PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371.

Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. FMS-like tyrosine kinase receptor-3 (FLT3) is one of the major oncogenic receptor tyrosine kinases aberrantly activated in AML. Although protein tyrosine phosphatase PRL2 is highly expressed in some subtypes of AML compared with normal human hematopoietic stem and progenitor cells, the mechanisms by which PRL2 promotes leukemogenesis are largely unknown. We discovered that genetic and pharmacological inhibition of PRL2 significantly reduce the burden of FLT3-internal tandem duplications-driven leukemia and extend the survival of leukemic mice. Furthermore, we found that PRL2 enhances oncogenic FLT3 signaling in leukemia cells, promoting their proliferation and survival. Mechanistically, PRL2 dephosphorylates the E3 ubiquitin ligase CBL at tyrosine 371 and attenuates CBL-mediated ubiquitination and degradation of FLT3, leading to enhanced FLT3 signaling in leukemia cells. Thus, our study reveals that PRL2 enhances oncogenic FLT3 signaling in leukemia cells through dephosphorylation of CBL and will likely establish PRL2 as a novel druggable target for AML.

Emerging potentials of Fe-based nanomaterials for chiral sensing and imaging.

Fe-based nanostructures have possessed promising properties that make it suitable for chiral sensing and imaging applications owing to their ultra-small size, non-toxicity, biocompatibility, excellent photostability, tunable fluorescence, and water solubility. This review summarizes the recent research progress in the field of Fe-based nanostructures and places special emphases on their applications in chiral sensing and imaging. The synthetic strategies to prepare the targeted Fe-based structures were also introduced. The chiral sensing and imaging applications of the nanostructures are discussed in details.

Interface-Engineered 2D Heterojunction with Photoelectric Dual Gain: Mxene@MOF-Enhanced SPR Spectroscopy for Direct Sensing of Exosomes.

MXene is widely used in the construction of optoelectronic interfaces due to its excellent properties. However, the hydrophilicity and metastable surface of MXene lead to its oxidation behavior, resulting in the degradation of its various properties, which seriously limits its practical application. In this work, a 2D metal-organic framework (2D MOF) with matching 2D morphology, excellent stability performance, and outstanding optoelectronic performance is grown in situ on the MXene surface through heterojunction engineering to suppress the direct contact between reactive molecules and the inner layer material without affecting the original advantages of MXene. The photoelectric dual gain MXene@MOF heterojunction is confirmed. As a photoelectric material, its properties are highly suitable for the demand of interface sensitization layer materials of surface plasmon resonance (SPR). Therefore, using SPR as a platform for the application of this interface material, the performance of MXene@MOF and its potential mechanism to enhance SPR are analyzed in depth using experiments combined with simulation calculations (FDTD/DFT). Finally, the MXene@MOF/peptides-SPR sensor is constructed for rapid and sensitive detection of the cancer marker exosomes to explore its potential in practical applications. This work offers a forward-looking strategy for the design of interface materials with excellent photoelectric performance.

2D MOF-enhanced SPR detector based on tunable supramolecular probes for direct and sensitive detection of DOX in serum.

Therapeutic drug monitoring of doxorubicin (DOX) is important to study pharmacokinetics in patients undergoing chemotherapy for reduction of side effects and improve patient survival by rationally controlling the dose of DOX. A fast and ultra-sensitive surface plasmon resonance (SPR) detector without sample pre-handling was developed for DOX monitoring. First, the two-dimensional metal-organic framework was modified on the Au film to enhance SPR, and then, the supramolecular probes with tunable cavity structure were self-assembled at the sensing interface for direct detection of DOX through specific host-guest interactions with a low detection limit of 60.24 pM. The precise monitoring of DOX in serum proved the possibility of clinical application with recoveries in the range 102.86-109.47%. The mechanisms of host-guest interactions between supramolecular and small-molecule drugs were explored in depth through first-principles calculations combined with SPR experiments. The study paves the way for designing facile and sensitive detectors and provides theoretical support and a new methodology for the specific detection of small molecules through calixarene cavity modulation.

Ultrasensitive electrochemical sensor based on synergistic effect of Ag@MXene and antifouling cyclic multifunctional peptide for PD-L1 detection in serum.

A sensing interface co-constructed from the two-dimensional conductive material (Ag@MXene) and an antifouling cyclic multifunctional peptide (CP) is described. While the large surface area of Ag@MXene loads more CP probes, CP binds to Ag@MXene to form a fouling barrier and ensure the structural rigidity of the targeting sequence. This strategy synergistically enhances the biosensor's sensitivity and resistance to contamination. The SPR results showed that the binding affinity of the CP to the target was 6.23 times higher than that of the antifouling straight-chain multifunctional peptide (SP) to the target. In the 10 mg/mL BSA electrochemical fouling test, the fouling resistance of Ag@MXene + CP (composite sensing interface of CP combined with Ag@MXene) was 30 times higher than that of the bare electrode. The designed electrochemical sensor exhibited good selectivity and wide dynamic response range at PD-L1 concentrations from 0.1 to 50 ng/mL. The lowest detection limit was 24.54 pg/mL (S/N = 3). Antifouling 2D materials with a substantial specific surface area, coupled with non-straight chain antifouling multifunctional peptides, offer a wide scope for investigating the sensitivity and antifouling properties of electrochemical sensors.

Enhanced photocatalytic ammonia oxidation activity and nitrogen selectivity over Ag/AgCl/N-TiO2 photocatalyst.

The removal of ammonia (NH3) emitted from agricultural and industrial activities is of great significance to protect human health and ecological environment. Photocatalytic NH3 oxidation to N2 under mild conditions is a promising strategy. However, developing visible light photocatalysts for NH3 oxidation is still in its infancy. Here, we fabricate N-TiO2 and Ag/AgCl/N-TiO2 photocatalysts by sol-gel and photodeposition methods, respectively. The introduction of N not only endows TiO2 with visible light response (absorption edge at 460 nm) but also results in the formation of heterophase junction (anatase and rutile). Thus, N-TiO2 shows 2.0 and 1.8 times higher than those over anatase TiO2 and commercial TiO2 for NH3 oxidation under full spectrum irradiation. Meanwhile, surface modification of Ag can simultaneously enhance visible light absorption (generating localized surface plasmon resonance effect) and charge separation efficiency. Therefore, the photocatalytic activity of Ag/AgCl/N-TiO2 is further improved. Furthermore, the presence of N and Ag also enhances the selectivity of N2 product owing to the change of reaction pathway. This work simultaneously regulates photocatalytic conversion efficiency and product selectivity, providing some guidance for developing highly efficient photocatalysts for NH3 elimination.

Tunable Au@SiO2/Au Film Metasurface as Surface Plasmon Resonance Enhancer for Direct and Ultrasensitive Detection of Exosomes.

Surface plasmon resonance (SPR) spectroscopy with non-labelling, sensitive, and real-time properties is critical for clinical diagnosis applications. However, conventional SPR sensors face the challenge of lower sensitivity and selectivity for trace exosomes assay in complex serum. We proposed a core-shell Au@SiO2-Au film (Au@SiO2-Au film) metasurface to enhance SPR signal based on systematic study on the relationship between gap modes and SPR enhancement. The self-assembled multifunctional peptide was designed as recognition layer with antifouling properties for ultrasensitive and selective detection of PD-L1+ exosomes in serum. The tuning electromagnetic (EM) field model by manipulating the gap was established to guide the preparation of Au@SiO2-Au film metasurface. The in-plane and out-of-plane coupling of Au@SiO2 nanoparticles (NPs) could greatly enlarge and enhance three-dimensional EM field to meet the size of exosomes located in the evanescent field. At the structural level, we achieved high sensitivity (0.16 particles/mL) and a broad response range (10-5 × 103 particles/mL) through optimizing the thickness of SiO2 and surface coverage of Au@SiO2. Furthermore, clinical sample assay achieved the optimal diagnostic accuracy (AUC = 0.97) for differentiating cancer patients from healthy controls. This work provides an opportunity for the construction of a tunable gap mode as SPR enhancer in a total internal reflection architecture. The systematic study on the relationship between gap modes and SPR sensitivity provides a broad scope for promoting direct, efficient, highly selective, and sensitive detection of SPR sensors for clinical application.

Huatanmaitong tablet alleviate cerebral ischemic reperfusion injury with hyperlipidaemia in rats by regulating OATPs/VEGF axis.

Stroke is the top priority pathogenesis of disability and death globally, affecting people worldwide. The presence of high levels of lipids in the blood has been confirmed as a vital factor of ischemic stroke. We aim to examine the effectiveness of Huatanmaitong tablet in hyperlipidemia rats that have experienced an ischemic stroke. We created a rat model of middle cerebral artery occlusion (MCAO) with hyperlipidemia as a basis. Following 8 weeks of high-fat diet, the model rats underwent MCAO surgery. Subsequently, the rats were administered huatanmaitong tablets and lipitor tablets as treatments. Therefore there are five groups, CONTROL, MCAO, hyperlipidemia (HLP), Huatanmaitong tablet (HTMTT) and Lipitor (LIPITOR) groups respective ly. To assess the efficacy of the medication, the serum lipid levels of rats were measured both prior to and following administration. Hematoxylin eosin staining was used to observe the alterations in the brain and liver structures within each group. VEGF and OATPs related factors were detected in brain, liver by using immunohistochemistry, Western blotting, and Quantitative PCR. After the model was established successfully, the infarct volume and behavioral scores of the model group, hyperlipidemia group, Huatan Maitong tablet group and Lipitor group had statistical differences (P<0.05). Blood lipid levels of rats were measured before and after treatment, and it was found that Huatanmaitong tablets effectively reduced these levels. Hematoxylin and eosin staining of the brain and liver showed that huatanmaitong tablets maintained the microstructure stability. Western blotting and real-time PCR revealed that Huatanmaitong tablets improved the expression level of organic anion transport (OATP1B1, OATP2B1) in rat tissues with ischemic stroke, enhancing the transmembrane transport of exogenous substances and maintaining homeostatic balance. Additionally, it down-regulated the expression of VEGF in various organs such as the brain, and liver, demonstrating the ability of Huatanmaitong tablets to remove phlegm, blood stasis, and promote circulation by regulating serum lipid levels, organic anion transport peptide, and VEGF in rats. The behavioral score of ischemic stroke rats can be improved and the neurological impairment symptoms of rats can be alleviated by Huatanmaitong tablet through the regulation of OATPS/VEGF axis.

The association among uric acid, microalbumin and estimated glomerular filtration rate in hypertensive patients: a case control study.

OBJECTIVE: To estimate the relationship among uric acid (UA), 24-h microalbumin (24 h-MAU) and estimated glomerular filtration rate (eGFR) in hypertensive patients. METHOD: The study enrolled adult patients hospitalized in TEDA International Cardiovascular Hospital. The study was used to explore the correlation among UA, 24 h-MAU and eGFR. Univariate analysis was used to compare continuous or categorical data groups according to data type. Multivariate analysis was used to explore the correlation among UA, Log 24 h-MAU and eGFR by linear regression, and the relationship among UA, 24 h-MAU ≥ 30 mg/24 h (increased 24 h-MAU) and eGFR < 90 ml·min-1·1.73 m-2 (mildly decreased eGFR) by logistic regression. Mediation effect analysis was used to explore the mediating effect of increased 24 h-MAU between UA and mildly decreased eGFR. Subgroup analysis was used to investigate the correlation among UA, 24 h-MAU and eGFR in different gender. RESULT: Seven hundred and thirty-three inpatients were enrolled in the study, including 257 patients with hyperuricemia. The level of UA was 377.8 ± 99.9 µmol/L in all patients enrolled, and it was about 50.1% higher in hyperuricemia group (482.3 ± 58.8 µmol/L vs. 321.4 ± 63.5 µmol/L, P < 0.001). The prevalence of hyperuricemia was 35.1% (95%CI 31.6-38.5%). The univariate regression analysis showed that UA was significant related to Log 24 h-MAU, increased 24 h-MAU, eGFR and mildly decreased eGFR. After adjusted confounding factors, UA was significant related to Log 24 h-MAU (ß = 0.163, P < 0.001), eGFR (ß = - 0.196, P < 0.001), increased 24 h-MAU (quantitative analysis: OR = 1.045, 95%CI 1.020-1.071, P < 0.001; qualitative analysis: OR = 2.245, 95%CI 1.410-3.572, P = 0.001), but had no significant relationship with mildly decreased eGFR. Mediating effect analysis showed that increased 24 h-MAU partially mediated the relationship between UA and mildly decreased eGFR (relative indirect effect: 25.0% and 20.3% in quantitative analysis and qualitative analysis respectively). In the subgroup analysis, the results were stable and similar to the analysis for entry patients. CONCLUSION: The prevalence of hyperuricemia was higher in hypertensive inpatients. UA was strongly associated with Log 24 h-MAU, eGFR and increased 24 h-MAU, while the correlation with mildly decreased eGFR was affected by multiple factors. And increased 24 h-MAU might be the intermediate factor between UA and mildly decreased eGFR.

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.

Evaluation of the community involvement of nursing experts in reducing unintentional injuries in children.

BACKGROUND: Nursing experts regularly visited the community to deliver safety education on the prevention of unintentional injuries in children to the parents of children aged 0-6 years and to pregnant women in a maternity school. This was undertaken to explore the effects of the measure on preventing unintentional injuries in children in Chizhou, China. METHODS: Using the convenience sampling method, the guardians(it means mother in this study)of children were investigated. The nursing experts visited communities in which the number of nursing experts is declining. Data on unintentional injuries in children in the previous year were collected retrospectively. RESULTS: After the nursing experts delivered safety education to the community, the scores of the questionnaire on unintentional injury prevention knowledge completed by children's guardians increased significantly (p < 0.01). Among the children whose guardians completed the questionnaire, there were 157 cases of unintentional injury in 2020 and 103 cases in 2021 (p < 0.05). The types of unintentional injuries included scratches, falls, sharp object injuries, swallowing of foreign bodies, burns and traffic accidents; there was no statistical difference (p > 0.05). However, there were significant differences in terms of gender ratio and location (p < 0.05). CONCLUSION: In conjunction with the maternity school for pregnant women and the vaccination programme, nursing experts delivered safety education regarding unintentional injuries in children; this may have promoted safety and protection awareness in the children's guardians and reduced unintentional injuries.

Cadmium facilitates the formation of large lipid droplets via PLCß2-DAG-DGKε-PA signal pathway in Leydig cells.

Cadmium (Cd) exposure damages the reproductive system. Lipid droplets (LDs) play an important role in steroid-producing cells to provide raw material for steroid hormone. We have found that the LDs of Leydig cells exposed to Cd are bigger than those of normal cells, but the effects on steroidogenesis and its underlying mechanism remains unclear. Using Isobaric tag for relative and absolute quantitation (iTARQ) proteomics, phosphodiesterase beta-2 (PLCß2) was identified as the most significantly up-regulated protein in immature Leydig cells (ILCs) and adult Leydig cells (ALCs) derived from male rats exposed to maternal Cd. Consistent with high expression of PLCß2, the size of LDs was increased in Leydig cells exposed to Cd, accompanied by reduction in cholesterol and progesterone (P4) levels. However, the high PLCß2 did not result in high diacylglycerol (DAG) level, because Cd exposure up-regulated diacylglycerol kinases ε (DGKε) to promote the conversion from DAG to phosphatidic acid (PA). Exogenous PA, which was consistent with the intracellular PA concentration induced by Cd, facilitated the formation of large LDs in R2C cells, followed by reduced P4 level in the culture medium. When PLCß2 expression was knocked down, the increased DGKε caused by Cd was reversed, and then the PA level was decreased to normal. As results, large LDs returned to normal size, and the level of total cholesterol was improved to restore steroidogenesis. The accumulation of PA regulated by PLCß2-DAG-DGKε signal pathway is responsible for the formation of large LDs and insufficient steroid hormone synthesis in Leydig cells exposed to Cd. These data highlight that LD is an important target organelle for Cd-induced steroid hormone deficiency in males.

Perspectives and trends in advanced optical and electrochemical biosensors based on engineered peptides.

With the advancement of life medicine, in vitro diagnostics (IVD) technology has become an auxiliary tool for early diagnosis of diseases. However, biosensors for IVD now face some disadvantages such as poor targeting, significant antifouling properties, low density of recognized molecules, and poor stability. In recent years, peptides have been demonstrated to have various functions in unnatural biological systems, such as targeting properties, antifouling properties, and self-assembly properties, which indicates that peptides can be engineered. These properties of peptides, combined with their good biocompatibility, can be well applied to the design of biosensors to solve the problems mentioned above. This review provides an overview of the properties of engineered functional peptides and their applications in enhancing biosensor performance, mainly in the field of optics and electrochemistry.

A dual-modality immunosensor for simple and reliable detection of nitrated alpha-synuclein in serum based on silver-coated MOF.

Nitrated α-syn (nitro-α-syn) is a biomarker for Parkinson's desease (PD), and its sensitive detection in serum is of great importance for early PD diagnosis. Silver-coated copper MOF (Cu-MOF@Ag) with outstanding oxidase activity and electrochemical response property was designed and synthesized. Cu-MOF@Ag exhibited excellent oxidase activity with a low Km value (0.568 mM), avoiding the addition of strong oxidant to catalyze chromogenic substrate, which enhanced the colorimetric stability. Silver nanoparticles as an electrochemical signal reporter can be easily decorated on the surface of Cu-MOF with bifunctional groups (-SH and -NH2) material, which can increase the electrochemical signal output. The α-syn antibody modified Cu-MOF@Ag and nitro-α-syn modified magnetic nanoparticle were used as immunoprobes to specifically capture nitro-α-syn. A dual-modal immunosensor was fabricated for the simple and reliable detection of nitro-α-syn based on Cu-MOF@Ag. Combing colorimetric and electrochemical detection, nitro-α-syn can be determined quantitatively within a wide linear range (10-350 ng/mL) with low detection limit (0.5 ng/mL). The ability of the sensor with magnetic separation and dual signal analysis allowed to successfully detect nitro-α-syn and distinguish PD patients from healthy people (P < 0.005). Thanks to its excellent selectivity, stability, and the precision of 2.69%, the dual-modal sensor has potential clinical application for nitro-α-syn detection and paves a new way for PD diagnosis at its early stage.

Aptamer-Assisted Protein Orientation on Silver Magnetic Nanoparticles: Application to Sensitive Leukocyte Cell-Derived Chemotaxin 2 Surface Plasmon Resonance Sensors.

Leukocyte cell-derived chemotaxin 2 (LECT2) has been proved to be a potential biomarker for the diagnosis of liver fibrosis. In this work, a sensitive surface plasmon resonance (SPR) assay for LECT2 analysis was developed. Tyrosine kinase with immune globulin-like and epidermal growth factor-like domains 1 (Tie1) is an orphan receptor of LECT2 with a C-terminal Fc tag, which is far away from the LECT2 binding sites. The Fc aptamer was intentionally used to capture the Tie1 through its Fc tag, connecting with Fe3O4-coated silver magnetic nanoparticles (Ag@MNPs) and ensuring the LECT2 binding site to be outward. Attributed to the orientation nature of the captured protein, Ag@MNPs were able to enhance the SPR signal. A sensitive LECT2 sensor was successfully fabricated with a detection limit of 10.93 pg/mL. The results showed that the immobilization method improved the binding efficiency of Tie1 protein. This strategy could be extended to attach antibodies or recombinant Fc label proteins to Fc aptamer-based nanoparticles.

CORO1A regulates lipoprotein uptake in Leydig cells exposed to cadmium.

Cadmium (Cd) is one of the most common environmental pollutants, which has a long biological half-life. Maternal Cd-exposure in the natural environment causes steroidogenesis defects resulting in spermatogenesis disorder in male offspring. For better understanding its underlying mechanism, we have employed iTRAQ to screen the differentially expressed protein and found that the expression of CORO1A and Cofilin 1 was up-regulated approximately 2 fold in Leydig cells of maternal Cd-exposure offspring. As the major source of steroid hormone, cholesterol is transported to cells via receptor-mediated endocytosis which relies on the remodel of cytoskeleton, then stores in lipid droplets (LDs). However, few studies have focused on the role of cytoskeleton in abnormal steroidogenesis. This study was performed to explore the role of CORO1A in androgen deficiency caused by Cd exposure and its involvement of low-density lipoprotein (LDL) uptake and effects on LDs. We found that Cd resulted in the up-regulation of CORO1A and Cofilin 1, and down-regulation of Profilin 1 in the testis of male offspring with maternal exposure. The structure of filamentous actin was broken, disordered and even crumpled up in Cd-treated R2C cells. F-actin disassembly led to a low uptake of LDL with a reduced number of LDs, followed by decreased total cholesterol and low progesterone production. When CORO1A was silenced, the expression of Cofilin 1 was down-regulated and Profilin 1 was up-regulated in Cd-treated R2C cells. The filamentous actin was rescued and the integrated cytoskeleton prompted LDL uptake, which resulted in the increased total cholesterol and high progesterone production. These findings highlight the crucial role of CORO1A as a cytoskeleton regulatory protein in steroidogenesis, which may help to better understand Cd-induced steroid hormone deficiency in children.

Colorimetric detection of sulfamethazine based on target resolved calixarene derivative stabilized gold nanoparticles aggregation.

Sulfamethazine (SMZ) is one of the most used broad-spectrum antibiotics owing to its low cost and high efficacy towards bacterial diseases. This workreports a novel label-free SMZ sensor based on para-sulfonatocalix[4]arene (pSC4) capped gold nanoparticles (pSC4-AuNPs) for colorimetric detection through the host-guest interaction. The existence of SMZ resulted in the aggregation of pSC4-AuNPs and can be observed through colorimetric assay. A good linear relationship in the range 2.5 ~ 20 nM was obtained with a correlation coefficient of 0.9908. The limit of detection for SMZ was 1.39 nM. High recoveries (90.18-107.06%) were obtained, and RSD ranged from 1.21 to 2.05%. The color changes can be observed from red to gray within 10 min. Combining the supermolecule's recognition and AuNP's optical performance, the method paves a new, easy, and rapid way for small target sensing.

Nanozyme-based cascade SPR signal amplification for immunosensing of nitrated alpha-synuclein.

A self-assembled nanozyme of iron porphyrin mediated supramolecular modified gold nanoparticles (FpA) was fabricated to determine nitrated alpha-synuclein as the Tyr 39 residue (nT39 α-Syn) of a potential biomarker for early diagnosis of Parkinson's disease (PD). Mechanically, localized surface plasmon resonance (LSPR) and the mass effect caused by catalytic deposition of the nanozyme contributed to a cascade signal amplification strategy. The sensor allowed a signal amplification and selective nT39 α-Syn bioanalysis with a 1.34-fold enhancement by cascade amplified SPR signal and double specific recognition. The detection limit was 1.78 ng/mL in the detection range of 7-240 ng/mL. Benefiting from the excellent immunosensor, this method can distinguish healthy people and PD patients using actual samples. Overall, this strategy provides a nanozyme-based biosensing platform for the early diagnosis of PD and can be applied to detect other protein biomarkers, such as PD-L1.

In situ vertical alignment of 2D MoS2 layers on GO film: enhanced electrochemical properties for PD-L1 sensing.

There is an urgent need for a flexible and simple programmed cell death ligand 1 (PD-L1) dynamic measurement method enabling real-time monitoring of cancer progression and assessment of immunotherapy efficacy. In the current study, we show facile in situ synthesis of vertical alignment two-dimensional molybdenum disulfide (2D MoS2) layers on graphene-oxide-modified ITO (MoS2┴GO-ITO) using a hydrothermal approach and demonstrate the importance of the alignment of 2D in achieving high-probe capturing, enhanced electrochemical properties and target selectivity during sensing. After modification of designed PD-L1 binding peptides on the MoS2┴GO-ITO, a sensitive PD-L1 electrochemical sensor was designed using vertical alignment MoS2 to capture more probes for PD-L1 recognition and excellent in plane electron transport to accelerate electrochemical signals. The fabricated electrochemical sensor could sensitively determine PD-L1 in a wide linear range of 25-500 ng/mL and exhibit desirable accuracy and reliability in clinical samples application. This simple and sensitive method is likely to investigate further research into the exploration of the perpendicular alignment of 2D surfaces for diverse applications.

A 5-gene DNA methylation signature is a promising prognostic biomarker for early-stage cervical cancer.

The demographic information and overall survival (OS) of patients with cervical cancer (CC) (pathological stage: IA-IIA) were extracted from the TCGA database. A univariate and multivariate Cox proportional hazard model was performed to identify methylation markers significantly associated with the OS of patients in the training dataset. Then such a prognostic classifier was tested on the validation set and all subgroups. The Kaplan-Meier analysis and ROC analysis were performed to detect the ability to discriminate between patients with different risks and different OS. A DNA methylation signature which contained five genes was found to be significantly associated with the OS of CC patients by the Cox regression analysis in the training dataset. Such a signature could efficiently distinguish the patients into two risk groups with significantly different OS in both datasets. The receiver operating characteristic (ROC) analysis showed it had high sensitivity and specificity. Moreover, such a prognostic model also could be effectively applied to different subgroups, including groups of different ages, tumour sizes, histologic types, etc. A 5-DNA methylation signature identified by this study may act as a novel prognostic indicator for early-stage CC, and it may be helpful for the timely diagnosis and intervention of CC at pathological stages IA-IIA.Impact StatementWhat is already known on this subject? Cervical cancer (CC) is one of the most common gynaecological malignant tumours.What the results of this study add? This study constructed a risk model based on a 5-DNA methylation signature for early-stage CC patients' survival prediction.What the implications are of these findings for clinical practice and/or further research? Methylated markers have the potential to discriminate patients of different risks and different OS. Our results may shed new light on the early diagnosis and intervention, and potential therapeutic targets for CC patients at pathological stages IA-IIA.