New G-Triplex DNA Dramatically Activates the Fluorescence of Thioflavin T and Acts as a Turn-On Fluorescent Sensor for Uracil-DNA Glycosylase Activity Detection.

G-triplexes are G-rich oligonucleotides composed of three G-tracts and have absorbed much attention due to their potential biological functions and attractive performance in biosensing. Through the optimization of loop compositions, DNA lengths, and 5'-flanking bases of G-rich sequences, a new stable G-triplex sequence with 14 bases (G3-F15) was discovered to dramatically activate the fluorescence of Thioflavin T (ThT), a water-soluble fluorogenic dye. The fluorescence enhancement of ThT after binding with G3-F15 reached 3200 times, which was the strongest one by far among all of the G-rich sequences. The conformations of G3-F15 and G3-F15/ThT were studied by circular dichroism. The thermal stability measurements indicated that G3-F15 was a highly stable G-triplex structure. The conformations of G3-F15 and G3-F15/ThT in the presence of different metal cations were studied thoroughly by fluorescent spectroscopy, circular dichroism, and nuclear magnetic resonance. Furthermore, using the G3-F15/ThT complex as a fluorescent probe, a robust and simple turn-on fluorescent sensor for uracil-DNA glycosylase activity was developed. This study proposes a new systematic strategy to explore new functional G-rich sequences and their ligands, which will promote their applications in diagnosis, therapy, and biosensing.

Dioscin decreases M2 polarization via inhibiting a positive feedback loop between RBM47 and NF-κB in glioma.

BACKGROUND: The role of the glioblastoma (GBM) microenvironment is pivotal in the development of gliomas. Discovering drugs that can traverse the blood-brain barrier and modulate the tumor microenvironment is crucial for the treatment of GBM. Dioscin, a steroidal saponin derived from various kinds of plants and herbs known to penetrate the blood-brain barrier, has shown its powerful anti-tumor activity. However, little is known about its effects on GBM microenvironment. METHODS: Bioinformatics analysis was conducted to assess the link between GBM patients and their prognosis. Multiple techniques, including RNA sequencing, immunofluorescence staining, Western blot analysis, RNA-immunoprecipitation (RIP) assays, and Chromatin immunoprecipitation (CHIP) analysis were employed to elucidate the mechanism through which Dioscin modulates the immune microenvironment. RESULTS: Dioscin significantly impaired the polarization of macrophages into the M2 phenotype and enhanced the phagocytic ability of macrophages in vitro and in vivo. A strong correlation between high expression of RBM47 in GBM and a detrimental prognosis for patients was demonstrated. RNA-sequencing analysis revealed an association between RBM47 and the immune response. The inhibition of RBM47 significantly impaired the recruitment and polarization of macrophages into the M2 phenotype and enhanced the phagocytic ability of macrophages. Moreover, RBM47 could stabilize the mRNA of inflammatory genes and enhance the expression of these genes by activating the NF-κB pathway. In addition, NF-κB acts as a transcription factor that enhances the transcriptional activity of RBM47. Notably, we found that Dioscin could significantly inhibit the activation of NF-κB and then downregulate the expression of RBM47 and inflammatory genes protein. CONCLUSION: Our study reveals that the positive feedback loop between RBM47 and NF-κB could promote immunosuppressive microenvironment in GBM. Dioscin effectively inhibits M2 polarization in GBM by disrupting the positive feedback loop between RBM47 and NF-κB, indicating its potential therapeutic effects in GBM treatment.

Qualitative and Quantitative Analytical Techniques of Nucleic Acid Modification Based on Mass Spectrometry for Biomarker Discovery.

Nucleic acid modifications play important roles in biological activities and disease occurrences, and have been considered as cancer biomarkers. Due to the relatively low amount of nucleic acid modifications in biological samples, it is necessary to develop sensitive and reliable qualitative and quantitative methods to reveal the content of any modifications. In this review, the key processes affecting the qualitative and quantitative analyses are discussed, such as sample digestion, nucleoside extraction, chemical labeling, chromatographic separation, mass spectrometry detection, and data processing. The improvement of the detection sensitivity and specificity of analytical methods based on mass spectrometry makes it possible to study low-abundance modifications and their biological functions. Some typical nucleic acid modifications and their potential as biomarkers are displayed, and efforts to improve diagnostic accuracy are discussed. Future perspectives are raised for this research field.

Mechanically strong micro-nano fibrillated cellulose paper with improved barrier and water-resistant properties for replacing plastic.

Replacing nonbiodegradable plastics with environmentally friendly cellulose materials has emerged as a key trend in environmental protection. This study highlights the development of a strong and hydrophobic micro-nano fibrillated cellulose paper (MNP) through the incorporation of micro-nano fibrillated cellulose fiber (MNF) and chitin nanocrystal (Ch), followed by the impregnation of polymethylsiloxane (PMHS). A low-acid, heat-assisted colloidal grinding strategy was employed to prepare MNF with a high aspect ratio effectively. Ch was incorporated as a reinforcing matrix into the cellulose fiber scaffold through straightforward mechanical mixing and mechanical hot-pressing treatments. Compared to pure MNP, the 5Ch-MNP exhibited a 25 % improvement in tensile strength, reaching 170 MPa, and showed enhanced barrier properties against oxygen and water vapor. The impregnation of PMHS rapidly confers environmentally resistant hydrophobic properties to 1 % PMHS-5Ch-MNP, leading to a water contact angle exceeding 112°, and a 290 % increase in tensile strength under wet conditions. Additionally, the paper demonstrated excellent antibacterial adhesion properties, with the adhesion rates for E. coli and S. aureus exceeding 98 %. This study successfully produced functional cellulose paper with remarkable mechanical properties and barrier properties, as well as hydrophobicity, using a simple, efficient, and environmentally friendly method, making it a promising substitute for petroleum-based plastics.

Micro- and nano-hybrid cellulose fibers prepared by straightforward and high-efficiency hot water soaking-assisted colloid grinding for high-performance cellulose paper.

Micro- and nano-hybrid cellulose fiber (MNCF) stands out as a versatile cellulosic nanomaterial with promising applications in various fields owing to its excellent intrinsic nature and outstanding characteristics. However, the inefficiency in preparing MNCF, attributed to a complex multi-step processing, hinders its widespread adoption. In this study, a straightforward and highly efficient method for MNCF preparation was developed via a hot water soaking-assisted colloid grinding strategy. Active water molecules in hot water facilitating stronger transverse shrinkage and longitudinal expansion in fiber crystallized region, and thus improving the fibrillation degree of cellulose fibers. As a result, MNCFs with a mean diameter of 37.5 ± 22.2 nm and high concentration (2 wt%) were successfully achieved though pure mechanical method. The micro and nano-hybrid structure leads to the corresponding resulting cellulose paper with micro- and nano-hybrid structure possesses a compact stacking and fewer defects, leading to extraordinary mechanical properties including tensile strength of 204.5 MPa, Young's modulus of 6.3 GPa and elongation of 10.1 %. This work achieves significant progress towards straightforward and highly efficient production of MNCFs, offering an appreciable prospect for the development of multifunctional MNCF-based materials.

Identification and Quantification of Locus-Specific 8-Oxo-7,8-dihydroguanine in DNA at Ultrahigh Resolution Based on G-Triplex-Assisted Rolling Circle Amplification.

Damage of reactive oxygen species to various molecules such as DNA has been related to many chronic and degenerative human diseases, aging, and even cancer. 8-Oxo-7,8-dihydroguanine (OG), the most significant oxidation product of guanine (G), has become a biomarker of oxidative stress as well as gene regulation. The positive effect of OG in activating transcription and the negative effect in inducing mutation are a double-edged sword; thus, site-specific quantification is helpful to quickly reveal the functional mechanism of OG at hotspots. Due to the possible biological effects of OG at extremely low abundance in the genome, the monitoring of OG is vulnerable to signal interference from a large amount of G. Herein, based on rolling circle amplification-induced G-triplex formation and Thioflavin T fluorescence enhancement, an ultrasensitive strategy for locus-specific OG quantification was constructed. Owing to the difference in the hydrogen-bonding pattern between OG and G, the nonspecific background signal of G sites was completely suppressed through enzymatic ligation of DNA probes and the triggered specificity of rolling circle amplification. After the signal amplification strategy was optimized, the high detection sensitivity of OG sites with an ultralow detection limit of 0.18 amol was achieved. Under the interference of G sites, as little as 0.05% of OG-containing DNA was first distinguished. This method was further used for qualitative and quantitative monitoring of locus-specific OG in genomic DNA under oxidative stress and identification of key OG sites with biological function.

Dimensioning Cuboid and Cylindrical Objects Using Only Noisy and Partially Observed Time-of-Flight Data.

One of the challenges of using Time-of-Flight (ToF) sensors for dimensioning objects is that the depth information suffers from issues such as low resolution, self-occlusions, noise, and multipath interference, which distort the shape and size of objects. In this work, we successfully apply a superquadric fitting framework for dimensioning cuboid and cylindrical objects from point cloud data generated using a ToF sensor. Our work demonstrates that an average error of less than 1 cm is possible for a box with the largest dimension of about 30 cm and a cylinder with the largest dimension of about 20 cm that are each placed 1.5 m from a ToF sensor. We also quantify the performance of dimensioning objects using various object orientations, ground plane surfaces, and model fitting methods. For cuboid objects, our results show that the proposed superquadric fitting framework is able to achieve absolute dimensioning errors between 4% and 9% using the bounding technique and between 8% and 15% using the mirroring technique across all tested surfaces. For cylindrical objects, our results show that the proposed superquadric fitting framework is able to achieve absolute dimensioning errors between 2.97% and 6.61% when the object is in a horizontal orientation and between 8.01% and 13.13% when the object is in a vertical orientation using the bounding technique across all tested surfaces.

Probabilistic Modeling of Multicamera Interference for Time-of-Flight Sensors.

The behavior of multicamera interference in 3D images (e.g., depth maps), which is based on infrared (IR) light, is not well understood. In 3D images, when multicamera interference is present, there is an increase in the amount of zero-value pixels, resulting in a loss of depth information. In this work, we demonstrate a framework for synthetically generating direct and indirect multicamera interference using a combination of a probabilistic model and ray tracing. Our mathematical model predicts the locations and probabilities of zero-value pixels in depth maps that contain multicamera interference. Our model accurately predicts where depth information may be lost in a depth map when multicamera interference is present. We compare the proposed synthetic 3D interference images with controlled 3D interference images captured in our laboratory. The proposed framework achieves an average root mean square error (RMSE) of 0.0625, an average peak signal-to-noise ratio (PSNR) of 24.1277 dB, and an average structural similarity index measure (SSIM) of 0.9007 for predicting direct multicamera interference, and an average RMSE of 0.0312, an average PSNR of 26.2280 dB, and an average SSIM of 0.9064 for predicting indirect multicamera interference. The proposed framework can be used to develop and test interference mitigation techniques that will be crucial for the successful proliferation of these devices.

Simulation of Single-Event Transient Effect for GaN High-Electron-Mobility Transistor.

A GaN high-electron-mobility transistor (HEMT) was simulated using the semiconductor simulation software Silvaco TCAD in this paper. By constructing a two-dimensional structure of GaN HEMT, combined with key models such as carrier mobility, the effects of a different state, different incidence position, different drain voltage, different LET values, and a different incidence angle on the single-event transient effect of GaN HEMT are simulated. LET stands for the linear energy transfer capacity of a particle, which refers to the amount of energy transferred by the particle to the irradiated substance on the unit path. The simulation results show that for GaN HEMTs, the single-event transient effect is more obvious when the device is in off-state than in on-state. The most sensitive location of GaN HEMTs to the single-event effect is in the region near the drain. The peak transient current increases with the increase in the drain bias and incident ion LET values. The drain charge collection time increases with the angle of incidence of heavy ion.

Effect of P-Type GaN Buried Layer on the Temperature of AlGaN/GaN HEMTs.

In this paper, a P-type GaN buried layer is introduced into the buffer layer of AlGaN/GaN HEMTs, and the effect of the P-type GaN buried layer on the device's temperature characteristics is studied using Silvaco TCAD software. The results show that, compared to the conventional device structure, the introduction of a P-type GaN buried layer greatly weakens the peak of the channel electric field between the gate and drain of the device. This leads to a more uniform electric field distribution, a substantial reduction in the lattice temperature of the device, and a more uniform temperature distribution. Therefore, the phenomenon of negative resistance caused by self-heating effect is significantly mitigated, while the breakdown performance of the device is also notably enhanced.

Exploring acoustic characteristics of different aircraft types by fusing with aircraft tracking data.

In this study, we develop a method that assigns acoustic signals with Automatic Dependent Surveillance-Broadcast (ADS-B) data to build a labeled dataset of acoustic signals from aircraft without expensive ground-truth experiments. An exploration of the resultant labeled dataset enables an assessment of the acoustic characteristics from three types of aircraft. The fusion framework is evaluated using data from an acoustic sensor and collocated ADS-B receiver in the middle of a large urban area at Southern Methodist University in Dallas, Texas. Our results demonstrate the benefit of combining multiple types of data to generate a labeled dataset leveraging open-source aircraft surveillance data. By studying three classes of aircraft, we find that the smaller fixed wing single engine (FWSE) class is mostly detected within approximately 5000 m, while the larger fixed wing multi-engine (FWME) class is commonly detected out to greater distances above 7500 m. The FWSE class has a median source frequency at 100 Hz, compared to FWME class with median source frequency at 80 Hz, while rotorcraft has a source frequency falling into a lower range of 30-100 Hz.

Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells.

Aged hematopoietic stem cells (HSC) exhibit compromised reconstitution capacity and differentiation-bias towards myeloid lineage, however, the molecular mechanism behind it remains not fully understood. In this study, we observed that the expression of pseudouridine (Ψ) synthase 10 is increased in aged hematopoietic stem and progenitor cells (HSPC) and enforced protein of Ψ synthase 10 (PUS10) recapitulates the phenotype of aged HSC, which is not achieved by its Ψ synthase activity. Consistently, we observed no difference of transcribed RNA pseudouridylation profile between young and aged HSPC. No significant alteration of hematopoietic homeostasis and HSC function is observed in young Pus10-/- mice, while aged Pus10-/- mice exhibit mild alteration of hematopoietic homeostasis and HSC function. Moreover, we observed that PUS10 is ubiquitinated by E3 ubiquitin ligase CRL4DCAF1 complex and the increase of PUS10 in aged HSPC is due to aging-declined CRL4DCAF1- mediated ubiquitination degradation signaling. Taken together, this study for the first time evaluated the role of PUS10 in HSC aging and function, and provided a novel insight into HSC rejuvenation and its clinical application.

Cancer-cell-derived fumarate suppresses the anti-tumor capacity of CD8+ T cells in the tumor microenvironment.

Metabolic alterations in the microenvironment significantly modulate tumor immunosensitivity, but the underlying mechanisms remain obscure. Here, we report that tumors depleted of fumarate hydratase (FH) exhibit inhibition of functional CD8+ T cell activation, expansion, and efficacy, with enhanced malignant proliferative capacity. Mechanistically, FH depletion in tumor cells accumulates fumarate in the tumor interstitial fluid, and increased fumarate can directly succinate ZAP70 at C96 and C102 and abrogate its activity in infiltrating CD8+ T cells, resulting in suppressed CD8+ T cell activation and anti-tumor immune responses in vitro and in vivo. Additionally, fumarate depletion by increasing FH expression strongly enhances the anti-tumor efficacy of anti-CD19 CAR T cells. Thus, these findings demonstrate a role for fumarate in controlling TCR signaling and suggest that fumarate accumulation in the tumor microenvironment (TME) is a metabolic barrier to CD8+ T cell anti-tumor function. And potentially, fumarate depletion could be an important strategy for tumor immunotherapy.

In-source fragmentation of nucleosides in electrospray ionization towards more sensitive and accurate nucleoside analysis.

Nucleosides have been found to suffer in-source fragmentation (ISF) in electrospray ionization mass spectrometry, which leads to reduced sensitivity and ambiguous identification. In this work, a combination of theoretical calculations and nuclear magnetic resonance analysis revealed the key role of protonation at N3 near the glycosidic bond during ISF. Therefore, an ultrasensitive liquid chromatography-tandem mass spectrometry system for 5-formylcytosine detection was developed with 300 fold signal enhancement. Also, we established a MS1-only platform for nucleoside profiling and successfully identified sixteen nucleosides in the total RNA of MCF-7 cells. Taking ISF into account, we can realize analysis with higher sensitivity and less ambiguity, not only for nucleosides, but for other molecules with similar protonation and fragmentation behaviors.

Ultrasensitive HPLC-MS Quantification of S-(2-Succino) Cysteine Based on Ethanol/Acetyl Chloride Derivatization in Fumarate Accumulation Cells.

Succination is a nonenzymatic and irreversible post-translational modification (PTM) with important biological significance, yielding S-(2-succino) cysteine (2SC) residue. This PTM is low in abundance and often requires a large amount of protein samples for 2SC quantification. In this work, an efficient quantification method based on ethanol/acetyl chloride chemical derivatization was developed. The three carboxyl groups of 2SC were all esterified to increase hydrophobicity, greatly improving its ionization efficiency. The sensitivity was increased by 112 times; the limit of detection was reduced to 0.885 fmol, and the protein usage was reduced by at least 10 times. The established method was used to detect the overall concentration of 2SC in fumarate accumulation cells quantitatively.

Corrigendum: Modifying SnS2 with carbon quantum dots to improve photocatalytic performance for Cr(VI) reduction.

[This corrects the article DOI: 10.3389/fchem.2022.911291.].

Ultrasensitive Simultaneous Detection of Multiple Rare Modified Nucleosides as Promising Biomarkers in Low-Put Breast Cancer DNA Samples for Clinical Multi-Dimensional Diagnosis.

Early cancer diagnosis is essential for successful treatment and prognosis, and modified nucleosides have attracted widespread attention as a promising group of cancer biomarkers. However, analyzing these modified nucleosides with an extremely low abundance is a great challenge, especially analyzing multiple modified nucleosides with a different abundance simultaneously. In this work, an ultrasensitive quantification method based on chemical labeling, coupled with LC-MS/MS analysis, was established for the simultaneous quantification of 5hmdC, 5fdC, 5hmdU and 5fdU. Additionally, the contents of 5mdC and canonical nucleosides could be obtained at the same time. Upon derivatization, the detection sensitivities of 5hmdC, 5fdC, 5hmdU and 5fdU were dramatically enhanced by several hundred times. The established method was further applied to the simultaneous detection of nine nucleosides with different abundances in about 2 µg genomic DNA of breast tissues from 20 breast cancer patients. The DNA consumption was less than other overall reported quantification methods, thereby providing an opportunity to monitor rare, modified nucleosides in precious samples and biology processes that could not be investigated before. The contents of 5hmdC, 5hmdU and 5fdU in tumor tissues and normal tissues adjacent to the tumor were significantly changed, indicating that these three modified nucleosides may play certain roles in the formation and development of tumors and be potential cancer biomarkers. While the detection rates of 5hmdC, 5hmdU and 5fdU alone as a biomarker for breast cancer samples were 95%, 75% and 85%, respectively, by detecting these three cancer biomarkers simultaneously, two of the three were 100% consistent with the overall trend. Therefore, simultaneous detection of multiple cancer biomarkers in clinical samples greatly improved the accuracy of cancer diagnosis, indicating that our method has great application potential in clinical multidimensional diagnosis.

A Silicone Resin Coating with Water-Repellency and Anti-Fouling Properties for Wood Protection.

The strong hygroscopicity of wood greatly shortens its service life. Here, a simple impregnation modification approach was used to construct superhydrophobic silicone resin coatings on wood surfaces. Briefly, with hydrofluorosilicone oil (HFSO), tetramethyl tetravinyl cyclotetrasiloxane (V4), and hydrophobic SiO2 from industrial production as raw materials, superhydrophobic wood samples (water contact angle ~160.8°, sliding angle ~3.6°) can be obtained by simply dipping the wood in the HFSO/V4/SiO2 modifier solutions. As a result, the superhydrophobic silicone resin coating constructed on the wood surface still has good water repellency after finger touching, tape peeling, and sandpaper abrasion. When the mass ratio of HFSO to V4 is 2:1, the water absorption of the resulting wood after soaking in water for 24 h is only 29.2%. Further, the resulting superhydrophobic wood shows excellent anti-fouling properties. Finally, we believe that the impregnation modification method proposed in this study can be applied to the protection of cellulose substrates.

Modifying SnS2 With Carbon Quantum Dots to Improve Photocatalytic Performance for Cr(VI) Reduction.

The photoreduction for hazardous Cr(VI) in industrial wastewater has been considered a "green" approach with low-cost and easy-to-go operation. SnS2 is a promising narrow bandgap photocatalyst, but its low charge carrier separation efficiency should be solved first. In this work, N-doped carbon quantum dots (CQDs) were prepared and loaded onto SnS2 nanoparticles via an in situ method. The resulting composite samples (NC@SnS2) were characterized, and their photocatalytic performance was discussed. SnS2 nanoparticles were obtained as hexagonal ones with a bandgap of 2.19 eV. The optimal doping level for NC@SnS2 was citric acid: urea:SnS2 = 1.2 mmol:1.8 mmol:3.0 mmol. It showed an average diameter of 40 nm and improved photocatalytic performance, compared to pure SnS2, following a pseudo-first-order reaction with a kinetic rate constant of 0.1144 min-1. Over 97% of Cr(VI) was photo-reduced after 30 min. It was confirmed that modification of SnS2 with CQDs can not only improve the light-harvesting ability but also stimulate the charge separation, which therefore can enhance the photoreactivity of SnS2 toward Cr(VI) reduction. The excellent stability of NC@SnS2 indicates that it is promising to be practically used in industrial wastewater purification.

Fumarate suppresses B-cell activation and function through direct inactivation of LYN.

Activated B cells increase central carbon metabolism to fulfill their bioenergetic demands, yet the mechanistic basis for this, as well as metabolic regulation in B cells, remains largely unknown. Here, we demonstrate that B-cell activation reprograms the tricarboxylic acid cycle and boosts the expression of fumarate hydratase (FH), leading to decreased cellular fumarate abundance. Fumarate accumulation by FH inhibition or dimethyl-fumarate treatment suppresses B-cell activation, proliferation and antibody production. Mechanistically, fumarate is a covalent inhibitor of tyrosine kinase LYN, a key component of the BCR signaling pathway. Fumarate can directly succinate LYN at C381 and abrogate LYN activity, resulting in a block to B-cell activation and function in vitro and in vivo. Therefore, our findings uncover a previously unappreciated metabolic regulation of B cells, and reveal LYN is a natural sensor of fumarate, connecting cellular metabolism to B-cell antigen receptor signaling.