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45 pages, 5089 KB  
Review
A Review on the Synthesis Methods, Properties, and Applications of Polyaniline-Based Electrochromic Materials
by Ge Cao, Yan Ke, Kaihua Huang, Tianhong Huang, Jiali Xiong, Zhujun Li and He Zhang
Coatings 2026, 16(1), 129; https://doi.org/10.3390/coatings16010129 - 19 Jan 2026
Viewed by 338
Abstract
Polyaniline (PANI), characterized by its proton-coupled redox mechanism and multicolor reversibility, is widely investigated for adaptive optical interfaces. Compared to inorganic oxides, PANI offers advantages in cost-effectiveness, mechanical flexibility, and molecular tunability; however, its practical implementation faces challenges related to kinetic limitations and [...] Read more.
Polyaniline (PANI), characterized by its proton-coupled redox mechanism and multicolor reversibility, is widely investigated for adaptive optical interfaces. Compared to inorganic oxides, PANI offers advantages in cost-effectiveness, mechanical flexibility, and molecular tunability; however, its practical implementation faces challenges related to kinetic limitations and environmental instability. This review presents a comprehensive analysis of PANI-based electrochromic materials, examining the intrinsic correlations among synthesis methodologies, microstructural characteristics, and optoelectronic performance. Synthesis strategies, including chemical oxidative polymerization, electrochemical deposition, and template-assisted techniques, are evaluated. Emphasis is placed on resolving the trade-off between optical contrast and switching kinetics by constructing high-surface-area porous nanostructures and inducing chain ordering via functional dopants to shorten ion diffusion paths and reduce charge transfer resistance. Fundamental electrochromic properties are subsequently discussed, with specific attention to degradation mechanisms triggered by environmental factors, such as pH drift, and stabilization strategies involving electrolyte engineering and composite design. Furthermore, the review addresses the evolution of applications from single-band monochromatic displays to dual-band smart windows for decoupled visible/near-infrared regulation and multifunctional integrated systems, including electrochromic supercapacitors and adaptive thermal management textiles. Finally, technical challenges regarding long-term durability, neutral color development, and large-area manufacturing are summarized to outline future research directions for PANI-based optical systems. Full article
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29 pages, 818 KB  
Article
Templated and Overlay HW/SW Co-Optimization for Crossbar-Free P4 Deparser FPGA Architectures
by Parisa Mashreghi-Moghadam, Tarek Ould-Bachir and Yvon Savaria
Electronics 2025, 14(24), 4850; https://doi.org/10.3390/electronics14244850 - 10 Dec 2025
Viewed by 311
Abstract
The deparser stage in the Protocol-Independent Switch Architecture (PISA) is often overshadowed by parser and match-action optimizations. Yet, it remains a critical performance bottleneck in P4-programmable FPGA data planes. Challenges associated with the deparser stem from dynamic header layouts, variable emission orders, and [...] Read more.
The deparser stage in the Protocol-Independent Switch Architecture (PISA) is often overshadowed by parser and match-action optimizations. Yet, it remains a critical performance bottleneck in P4-programmable FPGA data planes. Challenges associated with the deparser stem from dynamic header layouts, variable emission orders, and alignment constraints, which often necessitate resource-intensive designs, such as wide, dynamic crossbar routing. While compile-time specialization techniques can reduce logic usage, they sacrifice runtime adaptability: any change to the protocol graph, including adding, removing, or reordering headers, requires full hardware resynthesis and re-implementation, limiting their practicality for evolving or multi-tenant workloads. This work presents a unified FPGA-targeted deparser architecture that merges templated and overlay concepts within a hardware–software co-design framework. At design time, template parameters define upper bounds on protocol complexity, enabling resource-efficient synthesis tailored to specific workloads. Within these bounds, runtime reconfiguration is supported through overlay control tables derived from static deparser DAG analysis, which capture the per-path emission order, header alignments, and offsets. These tables drive protocol-agnostic, chunk-based emission blocks that eliminate the overhead of crossbar interconnects, thereby significantly reducing complexity and resource usage. The proposed design sustains high throughput while preserving the flexibility needed for in-field updates and long-term protocol evolution. Full article
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14 pages, 1733 KB  
Article
Anisotropic Resistive Switching in NiO Thin Films Deposited on Stepped MgO Substrates
by Tolagay Duisebayev, Mergen Zhazitov, Muhammad Abdullah, Yerbolat Tezekbay, Askar Syrlybekov, Margulan Ibraimov, Bakyt Khaniyev, Timur Serikov, Nurxat Nuraje and Olzat Toktarbaiuly
Nanomaterials 2025, 15(22), 1703; https://doi.org/10.3390/nano15221703 - 11 Nov 2025
Viewed by 662
Abstract
Thin films of nickel oxide (NiO) were deposited on a 5° miscut magnesium oxide (MgO)(100) substrate using electron-beam evaporation to pursue morphology-directed resistive switching. The atomic force microscope (AFM) confirmed a stepped surface with a terrace width of ~85 nm and a step [...] Read more.
Thin films of nickel oxide (NiO) were deposited on a 5° miscut magnesium oxide (MgO)(100) substrate using electron-beam evaporation to pursue morphology-directed resistive switching. The atomic force microscope (AFM) confirmed a stepped surface with a terrace width of ~85 nm and a step height of ~7 nm. After deposition, the film resistance decreased from 200 MΩ to 25 MΩ by annealing under ambient air at 400 °C, attributed to the increase in the p-type conductivity through nickel vacancy formation. Top electrodes of Ag (500 nm width, 180 nm gap) were patterned parallel or perpendicular to the substrate steps using UV and electron-beam lithography. Devices aligned parallel to the step showed reproducible unipolar switching with 100% yield between forming voltages 20–70 V and HRS/LRS~102 at ±5 V. In contrast, devices formed perpendicular to the steps (8/8) subsequently failed catastrophically during electroforming, with scanning electron microscopy (SEM) showing breakdown holes on the order of ~100 nm at the step crossings. The anisotropic electrodynamic response is due to step-guided electric field distribution and directional nickel vacancy migration, illustrating how substrate morphology can deterministically influence filament nucleation. These results highlighted stepped MgO as a template to engineer the anisotropic charge transport of NiO, exhibiting a reliable ReRAM as well as directional electrocatalysis for energy applications. Full article
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28 pages, 2421 KB  
Review
Roles of RNA Structures in the Genome Translation of (+) Sense RNA Viruses
by Guangming Lu, Bethel G. Beyene, Joshua Miguele Camacho and Deepak Koirala
Viruses 2025, 17(11), 1404; https://doi.org/10.3390/v17111404 - 22 Oct 2025
Cited by 1 | Viewed by 2131
Abstract
Positive (+) sense RNA viruses include many important pathogens that exploit noncanonical translation mechanisms to express their genomes within the host cells. Unlike DNA or negative (−) sense RNA viruses, (+) sense RNA viruses can directly function as mRNAs, even though they lack [...] Read more.
Positive (+) sense RNA viruses include many important pathogens that exploit noncanonical translation mechanisms to express their genomes within the host cells. Unlike DNA or negative (−) sense RNA viruses, (+) sense RNA viruses can directly function as mRNAs, even though they lack typical features of host mRNAs, such as the 5′ cap structure required for canonical translation initiation. Instead, they exploit structured RNA elements to recruit host translational machinery without the 5′ cap, bypassing the canonical translation initiation mechanism. Prominent examples include internal ribosome entry sites (IRESs) and 3′ cap-independent translation enhancers (3′ CITEs). These RNA modules facilitate translation initiation by recruiting the ribosomal subunits, either directly or through initiation factors, and mediating long-range RNA-RNA interactions. Other regulatory motifs, such as frameshifting signals, allow the ribosome to shift reading frames to regulate protein output. All these RNA elements function through RNA-protein interactions and often utilize host and virus-encoded proteins to hijack the host’s translational apparatus. Over the past several years, various structural biology approaches, including biochemical and enzymatic probing, X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryogenic electron microscopy (cryo-EM), have revealed the unique structural roles of these viral RNA elements and their protein complexes. Although a few structures of IRES and CITE domains have been solved through these methods, the structures of these RNA elements and their structure-function relationship have remained largely unknown. This review discusses the current understanding of translation-related RNA structures in (+) sense RNA viruses, the critical RNA-protein interactions they mediate, and various structural biology approaches used to study them. Since the genome of these viruses serves as a template for two mutually exclusive virological processes, namely genome translation and replication, the review also discusses how viruses can utilize RNA structure-based strategies to regulate the switch between genome translation and replication, highlighting future directions for exploring these fundamental virological processes to develop antiviral therapeutics able to combat diseases caused by these pathogens. Full article
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10 pages, 474 KB  
Communication
Compound Heterozygous Complete Loss-of-Function SPINK1 Variants as a Novel Cause of Severe Infantile Isolated Exocrine Pancreatic Insufficiency
by Emmanuelle Masson, Marc Wangermez, David Tougeron, Vinciane Rebours, Claude Férec and Jian-Min Chen
Genes 2025, 16(9), 998; https://doi.org/10.3390/genes16090998 - 25 Aug 2025
Viewed by 1024
Abstract
Background/Objectives: While complete loss-of-function (LoF) SPINK1 variants in the simple heterozygous state cause chronic pancreatitis, biallelic complete LoF variants result in a rare pediatric disorder termed severe infantile isolated exocrine pancreatic insufficiency (SIIEPI). To date, only two individuals with a null SPINK1 genotype [...] Read more.
Background/Objectives: While complete loss-of-function (LoF) SPINK1 variants in the simple heterozygous state cause chronic pancreatitis, biallelic complete LoF variants result in a rare pediatric disorder termed severe infantile isolated exocrine pancreatic insufficiency (SIIEPI). To date, only two individuals with a null SPINK1 genotype have been reported—one homozygous for a whole-gene deletion and the other for an Alu insertion in the 3′ untranslated region. Here, we report the genetic basis of a third SIIEPI case, presenting in early infancy with severe exocrine pancreatic insufficiency and diffuse pancreatic lipomatosis. Methods: Targeted next-generation sequencing (NGS) was used to analyze the entire coding region and exon–intron boundaries of the SPINK1 gene. Copy number variant (CNV) analysis was performed with SeqNext, based on normalized amplicon coverage. Results: The proband harbored compound heterozygous complete LoF SPINK1 variants. One was the known NM_001379610.1:c.180_181del (p.(Cys61PhefsTer2)), inherited from the father. The second, initially detected as an exon 2 deletion and confirmed by quantitative fluorescent multiplex PCR (QFM-PCR), was further characterized by long-range PCR as a complex rearrangement comprising a 1185 bp deletion removing exon 2, a 118 bp templated insertion followed by a non-templated nucleotide, and an 8 bp deletion. The mutational signature is consistent with serial replication slippage or template switching involving translesion synthesis. This maternally inherited variant has not been previously reported. Conclusions: This study expands the mutational spectrum of SPINK1-related SIIEPI and suggests that this distinct pediatric disorder may be under recognized in clinical practice. Full article
(This article belongs to the Special Issue Genetics and Genomics of Heritable Pediatric Disorders)
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13 pages, 3561 KB  
Article
Preparing Surface-Functionalized Polymer Films with Hierarchically Ordered Structure by a Combination of Nanoimprinting and Controlled Graft Polymerization
by Masahiko Minoda, Daichi Shimizu, Tatsuya Nohara and Jin Motoyanagi
Surfaces 2025, 8(3), 48; https://doi.org/10.3390/surfaces8030048 - 11 Jul 2025
Viewed by 1133
Abstract
It is widely recognized that fine surface structures found in nature contribute to surface functionality, and studies on the design of functional materials based on biomimetics have been actively conducted. In this study, polymer thin films with hierarchically ordered surface structure were prepared [...] Read more.
It is widely recognized that fine surface structures found in nature contribute to surface functionality, and studies on the design of functional materials based on biomimetics have been actively conducted. In this study, polymer thin films with hierarchically ordered surface structure were prepared by combining both nanoimprinting using anodically oxidized porous alumina (AAO) as a template and surface-initiated atom transfer radical polymerization (SI-ATRP). To prepare such polymer films, we designed a new copolymer (poly{[2-(4-methyl-2-oxo-2H-chromen-7-yloxy)ethyl methacrylate]-co-[2-(2-bromo-2-methylpropionyloxy)ethyl methacrylate]}; poly(MCMA-co-HEMABr)) with coumarin moieties and α-haloester moieties in the pendants. The MCMA repeating units function to fix the pillar structure by photodimerization, and the HEMABr ones act as the polymerization initiation sites for SI-ATRP on the pillar surfaces. Surface structures consisting of vertically oriented multiple pillars were fabricated on the spin-coated poly(MCMA-co-HEMABr) thin films by nanoimprinting using an AAO template. Then, the coumarin moieties inside each pillar were crosslinked by UV light irradiation to fix the pillar structure. SEM observation confirmed that the internally crosslinked pillar structures were maintained even when immersed in organic solvents such as 1,2-dichloroethane and anisole, which are employed as solvents under SI-ATRP conditions. Finally, poly(2,2,2-trifluoroethyl methacrylate) and poly(N-isopropylacrylamide) chains were grafted onto the thin film by SI-ATRP, respectively, to prepare the hierarchically ordered surface structure. Furthermore, in this study, the surface properties as well as the thermoresponsive hydrophilic/hydrophobic switching of the obtained polymer films were investigated. The surface morphology and chemistry of the films with and without pillar structures were compared, especially the interfacial properties expressed as wettability. Grafting poly(TFEMA) increased the static contact angle for both flat and pillar films, and the con-tact angle of the pillar film surface increased from 104° for the flat film sample to 112°, suggesting the contribution of the pillar structure. Meanwhile, the pillar film surface grafted with poly(NIPAM) brought about a significant change in wettability when changing the temperature between 22 °C and 38 °C. Full article
(This article belongs to the Special Issue Surface Science: Polymer Thin Films, Coatings and Adhesives)
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22 pages, 882 KB  
Article
HLSCAM: Fine-Tuned HLS-Based Content Addressable Memory Implementation for Packet Processing on FPGA
by Mostafa Abbasmollaei, Tarek Ould-Bachir and Yvon Savaria
Electronics 2025, 14(9), 1765; https://doi.org/10.3390/electronics14091765 - 26 Apr 2025
Cited by 3 | Viewed by 1814
Abstract
Content Addressable Memories (CAMs) are pivotal in high-speed packet processing systems, enabling rapid data lookup operations essential for applications such as routing, switching, and network security. While traditional Register-Transfer Level (RTL) methodologies have been extensively used to implement CAM architectures on Field-Programmable Gate [...] Read more.
Content Addressable Memories (CAMs) are pivotal in high-speed packet processing systems, enabling rapid data lookup operations essential for applications such as routing, switching, and network security. While traditional Register-Transfer Level (RTL) methodologies have been extensively used to implement CAM architectures on Field-Programmable Gate Arrays (FPGAs), they often involve complex, time-consuming design processes with limited flexibility. In this paper, we propose a novel templated High-Level Synthesis (HLS)-based approach for the design and implementation of CAM architectures such as Binary CAMs (BCAMs) and Ternary CAMs (TCAMs) optimized for data plane packet processing. Our HLS-based methodology leverages the parallel processing capabilities of FPGAs through employing various design parameters and optimization directives while significantly reducing development time and enhancing design portability. This paper also presents architectural design and optimization strategies to offer a fine-tuned CAM solution for networking-related arbitrary use cases. Experimental results demonstrate that HLSCAM achieves a high throughput, reaching up to 31.18 Gbps, 9.04 Gbps, and 33.04 Gbps in the 256×128, 512×36, and 1024×150 CAM sizes, making it a competitive solution for high-speed packet processing on FPGAs. Full article
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22 pages, 17696 KB  
Article
The Yeast HMGB Protein Hmo1 Is a Multifaceted Regulator of DNA Damage Tolerance
by Jinlong Huo, Anhui Wei, Na Guo, Ruotong Wang and Xin Bi
Int. J. Mol. Sci. 2025, 26(7), 3255; https://doi.org/10.3390/ijms26073255 - 1 Apr 2025
Viewed by 1201
Abstract
The Saccharomyces cerevisiae chromosomal architectural protein Hmo1 is categorized as an HMGB protein, as it contains two HMGB motifs that bind DNA in a structure-specific manner. However, Hmo1 has a basic C-terminal domain (CTD) that promotes DNA bending instead of an acidic one [...] Read more.
The Saccharomyces cerevisiae chromosomal architectural protein Hmo1 is categorized as an HMGB protein, as it contains two HMGB motifs that bind DNA in a structure-specific manner. However, Hmo1 has a basic C-terminal domain (CTD) that promotes DNA bending instead of an acidic one found in a canonical HMGB protein. Hmo1 has diverse functions in genome maintenance and gene regulation. It is implicated in DNA damage tolerance (DDT) that enables DNA replication to bypass lesions on the template. Hmo1 is believed to direct DNA lesions to the error-free template switching (TS) pathway of DDT and to aid in the formation of the key TS intermediate sister chromatid junction (SCJ), but the underlying mechanisms have yet to be resolved. In this work, we used genetic and molecular biology approaches to further investigate the role of Hmo1 in DDT. We found extensive functional interactions of Hmo1 with components of the genome integrity network in cellular response to the genotoxin methyl methanesulfonate (MMS), implicating Hmo1 in the execution or regulation of homology-directed DNA repair, replication-coupled chromatin assembly, and the DNA damage checkpoint. Notably, our data pointed to a role for Hmo1 in directing SCJ to the nuclease-mediated resolution pathway instead of the helicase/topoisomerase mediated dissolution pathway for processing/removal. They also suggested that Hmo1 modulates both the recycling of parental histones and the deposition of newly synthesized histones on nascent DNA at the replication fork to ensure proper chromatin formation. We found evidence that Hmo1 counteracts the function of histone H2A variant H2A.Z (Htz1 in yeast) in DDT possibly due to their opposing effects on DNA resection. We showed that Hmo1 promotes DNA negative supercoiling as a proxy of chromatin structure and MMS-induced DNA damage checkpoint signaling, which is independent of the CTD of Hmo1. Moreover, we obtained evidence indicating that whether the CTD of Hmo1 contributes to its function in DDT is dependent on the host’s genetic background. Taken together, our findings demonstrated that Hmo1 can contribute to, or regulate, multiple processes of DDT via different mechanisms. Full article
(This article belongs to the Section Molecular Biology)
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26 pages, 3630 KB  
Article
Tailoring Spectral Response of Grating-Assisted Co-Directional Couplers with Weighting Techniques and Rational Transfer Functions: Theory and Experiment
by Anatole Lupu
Photonics 2025, 12(1), 73; https://doi.org/10.3390/photonics12010073 - 15 Jan 2025
Viewed by 1473
Abstract
This work addresses the tailoring spectral response of grating-assisted co-directional couplers (GADCs) in the context of wavelength filtering for fiber-to-the-home (FTTH) applications. Design methods for spectral response engineering by means of coupling profile apodization-type weighting techniques and also more advanced rational transfer functions [...] Read more.
This work addresses the tailoring spectral response of grating-assisted co-directional couplers (GADCs) in the context of wavelength filtering for fiber-to-the-home (FTTH) applications. Design methods for spectral response engineering by means of coupling profile apodization-type weighting techniques and also more advanced rational transfer functions fitting a predefined spectral window template are presented. Modeling results based on coupled mode theory are then applied for the design and experimental fabrication of InGaAsP/InP GADCs targeting 1.3+/1.3− µm diplexer application in FTTH access networks. The experimental results are found to be in good agreement with the modeling predictions. The design tools presented are quite general and can be easily adapted to other technology platforms, such as silicon photonics for the use of GADCs as add-drop wavelength division multiplexers. The field of parity–time symmetry is another avenue where these types of gain–loss-assisted GADCs as active components are of interest for switching applications, and the design methods presented here may find utility. Full article
(This article belongs to the Special Issue Silicon-Based Integrated Optics: From Design to Applications)
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11 pages, 3947 KB  
Article
BSA-Assisted Synthesis of Au Nanoclusters/MnO2 Nanosheets for Fluorescence “Switch-On” Detection of Alkaline Phosphatase
by Yijiong Xue, Chengqi Bao, Hui Liu, Fanghui Ma, Minghui Yang and Xiaoqing Li
Biosensors 2025, 15(1), 49; https://doi.org/10.3390/bios15010049 - 15 Jan 2025
Cited by 6 | Viewed by 2212
Abstract
A fluorescence probe for “switch-on” detection of alkaline phosphatase (ALP) was developed based on Au nanoclusters anchored MnO2 nanosheets (Au NCs-MnO2 NSs), which were synthesized using bovine serum albumin (BSA) as template through a simple one-pot approach. In the sensing system, [...] Read more.
A fluorescence probe for “switch-on” detection of alkaline phosphatase (ALP) was developed based on Au nanoclusters anchored MnO2 nanosheets (Au NCs-MnO2 NSs), which were synthesized using bovine serum albumin (BSA) as template through a simple one-pot approach. In the sensing system, MnO2 NSs function as both energy acceptors and target identifiers, effectively quenches the fluorescence of Au NCs via fluorescence resonance energy transfer (FRET). The presence of ALP catalyzes the hydrolysis of L-ascorbic acid-2-phosphate (AAP) to ascorbic acid (AA), reducing MnO2 NSs to Mn2+ and facilitate the fluorescence recovery of Au NCs. The fluorescence assay offers the advantages of facile preparation, cost-effectiveness, good specificity, and high sensitivity. Moreover, the assay exhibits a broad linear range (0.005 U/mL to 8 U/mL) for ALP detection with a remarkable limit of detection of 0.0015 U/mL. Notably, this assay demonstrates promising applicability for detection ALP in human serum samples, thereby providing valuable potential for clinical applications. Full article
(This article belongs to the Special Issue Feature Paper in Biosensor and Bioelectronic Devices 2024)
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16 pages, 12347 KB  
Article
Nanoscale Titanium Oxide Memristive Structures for Neuromorphic Applications: Atomic Force Anodization Techniques, Modeling, Chemical Composition, and Resistive Switching Properties
by Vadim I. Avilov, Roman V. Tominov, Zakhar E. Vakulov, Daniel J. Rodriguez, Nikita V. Polupanov and Vladimir A. Smirnov
Nanomaterials 2025, 15(1), 75; https://doi.org/10.3390/nano15010075 - 6 Jan 2025
Cited by 1 | Viewed by 1689
Abstract
This paper presents the results of a study on the formation of nanostructures of electrochemical titanium oxide for neuromorphic applications. Three anodization synthesis techniques were considered to allow the formation of structures with different sizes and productivity: nanodot, lateral, and imprint. The mathematical [...] Read more.
This paper presents the results of a study on the formation of nanostructures of electrochemical titanium oxide for neuromorphic applications. Three anodization synthesis techniques were considered to allow the formation of structures with different sizes and productivity: nanodot, lateral, and imprint. The mathematical model allowed us to calculate the processes of oxygen ion transfer to the reaction zone; the growth of the nanostructure due to the oxidation of the titanium film; and the formation of TiO, Ti2O3, and TiO2 oxides in the volume of the growing nanostructure and the redistribution of oxygen vacancies and conduction channel. Modeling of the nanodot structure synthesis process showed that at the initial stages of growth, a conductivity channel was formed, connecting the top and bottom of the nanostructure, which became thinner over time; at approximately 640 ms, this channel broke into upper and lower nuclei, after which the upper part disappeared. Modeling of the lateral nanostructure synthesis process showed that at the initial stages of growth, a conductivity channel was also formed, which quickly disappeared and left a nucleus that moved after the moving AFM tip. The simulation of the imprint nanostructure synthesis process showed the formation of two conductivity channels at a distance corresponding to the dimensions of the template tip. After about 460 ms, both channels broke, leaving behind embryos. The nanodot, lateral, and imprint nanostructure XPS spectra confirmed the theoretical calculations presented earlier: in the near-surface layers, the TiO2 oxide was observed, with the subsequent titanium oxide nanostructure surface etching proportion of TiO2 decreasing, and proportions of Ti2O3 and TiO oxides increasing. All nanodot, lateral, and imprint nanostructures showed reproducible resistive switching over 1000 switching cycles and holding their state for 10,000 s at read operation. Full article
(This article belongs to the Special Issue Neuromorphic Devices: Materials, Structures and Bionic Applications)
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13 pages, 765 KB  
Article
Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus Transcriptomes
by James J. Kelley and Andrey Grigoriev
Viruses 2025, 17(1), 36; https://doi.org/10.3390/v17010036 - 30 Dec 2024
Viewed by 1435
Abstract
The nucleocapsid (N) protein is the most expressed protein in later stages of SARS-CoV-2 infection with several important functions. It is translated from a subgenomic mRNA (sgmRNA) formed by template switching during transcription. A recently described translation initiation site (TIS) with a CTG [...] Read more.
The nucleocapsid (N) protein is the most expressed protein in later stages of SARS-CoV-2 infection with several important functions. It is translated from a subgenomic mRNA (sgmRNA) formed by template switching during transcription. A recently described translation initiation site (TIS) with a CTG codon in the leader sequence (TIS-L) is out of frame with most structural and accessory genes including the N gene and may act as a translation suppressor. We analyzed multiple sequenced samples infected by SARS-CoV-2 and found that any single variant of this virus produces multiple isoforms of the N sgmRNA. The main isoform starting at TIS-L is out of frame, but two secondary dominant isoforms (present in nearly all samples) were found to restore the reading frame and likely involved in the regulation of N protein production. Analysis of sequenced samples infected by other coronaviruses revealed that such isoforms are also produced in their transcriptomes. In SARS-CoV, they restore the reading frame for a putative TIS (also a CTG codon) in the same relative position as in SARS-CoV-2. Positions of junction breakpoints relative to stem loop 3 in the 5′-UTR suggest similar mechanisms in SARS-CoV, SARS-CoV-2, and OC43, but not in MERS-CoV. These observations may be pertinent for antisense-based antiviral strategies. Full article
(This article belongs to the Section Coronaviruses)
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12 pages, 1584 KB  
Article
Diverse Head-to-Tail Sequences in the Circular Genome of Human Bocavirus Genotype 1 among Children with Acute Respiratory Infections Implied the Switch of Template Chain in the Rolling-Circle Replication Model
by Kexiang Zhang, Ri De, Yanpeng Xu, Zhenzhi Han, Runan Zhu, Yu Sun, Liping Jia, Dongmei Chen, Yutong Zhou, Qi Guo, Yao Yao, Shuang Liu, Dong Qu, Yuan Qian and Linqing Zhao
Pathogens 2024, 13(9), 757; https://doi.org/10.3390/pathogens13090757 - 3 Sep 2024
Cited by 3 | Viewed by 1836
Abstract
Head-to-tail sequences have been reported in human bocavirus (HBoV) 1-4. To reveal their features and functions, HBoV DNA was screened among respiratory specimens from pediatric patients with an acute respiratory infection (ARI) between April 2020 and December 2022, followed by HBoV genotyping. Head-to-tail [...] Read more.
Head-to-tail sequences have been reported in human bocavirus (HBoV) 1-4. To reveal their features and functions, HBoV DNA was screened among respiratory specimens from pediatric patients with an acute respiratory infection (ARI) between April 2020 and December 2022, followed by HBoV genotyping. Head-to-tail sequences were detected using nested PCR, TA cloning, and Sanger sequencing, and these findings were confirmed by mNGS and amplicon sequencing. The secondary structure was predicted using the Mfold web server. The results indicated that head-to-tail sequences were detected in 42 specimens through TA cloning from 351 specimens positive for HBoV1 DNA, yielding 92 sequences into 32 types and 2 categories. Additionally, head-to-tail sequences were detected in 16 specimens by amplicon sequencing, yielding 60 sequences categorized into 23 types. The 374nt type, detected in 13 specimens, contains variants 374a and 374b, which differ in the unpaired loop regions of the palindrome or complementary reverse sequences, implying a switch of template chains during the replication process. The mNGS results in three specimens confirmed the presence of circular genome in copies below 1%. In conclusion, head-to-tail sequences of HBoV1 were common in children with ARI and were highly diverse in length and sequences. The variants may be generated by the switch of the template chain in the rolling-circle replication model. Full article
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13 pages, 535 KB  
Review
Strain-Specific Targeting and Destruction of Cells by Prions
by Sara M. Simmons and Jason C. Bartz
Biology 2024, 13(1), 57; https://doi.org/10.3390/biology13010057 - 20 Jan 2024
Cited by 3 | Viewed by 3448
Abstract
Prion diseases are caused by the disease-specific self-templating infectious conformation of the host-encoded prion protein, PrPSc. Prion strains are operationally defined as a heritable phenotype of disease under controlled conditions. One of the hallmark phenotypes of prion strain diversity is tropism [...] Read more.
Prion diseases are caused by the disease-specific self-templating infectious conformation of the host-encoded prion protein, PrPSc. Prion strains are operationally defined as a heritable phenotype of disease under controlled conditions. One of the hallmark phenotypes of prion strain diversity is tropism within and between tissues. A defining feature of prion strains is the regional distribution of PrPSc in the CNS. Additionally, in both natural and experimental prion disease, stark differences in the tropism of prions in secondary lymphoreticular system tissues occur. The mechanism underlying prion tropism is unknown; however, several possible hypotheses have been proposed. Clinical target areas are prion strain-specific populations of neurons within the CNS that are susceptible to neurodegeneration following the replication of prions past a toxic threshold. Alternatively, the switch from a replicative to toxic form of PrPSc may drive prion tropism. The normal form of the prion protein, PrPC, is required for prion formation. More recent evidence suggests that it can mediate prion and prion-like disease neurodegeneration. In vitro systems for prion formation have indicated that cellular cofactors contribute to prion formation. Since these cofactors can be strain specific, this has led to the hypothesis that the distribution of prion formation cofactors can influence prion tropism. Overall, there is evidence to support several mechanisms of prion strain tropism; however, a unified theory has yet to emerge. Full article
(This article belongs to the Special Issue Selective Vulnerability in Neurodegenerative Diseases)
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18 pages, 5341 KB  
Article
Substrate Specificity Diversity of Human Terminal Deoxynucleotidyltransferase May Be a Naturally Programmed Feature Facilitating Its Biological Function
by Aleksandra A. Kuznetsova, Svetlana I. Senchurova, Anastasia A. Gavrilova, Timofey E. Tyugashev, Elena S. Mikushina and Nikita A. Kuznetsov
Int. J. Mol. Sci. 2024, 25(2), 879; https://doi.org/10.3390/ijms25020879 - 10 Jan 2024
Cited by 6 | Viewed by 2741
Abstract
Terminal 2′-deoxynucleotidyl transferase (TdT) is a unique enzyme capable of catalysing template-independent elongation of DNA 3′ ends during V(D)J recombination. The mechanism controlling the enzyme’s substrate specificity, which is necessary for its biological function, remains unknown. Accordingly, in this work, kinetic and mutational [...] Read more.
Terminal 2′-deoxynucleotidyl transferase (TdT) is a unique enzyme capable of catalysing template-independent elongation of DNA 3′ ends during V(D)J recombination. The mechanism controlling the enzyme’s substrate specificity, which is necessary for its biological function, remains unknown. Accordingly, in this work, kinetic and mutational analyses of human TdT were performed and allowed to determine quantitative characteristics of individual stages of the enzyme–substrate interaction, which overall may ensure the enzyme’s operation either in the distributive or processive mode of primer extension. It was found that conformational dynamics of TdT play an important role in the formation of the catalytic complex. Meanwhile, the nature of the nitrogenous base significantly affected both the dNTP-binding and catalytic-reaction efficiency. The results indicated that neutralisation of the charge and an increase in the internal volume of the active site caused a substantial increase in the activity of the enzyme and induced a transition to the processive mode in the presence of Mg2+ ions. Surrogate metal ions Co2+ or Mn2+ also may regulate the switching of the enzymatic process to the processive mode. Thus, the totality of individual factors affecting the activity of TdT ensures effective execution of its biological function. Full article
(This article belongs to the Special Issue Molecular Mechanism of DNA Replication and Repair, 2nd Edition )
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