Our study aimed to investigate whether CAF (cancer-associated fibroblasts) were involved in long noncoding RNAs (lncRNA)-regulated radioresponse in esophageal squamous cell carcinoma (ESCC).
By use ...of lncRNAs PCR array, 38 lncRNAs were screened in esophageal cancer cells and in normal esophageal epithelial cells Het-1A. LncRNA DNM3OS was detected in tumor tissues of patients with ESCC and in matched normal esophageal epithelial tissues by qRT-PCR analysis and
hybridization assay. The association of DNM3OS and tumor radioresistance was investigated
and
. The influences of DNM3OS on DNA damage response (DDR) was investigated by Western blotting, immunofluorescence imaging, and comet assay. The mechanisms by which CAFs promoted DNM3OS expression was investigated by kinase inhibitors' screening, luciferase assay, and chromatin immunoprecipitation.
Among the 38 lncRNAs tested, DNM3OS was found to have a much higher expression level in esophageal cancer cells than in Het-1A. In tumor tissues of 16 patients with ESCC, the expression level of DNM3OS showed an average increase of 6.3429-fold compared with that in matched normal tissues. DNM3OS conferred significant radioresistance
and
by regulating DDR. CAFs promoted the expression of DNM3OS with a 39.2554-fold and 38.3163-fold increase in KYSE-30 and KYSE-140, respectively. CAFs promoted the expression of DNM3OS in a PDGFβ/PDGFRβ/FOXO1 signaling pathway-dependent manner. FOXO1, a transcription factor downstream of PDGFβ/PDGFRβ signaling pathway, initiated the transcription of DNM3OS by binding to DNM3OS promoter.
Our study highlighted CAF-promoted DNM3OS as an attractive target to reverse tumor radioresistance in ESCC.
A novel glucose biosensor based on biomediated gold nanoparticles (AuNPs)–glucose oxidase (GOD)–carbon nanotubes–polyvinyl alcohol biocomposite film was fabricated for the first time. Direct ...electrochemistry of GOD in the film was obtained, proved by one pair of well-defined, quasi-reversible redox peaks with the formal potential of −0.504
V in pH 7.0 phosphate buffer solution at the scan rate of 100
mV
s
−1. And the electron transfer rate constant of the direct electron communication between GOD and the electrode was calculated to be 2.2
s
−1. The biomediated AuNPs play an important role in facilitating the electron exchange between the electroactive center of GOD and the electrode. Furthermore, the fabricated electrode displayed a linear amperometric response in the glucose concentration range from 0.5 to 8.0
mM with a relatively high sensitivity of 16.6
μA
mM
−1
cm
−2. Therefore, the AuNPs based biosensor described here provides a different mode to design electrochemical devices.
Five-year survival rate of esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is <20%. Our study aimed to investigate whether cancer-associated fibroblasts (CAFs), one major ...component of tumor microenvironment, were involved in tumor radioresistance in ESCC. By use of human chemokine/cytokine array, human chemokine CXCL1 was found to be highly expressed in CAFs compared with that in matched normal fibroblasts. Inhibition of CXCL1 expression in CAFs significantly reversed CAF-conferred radioresistance in vitro and in vivo. CAF-secreted CXCL1 inhibited the expression of reactive oxygen species (ROS)-scavenging enzyme superoxide dismutase 1, leading to increased ROS accumulation following radiation, by which DNA damage repair was enhanced and the radioresistance was mediated. CAF-secreted CXCL1 mediated the radioresistance also by activation of Mek/Erk pathway. The cross talk of CAFs and ESCC cells induced CXCL1 expression in an autocrine/paracrine signaling loop, which further enhanced tumor radioresistance. Together, our study highlighted CAF-secreted CXCL1 as an attractive target to reverse tumor radioresistance and can be used as an independent prognostic factor of ESCC patients treated with chemoradiotherapy.
It is very important to analyze the performance of the model rainstorm forecast for understanding the intensity and position deviation of the model precipitation and improving the forecast ability. ...This paper uses classical scoring and the MODE (Method for Object-Based Diagnostic Evaluation) method to evaluate the forecast performance of different products. The forecast and observation data used in the article mainly include CMA (China Meteorological Administration) multi-source merged precipitation analysis, the precipitation forecast of ECMWF (European Centre for Medium-Range Weather Forecasts), CMA-Meso (Mesoscale model forecast of CMA) and SCMOC (National Meteorological Center grid precipitation forecast guidance product) data. At the same time, the possible correction method of heavy rainfall area is explored by using the high and low-level circulation configuration of the ECMWF model. The main conclusions are as follows: ① MODE spatial verification shows that the number, intensity, area and location of ECMWF rainstorm precipitation objects match the observed precipitation best, which is obviously better than SCMOC and CMA-Meso precipitation forecasts. There are significantly fewer SCMOC rainstorm precipitation objects, and the area of each single precipitation object is significantly larger, which often fails to report the small area objects of convective precipitation. ② The reason for the high TS score of SCMOC is that it reduces the number of small area rainstorm objects and avoids the “double punishment” phenomenon caused by position forecast error, which leads to the failure of SCMOC in local rainstorm forecasts. ③ Analyzing the relationship between the circulation situation of the ECMWF model and the location of rainstorm forecasts by the model, it is found that the location of the rainstorm area is consistent with the upper circulation system, especially with the strong rising area of the vertical velocity of 700 hPa and the high value area of the specific humidity of 850 hPa. When the rainstorm area coincides with the upper air system but is not consistent with the ground convergence area and the high value area of velocity potential, the rainstorm location often has a large deviation. The location of the surface convergence area can be used as a reference to improve the performance of the rainstorm forecast.
Both Gram-positive and Gram-negative bacteria can secrete extracellular vesicles (EVs), which contain numerous active substances. EVs mediate bacterial interactions with their hosts or other ...microbes. Bacterial EVs play a double-edged role in infections through various mechanisms, including the delivery of virulence factors, modulating immune responses, mediating antibiotic resistance, and inhibiting competitive microbes. The spread of antibiotic resistance continues to represent a difficult clinical challenge. Therefore, the investigation of novel therapeutics is a valuable research endeavor for targeting antibiotic-resistant bacterial infections. As a pathogenic substance of bacteria, bacterial EVs have gained increased attention. Thus, EV inhibitors are expected to function as novel antimicrobial agents. The inhibition of EV production, EV activity, and EV-stimulated inflammation are considered potential pathways. This review primarily introduces compounds that effectively inhibit bacterial EVs and evaluates the prospects of their application.
Paleokarst systems are major carbonate reservoirs that can form significant and very large oilfields. The Ordovician carbonate reservoirs of the Tahe Oilfield represent a special type of hydrocarbon ...reservoir consisting primarily of paleokarst caves and fractures. Detailed characterization of paleokarst reservoirs in the Tahe area is challenging because of their heterogeneous distribution and, in particular, because these reservoirs are at depths exceeding 5500 m.
This paper describes a detailed approach for integrating data from cores, imaging and conventional well logs, and high-quality seismic datasets to delineate the complex paleokarst systems in the Tahe Oilfield, particularly the paleocaves in the run-off zone. Based on the hydrologic genetic relationships between the karst and paleocaves observed in outcrops, we divided the paleocaves in the run-off zone into chambers, main channels, and branch channels. The chambers, which are generally taller than 15 m, are generally collapsed. The main channels, mostly 5–15 m tall, were the main passages for underground water flow and display good connectivity. The branch channels, typically less than 5 m tall, are relatively dispersed and still have a considerable volume.
This method was applied to the area around Well T615, and two layers of paleocaves in the run-off zone were interpreted. Seismic mapping and three-dimensional modeling of the paleocaves were performed, and the lengths, widths, areas and volumes of these three types of paleocaves were statistically analyzed. Although most of the chambers have been penetrated by existing wells, the areas where the main channels and a dense network of branch channels developed are favorable targets for future drilling in the Tahe Oilfield. Our method of detecting and analyzing the paleokarst reservoir structure is applicable to similar paleokarst reservoirs.
•Cave, fracture and protoconduit recognition equations are built using conventional logging.•After tying caves to impedance dataset using synthetic seismograms, the 3D structure of paleokarst system is detected.•The paleokarst area's genetic structure around Well T615 is analyzed quantitatively.•The 3D structure of the paleokarst reservoir in the run-off zone is delineated.
The clinical utility of CPT-11 is restricted by factors such as the low conversion rate to SN38, high interpatient variability and dose-limiting toxicity. SN38 is significantly more potent than ...CPT-11, but parental administration of SN38 is impossible due to its poor solubility and low stability. This study aimed to develop a novel SN38 prodrug (OEG-SN38) that may overcome the various drawbacks of CPT-11 and SN38 and be useful for clinics. We attached a very low molecular weight oligo (ethylene glycol) (OEG) chain selected as the hydrophilic part to hydrophobic SN38 via ester bond at the C20 position to form the amphiphilic OEG-SN38. In aqueous solution OEG-SN38 formed micelles with diameter of 28.74±2.51nm, and showed greatly improved drug loading, solubility and stability, with drug loading as high as 36% (wt.%). Moreover, these micelles were stable in PBS with only 4.71% SN38 released from the prodrug even after 35h incubation, but released SN38 promptly by esterase hydrolysis. Most importantly, OEG-SN38 exhibited potent antitumor activity against a panel of human tumor cell lines, as well as favorable antitumor activity and high safety in human xenograft models. These encouraging data merit further preclinical and clinical investigation on this novel SN38 delivery system.
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n-Butanol has several favourable properties as an advanced fuel or a platform chemical. Bio-based production of n-butanol is becoming increasingly important for sustainable chemical industry. ...Synthesis of n-butanol can be achieved via more than one metabolic pathway. Here we report the metabolic engineering of Saccharomyces cerevisiae to produce n-butanol through a synergistic pathway: the endogenous threonine pathway and the introduced citramalate pathway. Firstly, we characterized and optimized the endogenous threonine pathway; then, a citramalate synthase (CimA) mediated pathway was introduced to construct the synergistic pathway; next, the synergistic pathway was optimized by additional overexpression of relevant genes identified previously; meanwhile, the n-butanol production was also improved by overexpression of keto-acid decarboxylases (KDC) and alcohol dehydrogenase (ADH). After combining these strategies with co-expression of LEU1 (two copies), LEU4, LEU2 (two copies), LEU5, CimA, NFS1, ADH7 and ARO10(*), we achieved an n-butanol production of 835 mg/L in the final engineered strain, which is almost 7-fold increase compared to the initial strain. Furthermore, the production showed a 3-fold of the highest titer ever reported in yeast. Therefore, the engineered yeast strain represents a promising alternative platform for n-butanol production.
Lipases and esterases are important catalysts with wide varieties of industrial applications. Although many methods have been established for detecting their activities, a simple and sensitive ...approach for picogram detection of lipolytic enzyme quantity is still highly desirable. Here we report a lipase detection assay which is 1000-fold more sensitive than previously reported methods. Our assay enables the detection of as low as 5 pg and 180 pg of lipolytic activity by direct spotting and zymography, respectively. Furthermore, we demonstrated that the detection sensitivity was adjustable by varying the buffering capacity, which allows for screening of both high and low abundance lipolytic enzymes. Coupled with liquid chromatography-mass spectrometry, our method provides a useful tool for sensitive detection and identification of lipolytic enzymes.
The BiFeO
3
/g-C
3
N
4
heterostructure, which is fabricated via a simple mixing-calcining method, benefits the significant enhancement of the pyrocatalytic performance. With the growth of g-C
3
N
4
...content in the heterostructure pyrocatalysts from 0 to 25%, the decomposition ratio of Rhodamine B (RhB) dye after 18 cold-hot temperature fluctuation (25–65 °C) cycles increases at first and then decreases, reaching a maximum value of ∼94.2% at 10% while that of the pure BiFeO
3
is ∼67.7%. The enhanced dye decomposition may be due to the generation of the internal electric field which strengthens the separation of the positive and negative carriers and further accelerates their migrations. The intermediate products in the pyrocatalytic reaction also have been detected and confirmed, which proves the key role of the pyroelectric effect in realizing the dye decomposition using BiFeO
3
/g-C
3
N
4
heterostructure catalyst. The pyroelectric BiFeO
3
/g-C
3
N
4
heterostructure shows the potential application in pyrocatalytically degrading dye wastewater.
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