IGSF8 is an innate immune checkpoint and cancer immunotherapy target.

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.

Effect of miR-1297 on Kidney Injury in Rats with Diabetic Nephropathy through the PTEN/PI3K/AKT Pathway.

PURPOSE: This study aimed to determine the influence of miR-1297 on kidney injury in rats with diabetic nephropathy (DN) and its causal role. METHODS: A DN rat model was established through right kidney resection and intraperitoneal injection of streptozotocin (STZ). Sham rats did not undergo right kidney resection or STZ injection. The DN rats were divided into the DN model and antagomiR-1297 treatment groups. Kidney morphology was observed using hematoxylin and eosin staining. Renal function indices, including blood urea nitrogen (BUN), serum creatinine (SCr), and urinary protein, were measured using kits. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined through enzyme-linked immunosorbent assay (ELISA). Fibrin (FN), collagen type I (Col I), and α-smooth muscle actin (α-SMA) were assessed through western blotting and real-time reverse transcription-polymerase chain reaction. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. miR-1297 targets were predicted using bioinformatic software and verified through luciferase reporter assay. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway expression was analyzed through western blotting. RESULTS: AntagomiR-1297 reduced BUN (p = 0.005), SCr (p = 0.012), and urine protein (p < 0.001) levels and improved kidney tissue morphology. It prevented renal interstitial fibrosis by decreasing FN, Col I, and α-SMA protein levels (all p < 0.001). AntagomiR-1297 increased SOD (p = 0.001) and GSH-Px (p = 0.002) levels. Additionally, it reduced levels of cell inflammatory factors, including TNF-α, IL-6, and IL-1ß (all p < 0.001), and alleviated apoptosis (p < 0.001) in rat kidney tissue with DN. miR-1297 was pinpointed as a target for PTEN. AntagomiR-1297 increased PTEN expression and suppressed PI3K and AKT phosphorylation (all p < 0.001). CONCLUSIONS: AntagomiR-1297 can mitigate renal fibrosis, renal inflammation, apoptosis, and oxidative stress levels through the PTEN/PI3K/AKT pathway.

Oral Microbiota and Porphyromonas gingivalis Kgp Genotypes Altered in Parkinson's Disease with Mild Cognitive Impairment.

Cognitive impairment (CI) is a common complication of the non-motor symptoms in Parkinson's disease (PD), including PD with mild cognitive impairment (PD-MCI) and PD dementia. Recent studies reported the oral dysbiosis in PD and CI, respectively. Porphyromonas gingivalis (P. gingivalis), a pathogen of oral dysbiosis, plays an important role in PD, whose lysine-gingipain (Kgp) could lead to AD-type pathologies. No previous study investigated the composition of oral microbiota and role of P. gingivalis in PD-MCI. This study aimed to investigate the differences of oral microbiota composition, P. gingivalis copy number, and Kgp genotypes among PD-MCI, PD with normal cognition (PD-NC) and periodontal status-matched control (PC) groups. The oral bacteria composition, the copy number of P. gingivalis, and the Kgp genotypes in gingival crevicular fluid from PD-MCI, PD-NC, and PC were analyzed using 16S ribosomal RNA sequencing, quantitative real-time PCR, and MseI restriction. We found that the structures of oral microbiota in PD-MCI group were significantly different compared to that in PD-NC and PC group. The relative abundances of Prevotella, Lactobacillus, Megasphaera, Atopobium, and Howardella were negatively correlated with cognitive score. Moreover, there was a significant difference of Kgp genotypes among the three groups. The predominant Kgp genotypes of P. gingivalis in the PD-MCI group were primarily Kgp II, whereas in the PD-NC group, it was mainly Kgp I. The Kgp II correlated with lower MMSE and MoCA scores, which suggested that Kgp genotypes II is related to cognitive impairment in PD.

Effect of miR-1297 on Kidney Injury in Rats with Diabetic Nephropathy through the PTEN/PI3K/AKT Pathway

Abstract Purpose: This study aimed to determine the influence of miR-1297 on kidney injury in rats with diabetic nephropathy (DN) and its causal role. Methods: A DN rat model was established through right kidney resection and intraperitoneal injection of streptozotocin (STZ). Sham rats did not undergo right kidney resection or STZ injection. The DN rats were divided into the DN model and antagomiR-1297 treatment groups. Kidney morphology was observed using hematoxylin and eosin staining. Renal function indices, including blood urea nitrogen (BUN), serum creatinine (SCr), and urinary protein, were measured using kits. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined through enzyme-linked immunosorbent assay (ELISA). Fibrin (FN), collagen type I (Col I), and α-smooth muscle actin (α-SMA) were assessed through western blotting and real-time reverse transcription-polymerase chain reaction. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. miR-1297 targets were predicted using bioinformatic software and verified through luciferase reporter assay. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway expression was analyzed through western blotting. Results: AntagomiR-1297 reduced BUN (p = 0.005), SCr (p = 0.012), and urine protein (p < 0.001) levels and improved kidney tissue morphology. It prevented renal interstitial fibrosis by decreasing FN, Col I, and α-SMA protein levels (all p < 0.001). AntagomiR-1297 increased SOD (p = 0.001) and GSH-Px (p = 0.002) levels. Additionally, it reduced levels of cell inflammatory factors, including TNF-α, IL-6, and IL-1β (all p < 0.001), and alleviated apoptosis (p < 0.001) in rat kidney tissue with DN. miR-1297 was pinpointed as a target for PTEN... (AU)

Nocturnal ozone enhancement in Shandong Province, China, in 2020-2022: Spatiotemporal distribution and formation mechanisms.

Nighttime ozone enhancement (NOE) can increase the oxidation capacity of the atmosphere by stimulating nitrate radical formation and subsequently facilitating the formation of secondary pollutants, thereby affecting air quality in the following days. Previous studies have demonstrated that when nocturnal ozone (O3) concentrations exceed 80 µg/m3, it leads to water loss and reduction of plant yields. In this study, the characteristics and mechanisms of NOE over Shandong Province as well as its 16 cities were analyzed based on observed hourly O3 concentrations from 2020 to 2022. The analysis results show that NOE predominantly occurred in the periods of 0:00-3:00 (41 %). The annual mean frequency of NOE events was ~64 days/year, approximately 4-7 days per month. The average concentration of nocturnal O3 peak (NOP) was ~72.6 µg/m3. Notably, high NOP was observed in the period from April to September with the maximum in June. Coastal cities experienced more NOE events. Typical NOE events characterized by high NOP concentrations in the coastal cities of QingDao, WeiHai and YanTai in June 2021 were selected for detailed analysis with a regional chemical transport model. The results showed that high levels of O3 in eastern coastal cities during NOE events primarily originate from horizontal transport over the sea, followed by vertical transport. During the daytime, O3 and its precursors are transported to the Yellow Sea by westerly winds, leading to the accumulation of O3 near the sea and coastline. Consequently, under the influence of prevailing winds, the movement of O3 pollution belts from the sea to land causes rapid increases in near-surface O3 levels. Meanwhile, vertical transport can also contribute to NOE in coastal areas. The high-level O3 in the upper atmosphere generally originates from long-distance transport and turbulent transport of O3 produced near the ground during the daytime. At night, the absence of chemicals that consume O3 in the upper air and descending air flow carries O3 to the near-surface. The impacts of other O3-depletion processes (such as dry deposition) on NOE are less pronounced than those of transport processes.

Ulcerative colitis complicated with hypermucinous dysplasia.

Patients with ulcerative colitis are at increased risk for colorectal neoplasia compared to the general population. The risk factors include family history of colorectal cancer, wide extent of colitis, disease duration, cumulative inflammatory burden, and primary sclerosing cholangitis. Here, we report a case of colorectal neoplasia developed in a patient with ulcerative colitis.

Spleen contributes to chronic restraint stress-induced lung injury through splenic CD11b+ cells.

Chronic stress can induce lung injury. The spleen, as the largest peripheral immune organ, plays a crucial role in various lung diseases. Our previous study found that the spleen underwent significant changes during chronic restraint stress (CRS). However, the exact role of the spleen in CRS-induced lung injury remains unclear. In this study, we found that CRS could increase lung index. CRS could lead to alterations of the lungs such as destruction of alveolar wall, thickening of alveolar septa, dilation of pulmonary capillaries, and increased inflammatory cell infiltration. CRS increases the concentration of malondialdehyde (MDA), decreases the level of surfactant protein A (SP-A), and elevates the levels of pro-inflammatory factors (TNF-α, IL-6, and IL-1ß) in the lungs. Additionally, CRS could increase the proportions and numbers of CD11b+Ly6ChiLy6G- monocytes in the lung, while cannot alter proportions and numbers of CD3-NK1.1+ NK cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD11b+Ly6G+ neutrophils. Moreover, the levels of inflammatory markers in lung tissues were positively correlated with the proportion of CD11b+Ly6ChiLy6G- monocytes. Interestingly, splenectomy inhibited CRS-induced lung injury and attenuated the alteration in the proportion of CD11b+Ly6ChiLy6G- monocytes in the lungs induced by CRS. Moreover, splenic CD11b+ cells, rather than splenic CD11b- cells, transfused into splenectomized mice, and subsequently exposed to CRS, can cause lung injury. These results suggest that CRS could induce lung injury and CD11b+Ly6ChiLy6G- monocytes aggregation in the lung. The spleen could contribute to CRS-induced lung injury. Furthermore, splenic CD11b+ cells might play an important role in CRS-induced lung injury.

Temporally and spatially resolved molecular profiling in fingerprint analysis using indium vanadate nanosheets-assisted laser desorption ionization mass spectrometry.

This study presents the first-ever synthesis of samarium-doped indium vanadate nanosheets (IVONSs:Sm) via microemulsion-mediated solvothermal method. The nanosheets were subsequently utilized as a nano-matrix in laser desorption/ionization mass spectrometry (LDI-MS). It was discovered that the as-synthesized IVONSs:Sm possessed the following advantages: improved mass spectrometry signal, minimal matrix-related background, and exceptional stability in negative-ion mode. These qualities overcame the limitations of conventional matrices and enabled the sensitive detection of small biomolecules such as fatty acids. The negative-ion LDI mechanism of IVONSs:Sm was examined through the implementation of density functional theory simulation. Using IVONSs:Sm-assisted LDI-MS, fingerprint recognitions based on morphology and chemical profiles of endogenous/exogenous compounds were also achieved. Notably, crucial characteristics such as the age of an individual's fingerprints and their physical state could be assessed through the longitudinal monitoring of particular biomolecules (e.g., ascorbic acid, fatty acid) or the specific biomarker bilirubin glucuronide. Critical information pertinent to the identification of an individual would thus be facilitated by the analysis of the compounds underlying the fingerprint patterns.

Characterization of the tumor microenvironment and identification of spatially predictive biomarkers associated with beneficial neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for patients with locally advanced rectal cancer (LARC). However, 20-40% of patients with LARC show little to no response to nCRT. Thus, comprehensively understanding the tumor microenvironment (TME), which might influence therapeutic efficacy, and identifying robust predictive biomarkers is urgently needed. Pre-treatment tumor biopsy specimens from patients with LARC were evaluated in detail through digital spatial profiling (DSP), public RNA sequencing datasets, and multiplex immunofluorescence (mIF). DSP analysis revealed distinct characteristics of the tumor stroma compared to the normal stroma and tumor compartments. We identified high levels of human leukocyte antigen-DR/major histocompatibility complex class II (HLA-DR/MHC-II) in the tumor compartment and B cells in the stroma as potential spatial predictors of nCRT efficacy in the Discovery cohort. Public datasets validated their predictive capacity for clinical outcomes. Using mIF in an independent nCRT cohort and/or the total cohort, we validated that a high density of HLA-DR/MHC-II+ cells in the tumor and CD20 + B cells in the stroma was associated with nCRT efficacy (all p ≤ 0.021). Spatial profiling successfully characterized the LARC TME and identified robust biomarkers with the potential to accurately predict nCRT response. These findings have important implications for individualized therapy.

A simplified prognostic score for T-cell large granular lymphocyte leukaemia.

BACKGROUND: T-cell large granular lymphocyte leukaemia (T-LGLL) generally has a favourable prognosis, but a small proportion of patients are facing a relatively short survival time. This study aimed to identify clinical factors associated with survival in patients with T-LGLL and develop a predictive model for guiding therapeutic decision-making. MATERIALS AND METHODS: We conducted a retrospective study on 120 patients with T-LGLL. Lasso regression was performed for feature selection followed by univariate and multivariate Cox regression analysis. A decision tree algorithm was employed to construct a model for predicting overall survival (OS) in T-LGLL. RESULTS: The median age of diagnosis for the entire cohort was 59 years, and 76.7% of patients reported disease-related symptoms. After a median follow-up of 75 months, the median OS was not reached. The 5-year OS rate was 82.2% and the 10-year OS rate was 63.8%. Multivariate analysis revealed that an Eastern Cooperative Oncology Group performance status over two and a platelet count below 100 × 109/L were independently associated with worse OS, leading to the development of a simplified decision tree model. The model's performance was adequate when internally validated. The median OS of the high- and intermediate-risk- risk groups was 43 and 100 months respectively, whereas the median OS of the low-risk group was not reached. Furthermore, we found that immunosuppressive agent-based conventional treatment was unsatisfactory for our high-risk patients. CONCLUSIONS: Our model is an easily applicable clinical scoring system for predicting OS in patients with T-LGLL. However, external validation is essential before implementing it widely.

Stratified management based on surface antibody for the prevention of hepatitis B virus reactivation in lymphoma patients.

This study aimed to investigate a stratified approach based on hepatitis B virus (HBV) surface antibody (anti-HBs) for managing HBV reactivation (HBVr) in lymphoma patients with serological protection against HBV. A retrospective analysis was conducted on 209 lymphoma patients with a baseline anti-HBs titre of ≥10 iu/L, who were either positive or negative for HBV core antibody (anti-HBc). The results revealed that 15.7% of patients lost serological protection following 6-month anti-lymphoma therapy. With a median follow-up of 28.1 months, the cumulative rates of HBVr at 6 months, 2 years and 4 years were 2.9%, 4.7% and 6.3% respectively. Without intervention, the overall rate of reactivation was 2.0% for patients with isolated anti-HBs and 10.5% for those with positive anti-HBs and anti-HBc. To identify patients at high risk of losing seroprotection and susceptible to HBVr, a predictive model was developed. The high-risk group had significantly higher rates of serological protection loss (27.8% vs. 2.2%) and cumulative incidence of HBVr (22.0% vs. 0%) compared to the low-risk group. Overall, this study highlights the risk of HBVr in lymphoma patients with positive anti-HBs, with or without positive anti-HBc, and recommends periodic monitoring for low-risk patients and early intervention for high-risk patients.

m6A-regulated tumor glycolysis: new advances in epigenetics and metabolism.

Glycolytic reprogramming is one of the most important features of cancer and plays an integral role in the progression of cancer. In cancer cells, changes in glucose metabolism meet the needs of self-proliferation, angiogenesis and lymphangiogenesis, metastasis, and also affect the immune escape, prognosis evaluation and therapeutic effect of cancer. The n6-methyladenosine (m6A) modification of RNA is widespread in eukaryotic cells. Dynamic and reversible m6A modifications are widely involved in the regulation of cancer stem cell renewal and differentiation, tumor therapy resistance, tumor microenvironment, tumor immune escape, and tumor metabolism. Lately, more and more evidences show that m6A modification can affect the glycolysis process of tumors in a variety of ways to regulate the biological behavior of tumors. In this review, we discussed the role of glycolysis in tumor genesis and development, and elaborated in detail the profound impact of m6A modification on different tumor by regulating glycolysis. We believe that m6A modified glycolysis has great significance and potential for tumor treatment.

Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin's lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton's tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

Treatment strategies and survival outcomes of primary mediastinal large B-cell lymphoma.

OBJECTIVES: Primary mediastinal large B-cel l lymphoma (PMBCL) is a rare subtype of B-cell lymphoma that is not yet fully understood. This population-based study aimed to assess the latest survival and treatment strategies for patients with PMBCL. METHODS: The study used the dataset from the Surveillance, Epidemiology, and End Results Program registry to retrospectively analyze adult patients diagnosed with PMBCL between 2001 and 2018. The primary outcome measures included overall survival (OS) and disease-specific survival (DSS). RESULTS: Among the 814 identified cases, the study revealed a 5-year OS rate of 86.7% and a 5-year DSS rate of 88.2% after a median follow-up of 54 months. Cox regression analysis indicated that age over 60 years, pre-2010 diagnosis, non-White ethnicity, advanced stage, and absence of chemotherapy significantly reduced both OS and DSS. It also found that chemotherapy has remained the primary therapeutic protocol for PMBCL over the last 20 years, whereas the utilization of surgery and radiation declined significantly. Patients diagnosed with PMBCL between 2010 and 2018 had a significantly reduced mortality risk (∼50%) compared to those diagnosed between 2001 and 2009. Notably, in the era of rituximab's widespread usage, recipients of radiotherapy exhibited a poorer OS rate than non-recipients. CONCLUSION: Survival outcomes for patients with PMBCL have significantly improved in the current era, possibly due to the evolving treatment paradigm. The value of radiotherapy in PMBCL is still debated and requires further prospective evaluation.

Global Disease Burden and Attributable Risk Factor Analysis of Asthma in 204 Countries and Territories From 1990 to 2019.

PURPOSE: Asthma is a common chronic inflammatory respiratory tract disease with high morbidity and mortality. The global trends in asthma burden remain poorly understood, and asthma incidence has increased during the worldwide coronavirus disease 2019 (COVID-19) pandemic. This study aimed to provide a comprehensive view of the global distribution of asthma burden and its attributable risk factors from 1990 to 2019. METHODS: Based on the Global Burden of Disease Study 2019 Database, asthma incidence, deaths, disability-adjusted life years (DALYs), the corresponding age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), age-standardized DALY rate, and estimated annual percentage change were analyzed according to age, sex, sociodemographic index (SDI) quintiles, and locations. Risk factors contributing to asthma deaths and DALYs were also investigated. RESULTS: Globally, the asthma incidence increased by 15%, but deaths and DALYs decreased. The corresponding ASIR, ASDR, and age-standardized DALY rate also decreased. The high SDI region had the highest ASIR, and the low SDI region had the highest ASDR. The ASDR and age-standardized DALY rate were negatively correlated with the SDI. The low-middle SDI region, particularly South Asia, showed the highest asthma-related deaths and DALYs. The incidence peak was under 9 years old, and more than 70% of all deaths occurred in the population over 60 years old. Smoking, occupational asthmagens, and a high body mass index were the main risk factors for asthma-related mortality and DALYs, and their distributions varied between sexes. CONCLUSIONS: Globally, the asthma incidence has increased since 1990. The greatest asthma burden is borne by the low-middle SDI region. The 2 groups that need special attention are those under 9 years old and those over 60 years old. Targeted strategies are needed to reduce the asthma burden based on geographic and sex-age characteristics. Our findings also provide a platform for further investigation into the asthma burden in the era of COVID-19.

Enhancing morphological analysis of peripheral blood cells in chronic lymphocytic leukemia with an artificial intelligence-based tool.

BACKGROUND: Real-time monitoring is essential for the management of chronic lymphocytic leukemia (CLL) patients. Utilizing peripheral blood is advantageous due to its affordability and convenience. Existing methods of assessing peripheral blood films have limitations that include lack of automation, dependence on personal experience, and low repeatability and reproducibility. To overcome these challenges, we have designed an artificial intelligence-driven system that provides a clinical perspective to objectively evaluate morphologic features in CLL patients' blood cells. METHODS: Based on our center's CLL dataset, we developed an automated algorithm using a deep convolutional neural network to precisely identify regions of interest on blood films and used the well-established Visual Geometry Group-16 as the encoder to segment cells and extract morphological features. This tool enabled us to extract morphological features of all lymphocytes for subsequent analysis. RESULTS: Our study's lymphocyte identification had a recall of 0.96 and an F1 score of 0.97. Cluster analysis identified three clear, morphological groups of lymphocytes that reflect distinct stages of disease development to some extent. To investigate the longitudinal evolution of lymphocyte, we extracted cellular morphology parameters at various time points from the same patient. The results showed some similar trends to those observed in the aforementioned cluster analysis. Correlation analysis further supports the prognostic potential of cell morphology-based parameters. CONCLUSION: Our study provides valuable insights and potential avenues for further exploration of lymphocyte dynamics in CLL. Investigating morphological changes may help in determining the optimal timing for intervening with CLL patients, but further research is needed.

Gold Nanotriangle-Assembled Nanoporous Structures for Electric Field-Assisted Surface-Enhanced Raman Scattering Detection of Adenosine Triphosphate.

A reliable, rapid, cost-effective, and simple method for the detection of biomolecules would greatly promote the research of analytical detection of single molecules. A nanopore-based analytical technique is promising for detecting biomolecules. Conventional electrochemical nanopores cannot distinguish biomolecules precisely because of their fast translocation speed and limited electrochemical information. Therefore, it is highly desirable to develop electrochemical surface-enhanced Raman scattering (SERS) nanopores to obtain multidimensional information. Herein, we designed and fabricated gold nanotriangle (AuNT)-assembled porous structures at the tip of a glass capillary using dithiol adenosine triphosphate (ATP) aptamers as cross-linking molecules. The AuNTs exhibited an edge length of 57.3 ± 6.2 nm and thickness of about 15 nm. The gold nanoporous structure (GPS) showed a strong ion rectification even at a high concentration of electrolyte (2 M) and a high SERS activity. Based on these designed structures, SERS and electrochemistry techniques were combined to control the rapid movement of ATP to the vicinity of the GPS by an applied potential of +1 V, where ATP was concentrated by ATP aptamers and the molecular signals were amplified by SERS. As a result, the GPS successfully detected ATP at a concentration as low as 10-7 M.