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Exosomes, key components of the tumour microenvironment, can mediate intercellular communication through the delivery of various signalling molecules, including microribonucleic acids (miRNAs), and ultimately participate in regulating the process of tumour development. In this study, we aimed to investigate the reason and mechanism by which exosomal miRNAs derived from gastric cancer cells affect carcinogenesis and metastasis. Among these miRNAs, microRNA-128-3p (miR-128-3p) was highly expressed in serum exosomes isolated from gastric cancer patients, as confirmed by high-throughput sequencing and subsequent experiments. Coculture of gastric cancer-derived exosomes overexpressing miR-128-3p with human umbilical vein endothelial cells (HUVECs) significantly enhanced HUVEC proliferation, migratio n and angiogenesis. Bioinformatics analysis suggested SASH1 as the target gene of miR-128-3p. The dual luciferase assay and Western blot analysis results confirmed that miR-128-3p directly targeted SASH1 to inhibit its expression in HUVECs. Therefore, this study provides preliminary evidence that gastric cancer-derived exosomal miR-128-3p promotes tumour angiogenesis by targeting SASH1, reveals the potential diagnostic and therapeutic value of cancer-derived exosomal miR-128-3p, and provides new insights into the novel molecular mechanisms regulating metastasis. This study provides further information for understanding the role of gastric cancer-derived exosomal miR-128-3p in cancer progression and to discover new therapeutic targets. [ABSTRACT FROM AUTHOR]

Background and purpose: Serum-thymidine kinase 1 (S-TK1) and macrophage inflammatory protein-1α (MIP-1α) are serum tumor markers, and their expression levels in serum are closely associated with disease severity and prognosis of thyroid cancer patient. Therefore, this article aimed to explore clinical value of the expression levels of S-TK1 and MIP-1α in the evaluation of postoperative radioactive 131 I treatment for thyroid carcinoma. Methods: A total of 158 preoperative patients with thyroid cancer and 128 healthy subjects were selected as study group and control group. Serum MIP-1α and S-TK1 levels were compared between the two groups. All patients with malignancy were divided into groups: the successful group (58 cases) and the unsuccessful group (40 cases), the metastasis positive group (20 cases) and the metastasis negative group (78 cases). The levels of serum MIP-1α and S-TK1 were compared, and immunohistochemical staining technique was used to detect the expressions of MIP-1α and S-TK1 in the thyroid tissues of different groups of patients. The factors affecting postoperative outcome were analyzed by single factor and logistic regression analysis. Results: The expression levels of MIP-1α and S-TK1 were significantly higher in the thyroid malignant group than in the benign group and the healthy control group (P ＜ 0.05). Compared with those who were unsuccessful, the serum expression levels of MIP-1α and S-TK1 in the successful group before the 131 I treatment were significantly reduced (P ＜ 0.05). The serum levels of MIP-1α and S-TK1 were significantly higher in the metastasis positive group than in the metastatic negative group (P ＜ 0.05). Immunohistochemical staining results showed that the positive expression rate of MIP-1α protein in the thyroid tissues of the malignant group (70.41%) was significantly higher than in the benign group (18.33%), and the positive expression rate of S-TK1 protein was significantly higher in the malignant group (68.37%) than in the benign group (15.00%) (P ＜ 0.05). Univariate analysis showed that maximum diameter, body mass index (BMI), thyroid-stimulating hormone (TSH), the expression levels of MIP- 1α and S-TK1 had significant effects on the first postoperative 131 I clearing effect in patients with thyroid cancer (P ＜ 0.05). Logistic regression analysis showed the largest diameter of the lesion and the expression levels of TSH, MIP-1α and S-TK1 were independent factors influencing the efficacy of the first postoperative clearing effect (P ＜ 0.05). Conclusion: The expression levels of MIP-1α and S-TK1 are significantly higher in thyroid cancer patients than in healthy people. The expression levels of MIP-1α and S-TK1 are significantly increased after metastasis in thyroid cancer patients, and the maximum diameter of lesion, TSH and the expression levels of MIP-1α and S-TK1 are independent factors affecting the efficacy of the first postoperative clearing effect (P ＜ 0.05).

Slanted gratings, commonly used for manipulating light in various applications, are typically fabricated using conventional top-down methods. However, these methods have limitations on material choice. This paper explores the use of glancing angle deposition (GLAD) to fabricate slanted gratings with various materials and slant angles on silicon (Si) and quartz (SiO2) substrates. The process involves the first step of creating a template using electron beam lithography, lift-off, and dry etching, and the second step of electron beam evaporation at a glancing angle on the prefabricated template. The template consists of grating structures with very shallow trenches. Different materials, such as chromium (Cr), copper (Cu), aluminum oxide (Al2O3), and titanium oxide (TiO2), were used in the GLAD process to create slanted grating structures on Si or SiO2 substrates, showcasing their versatility. Here, the formation of the slanted grating is due to the shadowing effect that leads to deposition onto the protruded grating lines but not into the trench. Using TiO2 as the source material, the GLAD technique can produce slanted gratings with various angles by adjusting the deposition angle. The optical characteristics of the slanted grating prepared using GLAD were verified through simulations with COMSOL software, confirming its excellent light guide performance. [ABSTRACT FROM AUTHOR]

Purpose: Metagenomic next-generation sequencing (mNGS) is a powerful yet unbiased method to identify pathogens in suspected infections. However, little is known about its clinical effectiveness. The present study aimed to assess the efficacy of mNGS in routine clinical practice. Patients and Methods: In this single-center retrospective cohort study, 518 patients with suspected infectious diseases were assessed for inclusion. Among them, each patient had undergone mNGS testing; 407 patients had undergone both microbial culture and mNGS testing. The result of mNGS testing was compared to microbial culture performed concurrently. The diagnostic performance of mNGS was evaluated using the comprehensive clinical diagnosis as the reference standard. Results: There was a significant difference in the positive detection rates of pathogens between mNGS and culture (331/407, 81.3% vs 79/407, 19.4%, P < 0.001). The sensitivity of mNGS was much higher than the culture method (79.5% vs 21.3%, P < 0.001), especially in sample types of sputum and bronchoalveolar lavage fluid (BALF). Notably, the sensitivity of blood mNGS was relatively lower than other sample types (67.4% vs 88.9– 93.8%). Pathogen cfDNA load based on standardized stringently mapped read number at the species level of microorganisms (SDSMRN) was significantly lower in blood than in other sample types from the same patient (P = 0.0003). Importantly, mNGS directly led to a change of treatment regimen in 142 (27.4%) cases, including antibiotic escalation (15.3%), antibiotic de-escalation (9.1%), and early definitive diagnosis to initiate appropriate treatment (3.1%). Conclusion: Our in-house mNGS platform significantly improved the sensitivity for the diagnosis of infectious diseases. mNGS has the potential to improve clinical outcomes by optimizing antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Background and purpose: Serum-thymidine kinase 1 (S-TK1) and macrophage inflammatory protein-1α (MIP-1α) are serum tumor markers, and their expression levels in serum are closely associated with disease severity and prognosis of thyroid cancer patient. Therefore, this article aimed to explore clinical value of the expression levels of S-TK1 and MIP-1α in the evaluation of postoperative radioactive 131I treatment for thyroid carcinoma. Methods: A total of 158 preoperative patients with thyroid cancer and 128 healthy subjects were selected as study group and control group. Serum MIP-1α and S-TK1 levels were compared between the two groups. All patients with malignancy were divided into groups: the successful group (58 cases) and the unsuccessful group (40 cases), the metastasis positive group (20 cases) and the metastasis negative group (78 cases). The levels of serum MIP-1α and S-TK1 were compared, and immunohistochemical staining technique was used to detect the expressions of MIP-1α and S-TK1 in the thyroid tissues of different groups of patients. The factors affecting postoperative outcome were analyzed by single factor and logistic regression analysis. Results: The expression levels of MIP-1α and S-TK1 were significantly higher in the thyroid malignant group than in the benign group and the healthy control group (P<0.05). Compared with those who were unsuccessful, the serum expression levels of MIP-1α and S-TK1 in the successful group before the 131I treatment were significantly reduced (P<0.05). The serum levels of MIP-1α and S-TK1 were significantly higher in the metastasis positive group than in the metastatic negative group (P<0.05). Immunohistochemical staining results showed that the positive expression rate of MIP-1α protein in the thyroid tissues of the malignant group (70.41%) was significantly higher than in the benign group (18.33%), and the positive expression rate of S-TK1 protein was significantly higher in the malignant group (68.37%) than in the benign group (15.00%) (P<0.05). Univariate analysis showed that maximum diameter, body mass index (BMI), thyroid-stimulating hormone (TSH), the expression levels of MIP-1α and S-TK1 had significant effects on the first postoperative 131I clearing effect in patients with thyroid cancer (P<0.05). Logistic regression analysis showed the largest diameter of the lesion and the expression levels of TSH, MIP-1α and S-TK1 were independent factors influencing the efficacy of the first postoperative clearing effect (P<0.05). Conclusion: The expression levels of MIP-1α and S-TK1 are significantly higher in thyroid cancer patients than in healthy people. The expression levels of MIP-1α and S-TK1 are significantly increased after metastasis in thyroid cancer patients, and the maximum diameter of lesion, TSH and the expression levels of MIP-1α and S-TK1 are independent factors affecting the efficacy of the first postoperative clearing effect (P<0.05). [ABSTRACT FROM AUTHOR]

Background and purpose: Serum-thymidine kinase 1 (S-TK1) and macrophage inflammatory protein-1α (MIP-1α) are serum tumor markers, and their expression levels in serum are closely associated with disease severity and prognosis of thyroid cancer patient. Therefore, this article aimed to explore clinical value of the expression levels of S-TK1 and MIP-1α in the evaluation of postoperative radioactive 131I treatment for thyroid carcinoma. Methods: A total of 158 preoperative patients with thyroid cancer and 128 healthy subjects were selected as study group and control group. Serum MIP-1α and S-TK1 levels were compared between the two groups. All patients with malignancy were divided into groups: the successful group (58 cases) and the unsuccessful group (40 cases), the metastasis positive group (20 cases) and the metastasis negative group (78 cases). The levels of serum MIP-1α and S-TK1 were compared, and immunohistochemical staining technique was used to detect the expressions of MIP-1α and S-TK1 in the thyroid tissues of different groups of patients. The factors affecting postoperative outcome were analyzed by single factor and logistic regression analysis. Results: The expression levels of MIP-1α and S-TK1 were significantly higher in the thyroid malignant group than in the benign group and the healthy control group (P<0.05). Compared with those who were unsuccessful, the serum expression levels of MIP-1α and S-TK1 in the successful group before the 131I treatment were significantly reduced (P<0.05). The serum levels of MIP-1α and S-TK1 were significantly higher in the metastasis positive group than in the metastatic negative group (P<0.05). Immunohistochemical staining results showed that the positive expression rate of MIP-1α protein in the thyroid tissues of the malignant group (70.41%) was significantly higher than in the benign group (18.33%), and the positive expression rate of S-TK1 protein was significantly higher in the malignant group (68.37%) than in the benign group (15.00%) (P<0.05). Univariate analysis showed that maximum diameter, body mass index (BMI), thyroid-stimulating hormone (TSH), the expression levels of MIP-1α and S-TK1 had significant effects on the first postoperative 131I clearing effect in patients with thyroid cancer (P<0.05). Logistic regression analysis showed the largest diameter of the lesion and the expression levels of TSH, MIP-1α and S-TK1 were independent factors influencing the efficacy of the first postoperative clearing effect (P<0.05). Conclusion: The expression levels of MIP-1α and S-TK1 are significantly higher in thyroid cancer patients than in healthy people. The expression levels of MIP-1α and S-TK1 are significantly increased after metastasis in thyroid cancer patients, and the maximum diameter of lesion, TSH and the expression levels of MIP-1α and S-TK1 are independent factors affecting the efficacy of the first postoperative clearing effect (P<0.05). [ABSTRACT FROM AUTHOR]

Haze from urban sites in Beijing was collected with a self-assembled electrostatic dust collector. The sizes and morphologies, thermal properties, and compositions of the particles in the haze were characterized by scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and X-ray photoelectric spectroscopy (XPS), respectively. Based on these results, the causes and pollutant sources of the chemicals in the haze were analyzed, and some countermeasures were further advanced to reduce the related pollutant sources. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to build alternative indices weighing using a measure of fundamental value rather than debt size. The official bond indices built to reflect general price trends are market weighted, meaning that the bonds are weighted by their debt size. The more indebted, the more weight in the index, which mechanically increments the investment risks that are inherent. Those market indices are shown to be return-to-risk inefficient in recent studies compared to indices with alternative weighting schemes. The authors contribute to this growing literature, which mostly focuses on equities, by testing on bonds. Design/methodology/approach – The authors build alternative indices weighing using a measure of fundamental value rather than debt size. The authors have done this for sovereign bonds using gross domestic product (GDP) figures and for corporates taking sales revenues. Findings – The authors find in empirical tests that the fundamental indices build tend to outperform the market-weighted indices. Originality/value – This article builds on two articles by Arnott et al. (2005, 2010), in the Financial Analysts Journal and Journal of Portfolio Management, respectively, and adds value in the sense that – it takes an appreciation-free fundamental measure, – tests on the European as opposed to the US bond markets. [ABSTRACT FROM AUTHOR]

Background: Targeting ferroptosis is an effective approach to mitigate hepatic fibrosis, yet no reports exist on the ferroptosis signature in liver fibrosis. This study aimed to explore ferroptosis characteristics in this disease., Methods: RNAseq data from GSE6764, GSE188604 and Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) were downloaded. Multiple machine learning methods, including Weighted Gene Co-expression Network Analysis (WGCNA), Random Forest (RF) and Support Vector Machine (SVM), were used to identify core genes in liver fibrosis and ferroptosis. WGCNA can pinpoint modules linked to clinical traits, aiding in discovering diagnostic and progression molecules in complex diseases. RF and SVM are often utilized for WGCNA validation to boost result accuracy. Carbon tetrachloride (CCl4) was used to establish a mouse liver fibrosis model to validate core gene expression, which was also assessed in test and validation GEO datasets. Finally, the diagnostic role of the core genes in liver fibrosis and hepatocellular carcinoma (HCC) was also investigated using ROC analysis., Results: Multiple machine learning methods screened nine core genes, including IL1B, GSTZ1, LIFR, SLC25A37, PTGS2, MT1G, HSPB1, ESR1, and PHGDH. In vivo experimental validation, RT-PCR showed ESR1 and GSTZ1 were significantly under-expressed in the liver fibrosis group compared to the normal group. Simultaneously, in GSE6764 and GSE188604, ESR1 and GSTZ1 were also identified as protective genes for liver fibrosis. More in-depth research found that ESR1 and GSTZ1 exhibited a good diagnostic performance both in liver fibrosis and HCC, suggesting that a persistent decrease in ESR1 and GSTZ1 in patients might signal the progression from hepatic fibrosis to HCC., Conclusion: The present study is the first to report the ferroptosis signature in liver fibrosis and identifies two novel biomarkers, ESR1 and GSTZ1, providing new insights for the diagnosis and treatment of liver fibrosis in the future., Competing Interests: This research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Luo et al.)

Objective: The study endeavors to elucidate AE signals associated with zanubrutinib data from the WHO-VigiAccess and FAERS databases. The aim is to furnish robust scientific evidence to inform clinical practice and regulatory decisions., Methods: We meticulously extracted all AE breports tied to zanubrutinib from the both databases, encompassing the period from the drug's market introduction until 30 April 2024. Retrospective quantitative analysis employing ROR, PRR, and BCPNN methodologies were utilized to analysis., Results: The investigation unveiled 1,304 reports from WHO-VigiAccess and 1,141 reports from FAERS related to zanubrutinib. Among the top 30 reported PTs in both databases, those not recorded in the drug label included pyrexia, dizziness, and death. In the FAERS database, signals for zanubrutinib were detected across 19 SOCs. Systems not covered in the drug label included reproductive system and breast disorders, metabolism and nutrition disorders, ear and labyrinth disorders, among others. Unmentioned signals included intestinal perforation, onychoclasis, night sweats, etc., Conclusion: This study confirms common AEs of zanubrutinib and identifies new ones, highlighting the need for careful monitoring and personalized treatment. It also emphasizes the importance of ongoing drug safety surveillance and patient management to maximize therapeutic benefits and minimize risks.

Background: This study aimed to investigate the real-world profile of adverse events (AEs) associated with gepant medications in the clinical treatment of migraines by analyzing data collected from the VigiAccess database and the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. As novel migraine therapies, gepants act by targeting the calcitonin gene-related peptide (CGRP) pathway, demonstrating effective control of migraine attacks and good tolerability. Nonetheless, comprehensive real-world studies on the safety of gepants are still lacking, particularly regarding their safety in large populations, long-term use, and potential adverse reactions in specific groups, which necessitates further empirical research. Leveraging these two international adverse event reporting system databases, we systematically gathered and analyzed reports of AEs related to gepant medications, such as rimegepant. Our focus encompasses but is not limited to severe, new, and rare adverse reactions induced by the drugs, as well as safety issues pertaining to the gastrointestinal, cardiovascular, hepatic, and renal systems. Through descriptive statistical analyses, we assessed the incidence and characteristics of AEs, compared AEs among gepants, and uncovered previously unknown AE information, all with the goal of providing a reference for the selection of clinical treatment regimens and AE monitoring., Methods: By extracting all AE reports concerning "rimegepant", "atogepant", and "ubrogepant" from the VigiAccess and FAERS database since its establishment up to 31 March 2024, a retrospective quantitative analysis was conducted. The reporting odds ratio (ROR) method were used to compare AEs among the three gepants., Results: In the VigiAccess and FAERS databases, 23542 AE reports in total, respectively, were identified as being related to gepant medications. Among gastrointestinal system AEs, rimegepant had the greatest proportion and greatest signal strength; nausea was most severe and had the strongest signal in rimegepant AEs, whereas constipation was most prominent and had the strongest signal in atogepant AEs. In skin and subcutaneous tissue disorders, rash and pruritus were more frequently observed with rimegepant, followed by ubrogepant. Alopecia emerged as a novel AE, being more severe in rimegepant and secondarily in atogepant. Regarding cardiac disorders, the three gepants showed comparable rates of cardiac AEs, yet rimegepant exhibited the strongest AE signal. In musculoskeletal and connective tissue AEs, ubrogepant presented the most positive signals for skeletal muscle AEs. Furthermore, among the rare blood and lymphatic system disorder AEs, rimegepant had the highest number of reports of Raynaud's phenomenon and the strongest signal. The study also revealed that while reports of AEs involving liver diseases were scarce across the three gepants, severe AEs were detected in clinical trials, highlighting the need for continued, enhanced monitoring of liver system AEs through large-scale datasets., Conclusion: Gepant medications exhibit similarities and differences in their safety profiles. Analysis of the two databases indicated the presence of AEs across various systems, including gastrointestinal disorders, skin and subcutaneous tissue diseases, musculoskeletal and connective tissue disorders, organ-specific effects, and liver diseases. However, each drug displays distinct incidences and signal intensities for these AEs. Additionally, the study revealed a rare AE in the form of Raynaud's phenomenon. These findings suggest that during clinical use, individualized medication selection and AE monitoring should be based on the patient's physiological condition and specific characteristics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liang, Liao, Wu, Huang, Liang and Li.)

The conformation of proteins is closely related to their biological functions, and it is affected by many factors, including the type of cations in solution. However, it is difficult to detect the conformational changes of a protein in situ . As a single-molecule sensing technology, nanopores can convert molecular structural information into analyzable current signals within a reasonable time range. Herein, we detect and analyze the effects of two different types of monovalent cations (Na + and Li + ) on a model protein bovine serum albumin (BSA) conformation using SiN x nanopores with different diameters. The quantitative analysis results show that the excluded volume of BSA in LiCl salt solutions is larger than the value in NaCl solution, indicating that Li + is more prone to unfolding the proteins and making them unstable. This study demonstrated that nanopores enable the in situ detection of the structure of proteins at the single-molecule level and provide a new approach for the quantitative analysis of proteins.

Background: The molecular mechanisms of hepatic fibrosis (HF), closely related to autophagy, remain unclear. This study aimed to investigate autophagy characteristics in HF., Methods: Gene expression profiles (GSE6764, GSE49541 and GSE84044) were downloaded, normalized, and merged. Autophagy-related differentially expressed genes (ARDEGs) were determined using the limma R package and the Wilcoxon rank sum test and then analyzed by GO, KEGG, GSEA and GSVA. The infiltration of immune cells, molecular subtypes and immune types of healthy control (HC) and HF were analyzed. Machine learning was carried out with two methods, by which, core genes were obtained. Models of liver fibrosis in vivo and in vitro were constructed to verify the expression of core genes and corresponding immune cells., Results: A total of 69 ARDEGs were identified. Series functional cluster analysis showed that ARDEGs were significantly enriched in autophagy and immunity. Activated CD4 T cells, CD56bright natural killer cells, CD56dim natural killer cells, eosinophils, macrophages, mast cells, neutrophils, and type 17 T helper (Th17) cells showed significant differences in infiltration between HC and HF groups. Among ARDEGs, three core genes were identified, that were ATG5, RB1CC1, and PARK2. Considerable changes in the infiltration of immune cells were observed at different expression levels of the three core genes, among which the expression of RB1CC1 was significantly associated with the infiltration of macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell. In the mouse liver fibrosis experiment, ATG5, RB1CC1, and PARK2 were at higher levels in HF group than those in HC group. Compared with HC group, HF group showed low positive area in F4/80, IL-17 and CD56, indicating decreased expression of macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell. Meanwhile, knocking down RB1CC1 was found to inhibit the activation of hepatic stellate cells and alleviate liver fibrosis., Conclusion: ATG5, RB1CC1, and PARK2 are promising autophagy-related therapeutic biomarkers for HF. This is the first study to identify RB1CC1 in HF, which may promote the progression of liver fibrosis by regulating macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Luo, Yang, Lan, Wei and Wu.)

We previously demonstrated that MnCl2 induces double-stranded DNA breaks in sperm in a process that we term as sperm chromatin fragmentation. Here, we tested if the levels of double-stranded DNA breaks were corelated to the concentration of MnCl2, and we compared this to another agent that causes single-stranded DNA breaks, H2O2. We found that both methods have the advantage of inducing DNA breaks in a concentration-dependent manner. Mouse sperm were treated with varying concentrations of either H2O2 or MnCl2, and the DNA damage was assessed by pulse-field gel electrophoresis, and the alkaline and neutral comet assays. Oocytes were injected with either treated sperm and the resulting embryos analyzed with an embryoscope to detect subtle changes in embryonic development. We confirmed that H2O2 treatment induced primarily single-stranded DNA breaks and MnCl2 induced primarily double-stranded DNA breaks, indicating different mechanisms of damage. These sperm were injected into oocytes, and the development of the resulting embryos followed with an embryoscope equipped with time lapse recording. We found that aberrations in early embryonic development by day 2 with even the lowest levels of DNA damage and that the levels of embryonic aberrations correlated to the concentration of either H2O2 or MnCl2. Low levels of H2O2 caused significantly more aberrations in embryonic development than low levels of MnCl2 even though the levels of DNA damage as measured by comet assays were similar. These data demonstrate that even low levels of sperm DNA damage cause delays and arrests in embryonic development., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Sperm nuclei present a highly organized and condensed chromatin due to the interchange of histones by protamines during spermiogenesis. This high DNA condensation leads to almost inert chromatin, with the impossibility of conducting gene transcription as in most other somatic cells. The major chromosomal structure responsible for DNA condensation is the formation of protamine-DNA toroids containing 25-50 kilobases of DNA. These toroids are connected by toroid linker regions (TLR), which attach them to the nuclear matrix, as matrix attachment regions (MAR) do in somatic cells. Despite this high degree of condensation, evidence shows that sperm chromatin contains vulnerable elements that can be degraded even in fully condensed chromatin, which may correspond to chromatin regions that transfer functionality to the zygote at fertilization. This chapter covers an updated review of our model for sperm chromatin structure and its potential functional elements that affect embryo development., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The detection and investigation of biomolecules at a single-molecule level is important for improving diagnosis in biomedicine. Solid-state nanopores are a unique tool that have the potential to accomplish this task because they are label-free and require only low sample consumption. However, the event-readouts of current small polymer molecules are still limited because of its relatively large size and low signal-to-noise ratios. Here, we present a rapid sensing approach for the detection of GR-5 DNAzyme cleaving specific substrate reactions using relatively larger size silicon nitride nanopores by introducing a type of nucleic acid nanostructure (DNA tetrahedron) as a carrier. The proposed method is convenient and sensitive enough to detect the cleavage reactions by identifying translocation events before and after reactions with nanomolar concentrations of the target sample. Furthermore, this assay was also carried out by using larger size nanopores (60 nm diameter) to achieve the DNAzyme cleavage sensing with the same sample concentration. This approach can improve event detectability of other smaller molecules' translocation, which opens up a wide range of applications for analytes detection by incorporating solid-state nanopores. Nucleic acid nanostructure-assisted nanopore sensing can promote the development of single-molecule studies.

Nanopores have been used as a high throughput tool for characterizing individual biomolecules and nanoparticles. Here, we present the translocation of rigid rod-shaped tobacco mosaic virus (TMV) through solid-state nanopores. Interestingly, due to the high rigidity of TMV, three types of events with distinctive characteristics at the capture process and a strong current fluctuation during the translocation of TMV are observed. A kinetic model is then proposed to address the dynamics of the translocation, followed by corresponding dynamics simulations. The results reveal that TMV has to rotate to fit and pass the pore when it is captured by a nanopore with an angle larger than the maximum angle that allows it to pass through. Then, we investigate the dependence of the rotation of TMV on the conductance fluctuations at the blockade stage. The results show that the rotation of TMV during the passage through the pore affects the current signal significantly. This study gives a fundamental understanding of the dynamics of rod-shaped particles translocating through the nanopore and how the current responds to it. It opens a new possible way to characterize the rigidity of analytes by nanopores.

In recent years, nanopore has attracted broad attention as an essential technique for DNA sequencing and nanoparticle sensing. This work presented a fundamental study of nanoparticle translocation through silicon nitride nanopores. Since particles with rather high charge to mass ratio, such as DNA and proteins, have been widely studied, there was still little information about the translocation behavior of nanoparticles with low charge/mass ratio. However, these nanoparticles include viruses and colloids are important potential sample for nanopore sensing technique. In order to screen nanoparticles' size, concentration, surface property by apply silicon nitride nanopores, and fulfill specific recognition which could be applied in laboratory medicine and environmental monitoring, optimal experimental conditions needed to be confirmed. In this paper, polystyrene (PS) bead was used as an example to provide reference towards this condition. The effects of nanopore/nanoparticle diameter ratio and bias voltage on sensing results were analyzed in this work. We found that lower precision accuracy might be demonstrated by the larger pore (120 nm) while the translocation velocity tended to be slowed down. By increasing the bias voltage could favor the detection productiveness. In spite of the intense interest, the baseline fluctuations and vague event bounds aggravated are far from understood.

Nanopores have become an important tool for molecule detection at single molecular level. With the development of fabrication technology, synthesized solid-state membranes are promising candidate substrates in respect of their exceptional robustness and controllable size and shape. Here, a 30-60 (tip-base) nm conical nanopore fabricated in 100 nm thick silicon nitride (Si(3)N(4)) membrane by focused ion beam (FIB) has been employed for the analysis of λ-DNA translocations at different voltage biases from 200 to 450 mV. The distributions of translocation time and current blockage, as well as the events frequencies as a function of voltage are investigated. Similar to previously published work, the presence and configurations of λ-DNA molecules are characterized, also, we find that greater applied voltages markedly increase the events rate, and stretch the coiled λ-DNA molecules into linear form. However, compared to 6-30 nm ultrathin solid-state nanopores, a threshold voltage of 181 mV is found to be necessary to drive DNA molecules through the nanopore due to conical shape and length of the pore. The speed is slowed down ∼5 times, while the capture radius is ∼2 fold larger. The results show that the large nanopore in thick membrane with an improved stability and throughput also has the ability to detect the molecules at a single molecular level, as well as slows down the velocity of molecules passing through the pore. This work will provide more motivations for the development of nanopores as a Multi-functional sensor for a wide range of biopolymers and nano materials.