Triggering receptor expressed on myeloid cells 2 (TREM2) is a DAP12-associated receptor expressed in microglia, macrophages, and other myeloid-derived cells. Previous studies have suggested that ...TREM2/DAP12 signaling pathway reduces inflammatory responses and promotes phagocytosis of apoptotic neurons. Recently, TREM2 has been identified as a risk gene for Alzheimer disease (AD). Here, we show that DAP12 stabilizes the C-terminal fragment of TREM2 (TREM2-CTF), a substrate for γ-secretase. Co-expression of DAP12 with TREM2 selectively increased the level of TREM2-CTF with little effects on that of full-length TREM2. The interaction between DAP12 and TREM2 is essential for TREM2-CTF stabilization as a mutant form of DAP12 with disrupted interaction with TREM2 failed to exhibit such an effect. Silencing of either Trem2 or Dap12 gene significantly exacerbated pro-inflammatory responses induced by lipopolysaccharides (LPS). Importantly, overexpression of either full-length TREM2 or TREM2-CTF reduced LPS-induced inflammatory responses. Taken together, our results support a role of DAP12 in stabilizing TREM2-CTF, thereby protecting against excessive pro-inflammatory responses.
TREM2 is a DAP12-coupled receptor associated with neurodegenerative diseases.
Co-expression of DAP12 increased the level of TREM2 C-terminal fragment (TREM2-CTF) which suppressed the release of pro-inflammatory cytokines.
A major function of DAP12 is to stabilize TREM2-CTF, which regulates inflammatory responses in microglia.
Our studies unraveled a novel function of DAP12 and provided new link between TREM2/DAP12 complexes and neuroinflammation.
Stacked 2D perovskites provide more possibilities for next generation photodetector with more new features. Compared with its excellent optoelectronic properties, the good dielectric performance of ...metal halide perovskite rarely comes into notice. Here, a bifunctional perovskite based photovoltaic detector capable of two wavelength demultiplexing is demonstrated. In the Black Phosphorus/Perovskite/MoS2 structured photodetector, the comprehensive utilization of the photosensitive and dielectric properties of 2D perovskite allows the device to work in different modes. The device shows normal continuous photoresponse under 405 nm, while it shows a transient spike response to visible light with longer wavelengths. The linear dynamic range, rise/decay time, and self‐powered responsivity under 405 nm can reach 100, 38 µs/50 µs, and 17.7 mA W‐1, respectively. It is demonstrated that the transient spike photocurrent with long wavelength exposure is related to the illumination intensity and can coexist with normal photoresponse. Two waveband‐dependent signals can be identified and used to reflect more information simultaneously. This work provides a new strategy for multispectral detection and demultiplexing, which can be used to improve data transfer rates and encrypted communications. This work mode can inspire more multispectral photodetectors with different stacked 2D materials, especially to the optoelectronic application of the wide bandgap, high dielectric photosensitive materials.
By employing the photosensitive dielectric property of 2D perovskite, this work provided a demonstration of a bi‐functional photovoltaic detector. A normal response of 405‐nm light and a spike response of long wavelength coexist in this device. The spike response is a result of the dielectric property of 2D perovskite and can be used for two‐wavelength demultiplexing.
Abstract
Strong Coulomb interactions in single-layer transition metal dichalcogenides (TMDs) result in the emergence of strongly bound excitons, trions, and biexcitons. These excitonic complexes ...possess the valley degree of freedom, which can be exploited for quantum optoelectronics. However, in contrast to the good understanding of the exciton and trion properties, the binding energy of the biexciton remains elusive, with theoretical calculations and experimental studies reporting discrepant results. In this work, we resolve the conflict by employing low-temperature photoluminescence spectroscopy to identify the biexciton state in BN-encapsulated single-layer WSe
2
. The biexciton state only exists in charge-neutral WSe
2
, which is realized through the control of efficient electrostatic gating. In the lightly electron-doped WSe
2
, one free electron binds to a biexciton and forms the trion–exciton complex. Improved understanding of the biexciton and trion–exciton complexes paves the way for exploiting the many-body physics in TMDs for novel optoelectronics applications.
In locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to ...predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone.
All patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959, n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts.
Three imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25-0.74, p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (p
< 0.001). This trend was also found in the validation cohort with high (n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06-0.51, p < 0.001) and low ICTOS (n = 175, p = 0.31), with a significant treatment interaction (p
= 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors.
An imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment.
ClinicalTrials.gov , NCT01245959 . Registered 23 November 2010.
Plants possess the remarkable ability to sense detrimental environmental stimuli and launch sophisticated signal cascades that culminate in tailored responses to facilitate their survival, and ...transcription factors (TFs) are closely involved in these processes. Phytochrome interacting factors (PIFs) are among these TFs and belong to the basic helix-loop-helix family. PIFs are initially identified and have now been well established as core regulators of phytochrome-associated pathways in response to the light signal in plants. However, a growing body of evidence has unraveled that PIFs also play a crucial role in adapting plants to various biological and environmental pressures. In this review, we summarize and highlight that PIFs function as a signal hub that integrates multiple environmental cues, including abiotic (i.e., drought, temperature, and salinity) and biotic stresses to optimize plant growth and development. PIFs not only function as transcription factors to reprogram the expression of related genes, but also interact with various factors to adapt plants to harsh environments. This review will contribute to understanding the multifaceted functions of PIFs in response to different stress conditions, which will shed light on efforts to further dissect the novel functions of PIFs, especially in adaption to detrimental environments for a better survival of plants.
PM2.5–bound toxic elements and organic pollutants have been extensively investigated, while limited information is available for environmental persistent free radicals (EPFRs) associated with PM2.5, ...which may lead to oxidative stress in the human lung when exposed to PM2.5. In this study, the levels and types of PM2.5–bound EPFRs present in Nanjing, a mega–city in China, were analyzed. PM2.5–bound EPFRs were found to mainly be a mixture of carbon– and oxygen–centered radicals. The concentration of PM2.5–bound EPFRs ranged from 2.78 × 1012 to 1.72 × 1013 spins m−3, with an average value of 7.61 × 1012 spins m−3. The half–life of the PM2.5–bound EPFRs was calculated to be an average of 83.5 days when stored at room temperature, with only weak correlations observed between EPFRs and conventional air pollutants (NO2, O3, CO and PM2.5)/PM2.5–bound transition metals (Cu, Zn, Cr, Mn, V, Cd, and Ni) and significant correlations between EPFRs and SO2/PM2.5–bound Fe. PM2.5–bound EPFRs can induce the formation of reactive oxygen species (ROS) in both water and a H2O2 solution, which are used to simulate lung solution of a healthy person and patient, respectively. Therefore, PM2.5–bound EPFRs can lead to potential oxidative stress in humans. Overall, PM2.5–bound EPFRs show an obvious temporal variation and can pose potential health risks to humans via the induction of ROS in the lung solution.
•Levels and types of PM2.5-bound environmental persistent free radicals were analyzed.•Average 83.5 days of half-life of PM2.5-bound EPFRs under room temperature.•Significant correlations between EPFRs and SO2/PM2.5–bound Fe.•Weak or no correlations between EPFRs and PM2.5/Cu/Zn/Cr/Mn/V/Cd/Ni.•Potential oxidative stress from ROS induced by EPFRs via inhalation exposure.
Inversion symmetry breaking and 3-fold rotation symmetry grant the valley degree of freedom to the robust exciton in monolayer transition-metal dichalcogenides, which can be exploited for ...valleytronics applications. However, the short lifetime of the exciton significantly constrains the possible applications. In contrast, the dark exciton could be long-lived but does not necessarily possess the valley degree of freedom. In this work, we report the identification of the momentum-dark, intervalley exciton in monolayer WSe2 through low-temperature magneto-photoluminescence spectra. Interestingly, the intervalley exciton is brightened through the emission of a chiral phonon at the corners of the Brillouin zone (K point), and the pseudoangular momentum of the phonon is transferred to the emitted photon to preserve the valley information. The chiral phonon energy is determined to be ∼23 meV, based on the experimentally extracted exchange interaction (∼7 meV), in excellent agreement with the theoretical expectation of 24.6 meV. The long-lived intervalley exciton with valley degree of freedom adds an exciting quasiparticle for valleytronics, and the coupling between the chiral phonon and intervalley exciton furnishes a venue for valley spin manipulation.
In the construction process of shallow subway tunnels, frequent collapses of the sand layer overlying the tunnel pose a serious threat to the safety of the construction operation. With the big data ...monitoring information, more effective treatments can be applied for sand-layer collapse. Based on the engineering background of the sand-layer collapse disaster in Qingdao Metro Line 2, detailed analysis of the process and mechanism of sand-layer collapse in tunnels was done. Grouting method was used to improve collapse-preventing treatment in the sand layer. For treating the water-bearing sand layer above the tunnel, an advancement of grouting reinforcement system was proposed. The results showed that the main causes of sand-layer collapse are the intrinsic characteristics of the sand layer itself. The cohesive soil content of the sand layer is low and the cementation ability of the sand layer is weak. The advancing grouting method applied in this project is an effective method to strengthen the sand layer; the grouting parameters obtained in this study can be used as a guidance for similar engineering projects.
Quick setting slurry is commonly used in rock fissure grouting projects due to short gel time, high early strength and high retention rate in groundwater. Generally, quick setting slurry is composed ...by grout material and quick set reagent, and can be injected by using two-shot injection systems, which mixing two components inside or outside injection hole. Resulting from two-shot injection style and quick setting property of slurry, the viscosity of slurry varies from the injection hole to the radius of grout spread in grouting process, which has significant influence on the fissured rock grouting calculation. In this paper, grouting process of quick setting slurry in a single horizontal fissure is studied. The step-wise calculation method is proposed to describe the grouting process, considering the uneven distribution of slurry viscosity in grouted zone. The circular grouted zone is divided into infinitesimal annular elements, according to the moment when the slurry particle is injected into the fissure from the injection hole. Case studies of two conditions (constant grouting flow and constant grouting pressure) are investigated to capture the distribution of slurry viscosity and pressure in grouted zone. Fissure grouting test is performed to verify that the developed step-wise calculation method is suitable for the analysis of the distribution of pressure in grouted zone. Cement-sodium silicate slurry with two volume ratios (C:S=1:1, 2:1), a typical quick setting slurry, is used in the grouting test, and the pressure field and visual grouted zone are monitored in grouting process. The computed results derived from the step-wise calculation method is well consistent with the measured results, and the effectiveness of step-wise method is verified.
A facile solvothermal method for the synthesis of multifunctional magnetic CuFeMnO4 nanospheres affinity probe (NSAP) with controllable morphology and size was developed for the first time. The ...CuFeMnO4 nanospheres combine the brilliant features of Cu2+, Fe3+, and Mn2+ ions, so their multifunction performances are embodied by strong coordination to carboxyl and amine groups of peptides (Cu2+ and Fe3+), special affinity to phosphate groups of phosphopeptides (Fe3+ and Mn2+), and high magnetic responsiveness in a magnetic field. Their potential as an affinity probe was evaluated for highly effective enrichment, rapid magnetic separation of low-abundance peptides (neutral condition), and effective selective capture of phosphopeptides (acid condition) from various complex biosamples. Notably, CuFeMnO4 NSAP was explored for highly selective capture and isolation of phosphopeptides from A549 cells after exposure to ZnO nanoparticles for different times. Consequently, we put forward a new nanospinel ferrite-based protocol here to analyze and identify the phosphoproteins/phosphopeptides involved in cellular signaling pathways in response to exogenous stimulation.
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