Oncogenic Signaling Pathways in The Cancer Genome Atlas.

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFß signaling, p53 and ß-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy.

An evolutionary continuum from nucleated dwarf galaxies to star clusters.

Systematic studies1-4 have revealed hundreds of ultra-compact dwarf galaxies (UCDs5) in the nearby Universe. With half-light radii rh of approximately 10-100 parsecs and stellar masses M* ≈ 106-108 solar masses, UCDs are among the densest known stellar systems6. Although similar in appearance to massive globular clusters7, the detection of extended stellar envelopes4,8,9, complex star formation histories10, elevated mass-to-light ratio11,12 and supermassive black holes13-16 suggest that some UCDs are remnant nuclear star clusters17 of tidally stripped dwarf galaxies18,19, or even ancient compact galaxies20. However, only a few objects have been found in the transient stage of tidal stripping21,22, and this assumed evolutionary path19 has never been fully traced by observations. Here we show that 106 galaxies in the Virgo cluster have morphologies that are intermediate between normal, nucleated dwarf galaxies and single-component UCDs, revealing a continuum that fully maps this morphological transition and fills the 'size gap' between star clusters and galaxies. Their spatial distribution and redder colour are also consistent with stripped satellite galaxies on their first few pericentric passages around massive galaxies23. The 'ultra-diffuse' tidal features around several of these galaxies directly show how UCDs are forming through tidal stripping and that this evolutionary path can include an early phase as a nucleated ultra-diffuse galaxy24,25. These UCDs represent substantial visible fossil remnants of ancient dwarf galaxies in galaxy clusters, and more low-mass remnants probably remain to be found.

Searching across-cohort relatives in 54,092 GWAS samples via encrypted genotype regression.

Explicitly sharing individual level data in genomics studies has many merits comparing to sharing summary statistics, including more strict QCs, common statistical analyses, relative identification and improved statistical power in GWAS, but it is hampered by privacy or ethical constraints. In this study, we developed encG-reg, a regression approach that can detect relatives of various degrees based on encrypted genomic data, which is immune of ethical constraints. The encryption properties of encG-reg are based on the random matrix theory by masking the original genotypic matrix without sacrificing precision of individual-level genotype data. We established a connection between the dimension of a random matrix, which masked genotype matrices, and the required precision of a study for encrypted genotype data. encG-reg has false positive and false negative rates equivalent to sharing original individual level data, and is computationally efficient when searching relatives. We split the UK Biobank into their respective centers, and then encrypted the genotype data. We observed that the relatives estimated using encG-reg was equivalently accurate with the estimation by KING, which is a widely used software but requires original genotype data. In a more complex application, we launched a finely devised multi-center collaboration across 5 research institutes in China, covering 9 cohorts of 54,092 GWAS samples. encG-reg again identified true relatives existing across the cohorts with even different ethnic backgrounds and genotypic qualities. Our study clearly demonstrates that encrypted genomic data can be used for data sharing without loss of information or data sharing barrier.

Spem2, a novel testis-enriched gene, is required for spermiogenesis and fertilization in mice.

Spermiogenesis is considered to be crucial for the production of haploid spermatozoa with normal morphology, structure and function, but the mechanisms underlying this process remain largely unclear. Here, we demonstrate that SPEM family member 2 (Spem2), as a novel testis-enriched gene, is essential for spermiogenesis and male fertility. Spem2 is predominantly expressed in the haploid male germ cells and is highly conserved across mammals. Mice deficient for Spem2 develop male infertility associated with spermiogenesis impairment. Specifically, the insufficient sperm individualization, failure of excess cytoplasm shedding, and defects in acrosome formation are evident in Spem2-null sperm. Sperm counts and motility are also significantly reduced compared to controls. In vivo fertilization assays have shown that Spem2-null sperm are unable to fertilize oocytes, possibly due to their impaired ability to migrate from the uterus into the oviduct. However, the infertility of Spem2-/- males cannot be rescued by in vitro fertilization, suggesting that defective sperm-egg interaction may also be a contributing factor. Furthermore, SPEM2 is detected to interact with ZPBP, PRSS21, PRSS54, PRSS55, ADAM2 and ADAM3 and is also required for their processing and maturation in epididymal sperm. Our findings establish SPEM2 as an essential regulator of spermiogenesis and fertilization in mice, possibly in mammals including humans. Understanding the molecular role of SPEM2 could provide new insights into future therapeutic treatment of human male infertility and development of non-hormonal male contraceptives.

Optical Fiber Surface Plasmon Resonance Sensor for Glyceryl Tributyrate Detection Based on the PAA/CS Composite Hydrogel Embedding Protease Method.

Glycerol tributyrate as a low-density lipoprotein plays a crucial role in drug development and food safety. In this work, a novel high-stability fiber optic sensor for glyceryl tributyrate based on the poly(acrylic acid) (PAA) and chitosan (CS) composite hydrogel embedding method is first proposed. Compared with traditional functionalization, the lipase in a polymer network structure used in this article can not only avoid chemical reactions that cause damage to the enzyme structure but also avoid the instability of ionic bonds and physical adsorption. Therefore, the PAA/CS hydrogel method proposed in this article can effectively retain enzyme structure. First, the impact of different layers (one to five layers) of PAA/CS on pH sensing performance was explored, and it was determined that layers 1-3 could be used for subsequent sensing experiments. Within the linear detection range of 0.5-10 mM, the detection sensitivities of the one to three layers of the biosensor are divided into 0.65, 0.95, and 1.51 nm/mM, respectively, with the three layers having the best effect. When the number of coating layers is three, the detection limit of the sensor is 0.47 mM, meeting the millimole level detection standard for anticancer requirement. Furthermore, the stability and selectivity of the sensor (in the presence of hemoglobin, urea, cholesterol, acetylcholine, and glucose) were analyzed. The three-layer sensor is used for sample detection. At concentrations of 1-10 mM, the absolute value of the recovery percentage (%) is 82-99%, which can accurately detect samples. The sensor proposed in this paper has the advantages of low sample consumption, high sensitivity, simple structure, and label-free measurement. The enzyme-embedding method provides a new route for rapid and reliable glyceryl tributyrate detection, which has potential applications in food safety as well as the development of anticancer drugs.

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

Over 104 -fold amplified upconversion luminescence of lanthanide nanocrystals through optical oscillator-like system.

Recently, lanthanide (Ln) luminescent nanocrystals have attracted increasing attention in various fields such as biomedical imaging, lasers, and anticounterfeiting. However, due to the forbidden 4f-4f transition of lanthanide ions, the absorption cross-section and luminescence brightness of lanthanide nanocrystals are limited. To address the challenge, we constructed an optical oscillator-like system to repeatedly simulate lanthanide nanocrystals to enhance the absorption efficiency of lanthanide ions on excitation photons. In this optical system, the upconversion luminescence (UCL) of Tm3+ emission of ~450 nm excited by a 980 nm laser can be amplified by a factor beyond 104 . The corresponding downshifting luminescence of Tm3+ at 1460 nm was enhanced by three orders of magnitude. We also demonstrated that the significant luminescence enhancement in the designed optical oscillator-like system was general for various lanthanide nanocrystals including NaYF4 :Yb3+ /Ln3+ , NaErF4 @NaYF4 and NaYF4 :Yb3+ /Ln3+ @NaYF4 :Yb3+ @NaYF4 (Ln = Er, Tm, Ho) regardless of the wavelengths of excitation sources (808 and 980 nm). The mechanism study revealed that both elevated laser power in the optical system and multiple excitations on lanthanide nanocrystals were the main reason for the luminescence amplification. Our findings may benefit the future development of low-threshold upconversion and downshifting luminescence of lanthanide nanocrystals and expand their applications.

Dissecting the PRSS37 interactome and potential mechanisms leading to ADAM3 loss in PRSS37-null sperm.

A disintegrin and metalloproteinase 3 (ADAM3) is a sperm membrane protein critical for sperm migration from the uterus into the oviduct and sperm-egg binding in mice. Disruption of PRSS37 results in male infertility concurrent with the absence of mature ADAM3 from cauda epididymal sperm. However, how PRSS37 modulates ADAM3 maturation remains largely unclear. Here, we determine the PRSS37 interactome by GFP immunoprecipitation coupled with mass spectrometry in PRSS37-EGFP knock-in mice. Three molecular chaperones (CLGN, CALR3 and PDILT) and three ADAM proteins (ADAM2, ADAM6B and ADAM4) were identified to be interacting with PRSS37. Coincidently, five of them (except ADAM4) have been reported to interact with ADAM3 precursor and regulate its maturation. We further demonstrated that PRSS37 also interacts directly with ADAM3 precursor and its deficiency impedes the association between PDILT and ADAM3. This could contribute to improper translocation of ADAM3 to the germ cell surface, leading to ADAM3 loss in PRSS37-null mature sperm. The understanding of the maturation mechanisms of pivotal sperm plasma membrane proteins will pave the way toward novel strategies for contraception and the treatment of unexplained male infertility.

Type I/type III IFN and related factors regulate JEV infection and BBB endothelial integrity.

BACKGROUND: Japanese encephalitis virus (JEV) remains a predominant cause of Japanese encephalitis (JE) globally. Its infection is usually accompanied by disrupted blood‒brain barrier (BBB) integrity and central nervous system (CNS) inflammation in a poorly understood pathogenesis. Productive JEV infection in brain microvascular endothelial cells (BMECs) is considered the initial event of the virus in penetrating the BBB. Type I/III IFN and related factors have been described as negative regulators in CNS inflammation, whereas their role in JE remains ambiguous. METHODS: RNA-sequencing profiling (RNA-seq), real-time quantitative PCR, enzyme-linked immunosorbent assay, and Western blotting analysis were performed to analyze the gene and protein expression changes between mock- and JEV-infected hBMECs. Bioinformatic tools were used to cluster altered signaling pathway members during JEV infection. The shRNA-mediated immune factor-knockdown hBMECs and the in vitro transwell BBB model were utilized to explore the interrelation between immune factors, as well as between immune factors and BBB endothelial integrity. RESULTS: RNA-Seq data of JEV-infected hBMECs identified 417, 1256, and 2748 differentially expressed genes (DEGs) at 12, 36, and 72 h post-infection (hpi), respectively. The altered genes clustered into distinct pathways in gene ontology (GO) terms and KEGG pathway enrichment analysis, including host antiviral immune defense and endothelial cell leakage. Further investigation revealed that pattern-recognition receptors (PRRs, including TLR3, RIG-I, and MDA5) sensed JEV and initiated IRF/IFN signaling. IFNs triggered the expression of interferon-induced proteins with tetratricopeptide repeats (IFITs) via the JAK/STAT pathway. Distinct PRRs exert different functions in barrier homeostasis, while treatment with IFN (IFN-ß and IFN-λ1) in hBMECs stabilizes the endothelial barrier by alleviating exogenous destruction. Despite the complex interrelationship, IFITs are considered nonessential in the IFN-mediated maintenance of hBMEC barrier integrity. CONCLUSIONS: This research provided the first comprehensive description of the molecular mechanisms of host‒pathogen interplay in hBMECs responding to JEV invasion, in which type I/III IFN and related factors strongly correlated with regulating the hBMEC barrier and restricting JEV infection. This might help with developing an attractive therapeutic strategy in JE.

Effect of volatile compounds produced by the cotton endophytic bacterial strain Bacillus sp. T6 against Verticillium wilt.

BACKGROUND: Verticillium wilt, caused by the fungus Verticillium dahliae, leads to significant losses in cotton yield worldwide. Biocontrol management is a promising means of suppressing verticillium wilt. The purpose of the study was to obtain and analyze endophytic bacteria with Verticillium wilt-resistant activities from the roots of Gossypium barbadense 'Xinhai15' and to explore the interactions between the soil and plants. RESULTS: An endophytic bacterium Bacillus sp. T6 was obtained from the Verticillium wilt-resistant cotton G. barbadense 'Xinhai15', which showed significant antagonistic abilities against cotton Verticillium wilt. The bioassay results indicated that the strain possessed strong antagonistic abilities that inhibited V. dahliae spore germination and mycelial growth without contact, and thus it was speculated that the active factor of the bacteria might be volatile compounds. A total of 46 volatile substances were detected via headspace solid-phase microextraction and gas chromatography-mass spectrometry analysis. The pure product verification experiment confirmed that the styrene produced by the T6 strain was the main virulence factor. Transcriptome analysis showed that following styrene induction, 247 genes in V. dahliae, including four hydrolase genes, eight dehydrogenase genes, 11 reductase genes, 17 genes related to transport and transfer were upregulated. Additionally, 72 genes, including two chitinase genes, two protease genes, five transport-related genes, and 33 hypothetical protein genes, were downregulated. The quantitative real-time PCR results confirmed that the expression of the four genes VDAG_02838, VDAG_09554, VDAG_045572, and VDAG_08251 was increased by 3.18, 78.83, 2.71, and 2.92 times, respectively, compared with the uninduced control group. CONCLUSIONS: The research provides a new reference for the development and application of the volatile compounds of endophytic bacteria as new biocontrol agents for the control of Verticillium wilt and as biological preservatives for agricultural products.

Structure optimization of heterogeneous compound eye camera for improving the detection performance.

To achieve fast location, precise tracking and accurate identification over a large field of view (FOV), we have proposed a heterogeneous compound eye camera (HeCECam), which consists of a heterogeneous compound eye array, an optical relay system and a CMOS detector. However, the current HeCECam can hardly acquire high-precision 3D information of the targets to realize these applications. To solve this challenge, we propose a scheme on optimizing the structure of the HeCECam to improving the detection performance, including the optimization of the distribution uniformity of the sub-eyes with the proposed "Three-direction center-of-gravity subdivision (TGS)" and the enhancement of the compatibility between heterogeneous compound eyes and the optical relay system with the proposed compensation method for tilt. The TGS significantly reduces the distribution unevenness of sub-eyes down to 117% from the previous 152%, and provides symmetry to the heterogeneous compound eye array. The tilt compensation effectively addresses previous imaging defects, such as distortion of sub-images, increased stray light, and support structures being imaged, and it improves the imaging clarity of the system, especially in external FOV. Based on two proposed methods, we re-design and fabricate the heterogeneous compound eye array to obtain a high-performance prototype. To verify the imaging capacities of the optimized HeCECam, a series of comparison experiments are performed, including blank scene imaging, FOV tests, resolution verification and real-world scene imaging. The results show that the previous imaging defects have been well eliminated, and the optimized prototype has stronger resolving power and wider FOV. This allow the HeCECam to perform better in subsequent practical applications, such as wide-area surveillance, forewarning, and navigation.

U-fiber-based biosensor for temperature-compensated acetylcholine-specific measurement.

This paper presents a U-fiber-based biosensor to achieve temperature-compensated acetylcholine-specific measurement. The surface plasmon resonance (SPR) and multimode interference (MMI) effects are simultaneously realized in a U-shaped fiber structure for the first time, to the best of our knowledge. The experimental results show refractive index (RI) sensitivities of 3042 and 2958 nm/RIU and temperature sensitivities of -0.47 and -0.40 nm/°C for the MMI and SPR, which are greatly improved compared with the traditional structure. Simultaneously, a sensitivity matrix for detecting two parameters is introduced to solve the problem of temperature interference of biosensors based on RI changes. Label-free detection of acetylcholine (ACh) was achieved by immobilizing acetylcholinesterase (AChE) on optical fibers. The experimental results show that the sensor can realize the specific detection of acetylcholine and has good stability and selectivity, and the detection limit of the sensor is 30 nM. The sensor has the advantages of simple structure, high sensitivity, convenient operation, direct insertion into small spaces, temperature compensation, etc., which provide an important supplement to traditional fiber-optic SPR biosensors.

COVID-19 victimization experience and university students' smartphone addiction: the mediating role of emotional intelligence.

OBJECTIVES: During the post-COVID-19 era, everyone has the risk of contracting the virus and becoming the victims of COVID-19. Examining the relationship between the COVID-19 victimization experience and its effects is more urgent. The aim of present study is to propose a mediation model to investigate the association between COVID-19 victimization experience and smartphone addiction, and the mediating role of emotional intelligence. METHODS: A online questionnaire including the COVID-19 Victimization Experience Scale, the Smartphone Addiction Scale, and the Emotional Intelligence Scale among Chinese university students, were employed in this study. Finally, 1154 valid questionnaires were collected. The reliability and confirmatory factor analysis results showed that all three scales had good reliability and validity. RESULTS: Structural Equation Model (SEM) demonstrated that COVID-19 victimization experience significantly predicted smartphone addiction in university students, and emotional intelligence partially mediated the association between COVID-19 victimization experience and smartphone addiction. Bootstrap results furthermore tested the rigor of the mediating effect. CONCLUSION: COVID-19 victimization experience was a important variables in predicting university students's martphone addiction, and emotional intelligence was a protective factor in decreasing the negative effect of COVID-19 victimization experience on addictive behaviors. It is suggested that instructors should integrate emotional intelligence training programs into mental health courses so as to improve students' emotional intelligence ability.

Development process and clinical application of collagenase chemonucleolysis in the treatment of lumbar disc herniation: a narrative review in China.

Lumbar disc herniation (LDH) is one of the most common causes of lumbocrural pain. In the past 20 years, the incidence of LDH has increased dramatically. There are many treatments for LDH, including conservative treatment (such as acupuncture and physiotherapy), minimally invasive interventional treatment (such as collagenase chemonucleolysis and radiofrequency ablation) and surgical treatment. The main purpose of this paper is to review the development process and application status of collagenase chemonucleolysis in the treatment of LDH at home and abroad and provide a reference for clinical treatment.

Development process and clinical application of collagenase chemonucleolysis in the treatment of lumbar disc herniation: a narrative review in China.

Lumbar disc herniation (LDH) is one of the most common causes of lumbocrural pain. In the past 20 years, the incidence of LDH has increased dramatically. There are many treatments for LDH, including conservative treatment (such as acupuncture and physiotherapy), minimally invasive interventional treatment (such as collagenase chemonucleolysis and radiofrequency ablation) and surgical treatment. The main purpose of this paper is to review the development process and application status of collagenase chemonucleolysis in the treatment of LDH at home and abroad and provide a reference for clinical treatment.

Quaternion Wavelet Transform and a Feedforward Neural Network-Aided Intelligent Distributed Optical Fiber Sensing System.

In this paper, aiming at a large infrastructure structural health monitoring network, a quaternion wavelet transform (QWT) image denoising algorithm is proposed to process original data, and a depth feedforward neural network (FNN) is introduced to extract physical information from the denoised data. A Brillouin optical time domain analysis (BOTDA)-distributed sensor system is established, and a QWT denoising algorithm and a temperature extraction scheme using FNN are demonstrated. The results indicate that when the frequency interval is less than 4 MHz, the temperature error is kept within ±0.11 °C, but is ±0.15 °C at 6 MHz. It takes less than 17 s to extract the temperature distribution from the FNN. Moreover, input vectors for the Brillouin gain spectrum with a frequency interval of no more than 6 MHZ are unified into 200 input elements by linear interpolation. We hope that with the progress in technology and algorithm optimization, the FNN information extraction and QWT denoising technology will play an important role in distributed optical fiber sensor networks for real-time monitoring of large-scale infrastructure.

Characterization of sonicated gluten protein and subsequent rheological properties of model dough and noodles.

BACKGROUND: The present study aimed to investigate the effects of the thermo-mechanical and rheological properties of a wheat gluten-sonicated model dough and noodles, as well as the effects of ultrasonic frequency (20, 28, 40, 68 and 80 kHz) on the functional properties and structural features of gluten. RESULTS: Water absorption, stability and developmental time, and viscoelastic behavior of gluten-sonicated model dough were all found to be improved. Water absorption, tensile resistance and stretching distance of noodles increased markedly, whereas cooking loss decreased. Ultrasonication at different frequencies also significantly affected gluten structure, including its surface hydrophobicity, micro-network structure, and secondary and tertiary structures. These alterations then caused changes in its functional characteristics. Compared to untreated gluten, sonicated gluten exhibited significantly increased oil and water capacities (8.75-15.26% and 100.65-127.71% higher than the untreated gluten, respectively), foaming and emulsifying properties, and increased solubility (63.46-98.83% higher than control). In addition, these findings indicated that 40 kHz was the likely resonance frequency of the cavitation bubble in the gluten solution. However, sodium dodecyl sulfate-polyacrylamide gel electrophoresis electropherograms revealed that such treatments did not affect the molecular weight of gluten, which was also consistent with its unchanged disulfide bond content. CONCLUSION: The present study clarified the impact of frequency on the properties of gluten and model dough. The best frequency for modification of gluten was 40 kHz. Collectively, these findings suggest that ultrasonic technology has the potential for use in modifying wheat gluten and commercial noodle processing. © 2022 Society of Chemical Industry.

Efficient Attack Scheme against SKINNY-64 Based on Algebraic Fault Analysis.

Lightweight block ciphers are normally used in low-power resource-constrained environments, while providing reliable and sufficient security. Therefore, it is important to study the security and reliability of lightweight block ciphers. SKINNY is a new lightweight tweakable block cipher. In this paper, we present an efficient attack scheme for SKINNY-64 based on algebraic fault analysis. The optimal fault injection location is given by analyzing the diffusion of a single-bit fault at different locations during the encryption process. At the same time, by combining the algebraic fault analysis method based on S-box decomposition, the master key can be recovered in an average time of 9 s using one fault. To the best of our knowledge, our proposed attack scheme requires fewer faults, is faster to solve, and has a higher success rate than other existing attack methods.

Hybrid Threshold Denoising Framework Using Singular Value Decomposition for Side-Channel Analysis Preprocessing.

The traces used in side-channel analysis are essential to breaking the key of encryption and the signal quality greatly affects the correct rate of key guessing. Therefore, the preprocessing of side-channel traces plays an important role in side-channel analysis. The process of side-channel leakage signal acquisition is usually affected by internal circuit noise, external environmental noise, and other factors, so the collected signal is often mixed with strong noise. In order to extract the feature information of side-channel signals from very low signal-to-noise ratio traces, a hybrid threshold denoising framework using singular value decomposition is proposed for side-channel analysis preprocessing. This framework is based on singular value decomposition and introduces low-rank matrix approximation theory to improve the rank selection methods of singular value decomposition. This paper combines the hard threshold method of truncated singular value decomposition with the soft threshold method of singular value shrinkage damping and proposes a hybrid threshold denoising framework using singular value decomposition for the data preprocessing step of side-channel analysis as a general preprocessing method for non-profiled side-channel analysis. The data used in the experimental evaluation are from the raw traces of the public database of DPA contest V2 and AES_HD. The success rate curve of non-profiled side-channel analysis further confirms the effectiveness of the proposed framework. Moreover, the signal-to-noise ratio of traces is significantly improved after preprocessing, and the correlation with the correct key is also significantly enhanced. Experimental results on DPA v2 and AES_HD show that the proposed noise reduction framework can be effectively applied to the side-channel analysis preprocessing step, and can successfully improve the signal-to-noise ratio of the traces and the attack efficiency.

Noninvasive Early Diagnosis of Allograft Rejection by a Granzyme B Protease Responsive NIR-II Bioimaging Nanosensor.

Early diagnosis of allograft rejection helps to improve the immune-related management of transplant recipients. The clinically-used core needle biopsy method is invasive and subject to sampling error. In vivo fluorescence imaging for monitoring immune-related processes has the advantages of non-invasiveness, fast feedback and high sensitivity. Herein, we report a responsive second near-infrared (NIR-II) fluorescent nanosensor (ErGZ) to detect early allograft rejection. ErGZ allows ratiometric in vivo fluorescence sensing of granzyme B, which is overexpressed in recipients' T cells during the onset of rejection. The sensor demonstrates efficacious detection of allograft rejection with high sensitivity and specificity, which accomplishes non-invasive diagnosis of rejection in skin and deep buried islets transplant mice models 2 d and 5 d earlier than biopsy, by in vivo fluorescence imaging and urinary detection, respectively, providing a valuable approach for therapeutical management.