Feasibility and Acceptability Evaluation of a Digital Therapeutic Program for Improving Cancer Prevention: A Quasi-experimental Pre-post Interventional Pilot Study.

Previous studies have proved that healthy behaviors hinder the onset and progression of tumors. Digital therapeutics (DTx), playing a pivotal role in facilitating behavioral adjustments through educational interventions, lifestyle support, and symptom monitoring, contribute to the goal of tumor prevention. We aim to optimize the evaluation of the feasibility and acceptability of DTx for cancer prevention. This involves assessing AITI's daily activity rates and user feedback, and comparing changes in behavioral habits and differences in SF-36 before and after the intervention. In a 4-week trial with 57 participants engaging actively, we found both the average daily activity rate and 4-week retention rate at 35 (61.4%). The USE Questionnaire scores (validity, ease of use, acquisition, and satisfaction) ranged from 68.06 to 83.10, indicating AITI's user-friendliness and acceptability. Furthermore, positive habit changes were noted among participants in exercise and diet (p < 0.0001), suggesting the effectiveness of the DTx approach in modifying behavioral habits related to physical activity and nutrition. This pilot study underscores the potential of DTx in advancing cancer prevention. However, larger and longer studies are needed to comprehensively assess its impact.

Self-propelled assembly of nanoparticles with self-catalytic regulation for tumour-specific imaging and therapy.

Targeted assembly of nanoparticles in biological systems holds great promise for disease-specific imaging and therapy. However, the current manipulation of nanoparticle dynamics is primarily limited to organic pericyclic reactions, which necessitate the introduction of synthetic functional groups as bioorthogonal handles on the nanoparticles, leading to complex and laborious design processes. Here, we report the synthesis of tyrosine (Tyr)-modified peptides-capped iodine (I) doped CuS nanoparticles (CuS-I@P1 NPs) as self-catalytic building blocks that undergo self-propelled assembly inside tumour cells via Tyr-Tyr condensation reactions catalyzed by the nanoparticles themselves. Upon cellular internalization, the CuS-I@P1 NPs undergo furin-guided condensation reactions, leading to the formation of CuS-I nanoparticle assemblies through dityrosine bond. The tumour-specific furin-instructed intracellular assembly of CuS-I NPs exhibits activatable dual-modal imaging capability and enhanced photothermal effect, enabling highly efficient imaging and therapy of tumours. The robust nanoparticle self-catalysis-regulated in situ assembly, facilitated by natural handles, offers the advantages of convenient fabrication, high reaction specificity, and biocompatibility, representing a generalizable strategy for target-specific activatable biomedical imaging and therapy.

Pulsatile Gonadotropin-Releasing Hormone Therapy Is Associated With Better Spermatogenic Outcomes than Gonadotropin Therapy in Patients With Pituitary Stalk Interruption Syndrome.

OBJECTIVE: To compare the effects of combined gonadotropin and pulsatile gonadotropin-releasing hormone (GnRH) therapy on spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS). METHODS: Male patients with PSIS (N = 119) were retrospectively studied. Patients received pulsatile GnRH therapy (N = 59) were divided into response and poor-response groups based on luteinizing hormone (LH) levels after 1-month treatment with a cutoff value of 1 or 2 IU/L. Participants with gonadotropin therapy were divided into human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) group (N = 60), and patients with pulsatile GnRH therapy were classified into GnRH group (N = 28) with treatment duration ≥6 months. RESULTS: The overall success rates of spermatogenesis for hMG/hCG and GnRH therapy were 51.67% (31/60) vs 33.90% (20/59), respectively. GnRH group required a shorter period to induce spermatogenesis (8 vs 15 months, P = .019). hMG/hCG group had higher median total testosterone than GnRH group [2.16, interquartile range(IQR) 1.06-4.89 vs 1.31, IQR 0.21-2.26 ng/mL, P = .004]. GnRH therapy had a beneficial effect on spermatogenesis compared to hMG/hCG therapy (hazard ratio 1.97, 95% confidence interval 1.08-3.57, P = .026). In patients with pulsatile GnRH therapy, compared with the poor-response group, the response group had a higher successful spermatogenesis rate (5.00% vs 48.72%, P = .002) and higher median basal total testosterone (0.00, IQR 0.00-0.03 vs 0.04, IQR 0.00-0.16 ng/mL, P = .026) with LH = 1 IU/L as the cutoff value after 1-month pulsatile GnRH therapy. CONCLUSIONS: Pulsatile GnRH therapy was superior to hMG/hCG therapy for spermatogenesis in patients with PSIS. Earlier spermatogenesis and higher concentrations of sperm could be obtained in the GnRH group if patients received therapy over 6 months.

Mixed hypogonadism: a neglected combined form of hypogonadism.

PURPOSE: Kallmann syndrome is a rare disease characterized by delayed puberty, infertility and anosmia. We report the clinical and genetic characteristics of three patients with Kallmann syndrome who presented with Klinefelter syndrome and defined this neglected combined form of hypogonadism as mixed hypogonadism. METHODS: Clinical data and examinations were obtained, including laboratory examination and magnetic resonance imagination (MRI) of the olfactory structures. Congenital hypogonadotropic hypogonadism (CHH) related genes were screened by next generation sequencing (NGS). RESULTS: Three patients with Kallmann syndrome were included. They had co-existence with Klinefelter syndrome and showed hypogonadotropic hypogonadism. Patient 1 was complicated with germinoma. CONCLUSION: Mixed hypogonadism was defined as hypogonadotropic hypogonadism in Klinefelter syndrome or primary testicular disease. Clinicians should be alert to mixed hypogonadism when spermatogenesis induction failed in patients with CHH or gonadotropin levels decrease in patients with Klinefelter syndrome.

Preparation of Novel Sea Cucumber Intestinal Peptides to Promote Tibial Fracture Healing in Mice by Inducing Differentiation of Hypertrophic Chondrocytes to the Osteoblast Lineage.

SCOPE: Hypertrophic chondrocytes have a decisive regulatory role in the process of fracture healing, and the fate of hypertrophic chondrocytes is not only apoptosis. However, the mechanism of sea cucumber (Stichopus japonicus) intestinal peptide (SCIP) on fracture promotion is still unclear. This study aims to investigate the effect of sea cucumber intestinal peptide on the differentiation fate of hypertrophic chondrocytes in a mouse tibial fracture model. METHODS AND RESULTS: Mice are subjected to open fractures of the right tibia to establish a tibial fracture model. The results exhibit that the SCIP intervention significantly promotes the mineralization of cartilage callus, decreases the expression of the hypertrophic chondrocyte marker Col X, and increases the expression of the osteoblast marker Col I. Mechanically, SCIP promotes tibial fracture healing by promoting histone acetylation and inhibiting histone methylation, thereby upregulating pluripotent transcription factors induced the differentiation of hypertrophic chondrocytes to the osteoblast lineage in a manner distinct from classical endochondral ossification. CONCLUSION: This study is the first to report that SCIP can promote tibial fracture healing in mice by inducing the differentiation of hypertrophic chondrocytes to the osteoblast lineage. SCIP may be considered raw material for developing nutraceuticals to promote fracture healing.

Population pharmacokinetics and pharmacogenetics of apatinib in adult cancer patients.

AIMS: Apatinib is widely used in Chinese cancer patients. As the in vivo drug disposition of apatinib has large individual differences, adverse events are prone to occur. Cytochrome P450 (CYP)3A5 and cancer types maybe the main factors affecting this individual differences. The objective of our study was to establish a population pharmacokinetics (PK) model of apatinib in adult cancer patients, and to explore optimal dosage regimens for individualized treatment. METHODS: Adult patients with various types of cancer treated with apatinib were enrolled. The concentration of apatinib in plasma was determined by high-performance liquid chromatography-tandem mass spectrometry. CYP3A5 genotype was determined using TaqMan allelic discrimination technique. The population PK model was developed by NONMEM V7.4. The dosing regimen was optimized based on Monte Carlo simulations. RESULTS: A population PK model of apatinib in adult cancer patient was established. CYP3A5 genotype and systemic cancer type (digestive system cancers, nondigestive system cancers) were the most significant covariates for PK parameters. Patients with CYP3A5*1 expressers (CYP3A5*1/*1 and CYP3A5*1/*3) had lower apparent clearance and apparent volume of distribution than patients who do not express CYP3A5*1 (CYP3A5*3/*3). Patients with nondigestive system cancer had higher apparent volume of distribution and absorption rate constant than digestive system cancer. The results of dose simulation suggest that the apatinib dose in patients who do not express CYP3A5*1 should be 33.33-50.00% higher than that in CYP3A5*1 expressers. CONCLUSIONS: A population PK model of apatinib in adult cancer patients was established. CYP3A5 genotype and systemic cancer type had concurrent effects on PK parameters. CYP3A5 patients who do not express CYP3A5*1 required higher doses.

A novel method for making cell blocks with higher cellular yield.

INTRODUCTION: Cytopathology is an important part of pathology that is used to diagnose disease on the cellular level. The application of the cell block (CB) technique plays a vital role in cytological diagnosis, as blocks and slides can be further used for special stains, immunohistochemistry (IHC), and molecular pathological analysis. Several methods for making CBs have been reported, but their procedures and cellular yield are still deemed unsatisfactory. In this article, we used gellan gum (GG) as an adjuvant for CBs, which resulted in higher cellular yield with simpler procedures. METHODS: CBs were prepared by using GG, copper sulfate, plasma/thrombin, or pregelatinized starch methods. The procedures of each of these four methods were then compared. CB sections were stained with hematoxylin and eosin (H&E), and the background and morphological features seen by H&E staining were compared. A preliminary IHC and fluorescence in situ hybridization (FISH) study was performed using cytology specimens from eleven and five cases, respectively. The expression of immunocomplex by IHC and the molecular signals detected by FISH were compared in CB sections made by the four methods and a section derived from the biopsy specimen block from the same patient. Feulgen staining, Alcian blue staining, and Masson trichrome staining were performed on the CB sections from 3 cases of pleural fluid. The cellular yield of CB sections from 83 cases according to the four methods was compared using NDP analysis software. RESULTS: The results demonstrated that sections derived from CBs made with GG had a clear background and good morphological features by H&E staining. The expression of immunocomplex by IHC and the molecular signals of FISH detection in the sections from CBs made by GG were accurately located just as those in biopsy sections from the same patient. The DNA, acidic mucus, and fibrin could be clearly identified through special stains in the CB sections. The procedures involved in the GG method were easily controllable and the coagulated gel increased the ease by which the CB was embedded and sectioned. Specifically, sections from CBs made by the GG method contained higher cellular yield because cells could be concentrated on the bottom of the gel after centrifugation. CONCLUSION: This novel method for making CBs is a practical, simple method that can result in higher cellular yield. This method is therefore worth promoting in clinical applications.

pH-responsive Sulfated Hyaluronic Acid Nanoparticles Targeting Tumor Cells and CAFs for the Treatment of Breast Cancer.

BACKGROUND: Tumor metastasis is a main cause of death in patients with breast cancer. The cross-talk between cancer-associated fibroblasts (CAFs) and tumor cells plays an important role in promoting tumor invasion and metastasis. It is important to develop a novel delivery system to inhibit tumor development by simultaneously targeting both CAFs and tumor cells. OBJECTIVES: The main objective of this research was to prepare nanoparticles to inhibit tumor proliferation and migration by blocking the cross-talk of tumor-CAFs. Additionally, a novel "MCF- 7+NIH/3T3" mixed cell model was established to mimic the tumor microenvironment (TME). METHODS: In this study, the pH-responsive nanoparticles (MIF/DOX-sul-HA NPs) based on sulfated hyaluronic acid (sul-HA) polymers were prepared for co-delivery of doxorubicin (DOX) and mifepristone (MIF). The effects of anti-proliferation and anti-metastasis of MIF/DOX-sul-HA NPs were investigated both in vitro and in vivo. RESULTS: The results showed that MIF/DOX-sul-HA NPs were nearly spherical in shape with narrow particle size distribution and pH-responsive drug release, and could be taken up by both MCF-7 and NIH/3T3 cells. Compared with MCF-7 cells alone, the anti-tumor effect of single DOX was weak in the "MCF-7+NIH/3T3" mixed cell model. MIF/DOX-sul-HA NPs exhibited strong effects of anti-proliferation and anti-metastasis than the free single drug. CONCLUSION: The sul-HA nanoparticles for co-delivery of DOX and MIF could be a promising combined therapy strategy for the treatment of breast cancer.

An electrochemical biosensor based on few-layer MoS2 nanosheets for highly sensitive detection of tumor marker ctDNA.

An electrochemical biosensor based on few-layer molybdenum disulfide (MoS2) nanosheets was fabricated for the highly sensitive detection of tumor marker circulating tumor DNA (ctDNA) in this paper. The MoS2 nanosheets with few layers were prepared by the shear stripping. Compared with the mechanical stripping method and the lithium ion intercalation method, this method is simpler to operate, and the prepared MoS2 nanosheets had good electrochemical activity. The biosensing platform was fabricated based on the discriminative affinity of MoS2 nanosheets towards single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Methylene blue (MB) was used as the signal molecule. The results showed that the detection of ctDNA by this sensor showed an excellent linear relationship in the concentration range of 1.0 × 10-7 M to 1.0 × 10-16 M, and the detection limit was 2.5 × 10-18 M. In addition, this sensor exhibited outstanding stability and specificity. This strategy provides an alternative approach for ctDNA detection and an effective sensing strategy for future in vitro cancer diagnosis by label-free detection.

Non-Invasive Monitoring of Human Health by Photoacoustic Spectroscopy.

For certain diseases, the continuous long-term monitoring of the physiological condition is crucial. Therefore, non-invasive monitoring methods have attracted widespread attention in health care. This review aims to discuss the non-invasive monitoring technologies for human health based on photoacoustic spectroscopy. First, the theoretical basis of photoacoustic spectroscopy and related devices are reported. Furthermore, this article introduces the monitoring methods for blood glucose, blood oxygen, lipid, and tumors, including differential continuous-wave photoacoustic spectroscopy, microscopic photoacoustic spectroscopy, mid-infrared photoacoustic detection, wavelength-modulated differential photoacoustic spectroscopy, and others. Finally, we present the limitations and prospects of photoacoustic spectroscopy.

Adjusted association between type 2 immunity and low risk thyroid nodules: a retrospective cohort study.

BACKGROUND: Immune responses, especially type 2 immunity, might be related to the prevalence of thyroid nodules, while the key regulators and potential pathways are remaining largely unknown. In addition, the immune status of individuals could be affected by mixed metabolic background. Herein our aim was to investigate the adjusted association between ultrasound-diagnosed low risk thyroid nodules and immune responses, excluding the interference of metabolic effects on immunity. METHODS: We retrospectively enrolled 1764 subjects who underwent a thorough thyroid ultrasound examination. To eliminate the interference of confounders, we used propensity score matching (PSM) to match age, gender, cigarette smoking and alcohol drinking, parameters that are related with metabolic syndrome (MetS). Then the potential effectors of immune responses involved in the laboratorial assays were evaluated. Binary logistic regression analysis was used to assess the independent predictors of thyroid nodules in a multivariate manner. RESULTS: The 1172 subjects were remained after PSM, and differences of demographic background between subjects with and without thyroid nodules were eliminated. Metabolic parameters comprising blood pressure, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein and serum uric acid were shown no significant difference between post-PSM subjects with and without thyroid nodules. Among the biochemistry and hematological parameters, white blood cell count and the positive rate of eosinophil percentage were increased in subjects with thyroid nodules than in those without thyroid nodules. In contrast, the positive rate of basophil percentage was lower in subjects with thyroid nodules than in those without thyroid nodules. In addition, the thyroid function test results showed that subjects with thyroid nodules had higher positive rates of antithyroglobulin antibody (TgAb) and antithyroid peroxidase antibody (TPOAb) than subjects without thyroid nodules. The logistic regression analysis indicated that the positive value of TgAb as well as high level of white blood cell count and BMI could serve as independent risk factors of thyroid nodules. CONCLUSIONS: The type 2 immune responses mediated by increased level of eosinophils, along with positive value of TgAb and TPOAb were associated with the presence of thyroid nodules. In addition, the potential role of basophils in protecting against thyroid nodules and the pathogenesis of immune-metabolic status remains to be elucidated.

Quench-Release-Based Fluorescent Immunosensor for the Rapid Detection of Tumor Necrosis Factor α.

Tumor necrosis factor α (TNF-α) is used as a biomarker for the diagnosis of various inflammatory and autoimmune diseases. In recent years, numerous approaches have been used for the qualitative and quantitative analyses of TNF-α. However, these methods have several drawbacks, such as a tedious and time-consuming process, high pH and temperature sensitivity, and increased chances of denaturation in vitro. Quenchbody (Q-body) is a fluorescence immunoprobe that functions based on the principle of photoinduced electron transfer and has been successful in detecting various substances. In this study, we constructed two Q-bodies based on a therapeutic antibody, adalimumab, to rapidly detect human TNF-α. Both sensors could detect TNF-α within 5 min. The results showed that the limit of detection (LOD) of TNF-α was as low as 0.123 ng/mL with a half-maximal effective concentration (EC50) of 25.0 ng/mL using the TAMRA-labeled Q-body, whereas the ATTO520-labeled Q-body had a LOD of 0.419 ng/mL with an EC50 of 65.6 ng/mL, suggesting that the Q-bodies could rapidly detect TNF-α with reasonable sensitivity over a wide detection range. These biosensors will be useful tools for the detection and monitoring of inflammatory biomarkers.

Mutant Allele Frequency-Based Intra-Tumoral Genetic Heterogeneity Related to the Tumor Shrinkage Mode After Neoadjuvant Chemotherapy in Breast Cancer Patients.

The shrinkage mode of tumor extent after neoadjuvant chemotherapy (NAC) is an important index to evaluate the odds of breast-conserving surgery. However, there is no sufficient measurement to predict the shrinkage mode after NAC. In this study, we analyzed 24 patients' formalin-fixed, paraffin-embedded samples before and after treatment and analyzed 456 cancer-related genes panel by using target next-generation sequencing. Meanwhile, the pathological shrinkage mode was reconstructed in three dimensions after surgery, and the genetic heterogeneity level was estimated by mutant-allele tumor heterogeneity (MATH). We measured the genetic intra-tumor heterogeneity and explored its correlation with the shrinkage mode after NAC. A total of 17 matched pair samples of primary tumor tissue and residual tumor tissue were successfully accessed. It was found that the most common mutated genes were TP53 and PIK3CA in both samples before and after NAC, and no recurrent mutations were significantly associated with the shrinkage mode. Besides, the MATH value of formalin-fixed, paraffin-embedded samples before and after NAC was analyzed by the area under the curve of the receiver operating characteristic, and it is feasible to classify patients into concentric shrinkage mode and non-concentric shrinkage mode in NAC based on the MATH threshold of 58. Our findings indicate that the MATH value was associated with the shrinkage mode of breast cancer in a non-linear model. Patients with the MATH value below the threshold of 58 before and after NAC displayed a concentric shrinkage mode. The area under the curve was 0.89, with a sensitivity of 0.69 and specificity of 1. Our study might provide a promising application of intra-tumor heterogeneity that is measured by MATH to make a choice of surgery.

Development of a Copper-Based Metal Organic Electrode for Nitrite Sensing.

BACKGROUND: Nitrite is naturally present in vegetables and added to processed meats to enhance their color and prolong their shelf life. It is of concern because it reacts to form nitrosamines, which have been linked to cancer. OBJECTIVE: To develop a quick, reliable, and inexpensive method for quantifying nitrite in foods. METHOD: A copper-based metal organic framework (Cu-MOF)/gold-platinum alloy nanoparticle(Au@Pt)-modified glassy carbon electrode (GCE) was developed via a simple wet chemical synthesis followed by electrochemical deposition of gold-platinum alloy nanoparticles onto the surface of a GCE. Morphological characterization and component analysis of the prepared nanomaterials were carried out by Fourier transform infrared spectroscopy and scanning electron microscopy. Cyclic voltammetry and electrochemical impedance spectroscopy were used to study the electrochemical behavior of the fabricated electrodes. RESULTS: The quantitative and specific detection of nitrite was obtained by the amperometric i-t method. At a pH of 7, temperature of 25°C, and ionic strength of 0.4 M, the electrode exhibited a linear range of 0.001-12.2 mM nitrite with a low detection limit of 72 nM (S/N = 3). CONCLUSIONS: The Cu-MOF/Au@Pt/GCE exhibited good repeatability, reproducibility, stability, and selectivity to provide a capable analysis method for food samples. HIGHLIGHTS: A Cu-MOF with a large surface area and high porosity was developed to provide an electrode with many active sites. The Au@Pt alloy nanoparticle improved the electrocatalytic activity toward nitrite. The synergistic action between the Cu-MOF and Au@Pt alloy nanoparticle enhanced the electrochemical performance of the sensor.

Recognizing lung cancer and stages using a self-developed electronic nose system.

Exhaled breath contains thousands of gaseous volatile organic compounds (VOCs) that could be used as non-invasive biomarkers of lung cancer. Breath-based lung cancer screening has attracted wide attention on account of its convenience, low cost and easy popularization. In this paper, the research of lung cancer detection and staging is conducted by the self-developed electronic nose (e-nose) system. In order to investigate the performance of the device in distinguishing lung cancer patients from healthy controls, two feature extraction methods and two different classification models were adopted. Among all the models, kernel principal component analysis (KPCA) combined with extreme gradient boosting (XGBoost) achieved the best results among 235 breath samples. The accuracy, sensitivity and specificity of e-nose system were 93.59%, 95.60% and 91.09%, respectively. Meanwhile, the device could innovatively classify stages of 90 lung cancer patients (i.e., 44 stage III and 46 stage IV). Experimental results indicated that the recognition accuracy of lung cancer stages was more than 80%. Further experiments of this research also showed that the combination of sensor array and pattern recognition algorithms could identify and distinguish the expiratory characteristics of lung cancer, smoking and other respiratory diseases.

Detection of lung cancer with electronic nose using a novel ensemble learning framework.

Breath analysis based on electronic nose (e-nose) is a promising new technology for the detection of lung cancer that is non-invasive, simple to operate and cost-effective. Lung cancer screening by e-nose relies on predictive models established using machine learning methods. However, using only a single machine learning method to detect lung cancer has some disadvantages, including low detection accuracy and high false negative rate. To address these problems, groups of individual learning models with excellent performance were selected from classic models, including support vector machine, decision tree, random forest, logistic regression andK-nearest neighbor regression, to build an ensemble learning framework (PCA-SVE). The output result of the PCA-SVE framework was obtained by voting. To test this approach, we analyzed 214 breath samples measured by e-nose with 11 gas sensors of four types using the proposed PCA-SVE framework. Experimental results indicated that the accuracy, sensitivity, and specificity of the proposed framework were 95.75%, 94.78%, and 96.96%, respectively. This framework overcomes the disadvantages of a single model, thereby providing an improved, practical alternative for exhaled breath analysis by e-nose.

Hyperhomocysteinemia Independently Associated with Adult Moyamoya Disease: Hospital Based Study of 237 Patients.

AIM: To clarify the risk factors for adult moyamoya disease (MMD) in patients from South China. MATERIAL AND METHODS: We prospectively studied adult patients who were diagnosed angiographically with MMD. The demographic profiles, medical history and clinical characteristics were compared between adult MMD and non-MMD stroke patients. Logistic regression analysis was used to determine the risk factors associated with adult MMD. RESULTS: A total of 35 adult MMD patients and 202 adults patients with non-MMD stroke were included. Of the 35 MMD patients, bilateral MMD occurred in 48.6% and bypass surgery was performed in 28.6%; these figures were significantly lower than those reported in patients from Korea and the United States (p < 0.05). After adjusting for baseline demographics and potential confounders, multivariate logistic regression analysis was conducted, which showed that the plasma homocysteine level (odds ratio [OR]: 1.10; 95% confidence interval [CI]: 1.06?1.14) and occupation as a technological worker (OR: 4.23; 95% CI: 1.65?10.89) were independently associated with adult MMD. CONCLUSION: Hyperhomocysteinemia and type of occupation were found to be independent risk factors for adult MMD in patients from South China. However, there is still a need for further research to clarify the pathogenesis of MMD. Given the lack of understanding about the risk factors and prevention measures for MMD, we suggest bypass surgery be used for MMD treatment in clinical practice in China to achieve more desirable effects in the management of the disease.

Recent advances in nanomaterial-based biosensors for the detection of exosomes.

Exosomes are a type of extracellular vesicle actively secreted by almost all eukaryotic cells. They are ideal candidates for reliable next-generation biomarkers in the early diagnosis and therapeutic response evaluation of cancer. Thus, the quantification of exosomes is crucial in facilitating clinical research and application. Compared with traditional materials, nanomaterials have better optical, magnetic, electrical, and catalytic properties due to their small size, high specific surface area, and variable structure. The incorporation of nanomaterials into sensing systems is an attractive approach towards improving sensitivity and can provide improved sensor selectivity and stability. In this paper, we summarize the progress in nanomaterial-based exosome detection methods, including electrochemical biosensors, photoelectrochemical biosensors, colorimetric biosensors, fluorescence biosensors, chemiluminescence biosensors, electrochemiluminescence biosensors, surface plasmon resonance biosensors, and surface-enhanced Raman spectroscopy biosensors. Moreover, future research directions and challenges in exosome detection methods are discussed. We hope that this article will offer an overview of nanomaterial-based exosome detection techniques and open new avenues in disease research.Graphical abstract.

The role of GtxA during Gallibacterium anatis infection of primary chicken oviduct epithelial cells.

Gallibacterium anatis (G. anatis), one of the major pathogens causing reproductive tract disorders in laying hens, leads to a reduction in egg production and increased mortality, caused by either single or mixed infections with other pathogens. As a specific virulence factor of G. anatis, the role of GtxA in layers' salpingitis remains unclear. In this study, we explored the effect of GtxA on G. anatis infection by comparing wild strain Yu-PDS-RZ-1-SLG (RZ) and its GtxA deleted counterpart RZΔgtxA in primary chicken oviduct epithelial cells (COEC). Their adherence, invasion, cytoxicity, and ability to induce apoptosis and and cytokine secretion were evaluated and the cytotoxicity and cytokine secretion of the recombinant GtxA protein and its N-terminal adenylate cyclase and C-terminal RTX hemolysin domain were also analyzed. We found that the adhesion ability of RZΔgtxA was significantly lower than that of parental strain RZ, and its toxicity to COEC was weakened; Meanwhile, apoptosis was inhibited and the expression of IL-6, IL-2, TNF-α and IFN-γ were dramatically reduced in COEC infected by RZΔgtxA. In contrast, the recombinant protein GtxA inhibited the proliferation of oviduct cells and induced obvious cytotoxicity, and the expression of IL-6, TNF-α and IFN-γ were up-regulated in COEC interacted with recombinant proteins. Our study indicates that GtxA promotes G. anatis adherence to cells, changes cells permeability and expression of inflammatory factors, resulting in cell damage and apoptosis.

Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer.

BACKGROUND: The high lethal rate of pancreatic cancer is partly due to a lack of efficient biomarkers for screening and early diagnosis. We attempted to develop effective and noninvasive methods using 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) markers from circulating cell-free DNA (cfDNA) for the detection of pancreatic ductal adenocarcinoma (PDAC). RESULTS: A 24-feature 5mC model that can accurately discriminate PDAC from healthy controls (area under the curve (AUC) = 0.977, sensitivity = 0.824, specificity = 1) and a 5hmC prediction model with 27 features demonstrated excellent detection power in two distinct validation sets (AUC = 0.992 and 0.960, sensitivity = 0.786 and 0.857, specificity = 1 and 0.993). The 51-feature model combining 5mC and 5hmC markers outperformed both of the individual models, with an AUC of 0.997 (sensitivity = 0.938, specificity = 0.955) and particularly an improvement in the prediction sensitivity of PDAC. In addition, the weighted diagnosis score (wd-score) calculated with the 5hmC model can distinguish stage I patients from stage II-IV patients. CONCLUSIONS: Both 5mC and 5hmC biomarkers in cfDNA are effective in PDAC detection, and the 5mC-5hmC integrated model significantly improve the detection sensitivity.