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1.
Artigo em Inglês | MEDLINE | ID: mdl-32167740

RESUMO

Low drug payload and lack of tumor-targeting for chemodynamic therapy (CDT) result in an insufficient reactive oxygen species (ROS) generation, which seriously hinders its further clinical application. Therefore, how to improve the drug payload and tumor targeting for amplification of ROS and combine it with chemotherapy has been a huge challenge in CDT. Herein, methotrexate (MTX), gadolinium (Gd), and artesunate (ASA) were used as theranostic building blocks to be coordinately assembled into tumor-specific endogenous FeII-activated and magnetic resonance imaging (MRI)-guided self-targeting carrier-free nanoplatforms (NPs) for amplification of ROS and enhanced chemodynamic chemotherapy. The obtained ASA-MTX-GdIII NPs exhibited extremely high drug payload (∼96 wt %), excellent physiological stability, long circulating ability (half-time: ∼12 h), and outstanding tumor accumulation. Moreover, ASA-MTX-GdIII NPs could be specifically uptaken by tumor cells via folate (FA) receptors and subsequently be disassembled via lysosomal acidity-induced coordination breakage, resulting in drug burst release. Most strikingly, the produced ASA could be catalyzed by tumor-specific overexpressed endogenous FeII ions to generate sufficient ROS for enhancing the main chemodynamic efficacy, which could exert a synergistic effect with the assistant chemotherapy of MTX. Interestingly, ASA-MTX-GdIII NPs caused a lower ROS generation and toxicity on normal cell lines that seldom expressed endogenous FeII ions. Under MRI guidance with assistance of self-targeting, significantly superior synergistic tumor therapy was performed on FA receptor-overexpressed tumor-bearing mice with a higher ROS generation and an almost complete elimination of tumor. This work highlights ASA-MTX-GdIII NPs as an efficient chemodynamic-chemotherapeutic agent for MRI imaging and tumor theranostics.

2.
Phys Rev Lett ; 124(3): 038003, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-32031851

RESUMO

Lotus leaves floating on water usually experience short-wavelength edge wrinkling that decays toward the center, while the leaves growing above water normally morph into a global bending cone shape with long rippled waves near the edge. Observations suggest that the underlying water (liquid substrate) significantly affects the morphogenesis of leaves. To understand the biophysical mechanism under such phenomena, we develop mathematical models that can effectively account for inhomogeneous differential growth of floating and freestanding leaves to quantitatively predict formation and evolution of their morphology. We find, both theoretically and experimentally, that the short-wavelength buckled configuration is energetically favorable for growing membranes lying on liquid, while the global buckling shape is more preferable for suspended ones. Other influencing factors such as the stem or vein, heterogeneity, and dimension are also investigated. Our results provide a fundamental insight into a variety of plant morphogenesis affected by water foundation and suggest that such surface instabilities can be harnessed for morphology control of biomimetic deployable structures using substrate or edge actuation.


Assuntos
Lotus/crescimento & desenvolvimento , Modelos Biológicos , Água/química , Fenômenos Biofísicos , Lotus/anatomia & histologia , Morfogênese , Folhas de Planta/anatomia & histologia , Folhas de Planta/crescimento & desenvolvimento
3.
Brief Bioinform ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32010933

RESUMO

Gastric cancer (GC) continues to be one of the major causes of cancer deaths worldwide. Meanwhile, liquid biopsies have received extensive attention in the screening and detection of cancer along with better understanding and clinical practice of biomarkers. In this work, 58 routine blood biochemical indices were tentatively used as integrated markers, which further expanded the scope of liquid biopsies and a discrimination system for GC consisting of 17 top-ranked indices, elaborated by random forest method was constructed to assist in preliminary assessment prior to histological and gastroscopic diagnosis based on the test data of a total of 2951 samples. The selected indices are composed of eight routine blood indices (MO%, IG#, IG%, EO%, P-LCR, RDW-SD, HCT and RDW-CV) and nine blood biochemical indices (TP, AMY, GLO, CK, CHO, CK-MB, TG, ALB and γ-GGT). The system presented a robust classification performance, which can quickly distinguish GC from other stomach diseases, different cancers and healthy people with sensitivity, specificity, total accuracy and area under the curve of 0.9067, 0.9216, 0.9138 and 0.9720 for the cross-validation set, respectively. Besides, this system can not only provide an innovative strategy to facilitate rapid and real-time GC identification, but also reveal the remote correlation between GC and these routine blood biochemical parameters, which helped to unravel the hidden association of these parameters with GC and serve as the basis for subsequent studies of the clinical value in prevention program and surveillance management for GC. The identification system, called GC discrimination, is now available online at http://lishuyan.lzu.edu.cn/GC/.

4.
J Cell Physiol ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990056

RESUMO

Apoptosis and fibrosis play a vital role in myocardial infarction (MI) induced tissue injury. Although microRNAs have been the focus of many studies on cardiac apoptosis and fibrosis in MI, the detailed effects of miR-26a is needed to further understood. The present study demonstrated that miR-26a was downregulated in ST-elevation MI (STEMI) patients and oxygen-glucose deprivation (OGD)-treated H9c2 cells. Downregulation of miR-26a was closely correlated with the increased expression of creatine kinase, creatine kinase-MB and troponin I in STEMI patients. Further analysis identified that ataxia-telangiectasia mutated (ATM) was a target gene for miR-26a based on a bioinformatics analysis. miR-26a overexpression effectively reduced ATM expression, apoptosis, and apoptosis-related proteins in OGD-treated H9c2 cells. In a mouse model of MI, the expression of miR-26a was significantly decreased in the infarct zone of the heart, whereas apoptosis and ATM expression were increased. miR-26a overexpression effectively reduced ATM expression and cardiac apoptosis at Day 1 after MI. Furthermore, we demonstrated that overexpression of miR-26a improved cardiac function and reduced cardiac fibrosis by the reduced expression of collagen type I and connective tissue growth factor (CTGF) in mice at Day 14 after MI. Overexpression of miR-26a or ATM knockdown decreased collagen I and CTGF expression in cultured OGD-treated cardiomyocytes. Taken together, these data demonstrate a prominent role for miR-26a in linking ATM expression to ischemia-induced apoptosis and fibrosis, key features of MI progression. miR-26a reduced MI development by affecting ATM expression and could be targeted in the treatment of MI.

5.
J Ethnopharmacol ; 254: 112572, 2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31940455

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Antipsychotics often induce hyperprolactinemia. The transforming growth factor (TGF)-beta1 signaling in the pituitary and hypothalamus inhibits prolactin synthesis and secretion, and its impairment is implicated in neuropsychiatric disorders. Longdan Xiegan Tang (LXT) alone or together with antipsychotics have been used to treat various neuropsychiatric diseases and hyperprolactinemia-associated disorders. AIM OF THE STUDY: To investigate the effect of LXT on hyperprolactinemia and involvement of the TGF-beta1 signaling. MATERIALS AND METHODS: Male rats were co-administered with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) (p.o., × 8 weeks). Plasma concentrations of prolactin and TGF-beta1 were determined by ELISA. Protein expression was analyzed by Western blot. RESULTS: Treatment of rats with LXT extract suppressed olanzapine-induced increase in plasma prolactin concentration and overexpression of pituitary and hypothalamic prolactin protein. Importantly, LXT restored olanzapine-induced decrease in protein expression of the key components of the TGF-beta1 signaling, TGF-beta1, type II TGF-beta receptor, type I TGF-beta receptor and phosphorylated SMAD3 in the pituitary and hypothalamus. Further, it antagonized downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein level, and inhibited pituitary estrogen receptor (ER) alpha and ERbeta protein expression. CONCLUSIONS: The present results suggest that LXT ameliorates antipsychotic-induced hyperprolactinemia in rats by repairing the pituitary and hypothalamic TGF-beta1 signaling possibly via D2R, ERs or/and other pathways. Our findings may also provide scientific elucidation for use of the ancient Chinese formula to treat the impaired TGF-beta1 signaling-associated neuropsychiatric disorders.

6.
Nat Biomed Eng ; 4(2): 159-171, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31659307

RESUMO

Mechanical mismatches between implanted electronics and biological tissues can lead to inaccurate readings and long-term tissue damage. Here, we show that functionalized multi-walled carbon nanotubes twisted into helical fibre bundles that mimic the hierarchical structure of muscle can monitor multiple disease biomarkers in vivo. The flexible fibre bundles are injectable, have a low bending stiffness and display ultralow stress under compression. As proof-of-concept evidence of the sensing capabilities of these fibre bundles, we show that the fibre bundles enable the spatially resolved and real-time monitoring of H2O2 when implanted in tumours in mice, and that they can be integrated with a wireless transmission system on an adhesive skin patch to monitor calcium ions and glucose in the venous blood of cats for 28 d. The versatility of the helical fibre bundles as chemically functionalized electrochemical sensors makes them suitable for multiple sensing applications in biomedicine and healthcare.

7.
J Gastroenterol Hepatol ; 35(2): 334-342, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31271681

RESUMO

BACKGROUND AND AIM: Biliary atresia (BA) is a progressive fibro-inflammatory cholangiopathy with an unclear etiology. Various liver disorders are associated with an altered microbiome. However, gut microbiome in BA remains unknown. Here, we performed a case-control study to investigate the gut microbiota in BA. METHODS: A cross-sectional analysis was first conducted for 34 BA patients and 34 healthy controls. Then we investigated the shift in gut microbiota 2 weeks after the Kasai procedure in 16 BA patients. Gut microbiome was initially analyzed using 16S ribosome RNA gene sequencing and further validated by metagenomic sequencing. Fecal bile acids were determined using ultra-high performance liquid chromatography. RESULTS: Compared with healthy controls, BA showed lower diversity and significant structural segregation in the microbiome. At phylum level, Proteobacteria numbers increased, whereas those of Bacteroidetes decreased in BA. At genus level, several potential pathogens such as Streptococcus and Klebsiella thrived in BA, while numbers for Bifidobacterium and several butyrate-producing bacteria declined. The microbiome was also disturbed after the Kasai procedure. Operational taxonomic units responding to BA showed significant correlation with liver function. Furthermore, the abundance ratio of Streptococcus/Bacteroides showed great promise in distinguishing BA from healthy controls. Intestinal bile acids were dramatically decreased in BA, and Clostridium XIVa positively correlated with the ratio of primary/secondary bile acids. CONCLUSIONS: Gut microbial dysbiosis, may be caused by decreased bile acids, was associated with liver function and had a good diagnostic potential for BA. Therefore, further exploration of gut microbiota may provide important insights into their potential diagnostic and therapeutic benefits.

8.
World Neurosurg ; 136: e83-e89, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31866456

RESUMO

BACKGROUND: Percutaneous endoscopic lumbar discectomy has been widely used to treat lumbar disc herniation; its advantages are less trauma, faster recovery, lower costs, and higher percentage of patient satisfaction compared with open surgery. Treatment of lumbar spinal stenosis with percutaneous full-endoscopic surgery is still challenging, especially for elderly patients with multiple comorbidities and complex pathologic factors. The aim of this study was to introduce percutaneous full-endoscopic lumbar foraminoplasty and decompression using a visualization reamer in elderly patients with lateral recess and foraminal stenosis and evaluate efficacy and safety. METHODS: This retrospective review comprised 65 consecutive elderly patients (30 men and 35 women) with lateral recess and foraminal stenosis who underwent percutaneous full-endoscopic lumbar foraminoplasty and discectomy from January 2017 to September 2017. Visual analog scale and Oswestry Disability Index were used to evaluate pain relief and neurologic improvement. RESULTS: Mean patient age was 71.58 years (range, 65-89 years). Mean follow-up period was 16.12 months (range, 12-20 months). Mean operative time was 98.59 minutes per level (range, 55-120 minutes). Mean intraoperative perspective frequency was 3.21 times (range, 2-6 times). Mean hospital stay after the procedure was 2.18 days (range, 1-4 days). Back and leg visual analog scale and Oswestry Disability Index scores at all time points in the postoperative period were significantly lower than preoperatively (P < 0.01). At final follow-up, modified MacNab criteria were rated as follows: excellent, 47 patients (72.31%); good, 12 patients (16.92%); fair, 3 patients (4.62%); and poor, 4 patients (6.15%). Therefore, excellent or good results were obtained in 89.23% of patients. CONCLUSIONS: Percutaneous full-endoscopic lumbar foraminoplasty and discectomy using a visualization reamer is an effective and safe treatment for elderly patients with lumbar lateral recess and foraminal stenosis. It improves safety and efficiency of decompression and reduces intraoperative fluoroscopy.

9.
Sheng Li Xue Bao ; 71(6): 846-854, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31879740

RESUMO

The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on pyroptosis of macrophages and the underlying molecular mechanisms. RAW264.7 macrophages were treated with AGE-alb (1, 2, 4 and 6 g/L) and control albumin (C-alb, 4 g/L) for 24 h, or preincubated with MCC950 (1 µmol/L) for 1 h and then treated with AGE-alb (4 g/L) for 24 h. Cell viability and caspase-1 activity were measured by MTT and assay kits, respectively. Lactate dehydrogenase (LDH) activity and the levels of interleukin-1ß (IL-1ß) and IL-18 in media were detected. Cell death degree was evaluated by TUNEL and Hoechst 33342/PI staining. The protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), procaspase-1 and cleaved caspase-1 were assessed by Western blot. The results showed that AGE-alb treatment caused obvious decrease in cell viability and increases in LDH leakage and the percentages of TUNEL- or PI-positive cells in a concentration-dependent manner. Additionally, AGE-alb promoted IL-1ß and IL-18 secretion, upregulated NLRP3 expression, and increased caspase-1 activity especially at the dose of 4 and 6 g/L. However, MCC950 (an NLRP3 inhibitor) pretreatment inhibited significantly the decrease in cell viability and the increases in LDH leakage and percentages of TUNEL- or PI-positive cells induced by AGE-alb. Furthermore, MCC950 attenuated obviously AGE-alb-induced IL-1ß and IL-18 secretion and caspase-1 activation. These results indicate that AGE-alb may induce macrophage pyroptosis, and the mechanism is at least partially by activating NLRP3-caspase-1 pathway.


Assuntos
Regulação da Expressão Gênica , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Albumina Sérica , Caspase 1 , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/genética , Macrófagos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Piroptose/efeitos dos fármacos , Albumina Sérica/farmacologia
10.
J Phys Chem Lett ; 10(24): 7617-7622, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31755717

RESUMO

By employing large-scale high-level EA-EOM-CCSD calculations, we have computed and analyzed the low-lying states of neutral Li@C60. Apart from one state, all states are found to be charge-separated states of the type Li+@C60-. The new state is the first reported non-charge-separated state in endohedral alkali fullerenes. This caged-electron state is analyzed in detail. Arguments are given that in larger highly symmetric endohedral fullerenes the caged-electron state can be the electronic ground state of the system. HF and DFT calculations on Li@C180 indeed find that the caged-electron state is the ground state and that in its equilibrium geometry Li sits at the center of the cage. Applications are mentioned.

11.
J Mater Chem B ; 7(45): 7141-7151, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31663577

RESUMO

Triple-negative breast cancer (TNBC) is characterized by a high metastatic rate, which can seriously threaten women's health. ROS play an important role in tumor development and metastasis. Excessive ROS can induce tumor cell apoptosis and inhibit tumor cell metastasis. This study investigated Fenton-reaction-stimulative nanoparticles (P@P/H NPs) containing ROS-responsive molecular switches for antitumor metastasis by amplifying the ROS and activating the cascade biological reaction of ROS in tumor cells. Spheroidal P@P/H NPs exhibited a uniform size of 68.18 ± 0.29 nm, high drug cumulative release of 97.59% in response to H2O2 at 24 h, and satisfactory cytotoxicity with the IC50 value of 0.50 ± 0.02 µg mL-1. The markedly elevated ROS level caused by P@P/H NPs generated an evident antitumor metastasis effect in vitro by facilitating the expressions of cytochrome c, caspase-9, and caspase-3 and blocking that of matrix metalloprotein 9 (MMP-9). Moreover, P@P/H NPs engendered an excellent tumor inhibition rate of 56.37% and antitumor metastasis effect in vivo. Therefore, P@P/H NPs could respond to H2O2 in tumor cells to rapidly disassemble and further increase the ROS to induce antitumor metastasis via the Fenton reaction.

12.
Front Pediatr ; 7: 403, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632941

RESUMO

Background/Aims: Biliary Atresia (BA) is a devastating pediatric liver disease and characterized by aggressive liver fibrosis progression. The Interleukin-33 (IL-33)/ST2 receptor signaling axis has been demonstrated to be involved in several autoimmune and liver diseases. Since immune dysregulation is a contributor to BA pathogenesis, we aimed to investigate the role of IL-33/ST2 receptor in the progression of liver fibrosis in BA patients. Materials and Methods: The study included 36 BA patients (18 good- and 18 poor-prognosis BA patients); and 8 cholestasis infants as the control group. Patients' information and clinical data were retrospectively collected and compared. Liver fibrosis stage was determined by Masson's trichrome staining. Gene expression levels of IL-33, ST2 receptor, and TFG-ß1 were detected by quantitative real-time PCR. MC count, IL-33, TGF-ß1, and Interleukin-13 (IL-13) expressions were evaluated by immunohistochemistry. Serum IL-33 expression level was detected by enzyme-linked immunosorbent assay. Co-expression of MC and ST2 receptor was detected by immunofluorescence. In vitro mast cell was cultured with IL-33 stimulation, and ST2 receptor and TGF-ß1 expressions were detected. Results: Compared with cholestasis control, BA patients had significantly higher GGT level and Masson score. Expression levels of IL-33, TGF-ß1, and IL-13 were significantly increased in BA patients compared to control group, especially in poor-prognosis BA patients. Co-expression of ST2 receptor and MC was found in BA liver tissues. The MC count was markedly higher in BA patients especially in poor-prognosis subgroup. Serum IL-33 level was significantly elevated in poor-prognosis BA patients and related to a higher Masson score. In vitro mast cell culture exhibited significant upregulation of ST2 receptor and TGF-ß1 mRNA expression after IL-33 stimulation. Conclusions: IL-33/ST2 receptor signaling axis is correlated with liver fibrosis progression in BA patients, and mast cells participates in this process. These indicate potential prognostic evaluation factors for BA patients and can help in the postoperative management to achieve better long-term prognosis in BA patients.

13.
J Chem Phys ; 151(11): 114306, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31542008

RESUMO

We report on high-level coupled-cluster calculations of electronic states of the neutral endohedral fullerene Li@C20. All computed states of neutral Li@C20 are found to be the charge separated states of the Li+@C20 - type. Using the state-of-the-art EA-EOM-CCSD method, we found that neutral Li@C20 (D3d) possesses several valence and superatomic charge separated states with considerable electron binding energies, the strongest bound state of Li+@C20 - being the 12Eu state (6.73 eV). The valence charge separated states correspond to two sets of states of C20 -. The states 12Eu, 12A2u, 22Eu, and 22A2u correspond to the respective bound states of C20 -, and the states 22A2g, 12Eg, 12A1g, and 42Eu correspond to the unbound states of C20 -. There are eight superatomic states with electron binding energy higher than 1.0 eV, being much stronger bound than the single weakly bound superatomic state of the parent fullerene anion. The analysis of the radial density distribution of the excess electron on the carbon cage indicates the important role of the inner part of the superatomic states in forming the charge separated states.

14.
Sensors (Basel) ; 19(19)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547194

RESUMO

Raman spectroscopy visualization is a challenging task due to the interference of complex background noise and the number of selected measurement points. In this paper, a super-resolution image reconstruction algorithm for Raman spectroscopy is studied to convert raw Raman data into pseudo-color super-resolution imaging. Firstly, the Raman spectrum data of a single measurement point is measured multiple times to calculate the mean value to remove the random background noise, and innovatively introduce the Retinex algorithm and the median filtering algorithm which improve the signal-to-noise ratio. The novel method of using deep neural network performs a super-resolution reconstruction operation on the gray image. An adaptive guided filter that automatically adjusts the filter radius and penalty factor is proposed to highlight the contour of the cell, and the super-resolution reconstruction of the pseudo-color image of the Raman spectrum is realized. The average signal-to-noise ratio of the reconstructed pseudo-color image sub-band reaches 14.29 db, and the average value of information entropy reaches 4.30 db. The results show that the Raman-based cell pseudo-color image super-resolution reconstruction algorithm is an effective tool to effectively remove noise and high-resolution visualization. The contrast experiments show that the pseudo-color image Kullback-Leiber (KL) entropy of the color image obtained by the method is small, the boundary is obvious, and the noise is small, which provide technical support for the development of sophisticated single-cell imaging Raman spectroscopy instruments.

15.
AAPS PharmSciTech ; 20(7): 302, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31489504

RESUMO

Docetaxel (DTX) was effective in the treatment of neoplasm but could only be administered intravenously with the poor oral bioavailability owing to its undesirable solubility, remarkably metabolic conversion, and other factors. Cimetidine (CMD), a classic CYP3A4 isozyme inhibitor, had exhibited a wide range of inhibition on the metabolism of many drugs. The aim of this study was to construct the novel docetaxel-cimetidine (DTX-CMD) complex and the chitosan-deoxycholate nanoparticles based on it to confirm whether this formulation could show advantages in terms of solubility, dissolution rate, small intestinal absorption, and oral bioavailability in comparison with the pure drug. The solid-state characterization was carried out by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), and simultaneous DSC-TGA (SDT). Dissolution rate and kinetic solubility study were determined by evaluating the amount of DTX in distilled water and phosphate buffer solution (pH = 7.4), respectively. And small intestinal absorption and pharmacokinetics study were conducted in rats. The results of this study demonstrated that we successfully constructed DTX-CMD complex and its chitosan-deoxycholate nanoparticles. Furthermore, the DTX-CMD complex increased the solubility of DTX by 2.3-fold and 2.1-fold in distilled water and phosphate buffer solution, respectively. The ultimate accumulative amount of DTX-CMD complex nanoparticles through rat small intestinal in 2 h was approximately 4.9-fold and the oral bioavailability of the novel nanoparticles was enhanced 2.8-fold, compared with the pure DTX. The superior properties of the complex nanoparticles could both improve oral bioavailability and provide much more feasibility for other formulations of DTX.


Assuntos
Antineoplásicos/química , Cimetidina/química , Docetaxel/química , Administração Oral , Animais , Disponibilidade Biológica , Quitosana/química , Cimetidina/farmacocinética , Ácido Desoxicólico/química , Docetaxel/farmacocinética , Composição de Medicamentos , Masculino , Nanopartículas/química , Ratos , Ratos Sprague-Dawley , Solubilidade
16.
Front Microbiol ; 10: 1770, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456757

RESUMO

Insomnia is a type of sleep disorder which is associated with various diseases' development and progression, such as obesity, type II diabetes and cardiovascular diseases. Recent investigation of the gut-brain axis enhances our understanding of the role of the gut microbiota in brain-related diseases. However, whether the gut microbiota is associated with insomnia remains unknown. In the present investigation, leveraging the 16S rDNA amplicon sequencing of V3-V4 region and the novel bioinformatic analysis, it was demonstrated that between insomnia and healthy populations, the composition, diversity and metabolic function of the gut microbiota are significantly changed. Other than these, redundancy analysis, co-occurrence analysis and PICRUSt underpin the gut taxa composition, signaling pathways, and metabolic functions perturbed by insomnia disorder. Moreover, random forest together with cross-validation identified two signature bacteria, which could be used to distinguish the insomnia patients from the healthy population. Furthermore, based on the relative abundance and clinical sleep parameter, we constructed a prediction model utilizing artificial neural network (ANN) for auxiliary diagnosis of insomnia disorder. Overall, the aforementioned study provides a comprehensive understanding of the link between the gut microbiota and insomnia disorder.

17.
J Cancer ; 10(16): 3678-3690, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333785

RESUMO

Chaetocin, a natural product extracted from Chaetomium species, possesses anticancer effects in several kinds of tumors. However, it remains unclear whether the potential indication for chaetocin could also include human gastric cancer. We found here that chaetocin induced caspase-dependent and -independent apoptosis in human gastric cancer cell lines, which greatly depended on BID-mediated AIF translocation. Despite not increasing the intercellular ROS levels in gastric cancer cells, chaetocin did cause a reduction in mitochondrial membrane potential probably through its regulation on the expression of Bcl-2 and BAX. Chaetocin could also induce autophagy in gastric cancer cells; blocking autophagy by chloroquine enhanced the cytotoxicity of chaetocin. Chaetocin was further found to suppress the growth of gastric cancer xenograft in nude mice. Therefore, our study provides first evidence that chaetocin has an anticancer efficacy against gastric cancer and the combined use of chaetocin with autophagy inhibitors may enhance the therapeutic effect for gastric cancer. As chronic and exorbitant ROS levels instigate drug resistance, chaetocin, which eradicates gastric cancer cells without increasing ROS levels, may initiate a new line of non-ROS-mediated anti-tumor strategy.

18.
Hortic Res ; 6: 72, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231530

RESUMO

The lignification triggered by biotic or abiotic stresses hardens fruits and vegetables and eventually influences their consumer appeal. Extensive prior efforts have been made to unveil the underlying mechanism of flesh lignification, primarily focused on its physicochemical and molecular biological properties. Nevertheless, most of these studies used destroyed and homogenized bulk tissues as analytes; as a result, potentially valuable spatial information was lost. In this study, the deposition of lignin in loquat flesh during lignification was visualized from the tissue level to the single-cell level by combining the advantages of stimulated Raman scattering (SRS) and spontaneous Raman microscopy using label-free in situ molecular imaging. SRS has the advantages of being fast and providing large-area chemical imaging to reveal the spatial heterogeneity of lignin and cell wall polysaccharide distribution in loquat flesh. After 2 days of storage at 0 °C, increased lignins were observed by large-area SRS imaging. In addition, microscopic SRS images of the flesh cells indicated that the increased lignins were trapped in the cell corner (CC) and middle lamella (ML). Furthermore, the compositional and structural features of lignified cells (LCs), CC and ML of loquat flesh were investigated by spontaneous Raman microscopy, and the results showed that the LCs were a combination of lignin, cellulose, and hemicellulose, whereas CC and ML showed only deposited lignin and pectin without cross-linked cellulose and hemicellulose. This result further suggests that the lignins in the CC and ML regions of loquats were later synthesized alone during postharvest storage. This innovative combination of SRS and spontaneous Raman microscopy allows the label-free macroscale and fine chemical imaging of plant cell walls and will enhance our fundamental understanding of the structures and functions of the plant cell wall.

19.
Sci Adv ; 5(5): eaaw2069, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31149637

RESUMO

Natural selection is thought to shape the evolution of aging patterns, although how life-history trajectories orchestrate the inherently stochastic processes associated with aging is unclear. Tracking clonal growth-arrested Escherichia coli cohorts in an homogeneous environment at single-cell resolution, we demonstrate that the Gompertz law of exponential mortality characterizes bacterial lifespan distributions. By disentangling the rate of aging from age-independent components of longevity, we find that increasing cellular maintenance through the general stress pathway reduces the aging rate and rescales the lifespan distribution at the expense of growth. This trade-off between aging and growth underpins the evolutionary tuning of the general stress response pathway in adaptation to the organism's feast-or-famine lifestyle. It is thus necessary to involve both natural selection and stochastic physiology to explain aging patterns.

20.
Sensors (Basel) ; 19(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035372

RESUMO

As the Internet-of-Things (IoT) and edge computing have been major paradigms for distributed data collection, communication, and processing, smart city applications in the real world tend to adopt IoT and edge computing broadly. Today, more and more machine learning algorithms would be deployed into front-end sensors, devices, and edge data centres rather than centralised cloud data centres. However, front-end sensors and devices are usually not so capable as those computing units in huge data centres, and for this sake, in practice, engineers choose to compromise for limited capacity of embedded computing and limited memory, e.g., neural network models being pruned to fit embedded devices. Visual object tracking is one of many important elements of a smart city, and in the IoT and edge computing context, high requirements to computing power and memory space severely prevent massive and accurate tracking. In this paper, we report on our contribution to object tracking on lightweight computing including (1) using limited computing capacity and memory space to realise tracking; (2) proposing a new algorithm region proposal correlation filter fitting for most edge devices. Systematic evaluations show that (1) our techniques can fit most IoT devices; (2) our techniques can keep relatively high accuracy; and (3) the generated model size is much less than others.

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