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1.
Plant Dis ; 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33822662

RESUMEN

Peach (Prunus persica L. Batsch) is one of the most important fruit crops in China (Wang et al. 2011). Yangshan Town of Jiangsu Province is one of the four major peach producing areas in China, with a growing area of 2,000 ha (Tian et al. 2018). During June 2020, a postharvest disease presenting with brown necrosis and rot occurred on peaches in Yangshan Town. The estimated damage was more than 10% of the total harvest. The symptoms included soft rot, and the lesion appeared sunken, accompanied with sour odor and white mycelia. Twelve peaches with representative symptom were sampled for pathogen isolation. Pieces (about 5 mm × 5 mm) from the lesion edge of symptomatic fruits were dissected and surface disinfected (3% NaClO for 10 s and 75% ethanol for 30 s), then rinsed three times with distilled water, dried on sterile filter paper and transferred to Potato Dextrose Agar (PDA) media plates supplemented with 150 ng/mL streptomycin sulfate. The plates were incubated at 28 ℃ for 3 days. Forty-eight isolations were obtained from the plates and isolates were single-spored. All isolates presented white, flat, milky yeast-like colonies with radial mycelia. Hyphae under microscope were septate, branched, disarticulating into arthroconidia measuring 3.39 to 9.27 × 2.05 to 7.71 µm. The morphological characteristics are consistent with Geotrichum candidum (De Hoog et al. 1986). Internal transcribed spacer (ITS) and 18s nuclear ribosomal small subunit (SSU) of the 48 isolates were amplified and sequenced using the primers ITS5/ITS4, and NS1/NS4 for molecular identification (Schoch et al. 2012). The resulted sequences showed no difference among all the isolates. Alignment by blastn showed the sequence of ITS and SSU were 100% (accession number. GQ376093) and 99.7% identical (accession number. KY977411.1) to Geotrichum candidum, respectively. The sequences of ITS (accession number MW493646) and SSU (accession number MW493648) were submitted to the GenBank. Commercial ripe peaches with the size of about 15 cm × 15 cm × 10 cm was used for pathogenicity test. Peaches were surface disinfected with 75% ethanol, then a wound with 4 mm in diameter and 5 mm in depth was made on the surface of each fruit. Ten peaches were inoculated with 10 µL (1×105 spores /mL) of the isolate suspension. Another ten peaches were inoculated with 10 µL sterile water as the control. Peaches were incubated individually at 28 ℃and a relative humidity of about 85%. After three days, large scale of pits and necrosis appeared on every peach inoculated, and the symptoms were consistent with the diseased peaches in Yangshan Town, while no symptoms non-inoculated on the control peaches were observed. The pathogen was re-isolated from the diseased fruit and was identified again by sequencing of ITS and SSU. All the tests were conducted three times. Considering the evidence, we identified the pathogen as G. candidum. This pathogen has been reported to cause sour rot was reported in kiwifruit, strawberry, melon and other fruits (Alonzo et al. 2020; Cheng et al. 2020; Halfeld-Vieira et al. 2020). To our knowledge, this is the first report of G. candidum causing sour rot of peach in China, which may cause a great loss to peach industry of China.

2.
Sensors (Basel) ; 21(7)2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807475

RESUMEN

The growing demand for intelligent equipment has greatly inspired the development of flexible devices. Thus, disparate flexible multifunctional devices, including pressure sensitive flexible/stretchable displays, have drawn worldwide research attention. Electrodes maintaining conductivity and mechanical strength against deformations are indispensable components in all prospective applications. In this work, a flexible pressure mapping sensor array is developed based on patterned Ag-nanofibers (Ag-NFs) electrode through electrospinning and lithography. The metallic Ag layer is sputtered onto the electrospinning polyvinyl alcohol (PVA) NFs. A uniform and super conductive electrode layer with outstanding mechanical performance is thus formed after dissolving PVA. Followed by the traditional lithography method, a patterned electrode array (4 × 4 sensors) is obtained. Based on the newly developed triboelectric nanogenerator (TENG) technology, a flexible pressure-mapping sensor with excellent stability towards bending deformations is further demonstrated. Moreover, a letter "Z" is successfully visualized by this pressure sensor array, encouraging more human-machine interactive implementations, such as multi-functional tactile screens.

3.
Artículo en Inglés | MEDLINE | ID: mdl-33817758

RESUMEN

BACKGROUND: Due to the high risk of ischemic and arterial or venous bleeding events in atrial fibrillation (AF) or venous thromboembolism (VTE) patients with renal impairment (RI), selection of appropriate anticoagulant regimen is important. Therefore, we systematically reviewed and compared the safety and effects of oral anticoagulants in AF and VTE patients with RI. METHODS: Eligible articles were identified through a literature search in PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library for studies published between January 2008 and November 2020. Network meta-analysis was conducted with STATA 14.0 to analyze the effects and safety of each drug with regard to different levels of renal function. RESULTS: 15 studies including 82,931 patients (76,957 with AF and 5974 with VTE) were analyzed. Compared with those of warfarin, the risk ratios of effect and safety outcomes of apixaban were 0.70 (95% confidence interval [CI] 0.60-0.82) and 0.56 (95% CI 0.42-0.76) in AF patients and 0.33 (95% CI 0.19-0.59) and 0.95 (95% CI 0.68-1.34) in VTE patients. Apixaban had the first or second highest probability of being ranked first with respect to surface under the cumulative ranking curve (SUCRA) scores in the prevention of major bleeding events, while in the prevention of ischemic events, rivaroxaban showed a higher SUCRA score (0.78-0.92) in mild RI patients and dabigatran showed a higher SUCRA value (0.90-0.99) in moderate RI patients. CONCLUSIONS AND RELEVANCE: In the systematic review and meta-analysis, for AF or VTE patients with RI, direct oral anticoagulants performed comparably to or better than warfarin with regard to safety and effects. The network meta-analysis indicated that for patients with mild RI, apixaban might be safer for patients with a lower risk of ischemic events, while rivaroxaban might be suitable for patients with a lower risk of bleeding events. For patients with moderate RI, apixaban could reduce the risk of ischemic events without increasing the risk of bleeding events. For AF patients with severe RI, apixaban, rivaroxaban, and warfarin showed a similar effect. These results might provide suggestions for clinical arterial and venous thrombosis prevention.

4.
J Integr Neurosci ; 20(1): 77-85, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33834693

RESUMEN

The social behavior mechanisms have not been thoroughly reported in the solitary female striped dwarf hamster (Cricetulus barabensis). In this study, the handling bag test and neutral arena measurements were used to detect the changes of aggression in the face of rivals of different genders of wild striped dwarf hamsters. We found that female hamsters had the highest aggressive performance in proestrus, followed by estrus, and the lowest in metestrus and the dioestrus, and the increased aggression during the proestrus or estrus period was low-intensity aggression such as intimidation, shock, boxing and counterattack, or even ritualized non-harmful behaviors to drive away opponents. When confronted with male individuals, aggression in females decreased significantly during estrus. The concentration of plasma estradiol was the highest in estrus and the lowest in metestrus and dioestrus. In contrast, estrogen receptor 2 relative expression in the hypothalamus is the lowest in proestrus and highest in metestrus and dioestrus. Besides, both estradiol levels in plasma and estrogen receptor 2 mRNA in the hypothalamus were associated with aggression. These results will broaden our understanding of the molecular mechanism of how breeding phenotype is an essential driver in changing the social behavior of female Cricetulus barabensis.

5.
Environ Sci Technol ; 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33793220

RESUMEN

Nitrated phenols (NPs) are important atmospheric pollutants that affect air quality, radiation, and health. The recent development of the time-of-flight chemical ionization mass spectrometer (ToF-CIMS) allows quantitative online measurements of NPs for a better understanding of their sources and environmental impacts. Herein, we deployed nitrate ions as reagent ions in the ToF-CIMS and quantified six classes of gaseous NPs in Beijing. The concentrations of NPs are in the range of 1 to 520 ng m-3. Nitrophenol (NPh) has the greatest mean concentration. Dinitrophenol (DNP) shows the greatest haze-to-clean concentration ratio, which may be associated with aqueous production. The high concentrations and distinct diurnal profiles of NPs indicate a strong secondary formation to overweigh losses, driven by high emissions of precursors, strong oxidative capacity, and high NOx levels. The budget analysis on the basis of our measurements and box-model calculations suggest a minor role of the photolysis of NPs (<1 ppb h-1) in producing OH radicals. NPs therefore cannot explain the underestimated OH production in urban environments. Discrepancies between these results and the laboratory measurements of the NP photolysis rates indicate the need for further studies aimed at understanding the production and losses of NPs in polluted urban environments.

7.
Oxid Med Cell Longev ; 2021: 8810698, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33815661

RESUMEN

Programmed necrosis of nucleus pulposus (NP) cells caused by excessive compression is a crucial factor in the etiopathogenesis of intervertebral disc degeneration (IVDD). The endoplasmic reticulum (ER) and mitochondria are crucial regulators of the cell death signaling pathway, and their involvement in IVDD has been reported. However, the specific role of ER stress (ERS) and ER-mitochondria interaction in compression-induced programmed necrosis of NP cells remains unknown. Our studies revealed that compression enhanced ERS and the association between ER and mitochondria in NP cells. Suppression of ERS via 4-phenylbutyrate (4-PBA) or ER-mitochondrial Ca2+ crosstalk by inhibiting the inositol 1,4,5-trisphosphate receptor, glucose-regulated protein 75, voltage-dependent anion-selective channel 1 complex (IP3R-GRP75-VDAC1 complex) protected NP cells against programmed necrosis related to the poly(ADP-ribose) polymerase (PARP) apoptosis-inducing factor (AIF) pathway. Moreover, excessive reactive oxygen species are critical activators of ERS, leading to mitochondrial Ca2+ accumulation and consequent programmed necrosis. These data indicate that ERS and ER-mitochondrial Ca2+ crosstalk may be potential therapeutic targets for the treatment of IVDD-associated disorders. These findings provide new insights into the molecular mechanisms underlying IVDD and may provide novel therapeutic targets.

8.
Biochem Pharmacol ; : 114539, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33819468

RESUMEN

The antitumor properties of cruciferous vegetables are mainly due to their high content of isothiocyanates, and sulforaphane (SFA) is the most well-known compound. The aim of this study was to determine the mechanism of SFA inhibiting gastric cancer (GC) progression. After verifying SFA suppressing GC growth in vivo, we utilized the GSE79973 and GSE118916 datasets to identify the GC development signatures that overlap with the RNA-seq analysis in SFA-treated AGS cells. GSEA of the RNA-seq data indicated that SFA regulation of GC progression was related to extracellular matrix and collagens; thus, we identified COL3A1 and COL5A1 as the targets of SFA, which functioned as oncogenes. We found positive correlations between COL3A1 and COL5A1 expression in GC cells, and confirmed that miR-29a-3p is the common regulator of their expression. RNA immunoprecipitation assays based on Ago2, Dicer, and exportin-5 showed that SFA could promote mature miR-29a-3p generation. We also proved that SFA inactivated the Wnt/ß-catenin pathway in GC cells in a miR-29a-3p-dependent manner. Overall, SFA boosts miR-29a-3p maturation to downregulate COL3A1 and COL5A1 and inactivate the Wnt/ ß -catenin pathway to suppress GC progression.

9.
Mol Cell Endocrinol ; : 111280, 2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33862186

RESUMEN

The elevated thyroid-stimulating hormone (TSH) levels contribute to the abnormal expression/activity of several key hepatic lipid metabolism enzymes. Although miRNAs have been shown to play key roles in hepatic lipid metabolism and are found in isolated mitochondria, very little is known about the pathological and physiological significance of their mitochondrial distributions in regulating liver lipid metabolism. Here, we found that TSH significantly reduced the distribution of some miRNAs in mitochondria of hepatocytes, especially miR-449a, miR-449b-5p, and miR-5194. These three miRNAs inhibited their target genes PGC1B, ABCD1, ADIPOR1 and the downstream molecule PPARA. These effects synergistically suppressed fatty acid (FA) ß-oxidation in mitochondria and peroxisomes and decreased the translocation of cytosolic very long chain fatty acids to peroxisomes, which noticeably reduced FA catabolism and promoted triglyceride accumulation in hepatocytes. This study reveals the functional significance of changed miRNA mitochondrial-cytoplasmic distribution in the regulation of hepatic lipid metabolism.

10.
J Mater Chem B ; 9(11): 2613-2622, 2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33683252

RESUMEN

Photothermal therapy (PTT) based on semiconducting polymer nanoparticles (SPNs) is a promising strategy to treat solid tumors, but its ability to combine with chemotherapy for immune remodeling to efficiently suppress metastatic cancers has rarely been studied. Here, we demonstrate that PTT combined with chemotherapy can efficiently elicit immunity to suppress metastatic tumor growth. Specifically, we rationally designed a new SPN (PDPSe NPs) as a photothermal agent for PTT with a large mass extinction coefficient in the near-infrared region (e.g., 44.9 L g-1 cm-1 at 808 nm), high photothermal conversion efficiency (62.5%) and excellent biocompatibility. A hypoxia-activated anti-tumor drug, tirapazamine (TPZ), was selected for chemotherapy. Strikingly, the combination therapy not only induced tumor cell death in the primary tumor, but also effectively suppressed the growth of distant tumors (mimicking metastatic tumors) without PTT. Importantly, the combined therapies exhibit synergistic effects on immune remodeling. Immunofluorescence data suggest that the inhibition of metastatic tumor growth is attributed to the immune remodeling triggered by PTT and chemotherapy. This work demonstrates a new paradigm of utilizing PTT together with hypoxia-activated drugs to effectively retard metastatic tumor growth.

11.
Mol Med Rep ; 23(5)2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33760166

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune disease often used as a model in genomics research. The downregulation of microRNA­101­3p (miR­101­3p) participates in the progression of SLE, although the underlying mechanisms remain to be elucidated. The present study aimed to evaluate the specific roles of miR­101­3p in the SLE inflammatory response and its potential mechanisms. Reverse transcription­quantitative (RT­q) PCR was used to profile miR­101­3p expression in the peripheral blood mononuclear cells (PBMCs) from 40 female patients with SLE and 20 female healthy volunteers. The interactions between miR­101­3p and MAPK1 were identified and evaluated using dual­luciferase reporter and RNA pull­down assays. The levels of IL­10 and IFN­Î³ were evaluated by enzyme­linked immunosorbent assay. The expression of NF­κB p65 and phosphorylated IκBα were evaluated using western blotting. miR­101­3p expression was demonstrated to be downregulated in SLE PBMCs. miR­101­3p negatively regulated IL­10 and IFN­Î³ expression in SLE samples and was demonstrated to target MAPK1. Increases in MAPK1 expression eliminated miR­101­3p inhibition of IL­10 and IFN­Î³. MAPK1 activated the NF­κB pathway in SLE PBMCs and this activation was inhibited when miR­101­3p was overexpressed. In addition, treatment with BAY11­7085 (NF­κB activator) was demonstrated to reverse the inhibitory effects of miR­101­3p expression on both IL­10 and IFN­Î³ in SLE PBMCs. BAY11­7082 also markedly reduced MAPK1­induced increases in IL­10 and IFN­Î³ in SLE PBMCs. miR­101­3p overexpression attenuated the inflammatory response in SLE PBMCs by inhibiting the expression of MAPK1 and blocking the NF­κB pathway. The results revealed a novel regulatory mechanism in SLE inflammation and offer a new direction for the development of SLE treatments.

12.
J Biochem Mol Toxicol ; : e22774, 2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33755276

RESUMEN

Osteoporosis is a skeletal condition that is characterized by decreasing bone density and deteriorating bone mass. The plant-based phytoconstituent such as geraniin possesses better therapeutic potentials in biomedical field. In the current experimental study, we planned to scrutinize the therapeutic potential of geraniin against ovariectomy (OVX)-induced osteoporosis in rats and find the possible mechanism. Healthy Sprague Dawley rats were randomized into six groups and subjected to geraniin and alendronate (ALN) treatment for 10 weeks. Body weight, uterus, femur weight, bone biochemical, bone turnover markers, inflammatory cytokine, calcium, phosphorus, vitamin D (Vit D), urine, hormones, and antioxidant level were estimated. Geraniin significantly (p < .001) reduced the level of bone turnover markers including beta-CrossLaps (ß-CTx), ALN, osteocalcin (OC), alkaline phosphatase (ALP), and bone Gla protein (BGP); reduced the biomechanical parameters including maximum load, energy, stiffness, maximum stress, and Young's modulus; reduced the level of calcium (Ca) and phosphorus (P); and increased the level of vitamin D (Vit D) as compared with OVX-induced osteoporosis rats. Geraniin increased the level of bone structure parameters, namely bone mineral density, bone mineral content, tissue mineral density, bone volume fraction, and trabecular number; increased the level of osteoprotegerin (OPG) and OPG/RANKL; and reduced the level of receptor activator of nuclear factor kappa-Β ligand (RANKL). Geraniin significantly (p < .001) increased the level of glutathione (GSH) and reduced the level of malonaldehyde (MDA) in the liver, intestine, and bone of OVX-induced osteoporosis rats. Geraniin significantly (p < .001) decreased the level of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) pro-inflammatory cytokines. We also argue that geraniin could be an excellent candidate to treat and control bone-related disease or disorders.

13.
Food Chem ; 352: 129450, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-33714803

RESUMEN

The unique flavor of and rich physiological activities exhibited by the Chinese JingJiu has made it become an essential part of the blended alcoholic beverage. In this study, the aromatic characteristics of Chinese JingJiu have been identified using sensory analysis, aroma extraction dilution analysis (AEDA), and quantitative analysis techniques. The odor activity values (OAVs) were also used to characterize the compound. A total of 136 aroma compounds were identified through the AEDA and gas chromatography-mass spectrometry (GC-MS) techniques. The flavor dilution (FD) factors were found to be in the range of 2-1024. Seventy aroma-active compounds with FD ≥ 8 were identified. Forty-three aroma-active compounds were identified using the molecular sensory science approach. Furthermore, 13 compounds were confirmed to be the key aroma-active compounds present in the Chinese JingJiu. The work provides a certain guiding effect on the regulation and optimization of the Chinese JingJiu production process.


Asunto(s)
Bebidas Alcohólicas/análisis , Análisis de los Alimentos/métodos , Odorantes/análisis , Cromatografía de Gases y Espectrometría de Masas , Técnicas de Dilución del Indicador , Gusto , Compuestos Orgánicos Volátiles/análisis
14.
J Cell Mol Med ; 2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33759378

RESUMEN

Renal cell carcinoma (RCC) is one of the leading causes of cancer-related death worldwide. Tumour metastasis and heterogeneity lead to poor survival outcomes and drug resistance in patients with metastatic RCC (mRCC). In this study, we aimed to assess intratumoural heterogeneity (ITH) in mRCC cells by performing a combined analysis of bulk data and single-cell RNA-sequencing data, and develop novel biomarkers for prognosis prediction on the basis of the potential molecular mechanisms underlying tumorigenesis. Eligible single-cell cohorts related to mRCC were acquired using the Gene Expression Omnibus (GEO) dataset to identify potential mRCC subpopulations. We then performed gene set variation analysis to understand the differential function in primary RCC and mRCC samples. Subsequently, we applied weighted correlation network analysis to identify coexpressing gene modules that were related to the external trait of metastasis. Protein-protein interactions were used to screen hub subpopulation-difference (sub-dif) markers (ACTG1, IL6, CASP3, ACTB and RAP1B) that might be involved in the regulation of RCC metastasis and progression. Cox regression analysis revealed that ACTG1 was a protective factor (HR < 1), whereas the other four genes (IL6, CASP3, ACTB and RAP1B) were risk factors (HR > 1). Kaplan-Meier survival analysis suggested the potential prognostic value of these sub-dif markers. The expression of sub-dif markers in mRCC was further evaluated in clinical samples by immunohistochemistry (IHC). Additionally, the genetic features of sub-dif marker expression patterns, such as genetic variation profiles, correlations with tumour-infiltrating lymphocytes (TILs), and targeted signalling pathway activities, were assessed in bulk RNA-seq datasets. In conclusion, we established novel subpopulation markers as key prognostic factors affecting EMT-related signalling pathway activation in mRCC, which could facilitate the implementation of a treatment for mRCC patients.

15.
Prenat Diagn ; 2021 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-33782977

RESUMEN

OBJECTIVE: To review the prenatal and postnatal clinical characteristics and pathological subtypes, as well as the surgical outcome for congenital mesoblastic nephroma (CMN) cases. METHOD: A retrospective review was performed in 11 cases with CMN prenatally diagnosed at a single center between 2015 and 2019. The clinical characteristics, surgical outcome, histopathology, and follow-up were retrospectively obtained and reviewed. RESULTS: The median gestational age at which the sonographic diagnosis was made was 35 weeks. Polyhydramnios was found in four (36.4%) cases, and all resulted in a preterm birth. Nine infants had hypertension. Ten cases underwent radical nephrectomy, and one underwent radical nephrectomy and partial adrenalectomy. The pathological results showed that six tumors were classical variants, four mixed variants, and one was a cellular variant. Three cases presented as a stage I, eight as stage II, and no stage III or IV cases were diagnosed. All patients are alive so far. At a median follow-up of 14 months, no local recurrence, or remote metastases were found. CONCLUSION: The prognosis of prenatal CMN cases is excellent after early surgery.

16.
Biochem Biophys Res Commun ; 552: 73-77, 2021 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-33743350

RESUMEN

The biogenesis of outer membrane proteins requires the function of ß-barrel assembly machinery (BAM), whose function is highly conserved while its composition is variable. The Escherichia coli BAM is composed of five subunits, while Thermus thermophilus seems to contain a single BAM protein, named TtOmp85. To search for the primitive form of a functional BAM, we investigated and compared the function of TtOmp85 and E. coli BAM by use of a reconstitution assay that examines the integration of OmpA and BamA from E. coli and TtoA from T. thermophilus, as well as the translocation of the E. coli Ag43. Our results show that a single TtOmp85 protein can substitute for the collective function of the five subunits constituting E. coli BAM.

17.
Math Biosci Eng ; 18(2): 1708-1721, 2021 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-33757206

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide. However, the mechanisms underlying the acquisition of the metastatic potential in PDAC has not been well understood. In this study, we identified a total of 154 genes upregulated in primary tissues of PDAC with liver metastasis using the Genome Cancer Atlas (TCGA) and GSE151580 cohorts. The epithelial-mesenchymal transition and glycolysis were enriched by the liver metastasis-related genes, indicating that the liver metastasis-related genes might be functionally relevant to liver metastasis in PDAC. Moreover, we also found that the liver metastasis-related genes were primarily regulated at epigenetic level. Particularly, SFN, a cell cycle checkpoint protein, and KRT19, a marker gene for ductal cells, were predicted to be regulated by multiple methylation sites at the promoter. Clinically, we for the first time defined a liver metastasis score (LMS), which was derived from liver metastasis-related genes, and closely associated with clinical characteristics such as disease type and tumor grade, in PDAC. Furthermore, we also divided the samples into high and low LMS groups using three cohorts with long-term follow-up (TCGA, GSE71729, and E-MTAB-6134), which exhibited significantly different prognostic outcomes across three PDAC cohorts, suggesting that the LMS might be a good indicator for risk stratification in PDAC. Furthermore, we also found that the liver metastasis-related genes were primarily expressed in malignant ductal cells by integrative analysis of the bulk and single-cell gene expression data. Moreover, the malignant ductal cells and M0 macrophages were highly correlated with LMS, indicating that the two cell types might function as tumor-promoting cells in PDAC. In summary, the systematic analysis for the first time defined an LMS score to evaluate the risk of liver metastasis in PDAC and revealed that malignant ductal cells might promote PDAC liver metastasis, which greatly improves our understanding of the liver metastasis-related genes, their underlying mechanisms, and association with prognosis in PDAC.

18.
Anal Chem ; 93(10): 4479-4487, 2021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-33646748

RESUMEN

Single-cell capillary electrophoresis mass spectrometry (CE-MS) is a promising platform to analyze cellular contents and probe cell heterogeneity. However, current single-cell CE-MS methods often rely on offline microsampling processes and may demonstrate low sampling precision and accuracy. We have recently developed an electrospray-assisted device, spray-capillary, for low-volume sample extraction. With the spray-capillary, low-volume samples (pL-nL) are drawn into the sampling end of the device, which can be used directly for CE separation and online MS detection. Here, we redesigned the spray-capillary by utilizing a capillary with a <15 µm tapered tip so that it can be directly inserted into single cells for sample collection and on-capillary CE-MS analysis. We evaluated the performance of the modified spray-capillary by performing single-cell microsampling on single onion cells with varying sample injection times and direct MS analysis or online CE-MS analysis. We have demonstrated, for the first time, online sample collection and CE-MS for the analysis of single cells. This application of the modified spray-capillary device facilitates the characterization and relative quantification of hundreds of metabolites in single cells.

19.
J Org Chem ; 86(7): 5401-5411, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33720721

RESUMEN

Herein, we describe a new approach for the activation of esters via a radical-mediated process enabled by a copper/Selectfluor system. A variety of para-methoxybenzyl esters derived from bulky carboxylic acids and amino acids can be easily converted into the corresponding acyl fluorides, directly used in the one-pot synthesis of amides and peptides. As a proof of concept, this method was applied to the iterative formation of sterically hindered amide bonds.

20.
Toxicol In Vitro ; 73: 105139, 2021 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-33705895

RESUMEN

(3α)-3-(tiglinoyloxy)-ent-kaur-16-en-19-oic acid (WT-26) is an ent-kaurane dieterpenoid extracted from Wedelia trilobata L., a widely cultivated ornamental plant with several scientific reports supporting its anti-inflammatory activity. WT-26 has better anti-inflammatory activity than its analog Kaurenoic acid (ent-kaur-16-en-19-oic acid). Nevertheless, the participation of WT-26 in the main signaling pathway associated with inflammation is lack of study. We aimed to study the anti-inflammatory effect of WT-26 and related signaling cascade in lipopolysaccharide (LPS)-stimulated macrophages. Here, we showed that WT-26 suppressed nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS-stimulated macrophages by downregulating the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in mRNA and protein level. WT-26 down-regulated tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and IL-1ß production as well. Moreover, WT-26 inhibited the activation of nuclear factor-κB (NF-κB) p65 and its upstream signaling. WT-26 also reduced phosphorylation of mitogen-activated protein kinases (MAPKs) and mTOR. Besides, WT-26 decreased the overproduction of reactive oxygen species (ROS) and protected the mitochondrial integrity in stimulated macrophages. Our study also demonstrated that the autophagy induced by LPS was attenuated by WT-26. Collectively, our data indicated that WT-26 has the potential to be developed as a novel therapeutic agent for inflammatory-related diseases.

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