, the nuclear translocation of NF-κB was inhibited, and meanwhile, the accumulation of reactive oxygen species (ROS) in the cells was reduced. Thus, we provide basic data for the negative regulation of miR-488 in LPS-induced inflammation by inhibiting ROS production and the AKT/NF-kB pathway in intimal epithelial cells.

17.
Anal Chem ; 92(1): 1431-1438, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31800227

RESUMO

The development of on-tissue chemical derivatization methods for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) of small endogenous metabolites in tissues has attracted great attention for their advantages in improving detection sensitivity and ionization efficiency of poorly ionized and low abundant metabolites. Herein, a laser-assisted tissue transfer (LATT) technique was developed to enhance on-tissue derivatization of small molecules. Using a focused blue laser, a thin-layer tissue film (∼1 µm) was transferred to an acceptor slide from a 6 µm dry tissue section preliminarily coated with derivatization and matrix reagents. The acceptor slide with its ablated constituents was then imaged by MALDI MS. On-tissue chemical derivatization with amino-specific derivatization reagent 4-hydroxy-3-methoxycinnamaldehyde (CA) was carried out on LATT system. 20-235 folds increase in signal intensity for CA derivatized metabolites such as amino acids, neurotransmitters, and dipeptides were observed from rat brain tissues in comparison with conventional incubation-based derivatization. This technique was further extended to derivatize steroids with Girard reagent T (GirT). The remarkable derivatization efficiency can mainly be attributed to the minimization of ion suppression effects due to the reduced thickness of tissue section and endogenous components. Additionally, shorter derivatization time with no obvious metabolite delocalization was achieved using LATT method. These results demonstrate the advantages of LATT in the enhancement of on-tissue derivatization for the more specific and sensitive imaging of small metabolites in tissues with MALDI MS.

18.
Int J Biometeorol ; 64(1): 17-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31520185

RESUMO

Although it is well-known and established that light plays important roles in plant development, up to now, there is no substantial improvements in how to deal with the light factor of spring phenology under natural condition. By monitoring the local meteorologic data and mature dates of two types (male and female) of flower from four pecan cultivars during 9 years, it was found that the complementary pattern of growing degree day and sunshine duration helped to maintain a threshold of driving force related to the maturity of pecan flower during 9 years. A novel photothermal time model based on the linear combination of growing degree day and sunshine duration was then proposed and validated to interpret the variance of mature dates of pecan cultivars. Comparative analysis showed that the new model had made extremely significant improvements to the traditional thermal time model. In addition, this model introduced the conversion coefficient K, which quantified the effect of light on the flowering drive, and revealed the differences of base temperature among cultivars. This was the first time that sunshine duration instead of photoperiod was adopted to develop into a verified model on spring phenological event of tree species. It will help to model the spring phenologies of other tree species more reasonably.


Assuntos
Carya , Flores , Masculino , Fotoperíodo , Estações do Ano
19.
Biophys J ; 118(1): 262-272, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31818463

RESUMO

The calcium-activated chloride channel TMEM16A is involved in many physiological processes, and insufficient function of TMEM16A may lead to the occurrence of various diseases. Therefore, TMEM16A activators are supposed to be potentially useful for treatment of TMEM16A downregulation-inducing diseases. However, the TMEM16A activators are relatively rare, and the underlying activation mechanism of them is unclear. In the previous work, we have proved that ginsenoside Rb1 is a TMEM16A activator. In this work, we explored the activation mechanism of ginsenoside analogs on TMEM16A through analyzing the interactions between six ginsenoside analogs and TMEM16A. We identified GRg2 and GRf can directly activate TMEM16A by screening five novel ginsenosids analogs (GRb2, GRf, GRg2, GRh2, and NGR1). Isolated guinea pig ileum assay showed both GRg2 and GRf increased the amplitude and frequency of ileum contractions. We explored the molecular mechanisms of ginsenosides activating TMEM16A by combining molecular simulation with electrophysiological experiments. We proposed a TMEM16A activation process model based on the results, in which A697 on TM7 and L746 on TM8 bind to the isobutenyl of ginsenosides through hydrophobic interaction to fix the spatial location of ginsenosides. N650 on TM6 and E705 on TM7 bind to ginsenosides through electrostatic interaction, which causes the inner half of α-helix 6 to form physical contact with ginsenosides and leads to the pore opening. It should be emphasized that TMEM16A can be activated by ginsenosides only when both the above two conditions are satisfied. This is the first, to our knowledge, report of TMEM16A opening process activated by small-molecule activators. The mechanism of ginsenosides activating TMEM16A will provide important clues for TMEM16A gating mechanism and for new TMEM16A activators screening.

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