Evaluation of the accuracy of cone-beam computed tomography image segmentation of isolated tooth roots based on the dynamic threshold method.

OBJECTIVE: Accurate quantification of the root surface area (RSA) plays a decisive role in the advancement of periodontal, orthodontic, and restorative treatment modalities. In this study, we aimed to develop a dynamic threshold-based computer-aided system for segmentation and calculation of the RSA of isolated teeth on cone-beam computed tomography (CBCT) and to assess the accuracy of the measured data. METHOD: We selected 24 teeth to be extracted, including single-rooted and multi-rooted teeth, from 22 patients who required tooth extraction. In the experimental group, we scanned 24 isolated teeth using CBCT with a voxel size of 0.3 mm. We designed a computer-aided system based on a personalized dynamic threshold algorithm to automatically segment the roots of 24 isolated teeth in CBCT images and calculate the RSA. In the control group, we employed digital intraoral scanner devices to perform optical scanning on 24 isolated teeth and subsequently manually segmented the roots using 3-matic software to calculate the RSA. We used the paired t-test (P < 0.05) and Bland-Altman plots to analyze the consistency of the two measurement methods. RESULTS: The results of the paired t-test showed that there was no significant difference in the RSAs obtained using the dynamic threshold method and the optical scanning image reconstruction (t = 1.005, P = 0.325 > 0.05). As per the Bland-Altman plot, the results were evenly distributed within the region of ± 1.96 standard deviations of the mean, with no increasing or decreasing trends and good consistency. CONCLUSION: In this study, we designed a computer-aided root segmentation system based on a personalized dynamic threshold algorithm to automatically segment the roots of isolated teeth in CBCT images with a voxel size of 0.3 mm. We found that the RSA calculated using this approach was highly accurate, and a voxel of 0.3 mm in size could accurately display the surface area data in CBCT images. Overall, our findings in this study provide a foundation for future work on accurate automatic segmentation of tooth roots in full-mouth CBCT images and the computation of RSA.

Clinicopathological features in two families with MARS-related Charcot-Marie-Tooth disease.

Mutations in MARS gene cause dominant Charcot-Marie-Tooth disease (CMT) 2U. The aim of this study is to investigate phenotypic heterogeneities and peripheral neuropathology of MARS-related CMT patients. We identified a heterozygous p. R199Q mutation and an already reported heterozygous p. P800T mutation of MARS gene in two unrelated families using targeted next-generation sequencing. The first pedigree comprised three patients over three generations and the second pedigree comprised two patients over two generations. In addition of an asymptomatic carrier in the second pedigree, all patients presented with childhood-onset length dependent sensorimotor neuropathy with pes cavus. Nerve conduction studies revealed slowing of motor nerve conduction velocities (MNCV) of the median nerve indicating intermediate neuropathy in the patient with the p. R199Q mutation, and normal MNCV with reduced compound muscle action potential indicating axonal neuropathy in the patient with the p. P800T mutation. Magnetic resonance imaging detected a pattern of nerve changes similar to those in demyelinating polyneuropathies in intermediate type (p. R199Q mutation) patients compared with normal in the axonal type (p. P800T mutation) patients. Additionally, sural nerve biopsy revealed loss of myelinated axons with onion bulb formation in both mutations. By electron microscopy, a marked decrease of myelinated and unmyelinated fiber, neurofilaments aggregate with degenerating mitochondria and microtubule loss in axons were frequently found. Denervated Schwann cell complexes and few collagen pockets indicated involvement of unmyelinated Schwann cells. Therefore, the investigated MARS mutations cause not only the known axonal type but also intermediate type neuropathy with involvement of both axons and Schwann cells. Those findings are useful for the differential diagnosis of CMT patients with unknown MARS variants.

PLEKHG5-related autosomal recessive lower motor neuron disease with dysmyelination in peripheral nerves.

OBJECTIVE: Pleckstrin homology domain-containing family G member 5 (PLEKHG5) is a nuclear factor-κ-B-activator gene that predominantly expresses in the neurons and Schwann cells of the peripheral nervous system. Variations in the PLEKHG5 have shown an intermediate form of autosomal recessive Charcot-Marie-Tooth disease and lower motor neuron disease in childhood. MATERIALS AND METHODS: This study investigated clinically, electrophysiologically, genetically, and pathologically a young girl with lower motor neuron disease who had weakness and wasting of all limbs starting in early childhood. RESULTS: Next-generation sequencing found a novel compound heterozygous missense variation c.2038-1G>A and c.1219G>T of PLEKHG5 gene. Electromyography revealed a neurogenic pattern, and nerve conduction study indicated subclinical sensory neuropathy. Sural biopsy showed hypomyelination, hypermyelination, and infolding myelin membranes coiled into the myelinated axon. CONCLUSION: This study identifies, pathologically, novel compound heterozygous mutations and phenotype in PLEKHG5-related lower motor neuron disease and dysmyelination in a patient with PLEKHG5 mutation.

In Vitro Evaluation of the Antibacterial Properties of Tea Tree Oil on Planktonic and Biofilm-Forming Streptococcus mutans.

Streptococcus mutans (S. mutans) is the principal etiologic agent in the occurrence of human dental caries and the formation of biofilms on the surface of teeth. Tea tree oil (TTO) has been demonstrated to exhibit a wide range of pharmacological actions that can effectively inhibit the activity of bacteria. In this context, we evaluated the in vitro antimicrobial effects of TTO on S. mutans both during planktonic growth and in biofilms compared with 0.2% CHX. We determined the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) using the microdilution method, the bacteriostatic rate using an MTT assay, and the antimicrobial time using a time-kill assay. Then, we explored the effects of TTO on acid production and cell integrity. Furthermore, the effects of TTO on the biomass and bacterial activity of S. mutans biofilms were studied. Finally, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to investigate the structure and activity of biofilms. The MIC and MBC values were 0.125% and 0.25%, and the bacterial inhibition rate was concentration dependent. TTO can effectively inhibit bacterial acid production and destroy the integrity of the cell membrane. Electron micrographs revealed a reduction in bacterial aggregation, inhibited biofilm formation, and reduced biofilm thickness. The effect of TTO was the same as that of 0.2% CHX at a specific concentration. In summary, we suggest that TTO is a potential anticariogenic agent that can be used against S. mutans.

Detection of microRNA using a polydopamine mediated bimetallic SERS substrate and a re-circulated enzymatic amplification system.

A surface-enhanced Raman scattering (SERS) method is described for the determination of microRNA that is associated with various forms of cancer. The substrate consists of functionalized gold-silver bimetallic structure, and the sensitivity is strongly enhanced by making use of a re-circulated enzymatic amplification system (REAS). Poly-dopamine acts as both a reductant and a protective of the substrates. It was employed to link the gold core and silver satellite. The unique "hot spots" consisting of a Au@PDA@Ag nanocomposite improve the Raman signal and sensitivity. The reductive feature of PDA can prevent the susceptible oxidation of metallic silver to maintain the high Raman activity. To improve the sensitivity of the assays, a re-circulated enzymatic amplification system was developed in which the nicking endonuclease triggers the nucleic acid reaction system to enter an amplified cycle. By integrating the bimetallic nanosubstrate and magnetic separation into the REAS, microRNA can be detected by SERS (best at the Raman band of 1586 cm-1) with a limit of detection as low as 0.2 fM. In our perception, the assay provides an exciting new avenue to study the expression of tumor genes. Thus, it holds vast promise in cancer diagnosis. Graphical abstract Schematic presentation of the SERS method based on poly-dopamine mediated bimetallic SERS substrate and re-circulated enzymatic amplification.

Association of IL-28B, TBX21 gene polymorphisms and predictors of virological response for chronic hepatitis C.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. The outcomes of both spontaneous HCV clearance and response to therapy depend on both viral and host factors. To investigate the influence of polymorphisms of IL-28B rs12979860 and TBX21 rs17250932, rs4794067 as well as viral factors (HCV genotype, F protein) on the outcome of HCV infection, we genotyped 565 patients with chronic HCV infection, 191 patients spontaneously resolved from HCV infection, 359 healthy controls and 383 treatment-naïve CHC patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV). Results showed that TBX21 rs4794067 variant genotypes significantly correlated with increased risk of HCV chronic infection (dominant model: OR = 5.690, 95% CI = 2.024-16.000) and susceptibility (dominant model: OR = 5.658, 95% CI = 2.514-12.735). We also found that the rs12979860, rs2227982 and rs36084323 polymorphisms showed no significant associations with susceptibility or spontaneous clearance of HCV in the anti-F antibody subgroup; however, the anti-F antibody positive subgroup might show an increased risk of N-SVR (all P < 0.001). Our results demonstrate that variant factors in both the host and pathogen are commonly important for HCV clearance. In addition rs4794067 and F protein status may be strong predictive markers in the Chinese population.

Hypoxia-Responsive 19F MRI Probes with Improved Redox Properties and Biocompatibility.

19F magnetic resonance imaging (MRI), an emerging modality in biomedical imaging, has shown promise for in vitro and in vivo preclinical studies. Here we present a series of fluorinated Cu(II)ATSM derivatives for potential use as 19F magnetic resonance agents for sensing cellular hypoxia. The synthesized complexes feature a hypoxia-targeting Cu2+ coordination core, nine equivalent fluorine atoms connected via a variable-length poly(ethylene glycol) linker. Introduction of the fluorine moiety maintains the planar coordination geometry of the Cu2+ center, while the linker length modulates the Cu2+/+ reduction potential, 19F NMR relaxation properties, and lipophilicity. In particular, the 19F NMR relaxation properties were quantitatively evaluated by the Solomon-Bloembergen model, revealing a regular pattern of relaxation enhancement tuned by the distance between Cu2+ and F atoms. Finally, the potential utility of these complexes for sensing reductive environments was demonstrated using both 19F MR phantom imaging and 19F NMR, including experiments in intact live cells.

Multifunctional Magnetic Gd(3+) -Based Coordination Polymer Nanoparticles: Combination of Magnetic Resonance and Multispectral Optoacoustic Detections for Tumor-Targeted Imaging in vivo.

To overcome traditional barriers in optical imaging and microscopy, optoacoustic-imaging has been changed to combine the accuracy of spectroscopy with the depth resolution of ultrasound, achieving a novel modality with powerful in vivo imaging. However, magnetic resonance imaging provides better spatial and anatomical resolution. Thus, a single hybrid nanoprobe that allows for simultaneous multimodal imaging is significant not only for cutting edge research in imaging science, but also for accurate clinical diagnosis. A core-shell-structured coordination polymer composite microsphere has been designed for in vivo multimodality imaging. It consists of a Fe3 O4 nanocluster core, a carbon sandwiched layer, and a carbocyanine-Gd(III) (Cy-Gd(III) ) coordination polymer outer shell (Fe3 O4 @C@Cy-Gd(III) ). Folic acid-conjugated poly(ethylene glycol) chains are embedded within the coordination polymer shell to achieve extended circulation and targeted delivery of probe particles in vivo. Control of Fe3 O4 core grain sizes results in optimal r2 relaxivity (224.5 × 10(-3) m(-1) s(-1) ) for T2 -weighted magnetic resonance imaging. Cy-Gd(III) coordination polymers are also regulated to obtain a maximum 25.1% of Cy ligands and 5.2% of Gd(III) ions for near-infrared fluorescence and T1 -weighted magnetic resonance imaging, respectively. The results demonstrate their impressive abilities for targeted, multimodal, and reliable imaging.

Benzoboroxole-functionalized magnetic core/shell microspheres for highly specific enrichment of glycoproteins under physiological conditions.

Efficient enrichment of specific glycoproteins from complex biological samples is of great importance towards the discovery of disease biomarkers in biological systems. Recently, phenylboronic acid-based functional materials have been widely used for enrichment of glycoproteins. However, such enrichment was mainly carried out under alkaline conditions, which is different to the status of glycoproteins in neutral physiological conditions and may cause some unpredictable degradation. In this study, on-demand neutral enrichment of glycoproteins from crude biological samples is accomplished by utilizing the reversible interaction between the cis-diols of glycoproteins and benzoboroxole-functionalized magnetic composite microspheres (Fe3O4/PAA-AOPB). The Fe3O4/PAA-AOPB composite microspheres are deliberately designed and constructed with a high-magnetic-response magnetic supraparticle (MSP) core and a crosslinked poly(acrylic acid) (PAA) shell anchoring abundant benzoboroxole functional groups on the surface. These nanocomposites possessed many merits, such as large enrichment capacity (93.9 mg/g, protein/beads), low non-specific adsorption, quick enrichment process (10 min) and magnetic separation speed (20 s), and high recovery efficiency. Furthermore, the as-prepared Fe3O4/PAA-AOPB microspheres display high selectivity to glycoproteins even in the E. coli lysate or fetal bovine serum, showing great potential in the identify of low-abundance glycoproteins as biomarkers in real complex biological systems for clinical diagnoses.

Rapid screening of the heterogeneity of DNA methylation by single-strand conformation polymorphism and CE-LIF in the presence of electro-osmotic flow.

DNA methylation is a complex event in epigenetic studies because of both the large CpG islands present upstream of the promoter region and the different distribution of DNA methylation despite similar methylation levels. For this reason, we proposed a fast, cost-effective method for the screening of DNA methylation based on SSCP and CE-LIF. In this study, the PCR products that were amplified from bisulfite-treated genomic DNA were denatured at 94°C, followed by immediate chilling in ice water to form the ssDNA. The ssDNA were separated by 1.5% poly(ethylene oxide) (Mavg 8 000 000 Da) in the presence of EOF according to the different conformations represented by their unique methylation states. This result demonstrated that four hepatocellular carcinoma cell lines represented a different heterogeneity of DNA methylation and could be distinguished by SSCP-CE. The results obtained from SSCP-CE also corresponded with those obtained from combined bisulfide restriction analysis and methylation-sensitive high-resolution melting analysis. Therefore, the proposed SSCP-CE method may potentially be used for rapid screening for determination of the heterogeneity of DNA methylation in further epigenetic studies and clinical diagnosis.

Enhanced homogeneity and flexibility in a humidity sensor using cellulose nanocrystal-based composite film with circular shear flow.

Cellulose nanocrystal (CNC) film is known to be one kind of dynamic color-sensing material, capable of reversible color changes in response to varying humidity levels. However, the brittleness, low hygroscopicity and poor homogeneity of these films have hindered their development. To address this limitation, we present a novel approach where we combine natural deep eutectic solvents (NADES) with sorbitol under the influence of circular shear flow to craft a CNC humidity-sensitive film with enhanced flexibility, hygroscopicity and homogeneity. The inclusion of sorbitol and NADES enhances hygroscopicity and improves the flexibility. Surprisingly, the introduction of circular shear flow was found not only to improve homogeneity, macroscopically and microscopically, but also to further enhance flexibility, toughness, and water absorption capability. The resulting composite films demonstrated highly reversible color changes across the whole visible spectrum depending on the relative humidity, showing their capability to be reliable humidity-sensing materials. Thanks to the improved homogeneity and flexibility, the obtained humidity-sensing composite film can be employed in its entirety without the need for cutting, making it a promising candidate for various applications.

High biocompatible bone screw enabled by a rapid and robust chitosan/silk fibroin composite material.

Hydrogel has attracted tremendous attentions due to its excellent biocompatibility and adaptability in biomedical field. However, it is challenging by the conflicts between inadequate mechanical properties and service requirements. Herein, a rapid and robust hydrogel was developed by interpenetrating networks between chitosan and silk fibroin macromolecules. Thanks to these unique networks, the chitosan-based hydrogel exhibited superior mechanical performances. The maximum breaking strength, Young's modulus and swelling ratio of the hydrogel were 1187.8 kPa, 383.1 MPa and 4.5 % respectively. The hydrogel also supported the proliferation of human umbilical vein endothelial cells for 7 days. Notably, the hydrogel was easily molded into bone screw, and demonstrated compressive strengths of 45.7 MPa, Young's modulus of 675.6 MPa, respectively. After 49-day biodegradation, the residual rate of the screw in collagenase I solution was up to 89.6 % of the initial weight. In vitro, the screws not only had high resistance to biodegradation, but also had outstanding biocompatibility of osteoblast. This study provided a promising physical-chemical double crosslinking strategy to build orthopedic materials, holding a great potential in biomedical devices.

Citrate Improves Biomimetic Mineralization Induced by Polyelectrolyte-Cation Complexes Using PAsp-Ca&Mg Complexes.

Magnesium ions are highly enriched in early stage of biological mineralization of hard tissues. Paradoxically, hydroxyapatite (HAp) crystallization is inhibited significantly by high concentration of magnesium ions. The mechanism to regulate magnesium-doped biomimetic mineralization of collagen fibrils has never been fully elucidated. Herein, it is revealed that citrate can bioinspire the magnesium-stabilized mineral precursors to generate magnesium-doped biomimetic mineralization as follows: Citrate can enhance the electronegativity of collagen fibrils by its absorption to fibrils via hydrogen bonds. Afterward, electronegative collagen fibrils can attract highly concentrated electropositive polyaspartic acid-Ca&Mg (PAsp-Ca&Mg) complexes followed by phosphate solution via strong electrostatic attraction. Meanwhile, citrate adsorbed in/on fibrils can eliminate mineralization inhibitory effects of magnesium ions by breaking hydration layer surrounding magnesium ions and thus reduce dehydration energy barrier for rapid fulfillment of biomimetic mineralization. The remineralized demineralized dentin with magnesium-doped HAp possesses antibacterial ability, and the mineralization mediums possess excellent biocompatibility via cytotoxicity and oral mucosa irritation tests. This strategy shall shed light on cationic ions-doped biomimetic mineralization with antibacterial ability via modifying collagen fibrils and eliminating mineralization inhibitory effects of some cationic ions, as well as can excite attention to the neglected multiple regulations of small biomolecules, such as citrate, during biomineralization process.

Infant friendly adhesive film containing glucose for neonatal hypoglycemia.

Neonatal hypoglycemia is a common disease in newborns, which can precipitate energy shortage and follow by irreversible brain and neurological injury. Herein, we present a novel approach for treating neonatal hypoglycemia involving an adhesive polyvinylpyrrolidone/gallic acid (PVP/GA) film loading glucose. The PVP/GA film with loose cross-linking can be obtained by mixing their ethanol solution and drying complex. When depositing this soft film onto wet tissue, it can absorb interfacial water to form a hydrogel with a rough surface, which facilitates tight contact between the hydrogel and tissue. Meanwhile, the functional groups in the hydrogels and tissues establish both covalent and non-covalent bonds, leading to robust bioadhesion. Moreover, the adhered PVP/GA hydrogel can be detached without damaging tissue as needed. Furthermore, the PVP/GA films exhibit excellent antibacterial properties and biocompatibility. Notably, these films effectively load glucose and deliver it to the sublingual tissue of newborn rabbits, showcasing a compelling therapeutic effect against neonatal hypoglycemia. The strengths of the PVP/GA film encompass excellent wet adhesion in the wet and highly dynamic environment of the oral cavity, on-demand detachment, antibacterial efficacy, biocompatibility, and straightforward preparation. Consequently, this innovative film holds promise for diverse biomedical applications, including but not limited to wearable devices, sealants, and drug delivery systems.

Superb Silk Hydrogels with High Adaptability, Bioactivity, and Versatility Enabled by Photo-Cross-Linking.

The exceptional biocompatibility and adaptability of hydrogels have garnered significant interest in the biomedical field for the fabrication of biomedical devices. However, conventional synthetic hydrogels still exhibit relatively weak and fragile properties. Drawing inspiration from the photosynthesis process, we developed a facile approach to achieve a harmonious combination of superior mechanical properties and efficient preparation of silk fibroin hydrogel through photo-cross-linking technology, accomplished within 60 s. The utilization of riboflavin and H2O2 enabled a sustainable cyclic photo-cross-linking reaction, facilitating the transformation from tyrosine to dityrosine and ultimately contributing to the formation of highly cross-linked hydrogels. These photo-cross-linking hydrogels exhibited excellent elasticity and restorability even after undergoing 1000 cycles of compression. Importantly, our findings presented that hydrogel-encapsulated adipose stem cells possess the ability to stimulate cell proliferation along with stem cell stemness. This was evidenced by the continuous high expression levels of OCT4 and SOX2 over 21 days. Additionally, the utilization of photo-cross-linking hydrogels can be extended to various material molding platforms, including microneedles, microcarriers, and bone screws. Consequently, this study offered a significant approach to fabricating biomedical hydrogels capable of facilitating real-time cell delivery, thereby introducing an innovative avenue for designing silk devices with exceptional machinability and adaptability in biomedical applications.

Clinical and Genetic Analysis of Multiple Idiopathic Cervical Root Resorption.

OBJECTIVE: To explore the genetic background and clinical phenotypes of multiple idiopathic cervical root resorption (MICRR) in a Chinese family. METHODS: The proband and his three family members were clinically examined and had radiographs taken with a radiovisiography (RVG) system and CBCT to define the diagnosis of MICRR. Genomic DNA (gDNA) was extracted from peripheral blood samples of the patient, his father, mother and younger sister for whole exome sequencing (WES). The pathogenicity of rare variants with minor allele frequency (MAF) less than 0.005 were analysed following possible inheritance patterns, predicted results from 12 software programs, the American College of Medical Genetics (ACMG) 2015 criteria, and information from ClinVar, OMIM and HGMD databases as well as gene function. RESULTS: The proband presented the typical MICRR phenotypes such as thin cervical pulp wall and apple core-like lesions in radiographs. Following the recessive inheritance pattern, WES analysis identified SHROOM2, SYTL5, MAGED1 and FLNA with a higher chance of causing MICRR. Four genes with compound heterozygous variants and another 27 genes with de novo variants either in autosomal-dominant or autosomal-recessive pattern were also found to have the potential pathogenicity. CONCLUSION: A total of 35 novel potential pathogenic genes were found to be associated with MICRR from a Chinese family through WES. The new genetic background of MICRR may be helpful for clinical and molecular diagnosis.

Pathogenic PSAT1 Variants and Autosomal Recessive Axonal Charcot-Marie-Tooth Disease With Ichthyosis.

BACKGROUND: Biallelic pathogenic phosphoserine aminotransferase 1 (PSAT1) variants generally cause a severe phenotype predominantly involving the central nervous system. Here, for the first time, we report two patients harboring pathogenic PSAT1 variants only manifested as polyneuropathy and ichthyosis. METHODS: Two patients from unrelated families presenting with polyneuropathy and ichthyosis were enrolled. Whole exome sequencing was performed to identify possible disease-causing variants. Their clinical, electrophysiological, imaging, biochemical, and pathologic changes were in detail assessed and investigated. RESULTS: Homozygous variant c.43G>C and compound heterozygous variants c.112A>C and c.43G>C in PSAT1 were identified in patients 1 and 2, respectively. Nerve conduction studies revealed preserved or mild slowing motor nerve conduction velocities of the median nerves in the two patients, whereas the compound motor action potential in patient 1 was severely decreased. Brain magnetic resonance imaging of the two patients found no abnormalities. Median nerve enlargement was observed on ultrasound in patient 1. Both patients had normal level of serine and glycine in plasma and cerebrospinal fluid. Sural nerve biopsy found severe loss of myelinated fibers. Electron microscopy revealed neurofilament accumulation and mitochondrial aggregation in axons. Both variants in PSAT1 were classified as likely pathogenic or pathogenic variants according to the standard guidelines. CONCLUSIONS: Our study confirms that pathogenic PSAT1 variants can cause a mild phenotype, predominantly as autosomal recessive axonal Charcot-Marie-Tooth disease.

Regulating droplet impact and wetting behaviors on hydrophobic leaves using a nonionic surfactant.

Droplet rebound from hydrophobic leaves is a major factor influencing pesticide utilization. The use of a surfactant is a major strategy to reduce droplet rebound, promoting pesticide deposition on hydrophobic agricultural plant leaves. However, most surfactants known to regulate droplet rebound are either anionic or cationic. In this study, ethoxylated propoxylated 2-ethyl-1-haxanol (EH 6) was identified as a nonionic surfactant that inhibits droplet rebound while promoting the complete spreading of the droplet on hydrophobic leaves. Compared with the widely reported nonionic surfactant Tween 20, EH 6 performs better at concentrations above 0.3%. This phenomenon can be attributed to the rapid migration of EH 6 from the bulk to the newly generated interface, significantly reducing the surface tension. We introduce a simple and effective strategy that can be used to enhance droplet deposition on hydrophobic plant surfaces, which may offer future economic and environmental benefits.

BMI1 Silencing Liposomes Suppress Postradiotherapy Cancer Stemness against Radioresistant Hepatocellular Carcinoma.

Radiotherapy causes DNA damage by direct ionization and indirect generation of reactive oxygen species (ROS) thereby destroying cancer cells. However, ionizing radiation (IR) unexpectedly elicits metastasis and invasion of cancer cells by inducing cancer stem cells' (CSCs) properties. As BMI1 is a crucial gene that causes radioresistance and an unfavorable prognosis of hepatocellular carcinoma (HCC), BMI1 inhibitor PTC-209 has been encapsulated in a ROS-responsive liposome (LP(PTC-209)) to be temporally and spatially delivered to radioresistant HCC tissue. The ROS generated during IR was not only considered to directly cause tumor cell death but also be used as a stimulator to trigger ROS-responsive drug release from LP(PTC-209). The PTC-209 released into resistant HCC tissue under radiotherapy further led to cancer stem cell (CSC) differentiation and then recovered radiosensitivity of HCC tumor. The suppression of the radioresistant performance of LP(PTC-209) has been proved on radiosensitive and radioresistant Hepa1-6 CSC tumor models, respectively. Our study clarified the relationship between radiotherapy and cancer stemness and provided insights to achieve complete suppression of radioresistant HCC tumor by inhibiting cancer stemness.

Bifunctional Cu(II)-containing PDA-PEI copolymer dots: Demonstration of a dual-mode platform for colorimetric-fluorescent detection of glyphosate in the environment.

The reliable and accurate detection of glyphosate is urgently demanded because it is related to food and environmental safety. In this contribution, a PDA-PEI/Cu2+ complex that possesses peroxidase-mimetic activity and stimulus-responsive fluorescence was fabricated by coordinating Cu2+ with polydopamine-polyethyleneimine copolymer dots (PDA-PEI CPDs). With the introduction of Cu2+, the fluorescence intensity of PDA-PEI CPDs dropped sharply owing to the electron transfer effect. As a peroxidase-mimicking nanozyme, the PDA-PEI/Cu2+ complex owns catalytic capacity to oxidize the colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxTMB, leading a further fluorescence quenching by internal filtering effect by oxTMB. Once the glyphosate participated, the fluorescence signal of PDA-PEI CPDs is recovered significantly because of the formation of more stable Glyp-Cu2+ complexes, meanwhile the peroxidase-mimicking activity of PDA-PEI/Cu2+ complex could be strongly hindered. According to this principle, a novel and extremely convenient 'turn off' colorimetric and 'turn on' fluorescence sensing platform can be established for dual-mode detection of glyphosate. The favorable sensitivity and selectivity and were verified in the analysis of glyphosate in the environment through the marriage of dual-signal sensing platform. The detection limit of the dual-mode glyphosate sensing platform was 103.82 ng/mL for colorimetric assay and 16.87 ng/mL for fluorescent assay, respectively. Satisfactory recoveries in the range of 96.40%-104.66% were obtained, indicating the potential of this method for application in complicated real sample. Thereby, this strategy broadens the applications of polydopamine nanomaterials and holds a promising application in determination of pesticide residues.