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1.
J Ethnopharmacol ; 246: 112221, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31494203

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Donkey (Equus asinus) milk has become a medical and nutrient product since ancient times. In addition, donkey milk was regarded as a medicinal food and substitute product for infant formula in some ancient western countries. Chinese ancient medical books documented the medicinal value of donkey milk, using donkey milk to treat diabetes, cough and jaundice. AIM OF THE STUDY: To investigate the donkey milk's components and anti-diabetic effect of donkey milk in vitro and in vivo and to study the molecular mechanism of donkey milk was an anti-diabetic medication. MATERIALS AND METHODS: In this study, the gastrointestinal digested donkey milk was simulated in vitro and its products of protein digestion were analyzed by SDS-PAGE. We then performed cell viability assay, insulin secretion assay, animal experiments and ELISA assays to study the anti-diabetic effect of donkey milk in vitro and in vivo. Donkey milk's anti-diabetic molecular mechanism and specific targets were detected by using quantitative real time PCR. RESULTS: Lysozyme (LZ) and α-lactalbumin (α-La) exhibited significantly lower digestibility and higher retention than the other components of donkey milk. In vitro, 500 µg/mL of donkey milk could improve damaged ß-cells viability significantly (P < 0.0001). In vivo, the blood glucose and HOMA-IR of diabetic rats treated with donkey milk were 14.23 ±â€¯5.18 mM and 74.94 ±â€¯23.62, respectively, whereas the diabetic group were 22.18 ±â€¯2.23 mM and 112.16 ±â€¯18.44, respectively (P < 0.01). The SOD value of donkey milk group was 265.87 ±â€¯21.29 U/L, while the SOD value of diabetic group was 193.20 ±â€¯52.07 U/L (P < 0.05). These results indicated that the blood glucose was reduced, the ability of the body to eliminate free radicals was enhanced, antioxidant levels in the body was increased, insulin resistance was improved in type 2 diabetic rats after donkey milk powder fed for 4 weeks. Furthermore, donkey milk could treat diabetes through down-regulating phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6PC). CONCLUSIONS: Donkey milk has played an important role in the treatment of type 2 diabetes, and contributed to the development of the donkey milk products.

2.
J Pharm Biomed Anal ; 177: 112809, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31541942

RESUMO

A simple and specific, rapid resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for determination of chlorogenic acid in human plasma using neochlorogenic acid as the internal standard. Plasma samples were precipitated with methanol and separated on a Zorbax C18 column (50 × 2.1 mm, i.d. 1.8 µm) at a flow rate of 0.4 mL/min using a gradient mobile phase of methanol-water containing 0.1% formic acid (v/v). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration range of 10-2000 ng/mL. The indicators of inter- and intra-day precision (RSD%) were all within 10.7%, and the accuracy (RE%) was ranged from -3.0% to 10.6%. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to pharmacokinetic study of CGA in Chinese subjects with advanced solid tumor after intramuscular injection administration of Chlorogenic acid for injection (CAFI).

3.
J Affect Disord ; 260: 194-199, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499375

RESUMO

BACKGROUND: To study the association of trans fatty acid intake from diet with depressive symptoms in midlife women. METHODS: Data for this cross-sectional study were retrieved from baseline assessment of the Study of Women's Health Across the Nation (SWAN). Linear regression, logistic regression and restricted cubic spline models were performed to examine the association trans fatty acid intake with depressive symptoms. RESULTS: A total of 3095 women aged 42-52 years were included in the present study. Trans fatty acid intake was positively associated with CES-D (Center for Epidemiological Studies-Depression) scores in unadjusted, age-, race/ethnicity-, total family income- and education-adjusted and fully adjusted linear regression model. The fully adjusted regression coefficient with 95% confidence intervals (CIs) of trans fatty acid intake were 0.146 (0.047-0.246) for CES-D score. Trans fatty acid intake was positively associated with depressive symptoms (CES-D score ≥16) in each logistic regression model. The fully adjusted odds ratios (ORs) with 95% CI of depressive symptoms were 1.410 (1.019-1.951) in quartile 4 compared with quartile 1 for trans fatty acid intake. Sensitivity analyses showed that the association between trans fatty acid and depressive symptoms were not affected by use of antidepressant. Stratified analysis showed that, in fully adjusted model, the trans fatty acid intake was not significantly associated with depressive symptoms in early perimenopausal women. LIMITATIONS: This was a cross-sectional study, limiting causal inferences. CONCLUSION: Trans fatty acid may be positively associated with depressive symptoms in premenopausal women, but not in early perimenopausal women.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31446160

RESUMO

Neuroinflammation and metabolic deficits contribute to the etiology of human affective disorders, such as anxiety and depression. The zebrafish (Danio rerio) has recently emerged as a powerful new model organism in CNS disease modeling. Here, we exposed zebrafish to 2% glucose and 10% cholesterol for 19 days to experimentally induce type 2 diabetes (DM) and to assess stress responses, microglia, inflammation and apoptosis. We analyzed zebrafish anxiety-like behavior in the novel tank and light-dark box (Days 15-16) tests, as well as examined their biochemical and genomic biomarkers (Day 19). Confirming DM-like state in zebrafish, we found higher whole-body glucose, triglyceride, total cholesterol, low-density lipoprotein levels and glucagon mRNA expression, and lower high-density lipoprotein levels. DM zebrafish also showed anxiety-like behavior, elevated whole-body cortisol and cytokines IFN-γ and IL-4, as well as higher brain mRNA expression of the glucocorticoid receptor, CD11b (a microglial biomarker), pro-inflammatory cytokines IL-6 and TNF-α (but not IL-1ß or anti-inflammatory cytokines IL-4 and IL-10), GFAP (an astrocytal biomarker), neurotrophin BDNF, its receptors p75 and TrkB, as well as apoptotic Bax and Caspase-3 (but not BCl-2) genes. Collectively, this supports the overlapping nature of DM-related affective pathogenesis and emphasizes the role of peripheral and central inflammation and apoptosis in DM-related affective and neuroendocrine deficits in zebrafish.

5.
Carbohydr Polym ; 227: 115338, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590863

RESUMO

New sources of AIE materials with good water solubility, biocompatibility, degradability, and mass production are urgently needed. Here, we found that chitosan, a very abundant polysaccharide in nature, has fluorescence emission in both solid and solution states with AIE effect, and explored its multifunctional applications. Chitosan can emit a variety of colors from blue to red at different excitation wavelengths with excellent multicolor imaging capabilities at the cellular level. Utilizing the cationic and antibacterial properties of chitosan, the quantification of bacteria can be achieved through the AIE effect. Concurrently, it can be used as fluorescent probes for multi-channel bacterial imaging via lighting-up bacteria. Furthermore, the chitosan solution exhibits a sensitive quenching response to Fe3+, which can be used as a biosensor for detecting the concentration of Fe3+. These interesting results indicate that chitosan will have broad application prospects as a new class of AIE material.

6.
Talanta ; 207: 120313, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594600

RESUMO

Peptidomics research is of great significance for discovering potential biomarkers and monitoring human diseases. As a kind of common clinical biofluid, saliva known for its noninvasive collection and easy accessibility has been widely used in peptidomics research. In this article, we combined immobilized metal ions affinity chromotography (IMAC) with mesoporous material and proposed the copper ion doped magnetic mesoporous silica material (denoted as Fe3O4@mSiO2-Cu2+) which had a large surface area of 221 m2 g-1 and pore volume of 0.20 cm3 g-1. By immobilizing copper ions onto the mesopore walls, the standard peptide Angiotensin II could be identified in an extremely low concentration of 0.1 fmol µl-1 and in a mass ratio of 1:500 (Angiotensin II:BSA, m/m), which indicated significant sensitivity and a great size-exclusive ability. In addition, the introduction of polydopamine (PDA) made Fe3O4@mSiO2-Cu2+ more hydrophilic and biocompatible which could improve the profiling of endogenous peptides in bio-sample. Finally, 131 endogenous peptides were identified in human saliva after enrichment with Fe3O4@mSiO2-Cu2+. Therefore, Fe3O4@mSiO2-Cu2+ nanoparticles provided a promising candidate protocol for biomarker discovery.

7.
Cancer Lett ; 468: 27-40, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31604115

RESUMO

Patients with recurrent nasopharyngeal carcinoma (NPC) have more co-existing distant metastasis than those of no-recurrence and are more likely to suffer distant metastasis after re-irradiation than patients with newly diagnosed NPC. However, the relationship between radioresistance and distant metastasis and the mechanisms involved in radioresistance-associated metastasis are still unclear. In this study, we proved that C-C motif chemokine ligand 2 (CCL2) expression was significantly elevated in HONE1-IR cells and recurrent NPC tumour. Inhibition of CCL2 enhanced sensitivity to radiotherapy in NPC cells. Moreover, autocrine CCL2 promoted NPC cell adaptive radioresistance, metastasis and epithelial-mesenchymal transition. Additionally, p53 activated CCL2 transcription. High CCL2 expression was highly associated with poorer locoregional recurrence free survival, progression free survival and overall survival in patients with newly diagnosed NPC. Notably, high CCL2 expression was an independent prognostic factor for distant metastasis free survival in recurrent NPC patients. Our results provide insights into the autocrine signalling mechanisms of CCL2 and suggest that inhibition of autocrine CCL2 may be a candidate treatment strategy for management of radioresistant NPC.

8.
Appl Opt ; 58(27): 7636-7642, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674420

RESUMO

One of the greatest challenges of long distance measurement is the beam drift caused by the air refractive index gradient. It has been established in many researches that optical phase conjugation (OPC) can be used to compensate for the beam bending. However, this method is limited to responding speed, phase conjugate reflectivity, flexibility, and specific source and medium. To reduce beam drift, instead of OPC, this study applies a digital OPC (DOPC) method, which is also creatively applied to collimation and flatness measurements. The main devices in the wavefront correction unit are the spatial light modulator and the Shack-Hartmann wavefront sensor. For the straightness measurement unit, the collimation and flatness of the optical rail are measured through the prism system and a position-sensing detector. After wavefront compensation, the root mean square is decreased from 0.0029λ to 0.0005λ. The beam drift is decreased from 1.22 mm to 0.70 mm in the x direction and from 2.49 mm to 1.55 mm in the y direction. The experimental data indicate that the straightness measurement system based on DOPC can effectively decrease the beam drift.

9.
Appl Opt ; 58(28): 7708-7715, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674451

RESUMO

Thermal analysis of a semiconductor laser array is carried out by establishing a packaging structure model of the array based on the use of copper as the base heat sink. A novel composite heat sink structure for a high-power semiconductor laser array with copper-implanted graphite microholes is proposed. The relationship between the location and quantity of microholes and the junction temperature of the semiconductor laser array is analyzed by numerical simulation. The packaging structure is found to effectively reduce the temperature generated by the semiconductor laser array in the process of operation, and the highest temperature is reduced by 4.52 K. Since the laser diode bar is composed of multiple emitters, the temperature of the intermediate emitters is higher than that of the edge emitters. The structure of the graphite heat sink is optimized to improve the temperature uniformity of the semiconductor laser array emitter. Without changing the parameters of the semiconductor laser array device, the temperature difference is calculated, and a reduction from 7.68 to 2 K is shown.

10.
J Agric Food Chem ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674784

RESUMO

L-Arabinose is a monosaccharide extracted from plants or fibers, which is known to have a variety of functional properties. In this study, we aim to investigate whether L-Arabinose could inhibit colitis by modulating gut microbiota. L-Arabinose was administrated in mice daily in a DSS-induced colitis model. The histological analysis, disease index and the expression of inflammatory genes were measured. 16S-rRNA sequence analysis was performed to investigate gut microbiota. Intriguingly, we found that L-Arabinose could repress DSS-induced colitis and inhibit p38-/p65-dependent inflammation activation. Besides that, our data revealed that L-Arabinose modulated gut microbiota disturbed by DSS treatment. Additionally, by antibiotic treatment, the perturbed gut microbiota was responsible for the suppressive effects of L-Arabinose on DSS-induced colitis. Lastly, Caco-2 cells was used to confirm the protective effects of L-Arabinose. As expected, the expression levels of pro-inflammatory proteins in Caco-2 cells treated with L-Arabinose in absence or presence of TNFα. Our work suggested that L-Arabinose exert anti-inflammation effect in DSS-induced colitis. These beneficial effects may be related to the diversity and composition of the gut microbiota regulated by L-Arabinose. L-Arabinose could be a remarkable candidate as a functional food or novel therapeutic strategies for intestinal health.

11.
Biochim Biophys Acta Mol Basis Dis ; : 165578, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672550

RESUMO

Atherosclerosis is an inflammatory disease of the arterial wall, which involves endothelial cells and immune cells. Endothelial dysfunction has been considered an important step in the initiation of the disease. TIPE1 is a newly identified protein of the TIPE family, and plays a vital role in inflammation and tumorigenesis. However, its role in atherogenesis remains unclear. In this study, we demonstrated that TIPE1 promoted atherogenesis by inducing endothelial dysfunction. When human umbilical vein endothelial cells (HUVECs) were exposed to oxidative stress, the level of TIPE1 was significantly up-regulated, and the ROS generation markedly increased in TIPE1 over-expressing HUVECs. As a result, the growth of HUVECs was inhibited, and the apoptosis was enhanced. However, the cell contact ability between HUVECs and THP-1 cells were augmented due to the up-regulation of adhesion molecules such as E-selectin and ICAM-1 induced by TIPE1 overexpression. Importantly, ApoE-/- mice injected with TIPE1 recombinant lentivirus developed significantly severe atherosclerosis accompanied by hyperglycemia, hypercholesterolemia and increased white blood count. These findings indicated that excessive ROS induced by the overexpression of TIPE1 in endothelial cells accelerated the process of atherogenesis.

12.
J Hazard Mater ; : 121492, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31677912

RESUMO

The development of high efficiency filter membranes, particularly those capable of removing trace heavy metals from drinking water sources, is a global challenge. In this study, a dual-functional membrane (PmGn@PVDF) was successfully developed by doping graphene oxide (GO) and then depositing polydopamine (PDA). The pure water flux (Jw) was 188 LMH/bar and Pb(II) could be effectively removed in the water volume of 2106.36 L m-2. Both PDA and GO performed positive functions. PDA layer exhibited a high affinity toward Pb(II) by chelating with amino groups. And doping GO maintained a high pure water flux, which had been decreased by the extra PDA layer. In addition, the effective treatment volume of Pb(II) was elevated to 5029.06 L/m2 by the co-existence of citric acid, since neutral PbHL coordinated with neutral NH2 and cationic PbL- interacted with NH3+ through electrostatic attraction. Furthermore, PmGn@PVDF showed the excellent anti-interference performance in high salt and nature organic matters solutions. Thus, this novel dual-functional membrane could be considered as a competitive alternative of NF/RO for the efficient and advanced removal towards heavy metals from natural water.

13.
Int J Pharm ; : 118806, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678519

RESUMO

Breast cancer is one of the most frequent malignancies in the female population. Recently, the development of medical products has been advanced for this disease; however, patients still suffer from the failure of current treatments and new therapeutic strategies are urgently required. In this study, due to the overexpression of the estrogen receptor (ER) in breast cancer and the ability of ER to specifically bind to its ligand estrone (ES), an ES-targeted PEGylated epirubicin (EPI) and paclitaxel (PTX) co-loaded liposomal nanoparticle (NP) (termed as ES-SSL-EPI/PTX) was developed. Physicochemical studies demonstrated that the ES-SSL-EPI/PTX had a nanoscaled particle size (∼ 120 nm) and a neutral zeta potential (∼ -5 mV) and presented favorable stability in physiological media. In vitro, the ES-SSL-EPI/PTX showed a significantly higher cellular uptake in human breast cancer MCF-7 cells mainly via the receptor-ligand mediated pathway resulting in effective cytotoxic activity. In vivo targeting study, the accumulation of targeted liposomes in tumor was significantly improved. The systemic circulation time and biodistribution in main organs of EPI and PTX delivered by ES-SSL-Liposomes were increased. Consequently, the ES-SSL-EPI/PTX significantly suppressed tumor growth in the MCF-7-derived tumor-bearing mouse model without inducing toxicity. These results suggested that the ES-SSL-EPI/PTX was a promising formulation for co-delivery of chemotherapeutics in the treatment of breast cancer.

14.
Neuroscience ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682947

RESUMO

K-complexes are important transient bio-signal waveforms in sleep stage 2. Detecting k-complexes visually requires a highly qualified expert. In this study, an efficient method for detecting k-complexes from electroencephalogram (EEG) signals based on fractal and frequency features coupled with an ensemble model of three classifiers is presented. EEG signals are first partitioned into segments, using a sliding window technique. Then, each EEG segment is decomposed using a dual- tree complex wavelet transform (DT-CWT) to a set of real and imaginary parts. A total of 10 sub-bands are used based on four levels of decomposition, and the high sub-bands are considered in this research for feature extraction. Fractal and frequency features based on DT-CWT and Higuchi's algorithm are pulled out from each sub-band and then forwarded to an ensemble classifier to detect k-complexes. A twelve-feature set is finally used to detect the sleep EEG characteristics using the ensemble model. The ensemble model is designed using a combination of three classification techniques including a least square support vector machine (LS-SVM), k-means and Naïve Bayes. The proposed method for the detection of the k-complexes achieves an average accuracy rate of 97.3 %. The results from the ensemble classifier were compared with those by individual classifiers. Comparisons were also made with existing k-complexes detection approaches for which the same datasets were used. The results demonstrate that the proposed approach is efficient in identifying the k-complexes in EEG signals; it yields optimal results with a window size 0.5s. It can be an effective tool for sleep stages classification and can be useful for doctors and neurologists for diagnosing sleep disorders.

15.
Acta Pharmacol Sin ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685976

RESUMO

Increasing levels of plasma urotensin II (UII) are positively associated with atherosclerosis. In this study we investigated the role of macrophage-secreted UII in atherosclerosis progression, and evaluated the therapeutic value of urantide, a potent competitive UII receptor antagonist, in atherosclerosis treatment. Macrophage-specific human UII-transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet for 16 weeks to induce atherosclerosis. Immunohistochemical staining of the cellular components (macrophages and smooth muscle cells) of aortic atherosclerotic lesions revealed a significant increase (52%) in the macrophage-positive area in only male transgenic rabbits compared with that in the nontransgenic littermates. However, both male and female transgenic rabbits showed a significant decrease (45% in males and 31% in females) in the smooth muscle cell-positive area compared with that of their control littermates. The effects of macrophage-secreted UII on the plaque cellular components were independent of plasma lipid level. Meanwhile the wild-type rabbits were continuously subcutaneously infused with urantide (5.4 µg· kg-1· h-1) using osmotic mini-pumps. Infusion of urantide exerted effects opposite to those caused by UII, as it significantly decreased the macrophage-positive area in male wild-type rabbits compared with that of control rabbits. In cultured human umbilical vein endothelial cells, treatment with UII dose-dependently increased the expression of the adhesion molecules VCAM-1 and ICAM-1, and this effect was partially reversed by urantide. The current study provides direct evidence that macrophage-secreted UII plays a key role in atherogenesis. Targeting UII with urantide may promote plaque stability by decreasing macrophage-derived foam cell formation, which is an indicator of unstable plaque.

16.
Tissue Eng Part A ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31686622

RESUMO

The human brain formation involves complicated processing which is regulated by a gene regulatory network influenced by different signaling pathways. The cross-regulatory interactions between elements of different pathways affect the process of cell fate assignment during neural and astroglial tissue patterning. In this study, the interactions between Wnt and Notch pathways, the two major pathways that influence neural and astroglial differentiation of humna induced plueripotent stem cells (hiPSCs) individually, were investigated. In particular, the synergistic effects of Wnt-Notch pathway on the neural patterning processes along the anterior-posterior (A-P) or dorsal-ventral (D-V) axis of hiPSC-derived cortical spheroids were explored. The human cortical spheroids derived from hiPSCs were treated with Wnt activator CHIR99021 (CHIR), Wnt inhibitor IWP4, Notch inhibitor (DAPT) individually, or in combinations (CHIR+DAPT, IWP4+DAPT). The results suggest that CHIR+DAPT can promote Notch signaling, similar or higher than CHIR alone, whereas IWP4+DAPT reduces Notch activity compared to IWP4 alone. Also, CHIR+DAPT promoted hindbrain marker HOXB4 expression more consistently than CHIR alone, while IWP4+DAPT promoted Olig2 expression, indicating the synergistic effects distinctly different from that of the individual small molecule. In addition, IWP4 simultaneously promoted dorsal and ventral identity. The patterned neural spheroids can be switched for astroglial differentiation using BMP4. This study should advance the derivations of neurons, astroglial cells, and brain region-specific organoids from hiPSCs for disease modeling, drug screening, as well as for hiPSC-based therapies.

17.
Chem Commun (Camb) ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31687688

RESUMO

We demonstrate herein an effective cascade reaction for combined photodynamic and starvation therapy in treating breast tumors based on a photosensitizer and CO prodrug decorated NMOF. The PDT-induced ROS can further trigger CO release, and the high antitumor efficiency derived from both 1O2 and CO is well confirmed by in vitro assays and in vivo trials.

18.
Medicine (Baltimore) ; 98(44): e17767, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689838

RESUMO

The aim of this study was to evaluate the efficacy and safety of prophylactic intraoperative bilateral uterine or internal iliac artery embolization in planned cesarean for pernicious placenta previa in the third trimester of pregnancy.The patients with pernicious placenta previa were retrospectively included from January 2011 to May 2018, being divided into embolization group and control group. Intraoperative uterine artery embolization (UAE) or internal iliac artery embolization (IIAE) was undertaken to stop intrapartum and postpartum hemorrhage in embolization group.There were no significant differences on age, pregnancy times, gestational age, neonatal weight, neonatal asphyxia, prenatal bleeding, placental implantation, and mortality between embolization group and control group (P > .05). The amount of intraoperative and postoperative bleeding in embolization group was significantly greater than that in control group (P < .05). However, the hysterectomy rate in the embolization group was significantly lower than that in the control group (P < .05). Two (6.25%, 2/32) cases had undergone the second time embolotherapy after 8 hours of cesarean surgery because of severe vaginal bleeding. One case (3.13%, 1/32) died of diffuse intravascular coagulation because of hemorrhagic shock in embolization group. Transient and self-remitted lumbosacral pain was present in 28 (95%, 28/32) patients and no other severe interventional complications were reported in embolization group. All babies in 2 groups were healthy at half to 5 years' follow-up.The prophylactic intraoperative embolization of bilateral UAE or IIAE may be an effective strategy to treat intractable peripartum hemorrhage and preserve the fertility in patients with pernicious placenta previa.

19.
Plant Cell ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690654

RESUMO

Stalk lodging, which is generally determined by stalk strength, results in considerable yield loss and has become a primary threat to maize yield under high-density planting. However, the molecular genetic basis of maize stalk strength remains unclear, and improvement methods remain inefficient. Here, we combined map-based cloning and association mapping and identified the gene stiff1 underlying a major quantitative trait locus (QTL) for stalk strength in maize. A 27.2-kilobase (kb) insertion of a transposable element was present in the promoter of the stiff1 gene, which encodes an F-box domain. This transposable element insertion repressed the transcription of stiff1, leading to the increased cellulose and lignin contents in the cell wall and consequently greater stalk strength. Furthermore, a new precisely edited allele of stiff1 generated through the CRISPR/Cas9 system created a stronger stalk than the natural control. Nucleotide diversity analysis revealed that the promoter of stiff1 was under strong selection in maize stiff-stalk group. Our cloning of stiff1 represents a significant discovery where a transposable element played an important role in maize improvement. The identification of stiff1 and our newly edited stiff1 allele pave the way for large-scale improvement in maize stalks with high efficiency.

20.
Cereb Cortex ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690946

RESUMO

The striatopallidal pathway is specialized for control of motor and motivational behaviors, but its causal role in striatal control of instrumental learning remains undefined (partly due to the confounding motor effects). Here, we leveraged the transient and "time-locked" optogenetic manipulations with the reward delivery to minimize motor confounding effect, to better define the striatopallidal control of instrumental behaviors. Optogenetic (Arch) silencing of the striatopallidal pathway in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS) promoted goal-directed and habitual behaviors, respectively, without affecting acquisition of instrumental behaviors, indicating striatopallidal pathway suppression of instrumental behaviors under physiological condition. Conversely, striatopallidal pathway activation mainly affected the acquisition of instrumental behaviors with the acquisition suppression achieved by either optogenetic (ChR2) or chemicogenetic (hM3q) activation, by strong (10 mW, but not weak 1 mW) optogenetic activation, by the time-locked (but not random) optogenetic activation with the reward and by the DMS (but not DLS) striatopallidal pathway. Lastly, striatopallidal pathway modulated instrumental behaviors through striatopallidal output projections into the external globus pallidus (GPe) since optogenetic activation of the striatopallidal pathway in the DMS and of the striatopallidal output projections in the GPe similarly suppressed goal-directed behavior. Thus, the striatopallidal pathway confers distinctive and inhibitory controls of animal's sensitivity to goal-directed valuation and acquisition of instrumental behaviors under normal and over-activation conditions, through the output projections into GPe.

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