Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the most important limiting factor for treatment efficiency in EGFR-mutant non-small cell lung cancer ...(NSCLC). Much work has linked the epithelial–mesenchymal transition (EMT) to the emergence of drug resistance, consequently, ongoing research has been focused on exploring the therapeutic options to reverse EMT for delaying or preventing drug resistance. Polyphyllin I (PPI) is a natural compound isolated from Paris polyphylla rhizomes and displayed anti-cancer properties. In the current work, we aimed to testify whether PPI could reverse EMT and overcome acquired EGFR-TKI resistance. We exposed HCC827 lung adenocarcinoma cells to erlotinib which resulted in acquired resistance with strong features of EMT. PPI effectively restored drug sensitivity of cells that obtained acquired resistance. PPI reversed EMT and decreased interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway activation in erlotinib-resistant cells. Moreover, addition of IL-6 partially abolished the sensitization response of PPI. Furthermore, co-treatment of erlotinib and PPI completed abrogation of tumor growth in xenografts, which was associated with EMT reversal. In conclusion, PPI serves as a novel solution to conquer the EGFR-TKI resistance of NSCLC via reversing EMT by modulating IL-6/STAT3 signaling pathway. Combined PPI and erlotinib treatment provides a promising future for lung cancer patients to strengthen drug response and prolong survival.
Despite many decades of study, the kinematics of the broad-line region of 3C 273 are still poorly understood. We report a new, high signal-to-noise, reverberation mapping campaign carried out from ...2008 November to 2018 March that allows the determination of time lags between emission lines and the variable continuum with high precision. The time lag of variations in Hβ relative to those of the 5100 continuum is days in the rest frame, which agrees very well with the Paschen- region measured by the GRAVITY at The Very Large Telescope Interferometer. The time lag of the Hγ emission line is found to be nearly the same as that for Hβ. The lag of the Fe ii emission is days, longer by a factor of ∼2 than that of the Balmer lines. The velocity-resolved lag measurements of the Hβ line show a complex structure that can be possibly explained by a rotation-dominated disk with some inflowing radial velocity in the Hβ-emitting region. Taking the virial factor of fBLR = 1.3, we derive a BH mass of and an accretion rate of from the Hβ line. The decomposition of its Hubble Space Telescope images yields a host stellar mass of , and a ratio of in agreement with the Magorrian relation. In the near future, it is expected to compare the geometrically thick BLR discovered by the GRAVITY in 3C 273 with its spatially resolved torus in order to understand the potential connection between the BLR and the torus.
As one paper in a series reporting on a large reverberation mapping campaign of super-Eddington accreting massive black holes (SEAMBHs) in active galactic nuclei (AGNs), we present the results of 10 ...SEAMBHs monitored spectroscopically during 2015-2017. Six of them are observed for the first time, and have generally higher 5100 luminosities than the SEAMBHs monitored in our campaign from 2012 to 2015; the remaining four are repeat observations to check if their previous lags change. Similar to the previous SEAMBHs, the Hβ time lags of the newly observed objects are shorter than the values predicted by the canonical RHβ-L5100 relation of sub-Eddington AGNs, by factors of ∼2-6, depending on the accretion rate. The four previously observed objects have lags consistent with previous measurements. We provide linear regressions for the RHβ-L5100 relation, solely for the SEAMBH sample and for low-accretion AGNs. We find that the relative strength of Fe ii and the profile of the Hβ emission line can be used as proxies of accretion rate, showing that the shortening of Hβ lags depends on accretion rates. The recent SDSS-RM discovery of shortened Hβ lags in AGNs with low accretion rates provides compelling evidence for retrograde accretion onto the black hole. These evidences show that the canonical RHβ-L5100 relation holds only in AGNs with moderate accretion rates. At low accretion rates, it should be revised to include the effects of black hole spin, whereas the accretion rate itself becomes a key factor in the regime of high accretion rates.
Small RNAs (smRNAs) in plants, mainly microRNAs and small interfering RNAs, play important roles in both transcriptional and post-transcriptional gene regulation. The broad application of ...high-throughput sequencing technology has made routinely generation of bulk smRNA sequences in laboratories possible, thus has significantly increased the need for batch analysis tools. PsRobot is a web-based easy-to-use tool dedicated to the identification of smRNAs with stem-loop shaped precursors (such as microRNAs and short hairpin RNAs) and their target genes/transcripts. It performs fast analysis to identify smRNAs with stem-loop shaped precursors among batch input data and predicts their targets using a modified Smith-Waterman algorithm. PsRobot integrates the expression data of smRNAs in major plant smRNA biogenesis gene mutants and smRNA-associated protein complexes to give clues to the smRNA generation and functional processes. Besides improved specificity, the reliability of smRNA target prediction results can also be evaluated by mRNA cleavage (degradome) data. The cross species conservation statuses and the multiplicity of smRNA target sites are also provided. PsRobot is freely accessible at http://omicslab.genetics.ac.cn/psRobot/.
Abstract
We present the results from a spectroscopic monitoring campaign to obtain reverberation mapping measurements and investigate the broad-line region (BLR) kinematics for active galactic nuclei ...(AGNs) of Mrk 817 and NGC 7469. This campaign was undertaken with the Lijiang 2.4 m telescope. The median spectroscopic sampling is 2.0 days for Mrk 817 and 1.0 day for NGC 7469. We detect time lags of the broad emission lines, including H
β
, H
γ
, He
ii,
and He
i
for both AGNs, including Fe
ii
for Mrk 817 with respect to the varying AGN continuum at 5100 Å. Investigating the relationship between line widths and time lags of the broad emission lines, we find that the BLR dynamics of Mrk 817 and NGC 7469 are consistent with the virial prediction. We estimate the masses of central supermassive black holes (SMBHs) and the accretion rates of both AGNs. Using the data of this campaign, we construct the velocity-resolved lag profiles of the broad H
γ
, H
β
, and He
i
lines for Mrk 817, which show almost the same kinematic signatures in that the time lags in the red wing are slightly larger than the time lags in the blue wing. For NGC 7469, we only clearly construct the velocity-resolved lag profiles of the broad Hγ and Hβ, which show very similar kinematic signatures to the BLR of Mrk 817. These signatures indicate that the BLR of Keplerian motion in both AGNs seemingly has outflowing components during the monitoring period. We discuss the kinematics of the BLR and the measurements, including SMBH mass and accretion rates.
2D lamellar materials can offer high surface area and abundant reactive sites, thus showing an appealing prospect in photocatalytic hydrogen evolution. However, it is still difficult to build ...cost‐efficient photocatalytic hydrogen evolution systems based on 2D materials. Herein, an in situ growth method is employed to build 2D/2D heterojunctions, with which 2D Ni‐based metal–organic layers (Ni‐MOLs) are closely grown on 2D porous CdS (P‐CdS) nanosheets, affording traditional P‐CdS/Ni‐MOL heterojunction materials. Impressively, the optimized P‐CdS/Ni‐MOL catalyst exhibits superior photocatalytic hydrogen evolution performance, with an H2 yield of 29.81 mmol g−1 h−1. This value is 7 and 2981 times higher than that of P‐CdS and Ni‐MOLs, respectively, and comparable to those of reported state of the art catalysts. Photocatalytic mechanism studies reveal that the enhanced photocatalytic performance can be attributed to the 2D/2D intimate interface between P‐CdS and Ni‐MOLs, which facilitates the fast charge carriers’ separation and transfer. This work provides a strategy to develop 2D MOL‐based photocatalysts for sustainable energy conversion.
The ultrathin structure and large specific surface area of the P‐CdS/Ni‐MOL composites are of great benefit for exposing more active sites and expanding contact surface area. In such a way, the recombination of photoinduced electrons/holes pairs can be efficiently inhibited. The synergistic effect of the intimate contact between P‐CdS and Ni‐MOLs can significantly enhance the photocatalytic H2 evolution performances.
This study aimed to examine the efficacy of Nutritional Risk Screening 2002 (NRS2002) and Mini Nutritional Assessment Short Form (MNA-SF) in recognizing sarcopenia and predicting its mortality in ...Chinese geriatric hospitalized patients.
A prospective analysis was performed in 430 hospitalized geriatric patients. Nutrition status was assessed using the NRS2002 and MNA-SF scales. Anthropometric measures and biochemical parameters were carried out for each patient. Sarcopenia was defined according to the revised consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP2). Patients were follow-up for up to 26 months.
The overall prevalence of sarcopenia was 35.3% in this population. In the sarcopenic patients, 53 (34.9%) were malnutrition/nutritional risk according to NRS2002 assessment and 101 (66.4%) patients were malnutrition/nutritional risk according to MNA-SF assessment. NRS2002 vs MNA-SF showed moderate agreement (κ = 0.460, P < 0.001). Receiver operating characteristic analysis showed that the area under the curve of MNA-SF was larger than NRS2002 in recognizing sarcopenia (0.763 vs 0.649, P = 0.001). During a median follow-up time of 20.22 months, 48 (31.6%) sarcopenic patients died. The Kaplan-Meier curve demonstrated that malnutrition/nutritional risk patients according to whether NRS2002 or MNA-SF assessment had a higher risk of death than the normal nutrition patients (χ
= 15.728, P < 0.001; χ
= 7.039, P = 0.008, respectively). Age, serum albumin levels, and NRS2002 score were independent factors influencing the mortality.
MNA-SF score may be better than the NRS2002 score to recognize sarcopenia in Chinese geriatric population. Both NRS2002 and MNA-SF scores could predict mortality, but NRS2002 score was the independent predict factor.
An overview of antimicrobial properties of kombucha Nyiew, Ke‐Ying; Kwong, Phek Jin; Yow, Yoon‐Yen
Comprehensive reviews in food science and food safety,
March 2022, 2022-03-00, 20220301, Volume:
21, Issue:
2
Journal Article
Peer reviewed
Kombucha is a traditional beverage of Manchurian origin, typically made by fermenting sugared black or green tea with the symbiotic consortium of bacteria and yeast (SCOBY). The beverage has gained ...increasing popularity in recent years, mainly due to its heralded health benefits. The fermentation process of kombucha also results in the production of various bioactive compounds with antimicrobial potential, making it a promising candidate in the exploration of alternative sources of antimicrobial agents, and may be helpful in combating the rising threat of antibiotic resistance. Literature survey performed on Web of Science, Scopus, and PubMed revealed the extensive research that has firmly established the antimicrobial activity of kombucha against a broad spectrum of bacteria and fungi. This activity could be attributed to the synergistic activities of the microbial species in the kombucha microbiota that led to the synthesis of compounds with antimicrobial properties such as acetic acid and various polyphenols. However, research thus far only involved screening for the antimicrobial activity of kombucha. Therefore, there is still a research gap about the molecular mechanism of the kombucha reaction against specific pathogens and its influence on human health upon consumption. Future research may focus on investigating this aspect. Further characterization of the biological activity of the microbial community in kombucha may also facilitate the discovery of novel antimicrobial compounds, such as bacteriocins produced by the microorganisms.
Objectives
To investigate the effects of geniposide in an iridoid found in Gardenia jasminoides var. radicans Makino (GJRM) in spontaneous hypertensive rat (SHR) and explore the possible mechanisms.
...Methods
In this study, we detected the content of geniposide in GJRM by high‐performance liquid chromatography (HPLC). Then, we used acute diuretic experiments to determine whether geniposide has diuretic effect. Moreover, we carried out experiments on SHR to further study the mechanism of hypertension, while real‐time PCR, Western blot and immunohistochemistry were used for the experiments in vivo test. Hypotonic model was used for in vitro test.
Key findings
Our data showed that the content of geniposide in the extract of GJRM is 27.54%. Meanwhile, 50 mg/kg geniposide showed the strongest effect on promoting urine volume. Further study indicated that the extract of GJRM and geniposide could significantly reduce blood pressure and promote the excretion of urine and Na+ in SHR. In addition, geniposide significantly inhibited the activation of the with‐no‐lysine kinase (WNK) signalling pathway and significantly increases the protein expressions of estrogen receptor α (ERα), estrogen receptor β (ERβ) and G protein‐coupled receptor 30 (GPR30) in SHR. In hypotonic model, geniposide significantly inhibits the phosphorylation of NKCC and NCC and could be antagonistic to estrogen receptor antagonists.
Conclusions
Collectively, we would suggest that geniposide may potentially be utilized as an adjunct to existing thiazide and thiazide‐like diuretics to control hypertension, mainly through inhibiting the activation of the WNK signalling pathway mediated by the estrogen receptor.
Transcranial direct current stimulation (tDCS) is a non-invasive brain modulation technique that has been proved to exert beneficial effects in the acute phase of stroke. To explore the underlying ...mechanism, we investigated the neuroprotective effects of cathodal tDCS on brain injury caused by middle cerebral artery occlusion (MCAO).
We established the MCAO model and sham MCAO model with an epicranial electrode implanted adult male Sprague-Dawley rats, and then they were randomly divided into four groups (MCAO + tDCS, MCAO + sham tDCS (Sham), Control + tDCS and Control + Sham group). In this study, the severity degree of neurological deficit, the morphology of brain damage, the apoptosis, the level of neuron-specific enolase and inflammatory factors, the activation of glial cells was detected. The results showed that cathodal tDCS significantly improved the level of neurological deficit and the brain morphology, reduced the brain damage area and apoptotic index, and increased the number of Nissl body in MCAO rats, compared with MCAO + Sham group. Meanwhile, the high level of NSE, inflammatory factors, Caspase 3 and Bax/Bcl2 ratio in MCAO rats was reduced by cathodal tDCS. Additionally, cathodal tDCS inhibited the activation of astrocyte and microglia induced by MCAO. No difference was found in two Control groups.
Our results suggested that cathodal tDCS could accelerate the recovery of neurologic deficit and brain damage caused by MCAO. The inhibition of neuroinflammation and apoptosis resulted from cathodal tDCS may be involved in the neuroprotective process.
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