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1.
Nat Commun ; 11(1): 792, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034155

RESUMO

Acyclic contiguous stereocenters are frequently seen in biologically active natural and synthetic molecules. Although various synthetic methods have been reported, predictable and unified approaches to all possible stereoisomers are rare, particularly for those containing non-reactive hydrocarbon substituents. Herein, a ß-boronyl group is employed as a readily accessible handle for predictable α-functionalization of enolates with either syn or anti selectivity depending on reaction conditions. Contiguous tertiary-tertiary and tertiary-quaternary stereocenters are thus accessed in generally good yields and diastereoselectivity. Based on experimental and computational studies, mechanism for syn selective alkylation is proposed, and Bpin (pinacolatoboronyl) behaves as a smaller group than most carbon-centered groups. The synthetic utility of this methodology is demonstrated by preparation of several key intermediates for bioactive molecules.

2.
Cardiovasc Res ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031586

RESUMO

AIMS: ß-Adrenergic receptors (ßARs) play pivotal roles in regulating cardiac excitation-contraction (E-C) coupling. Global signaling of ß1ARs upregulates both the influx of Ca2+ through sarcolemmal L-type Ca2+ channels (LCCs) and the release of Ca2+ from the sarcoplasmic reticulum (SR) through the ryanodine receptors (RyRs). However, we recently found that ß2AR stimulation meditates "offside compartmentalization", confining ß1AR signaling into subsarcolemmal nanodomains without reaching SR proteins. In the present study, we aim to investigate the new question whether and how compartmentalized ß1AR signaling regulates cardiac E-C coupling. METHODS AND RESULTS: By combining confocal Ca2+ imaging and patch clamp techniques, we investigated the effects of compartmentalized ßAR signaling on E-C coupling at both cellular and molecular levels. We found that simultaneous activation of ß2 and ß1ARs, in contrast to global signaling of ß1ARs, modulated neither the amplitude and spatiotemporal properties of Ca2+ sparks nor the kinetics of the RyR response to LCC Ca2+ sparklets. Nevertheless, by upregulating LCC current, compartmentalized ß1AR signaling synchronized RyR Ca2+ release and increased the functional reserve (stability margin) of E-C coupling. In circumstances of briefer excitation durations or lower RyR responsivity, compartmentalized ßAR signaling, by increasing the intensity of Ca2+ triggers, helped stabilize the performance of E-C coupling and enhanced the Ca2+ transient amplitude in failing heart cells. CONCLUSION: Given that compartmentalized ßAR signaling can be induced by stress-associated levels of catecholamines, our results revealed an important, yet unappreciated, heart regulation mechanism that is autoadaptive to varied stress conditions.

4.
Mol Plant Pathol ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32077242

RESUMO

Copper-based antimicrobial compounds are widely and historically used to control plant diseases, such as late blight caused by Phytophthora infestans, which seriously affects the yield and quality of potato. We previously identified that copper ion (Cu2+ ) acts as an extremely sensitive elicitor to induce ethylene (ET)-dependent immunity in Arabidopsis. Here, we found that Cu2+ induces the defence response to P. infestans in potato. Cu2+ suppresses the transcription of the abscisic acid (ABA) biosynthetic genes StABA1 and StNCED1, resulting in decreased ABA content. Treatment with ABA or inhibitor fluridone made potato more susceptible or resistance to late blight, respectively. In addition, potato with knockdown of StABA1 or StNCED1 showed greater resistance to late blight, suggesting that ABA negatively regulates potato resistance to P. infestans. Cu2+ also promotes the rapid biosynthesis of ET. Potato plants treated with 1-aminocyclopropane-1-carboxylate showed enhanced resistance to late blight. Repressed expression of StEIN2 or StEIN3 resulted in enhanced transcription of StABA1 and StNCED1, accumulation of ABA and susceptibility to P. infestans. Consistently, StEIN3 directly binds to the promoter regions of StABA1 and StNCED1. Overall, we concluded that Cu2+ triggers the defence response to potato late blight by activating ET biosynthesis to inhibit the biosynthesis of ABA.

5.
Cancer Lett ; 475: 136-142, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032679

RESUMO

Bone metastasis is a common complication of cancer, and bone is the third most common metastatic site following the lung and liver. Among the various bones, spine is the most common site of metastatic tumors. The treatment goals of patients with spinal metastases are mostly palliative, with the aim of reducing pain and improving quality of life. The treatment of spinal metastases has made significant progress over the past few decades. Each new technology has tried to solve the shortcomings of its predecessors. Currently, there are no mature algorithms or specific techniques that have proven to be the best for spinal metastases, and the treatment method often relies on operator and institutional preferences or biases in some cases. Percutaneous vertebral augmentation has unique value in the management of spinal metastases, understanding its indications, surgical techniques, uses, advantages and complications is critical to providing optimal patient care. We believe that the application of percutaneous vertebral augmentation alone or combined with other techniques can achieve optimal pain relief and functional improvement in the patients with spinal metastases.

6.
BMC Med Genomics ; 13(1): 24, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046717

RESUMO

BACKGROUND: Kidney transplantation is the most effective treatment for end-stage renal disease. Allograft rejections severely affect survivals of allograft kidneys and recipients. METHODS: Using bioinformatics approaches, the present study was designed to investigate immune status in renal transplant recipients. Fifteen datasets from Gene Expression Omnibus (GEO) were collected and analysed. Analysis of gene enrichment and protein-protein interactions were also used. RESULTS: There were 40 differentially expressed genes (DEGs) identified in chronic rejection group when compared with stable recipients, which were enriched in allograft rejection module. There were 135 DEGs identified in acute rejection patients, compared with stable recipients, in which most genes were enriched in allograft rejection and immune deficiency. There were 288 DEGs identified in stable recipients when compared to healthy subjects. Most genes were related to chemokine signalling pathway. In integrated comparisons, expressions of MHC molecules and immunoglobulins were increased in both acute and chronic rejection; expressions of LILRB and MAP 4 K1 were increased in acute rejection patients, but not in stable recipients. There were no overlapping DEGs in blood samples of transplant recipients. CONCLUSION: By performing bioinformatics analysis on the immune status of kidney transplant patients, the present study reports several DEGs in the renal biopsy of transplant recipients, which are requested to be validated in clinical practice.

7.
Sci Total Environ ; 717: 137180, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32065893

RESUMO

Bacterial communities play an important role in diffuse sediment pollution in aquaculture farms. Previous studies have revealed the short-term influence of wastewater drainage on the bacterial communities but the seasonal response of the sediment bacterial communities to wastewater drainage from aquaculture farms remains unclear. This study used the 16S rRNA approach to explore the profiles of bacterial communities over four seasons in a typical crab aquaculture farm that included a pond and an outlet ditch. Nineteen sediment samples and an equal number of water samples were collected and analysed during spring, summer, autumn, and winter during 2018-19. Our results showed that Proteobacteria, Chloroflexi, and Bacteroides were the predominant phyla in aquaculture pond sediment with the relative abundance of 28.95%, 17.32%, and 15.31%, respectively. The relative abundance of Proteobacteria and Bacteroides was higher in autumn and winter, and the relative abundance of Chloroflexi was highest in spring. The Shannon diversity index value ranged from 6.17 to 9.30 and showed significant positive correlation (P < 0.01) with the concentrations of TN, NH4+-N, and TP in the water. The variation in the bacterial community and relative abundance in outlet ditch sediment were consistent with those in the pond sediment. Our results show that determinisation of the bacterial community composition in the outlet ditch sediment provides a novel tool to monitor watersheds sensitive to the influence of aquacultures.

8.
Medicine (Baltimore) ; 99(8): e19067, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080080

RESUMO

Unplanned resection of soft-tissue sarcomas (STS) predispose the patients to recurrences and metastases, secondary wide resection is usually warranted.To investigate the outcomes of re-excision of STS after unplanned initial resection.The records of 39 patients undergoing re-excision of STS after unplanned initial resection from January 2006 through December 2015 were retrospectively investigated.There were 17 males and 22 females, the mean age was 45.7 years. Most initial unplanned resections were performed in rural hospitals by surgeons from general surgery department, dermatology department, plastic surgery department, and orthopedic department. Thirty-five patients underwent secondary wide resections in our department. Histopathological findings indicated positive margins after primary surgeries in 18 patients. Until the conclusion of 37.2-month follow-up, 7 patients developed metastasis, 3 had local recurrence, and 7 were dead. Positive margins were associated with increased metastases and lower survival rates (P < .05). There was no significant difference in recurrences between the 2 groups.Unplanned initial resection of STS often lead to unfavorable prognosis. Primary wide resections are warranted for this disease entity.

9.
J Transl Med ; 18(1): 92, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070368

RESUMO

BACKGROUND: Metabolic reprogramming, immune evasion and tumor-promoting inflammation are three hallmarks of cancer that provide new perspectives for understanding the biology of cancer. We aimed to figure out the relationship of tumor glycolysis and immune/inflammation function in the context of breast cancer, which is significant for deeper understanding of the biology, treatment and prognosis of breast cancer. METHODS: Using mRNA transcriptome data, tumor-infiltrating lymphocytes (TILs) maps based on digitized H&E-stained images and clinical information of breast cancer from The Cancer Genome Atlas projects (TCGA), we explored the expression and prognostic implications of glycolysis-related genes, as well as the enrichment scores and dual role of different immune/inflammation cells in the tumor microenvironment. The relationship between glycolysis activity and immune/inflammation function was studied by using the differential genes expression analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analyses (GSEA) and correlation analysis. RESULTS: Most glycolysis-related genes had higher expression in breast cancer compared to normal tissue. Higher phosphoglycerate kinase 1 (PGK1) expression was associated with poor prognosis. High glycolysis group had upregulated immune/inflammation-related genes expression, upregulated immune/inflammation pathways especially IL-17 signaling pathway, higher enrichment of multiple immune/inflammation cells such as Th2 cells and macrophages. However, high glycolysis group was associated with lower infiltration of tumor-killing immune cells such as NKT cells and higher immune checkpoints expression such as PD-L1, CTLA4, FOXP3 and IDO1. CONCLUSIONS: In conclusion, the enhanced glycolysis activity of breast cancer was associated with pro-tumor immunity. The interaction between tumor glycolysis and immune/inflammation function may be mediated through IL-17 signaling pathway.

10.
Cytokine ; 128: 155019, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32018068

RESUMO

BACKGROUND: Previous studies showed that GTS-21, a selective alpha 7 nAchR agonist, can trigger anti-inflammatory effects and improve the survival of septic animals. However, whether GTS-21 affects autophagy responses remains unclear. Here, we tested the hypothesis that GTS-21 ameliorates sepsis-induced hepatic injury by modulating autophagy in mice. METHOD: C57BL/6 male mice were randomly separated and categorized into four groups: the sham group, and CLP group subjected to caecal ligation and puncture (CLP, a model of polymicrobial sepsis). The CLP + GTS-21 group was administered GTS-21 immediately after CLP challenge. α-Bungarotoxin (an alpha 7 nAchR antagonist) was injected before CLP was performed, and then, after CLP challenge, GTS-21 was administered to α-BGT + CLP + GTS-21 group. The hepatic tissue and blood samples were harvested 6 h after the operation. RESULTS: CLP challenge increased TNF-α and IL-6 production, and hepatic enzyme alanine aminotransferase and aspartate transaminase levels. CLP also elevated the expression of hepatic LC3-II, sequestosome-1/p62, Atg7 and Atg5. The administration of GTS-21 inhibited pro-inflammatory cytokine production and hepatic enzymatic marker expression, promoted the expression of LC3-II, Atg7, Atg5, and decreased the expression of p62, which could be reversed by α-BGT treatment. CONCLUSION: Our findings suggested that α7nAchR is involved in diminishing hepatic damage by inhibiting inflammatory responses and improving autophagy in mice with polymicrobial sepsis.

11.
World J Microbiol Biotechnol ; 36(1): 13, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897764

RESUMO

Streptomyces is famous for its capability to produce the most abundant antibiotics in all kingdoms. All Streptomyces antibiotics are natural products, whose biosynthesis from the so-called gene clusters are elaborately regulated by pyramidal transcriptional regulatory cascades. In the past decades, scientists have striven to unveil the regulatory mechanisms involved in antibiotic production in Streptomyces. Here we mainly focus on three aspects of the regulation on antibiotic production. 1. The onset of antibiotic production triggered by hormones and their coupled receptors as regulators; 2. The cascades of global and pathway-specific regulators governing antibiotic production; 3. The feedback regulation of antibiotics and/or intermediates on the gene cluster expression for their coordinated production. This review will summarize how the antibiotic production is stringently regulated in Streptomyces based on the signaling, and lay a theoretical foundation for improvement of antibiotic production and potentially drug discovery.


Assuntos
Antibacterianos/metabolismo , Redes Reguladoras de Genes , Streptomyces/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Hormônios/metabolismo , Família Multigênica , Streptomyces/genética
12.
Int J Mol Sci ; 21(3)2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-31991936

RESUMO

The FW2.2-like (FWL) genes encode cysteine-rich proteins with a placenta-specific 8 domain. They play roles in cell division and organ size control, response to rhizobium infection, and metal ion homeostasis in plants. Here, we target eight rice FWL genes using the CRISPR/Cas9 system delivered by Agrobacterium-mediated transformation. We successfully generate transgenic T0 lines for 15 of the 16 targets. The targeted mutations are detected in the T0 lines of all 15 targets and the average mutation rate is found to be 81.6%. Transfer DNA (T-DNA) truncation is a major reason for the failure of mutagenesis in T0 plants. T-DNA segregation analysis reveals that the T-DNA inserts in transgenic plants can be easily eliminated in the T1 generation. Of the 30 putative off-target sites examined, unintended mutations are detected in 13 sites. Phenotypic analysis reveals that tiller number and plant yield of OsFWL4 gene mutants are significantly greater than those of the wild type. Flag leaves of OsFWL4 gene mutants are wider than those of the wild type. The increase in leaf width of the mutants is caused by an increase in cell number. Additionally, grain length of OsFWL1 gene mutants is higher than that of the wild type. Our results suggest that transgene-free rice plants with targeted mutations can be produced in the T1 generation using the Agrobacterium-mediated CRISPR/Cas9 system and that the OsFWL4 gene is a negative regulator of tiller number and plant yield.

13.
Chem Commun (Camb) ; 56(7): 1097-1100, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31894765

RESUMO

A titanium-polyoxomolybdate K6(H3O)8[{PMo9O34TiO}2]·32H2O (1) was successfully synthesized and structurally characterized. It is an unprecedented instance that the titanium-containing polyoxomolybdate is water-soluble and was synthesized by using a conventional aqueous solution method. The Ti4+ ions exist in an unusual coordination mode. Besides, compound 1 as a wide band gap semiconductor showed evident photocatalytic activity for the oxidation of benzaldehyde into benzoic acid.

14.
Int J Mol Med ; 45(1): 234-244, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31939613

RESUMO

The treatment of colorectal cancer is currently hampered by the lack of early detection technology. The identification of molecular biomarkers for colorectal cancer is crucial for improving prognosis. Synaptotagmin (SYT) 13 has been reported to be associated with several human tumors, but its role in colorectal cancer remains elusive. In the present study, immunohistochemistry was utilized to detect the expression of SYT13 in colorectal cancer tissues and cells. MTT, colony formation, wound healing and Transwell assays were conducted to evaluate the effect of SYT13 knockdown on the biological behavior of RKO and HCT116 cells. Cell apoptosis and cell cycle profiles were detected by FACS. A mouse xenograft model was constructed to investigate the effect of SYT13 on colorectal cancer in vivo. The results indicated that SYT13 was upregulated in colorectal tumor tissues compared with paracancerous tissues. Silencing of SYT13 inhibited the proliferation, colony formation, migration and invasion ability of RKO and HCT116 cells. Moreover, SYT13 knockdown arrested the cell cycle in the G2 phase, thus inducing cell apoptosis. The in vivo experiments also demonstrated the inhibitory effect of SYT13 on tumor growth. In conclusion, the present study demonstrated that SYT13 may act as a promoter in the development and progression of colorectal cancer and, therefore, may be of value as a target for the development of novel treatment strategies.

15.
Aging Cell ; : e13106, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31971661

RESUMO

Adipose-derived mesenchymal stem cell (ADSC)-based regenerative therapies have shown potential for use in many chronic diseases. Aging diminishes stem cell regenerative potential, yet it is unknown whether stem cells from aged donors cause adverse effects in recipients. ADSCs can be obtained using minimally invasive approaches and possess low immunogenicity. Nevertheless, we found that transplanting ADSCs from old donors, but not those from young donors, induces physical dysfunction in older recipient mice. Using single-cell transcriptomic analysis, we identified a naturally occurring senescent cell-like population in ADSCs primarily from old donors that resembles in vitro-generated senescent cells with regard to a number of key pathways. Our study reveals a previously unrecognized health concern due to ADSCs from old donors and lays the foundation for a new avenue of research to devise interventions to reduce harmful effects of ADSCs from old donors.

16.
Int J Mol Sci ; 21(3)2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31979101

RESUMO

Chromium (Cr) is one of the top seven toxic heavy metals, being ranked 21st among the abundantly found metals in the earth's crust. A huge amount of Cr releases from various industries and Cr mines, which is accumulating in the agricultural land, is significantly reducing the crop development, growth, and yield. Chromium mediates phytotoxicity either by direct interaction with different plant parts and metabolic pathways or it generates internal stress by inducing the accumulation of reactive oxygen species (ROS). Thus, the role of Cr-induced ROS in the phytotoxicity is very important. In the current study, we reviewed the most recent publications regarding Cr-induced ROS, Cr-induced alteration in the enzymatic antioxidant system, Cr-induced lipid peroxidation and cell membrane damage, Cr-induced DNA damage and genotoxicity, Cr-induced ultrastructural changes in cell and subcellular level, and Cr-induced alterations in photosynthesis and photosynthetic apparatus. Taken together, we conclude that Cr-induced ROS and the suppression of the enzymatic antioxidant system actually mediate Cr-induced cytotoxic, genotoxic, ultrastructural, and photosynthetic changes in plants.

17.
Cell Mol Biol Lett ; 25: 1, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31988639

RESUMO

The ubiquitin system, known as a common feature in eukaryotes, participates in multiple cellular processes, such as signal transduction, cell-cycle progression, receptor trafficking and endocytosis, and even the immune response. In lung cancer, evidence has revealed that aberrant events in ubiquitin-mediated processes can cause a variety of pathological outcomes including tumorigenesis and metastasis. Likewise, ubiquitination on the core components contributing to the activity of cell signaling controls bio-signal turnover and cell final destination. Given this, inhibitors targeting the ubiquitin system have been developed for lung cancer therapies and have shown great prospects for clinical application. However, the exact biological effects and physiological role of the drugs used in lung cancer therapies are still not clearly elucidated, which might seriously impede the progress of treatment. In this work, we summarize current research advances in cell signal regulation processes mediated through the ubiquitin system during the development of lung cancer, with the hope of improving the therapeutic effects by means of aiming at efficient targets.

19.
Mol Pharm ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31910019

RESUMO

Biomedical nanoplatforms have been widely investigated for ultrasound (US) imaging and cancer therapy. Herein, perfluorocarbon (PFC) is encapsulated into biocompatible polydopamine (PDA) to form a theranostic nanosystem, followed by the modification of polyethylene glycol (PEG) to stabilize the nanoparticle via a facile one-pot method. Under 808 nm near-infrared laser irradiation, PDA can generate hyperthermia to transform PFC droplets to bubbles with high US imaging sensitivity. The US imaging detection of the PFC-PDA-PEG nanosystem is achievable in a time span of up to 25 min in vitro at a low US frequency and mechanical index, manifesting a US imaging performance for in vivo application. Moreover, tumor cells incubated with the nanosystem are ablated effectively under laser irradiation at 808 nm. The results illustrate the potential of the PDA-based theranostic agent in US imaging-guided photothermal therapy of tumor.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31943728

RESUMO

BACKGROUND: The Coronary Artery Tree description and Lesion EvaluaTion (CatLet) score accommodating the variability in coronary anatomy is a recently developed and comprehensive angiographic scoring system aimed at assisting in risk-stratification of patients with coronary artery disease. However, a validation of this angiographic scoring system is lacking. METHODS: The CatLet score was calculated retrospectively in 308 consecutively enrolled patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention. The primary endpoint, major adverse cardiac or cerebrovascular events (MACCEs), was stratified according to CatLet tertiles: CatLetlow ≤14 (n = 124), CatLetmid 15-21 (n = 82) and CatLettop ≥22 (n = 102). RESULTS: The CatLet score alone or after adjusting for a broad spectrum of risk factors, significantly predicted clinical outcomes at a median 4.3-year follow-up. Multivariable-adjusted hazard ratios (95%CI)/unit higher score were 1.05 (1.04-1.07) for MACCE, 1.06 (1.04-1.07) for cardiac death, and 1.05 (1.04-1.07) for all-cause death. When compared to the SYNTAX score, improved discrimination and better calibration of this CatLet score resulted in a significantly refined risk stratification. The overall category-free net reclassification improvement afforded by this CatLet score was as follows: 37.2% (p = .008) for MACCEs, 35.5% (p = .0249) for cardiac death, and 31.8% (p = .0316) for all-cause death. CONCLUSIONS: The ability to integrate the variability in coronary anatomy into angiographic scoring makes the CatLet score a more specific tool for outcome predictions in AMI. (http://www.chictr.org.cn. Unique identifiers: ChiCTR-POC-17013536).

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