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1.
BMC Genomics ; 20(1): 813, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694534

RESUMO

BACKGROUND: Nsa cytoplasmic male sterility (CMS) is a novel alloplasmic male sterility system derived from somatic hybridization between Brassica napus and Sinapis arvensis. Identification of the CMS-associated gene is a prerequisite for a better understanding of the origin and molecular mechanism of this CMS. With the development of genome sequencing technology, organelle genomes of Nsa CMS line and its maintainer line were sequenced by pyro-sequencing technology, and comparative analysis of the organelle genomes was carried out to characterize the organelle genome composition of Nsa CMS as well as to identify the candidate Nsa CMS-associated genes. RESULTS: Nsa CMS mitochondrial genome showed a higher collinearity with that of S. arvensis than B. napus, indicating that Nsa CMS mitochondrial genome was mainly derived from S. arvensis. However, mitochondrial genome recombination of parental lines was clearly detected. In contrast, the chloroplast genome of Nsa CMS was highly collinear with its B. napus parent, without any evidence of recombination of the two parental chloroplast genomes or integration from S. arvensis. There were 16 open reading frames (ORFs) specifically existed in Nsa CMS mitochondrial genome, which could not be identified in the maintainer line. Among them, three ORFs (orf224, orf309, orf346) possessing chimeric and transmembrane structure are most likely to be the candidate CMS genes. Sequences of all three candidate CMS genes in Nsa CMS line were found to be 100% identical with those from S. arvensis mitochondrial genome. Phylogenetic and homologous analysis showed that all the mitochondrial genes were highly conserved during evolution. CONCLUSIONS: Nsa CMS contains a recombined mitochondrial genome of its two parental species with the majority form S. arvensis. Three candidate Nsa CMS genes were identified and proven to be derived from S. arvensis other than recombination of its two parental species. Further functional study of the candidate genes will help to identify the gene responsible for the CMS and the underlying molecular mechanism.

2.
Fitoterapia ; : 104378, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31676395

RESUMO

Five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy-N-demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N-oxide (5), were isolated from the whole plants of Lycopodiastrum casuarinoides (Lycopodiaceae), along with ten known analogues. The structures of the new compounds were elucidated by means of spectroscopic technique (IR, UV, MS and NMR). The absolute configurations of the new compounds were established on the basis of comparison of their experimental and TD-DFT (time-dependent density functional theory) calculated ECD spectra. Moreover, all the isolates were evaluated for acetylcholinesterase (AChE) inhibitory activity. Only huperzine C showed moderate activity, with an IC50 value of 0.525 ±â€¯0.140 µM, which was comparable with the positive control, huperzine A (IC50 = 0.143 ±â€¯0.029 µM).

3.
Stem Cell Res ; 41: 101628, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31678776

RESUMO

CUL4B gene mutation can cause intelligence deficiency 15, a syndromic form of X-linked mental retardation characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, speech delay and impairment, tremor and gait ataxia. Here, we generated iPSCs from a Chinese patient with c.1007_1011del (p.(Ile336fs)) in CUL4B gene by reprogramming peripheral blood mononuclear cells with non-integrating vectors. The generated iPSC line (SDQLCHi015-A) expresses pluripotency markers, presents a normal karyotype and is able to differentiate into three germ layers.

4.
Cancer Discov ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699796

RESUMO

We explored the mechanism of action of CD39 antibodies that inhibit ecto-enzyme CD39 conversion of extracellular ATP (eATP) to AMP and thus potentially augment eATP-P2-mediated pro-inflammatory responses. Using syngeneic and humanized tumor models, we contrast the potency and mechanism of anti-CD39 mAbs compared with other agents targeting the adenosinergic pathway. We demonstrate the critical importance of an eATP-P2X7-ASC-NALP3-inflammasome-IL-18 pathway in the anti-tumor activity mediated by CD39 enzyme blockade, rather than simply reducing adenosine as mechanism of action. Efficacy of anti-CD39 activity was underpinned by CD39 and P2X7 co-expression on intratumor myeloid subsets, an early signature of macrophage depletion, and active IL-18 release that facilitated the significant expansion of intratumor effector T cells. More importantly, anti-CD39 facilitated infiltration into T cell-poor tumors and rescued anti-PD1 resistance. Anti-human CD39 enhanced human T-cell proliferation and Th1 cytokine production and suppressed human B cell lymphoma in the context of autologous EBV-specific T cell transfer.

5.
Acta Pharmacol Sin ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586134

RESUMO

Abnormal protein aggregation has been linked to many neurodegenerative diseases, including Parkinson's disease (PD). The main pathological hallmark of PD is the formation of Lewy bodies (LBs) and Lewy neurites, both of which contain the presynaptic protein alpha-synuclein (α-syn). Under normal conditions, native α-syn exists in a soluble unfolded state but undergoes misfolding and aggregation into toxic aggregates under pathological conditions. Toxic α-syn species, especially oligomers, can cause oxidative stress, membrane penetration, synaptic and mitochondrial dysfunction, as well as other damage, leading to neuronal death and eventually neurodegeneration. Early diagnosis and treatments targeting PD pathogenesis are urgently needed. Given its critical role in PD, α-syn is an attractive target for the development of both diagnostic tools and effective therapeutics. This review summarizes the progress toward discovering imaging probes and aggregation inhibitors for α-syn. Relevant strategies and techniques in the discovery of α-syn-targeted drugs are also discussed.

7.
J Mater Chem B ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31638633

RESUMO

Phototherapy, particularly photothermal therapy (PTT) and photodynamic therapy (PDT), has become a promising therapeutic technique for the treatment of skin cancers because of its minial invasiveness, high efficacy, and low side effects. Nevertheless, single modality therapy, either PTT or PDT, has limited clinical effectiveness in treating skin cancers. Thus, combined applications of PTT and PDT have been frequently reported; however, PTT and PDT often require their respective photoagents and excitation light sources, resulting in challenges in clinical transformation. In this study, to address these issues, we report the use of biocompatible gold nanoclusters Au25(Capt)18 for the concurrent PTT and PDT treatment of cutaneous squamous cell carcinoma (cSCC) using an 808 nm near-infrared (NIR) laser. Utilizing their high light-thermal conversion efficiency, potent generation of singlet oxygen, and strong photothermal stability, Au25(Capt)18 nanoclusters potentiated a significant proliferation suppression of cSCC XL50 cells in vitro and the inhibition of cSCC tumors on SKH-1 mice in vivo. In particular, under 808 nm light irradiation, the tumor-cell-killing contributions of PTT and PDT were estimated to be 28.86% and 71.14%, respectively, by using an ROS scavenger to quench the PDT effect. Tumor-infiltrating CD4+ T and CD8+ T cells were observed after one course of concurrent PTT and PDT. Preliminary toxicity studies indicated low adverse effects of the Au25(Capt)18 nanoclusters. Through this study, we report the use of a simple nanostructure for simultaneous PTT and PDT applications to effectively kill cSCC and to induce anti-tumor immune responses. Our study could lead to the development of effective photoagents for current, synergistic applications of different phototherapies with targeted immunological responses for the treatment of cancers.

8.
Am J Hematol ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591739

RESUMO

We conducted a prospective, multicenter study to evaluate the efficacy and safety of low-dose decitabine in adult patients with refractory immune thrombocytopenia. Adult patients who did not respond to, did not tolerate, or were unwilling to undergo splenectomy, with either a baseline platelet count less than 30 × 109 /L or the presence of bleeding symptoms and further need of ITP-specific treatments, were enrolled. Patients received decitabine at 3.5 mg/m2 intravenously for three consecutive days per cycle, for three cycles with a four-week interval between cycles. All patients were assessed every week during the first 12 weeks and at four-week intervals thereafter. We screened 49 patients for eligibility. Four patients were excluded and 45 received decitabine. At the end of decitabine treatment, complete response was achieved in eight patients (17.78%), and partial response was achieved in 15 patients (33.33%). The median time to initial response was 28 days (range, 14-70 days). Furthermore, seven relapsed patients received decitabine retreatment and all showed platelet response, including one complete response and six partial responses. Sustained response rates at 6, 12 and 18 months were 44.44% (20/45), 31.11% (14/45) and 20.0% (9/45), respectively. For responders, immune thrombocytopenia-related symptoms, fatigue, psychological health, fear, and overall quality of life were significantly improved. Adverse events were observed in 13 (28.89%) patients. No serious adverse events were recorded. In conclusion, low dose decitabine is potentially effective and safe in the management of adults with refractory immune thrombocytopenia. This trial is registered with clinicaltrials.gov identifier: NCT01568333.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31628524

RESUMO

PURPOSE: To evaluate the efficacy of metformin plus first-line chemotherapy versus chemotherapy alone in the treatment of epithelial ovarian cancer. METHODS: Epithelial ovarian cancer patients without diabetes mellitus were allocated to non-metformin group (paclitaxel plus carboplatin) or metformin group (paclitaxel plus carboplatin plus metformin). The primary endpoint was progression-free survival (PFS) and disease-free survival (DFS). RESULTS: A total of 20 patients were assigned to metformin group and 24 patients to non-metformin group. The baseline information in two groups had no significant difference. The PFS and DFS of patients with metformin intake versus without metformin intake was 23 versus 21 months (p = 0.68) and 29 versus 26 months (p = 0.61), respectively. The PFS and DFS of patients with normal weight versus obese/overweight were 23 versus 17 months (p = 0.14) and 27 versus 23 months (p = 0.50), respectively. Metformin effectively inhibited the increase of IGF-1 and maintained the IGFBP-1. CONCLUSIONS: Within the limitations of the small sample size, there was no evidence of meaningful effect on PFS by metformin even though evidence of modulation of IGF-1 signaling axis was apparent.

10.
Stem Cell Res ; 40: 101579, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31610500

RESUMO

Maple syrup urine disease type Ib (MSUD Ib) is an autosomal recessive genetic metabolic disease caused by homozygous or compound heterozygous mutation in BCKDHB on chromosome 6q14. We generated an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a 5-day-old boy with MSUD Ib carrying compound heterozygous mutations of c.502C > T/p.R168C and c.965C > T/p.T322I in BCKDHB. The iPSCs had normal karyotype, expressed pluripotency markers, free of genomically integrated episomal plasmids and demonstrated trilineage differentiation potential in vitro.

11.
Cancer Sci ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31599076

RESUMO

Circular RNAs (circRNAs) have a covalently closed circular conformation and are structurally stable. Those circRNAs with tumor-suppressive properties play an important role in tumorigenesis and metastasis and thus may be used as therapeutic targets of cancers. Herein, we review the current understanding of the classification of circRNAs and summarize the functions and mechanisms of circRNAs that have tumor-suppressive roles in various cancers, including liver cancer (circARSP91, circADAMTS13, circADAMTS14, circMTO1, hsa_circ_0079299, and circC3P1), bladder cancer (circFNDC3B, circITCH, circHIPK3, circRNA-3, cdrlas, and circLPAR1), gastric cancer (circLARP4, circYAP1, hsa_cric_0000096, hsa_circ_0000993, and circPSMC3), breast cancer (circ_000911, hsa_circ_0072309, and circASS1), lung cancer (hsa_circ_0000977, circPTK2, circ_0001649, hsa_circ_100395, and circ_0006916), glioma (circ_0001946, circSHPRH, and circFBXW7), and colorectal cancer (circITGA7 and hsa_circ_0014717). Thanks to their structural stability, these tumor-suppressive circRNAs may be used as potential and potent therapeutic targets. Moreover, we propose a new method for the classification of circRNAs. Based on whether they can be translated, circRNAs can be divided into noncoding circRNAs and coding circRNAs.

13.
Life Sci ; 237: 116902, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610195

RESUMO

AIMS: Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) promotes hepatic stellate cell (HSC) autophagy and activation. However, the underlying mechanism remains unknown. Noncoding RNAs (ncRNAs) including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), have received increasing attention. We aimed to investigate the roles of the lncRNA nuclear enriched abundant transcript 1 (NEAT1), miR-29b, and autophagy related protein 9a (Atg9a), and their relationships with each other during IGFBPrP1-induced HSC autophagy and activation. MAIN METHODS: Levels of NEAT1, miR-29b, Atg9a, and autophagy were detected in adenovirus-mediated IGFBPrP1 (AdIGFBPrP1)-treated mouse liver tissue and immortalized mouse hepatic stellate cell line JS1 transfected with either AdIGFBPrP1 or siIGFBPrP1. In AdIGFBPrP1-treated JS1 cells, autophagy and activation were detected after altering NEAT1, miR-29b, or Atg9a levels. In AdIGFBPrP1-treated JS1 cells, relationships among NEAT1, miR-29b, and Atg9a were explored using dual-luciferase reporter assays, Western blot, qRT-PCR, and immunofluorescence. KEY FINDINGS: IGFBPrP1 increased levels of NEAT1, Atg9a, and autophagy while decreasing the level of miR-29b in mouse liver tissues and mouse HSCs. Moreover, NEAT1 increased HSC autophagy and activation while miR-29b decreased both processes. Atg9a also participated in IGFBPrP1-induced HSC autophagy and activation. Importantly, NEAT1, miR-29b, and Atg9a formed a NEAT1/miR-29b/Atg9a regulatory axis for IGFBPrP1-induced HSC autophagy and activation. SIGNIFICANCE: Our study unveiled the new NEAT1/miR-29b/Atg9a regulatory axis involved in IGFBPrP1-induced mouse HSC autophagy and activation. The study thus provides new insights in the pathogenesis and potential therapeutic strategies of liver fibrosis.

14.
Sensors (Basel) ; 19(21)2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31661867

RESUMO

High-precision ultrasound imaging of void defects is critical for the performance and safety assessment of ballastless track structures. The sound propagation velocity of each layer in the ballastless track structure is quite different. However, the traditional concrete Synthetic Aperture Focusing Technique (SAFT) ultrasound imaging method is based on the assumption that the concrete has a single constant shear wave velocity. Thus, it is not a suitable method for the ultrasonic imaging of multilayer structures. In this paper, a Multilayer SAFT high-precision ultrasound imaging method is proposed. It is based on the ray-tracing technique and uses the Fermat principle to find the refraction point that minimizes the delay of the acoustic wave propagation path at the interface of the discrete layers. Then, the acoustic wave propagation path is segmented by the position of the refraction point, and the propagation delay of the ultrasonic wave is obtained segment by segment. Thus, the propagation delay of the ultrasonic wave is obtained one by one, so that the propagation delay of the ultrasonic wave in the multilayer structure can be accurately obtained. Finally, the focused image is obtained according to the SAFT imaging algorithm. The finite element simulation and experimental results show that the Multilayer SAFT imaging method can accurately track the propagation path of the ultrasonic wave in ballastless track structures, as well as accurately calculate the propagation delay of the ultrasonic wave and the lengths of void defects. The high accuracy of the Multilayer SAFT imaging represents a significant improvement compared to traditional SAFT imaging.

15.
Stem Cell Res ; 41: 101577, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31648101

RESUMO

Induced pluripotent stem cell (iPSC) line (SDQLCHi012-A) was generated from peripheral blood mononuclear cells of an 11-month-old male who was diagnosed as inflammatory bowel disease-28 caused by compound heterozygote for IL10RA mutations (c.188 + 1G > A and c.301C > T). Non-integrating episomal vectors coding OCT4, SOX2, KLF4, BCL-XL and MYC were used for reprogramming. The established iPSC line contained the same mutations identified in the patient, showed a normal karyotype, differentiation potential in vitro and expressed pluripotency markers.

16.
Ecotoxicol Environ Saf ; 184: 109608, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31505407

RESUMO

Typical thermal processes are common sources of polychlorinated, polybrominated and mixed polybrominated/chlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, PBDD/Fs, and PBCDD/Fs); however, very few reports have investigated their coemission. To clarify the emission characteristics of these DD/Fs, two municipal waste incinerators (MWIs), three hazardous waste incinerators (HWIs), one cement kiln coprocessing municipal waste incinerator (CMWI), one secondary copper smelter (SCu), and one iron and steel sintering smelter (ISS) in China were investigated. In total, 17 congeners of PCDD/Fs, 14 congeners of PBDD/Fs, and 12 congeners of PBCDDs in stack flue gases from these thermal processes were analyzed using a high-resolution gas chromatograph/high-resolution mass spectrometer (HRGC/HRMS) in this study. PCDD/Fs, PBDD/Fs and PBCDD/Fs were detectable in all samples, with total concentrations of 911-5.15 × 103 pg/Nm3 (80.2-414 pg TEQ/Nm3). The concentrations of each DD/F were similar within the same type of facility and varied among different types of facilities. The contributions of PBDD/Fs and PBCDD/Fs to the total concentrations exceeded that of PCDD/Fs in some cases, such as in HWIs and SCu. In general, the ∑Cl4-7 CDFs and ∑Cl7-8 CDDs, 1,2,3,4,6,7,8-HpBDF, and 1-B-2,3,7,8-TeCDD and 2-B-1,3,7,8-TeCDD were the dominant congeners in the PCDD/F, PBDD/F, and PBCDD/F mass concentrations, respectively. Several other congeners present at low mass concentrations, such as 1,2,3,4,7,8-HxBDF, have potential as major contributors to the TEQs due to their high toxic equivalency factors. These results reveal the necessity of synergistically inhibiting the occurrences of PCDD/Fs, PBDD/Fs, and PBCDD/Fs from these sources and provide valuable information for use in the source identification of these pollutants in the environment.

17.
J Clin Lab Anal ; : e23049, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31556152

RESUMO

BACKGROUND: In addition to non-coding RNAs (lncRNAs) and microRNAs (miRNAs), circular RNAs (circRNAs) are endogenous RNAs with various functions, which have recently become a research hotspot. CircRNAs are a kind of closed circular RNA molecule widely existing in transcriptomes. Due to lack of free ends, they are not easily cleaved by RNase R, thus avoiding degradation. They are more stable than linear RNAs. METHODS: Data were collected through PubMed. The following search terms were used: "circular RNA," "circRNA," "cancer," "mechanism," "biogenesis," "biomarker," "diagnosis." Only articles published in English were included. RESULTS: Most circRNAs express tissue/developmental stage specificity. Moreover, circRNAs are involved in the regulation of a variety of biological activities. In this review, we discuss the formation, classification, and biological functions of circRNAs, especially their molecular diagnostic values in common cancers, including gastric cancer (hsa_circ_002059, circ_LARP4, hsa_circ_0000190, hsa_circ_0000096, circ-SFMBT2, and circ_PVT1), hepatocellular carcinoma (circ_104075, circRNA_100338, circ_MTO1, and circZKSCAN1), colorectal cancer (hsa_circ_0136666 and hsa_circ_0000523), lung cancer (hsa_circ_0006427, circ_100876, and circ_ABCB10), breast cancer (hsa_circ_0089105, circAGFG1, and circEPSTI1), bladder cancer (circFNDC3B and circTFRC), and esophageal squamous cell carcinoma (circ_100876 and circ-DLG1). CONCLUSION: CircRNAs not only play important roles in tumorigenesis, but also may become new diagnostic biomarkers.

18.
Sensors (Basel) ; 19(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470640

RESUMO

Wavenumber imaging with Green's function reconstruction of ultrasonic diffuse fields is used to realize fast imaging of near-surface defects in rails. Ultrasonic phased array has been widely used in industries because of its high sensitivity and strong flexibility. However, the directly measured signal is always complicated by noise caused by physical limitations of the acquisition system. To overcome this problem, the cross-correlations of the diffuse field signals captured by the probe are performed to reconstruct the Green's function. These reconstructed signals can restore the early time information from the noise. Experiments were conducted on rails with near-surface defects. The results confirm the effectiveness of the cross-correlation method to reconstruct the Green's function for the detection of near-surface defects. Different kinds of ultrasonic phased array probes were applied to collect experimental data on the surface of the rails. The Green's function recovery is related to the number of phased array elements and the excitation frequency. In addition, the duration and starting time of the time-windowed diffuse signals were explored in order to achieve high-quality defect images.

19.
Bioresour Technol ; 293: 122016, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31473375

RESUMO

Pretreatment is a key step in the energy utilization of lignocellulosic biomass. Different types of pretreatments (ultrafine grinding pretreatment, alkaline hydroxide peroxide pretreatment, dilute acid pretreatment, and ammonia fiber expansion pretreatment) were conducted on corn stover. The lignocellulosic composition, microstructural parameters, and glucose yield of differently pretreated corn stover were characterized and compared. Then qualitative and quantitative correlation analyses of the parameters were carried out to explore the correlations among the composition, microstructure properties, and enzymatic hydrolysis efficacy of corn stover after different types of pretreatments and identify the main properties affecting enzymatic hydrolysis. Qualitative correlation analysis found that cellulose content, specific surface area, pore volume, enzyme-accessible pore volume, and surface area of cellulose had significant positive correlations with glucose yield. The results of quantitative correlation analysis were GY = 15.01 × cellulose content-339.05, GY = 13.06 × SSA + 172.35, GY = 7226.27 × PV + 129.14, GY = 8628.61 × EAPV + 125.61, and GY = 1.18 × SAC-287.21.


Assuntos
Celulose , Zea mays , Biomassa , Carboidratos , Hidrólise
20.
Cell Res ; 29(10): 787-803, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31488882

RESUMO

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

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