A previous genome‐wide association study (GWAS) revealed an association of the noncoding SNP rs1663689 with susceptibility to lung cancer in the Chinese population. However, the underlying mechanism ...is unknown. In this study, using allele‐specific 4C‐seq in heterozygous lung cancer cells combined with epigenetic information from CRISPR/Cas9‐edited cell lines, we show that the rs1663689 C/C variant represses the expression of ADGRG6, a gene located on a separate chromosome, through an interchromosomal interaction of the rs1663689 bearing region with the ADGRG6 promoter. This reduces downstream cAMP‐PKA signaling and subsequently tumor growth both in vitro and in xenograft models. Using patient‐derived organoids, we show that rs1663689 T/T—but not C/C—bearing lung tumors are sensitive to the PKA inhibitor H89, potentially informing therapeutic strategies. Our study identifies a genetic variant‐mediated interchromosomal interaction underlying ADGRG6 regulation and suggests that targeting the cAMP‐PKA signaling pathway may be beneficial in lung cancer patients bearing the homozygous risk genotype at rs1663689.
Synopsis
This study shows a trans‐effect of a noncoding genetic variant and suggests a personalized treatment strategy for lung cancer patients harboring the T/T genotype at rs1663689.
rs1663689 regulates lung cancer progression.
rs1663689 regulates ADGRG6 expression through interchromosomal interaction.
Organoids derived from lung cancer patients carrying the risk allele at rs1663689 respond to PKA inhibitor.
This study shows a trans‐effect of a noncoding genetic variant and suggests a personalized treatment strategy for lung cancer patients harboring the T/T genotype at rs1663689.
Approximately half of patients with Crohn's disease (CD) may inevitably receive surgical intervention as the disease progress. However, about 75% of CD patients will experience postoperative ...recurrence (POR). Biologics are appealing alternatives for the prevention of POR; however, it is still unclear which biological agents are more efficient. This meta-analysis aimed to investigate the efficacy of biologics for POR prevention and to compare the superiority of different biologics.
We conducted a thorough search of online databases and screened for studies on the efficacy of biologics in preventing POR (clinical, endoscopic, or histological) that were published until January 2021. The results were presented as forest plots and odds ratios (ORs) with 95% confidence intervals (CIs).
We included 26 studies with 2,136 participants. Overall, biologics were more efficient over non-biological treatments in preventing endoscopic, severe endoscopic, and clinical POR without increasing the frequency of adverse events. Among the various types of biologics, anti-TNFα agents were better than vedolizumab in preventing endoscopic POR. Moreover, infliximab had a similar curative effect to adalimumab in preventing endoscopic, severe endoscopic, and clinical recurrence.
Biologics, especially anti-TNFα agents, still play a vital role in preventing POR in the biological era.
Litter decomposition is of utmost importance to elemental cycling in terrestrial ecosystems, with litter quality being frequently considered to predominantly control litter decomposition. However, ...how acid rain (AR) would affect litter decomposition and its elements release remains inconclusive, although AR has widely occurred in Europe, North America, and East Asia. This study was conducted to observe leaf litter decomposition and release of carbon (C), nitrogen (N), and phosphorus (P) of three crops (maize, rice, and soybean) under simulated AR treatments. Results showed that the accumulated mass loss during decomposition was significantly different among species, supporting the view of litter quality predominantly controlling decomposition. Specifically, quality dependence of litter decomposition was observed in the late stage of decomposition, while mass loss of litters was comparable in the first month among species. With decomposition, the litter C/N ratio significantly increased for the three species while the C/P and N/P ratios significantly decreased or tended to decrease, suggesting that litter N was released preferentially over C and P. However, AR treatments did not significantly affect litter decomposition and its elements release in our investigation period. Moreover, litter P content appeared to strongly affect the release of C, N, and P during litter decomposition, and such P dependence could to some extent be alleviated by AR treatments. Our results suggest that AR may change the quality dependence of litter decomposition and further studies are needed to illustrate its potential mechanisms.
Active galactic nuclei (AGNs) have long been observed to "twinkle" (i.e., their brightness varies with time) on timescales from days to years in the UV/optical bands. Such AGN UV/optical variability ...is essential for probing the physics of supermassive black holes (SMBHs), the accretion disk, and the broad-line region. Here, we show that the temperature fluctuations of an AGN accretion disk, which is magnetically coupled with the corona, can account for observed high-quality AGN optical light curves. We calculate the temperature fluctuations by considering the gas physics of the accreted matter near the SMBH. We find that the resulting simulated AGN UV/optical light curves share the same statistical properties as the observed ones as long as the dimensionless viscosity parameter , which is widely believed to be controlled by magnetohydrodynamic (MHD) turbulence in the accretion disk, is about 0.01-0.2. Moreover, our model can simultaneously explain the larger-than-expected accretion disk sizes and the dependence of UV/optical variability upon wavelength for NGC 5548. Our model also has the potential to explain some other observational facts of AGN UV/optical variability, including the timescale-dependent bluer-when-brighter color variability and the dependence of UV/optical variability on AGN luminosity and black-hole mass. Our results also demonstrate a promising way to infer the black-hole mass, the accretion rate, and the radiative efficiency, thereby facilitating understanding of the gas physics and MHD turbulence near the SMBH and its cosmic mass growth history by fitting the AGN UV/optical light curves in the era of time-domain astronomy.
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•Chlorella mutant MS700 had a higher carbon fixation efficiency than the wild type.•MS700 had a 104.2% higher chlorophyll-based flash oxygen yield.•MS700 had a more efficient ...downstream process pulling electrons in PQ pool.•MS700 had a 27.7% higher capability of incorporating its dissolved inorganic carbon.
Chlorophyll a variable fluorescence and oxygen evolution were measured in microalgae Chlorella and its mutant MS700, which was mutated by nuclear radiation with an increased biomass yield. The mutant MS700 showed an improvement in photosynthetic characteristics under various CO2 concentrations. Results showed that chlorophyll-based flash oxygen yield was 104% higher in MS700 than in the wild type, indicating more available electron acceptors in the plastoquinone pool and a higher light to chemical energy conversion efficiency. The higher chlorophyll a variable fluorescence at the end of PQ pool-regulated phase implied a more robust mechanism for consumption of electrons generated in PSII, indicating a more efficient downstream process. Monitoring of CO2 fixation in the Calvin cycle showed that the mutant had a 27.7% higher capability of incorporating its dissolved inorganic carbon. The oxygen evolution rate was 31.4% higher in MS700, which also indicated a higher CO2 fixation rate. These results consistently demonstrated carbon fixation efficiency in the mutant MS700, resulting in the higher biomass yield.
As an ideal reinforcing phase, nano-carbon has been widely used to improve the properties of composites. In this paper, Mo–Cu–Zr ternary composites were reinforced with various types and contents of ...nano-carbon to find the optimal composition and the microstructure and mechanical properties of the composites were systematically characterized and analyzed. The composites were fabricated via a powder metallurgy method to achieve high compactness and structural uniformity. The analysis results show that the increase of nano-carbon may cause a serious agglomeration and subsequent decrease of the composite compactness, while the synergetic effect of carbon nanotubes (CNTs) and graphene nanoplatelets (GNPs) can improve their dispersion. The 0.8C + 0.2G-MCZ3 composite showed the best comprehensive properties, which achieved a relative density, hardness and compressive strength of 99.7%, 343.6 HV and 953.5 MPa, respectively. Moreover, the component Zr mainly formed solid solution and compound particles with Cu or C through in-situ chemical reactions. It played an important role in solid solution strengthening and dispersion strengthening, and the in-situ synthesized ZrC nanoparticles on nano-carbon surfaces can pin interfaces and improve the effect of load transfer. The synergetic effects and multiple strengthening mechanisms result in the improvement of the microstructure and properties of the composites.
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•Interfaces between nano-carbons and matrix are improved by the in-situ synthesized phase.•The synergy of CNTs and GNPs shows a better reinforcing effect.•The increase of Zr content is beneficial to the improvement of the properties of composites.•Multiple strengthening mechanisms synergistically act on the improvement of composite properties.
Background:
Cardiac pacing in patients with bradyarrhythmia may employ variable pacing sites, which may have different effects on cardiac function. Left bundle branch pacing (LBBP) is a new ...physiological pacing modality, and the acute outcomes on cardiac mechanical synchrony during LBBP remain uncertain. We evaluated the acute effects of four pacing sites on cardiac synchrony and contraction using speckle-tracking echocardiography, and comparisons among four different pacing sites were rare.
Methods:
We enrolled 21 patients with atrioventricular block or sick sinus syndrome who each sequentially underwent acute pacing protocols, including right ventricular apical pacing (RVAP), right ventricular outflow tract pacing (RVOP), His bundle pacing (HBP), and left bundle branch pacing (LBBP). Electrocardiograms and echocardiograms were recorded at baseline and during pacing. The interventricular mechanical delay (IVMD), the standard deviation of the times to longitudinal peak strain during 17 segments (PSD), and the Yu index were used to evaluate ventricular mechanical synchrony. Layer-specific strain was computed using two-dimensional speckle tracking technique to provide in-depth details about ventricular synchrony and function.
Results:
Left ventricular ejection fraction (LVEF) and tricuspid annulus plane systolic excursion (TAPSE) were significantly decreased during RVAP and RVOP but were not significantly different during HBP and LBBP compared with baseline. RVAP and RVOP significantly prolonged QRS duration, whereas HBP and LBBP showed non-significant effects. IVMD and PSD were significantly increased during RVAP but were not significantly different during RVOP, HBP, or LBBP. LBBP resulted in a significant improvement in the IVMD and Yu index compared with RVAP. No significant differences in mechanical synchrony were found between HBP and LBBP.
Conclusion:
Among these pacing modalities, RVAP has a negative acute impact on cardiac synchrony and contraction. HBP and LBBP best preserve physiological cardiac synchrony and function.
In the field of organic light-emitting diodes (OLEDs), research interests focus on making the optically dark triplet excitons shine in order to increase the electro-optic conversion efficiency of ...devices. In this work, two kinds of phenazine compounds,
i.e.
dibenzo
a
,
c
phenazine (DBP) and tribenzo
a
,
c
,
i
phenazine (TBP), were synthesized and used as model compounds to regulate the emission efficiency of the dark triplet excitons by chemical modification. Charge-transfer induced ultrafast intersystem crossing (CT-ISC) with a time constant of ∼1 ps was observed for these two phenazine derivatives upon photoexcitation with a high triplet yield of 77.1% for DBP and 58.7% for TBP. The triplet excited states of DBP can produce ultra-long phosphorescence with lifetime as long as 318 ms at 77 K. The quantum yield for phosphorescence (
Φ
P
) is determined to be 8.45%. In sharp contrast, the triplet-excited
3
TBP* undergoes an efficient reverse intersystem crossing (RISC) process, resulting in bright delayed fluorescence emission with negligible phosphorescence. A controllable luminescence behavior from the triplet states between fluorescence and phosphorescence in phenazine derivatives is demonstrated. Theoretical calculations reveal that the structure-dependent triplet evolution is due to the charge-transfer induced energy level alignment within these compounds. Our results may have potential applications in the design of OLEDs and high triplet yield pure organic materials.
Type 2 diabetes mellitus (T2DM) commonly complicates kidney stone disease (KSD). Our objective is to investigate the variations in the urinary microbiota between individuals with KSD alone and those ...with KSD plus T2DM. This exploration could have implications for disease diagnosis and treatment strategies.
During lithotripsy, a ureterscope was employed, and 1 mL of urine was collected from the renal pelvis after bladder disinfection. Sequencing targeting the V3-V4 hypervariable region was performed using the 16S rRNA and Illumina Novaseq platform.
The Shannon index showed a significant decrease in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.041). Principal Coordinate Analysis (PCoA) demonstrated a distinct bacterial community in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.027). The abundance of
,
, and
was significantly higher in the KSD plus T2DM group than in the KSD-only group (false discovery rate < 0.05). Furthermore,
,
, and
were positively correlated with fasting blood glucose and HbA1c values (
< 0.05).
The urinary microbiota in the renal pelvis exhibits differences between patients with KSD plus T2DM and those with KSD alone. Further studies employing animal models are necessary to validate these distinctions, potentially paving the way for therapeutic developments based on the urinary microbiota.
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