•ACPM was produced by mixing CaO2, water purification sludge and cement in a ratio of 5:3:2.•The ACPM enhanced the external P immobilization due to the bigger sorption capacity and the strong ...oxidation.•The micro-environment kept oxic conditions under the capping of ACPM.•The ACPM is beneficial for the permanent burial of sedimentary P.
The immobilization of sedimentary phosphorus (P) by capping sediments with amended calcium peroxide material (ACPM) and CaO2 was investigated, the sediments and overlying water from a black-odor river. Under the capping with ACPM and CaO2, the pH and dissolved oxygen (DO) in the overlying water were higher than in the control. This contributed to the more loss of external P under the ACPM (the phosphate sorption was fitted well by the Langmuir equation, the maximum P sorption capacity up to 29.28 mg P g−1). Additionally, ACPM improves the decrease of the reduction materials (e.g., NH4+-N, Fe2+) in the pore water compared to that associated with CaO2, resulting in a less obvious dissolved inorganic P (DIP) in the pore water, but the accumulation of DIP in the pore water with CaO2 suggested an explosive release once the micro-environment conditions encounters adverse conditions. The sharp reduction of Fe/Al-P and Res-P contributes to the increase of DIP in the pore water, with a release of up to 390.60 mg P kg−1 DW (dry weight), whereas the value is only 62.55 mg P kg−1 DW when capped with ACPM. Correspondingly, the percentage of the bioavailable P to Tot-P decreases rapidly from 17.27% (control, 0–2 cm) to 7.21% (ACPM, 0–2 cm) and 10.57% (CaO2, 0–2 cm), indicating the obvious P immobilization. The implication is that the application of CaO2 is not suitable for direct use, while the combination with other materials (e.g., WPS) is a better choice.
The aim of this work is to obtain Sn-doped MAO coatings with yellow color on magnesium alloy in a new sodium stannate (Na2SnO3) electrolyte system, which is different from traditional micro arc ...oxidation (MAO) colored-coating with transition metal salt addition. The formation mechanism, microstructure and corrosion resistance of these yellow MAO coatings were comparatively investigated using SEM, EDS, XRD, XPS and electrochemical experiment. Results indicated that, although Sn element had been adsorbed on the sample surface with only Na2SnO3 addition, a high-impedance film could not be formed and the phenomenon of micro arc discharge did not occur. Yellow MAO coatings were obtained as adding Na2SiO3 into different concentrations of Na2SnO3 solution and the color was gradually deepened with the increase of Na2SnO3 concentrations. It had been proved that the obtained yellow MAO coating could be attributed to the formation of SnO2 phase under high temperature and high pressure. Compared with the white MAO coating, the yellow MAO coating with 15 g/L Na2SnO3 addition showed an excellent corrosion resistance. The stability of preparing yellow MAO coating and its superior anti-corrosion property made it a good candidate as decorative coating on magnesium alloy.
•Yellow MAO coatings with SnO2 phase were formed on Mg alloy.•Deep yellow MAO coating had excellent corrosion resistance.•Formation mechanism of yellow MAO coatings had been illustrated.
Mps one binder 2 (MOB2) regulates the NDR kinase family, however, whether and how it is implicated in cancer remain unknown. Here we show that MOB2 functions as a tumor suppressor in glioblastoma ...(GBM). Analysis of MOB2 expression in glioma patient specimens and bioinformatic analyses of public datasets revealed that MOB2 was downregulated at both mRNA and protein levels in GBM. Ectopic MOB2 expression suppressed, while depletion of MOB2 enhanced, the malignant phenotypes of GBM cells, such as clonogenic growth, anoikis resistance, and formation of focal adhesions, migration, and invasion. Moreover, depletion of MOB2 increased, while overexpression of MOB2 decreased, GBM cell metastasis in a chick chorioallantoic membrane model. Overexpression of MOB2-mediated antitumor effects were further confirmed in mouse xenograft models. Mechanistically, MOB2 negatively regulated the FAK/Akt pathway involving integrin. Notably, MOB2 interacted with and promoted PKA signaling in a cAMP-dependent manner. Furthermore, the cAMP activator Forskolin increased, while the PKA inhibitor H89 decreased, MOB2 expression in GBM cells. Functionally, MOB2 contributed to the cAMP/PKA signaling-regulated inactivation of FAK/Akt pathway and inhibition of GBM cell migration and invasion. Collectively, these findings suggest a role of MOB2 as a tumor suppressor in GBM via regulation of FAK/Akt signaling. Additionally, we uncover MOB2 as a novel regulator in cAMP/PKA signaling. Given that small compounds targeting FAK and cAMP pathway have been tested in clinical trials, we suggest that interference with MOB2 expression and function may support a theoretical and therapeutic basis for applications of these compounds.
Quantum computers have made extraordinary progress over the past decade, and significant milestones have been achieved along the path of pursuing universal fault-tolerant quantum computers. Quantum ...advantage, the tipping point heralding the quantum era, has been accomplished along with several waves of breakthroughs. Quantum hardware has become more integrated and architectural compared to its toddler days. The controlling precision of various physical systems is pushed beyond the fault-tolerant threshold. Meanwhile, quantum computation research has established a new norm by embracing industrialization and commercialization. The joint power of governments, private investors, and tech companies has significantly shaped a new vibrant environment that accelerates the development of this field, now at the beginning of the noisy intermediate-scale quantum era. Here, we first discuss the progress achieved in the field of quantum computation by reviewing the most important algorithms and advances in the most promising technical routes, and then summarizing the next-stage challenges. Furthermore, we illustrate our confidence that solid foundations have been built for the fault-tolerant quantum computer and our optimism that the emergence of quantum killer applications essential for human society shall happen in the future.
Abstract
Background
Chimeric antigen receptor (CAR) T-cell therapy using brexucabtagene autoleucel (BA) induces remission in many patients with mantle cell lymphoma (MCL), and BA is the only CAR ...T-cell therapy approved by the FDA for MCL. However, development of relapses to BA is recognized with poor patient outcomes. Multiple CAR T-cell therapies have been approved for other lymphomas and the resistance mechanisms have been investigated. However, the mechanisms underlying BA relapse in MCL have not been investigated and whether any previously reported resistance mechanisms apply to BA-relapsed patients with MCL is unknown.
Methods
To interrogate BA resistance mechanisms in MCL, we performed single-cell RNA sequencing on 39 longitudinally collected samples from 15 BA-treated patients, and multiplex cytokine profiling on 80 serial samples from 20 patients.
Results
We demonstrate that after BA relapse, the proportion of T cells, especially cytotoxic T cells (CTLs), decreased among non-tumor cells, while the proportion of myeloid cells correspondingly increased.
TIGIT
,
LAG3
, and
CD96
were the predominant checkpoint molecules expressed on exhausted T cells and CTLs; only
TIGIT
was significantly increased after relapse. CTLs expanded during remission, and then contracted during relapse with upregulated
TIGIT
expression. Tumor cells also acquired TIGIT expression after relapse, leading to the enhanced interaction of tumor cell TIGIT with monocyte CD155/PVR. In myeloid cells, post-relapse HLA-II expression was reduced relative to pretreatment and during remission. Myeloid-derived suppressor cells (MDSCs) were enriched after relapse with elevated expression of activation markers, including
CLU
(clusterin) and
VCAN
(versican). Extracellular chemokines (CCL4, CXCL9, CXCL13), soluble checkpoint inhibitors (sPD-L1, sTIM3, s4-1BB), and soluble receptors (sIL-2R, sTNFRII) were decreased during remission but elevated after relapse.
Conclusions
Our data demonstrate that multiple tumor-intrinsic and -extrinsic factors are associated with T-cell suppression and BA relapse. Among these, TIGIT appears to be the central player given its elevated expression after BA relapse in not only CTLs but also MCL cells. The acquisition of TIGIT expression on tumor cells is MCL-specific and has not been reported in other CAR T-treated diseases. Together, our data suggest that co-targeting TIGIT may prevent CAR T relapses and thus promote long-term progression-free survival in MCL patients.
•Graphene-CdS hybrid materials were prepared via one-step hydrothermal method.•Graphene-CdS was used as non-enzymatic photoelectrochemical sensor to detect glucose.•Glucose in real sample was ...detected and showed good specificity and sensitivity.
Graphene-CdS quantum dots (QDs) hybrid materials were successfully prepared via one-step hydrothermal method. CdS QDs with average size of ∼6nm were dispersed on graphene sheets with high coverage through non-covalent bonding. Photocurrent and electrochemical impedance spectroscopy (EIS) results suggested that the best dosage of graphene oxide for graphene-CdS hybrid materials is 0.5% (G0.5-CdS). When G0.5-CdS QDs was used as photoanode materials in non-enzymatic sensor, and the sensor was used to detect glucose and displayed satisfactory analytical performance with good linear range from 0.1∼4mmol dm−3 with a detection limit of 7μmol dm−3 at a signal-to-noise ratio of 3. The sensor also possessed high selectivity and durability in trace detection of glucose.
Rice blast is regarded as one of the major diseases of rice. Screening rice genotypes with high resistance to rice blast is a key strategy for ensuring global food security. Unmanned aerial vehicles ...(UAV)-based imaging, coupled with deep learning, can acquire high-throughput imagery related to rice blast infection. In this study, we developed a segmented detection model (called RiceblastSegMask) for rice blast detection and resistance evaluation. The feasibility of different backbones and target detection models was further investigated. RiceblastSegMask is a two-stage instance segmentation model, comprising an image-denoising backbone network, a feature pyramid, a trinomial tree fine-grained feature extraction combination network, and an image pixel codec module. The results showed that the model combining the image-denoising and fine-grained feature extraction based on the Swin Transformer and the feature pixel matching feature labels with the trinomial tree recursive algorithm performed the best. The overall accuracy for instance segmentation of RiceblastSegMask reached 97.56%, and it demonstrated a satisfactory accuracy of 90.29% for grading unique resistance to rice blast. These results indicated that low-altitude remote sensing using UAV, in conjunction with the proposed RiceblastSegMask model, can efficiently calculate the extent of rice blast infection, offering a new phenotypic tool for evaluating rice blast resistance on a field scale in rice breeding programs.
The present study was conducted to investigate the protective effects of selenium on the oxidative damage of kidney cells (CIK) caused by nitrite exposure in grass carp (
Ctenopharyngodon idella
). ...Cells were pre-incubated by Na
2
SeO
3
(10 μmol/L) for 12 h and then exposed to NaNO
2
(25 mg/L) for 24 h, the cell viability, apoptosis, gene expression, and antioxidant enzyme activity were assayed. The results show that nitrite reduced cell viability and induced apoptosis, and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) as well as the
sod
,
cat
, and
gpx
genes reduced (
p
< 0.05), while the intracellular calcium ion concentration increased (
p
< 0.05). Interestingly, selenium treatment significantly alleviated the nitrite induced changes in cell growth, apoptosis, and calcium influx. The cell viability after low-concentration selenium treatment is higher than that of normal cells (
p
< 0.05). CIK cells were pre-incubated with Na
2
SeO
3
and then exposed to NaNO
2
, the antioxidant indicators could be maintained at normal levels. And compared with nitrite exposure, intracellular calcium ion concentration and apoptotic rate of selenium-incubated still decreased. The expressions of
Nrf2
and
Keap1
genes increased significantly in CIK cells treated with sodium selenite for 12 h, and the same trend as the enzyme activities of this group. The results show that the supplement of selenium can enhance the cell’s resistance to sodium nitrite exposure to a certain extent, by alleviating the antioxidant imbalance, high apoptosis rate, and intracellular calcium ion disturbance caused by nitrite exposure. And the Nrf2-Keap1 pathway may play an important role in the process.
•The effectiveness of DL and TL in predicting alpine river discharge was tested.•DL and TL models were pretrained using data from 671 catchments across the U.S.•Conformance to rainfall-runoff ...principles determines the training observations.•Climate forcing data influence streamflow prediction more than hydrogeological attributes.•DL and TL models were ineffective in areas with abundant groundwater contribution.
The Tibetan Plateau (TP) is an important Asian water tower for livelihood, irrigation, hydropower, and downstream ecosystems. Hydrological predictions in the TP have long been limited by sparse and discontinuous observations. Transfer learning (TL) technology may improve hydrological predictions by pre-training deep learning (DL) models on data-rich areas and then applying them to data-limited areas. However, the extent to which the DL and TL models work in alpine regions and the physical knowledge they provide remain unclear. Models were pretrained using data from 671 catchments across the U.S. and fine-tuned using data from four basins around the TP. Our results show that streamflow data with different temporal resolutions (monthly or daily) have little effect on discharge predictions when using DL. The number of discharge observations needed to enable acceptable performance of the DL models (Nash-Sutcliffe Efficiency coefficient greater than 0.6) depends on the hydrological characteristics of the catchments, in particular, how closely they conform to a general rainfall-runoff system. Climate forcing data determine the performance of streamflow prediction, whereas other attributes (i.e., soil and geology) have less significant impacts on prediction. The effectiveness of the DL and TL models is limited because groundwater contributes significantly to river discharge. This study provides an updated understanding of the application of DL and TL to quantify hydrological changes in the global cryosphere environment.
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