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1.
Talanta ; 221: 121621, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076149

RESUMO

The profiling of bacterial metabolism is of great significance in practical applications. Therefore, the development of ultrasensitive and highly selective probe for bacterial metabolism detection and imaging is extremely desirable. Herein, a novel dual-emission pH-response bacterial metabolism detection and imaging probe is successfully developed. This probe consists of large-sized and easily separated SiO2 microspheres, copper nanoclusters (Cu NCs) with red emission, and carbon dots (CDs) with blue emission through in-situ self-assembly. In this system, the fluorescence of Cu NCs is sensitive to pH change due to their obvious aggregation-induced emission enhancement (AIEE) property, while the blue fluorescence of CDs remained almost stable. Therefore, red fluorescence and blue fluorescence are compounded with different fluorescence intensity at different pH values, and their fluorescence ratio is also different. By observation of composite fluorescence color, the visual colorimetric pH detection can be realized with the change of pH value of 0.2 units. Utilizing this system, we are able to detect bacterial metabolism with high signal-to-noise ratio, and it can also be used for bacterial metabolic imaging. Therefore, the pH-responsive Cu NCs-based dual-emission ratiometric fluorescent probe we constructed can provide new ideas for bacterial detection, antimicrobial sterilization, and biological imaging.

2.
Clin Lung Cancer ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33187913

RESUMO

BACKGROUND: Lobectomy with systematic lymph node dissection (SND) remains the standard procedure for resectable non-small-cell lung cancer (NSCLC), whereas lobe-specific lymph node dissection (LSND) was reported to have more advantages in perioperative recovery and complication reduction in treating early-stage diseases. Survival outcomes after LSND remains controversial compared with SND. PATIENTS AND METHODS: From 2014 to 2017, data of 546 patients with clinical stage IA solid-dominant NSCLC and who underwent curative lobectomies with LSND (n = 100) or SND (n = 446) at our institution were collected. Propensity score matching was conducted to eliminate the biases. Five-year disease-free survival and overall survival were compared between the groups. Perioperative parameters and postoperative complications were also analyzed. RESULTS: Lobectomies with LSND or SND were performed in 100 patients and 446 patients, respectively. After matching, there were 100 patients in each group and no significant differences in 5-year overall survival (P = .473) and disease-free survival (P = .789) were found between the groups. Recurrence patterns were also similar (P = .733). Perioperative parameters were similar, whereas the incidence of postoperative complications in the SND group was found to be significantly higher than that in the LSND group (P = .003). CONCLUSIONS: Our study demonstrated that LSND has similar efficiency to SND in terms of survival, recurrence, lymph node dissection, and perioperative recovery of patients with clinical stage IA solid-dominant NSCLC, as well as significant advantages in reducing postoperative complications. Therefore, curative lobectomies with LSND may be more suitable and practical for clinical stage IA solid-dominant patients with NSCLC.

3.
Nat Commun ; 11(1): 5767, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188189

RESUMO

Enhancing the intrinsic activity and space time yield of Cu based heterogeneous methanol synthesis catalysts through CO2 hydrogenation is one of the major topics in CO2 conversion into value-added liquid fuels and chemicals. Here we report inverse ZrO2/Cu catalysts with a tunable Zr/Cu ratio have been prepared via an oxalate co-precipitation method, showing excellent performance for CO2 hydrogenation to methanol. Under optimal condition, the catalyst composed by 10% of ZrO2 supported over 90% of Cu exhibits the highest mass-specific methanol formation rate of 524 gMeOHkgcat-1h-1 at 220 °C, 3.3 times higher than the activity of traditional Cu/ZrO2 catalysts (159 gMeOHkgcat-1h-1). In situ XRD-PDF, XAFS and AP-XPS structural studies reveal that the inverse ZrO2/Cu catalysts are composed of islands of partially reduced 1-2 nm amorphous ZrO2 supported over metallic Cu particles. The ZrO2 islands are highly active for the CO2 activation. Meanwhile, an intermediate of formate adsorbed on the Cu at 1350 cm-1 is discovered by the in situ DRIFTS. This formate intermediate exhibits fast hydrogenation conversion to methoxy. The activation of CO2 and hydrogenation of all the surface oxygenate intermediates are significantly accelerated over the inverse ZrO2/Cu configuration, accounting for the excellent methanol formation activity observed.

4.
Clin Cancer Res ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148670

RESUMO

PURPOSE: The BCL2 inhibitor, venetoclax (VEN), has transformed clinical care in acute myeloid leukemia (AML). However, subsets of patients do not respond or eventually acquire resistance. VEN-based regimens can potentially lead to marrow suppression. Bromodomain and extra-terminal inhibitors (BETi) are potential treatments for AML, as regulators of critical AML oncogenes. We tested the efficacy of novel BET inhibitor INCB054329, and its synergy with VEN to reduce AML without induction of hematopoietic toxicity. EXPERIMENTAL DESIGN: INCB054329 efficacy was assessed by changes in cell cycle and apoptosis in treated AML cell lines. In vivo efficacy was assessed by tumor reduction in MV-4-11 cell line derived xenografts. Precision run-on and sequencing (PRO-Seq) evaluated effects of INCB054329. Synergy between low dose BETi and VEN was assessed in cell lines and patient samples while efficacy and toxicity was assessed in patient derived xenograft (PDX) models. RESULTS: INCB054329 induced dose-dependent apoptosis and quiescence in AML cell lines. PRO-Seq analysis evaluated the effects of INCB054329 on transcription and confirmed reduced transcriptional elongation of key oncogenes, MYC and BCL2, and genes involved in the cell cycle and metabolism. Combinations of BETi and VEN led to reduced cell viability in cell lines and patient samples. Low dose combinations of INCB054329 and VEN in cell line and PDX models reduced AML burden, regardless of the sensitivity to monotherapy without development of toxicity. CONCLUSIONS: Our findings suggest low dose combinations of VEN and BETi may be more efficacious for AML patients than either monotherapy, potentially providing a longer, more tolerable dosing regimen.

6.
Food Chem ; : 128509, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33199116

RESUMO

Dajiang, or naturally fermented soybean paste, has a unique flavor that is influenced by the resident microflora. However, the association between flavor and the core microbiota is unclear. Recent advances in RNA sequencing have identified genes that are actively expressed in complex microbial communities. To this end, we analyzed the time-dependent changes in the microbiota and the metabolite profiles of Dajiang using metatranscriptome sequencing, HS-SPME-GC-MS and amino acid analysis identified 10 volatile compounds that contribute to the development of soybean paste flavor. Further analysis of the correlation between the active microorganisms and the physicochemical characteristics and flavor substances in soybean paste indicated that Lactobacillus and Tetragenococcus were the core genera affecting chromaticity and flavor. These microorganisms produce enzymes that catalyze a series of metabolic pathways that generate flavor substances. Our findings provide new insights into the role of the microbiota in the development of flavor in fermented foods.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33135308

RESUMO

Spatial positioning and proximity of DNA epigenetic marks are fundamental to a deeper understanding of gene regulation and chromatin architecture. However, it remains poorly explored and technically challenging. Here we report pairwise proximity-differentiated visualization of single-cell 5-formylcytosine (5fC) and 5-hydroxymethylcytosine (5hmC). These two marks on chromatin in fixed cells are successively labeled and crosslinked with their DNA primer probes via click chemistry. Based on a pairwise proximity-differentiated mechanism, proximal 5fC/5hmC sites firstly and residual 5fC or 5hmC sites then are encoded with respective circularized barcodes. These barcodes are simultaneously amplified for multiplexed single-molecule imaging. Thus we demonstrate differentiated visualization of 5fC or 5hmC spatial positioning and their pairwise proximity in single cells. Such multi-level subcellular information may provide insights into regulation functions and mechanisms of chromatin modifications, and the spatial proximity can expose the potential crosstalk or interaction between their reader proteins.

8.
Cancer Lett ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33129955

RESUMO

Colorectal cancer (CRC) is one of the most common malignancies worldwide and is associated with poor prognosis and high mortality. Despite advances in treatment with chemotherapy, CRC remains a major cause of drug resistance-related cancer deaths. One of the main reasons for such resistance is dysregulation of Mcl-1 expression. In this study, we identified LZT-106 as a novel kinase inhibitor that was able to bind to CDK9 with potent inhibitory ability, and indirectly regulate the expression of Mcl-1. However, different regulatory profiles were observed between LZT-106 and the well-studied CDK9 inhibitor flavopiridol with regards to Mcl-1 inhibition. Via Western blotting, real-time PCR and immunoprecipitation, we confirmed that LZT-106 was also able to target GSK-3ß signaling and facilitate the degradation of Mcl-1. And LZT-106 was shown to synergize with ABT-199 to induce apoptosis even in the RKO cell line that overexpressed Mcl-1. Finally, LZT-106 significantly inhibited tumor growth in a xenograft mouse model with minimal toxicity. Overall, our findings suggest that LZT-106 is a promising candidate drug for the treatment of patients with CRC.

9.
Trop Med Int Health ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33159827

RESUMO

OBJECTIVES: To evaluate the prevalence of Helicobacter pylori infection and risk factors and to serotype the strains in Wuwei, located in northwestern China, which has a high incidence of gastric cancer. METHODS: H. pylori infection was analyzed in 21291 adults by 14 C-urea breath test, and H. pylori antibody were detected in 9183 serum samples by latex immunoturbidimetric method. The correlation of H. pylori infection with demographic-economic, lifestyle factors, and medical history among the participants was determined by questionnaire. The antibodies against H. pylori urease, VacA, and CagA in serum were determined by dot immunobinding assay. RESULTS: The infection rate of H. pylori was 53.0%, and 90.1% of strains were type I strains. The H. pylori infection rate was higher among farmers (OR=1.34, 95% CI: 1.19-1.50) and individuals who had a junior high school or higher education level (OR=1.10, 95% CI: 1.06-1.15), and was lower in older individuals (OR=0.86, 95% CI: 0.83-0.90), individuals with high income (OR=0.93, 95% CI: 0.90-0.95), individuals with a habit of eating quickly (OR=0.93, 95% CI: 0.87-0.99), and individuals who consumed more fruit and vegetabless (OR=0.90, 95% CI: 0.85-0.95). Individuals with history of cholecystitis/cholecystolithiasis, hypertension, and asthma were negatively correlated with H. pylori infection (P<0.05). CONCLUSION: The prevalence of H. pylori infection is high in Wuwei. The major prevalent strain is type I strain. Age, education, occupation, household income, consumption of fruit and vegetabless, and habit of eating quickly are independent risk factors for H. pylori infection, which is also associated with individuals with a history of extra-gastric diseases.

10.
Fertil Steril ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33153705

RESUMO

OBJECTIVE: To explore the relationship between KLOTHO expression and diminished ovarian reserve (DOR). DESIGN: A case-control study. SETTING: Reproductive medicine center. PATIENT(S): A total of 157 patients with DOR and 159 control women were recruited from the Centre of Reproductive Medicine, Peking University Third Hospital. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The granulosa cells were isolated from follicular fluid after oocyte retrieval, and the KLOTHO level of granulosa cell was measured using a modified quantitative polymerase chain reaction technique. The serum KLOTHO level was measured by solid-phase sandwich enzyme-linked immunosorbent assay. RESULT(S): In both granulosa cells and serum derived from women with DOR, KLOTHO expressions were significantly lower compared with normal ovarian reserve controls. Moreover, KLOTHO expression diminished with advancing age. CONCLUSION(S): Diminished KLOTHO expression was associated with DOR. Further longitudinal studies in a similar population accompanying disease progression and mechanism exploration are needed to substantiate the rules of KLOTHO in reproductive aging.

11.
Nano Lett ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174417

RESUMO

Weyl semimetals have drawn considerable attention for their exotic topological properties in many research fields. When in combination with s-wave superconductors, the supercurrent can be carried by their topological surface channels, forming junctions mimicking the behavior of Majorana bound states. Here, we present a transmon-like superconducting quantum intereference device (SQUID) consisting of lateral junctions made of Weyl semimetal Td-MoTe2 and superconducting leads of niobium nitride (NbN). The SQUID is coupled to a readout cavity made of molybdenum rhenium (MoRe), whose response at high power reveals the existence of the constituting Josephson junctions (JJs). The loop geometry of the circuit allows the resonant frequency of the readout cavity to be tuned by the magnetic flux. We demonstrate a JJ made of MoTe2 and a flux-tunable transmon-like circuit based on Weyl semimetals. Our study provides a platform to utilize topological materials in SQUID-based quantum circuits for potential applications in quantum information processing.

13.
BMC Plant Biol ; 20(1): 516, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183241

RESUMO

BACKGROUND: Crown gall disease, caused by the pathogenic bacterium Agrobacterium tumefaciens, is responsible for extensive economic losses in orchards. Cherry rootstock 'CDR-1' (Prunus mahaleb) shows high resistance but the mechanism remains unclear. Here, we examined the morphology of pathogen-infected root neck surface, determined the activity of 10 defense-related enzymes and the content of salicylic acid (SA) and jasmonic acid (JA), and also applied transcriptome analysis, transient expression and transgenic verification to explore the crown gall resistance genes in 'CDR-1' plants. RESULTS: In our study, peroxidase increased in the first 10 days, while phenylalanine ammonialyase and lipoxygenase increased in the first 15 days post-infection. Four key enzymes in the AsA-GSH cycle also responded, to a certain extent; although JA content increased significantly after the treatment, the SA content did not. In a follow-up transcriptome analysis, the differentially expressed genes Pm4CL2, PmCYP450, PmHCT1, PmHCT2, and PmCAD were up-regulated. Based on the above results, we focused on the lignin biosynthetic pathway, and further measured lignin content, and found it increased significantly. The Pm4CL2 gene was used to conduct transient expression and transgenic experiments to verify its function in crown gall disease resistance. It showed the relative expression of the treatment group was almost 14-fold that of the control group at 12 h post-treatment. After the infection treatment, clear signs of resistance were found in the transgenic lines; this indicated that under the higher expression level and earlier activation of Pm4CL2, plant resistance was enhanced. CONCLUSIONS: The crown gall resistance of 'CDR-1' is likely related to the lignin biosynthetic pathway, in which Pm4CL2 functions crucially during the plant defense response to the pathogen A. tumefaciens. The results thus offer novel insights into the defense responses and resistance mechanism of cherry rootstock 'CDR-1' against crown gall disease.

14.
Spectrochim Acta A Mol Biomol Spectrosc ; 247: 119108, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33161263

RESUMO

AIM: Metabolites present in urine reflect the current phenotype of the cancer state. Surface-enhanced Raman spectroscopy (SERS) can be used in urine supernatant or sediment to largely reflect the metabolic status of the body. MATERIALS & METHODS: SERS was performed to detect bladder cancer (BCa) and predict tumour grade from urine supernatant, which contains various system metabolites, as well as from urine sediment, which contains exfoliated tumour cells. RESULTS & DISCUSSION: Upon combining the urinary supernatant and sediment results, the total diagnostic sensitivity and specificity of SERS were 100% and 98.85%, respectively, for high-grade tumours and 97.53% and 90.80%, respectively, for low-grade tumours. CONCLUSION: The present results suggest high potential for SERS to detect BCa from urine, especially when combining both urinary supernatant and sediment results.

15.
EBioMedicine ; 62: 103108, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33186807

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, with unmet need for the pharmacological therapy. The functions of ATXN7L3 in HCC progression are not known. METHODS: RNA sequence, quantitative real-time PCR, and western blot were performed to detect gene expression. Chromatin immunoprecipitation was performed to detect possible mechanisms. Immunohistochemical stain was performed to examine the protein expression. Colony formation, cell growth curve and xenograft tumor experiments were performed to examine cell growth in vitro and in vivo. FINDINGS: ATXN7L3 functions as a coactivator for ERα-mediated transactivation in HCC cells, thereby contributing to enhanced SMAD7 transcription. ATXN7L3 is recruited to the promoter regions of SMAD7 gene, thereby regulating histone H2B ubiquitination level, to enhance the transcription of SMAD7. A series of genes regulated by ATXN7L3 were identified. Moreover, ATXN7L3 participates in suppression of tumor growth. In addition, ATXN7L3 is lower expressed in HCC samples, and the lower expression of ATXN7L3 positively correlates with poor clinical outcome in patients with HCC. INTERPRETATION: This study demonstrated that ATXN7L3 is a novel regulator of SMAD7 transcription, subsequently participating in inhibition of tumor growth in HCC, which provides an insight to support a previously unknown role of ATXN7L3 in HCC progression. FUND: This work was funded by 973 Program Grant from the Ministry of Science and Technology of China (2013CB945201), National Natural Science Foundation of China (31871286, 81872015, 31701102, 81702800, 81902889), Foundation for Special Professor of Liaoning Province, Natural Science Foundation of Liaoning Province (No.20180530072); China Postdoctoral Science Foundation (2019M651164).

16.
Macromol Rapid Commun ; : e2000441, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33089609

RESUMO

Diabetic foot ulcers (DFU) remain a very considerable health care burden, and their treatment is difficult. Hydrogel-based wound dressings are appealing to provide an optimal environment for wound repair. However, the currently available hydrogel dressings still need surgical or mechanical debridement from the wound, causing reinjury of the newly formed tissues, wound infection, delayed healing time, and personal suffering. Additionally, to meet people's increasing demand, hydrogel wound dressings with improved performance and multifunctionality are urgently required. Here, a new multifunctional supramolecular hydrogel for on-demand dissolvable diabetic foot wound dressings is designed and constructed. Based on multihydrogen bonds between hydrophilic polymers, the resultant supramolecular hydrogels present controlled and excellent properties, such as good transparency, antibacterial ability, conductive, and self-healing properties. Thus, the supramolecular hydrogels improve the new tissue formation and provide a significant therapeutic effect on DFU by inducing angiogenesis, enhancing collagen deposition, preventing bacterial infection, and controlling wound infection. Remarkably, the resultant hydrogels also exhibit stimuli-responsive ability, which renders its capability to be dissolved on-demand, allowing for a facile DFU dressing removal. This multifunctional supramolecular hydrogel may provide a novel concept in the design of on-demand dissolvable wound dressings.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33006928

RESUMO

Recently, super-harmonic ultrasound imaging technology has caused much attention due to its capability of distinguishing microvessles from the tissues surrounding them. However, the fabrication of a dual-frequency confocal transducer is still a challenge. In this work, 270µm PMN-PT single crystal 1-3 composite and 28µm PVDF thick film, acting as transmission layer and receiving layer, respectively, are integrated in a novel co-focusing structure. To realize delicate wave propagation control, microwave transmission line theory is introduced to design such structure. Two acoustic filter layers, 13µm copper layer and 39µm Epoxy 301 layer, are indispensable and should be added between two piezoelectric layers. Therefore, an acoustic issue can be overcome via an electrical method and the successful achievement of a dual-frequency (5MHz/30MHz) ultrasound transducer with confocal distance of 8mm can be realized. The super harmonic ultrasound imaging experiment is conducted using this kind of device. 3D image of 110µm diameter phantom tube injected with microbubbles can be obtained. These promising results demonstrate that this novel dual-frequency (5MHz/30MHz) confocal ultrasound transducer is potentially usable for microvascular medical imaging application in the future.

19.
Nucleic Acids Res ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010163

RESUMO

RNA endowed with both protein-coding and noncoding functions is referred to as 'dual-function RNA', 'binary functional RNA (bifunctional RNA)' or 'cncRNA (coding and noncoding RNA)'. Recently, an increasing number of cncRNAs have been identified, including both translated ncRNAs (ncRNAs with coding functions) and untranslated mRNAs (mRNAs with noncoding functions). However, an appropriate database for storing and organizing cncRNAs is still lacking. Here, we developed cncRNAdb, a manually curated database of experimentally supported cncRNAs, which aims to provide a resource for efficient manipulation, browsing and analysis of cncRNAs. The current version of cncRNAdb documents about 2600 manually curated entries of cncRNA functions with experimental evidence, involving more than 2,000 RNAs (including over 1300 translated ncRNAs and over 600 untranslated mRNAs) across over 20 species. In summary, we believe that cncRNAdb will help elucidate the functions and mechanisms of cncRNAs and develop new prediction methods. The database is available at http://www.rna-society.org/cncrnadb/.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33013697

RESUMO

As important metabolic substrates, branched-chain amino acids (BCAAs) and fatty acids (FAs) participate in many significant physiological processes, such as mitochondrial biogenesis, energy metabolism, and inflammation, along with intermediate metabolites generated in their catabolism. The increased levels of BCAAs and fatty acids can lead to mitochondrial dysfunction by altering mitochondrial biogenesis and adenosine triphosphate (ATP) production and interfering with glycolysis, fatty acid oxidation, the tricarboxylic acid cycle (TCA) cycle, and oxidative phosphorylation. BCAAs can directly activate the mammalian target of rapamycin (mTOR) signaling pathway to induce insulin resistance, or function together with fatty acids. In addition, elevated levels of BCAAs and fatty acids can activate the canonical nuclear factor-κB (NF-κB) signaling pathway and inflammasome and regulate mitochondrial dysfunction and metabolic disorders through upregulated inflammatory signals. This review provides a comprehensive summary of the mechanisms through which BCAAs and fatty acids modulate energy metabolism, insulin sensitivity, and inflammation synergistically.

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