Regeneration mechanism of a novel high-performance biochar mercury adsorbent directionally modified by multimetal multilayer loading.

Biochar that is directly obtained by pyrolysis exhibits a low adsorption efficiency; furthermore, the process of recycling adsorbents is ineffective. To solve these problems, conventional chemical coprecipitation, sol-gel, multimetal multilayer loading and biomass pyrolysis coking processes have been integrated. After selecting specific components for structural design, a novel high-performance biochar adsorbent was obtained. The effects of the O2 concentration and temperature on the regeneration characteristics were explored. An isothermal regeneration method to repair the deactivated adsorbent in a specific atmosphere was proposed, and the optimal regeneration mode and conditions were determined. The microscopic characteristics of the regenerated samples were revealed along with the mechanism of Hg0 removal and regeneration by using temperature-programmed desorption technology and adsorption kinetics. The results show that doping multiple metals can reduce the pyrolysis reaction barrier of the modified biomass. On the modified surface of the sample, the doped metals formed aggregated oxides, and the resulting synergistic effect enhanced the oxidative activity of the biochar carriers and the threshold effect of Ce oxide. The optimal regeneration conditions (5% O2 and 600 °C) effectively coordinated the competitive relationship between the deep carbonization process and the adsorption/oxidation site repair process; in addition, these conditions provided outstanding structure-effect connections between the physico-chemical properties and Hg0 removal efficiency of the regenerated samples. Hg0 adsorption by the regenerated samples is a multilayer mass transfer process that involves the coupling of physical and chemical effects, and the surface adsorption sites play a leading role.

Relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with systemic lupus erythematosus.

OBJECTIVES: To characterize the relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with moderate to severe SLE despite standard therapy, using pooled data from two phase 3 trials. METHODS: TULIP-1 and TULIP-2 were randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (every 4 weeks for 48 weeks). For the exposure-response analysis, BILAG-based Composite Lupus Assessment (BICLA) or SLE Responder Index [SRI(4)] response rates at week 52 in each quartile/tertile of average anifrolumab serum concentration (Cave) were compared for anifrolumab and placebo in all-comers, patients who completed treatment, and IFN gene signature (IFNGS)-high patients who completed treatment, using average marginal effect logistic regression. Relationships between exposure and key safety events were assessed graphically. RESULTS: Of patients in TULIP-1/TULIP-2 who received anifrolumab (150 mg, n = 91; 300 mg, n = 356) or placebo (n = 366), 574 completed treatment, of whom 470 were IFNGS high. In the exposure-efficacy analyses, BICLA and SRI(4) treatment differences favouring anifrolumab 300 mg vs placebo were observed across Cave subgroups and all analysis populations. Logistic regression identified Cave as a significant covariate for predicted BICLA response, as higher anifrolumab Cave predicted greater efficacy. There was no evidence of exposure-driven incidence of key safety events through week 52 in patients receiving anifrolumab 150 or 300 mg. CONCLUSION: While higher Cave predicted greater efficacy, consistent positive benefit favouring anifrolumab 300 mg vs placebo was observed in BICLA and SRI(4) responses across Cave subgroups in the TULIP trials. There was no evidence of exposure-driven safety events. CLINICALTRIAL.GOV NUMBERS: NCT02446912, NCT02446899.

Ultrasensitive fluorescent detection of telomerase activity based on tetrahedral DNA nanostructures as carriers for DNA-templated silver nanoclusters.

Precise evaluation of telomerase activity is essential for the clinical diagnosis of early tumors. Herein, we have ingeniously designed a tetrahedral DNA nanostructure, with hairpin-shaped DNA probes rich in cytosine bases at four vertices for telomerase detection. The DNA-templated silver nanoclusters can be formed after the addition of Ag. Then the introduction of telomerase adds the single-strand TTAGGG extension, which can "turn on" the fluorescence of silver nanoclusters quickly by the proximity of the resulting guanine-rich sequences to silver nanoclusters and realize accurate detection of telomerase activity. In this study, integration of high stability tetrahedral DNA nanostructure and fluorescence signal amplification of four DNA-templated silver nanoclusters offers the advantage of high sensitivity, with a low detection limit of 1 cell. More than that, this method is low-cost, facile, and feasible for practical clinical applications.

[Research progress on the effects of plateau hypoxia on blood-brain barrier structure and drug permeability].

Drugs for the treatment of central nervous system diseases need to enter the brain tissue through the blood-brain barrier to function. In high altitude hypoxic environment, there are changes in tight junction proteins of blood-brain barrier tissue structure, transporters in astrocytes and endothelial cells and ATP in endothelial cells; at the same time the permeability of the blood-brain barrier is increased. These changes are an important reference for rational drug use in patients with central nervous system disease in the plateau region. This article reviews the research progress on the effects of plateau hypoxia on the structure of the blood-brain barrier and related drug permeability.

Association of Difference in Coronary Sinus Diameter by Computed Tomographic Angiography Between Patients in and Not in Stable Atherosclerotic Plaque(S).

BACKGROUND Pathological finding fail to describe the morphology of coronary arterial plaques. Retrograde cardiac arteriography is a complicated procedure and does not detect all left posterior and marginal veins of the heart. Magnetic resonance angiography has long scan time and low spatial resolution. The objective of the present study was to assess the possible utility of the difference in coronary sinus diameter to quantify stable atherosclerotic plaque(s) using 256-slice coronary computed tomographic angiography. MATERIAL AND METHODS A total of 336 patients were divided into 2 groups with 168 patients each. Patients who had heart failure were included in the study group and those who did not were included in the non-study group. Patients were subjected to cross-sectional study. Cardiovascular images were performed with 256-slice coronary computed tomographic angiography with a prospective electrocardiogram and clinical manifestation. Two-tailed paired t test following Dunnett's multiple comparison tests was performed for the quantitative measurement of coronary computed tomographic angiography and clinical manifestation at 99% confidence level. RESULTS The clinical manifestation did not clearly show cardiac abnormality. The diameters of the superoinferior coronary sinus ostium was than that of the anteroposterior coronary sinus ostium, (p<0.0001, q=26.325). There was the difference in size of the coronary sinus ostium between patients in and not in heart failure (p<0.0001). The study group patients had longer coronary sinuses than patients in the non-study group (p<0.0001). CONCLUSIONS 256-slice computed tomographic angiography is a feasible and is non-invasive bio-tool for evaluation of coronary artery anatomy.

Low-dose IL-2 expands CD4+ regulatory T cells with a suppressive function in vitro via the STAT5-dependent pathway in patients with chronic kidney diseases.

BACKGROUND: Patients with chronic kidney disease (CKD) often have CD4+ regulatory T cells (Tregs) dysfunction and chronic inflammation. We aim to investigate the effect, function, and related mechanism of low-dose IL-2 on CD4+ regulatory T cells expansion in vitro from patients with CKD. METHODS: A total of 148 newly diagnosed patients with CKD at Stage III and 35 healthy volunteer subjects were recruited into our studies. The number of peripheral Tregs in peripheral blood mononuclear cells isolated from CKD patients, which were characterized by FACS as CD4+CD25hi and CD4+CD25+FoxP3+. The effect of low-dose IL-2 on expansion of Tregs, and the suppressive function of expanded Tregs were also analyzed by FACS. The levels of FoxP3 mRNA were detected by qRT-PCR. The activation of IL-2 induced Stat5 and blocking experiments were assessed by Western Blotting and FACS. RESULTS: We found that the frequency of peripheral Tregs from CKD patients was significantly lower than that in healthy volunteer subjects. We also showed that IL-2 selectively expanded CD4+CD25hi and CD4+CD25+FoxP3+ regulatory T cells, and also upregulated the expression of FoxP3 mRNA. Our in vitro studies demonstrated that expanded CD4+ regulatory T cells from CKD patients suppressed proinflammatory Th1 and Th17 cell response. Furthermore, STAT5 activation is required for IL-2-induced expansion of regulatory T cells and expression of FoxP3 mRNA from CKD patients. CONCLUSIONS: Our findings support the clinical Treg defects in CKD patients with glomerular diseases, and the rationale of evaluating low-dose IL-2 treatment for selectively modulating CD4+ Tregs.

Bioactive spirans and other constituents from the leaves of Cannabis sativa f. sativa.

In this paper, 17 compounds (1-17) were isolated from the leaves of Hemp (Cannabis sativa f. sativa). Among the isolates, two were determined to be new spirans: cannabispirketal (1), and α-cannabispiranol 4'-O-ß-D-glucopyranose (2) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known compounds 7, 8, 10, 13, 15, and 16 were isolated from Hemp (C. sativa f. sativa) for the first time. Furthermore, compounds 8 and 13 were isolated from the nature for the first time. All isolated compounds were evaluated for cytotoxicity on different tissue-derived passage cancer cell lines through cell viability and apoptosis assay. Among these compounds, compounds 5, 9 and 16 exhibited a broad-spectrum antitumor effect via inhibiting cell proliferation and promoting apoptosis. These results obtained have provided valuable clues to the understanding of the cytotoxic profile for these isolated compounds from Hemp (C. sativa f. sativa).

Serum A08 C1q antibodies are associated with disease activity and prognosis in Chinese patients with lupus nephritis.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by overproduction of numerous autoantibodies. Many studies have sought to identify such biomarkers to distinguish patients with active lupus nephritis from SLE patients without renal involvement. Because antibodies to complement C1q appear to be prevalent in patients with active lupus nephritis, we analyzed the frequency of antigenic epitopes of C1q and their clinical significance in a large multicenter study of Chinese patients. The lupus cohort consisted of 210 patients with active lupus nephritis as a discovery cohort, 130 active patients as a validation cohort along with 130 SLE patients without clinical renal involvement, and 100 healthy controls. Serum antibodies to intact C1q, the collagen-like region, the globular head region, and the new linear A08 epitope to C1q were screened by specific ELISA. The frequency of antibodies to intact C1q, the C1q-collagen-like region, and the A08 antibodies in the discovery cohort were significantly higher than that in patients without renal involvement or healthy controls. Antibodies to the globular head region were not prevalent enough for further study. The results were confirmed in the validation cohort. The area under the curve for anti-A08 antibodies was significantly greater than those for both the intact and collagen-like region antibodies to discriminate between active lupus nephritis and active SLE without clinical renal involvement. The A08 antibodies were all negative at remission. The serum A08 antibody level correlated better with disease relapse than that of antibodies to either the intact or the collagen-like region, significantly predicting renal prognosis. Thus, serum levels of A08 C1q antibodies are closely associated with disease activity and prognosis in lupus nephritis.

The Effects of Indoxyl Sulfate on Human Umbilical Cord-Derived Mesenchymal Stem Cells In Vitro.

BACKGROUND/AIMS: Indoxyl sulfate, an important protein-bound uremic toxin, can damage stem cells, thus hampering stem cell-based regenerative medicine approaches targeting chronic kidney diseases (CKD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are thought to have promising clinical application because of their high proliferative potential and ease of isolation than MSCs from other sources. In the present study, we aimed to determine the harmful effects of indoxyl sulfate on the phenotype and functional potential of hUC-MSCs in vitro. METHODS: The toxicity and cell viability was examined by Trypan blue exclusion and MTT assay. The cellular surface markers and the percentage of apoptotic cells by Annexin-V/PI staining were analyzed by flow cytometry. Proliferation was evaluated based on cell number counting and Ki-67 immunostaining. Cell senescence was measured using senescence-associated ß-Galactosidase activity. The ability to stimulate the development of CD4+CD25+FoxP3+ regulatory T cells was assessed by incubating hUC-MSCs with peripheral blood mononuclear cells from the healthy volunteers. RESULTS: Our results demonstrated that the immunophenotype of hUC-MSCs was not affected by indoxyl sulfate flow cytometry. However, a significant decrease in cell numbers and fraction of Ki-67 positive proliferating cells, along with a significant increase in cellular senescence were detected in hUC-MSCs after exposure to indoxyl sulfate. Additionally, their ability to stimulate CD4+CD25+FoxP3+ regulatory T cell production was compromised when hUC-MSCs were pretreated with indoxyl sulfate. CONCLUSION: Taken together, our study clearly demonstrated that the molecular alterations and functional incompetence in hUC-MSCs under the challenge of indoxyl sulfate in vitro.

A Sputum Proteomic Signature That Associates with Increased IL-1ß Levels and Bacterial Exacerbations of COPD.

PURPOSE: Activation of the interleukin-1ß (IL-1ß) signaling pathway has been implicated in COPD, but the proportion of COPD subjects whose disease is principally driven by activation of this pathway is poorly understood. In this study, we sought to differentiate an IL-1ß-associated sputum signature from other inflammation-associated COPD phenotypes. METHODS: Luminex-multiplex assays were used to study IL-1ß-mediated signature proteins within airway epithelium, smooth muscle, and vascular endothelial cell cultures. The IL-1ß-mediated signature was tested in a longitudinal study comprising of 35 paired stable-COPD and acute exacerbation (AECOPD) sputum samples. The presence of respiratory pathogens (H. influenzae, M. catarrhalis, S. pneumoniae, and P. aeruginosa) was evaluated by sputum cultures. RESULTS: Five proteins namely TNF-α, GCSF, IL-6, CD-40L, and MIP-1ß were found to be IL-1ß-regulated across all donors and cell types. All five of these IL-1ß-mediated proteins were significantly increased (p < 0.05) in sputum corresponding to AECOPD events showing at least a twofold increase in IL-1ß (IL-1ß(+) events, 18 of 35 total events), relative to preceding stable-COPD state. Sputum IL-1ß levels showed no significant association (p > 0.05, spearman) with known markers of other major COPD inflammation phenotypes. In addition, there was a significant association with bacterial presence in sputum culture with an odds ratio of 9 (95 % CI 1.56, 51.9) in IL-1ß(+) events versus IL-1ß(-) events. CONCLUSION: Our findings provide insights into potential markers of IL-1ß-associated AECOPD, and reaffirm association between IL-1ß pathway activation and airway bacterial infection in COPD. Taken together, our findings could help identify COPD patient subsets who may benefit from therapies targeting IL-1ß pathway.

HIV-1 prevalence and subtype/recombinant distribution among travelers entering China from Vietnam at the HeKou port in the Yunnan province, China, between 2003 and 2012.

The aim of this study was to assess HIV-1 prevalence and the distribution of HIV-1 subtypes among travelers crossing the border at the HeKou land port. Between 2003 and 2012, 22,799 persons were randomly recruited from people entering China from Vietnam. In this crossing border population, a total of 161 (0.71%) travelers were determined as HIV-1-positive. From them, 140 HIV-1-positive serum samples were collected for RNA extraction and subsequent RT-nested PCR amplification of the group-specific antigen (gag)-RT with a length of 2.6 kb. The DNA sequences were analyzed to determine the HIV-1 subtypes/recombinants. We found that the circulating recombinant form 01_AE (CRF01_AE) was the most common HIV-1 subtype, accounting for 49.4% (41/83) of the subtyped 83 samples, followed by CRF08_BC (26.5%, 22/83) and CRF07_BC (7.2%, 6/83). Only 1 sample was classified as subtype C. Thirteen cases could not be clustered into any known subtypes or CRFs and presented as unique recombinant forms (URFs). Of them, 6 recombination patterns were identified. They had distinct structures consisting of fragments of subtypes B, C, CRF01_AE, CRF07_BC and CRF08_BC. Between 2003 and 2012, CRF01_AE and CRE08_BC were shown to be the most prevalent recombinant forms identified each year. But yearly change of each subtype is uncertain regular among in these travelers during the past decade. Understanding the distribution of HIV-1 subtypes/recombinants and how it changes across time among individuals entering China from Vietnam through this land port is crucial to establish strategies for the prevention of HIV cross-border transmission.

Non-normal random effects models for immunogenicity assay cut point determination.

Administration of biological therapeutics can generate undesirable immune responses that may induce anti-drug antibodies (ADAs). Immunogenicity can negatively affect patients, ranging from mild reactive effect to hypersensitivity reactions or even serious autoimmune diseases. Assessment of immunogenicity is critical as the ADAs can adversely impact the efficacy and safety of the drug products. Well-developed and validated immunogenicity assays are required by the regulatory agencies as tools for immunogenicity assessment. Key to the development and validation of an immunogenicity assay is the determination of a cut point, which serves as the threshold for classifying patients as ADA positive(reactive) or negative. In practice, the cut point is determined as either the quantile of a parametric or nonparametric empirical distribution. The parametric method, which is often based on a normality assumption, may lead to biased cut point estimates when the normality assumption is violated. The non-parametric method, which yields unbiased estimates of the cut point, may have low efficiency when the sample size is small. As the distribution of immune responses are often skewed and sometimes heavy-tailed, we propose two non-normal random effects models for cut point determination. The random effects, following a skew-t or log-gamma distribution, can incorporate the skewed and heavy-tailed responses and the correlation among repeated measurements. Simulation study is conducted to compare the proposed method with the current normal and nonparametric alternatives. The proposed models are also applied to a real dataset generated from assay validation studies.

Sample size consideration for immunoassay screening cut-point determination.

Past decades have seen a rapid growth of biopharmaceutical products on the market. The administration of such large molecules can generate antidrug antibodies that can induce unwanted immune reactions in the recipients. Assessment of immunogenicity is required by regulatory agencies in clinical and nonclinical development, and this demands a well-validated assay. One of the important performance characteristics during assay validation is the cut point, which serves as a threshold between positive and negative samples. To precisely determine the cut point, a sufficiently large data set is often needed. However, there is no guideline other than some rule-of-thumb recommendations for sample size requirement in immunoassays. In this article, we propose a systematic approach to sample size determination for immunoassays and provide tables that facilitate its applications by scientists.

Prediction of outcomes in crescentic IgA nephropathy in a multicenter cohort study.

Crescentic IgA nephropathy (IgAN), defined as >50% crescentic glomeruli on kidney biopsy, is one of the most common causes of rapidly progressive GN. However, few studies have characterized this condition. To identify risk factors and develop a prediction model, we assessed data from patients ≥ 14 years old with crescentic IgAN who were followed ≥ 12 months. The discovery cohort comprised 52 patients from one kidney center, and the validation cohort comprised 61 patients from multiple centers. At biopsy, the mean serum creatinine (SCr) level ± SD was 4.3 ± 3.4 mg/dl, and the mean percentage of crescents was 66.4%± 15.8%. The kidney survival rates at years 1, 3, and 5 after biopsy were 57.4%± 4.7%, 45.8%± 5.1%, and 30.4%± 6.6%, respectively. Multivariate Cox regression revealed initial SCr as the only independent risk factor for ESRD (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.10 to 1.57; P=0.002). Notably, the percentage of crescents did not associate independently with ESRD. Logistic regression showed that the risk of ESRD at 1 year after biopsy increased rapidly at SCr>2.7 mg/dl and reached 90% at SCr>6.8 mg/dl (specificity=98.5%, sensitivity=64.6% for combined cohorts). In both cohorts, patients with SCr>6.8 mg/dl were less likely to recover from dialysis. Analyses in additional cohorts revealed a similar association between initial SCr and ESRD in patients with antiglomerular basement membrane disease but not ANCA-associated systemic vasculitis. In conclusion, crescentic IgAN has a poor prognosis, and initial SCr concentration may predict kidney failure in patients with this disease.

Reliability-based anti-disturbance control for systems with parametric stochastic uncertainty: A probabilistic LMI approach.

We propose a reliability-based anti-disturbance control (RADC) method for systems with parametric stochastic uncertainty based on the linear matrix inequality (LMI) and the limit state function. Differing from the existing anti-disturbance control, the parametric stochastic uncertainty is considered in both the concerned system and the exogenous disturbance system. With this consideration, the condition for system stability and performance robustness is described by a stochastic LMI which holds with a certain probability (reliability). Through the limit state function method, the stochastic LMI is subtly transformed into two probabilistic LMIs for two different cases. The proposed probabilistic LMIs contain two probabilistic parameters of reliability indexes that quantify the effect of parametric stochastic uncertainty. At different prescribed reliability indexes, controllers with different reliability can be flexibly and reliably designed. Two illustrative examples with Monte-Carlo verification are presented to demonstrate the feasibility and effectiveness of the proposed RADC method.

Reproductive Ability Disparity in the Pacific Whiteleg Shrimp (Penaeus vannamei): Insights from Ovarian Cellular and Molecular Levels.

The Pacific whiteleg shrimp (Penaeus vannamei) is a highly significant species in shrimp aquaculture. In the production of shrimp larvae, noticeable variations in the reproductive capacity among female individuals have been observed. Some females experience slow gonadal development, resulting in the inability to spawn, while others undergo multiple maturations and contribute to the majority of larval supply. Despite numerous studies that have been conducted on the regulatory mechanisms of ovarian development in shrimp, the factors contributing to the differences in reproductive capacity among females remain unclear. To elucidate the underlying mechanisms, this study examined the differences in the ovarian characteristics between high and low reproductive bulks at different maturity stages, focusing on the cellular and molecular levels. Transmission electron microscopy analysis revealed that the abundance of the endoplasmic reticulum, ribosomes, mitochondria, and mitochondrial cristae in oocytes of high reproductive bulk was significantly higher than that of the low reproductive bulk in the early stages of ovarian maturation (stages I and II). As the ovaries progressed to late-stage maturation (stages III and IV), differences in the internal structures of oocytes between females with different reproductive capacities gradually diminished. Transcriptome analysis identified differentially expressed genes (DEGs) related to the mitochondria between two groups, suggesting that energy production processes might play a crucial role in the observed variations in ovary development. The expression levels of the ETS homology factor (EHF) and PRDI-BF1 and RIZ homology domain containing 9 (PRDM9), which were significantly different between the two groups, were compared using qRT-PCR in individuals at different stages of ovarian maturation. The results showed a significantly higher expression of the EHF gene in the ovaries of high reproductive bulk at the II and IV maturity stages compared to the low reproductive bulk, while almost no expression was detected in the eyestalk tissue of the high reproductive bulk. The PRDM9 gene was exclusively expressed in ovarian tissue, with significantly higher expression in the ovaries of the high reproductive bulk at the four maturity stages compared to the low reproductive bulk. Fluorescence in situ hybridization further compared the expression patterns of EHF and PRDM9 in the ovaries of individuals with different fertility levels, with both genes showing stronger positive signals in the high reproductive bulk at the four ovarian stages. These findings not only contribute to our understanding of the regulatory mechanisms involved in shrimp ovarian development, but also provide valuable insights for the cultivation of new varieties aimed at improving shrimp fecundity.

Multiplicative fault concept and fault observer design for reliability study of degrading reaction wheel.

The reaction wheel is a typical actuator and a crucial weak link in the spacecraft attitude control system, and much attention has been paid to its reliability problem. Due to limited samples and high cost for reaction wheel life tests, a simulation method by introducing attitude coupling dynamics and multiplicative fault concept is developed to analyze the logic of electric current as a performance indicator and verify its accuracy for reliability modeling. Furthermore, a new and intrinsic performance indicator of multiplicative fault is proposed for more application scenarios of reliability modeling and an adaptive sliding mode observer is designed for fault estimation. An illustrative example shows that the performance indicator of multiplicative fault can be used for various mission scenarios but requires certain persistent excitation, while electric current is the opposite.

Combining a protein-targeting small molecule and a thiol-targeting small molecule for detecting a serum risk marker of liver tumor recurrence.

This work proposes a novel bioassay designed to detect the 2B receptor of serotonin in serum samples, which can serve as a risk marker for cancer recurrence after surgical resection. Traditional methods for detecting this marker are often costly and time-consuming, requiring specialized reagents and equipment. The new bioassay is designed to enable direct and reagent-less detection of the 2B receptor in serum samples, without the need of antibodies or enzymes. The assay uses a small molecule ligand for the 2B receptor combined with a thiol-targeting fluorescent dye on a compact peptide-based molecular frame. This design allows for a rapid and specific readout of the fluorescent signal upon probe-protein interaction. In addition, the covalent biosensing process used in the assay allows for signal enhancement by electrochemical cross-linking of serum proteins. The bioassay was successfully used to detect the 2B receptor in serum samples from hepatocarcinoma patients, indicating its potential as a powerful tool for early cancer detection and monitoring.

A novel peptide-templated AgNPs nanoprobe for theranostics of prostate cancer.

Prostate specific membrane antigen (PSMA)-positive exosomes have the potential to serve as highly sensitive biomarkers for prostate cancer detection. Herein, a sensitive electrochemical biosensor for the ultrasensitive detection of PSMA-positive exosomes has been constructed based on a peptide-templated AgNPs nanoprobe. In this work, PSMA-specific binding peptides immobilized on a gold electrode were responsible for prostate cancer-derived exosomes capturing. Well-designed peptide (CCY- LWYIKC) serves a dual role: as a signal probe and as a recognizer in the exosomes-identification process. Specifically, LWYIKC bind to cholesterol at the exosome membranes, and CCY function as peptide templates to host a large number of silver nanoparticles, leading to a strong electrochemical signal. Thus, the concentration of exosomes can be quantified via electrochemical signal. This innovative method displayed a wide detection range of 102 to 108 particles/µL and a detection limit as low as 37 particles/µL. Notably, the method has shown outstanding performance when validated using clinical samples, suggesting its potential for clinical applications.

Survival benefit of local consolidative therapy for patients with single-organ metastatic pancreatic cancer: a propensity score-matched cross-sectional study based on 17 registries.

Background: The continuous exploration of oligometastatic disease has led to the remarkable achievements of local consolidative therapy (LCT) and favorable outcomes for this disease. Thus, this study investigated the potential benefits of LCT in patients with single-organ metastatic pancreatic ductal adenocarcinoma (PDAC). Methods: Patients with single-organ metastatic PDAC diagnosed between 2010 - 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to minimize selection bias. Factors affecting survival were assessed by Cox regression analysis and Kaplan-Meier estimates. Results: A total of 12900 patients were identified from the database, including 635 patients who received chemotherapy combined with LCT with a 1:1 PSM with patients who received only chemotherapy. Patients with single-organ metastatic PDAC who received chemotherapy in combination with LCT demonstrated extended median overall survival (OS) by approximately 57%, more than those who underwent chemotherapy alone (11 vs. 7 months, p < 0.001). Furthermore, the multivariate Cox regression analysis revealed that patients that received LCT, younger age (< 65 years), smaller tumor size (< 50 mm), and lung metastasis (reference: liver) were favorable prognostic factors for patients with single-organ metastatic PDAC. Conclusion: The OS of patients with single-organ metastatic pancreatic cancer who received LCT may be prolonged compared to those who received only chemotherapy. Nevertheless, additional prospective randomized clinical trials are required to support these findings.