Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy.

Cancer therapies kill tumors either directly or indirectly by evoking immune responses and have been combined with varying levels of success. Here, we describe a paradigm to control cancer growth that is based on both direct tumor killing and the triggering of protective immunity. Genetic ablation of serine protease inhibitor SerpinB9 (Sb9) results in the death of tumor cells in a granzyme B (GrB)-dependent manner. Sb9-deficient mice exhibited protective T cell-based host immunity to tumors in association with a decline in GrB-expressing immunosuppressive cells within the tumor microenvironment (TME). Maximal protection against tumor development was observed when the tumor and host were deficient in Sb9. The therapeutic utility of Sb9 inhibition was demonstrated by the control of tumor growth, resulting in increased survival times in mice. Our studies describe a molecular target that permits a combination of tumor ablation, interference within the TME, and immunotherapy in one potential modality.

Maternal Exposure to PM2.5 and the Risk of Congenital Heart Defects in 1.4 Million Births: A Nationwide Surveillance-Based Study.

BACKGROUND: Evidence remains limited about the association of maternal exposure to ambient fine particulate matter (airborne particles with an aerodynamic diameter ≤2.5 µm [PM2.5]) with fetal congenital heart defects (CHDs) in highly polluted regions, and few studies have focused on preconception exposure. METHODS: Using a nationwide surveillance-based case-control design in China, we examined the association between maternal exposure to PM2.5 during periconception (defined as 3 months before conception until 3 months into pregnancy) and risk of CHD in offspring. The study included 1 434 998 births involving 7335 CHDs from 2014 through 2017 on the basis of the National Population-Based Birth Defects Surveillance System, covering 30 provinces, municipalities, or municipal districts in China. We assigned maternal PM2.5 exposure during the periconception period to each participant using satellite-based PM2.5 concentrations at 1-km spatial resolution. Multilevel logistic regression models were used to calculate the multivariable-adjusted odds ratio and 95% CI for CHDs in offspring associated with maternal PM2.5 exposure, and the exposure-response association was investigated using restricted cubic spline analysis. Subgroup or sensitivity analyses were conducted to identify factors that may modify the association. RESULTS: The average maternal exposure to PM2.5 levels across all participants was 56.51 µg/m3 (range, 10.95 to 182.13 µg/m3). For each 10 µg/m³ increase in maternal PM2.5 exposure, the risk of CHDs in offspring was increased by 2% (odds ratio, 1.02 [95% CI, 1.00 to 1.05]), and septal defect was the most influenced subtype (odds ratio, 1.04 [95% CI, 1.01 to 1.08]). The effect of PM2.5 on CHD risk was more pronounced during the preconception period. Mothers <35 years of age, those living in northern China, and those living in low-income areas were more susceptible to PM2.5 exposure than their counterparts (all P<0.05). PM2.5 exposure showed a linear association with total CHDs or specific CHD types. CONCLUSIONS: High maternal PM2.5 exposure, especially during the preconception period, increases risk of certain types of CHD in offspring. These findings are useful for CHD prevention and highlight the public health benefits of improving air quality in China and other highly polluted regions.

Studying the role of Bombyx mori molybdenum cofactor sulfurase in Bombyx mori nucleopolyhedrovirus infection.

Molybdenum cofactor sulfurase (MoCoS) is a key gene involved in the uric acid metabolic pathway that activates xanthine dehydrogenase to synthesise uric acid. Uric acid is harmful to mammals but plays crucial roles in insects, one of which is the immune responses. However, the function of Bombyx mori MoCoS in response to BmNPV remains unclear. In this study, BmMoCoS was found to be relatively highly expressed in embryonic development, gonads and the Malpighian tubules. In addition, the expression levels of BmMoCoS were significantly upregulated in three silkworm strains with different levels of resistance after virus infection, suggesting a close link between them. Furthermore, RNAi and overexpression studies showed that BmMoCoS was involved in resistance to BmNPV infection, and its antivirus effects were found to be related to the regulation of uric acid metabolism, which was uncovered by inosine- and febuxostat-coupled RNAi and overexpression. Finally, the BmMoCoS-mediated uric acid pathway was preliminarily confirmed to be a potential target to protect silkworms from BmNPV infection. Overall, this study provides new evidence for elucidating the molecular mechanism of silkworms in response to BmNPV infection and new strategies for the prevention of viral infections in sericulture.

Uridine diphosphate glucosyltransferase is vital for fenpropathrin resistance in Bombyx mori (Lepidoptera).

The silkworm (Bombyx mori) is an important model lepidopteran insect and can be used to identify pesticide resistance-related genes of great significance for biological control of pests. Uridine diphosphate glucosyltransferases (UGTs), found in all organisms, are the main secondary enzymes involved in the metabolism of heterologous substances. However, it remains uncertain if silkworm resistance to fenpropathrin involves UGT. This study observes significant variations in BmUGT expression among B. mori strains with variable fenpropathrin resistance post-feeding, indicating BmUGT's role in fenpropathrin detoxification. Knockdown of BmUGT with RNA interference and overexpression of BmUGT significantly decreased and increased BmN cell activity, respectively, indicating that BmUGT plays an important role in the resistance of silkworms to fenpropathrin. In addition, fenpropathrin residues were significantly reduced after incubation for 12 h with different concentrations of a recombinant BmUGT fusion protein. Finally, we verified the conservation of UGT to detoxify fenpropathrin in Spodoptera exigua: Its resistance to fenpropathrin decreased significantly after knocking down SeUGT. In a word, UGT plays an important role in silkworm resistance to fenpropathrin by directly degrading the compound, a function seen across other insects. The results of this study are of great significance for breeding silkworm varieties with high resistance and for biological control of pests.

Dual-specificity phosphatase 1 inhibits Singapore grouper iridovirus replication via regulating apoptosis in Epinephelus coioides.

The dual-specificity phosphatase (DUSP) family plays key roles in the maintenance of cellular homeostasis and apoptosis etc. In this study, the DUSP member DUSP1 of Epinephelus coioides was characterized: the length was 2371 bp including 281 bp 5' UTR, 911 bp 3' UTR, and a 1125 bp open reading frame encoding 374 amino acids. E. coioides DUSP1 has two conserved domains, a ROHD and DSPc along with a p38 MAPK phosphorylation site, localized at Ser308. E. coioides DUSP1 mRNA can be detected in all of the tissues examined, and the subcellular localization showed that DUSP1 was mainly distributed in the nucleus. Singapore grouper iridovirus (SGIV) infection could induce the differential expression of E. coioides DUSP1. Overexpression of DUSP1 could inhibit SGIV-induced cytopathic effect (CPE), the expressions of SGIV key genes, and the viral titers. Overexpression of DUSP1 could also regulate SGIV-induced apoptosis, and the expression of apoptosis-related factor caspase 3. The results would be helpful to further study the role of DUSP1 in viral infection.

Long-acting anti-inflammatory injectable DEX-Gel with sustained release and self-healing properties regulates TH1/TH2 immune balance for minimally invasive treatment of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a prevalent immune-related allergic disease, and corticosteroid nasal sprays serve as the primary treatment for this patient population. However, their short duration of efficacy and frequent administration pose challenges, leading to drug wastage and potential adverse effects. To overcome these limitations, we devised a novel approach to formulate DEX-Gel by incorporating dexamethasone (DEX) into a blend of Pluronic F127, stearic acid (SA), and polyethylene glycol 400 (PEG400) to achieve sustained-release treatment for AR. RESULTS: Following endoscopic injection into the nasal mucosa of AR rats, DEX-Gel exhibited sustained release over a 14-day period. In vivo trials employing various assays, such as flow cytometry (FC), demonstrated that DEX-Gel not only effectively managed allergic symptoms but also significantly downregulated helper T-cells (TH) 2 and TH2-type inflammatory cytokines (e.g., interleukins 4, 5, and 13). Additionally, the TH1/TH2 cell ratio was increased. CONCLUSION: This innovative long-acting anti-inflammatory sustained-release therapy addresses the TH1/TH2 immune imbalance, offering a promising and valuable approach for the treatment of AR and other inflammatory nasal diseases.

Effects of sleep-disordered breathing on serum lipid levels in children:a case control study.

BACKGROUND: Sleep-disordered breathing (SDB) during childhood is common and includes a range of breathing abnormalities that range from primary snoring (PS) to obstructive sleep apnea syndrome (OSAS).Studies have shown that not only OSAS, but also PS, which is originally considered harmless, could cause cardiovascular, cognitive, behavioral, and psychosocial problems. Many researches are focused on the relation of OSA and serum lipid levels. However, little studies are focused on PS and serum lipid levels in children.We evaluated whether serum lipid (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)) concentrations were associated with specific components of SDB, including indices of oxygen reduction index, lowest oxygen saturation, mean oxygen saturation. And we explored whether serum lipid levels were associated with different degree sleep disordered (PS and OSA group) and obese. METHODS: This was a cross-sectional study. Children who were complained by their guardians with habitual snoring and(or) mouth breathing were collected in the SDB group. Normal children without sleep problem were matched in the control group. Subjects in the SDB group underwent polysomnography. The serum lipid profiles of all the children included TC, TG, HDL-C and LDL-C concentrations were measured by appropriate enzymatic assays. RESULTS: A total of 241 with Apnea/Hypopnea Index ≥ 5 (AHI) were assigned to the OSAS group and the remaining 155 with normal AHI were assigned to the PS group. The values of TC, TG, LDL-C and LDL/HDL were significantly higher in the OSAS group than in the PS group, and the values in the PS group were significantly higher than the control group. Multiple regression analysis revealed serum TG only correlated negatively with lowest oxygen saturation. Body mass index-z score has a positive effect on TG in all the 1310 children (P = 0.031) and in SDB 396 children(P = 0.012). The level of serum TG in obese group was significantly higher than that in non-obese group. CONCLUSIONS: SDB had a very obvious effect on blood lipids, whereas PS without apnea and hypoxia. Obese only affects the aggregation of TG. TRIAL REGISTRATION: ChiCTR1900026807(2019.10.23).

TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection.

As both host and pathogen require iron for survival, iron is an important regulator of host-pathogen interactions. However, the molecular mechanism by which how the availability of iron modulates host innate immunity against bacterial infections remains largely unknown. Using the metazoan Caenorhabditis elegans as a model, we demonstrate that infection with a pathogenic bacterium Salmonella enterica serovar Typhimurium induces autophagy by inactivating the target of rapamycin (TOR). Although the transcripts of ftn-1 and ftn-2 encoding two H-ferritin subunits are upregulated upon S. Typhimurium infection, the ferritin protein is kept at a low level due to its degradation mediated by autophagy. Autophagy, but not ferritin, is required for defense against S. Typhimurium infection under normal circumstances. Increased abundance of iron suppresses autophagy by activating TOR, leading to an increase in the ferritin protein level. Iron sequestration, but not autophagy, becomes pivotal to protect the host from S. Typhimurium infection in the presence of exogenous iron. Our results show that TOR acts as a regulator linking iron availability with host defense against bacterial infection.

A Two-Step Mendelian Randomization Involving Chronic Obstructive Pulmonary Disease, COVID-19 and Risk Factors.

Introduction and Objectives: Smoking is a risk factor for Covid-19 due to the destruction of heart and lungs from tobacco products. Increased smoking increases complications related to Covid-19, however, the association between chronic obstructive pulmonary disorder (COPD), environmental factors, and how the lung function mediates the association remains unclear. Therefore, our primary objective is to conduct a Mendelian randomization to investigate whether COPD, environmental factors and lung function has a mediating effect between smoking and the severity of COVID-19. Methods: A two-step Mendelian randomization design was employed using genetic data from genome-wide association studies (GWAS). The instrumental variable was the genetic variants (Z) associated with smoking, COPD, lung function (forced expiratory volume per second (FEV1), and COVID-19 phenotypes (hospitalized, severe and overall covid-19) were selected. The first step involved estimating the associations between instruments and their respective phenotypes, while the second step examined the relationships between instruments and outcomes, as well as instruments and mediators. Various sensitivity analyses were conducted to assess the robustness of the findings. Participants: A sample size ranging between 195 773 to 289 887. Measurements: Lung function was measured per second [forced expiratory volume per second (FEV1)], genetic determinants of lifetime smoking index, and varying severities of COVID-19 and COPD. Results: COVID-19 Severe (OR =1.48, 95% CI = 1.10 to 1.98) and COVID-19 Hospitalized (OR = 1.67, 95% CI = 1.42 to 1.97), alongside additional sensitivity analyses showed consistent directional effects. Smoking exacerbated COVID-19's risk in the experimental group more than in control populations: Odds Rations (OR) of 1.19 per standard deviation (SD), based on the lifetime smoking index, and a 95% Confidence Interval (CI) of 1.11 to 1.27. COPD and lung function did not mediate the associations. Conclusions: There exists strong genetic evidence linking environmental factors, smoking and lung function, and COVID-19's severity. Mild COVID-19 is also captured, but to a lesser extent, through minimal evidence. Low lung function exacerbates COPD but does not mediate the implications of smoking on the risk of COVID-19. Our study has implications in the public health policy and messaging for smokers and risks of COVID-19.

A signal polarity conversion photoelectrochemical immunosensor for neuron-specific enolase detection based on MgIn2S4-sensitized CsPbBr3.

A photoelectrochemical (PEC) immunosensor was designed based on MgIn2S4-decorated inorganic halide perovskite CsPbBr3 combined with the signal polarity conversion strategy for neuron-specific enolase (NSE) detection. CsPbBr3 was applied as the basic photoactive material owing to its excellent optical and electronic properties, which provide a good PEC performance for sensor construction. In order to improve the stability of this perovskite, the three-dimensional flower-like MgIn2S4 with a desirable direct band gap was applied to enhance the PEC response. Also, the excellent structure of MgIn2S4 provides large surface-active sites for CsPbBr3 loaded. For enhancing the detection sensitivity of PEC immunosensor, p-type CuInS2 was used as a signal probe which fixed on detection antibody (Ab2). When the target NSE was present, the photogenerated electrons produced by CuInS2 were transferred to the test solution, and the polarity of PEC signal changes. Based on the above photosensitive materials and signal conversion strategy, the proposed PEC immunosensor showed favorable detection performance, and the linear detection range is 0.0001 ~ 100 ng/mL with a 38 fg/mL of detection limit. The proposed strategy improved the adhibition of CsPbBr3 in the analytical chemistry field as well as provided a reference method for other protein detections.

Enhancing the Efficacy of Chiral Ligands and Catalysts: Siloxane-Substituted Oxazoline Ferrocenes as Next-Generation Candidates.

Since the discovery of classical chiral oxazoline ferrocene ligands in 1995, they have become pivotal in transition metal-catalyzed asymmetric transformations. Over the past decade, a notable evolution has been observed with the emergence of siloxane-substituted oxazoline ferrocenes, demonstrating significant potential as chiral ligands and catalysts. These compounds have consistently delivered exceptional results in diverse and mechanistically distinct transformations, surpassing the capabilities of classical oxazoline ferrocene ligands. This review meticulously delineates the research progress on siloxane-substituted oxazoline ferrocene compounds. It encompasses the synthesis of crucial precursors and desired products, highlights their achievements in asymmetric catalysis reactions, and delves into the exploration of the derivatization of these compounds, emphasizing the introduction of ionophilic groups and their impact on the recovery of transition metal catalysts. In addition to presenting the current state of knowledge, this review propels future research directions by identifying potential topics for further investigation concerning the siloxane-tagged derivatives. These derivatives are poised to be promising candidates for the next generation of highly efficient ligands and catalysts.

A multiplex direct PCR method for the rapid and accurate discrimination of three species of spider mites (Acari: Tetranychidae) in fruit orchards in Beijing.

Spider mites (Acari: Tetranychidae) are polyphagous pests of economic importance in agriculture, among which the two-spotted spider mite Tetranychus urticae Koch has spread widely worldwide as an invasive species, posing a serious threat to fruit tree production in China, including Beijing. The hawthorn spider mite, Amphitetranychus viennensis Zacher, is also a worldwide pest of fruit trees and woody ornamental plants. The cassava mite, Tetranychus truncatus Ehara, is mainly found in Asian countries, including China, Korea and Japan, and mainly affects fruit trees and agricultural crops. These three species of spider mites are widespread and serious fruit tree pests in Beijing. Rapid and accurate identification of spider mites is essential for effective pest and plant quarantine in Beijing orchard fields. The identification of spider mite species is difficult due to their limited morphological characteristics. Although the identification of insect and mite species based on PCR and real-time polymerase chain reaction TaqMan is becoming increasingly common, DNA extraction is difficult, expensive and time-consuming due to the minute size of spider mites. Therefore, the objective of this study was to establish a direct multiplex PCR method for the simultaneous identification of three common species of spider mites in orchards, A. viennensis, T. truncatus and T. urticae, to provide technical support for the differentiation of spider mite species and phytosanitary measures in orchards in Beijing. Based on the mitochondrial cytochrome c oxidase subunit I (COI) of the two-spotted spider mite and the cassava mite and the 18S gene sequence of the hawthorn spider mite as the amplification target, three pairs of specific primers were designed, and the primer concentrations were optimized to establish a direct multiplex PCR system for the rapid and accurate discrimination of the three spider mites without the need for DNA extraction and purification. The method showed a high sensitivity of 0.047 ng for T. truncatus and T. urticae DNA and 0.0002 ng for A. viennensis. This method eliminates the DNA extraction and sequencing procedures of spider mite samples, offers a possibility for rapid monitoring of multiple spider mites in an integrated microarray laboratory system, reducing the time and cost of leaf mite identification and quarantine monitoring in the field.

Incidence and Predictors of Acute Coronary Syndrome in Patients on Maintenance Hemodialysis: A Prospective Cohort Study.

Background: Cardiovascular diseases are the leading cause of death among patients on hemodialysis, with approximately 40% of the cardiovascular deaths linked to acute coronary syndrome. We aimed to investigate the incidence and risk factors of acute coronary syndrome in patients undergoing hemodialysis. Methods: Patients undergoing hemodialysis were prospectively enrolled from January 2018. Data regarding hospitalization due to acute coronary syndrome were collected at 3-month intervals through December 31, 2021. Cox regression model was used to estimate the association between baseline factors and incident acute coronary syndrome during follow-up. Results: Patients' mean age was 66 years, 48% were men, and 16% had a history of coronary artery disease at enrolment. Over a median follow-up of 1,187 days, 85 patients were hospitalized due to acute coronary syndrome. Left main or triple vessel disease was identified in 67 patients. Risk factors associated with incident acute coronary syndrome included aging, male sex, smoking, low diastolic blood pressure, and baseline comorbidities, in addition to dialysis factors including low urea clearance, central venous catheter use, and history of dialysis access dysfunction. After multivariate analysis, age, diabetes, hyperlipidemia, smoking, and frequent interventions for vascular access remained significant risk factors. Conclusions: A high acute coronary syndrome incidence was observed in our cohort, with traditional risk factors playing a consistent role with that in the general population. A history of frequent dialysis access dysfunction was also associated with incident acute coronary syndrome.

Experimental study on the antifatigue effect of icariin.

Fatigue is a serious disturbance to human health, especially in people who have a severe disease such as cancer, or have been infected with COVID-19. Our research objective is to evaluate the anti-fatigue effect and mechanism of icariin through a mouse experimental model. Mice were treated with icariin for 30 days and anti-fatigue effects were evaluated by the weight-bearing swimming test, serum urea nitrogen test, lactic acid accumulation and clearance test in blood and the amount of liver glycogen. The protein expression levels of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1-α) in the skeletal muscle of mice in each group were measured by western blotting. Results showed that icariin prolonged the weight-bearing swimming time of animals, reduced the serum urea nitrogen level after exercise, decreased the blood lactic acid concentration after exercise and increased the liver glycogen content observably. Compared to that in the control group, icariin upregulated AMPK and PGC1-α expression in skeletal muscle. Icariin can improve fatigue resistance in mice and its mechanism may be through improving the AMPK/PGC-1α pathway in skeletal muscle to enhance energy synthesis, decreasing the accumulation of metabolites and slowing glycogen consumption and decomposition.

[Chest computed tomography manifestations in neonates with chronic granulomatous disease]. / æ–°ç”Ÿå„¿æ ¢æ€§è‚‰èŠ½è‚¿ç— èƒ¸éƒ¨è®¡ç®—æœºæ–­å±‚æ‰«æçš„ç‰¹å¾åˆ†æž.

OBJECTIVES: To study chest computed tomography (CT) manifestations in neonates with chronic granulomatous disease (CGD) to provide clues for early diagnosis of this disease. METHODS: A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital. RESULTS: Nine neonates with CGD were included, with eight presenting respiratory symptoms as the initial sign. Chest CT findings included: consolidation in all 9 cases; nodules in all 9 cases, characterized by multiple, variably sized scattered nodules in both lungs; masses in 4 cases; cavities in 3 cases; abscesses in 6 cases; bronchial stenosis in 2 cases; pleural effusion, interstitial changes, and mediastinal lymphadenopathy each in 1 case. CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement; no signs of pulmonary emphysema, lung calcification, halo signs, crescent signs, bronchiectasis, or scar lesions were observed. There was no evidence of rib or vertebral bone destruction. Fungal infections were present in 8 of the 9 cases, including 6 with Aspergillus infections; three of these involved mixed infections with Aspergillus, with masses most commonly associated with mixed Aspergillus infections (3/4). CONCLUSIONS: The primary manifestations of neonatal CGD on chest CT are consolidation, nodules, and/or masses, with Aspergillus as a common pathogen. These features can serve as early diagnostic clues for neonatal CGD.

Core transcriptional networks in Williams syndrome: IGF1-PI3K-AKT-mTOR, MAPK and actin signaling at the synapse echo autism.

Gene networks for disorders of social behavior provide the mechanisms critical for identifying therapeutic targets and biomarkers. Large behavioral phenotypic effects of small human deletions make the positive sociality of Williams syndrome (WS) ideal for determining transcriptional networks for social dysfunction currently based on DNA variations for disorders such as autistic spectrum disorder (ASD) and schizophrenia (SCHZ). Consensus on WS networks has been elusive due to the need for larger cohort size, sensitive genome-wide detection and analytic tools. We report a core set of WS network perturbations in a cohort of 58 individuals (34 with typical, 6 atypical deletions and 18 controls). Genome-wide exon-level expression arrays robustly detected changes in differentially expressed gene (DEG) transcripts from WS deleted genes that ranked in the top 11 of 12 122 transcripts, validated by quantitative reverse transcription PCR, RNASeq and western blots. WS DEG's were strictly dosed in the full but not the atypical deletions that revealed a breakpoint position effect on non-deleted CLIP2, a caveat for current phenotypic mapping based on copy number variants. Network analyses tested the top WS DEG's role in the dendritic spine, employing GeneMANIA to harmonize WS DEGs with comparable query gene-sets. The results indicate perturbed actin cytoskeletal signaling analogous to the excitatory dendritic spines. Independent protein-protein interaction analyses of top WS DEGs generated a 100-node graph annotated topologically revealing three interacting pathways, MAPK, IGF1-PI3K-AKT-mTOR/insulin and actin signaling at the synapse. The results indicate striking similarity of WS transcriptional networks to genome-wide association study-based ASD and SCHZ risk suggesting common network dysfunction for these disorders of divergent sociality.

Signal "On-Amplified-Off" Strategy Based on Hafnium Dioxide Nanomaterials as Electrochemiluminescence Emitters for Progesterone Detection.

When consumed, excess progesterone (P4)─found in food and the environment─can lead to severe illnesses in humans. Therefore, quantitative analysis of P4 is critical for identifying its hazardous levels. In this study, a novel signal "on-amplified-off" P4 detection mode was proposed, which was based on the utilization of hafnium oxide (HfO2) as a unique electrochemiluminescence (ECL) emitter, produced by calcining UiO-66(Hf). This is the first time that HfO2 has been used as an ECL emitter. HfO2 displayed excellent conductivity and a high specific surface area, allowing it to connect with numerous aptamers and produce a "signal-on" effect. Ni-doped ZnO (Ni-ZnO) acted as a coreaction accelerator, enhancing the ECL strength of HfO2 by generating more tripropylamine radicals. cDNA was labeled with Ni-ZnO, and Ni-ZnO was linked to the aptamer via base complementary pairing, affording "signal-amplified". The presence of the target molecule P4 instigated a specific binding process with the aptamer, triggering the shedding of cDNA-Ni-ZnO and resulting in "signal-off". This novel "on-amplified-off" strategy effectively improved the sensitivity and specificity of P4 analysis, introducing a practical method for detecting biomolecules beyond the scope of this study, which holds immense potential for future applications.

High-Performance Electrochemiluminescence of a Coordination-Driven J-Aggregate K-PTC MOF Regulated by Metal-Phenolic Nanoparticles for Biomarker Analysis.

The elimination of aggregation-caused quenching of polycyclic aromatic hydrocarbons by metal-ligand coordination is of immense scientific interest in solid-state electrochemiluminescence (ECL) sensing. Herein potassium ion (K+)-mediated J-aggregate K-PTC MOF (PTCA, perylene-3,4,9,10-tetracarboxylic) was synthesized and employed to formulate an ECL immunosensor for biomarker detection. The coordination-driven aggregates are arranged in an end-to-end side mode, which overcomes the aggregation-caused quenching related to PTCA concentration. Compared with PTCA, K-PTC MOF shows a more stable ECL emission with an unprecedented red shift to 718 nm and is equipped with ECL activity for analytical applications at a voltage of -1.1 V. Considering the requirements of accurate detection, metal-phenolic bioactive nanoparticles (MPNPs) were synthesized for the construction of a sandwich sensing platform to realize the steady-state regulation of ECL. As proof of applicability, a constructive experiment was carried out with neuron-specific enolase (NSE), a marker of small cell lung cancer (SCLC), as a targeted analyte. With optimal requirements, the configuration can provide a detection range of 10 pg/mL to 50 ng/mL and a detection limit of 7.4 pg/mL, accompanied by sufficient practical analytical performance. Collectively, this paradigm provides a deeper understanding of the ECL characteristics of coordination-driven J-aggregation and provides more possibilities for the development of ECL patterns based on luminescent metal-organic frameworks.

Dual Direct Z-Scheme Heterojunction with Stable Electron Supply to a Au/PANI Photocathode for Ultrasensitive Photoelectrochemical and Electrochromic Visualization Detection of Ofloxacin in a Microfluidic Sensing Platform.

A novel dual-mode microfluidic analytical device integrating self-powered photoelectrochemical (PEC) sensing with electrochromic visualization analysis was developed for ultrasensitive ofloxacin (OFL) detection. First, an advanced dual direct Z-scheme BiVO4@Ni-ZnIn2S4/Bi2S3 (BVZIS) heterojunction was designed as a photoanode matrix to steadily provide electrons. The dual Z-scheme structure formed in photoactive BVZIS composites greatly accelerated the migration of electrons. In addition, the doping of Ni in ZnIn2S4 markedly enhanced the optical absorption and promoted the separation of the photocarrier. Second, electrochromic material polyaniline-modified Au (Au/PANI) was first electrodeposited on the photocathode for immobilizing aptamers and realizing visualized readout. On the one hand, Au/PANI with excellent conductivity could receive electrons from the photoanode without external energy supply. On the other hand, PANI would be rapidly reduced by the received electrons and change its color from blue to green obviously. With the increase in OFL, the increased steric hindrance resulted in the significant decline in the PEC signal and RGBgreen value. Third, wide linear ranges of PEC (0.05 pg/mL to 150 ng/mL) and electrochromic technique (0.1 pg/mL to 100 ng/mL) as well as low detection limits of PEC (18 fg/mL) and electrochromic (30 fg/mL) sensors could achieve the ultrasensitive detection of OFL in milk and river water.

Antioxidant Cascade Modulated Electrochemiluminescence by a Biomimetic Metal-Organic Framework with Dual Enzymatic Activity for Disease Marker Immunoassays.

High-performance electrochemiluminescence is a significant approach for the examination of disease biomarkers, and the utilization of innovative electrochemiluminescence detection systems represents a viable strategy to enhance the efficacy of ECL analysis. In this work, the biomimetic engineering metal-organic framework (MOF-818) has realized the ultrasensitive ECL immunoassay of disease markers based on the guidance of the free radical scavenging strategy provided by the antioxidant cascade. Initially, we synthesized a hydrogen-bonded organic framework (HOF) consisting of luminol and three active ligands based on simple room-temperature self-assembly. The luminol-HOF (L-HOF) showed more stable and brighter ECL luminescence activity than the monomer due to the nano-confinement enhancement of the coordinated luminol units. Subsequently, MOF-818 with biomimetic superoxide dismutase (SOD) and catalase (CAT) activities were recruited for the first time as quenching agents for sandwich immunoassay mode. The enzyme activity leads to the reverse transformation of superoxide anion radicals (O2-) and further antioxidant decomposition, decreasing in the responsiveness of luminol ECL signals. Using carcinoembryonic antigen (CEA) as an analytical model, a detection limit of 0.457 pg/mL was obtained within a detection range of 0.001-50 ng/mL. We believe that this novel sandwich sensing model based on enzyme activity provides a meaningful potential tool for precise detection, expanding the broader application of nanoenzymes in analysis.