Heterogeneous changes in gut and tumor microbiota in patients with pancreatic cancer: insights from clinical evidence.

BACKGROUND: Pancreatic cancer is the foremost contributor to cancer-related deaths globally, and its prevalence continues to rise annually. Nevertheless, the underlying mechanisms behind its development remain unclear and necessitate comprehensive investigation. METHODS: In this study, a total of 29 fresh stool samples were collected from patients diagnosed with pancreatic cancer. The gut microbial data of healthy controls were obtained from the SRA database (SRA data number: SRP150089). Additionally, 28 serum samples and diseased tissues were collected from 14 patients with confirmed pancreatic cancer and 14 patients with chronic pancreatitis. Informed consent was obtained from both groups of patients. Microbial sequencing was performed using 16s rRNA. RESULTS: The results showed that compared with healthy controls, the species abundance index of intestinal flora in patients with pancreatic cancer was increased (P < 0.05), and the number of beneficial bacteria at the genus level was reduced (P < 0.05). Compared with patients with chronic pancreatitis, the expression levels of CA242 and CA199 in the serum of patients with pancreatic cancer were increased (P < 0.05). The bacterial richness index of tumor microorganisms in patients with pancreatic cancer increased, while the diversity index decreased(P < 0.05). Furthermore, there was a change in the species composition at the genus level. Additionally, the expression level of CA242 was found to be significantly positively correlated with the relative abundance of Acinetobacter(P < 0.05). CONCLUSION: Over all, the expression levels of serum tumor markers CA242 and CA19-9 in patients with pancreatic cancer are increased, while the beneficial bacteria in the intestine and tumor microenvironment are reduced and pathogenic bacteria are increased. Acinetobacter is a specific bacterial genus highly expressed in pancreatic cancer tissue.

Optical fiber surface plasmon resonance sensor using electroless-plated gold film for thrombin detection.

This paper describes the simple and label-free detection of thrombin using optical fiber surface plasmon resonance (SPR) sensors based on gold films prepared by the cost-effective method of electroless plating. The plating conditions for simultaneously obtaining gold film on cylindrical core and end surfaces of an optical fiber suitable for measurement were optimized. The fabricated sensor exhibited a linear refractive index sensitivity of 2150 nm/RIU and 7.136 (a.u.)/RIU in the refractive index of 1.3329-1.3605 interrogated by resonance wavelength and amplitude methods respectively and a single wavelength monitoring method was proposed to investigate the sensing performance of this sensor. Polyadenine diblock and thiolated thrombin aptamers were immobilized on gold nanoparticles and gold films respectively to implement a sandwich optical fiber assay for thrombin. The developed optical fiber SPR sensors were successfully used in the determination of thrombin down to 0.56 nM over a wide range from 2 to 100 nM and showed good selectivity for thrombin, which indicated their potential clinical applications for biomedical samples.

CPA-Cas12a-based lateral flow strip for portable assay of Methicillin-resistant Staphylococcus aureus in clinical sample.

The rapid and accurate identification of methicillin-resistant Staphylococcus aureus at an early antibiotic therapy stage would be benefit to disease diagnosis and antibiotic selection. Herein, we integrated cross-priming amplification (CPA) and CRISPR/Cas 12a (designated as CPA-Cas 12a) systems to establish a sensitive and efficient lateral flow assay to detect methicillin-resistant Staphylococcus aureus. This assay relies on the CPA isothermal nucleic acid amplification strategy which can amplify the DNA extracted from Staphylococcus aureus and accompanying the indiscriminately trans-cleavage process of Cas 12a/CrRNA duplex after recognizing specific sequence. Taking the advantage of reporter and high turnover Cas 12a activity, a dramatic change in response was achieved to produce a significant increase in the analytical sensitivity. The signal conversion and output were realized using a lateral flow strip to achieve field-deployable detection. Furthermore, this bioassay was accommodated with a microfluidic device to realize automatically portable detection. This proposed assay completed within 30 min with the detection limit of 5 CFU mL-1, was verified by testing bacterial suspension and 202 clinical samples. Given the high sensitivity, specificity and efficiency, this colorimetric readout assay through strip could be further promoted to the clinical diagnosis, clinical medication of multidrug-resistant bacteria.

Electrochemical Biosensor for Detection of the CYP2C19*2 Allele Based on Exonuclease â ¢.

Currently, the therapeutic effect of clopidogrel differs considerably among individuals and is thought to be closely related to the genetic polymorphism of CYP2C19. The CYP2C19*2 gene can reduce the antiplatelet aggregation effect of clopidogrel, which increases the risk of major cardiovascular adverse events in patients. In this research, we report a new type of biosensor for the highly sensitive detection of the CYP2C19*2 gene based on exonuclease III assisted electric signal amplification and the use of calixarene to enrich electrical signal substances. Specifically, under the best conditions, the logarithmic concentrations of the analytes have a good linear relationship with the peak current in the range of 0.01 fM to 100 pM and the detection limit is 13.49 aM. The results have also shown that this method has good selectivity, high sensitivity, and stability, etc., and will provide a very promising application for the detection of the CYP2C19*2 gene and other biological molecules by replacing corresponding nucleic acid sequences.

Detection of carcinoembryonic antigens using a wavy gold-silver alloy nanoplate enhanced surface plasmon resonance imaging biosensor.

Carcinoembryonic antigen (CEA) is regarded as a promising broad spectrum tumor biomarker for clinical diagnosis, progression, and prognosis. Surface plasmon resonance imaging (SPRi) was considered as one of the powerful tools for immunoassay with advantages of label-free, real-time detection with high-throughput. Herein, wavy gold-silver alloy nanoplates functionalized with anti-CEA antibodies providing high protein loading capacity and high mass are used as signal enhancers for CEA detection through SPRi sandwich assay. The present method exhibits a dynamic range for CEA determination from 0.1 to 312.5 ng mL-1 and a detection limit of 0.55 ng mL-1, well below normal physiological levels. This biosensing approach demonstrates the advantages of wavy gold-silver alloy nanoplates compared to conventional gold nanoparticles as a signal amplifier to enhance the SPRi signal, which is expected to become a new prospect for detection of cancer markers in biomedical research and clinical diagnosis.

Nanoparticle-based drug delivery systems for the treatment of cardiovascular diseases.

Cardiovascular disease is the most common health problem worldwide and remains the leading cause of morbidity and mortality. Despite recent advances in the management of cardiovascular diseases, pharmaceutical treatment remains suboptimal because of poor pharmacokinetics and high toxicity. However, since being harnessed in the cancer field for the delivery of safer and more effective chemotherapeutics, nanoparticle-based drug delivery systems have offered multiple significant therapeutic effects in treating cardiovascular diseases. Nanoparticle-based drug delivery systems alter the biodistribution of therapeutic agents through site-specific, target-oriented delivery and controlled drug release of precise medicines. Metal-, lipid-, and polymer-based nanoparticles represent ideal materials for use in cardiovascular therapeutics. New developments in the therapeutic potential of drug delivery using nanoparticles and the application of nanomedicine to cardiovascular diseases are described in this review. Furthermore, this review discusses our current understanding of the potential role of nanoparticles in metabolism and toxicity after therapeutic action, with a view to providing a safer and more effective strategy for the treatment of cardiovascular disease.

Distinct immune responses in the early phase to natural SARS-CoV-2 infection or vaccination.

Immune responses elicited by viral infection or vaccination play key roles in the viral elimination and the prevention of reinfection, as well as the protection of healthy persons. As one of the most widely used Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there have been increasing concerns about the necessity of additional doses of inactivated vaccines, due to the waning immune response several months after vaccination. To further optimize inactivated SARS-CoV-2 vaccines, we compared immune responses to SARS-CoV-2 elicited by natural infection and immunization with inactivated vaccines in the early phase. We observed the lower antibody levels against SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in the early phase of postvaccination with a slow increase, compared to the acute phase of SARS-CoV-2 natural infection. Specifically, IgA antibodies have the most significant differences. Moreover, we further analyzed cytokine expression between these two groups. A wide variety of cytokines presented high expression in the infected individuals, while a few cytokines were elicited by inactivated vaccines. The differences in antibody responses and cytokine levels between natural SARS-CoV-2 infection and vaccination with the inactivated vaccines may provide implications for the optimization of inactivated SARS-CoV-2 vaccines and the additional application of serological tests.

Novel Ti3C2Tx MXene nanozyme with manageable catalytic activity and application to electrochemical biosensor.

In this work, Ti3C2Tx MXene was identified as efficient nanozyme with area-dependent electrocatalytic activity in oxidation of phenolic compounds, which originated from the strong adsorption effect between the phenolic hydroxyl group and the oxygen atom on the surface of Ti3C2Tx MXene flake. On the basis of the novel electrocatalytic activity, Ti3C2Tx MXene was combined with alkaline phosphatase to construct a novel cascading catalytic amplification strategy using 1-naphthyl phosphate (1-NPP) as substrate, thereby realizing efficient electrochemical signal amplification. Taking advantage of the novel cascading catalytic amplification strategy, an electrochemical biosensor was fabricated for BCR/ABL fusion gene detection, which achieved excellent sensitivity with linear range from 0.2 fM to 20 nM and limit of detection down to 0.05 fM. This biosensor provided a promising tool for ultrasensitive fusion gene detection in early diagnosis of chronic myelogenous leukemia and acute lymphocytic leukemia. Moreover, the manageable catalytic activity of MXene broke a path for developing nanozymes, which possessed enormous application potential in not only electrochemical analysis but also the extensive fields including organic synthesis, pollutant disposal and so on.

An enzyme-powered, three-dimensional lame DNA walker.

Molecular machines constructed by three-dimensional (3-D) DNA walker have emerged as a hot topic in applications such as novel biosensors, cargo delivery platforms and intracellular imaging. Herein, we first propose a lame DNA walker that can randomly and autonomously move on microsphere-based 3-D track. The stochastic lame walker has a long leg mainly responsible for persistent movement and a short leg cutting substrates rapidly. Its motion is propelled by a nicking endonuclease cleavage of hybridized DNA tracks. Kinetic and persistent study show that the lame DNA walker enables reaction equilibrium at 30 min, need a cleat domain of at least 14 nucleotides and can persistently move on 3-D tracks with an average rate of 6.467 × 10-11 M s-1. We also demonstrate that the lame walker can be used to detect target DNA in the detection range of 10 pM-5 nM with high specificity by toehold exchange mechanism. This work will further expand the performance of 3-D DNA walkers and substantially contributes to the improved understanding of DNA walking systems.

A triple-amplification differential pulse voltammetry for sensitive detection of DNA based on exonuclease III, strand displacement reaction and terminal deoxynucleotidyl transferase.

In this research, a sensitive and specific electrochemical biosensor for DNA detection was constructed. The highly sensitivity of this biosensor is due to the exploitation of exonuclease III-assisted double recycling and toehold-mediated strand displacement recycling to achieve the target triple recycling amplification, thus generating a large amount of Y-shaped DNA structures. Combination with a terminal deoxynucleotidyl transferase (TDT)-mediated cascaded signal amplification strategy can catalyze the repetitive incorporation of biotin-dUTP to the 3'-OH of the Y-shaped DNA. Via biotin-streptavidin interaction, multiple streptavidin-alkaline phosphatases were conjugated to the surface of an Au electrode and generated a sharply increasing electrochemical signal in a 1-naphthyl phosphate (1-NP) solution. In this method, an impressive detection limit of 0.05 fM was obtained, presenting outstanding selectivity with a dynamic response scope between 0.1 fM and 1 nΜ. Thus, the designed biosensor opens an avenue for DNA detection in clinical molecular diagnostics, pathogen detection, gene therapy, food safety and environmental monitoring.

Bronchopulmonary infection of Lophomonas blattarum: a case and literature review.

Human infections with Lophomonas blattarum are rare. However, the majority of the infections occurred in China, 94.4% (136 cases) of all cases in the world. This infection is difficult to differentiate from other pulmonary infections with similar symptoms. Here we reported a case of L. blattarum infection confirmed by bronchoalveolar lavage fluid smear on the microscopic observations. The patient was a 21-year-old female college student. The previous case which occurred in Chongqing was 20 years ago. We briefly reviewed on this infection reported in the world during the recent 20 years. The epidemiological characteristics, possible diagnostic basis, and treatment of this disease is discussed in order to provide a better understanding of recognition, diagnosis, and treatment of L. blattarum infection.