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Many studies have shown that paint with reflective heat can effectively reduce the temperature of the building envelope and reduce the future energy consumption of the building. This study inspired the next-generation inorganic geopolymer material (IGM) color paint without volatile matter, which could be applied on concrete surfaces to reduce energy consumption in warm seasons. In this study, a total of five insulating IGM paints, white, red, green, blue, and yellow, were applied to a 50 cm × 50 cm × 12 cm concrete slab top surface. The highest average light reflectance of all the paints was 87.5% of white IGM paint, which was higher than plain concrete (36.4%). The heat flux and surface temperature were examined in the laboratory, and those test results were verified outdoor. The results showed that the IGM paints could effectively reduce the surface temperature and heat flux of the upper and lower surfaces of concrete slabs, and the white colored IGM paint was the best performer among all five colors, whereas the heat storage coefficient (Sf) of red, white, yellow, blue, and green IGM painted concrete slabs were 0.57, 0.53, 3.62, 2.95, and 1.91 W·m−2·K−1, respectively, lower than plain concrete (24.40 W·m−2·K−1). This coefficient was presented to externalize the thermal admittance. The overall measurement results showed that the concrete slab with colored IGM paints had better heat insulation ability than the plain concrete slab, especially in white IGM paint.

In this brief, a kernel adaptive filter based on the Student’s ${t}$ distribution in the reproducing kernel Hilbert space (RKHS) is presented, which is distinct from the traditional kernel adaptive filtering algorithms as follows: first, a Student’s ${t}$ reproducing kernel function is proposed to fight against the abrupt noise together with Gaussian noise depicted by the impulsive-Gaussian mixed noise model; and second, a Strengthened Surprise Criterion (SSC) is devised to reduce the size of the neural networks, which is utilized to implement the proposed Student’s ${t}$ -based kernel filter. The proposed algorithms are compared with the widely used KLMS and recently proposed KRLS-type filters in terms of the accuracy error under both Gaussian and abrupt noise. Experimental results show that the proposed Student’s ${t}$ -based kernel adaptive filter can improve the estimation accuracy at least by 20% while having more compact size of neural networks compared with the existed kernel adaptive algorithms.

Cerebral vasospasm (CVS) is a frequent and serious neurosurgical complication, without sufficient therapy. This retrospective study was performed to analyze if nimodipine can improve prognosis and reduce ischaemia secondary to delayed CVS after intracranial tumour surgery. A retrospective review was performed over the years 2011 to 2012 for patients with an anterior cranial fossa tumour and underwent intracranial tumour surgery. The surgical field was soaked with nimodipine solution or normal saline. Transcranial Doppler ultrasonography was used to measure velocity in the middle cerebral artery (MCA) and the distal extracranial internal carotid artery (eICA). Follow-up was performed using the Glasgow Outcome Scale (GOS) after discharge. There were 94 patients that met the inclusion criteria. They included 50 males and 44 females, with a mean age of 49.6 years. In the nimodipine group, CVS occurred in 13 patients; 9 patients had CVS between 4 and 7 days, and 4 had CVS between 8 and 14 days. In the normal saline group, 19 patients had CVS, 3 presented with CVS within 3 days, 11 between 4-7 days and 5 between 8-14 days. A significant difference in the occurrence of CVS was observed between the two groups. Preoperative and postoperative the MCA velocities were compared, revealing a significant change in the normal saline group but not in the nimodipine group. Nimodipine markedly improves prognosis and significantly reduces ischaemia secondary to delayed CVS after intracranial tumour surgery, as well as the risks of mortality and morbidity.

To develop an effective strategy for accurate diagnosis of focal liver lesions (FLLs) in patients with non-high risk for hepatocellular carcinoma (HCC).From January 2012 to December 2015, consecutive patients with non-high risk for HCC who underwent contrast-enhanced ultrasound (CEUS) were included in this retrospective double-reader study. All patients were stratified into 2 different risks (intermediate, low-risk) groups according to criteria based on clinical characteristics, known as clinical risk stratification criteria. For the intermediate-risk group, the CEUS criteria for identifying benign lesions and HCCs were constructed based on selected CEUS features. The diagnostic performance of the clinical risk stratification criteria, and CEUS criteria for identifying benign lesions and HCCs was evaluated.This study included 348 FLLs in 348 patients. The sensitivity and specificity of the clinical risk stratification criteria for malignancy was 97.8 and 69.8%. Patients were classified as intermediate risk if they were male, or older than 40 years of age, or HBcAb positive, or having positive tumor markers. Otherwise, patients were classified as low risk. Among the 348 patients, 327 were in the intermediate-risk group and 21 were in the low-risk group. In the intermediate-risk group, the CEUS criteria for identifying benign lesions were any of the following features: 1) hyper/isoenhancement in the arterial phase without washout, 2) nonenhancement in all phases, 3) peripheral discontinuous globular enhancement in the arterial phase, 4) centrifugal enhancement or peripheral enhancement followed by no central enhancement, or 5) enhanced septa. The accuracy, sensitivity, and specificity of the CEUS criteria for identifying benign lesions were 94.5, 83.0, and 99.6%, respectively. Arterial phase hyperenhancement followed by mild and late washout (60 seconds) was more common in HCC patients than in non-HCC patients (P .001). Using arterial phase hyperenhancement followed by mild and late washout as the CEUS criteria for identifying HCCs, the sensitivity and specificity were 52.6 and 95.3%, but unfortunately, the positive predictive value was only 82.0%. For the low-risk group, no further analysis was performed due to the small sample size.Initial clinical risk stratification followed by assessment of certain CEUS features appears to be a promising strategy for the accurate diagnosis of FLLs in patients not at high risk for HCC.

Numerous human tumors have been demonstrated to develop in a manner that is correlated with the S1P/S1P3 axis. However, it is yet unclear how this axis could affect the development of glioma, specifically TME cell invasion. We examined the clinicopathological data and gene expression data of gliomas to evaluate overall survival using univariate and multivariate Cox regression. By using Gene Set Enrichment Analysis, we investigated the signaling pathways and genes linked to S1P3 overexpression. We also examined the traits of biological pathways, TME immune cell infiltration, and oncogenic pathways (OP) in glioma samples with different S1P3 expression levels, and we validated the findings using PCR, CCK8, and wound healing assays. S1P3 overexpression was substantially linked with molecular typing and overall survival, according to Cox regression analysis. The Nomogram for predicting prognosis was successfully constructed by using S1P3 and other molecular signatures of gliomas, and Gene Set Enrichment Analysis revealed the relationship between S1P3 overexpression and DNA replication, cell cycle, MAPK, p53 and TGF-β signaling pathways. In addition, S1P3 was significantly correlated with many immune checkpoints and immune cell infiltration. Overall, S1P3 overexpression is a potential prognostic molecular marker for poor prognosis in glioma. Additionally, S1P3 acts as an important player in TME immune cell infiltration. The identification of S1P3-regulated signaling pathways and immune checkpoints strengthens our understanding of TME infiltration signatures and contributes to the development of immunotherapeutic strategies.

In health service and implementation research, randomised trials have been used to examine the delivery, organisation, quality, financing, and outcomes of health care services, policies and programmes. And there has been a growing emphasis on improving trial quality and efficiency; for example, funding bodies such as the National Institute of Health Research (NIHR) have been promoting efficient trial design and delivery over the last decade. However, there is a lack of agreement on what is meant by an efficient trial, and it is unclear what are the critical aspects that constitute trial efficiency. Agreeing on a clear definition of trial efficiency is fundamental in trial planning and execution. Being aware of critical attributes that impact trial efficiency allows trialists to prioritise the tasks on enhancing the efficiency of trial conduct, thereby improving the overall quality; Policy makers and funders will be able to detail the guidance on good trial practice and allocate research funding effectively to boost efficiency. In this project, we propose to employ the Delphi technique to achieve expert consensus on the definition and attributes of trial efficiency. The objectives are to 1) review and collate existing discussions on an efficient trial, including definitions of and attributes that constitute an efficient trial; 2)gain expert opinions on the definitions of trial efficiency and the essential aspects that comprise an efficient trial; 3) achieve consensus on what is meant by an efficient trial; 4)develop a conceptual framework for defining/explaining the trial efficiency. This is the final version of the e-Delphi protocol, published as a preprint to create full transparency about the research process.

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Emerging evidence suggests different intratumoral microbiome exists in different tumors and plays a crucial function in carcinogenesis. However, whether intratumoral microbiome in esophageal squamous cell carcinoma (ESCC) impacts clinical outcomes and its mechanism remains unclear. 16S rDNA amplicon sequencing was performed on surgical resected samples from 106 ESCC patients including 25 paired tumorous and non-tumorous tissues (NTs) to analyze intratumoral microbiome abundance and its composition. Multiplex fluorescent immunohistochemistry (mfIHC) staining was used to profile the phenotypes of immune infiltrates in tumor microenvironment (TME). Both Shannon index and operational taxonomic units (OTUs), representing alpha-diversity of microbiome, were found significantly lower in tumors comparing to the corresponding NTs. Multivariate analysis revealed that the intratumoral Shannon index, the relative abundance of Lactobacillus and the pTNM stage were independently associated with patients’ overall survival. Furthermore, the relative abundance of Lactobacillus and Shannon index were both positively correlated with the proportions of PD-L1+ epithelial cells (ECs) and tumor-associated macrophages (TAMs, and Shannon index was negatively correlated with the proportions of natural killer cells (NKs) and activated cytotoxic T cells (aCTLs) in TME, indicating an immunosuppressive microenvironment. These findings underscored for the first time that the high abundance of intratumoral Lactobacillus and microbiome alpha-diversity were associated with poor long-term survival of ESCC patients, which might be achieved by increasing PD-L1 + ECs and PD-L1 + TAMs and decreasing aCTLs and NKs in TME.

Morphology transformation and crystal growth strategies of metal oxide semiconductors are extensive studied in material science recently, because the morphology and crystallinity of the nanomaterial have significant effect on the physicochemical characteristics. However, understanding the morphology changes of α-MoO3 induced by annealing temperature is still a challenge. Herein, the nanostructure transition of MoO3 induced by calcined temperature has been investigated through XRD and SEM method. It can be found that crystallization is highly dependent on the annealing temperature. In addition, the MoO3 nanoflowers can change into nanosheets at 500 ºC. Afterwards, the nanosheets turn into microrods, especially at 900 ºC due to the growth of MoO3 crystal. On the other hand, MoO3 is a traditional sensing material, which is sensitive to many volatile organic compounds. Thus, the sensing performances of various MoO3 nanostructures were measured. Compared with MoO3 nanoflowers and microrods. The MoO3 nanosheets based sensor has excellent sensing performance towards ethanol, and the maximum gas response value is 8.06.

To enhance the friction and wear resistance of GCr15/PTFE sliding contact surfaces, the synergistic lubrication effect of micro-textures and solid lubricants were studied in this paper. Micro-textures were processed on GCr15 samples by Nd:YAG laser, which were filled with MoS2. Tribological performance tests were carried out on a Rtec-MFT 5000 tester. Tribological properties were optimal with the textures density of 20% and depth of 9 µm. A continuous composite solid lubricating film was formed by PTFE and MoS2. As load increases, friction coefficient of the sample shows a rapid decline and then stabilizes. With the increase of reciprocating frequency, friction curve of the sample shows a trend of slight fluctuation. When frequency is 2.7 Hz, friction coefficient is the lowest. Tribological properties of PTFE/GCr15 contact surfaces could be significantly optimized by micro-textures and MoS2, which performs favorable prospect of engineering application such as guide rails, bearings, machinery seal, etc.

Based on the ‘resource curse’ theory, this study uses panel data for 256 prefecture‐level cities in China from 2003 to 2016 to test the relationship and mechanism between natural resource dependence and economic development. The panel model and instrumental variable regression results show that natural resources generally promote economic development, but for 109 resource‐based cities, the influence of natural resources on economic development seems quite different. The panel threshold model shows that in the resource‐based cities, (i) resources have a ‘blessing effect’ on economic development during economic prosperity (GDP growth rate is greater than 12.1 per cent); (ii) the relationship is not statistically significant when the GDP growth rate is between 5 per cent and 12.1 per cent; and (iii) when the GDP growth rate is lower than 5 per cent, natural resources have a ‘curse effect’ on economic development. Furthermore, the results of the mediation effect model show that the mediation effect of industrial diversification on the relationship between resource dependence and economic development suppresses the promotion of natural resource on economy. An excessive concentration of resource industries has a crowding‐out effect on non‐resource industries in resource‐based cities, which reduces the level of industrial diversification and is not conducive to economic development.

The aim of this study was to test whether vitrification of sterlet Acipenser ruthenus and Russian sturgeon Acipenser gueldenstaedtii ovarian tissue through needle-immersed vitrification (NIV) is an efficient strategy for the preservation of oogonia (OOG) in order to supplement the current conservation efforts for these endangered fish species. Histological analyses of the gonads displayed that the ovaries of both species were immature and contained predominantly OOG and primary oocytes. The germline origin of these cells was verified by localization of the vasa protein through immunocytochemistry. NIV protocol was optimized by testing different equilibration (ES) and vitrification solutions (VS) containing various concentrations of dimethyl sulfoxide (Me

In order to investigate the characteristics of typical pesticide residues in farmland soil of different plant types in Shaya County and to evaluate the level of human health risk and ecological risk caused by pesticide residues, a total of 55 samples of plants, soil, and water from nine areas of Shaya county were collected on September 29, 2020. The occurrence levels of 47 typical pesticides in the samples were analyzed using gas chromatography-mass spectrometry (GC-MS). The results showed that a total of 23 pesticides were detected in three environmental media, and the maximum concentrations of pesticides in soil, plants, and water were 70.58 μg·kg

PIM1 has been shown to be associated with the development of multiple human cancers, but the biological mechanisms of PIM1 in glioma development, particularly the role of TME immune cell infiltration, remain unclear. We analyzed clinical information and gene expression data of all glioma samples and evaluated the relationship with overall survival by univariate and multivariate Cox regression. We also analyzed genes and downstream signaling pathways associated with PIM1 by gene set enrichment analysis. And we analyzed characterized oncogenic pathways, biological pathways, and TME immune cell infiltration in glioma samples with different PIM1 expressions, and validated it by in vitro experiments. The results of Cox regression analysis confirmed that overexpression of PIM1 was significantly associated with malignant progression and poorer survival of gliomas. Using PIM1 and other clinical features, we successfully constructed a nomogram to predict the prognosis of glioma, and Gene Set Enrichment Analysis revealed the association between PIM1 overexpression with cell cycle, cAMP signaling pathway, et al. Meanwhile, overexpression of PIM1 was significantly associated with increased expression of many immune checkpoints and immune cell infiltration. In conclusion, our study confirmed that overexpression of PIM1 is a potential molecular marker of poor prognosis in glioma and that PIM1 plays an important role in TME immune cell infiltration. By identifying PIM1-regulated signaling pathways and immune checkpoints enhances our understanding of the TME immune cell infiltration characteristics of glioma and contributes to the development of immunotherapeutic strategies.

A proper design and ingenious preparation of advanced nonnoble metal catalysts with high cost performance and durability for the oxygen reduction reaction (ORR) is in great demand and still full of great challenges. In this study, nickel–cobalt bimetallic nanoparticles uniformly embedded in nitrogen-doped carbon nanofibers (NiCo@NCNFs) were fabricated via a facile electrospinning technique, followed by a carbonization process. The Ni–Co nanoparticles are highly dispersed and uniformly embedded in highly conductive nitrogen-doped carbon fibers, providing a high specific surface area (640.8 m2 g−1), abundantly exposed active sites and easily accessible electronic channels, thus achieving high ORR performance. In particular, the optimized Ni0.5Co1@NCNF catalyst exhibits a high onset potential (Eonset = 0.90 V vs. RHE) and half-wave potential (E1/2 = 0.83 V vs. RHE) in an alkaline medium. Moreover, it possessed an extraordinary long-term stability and methanol tolerance in comparison to a commercial 20% Pt/C catalyst. This simple and cost-effective strategy provides a basis for the large-scale production of highly efficient catalysts that are used in numerous renewable energy systems.

An electromechanical coupling model for the thickness shear vibration of a size dependent quartz crystal plate with mass loading is established from the Hamilton’s principle and the modified couple...

Cholesteric liquid crystals with selective reflection have important applications in the field of light control and optical thin films. In this study, a series of side-chain cholesteric liquid-crys...

Neurotransmitters are essential chemical mediators for neuronal communication in variable neuromodulations. However, the progress of neuroscience is hampered by the shortage of suitable sensors to track neurotransmitters with high spatial and temporal resolution. Here, we introduce a self-assembled DNA-nanoprism fluorescent probe capable of nongenetically engineering the cell surface for ultrasensitive imaging of the neurotransmitter release at a single live-cell level. The DNA-nanoprism structure conjugated with three cholesterol tails enables the probe to rapidly and stably anchor on the cell surface within 10 min. The in situ detection of neurotransmitters is achieved by equipping the DNA-nanoprism with an aptamer-based "turn-on" fluorescent sensory module for the transmitter of interest. In a proof-of-concept study, we directly visualized the transient dopamine (DA) release on the cell surface with selective responsivity and high spatiotemporal precision and further explored the dynamic correlation between DA release and calcium influx triggered by high K+. This study provides a robust and sensitive tool for cell-surface-targeted imaging of neuromodulations, which might open up a new avenue to improve the understanding of neurochemistry and advance neuroscience research.

Relevant fundamentals of the electrochemical double layer and supercapacitors utilizing the interfacial capacitance as well as superficial redox processes at the electrode/solution interface are briefly reviewed. Experimental methods for the determination of the capacity of electrochemical double layers, of charge storage electrode materials for supercapacitors, and of supercapacitors are discussed and compared. Intrinsic limitations and pitfalls are indicated; popular errors, misconceptions, and mistakes are evaluated. The suitability of available methods is discussed, and practical recommendations are provided.

Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg·kg(−1) ·d(−1), ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARα/PPARγ coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor α, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 μM), which was attenuated by co-treatemnt with puerarin (100 μM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARα antagonist GW6471 (10 μM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARα/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.

In this article, proposed is a hysteresis effects model of a bimorph circular flexural-mode piezoelectric actuator for a deformable mirror of adaptive optics system. The analytical solutions are derived from the three-dimensional equations of piezoelectricity, and the dependence of the nonlinear hysteresis performance of the actuator on the physical parameters is evaluated. Numerical results illustrate that the hysteresis loops of the strokes of the actuator are affected by the start values of the electric field and the thickness of the metallic layer. Besides, the results also suggest that an appropriate thickness of metallic layer could compensate some hysteresis effects. Moreover, the results of the analytical method have been demonstrated by those of the finite element method.

Novel Fe3C nanoparticles that decorate three-dimensional N-rich porous carbon (Fe3C@3DNC) catalysts were designed and synthesized by double templates assisted high-energy ball milling and subsequent high-temperature pyrolysis for the oxygen reduction reaction (ORR). NaCl and Na2SiO3 are used as the mixed template while Fe(NO3)3·9H2O and 2-Methylimidazole were used as the iron, nitrogen and carbon sources. The optimized Fe3C@3DNC catalyst (Fe3C@3DNC-1-900) had good ORR performance in alkaline medium, with an Eonest value of 0.968 V and E1/2 value of 0.861. In addition, the catalytic process exhibited selectivity–nearly four-electron transfer kinetics and possesses a lower Tafel slope compared to commercial Pt/C catalyst as well as good methanol tolerance. In addition, the Fe3C@3DNC-1-900 catalyst also had excellent ORR activity (E1/2 = 0.72 V) and long-term stability (the half-wave potential only occurs at 10 mV after 5000 cycles) in acidic media. The good catalytic performance of the Fe3C@3DNC-1-900 catalyst can be attributed to the 3D hierarchically porous structure and extremely high number of active sites around the porous carbon. The double template assisted high-energy ball milling strategy can be a promising and scalable method to prepare three-dimensional porous carbon-based composite materials for energy conversion and storage applications.

This article aims to investigate tribological properties of a surface modified by laser texturing under full oil lubrication as well as the effect of laser texturing on the abrasion resistance prop...

Aim and Objective: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common chronic kidney disease that leads to End-Stage Renal Disease (ESRD). The key target of this therapy is to prevent the progression of kidney failure. Tolvaptan could slow kidney cyst growth and are proven highly effective. The aims of this analysis are to perform a systematic review, estimate and evaluate the efficacy and safety of tolvaptan in ADPKD patients. Materials and Methods: Randomized controlled trials of tolvaptan in ADPKD were identified in PubMed, Ovid, Web of Science and the Cochrane Library electronic database. The changes observed in kidney function, treatment efficiency and the incidence of adverse events between the tolvaptan and placebo groups were compared. Data were analyzed by the RevMan software. Results: Eight trials, including 7 double-blinded randomised controlled trials and 1 quasi RCT involving 1,536 patients were extracted. Significant differences in the annual rate of change in the total kidney volume TKV at any stages of CKD (MD = -3.32, 95%CI =-4.57,-2.07, I2 =70%) and the glomerular filtration rate (MD = 1.4, 95%CI = 0.83,1.97, I2 =0%) were observed between the tolvaptan group and the placebo group. Subgroup analysis of patients in different CKD stages also showed the same conclusion. There was an increase in the urine osmolality, and 24-hour urine volume in patients receiving tolvaptan. Tolvaptan reduced the rate of serious hypertension and kidney pain events in ADPKD patients. At higher doses, it increased the rate of adverse events (liver injuries, thirst, pollakiuria, and nocturia). There was no significant risk of bias in the included studies. Conclusions: Tolvaptan has a beneficial effect on ADPKD, but is associated with an increase in adverse events at high doses when compared with the placebo. Further RCTs on tolvaptan may be required to support this conclusion.

The S1P/S1PR3 axis has been demonstrated to be associated with the development of a variety of human cancers. Still, the potential role of this axis in the biological mechanisms of glioma, particularly TME cell infiltration, remains unknown. We analyzed gene expression data of gliomas and corresponding clinicopathological information to assess overall survival by univariate and multivariate Cox regression. We also examined the signaling pathways and genes associated with S1PR3 overexpression by Gene Set Enrichment Analysis, and analyzed the characteristics of oncogenic pathways (OP), biological pathways, and TME immune cell infiltration in glioma samples with different S1PR3 expressions, and validated the results with PCR, cell proliferation, and migration assays. Cox regression analysis confirmed that S1PR3 overexpression was significantly correlated with overall survival and clinicopathological features. Nomogram for prognostic prediction was successfully constructed using S1PR3 and related genes, and Gene Set Enrichment Analysis revealed the association of S1PR3 overexpression with cell cycle, DNA replication, MAPK, p53 and TGF-β signaling pathway. Meanwhile, S1PR3 was significantly associated with many immune checkpoints and immune cell infiltration. In conclusion, S1PR3 overexpression is a potential prognostic molecular marker for poor prognosis in glioma. In addition, S1PR3 plays an important role in immune cell infiltration in TME. And identification of S1PR3-regulated signaling pathways and immune checkpoints enhances our understanding of TME infiltration characteristics, and contributes to the development of immunotherapeutic strategies.

Based on the fluorescence resonance energy transfer (FRET), a ratiometric fluorescent probe (NQ) was successfully designed and synthesized, in which quinolinone moiety was selected as the energy donor and naphthalimide block as the energy acceptor. NQ has a super large Stokes shift (231 nm) and a big quantum yield (0.463). Compared with previously reported probes with similar recognition sites, NQ can high sensitively and selectively recognize ClO

A central challenge in genetics, evolutionary biology and biotechnology is to understand and predict how mutations combine to alter phenotypes, including molecular activities, fitness and disease. In diploid organisms, two mutations in the same gene can either combine on the same chromosome or on different chromosomes, with interactions between the mutations quantified as epistasis and dominance, respectively. However, a direct comparison of the extent, sign and stability of interactions within and between alleles is lacking. Here we show that, even in the simplest biophysical systems, interactions between mutations are frequent, context-dependent and different when variants are combined within and between alleles. Whereas protein folding alone generates epistasis, the addition of a single molecular interaction is sufficient to cause dominance. Epistasis and dominance interactions change quantitatively, qualitatively and differently as a system becomes more complicated or the conditions change. Altering the concentration of a ligand can, for example, switch an allele from dominant to recessive. Our results show that epistasis and dominance should be widely expected in even the simplest biological systems but also reinforce the view that they are plastic system properties and so a formidable challenge to predict. Accurate prediction of epistasis and dominance will require either detailed mechanistic understanding and experimental parameterization or brute-force measurement and learning.