Correlation between tooth decay and insulin resistance in normal weight males prompts a role for myo-inositol as a regenerative factor in dentistry and oral surgery: a feasibility study.

Background: In an era of precision and stratified medicine, homogeneity in population-based cohorts, stringent causative entry, and pattern analysis of datasets are key elements to investigate medical treatments. Adhering to these principles, we collected in vivo and in vitro data pointing to an insulin-sensitizing/insulin-mimetic effect of myo-inositol (MYO) relevant to cell regeneration in dentistry and oral surgery. Confirmation of this possibility was obtained by in silico analysis of the relation between in vivo and in vitro results (the so-called bed-to-benchside reverse translational approach). Results: Fourteen subjects over the 266 screened were young adult, normal weight, euglycemic, sedentary males having normal appetite, free diet, with a regular three-times-a-day eating schedule, standard dental hygiene, and negligible malocclusion/enamel defects. Occlusal caries were detected by fluorescence videoscanning, whereas body composition and energy balance were estimated with plicometry, predictive equations, and handgrip. Statistically significant correlations (Pearson r coefficient) were found between the number of occlusal caries and anthropometric indexes predicting insulin resistance (IR) in relation to the abdominal/visceral fat mass, fat-free mass, muscular strength, and energy expenditure adjusted to the fat and muscle stores. This indicated a role for IR in affecting dentin reparative processes. Consistently, in vitro administration of MYO to HUVEC and Swiss NIH3T3 cells in concentrations corresponding to those administered in vivo to reduce IR resulted in statistically significant cell replication (ANOVA/Turkey tests), suggesting that MYO has the potential to counteract inhibitory effects of IR on dental vascular and stromal cells turnover. Finally, in in silico experiments, quantitative evaluation (WOE and information value) of a bioinformatic Clinical Outcome Pathway confirmed that in vitro trophic effects of MYO could be transferred in vivo with high predictability, providing robust credence of its efficacy for oral health. Conclusion: Our reverse bed-to-benchside data indicate that MYO might antagonize the detrimental effects of IR on tooth decay. This provides feasibility for clinical studies on MYO as a regenerative factor in dentistry and oral surgery, including dysmetabolic/aging conditions, bone reconstruction in oral destructive/necrotic disorders, dental implants, and for empowering the efficacy of a number of tissue engineering methodologies in dentistry and oral surgery.

Comparative analyses suggest a link between mRNA splicing, stability, and RNA covalent modifications in flowering plants.

BACKGROUND: In recent years, covalent modifications on RNA nucleotides have emerged as pivotal moieties influencing the structure, function, and regulatory processes of RNA Polymerase II transcripts such as mRNAs and lncRNAs. However, our understanding of their biological roles and whether these roles are conserved across eukaryotes remains limited. RESULTS: In this study, we leveraged standard polyadenylation-enriched RNA-sequencing data to identify and characterize RNA modifications that introduce base-pairing errors into cDNA reads. Our investigation incorporated data from three Poaceae (Zea mays, Sorghum bicolor, and Setaria italica), as well as publicly available data from a range of stress and genetic contexts in Sorghum and Arabidopsis thaliana. We uncovered a strong enrichment of RNA covalent modifications (RCMs) deposited on a conserved core set of nuclear mRNAs involved in photosynthesis and translation across these species. However, the cohort of modified transcripts changed based on environmental context and developmental program, a pattern that was also conserved across flowering plants. We determined that RCMs can partly explain accession-level differences in drought tolerance in Sorghum, with stress-associated genes receiving a higher level of RCMs in a drought tolerant accession. To address function, we determined that RCMs are significantly enriched near exon junctions within coding regions, suggesting an association with splicing. Intriguingly, we found that these base-pair disrupting RCMs are associated with stable mRNAs, are highly correlated with protein abundance, and thus likely associated with facilitating translation. CONCLUSIONS: Our data point to a conserved role for RCMs in mRNA stability and translation across the flowering plant lineage.

Unveiling the kinetic versatility of aryl-alcohol oxidases with different electron acceptors.

Introduction: Aryl-alcohol oxidase (AAO) shows a pronounced duality as oxidase and dehydrogenase similar to that described for other glucose-methanol-choline (GMC) oxidase/dehydrogenase superfamily proteins involved in lignocellulose decomposition. In this work, we detail the overall mechanism of AAOs from Pleurotus eryngii and Bjerkandera adusta for catalyzing the oxidation of natural aryl-alcohol substrates using either oxygen or quinones as electron acceptors and describe the crystallographic structure of AAO from B. adusta in complex with a product analogue. Methods: Kinetic studies with 4-methoxybenzyl and 3-chloro-4- methoxybenzyl alcohols, including both transient-state and steady-state analyses, along with interaction studies, provide insight into the oxidase and dehydrogenase mechanisms of these enzymes. Moreover, the resolution of the crystal structure of AAO from B. adusta allowed us to compare their overall folding and the structure of the active sites of both AAOs in relation to their activities. Results and Discussion: Although both enzymes show similar mechanistic properties, notable differences are highlighted in this study. In B. adusta, the AAO oxidase activity is limited by the reoxidation of the flavin, while in P. eryngii the slower step takes place during the reductive half-reaction, which determines the overall reaction rate. By contrast, dehydrogenase activity in both enzymes, irrespective of the alcohol participating in the reaction, is limited by the hydroquinone release from the active site. Despite these differences, both AAOs are more efficient as dehydrogenases, supporting the physiological role of this activity in lignocellulosic decay. This dual activity would allow these enzymes to adapt to different environments based on the available electron acceptors.

Isomeric Effects of Au28(S-c-C6H11)20 Nanoclusters on Photoluminescence: Roles of Electron-Vibration Coupling and Higher Triplet State.

The exploration of near-infrared photoluminescence (PL) from atomically precise nanoclusters is currently a prominent area of interest owing to its importance in both fundamental research and diverse applications. In this work, we investigate the near-infrared (NIR) photoluminescence mechanisms of two structural isomers of atomically precise gold nanoclusters of 28 atoms protected by cyclohexanethiolate (CHT) ligands, i.e., Au28i(CHT)20 and Au28ii(CHT)20. Based on their structures, analysis of 3O2 (triplet oxygen) quenching of the nanocluster triplet states, temperature-dependent photophysical studies, and theoretical calculations, we have elucidated the intricate processes governing the photoluminescence of these isomeric nanoclusters. For Au28i(CHT)20, its emission characteristics are identified as phosphorescence plus thermally activated delayed fluorescence (TADF) with a PL quantum yield (PLQY) of 0.3% in dichloromethane under ambient conditions. In contrast, the Au28ii(CHT)20 isomer exhibits exclusive phosphorescence with a PLQY of 3.7% in dichloromethane under ambient conditions. Theoretical simulations reveal a larger singlet (S1)-triplet (T1) gap in Au28ii than that in Au28i, and the higher T2 state plays a critical role in both isomers' photophysical processes. The insights derived from this investigation not only contribute to a more profound comprehension of the fundamental principles underlying the photoluminescence of atomically precise gold nanoclusters but also provide avenues for tailoring their optical properties for diverse applications.

Splice-switching antisense oligonucleotides for pediatric neurological disorders.

Pediatric neurological disorders are frequently devastating and present unmet needs for effective medicine. The successful treatment of spinal muscular atrophy with splice-switching antisense oligonucleotides (SSO) indicates a feasible path to targeting neurological disorders by redirecting pre-mRNA splicing. One direct outcome is the development of SSOs to treat haploinsufficient disorders by targeting naturally occurring non-productive splice isoforms. The development of personalized SSO treatment further inspired the therapeutic exploration of rare diseases. This review will discuss the recent advances that utilize SSOs to treat pediatric neurological disorders.

Integration of simulated annealing into pigeon inspired optimizer algorithm for feature selection in network intrusion detection systems.

In the context of the 5G network, the proliferation of access devices results in heightened network traffic and shifts in traffic patterns, and network intrusion detection faces greater challenges. A feature selection algorithm is proposed for network intrusion detection systems that uses an improved binary pigeon-inspired optimizer (SABPIO) algorithm to tackle the challenges posed by the high dimensionality and complexity of network traffic, resulting in complex models, reduced accuracy, and longer detection times. First, the raw dataset is pre-processed by uniquely one-hot encoded and standardized. Next, feature selection is performed using SABPIO, which employs simulated annealing and the population decay factor to identify the most relevant subset of features for subsequent review and evaluation. Finally, the selected subset of features is fed into decision trees and random forest classifiers to evaluate the effectiveness of SABPIO. The proposed algorithm has been validated through experimentation on three publicly available datasets: UNSW-NB15, NLS-KDD, and CIC-IDS-2017. The experimental findings demonstrate that SABPIO identifies the most indicative subset of features through rational computation. This method significantly abbreviates the system's training duration, enhances detection rates, and compared to the use of all features, minimally reduces the training and testing times by factors of 3.2 and 0.3, respectively. Furthermore, it enhances the F1-score of the feature subset selected by CPIO and Boost algorithms when compared to CPIO and XGBoost, resulting in improvements ranging from 1.21% to 2.19%, and 1.79% to 4.52%.

The influence of vertebrate scavengers on leakage of nutrients from carcasses.

The decomposition of carcasses by scavengers and microbial decomposers is an important component of the biochemical cycle that can strongly alter the chemical composition of soils locally. Different scavenger guilds are assumed to have a different influence on the chemical elements that leak into the soil, although this assumption has not been empirically tested. Here, we experimentally determine how different guilds of vertebrate scavengers influence local nutrient dynamics. We performed a field experiment in which we systematically excluded different subsets of vertebrate scavengers from decomposing carcasses of fallow deer (Dama dama), and compared elemental concentrations in the soil beneath and in the vegetation next to the carcasses over time throughout the decomposition process. We used four exclusion treatments: excluding (1) no scavengers, thus allowing them all; (2) wild boar (Sus scrofa); (3) all mammals; and (4) all mammals and birds. We found that fluxes of several elements into the soil showed distinct peaks when all vertebrates were excluded. Especially, trace elements (Cu and Zn) seemed to be influenced by carcass decomposition. However, we found no differences in fluxes between partial exclusion treatments. Thus, vertebrate scavengers indeed reduce leakage of elements from carcasses into the soil, hence influencing local biochemical cycles, but did so independent of which vertebrate scavenger guild had access. Our results suggest that carcass-derived elements are dispersed over larger areas rather than locally leak into the soil when vertebrate scavengers dominate the decomposition process.

Dual-element substitution induced integrated defect structure to suppress voltage decay and capacity fading of Li-rich Mn-based cathode.

Li-rich manganese-based oxide (LRMO) is considered one of the most promising cathode materials for next-generation lithium-ion batteries due to its high energy density. However, many issues need to be addressed before its large-scale commercialization, including significant voltage decay and capacity fading. Herein, a Sn4+/Na+ co-doping induced integrated defect structure (oxygen vacancies, stacking faults, and surface spinel phase) strategy is proposed to suppress the voltage decay and enhance the cycling performance of LRMO. The integrated surface defect structures have significantly favorable effects on the LRMO, where the oxygen vacancies remove surface labile oxygen and suppress surface oxygen release, the induced stacking faults alleviate the stress accumulation during cycling, the surface spinel phase promotes the Li+ diffusion and prevents the outward migration of cations, and the co-doped Sn4+/Na+ stabilize the layered structure. As a result, the modified sample Na2SnO3-1 % (NSO-1) achieves excellent cycling performance (capacity of 207 mAh/g and capacity retention of 96.71 % after 100 cycles at 0.5C) and a smaller voltage decay (less than 1.5 mV per cycle) compared with the unmodified LRMO. This work provides a new valuable strategy to suppress capacity fading and voltage decay of LRMO through dual-element substitution induced surface defect engineering.

m6A modification plays an integral role in mRNA stability and translation during pattern-triggered immunity.

Plants employ distinct mechanisms to respond to environmental changes. Modification of mRNA by N 6-methyladenosine (m6A), known to affect the fate of mRNA, may be one such mechanism to reprogram mRNA processing and translatability upon stress. However, it is difficult to distinguish a direct role from a pleiotropic effect for this modification due to its prevalence in RNA. Through characterization of the transient knockdown-mutants of m6A writer components and mutants of specific m6A readers, we demonstrate the essential role that m6A plays in basal resistance and pattern-triggered immunity (PTI). A global m6A profiling of mock and PTI-induced Arabidopsis plants as well as formaldehyde fixation and cross-linking immunoprecipitation-sequencing of the m6A reader, EVOLUTIONARILY CONSERVED C-TERMINAL REGION2 (ECT2) showed that while dynamic changes in m6A modification and binding by ECT2 were detected upon PTI induction, most of the m6A sites and their association with ECT2 remained static. Interestingly, RNA degradation assay identified a dual role of m6A in stabilizing the overall transcriptome while facilitating rapid turnover of immune-induced mRNAs during PTI. Moreover, polysome profiling showed that m6A enhances immune-associated translation by binding to the ECT2/3/4 readers. We propose that m6A plays a positive role in plant immunity by destabilizing defense mRNAs while enhancing their translation efficiency to create a transient surge in the production of defense proteins.

Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro.

Reports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of adequate immune responses have been excluded. We now present virologic findings that provide a clue to the cause of viral rebound, which occurs in ∼20% of the treated cases. Persistence of infectious SARS-CoV-2 was experimentally documented in vitro after treatment with nirmatrelvir or another 3CL protease inhibitor, but not with a polymerase inhibitor, remdesivir. This infectious form decayed slowly with a half-life of ∼1 day, suggesting that its persistence could outlive the treatment course to re-ignite SARS-CoV-2 infection as the drug is eliminated. Notably, extending nirmatrelvir treatment beyond 8 days abolished viral rebound in vitro. Our findings point in a particular direction for future investigation of virus persistence and offer a specific treatment recommendation that should be tested clinically.

End Cap Effect on Solution-Processable Deep Blue Lasing Materials with Low-Amplified Spontaneous Emission Thresholds.

Organic lasers have attracted increasing attention owing to their superior characteristics such as lightweight, low-cost manufacturing, high mechanical flexibility, and high emission-wavelength tunability. Recent breakthroughs include electrically pumped organic laser diodes and an electrically driven organic laser, integrated with an organic light-emitting diode pumping. However, the availability of efficient deep blue organic laser chromophores remains limited. In this study, we develop two novel rigid oligophenylenes, end-capped with carbazole and phenylcarbazole groups, to demonstrate exceptional optical and amplified spontaneous emission (ASE) properties. These oligophenylenes are not only solution processable but also exhibit remarkably high solution photoluminescence quantum yields (PLQYs) of 90% and high radiative rates of 1.35 × 109 s-1 in the deep blue range. Our theoretical calculations confirm that the carbazole and phenylcarbazole end groups play a pivotal role in enhancing the optical transitions of the oligophenylene laser chromophores, thereby elevating their emission oscillator strengths. Remarkably, these materials demonstrate low solid-state ASE threshold values of 1.0 and 1.5 µJ/cm2 (at 431 and 418 nm, respectively). To the best of our knowledge, these ASE thresholds represent the lowest reported at these specific ASE wavelengths in the literature, regardless of whether they are solution-processed or thermally evaporated films. Furthermore, they exhibit excellent thermal and photostability, low triplet quantum yields, as well as negligible overlap of excited-state absorption within the ASE emission region, making them excellent candidates for a new class of deep blue materials for organic lasers. By integrating insights from theoretical calculations and experimental validation, our study provides a comprehensive understanding of the design principles behind these high-performing organic laser chromophores, paving the way for the development of advanced organic lasers with enhanced performance characteristics.

Recessive loss-of-function variants in DPH1 identified as the molecular cause in a sibling pair previously diagnosed with Fine-Lubinsky syndrome.

Fine-Lubinsky syndrome is a rare clinically defined syndrome sometimes referred to as brachycephaly, deafness, cataract, microstomia, and impaired intellectual development syndrome. Here we provide a clinical and molecular update for a sibling pair diagnosed with Fine-Lubinsky syndrome. An extensive genetic work-up, including chromosomal microarray analysis and quad exome sequencing, was nondiagnostic. However, a research reanalysis of their exome sequencing data revealed that both were homozygous for an intronic c.749+39G>A [NM_001383.6] variant in DPH1. RNAseq analysis performed on RNA from fibroblasts revealed significantly reduced expression of DPH1 transcripts suggestive of abnormal splicing followed by nonsense mediated mRNA decay. Since the phenotypes of this sibling pair were consistent with those associated with the inheritance of biallelic pathogenic variants in DPH1, they were given a diagnosis of developmental delay with short stature, dysmorphic facial features, and sparse hair 1 (DEDSSH1). This leads us to recommend that all individuals with a clinical diagnosis of Fine-Lubinsky syndrome be screened for variants in DPH1. The clinical histories of this sibling pair emphasize that hearing loss associated with DEDSSH1 may remit over time and that individuals with DEDSSH1 should be monitored for the development of cardiomyopathy. This case also demonstrates the clinical utility of RNAseq as a means of functionally validating the effects of intronic variants that may affect splicing.

Quantum dot-protein interface: Interaction of the CdS quantum dot with human hemoglobin for the study of the energy transfer process and binding mechanism along with detection of the unfolding of hemoglobin.

In this study, the interaction of the human hemoglobin with cost effective and chemically fabricated CdS quantum dots (QDs) (average sizes ≈3nm) has been investigated. The semiconductor QDs showed maximum visible absorption at 445 nm with excitonic formation and band gap of ≈ 2.88 eV along with hexagonal crystalline phase. The binding of QDs-Hb occurs through corona formation to the ground sate complex formation. The life time of the heme pocket binding and reorganization were found to be t1 = 43 min and t2 = 642 min, respectively. The emission quenching of the Hb has been indicated large energy transfer between CdS QDs and Hb with tertiary deformation of Hb. The binding thermodynamics showed highly exothermic nature. The ultrafast decay during corona formation was studied from TCSPC. The results showed that the energy transfer efficiency increases with the increase of the QDs concentration and maximum ≈71.5 % energy transfer occurs and average ultrafast lifetime varies from 5.45 ns to1.51 ns. The deformation and unfolding of the secondary structure of Hb with changes of the α-helix (≈74 % to ≈51.07 %) and ß-sheets (≈8.63 % to ≈10.25 %) have been observed from circular dichroism spectrum. The SAXS spectrum showed that the radius of gyration of CdS QDs-Hb bioconjugate increased (up to 23 ± 0.45 nm) with the increase of the concentration of QDs compare with pure Hb (11 ± 0.23 nm) and Hb becoming more unfolded.

Implications of long-term sample storage on the recovery of viruses from wastewater and biobanking.

Wastewater-based monitoring has been widely implemented worldwide for the tracking of SARS-CoV-2 outbreaks and other viral diseases. In many surveillance programmes, unprocessed and processed wastewater samples are often frozen and stored for long periods of time in case the identification and tracing of an emerging health threat becomes necessary. However, extensive sample bioarchives may be difficult to maintain due to limitations in ultra-freezer capacity and associated cost. Furthermore, the stability of viruses in such samples has not been systematically investigated and hence the usefulness of bioarchives is unknown. In this study, we assessed the stability of SARS-CoV-2, influenza viruses, noroviruses and the faecal indicator virus, crAssphage, in raw wastewater and purified nucleic aacid extracts stored at -80 °C for 6-24 months. We found that the isolated viral RNA and DNA showed little signs of degradation in storage over 8-24 months, whereas extensive decay viral and loss of qPCR signal was observed during the storage of raw unprocessed wastewater. The most stable viruses were noroviruses and crAssphage, followed by SARS-CoV-2 and influenza A virus. Based on our findings, we conclude that bioarchives comprised of nucleic acid extracts derived from concentrated wastewater samples may be archived long-term, for at least two years, whereas raw wastewater samples may be discarded after one year.

Eco-safe hot water dip alleviates antioxidant level and sensory quality of Indian jujube fruits.

Indian jujube (Ber) is highly perishable climacteric fruit owing to high decay index limiting its marketability and demands interventions to prolong shelf life. Fungicides are normally used to control rot during postharvest storage, however, residues left necessitate eco-safe alternatives like hot water dipping. Mature, pre-climacteric jujubes were dipped in 45, 50 or 55 °C water for 8, 6 or 4 min, respectively and then stored at 5 °C for periodic quality evaluation. Dipping fruits in 55 °C water resulted in 32.69 and 35.27, 64.21 and 58.57, 30.41 and 30.42, 38.50 and 52.20 % lower weight loss, decay index, malondialdehyde (MDA) and electrolyte leakage, whereas 15.40 and 16.77, 19.51 and 20.48 % greater antioxidant activity and ascorbic acid respectively for Umran and Pakwhite compared to 25 °C water dip. The highest glucose, fructose, malic, citric, and tartaric acids were 23.44 ± 1.04 and 29.9 ± 0.95, 30.68 ± 1.72 and 41.17 ± 2.34 mg/100 g, 138.1 ± 6.45 and 112.97 ± 6.16, 57.49 ± 1.71 and 53.78 ± 1.90, 79.58 ± 5.1 and 65.3 ± 4.83 µg/100 g whereas lower sucrose 12.34 ± 0.94 and 16.33 ± 1.05 mg/100 g were respectively recorded in 55 °C water dipped Umran and Pakwhite fruits. High dip water temperature (55 °C) exhibited better quality with the lowest decay index and weight loss, greater membrane integrity, bioactives content and sensory acceptance scores. Hence, hot water dipping was shown to be an effective residue-free option to extend the marketable period of jujubes to capture distant markets.

The effect of SiO2 crystallization in enhancing the luminescence of Dy3+-Sm3+ co-doped glass ceramics for cool white light application.

The present work investigates the structural and luminescence behaviour of Dy3+-Sm3+ co-doped glass ceramics obtained through heat treatment of precursor glasses. The growth of SiO2 polycrystalline particles and evolution of these crystallites in the glass domain are witnessed via XRD and FESEM study. The presence of network vibrational bands, hydroxyl groups and the increased quantity of bridging oxygens (BOs) in glass ceramics are analysed through FTIR spectroscopy study. The absorption study (UV-Visible-NIR) showed the possible electronic transitions of Dy3+ and Sm3+ ions. The red shift in the absorption band edges and the lower bandgap values are obtained as a result of improved heat treatment in glass ceramics. Emission studies show the enhanced luminescence intensity of glass ceramics under 350 and 402 nm excitations. Decay measurement of glass ceramics showed the improved lifetimes of Dy3+ and Sm3+ ions to have appeared in microseconds (×10-6 s). The colour characteristics of glass ceramics analysed using CIE colour chromaticity diagram and correlated colour temperature (CCT) values suggest the neutral to cool white light emissions. Therefore, prepared glass ceramics with SiO2 polycrystalline phase are considered to be suitable materials in cool white LEDs applications.

The Engineered Drug 3'UTRMYC1-18 Degrades the c-MYC-STAT5A/B-PD-L1 Complex In Vivo to Inhibit Metastatic Triple-Negative Breast Cancer.

c-MYC is overexpressed in 70% of human cancers, including triple-negative breast cancer (TNBC), yet there is no clinically approved drug that directly targets it. Here, we engineered the mRNA-stabilizing poly U sequences within the 3'UTR of c-MYC to specifically destabilize and promote the degradation of c-MYC transcripts. Interestingly, the engineered derivative outcompetes the endogenous overexpressed c-MYC mRNA, leading to reduced c-MYC mRNA and protein levels. The iron oxide nanocages (IO-nanocages) complexed with MYC-destabilizing constructs inhibited primary and metastatic tumors in mice bearing TNBC and significantly prolonged survival by degrading the c-MYC-STAT5A/B-PD-L1 complexes that drive c-MYC-positive TNBC. Taken together, we have described a novel therapy for c-MYC-driven TNBC and uncovered c-MYC-STAT5A/B-PD-L1 interaction as the target.

Stress Wave Propagation and Decay Based on Micro-Scale Modelling in the Topology of Polymer Composite with Circular Particles.

This article deals with stress wave decay performance, analysing the stress wave propagation generated by an impulsive unit load in a 2D representative unit cell (RUC) of a polymer composite with circular particles representing spherical particles, elliptical particles, and short fibres. The micro-scale numerical simulation uses explicit finite element analysis (FEA). The micro-response to an impulsive unit load creates a stress wave amplitude interacting with the material structure and tends to weaken and absorb energy. The stress wave damping is determined by the decaying amplitudes of Mises stress at the front of the stress wave. The stress wave damping is evaluated for different ratios of tensile modules and material densities of matrix and reinforcing material and other factors, such as percentage and particle size, applied to nine topologies of RUCs, and even the presence of an interfacial region is analysed. Moreover, the article visualises the phases of stress wave decay in various particle distributions, i.e., various topologies. Analysing the different topologies of the same particle volume (area) percentage, the study proved that the composite topology and resulting wave-particle and wave-wave interactions are other sources of material damping. The presence of even a small percentage, 3.5 area%, of reinforcing circular particles in the matrix brings a significant increase in stress wave damping up to about 40-43% (depending on the topology) compared to a homogeneous matrix with stress wave damping of 12.5% under the same conditions. Moreover, the topology with the same volume (area) percentage can increase particle stress wave damping by 15.3%.

NMDtxDB: Data-driven identification and annotation of human NMD target transcripts.

The nonsense-mediated RNA decay (NMD) pathway is a crucial mechanism of mRNA quality control. Current annotations of NMD substrate RNAs are rarely data-driven, but use general established rules. We present a dataset with 4 cell lines and combinations for SMG5, SMG6 and SMG7 knockdowns or SMG7 knockout. Based on this dataset, we implemented a workflow that combines Nanopore and Illumina sequencing to assemble a transcriptome, which is enriched for NMD target transcripts. Moreover, we use coding sequence information from Ensembl, Gencode consensus RiboSeq ORFs and OpenProt to enhance the CDS annotation of novel transcript isoforms. In summary, 302,889 transcripts were obtained from the transcriptome assembly process, out of which, 24% are absent from Ensembl database annotations, 48,213 contain a premature stop codon and 6,433 are significantly upregulated in three or more comparisons of NMD active vs deficient cell lines. We present an in-depth view on these results through the NMDtxDB database, which is available at https://shiny.dieterichlab.org/app/NMDtxDB, and supports the study of NMD-sensitive transcripts. We open sourced our implementation of the respective web-application and analysis workflow at https://github.com/dieterich-lab/NMDtxDB and https://github.com/dieterich-lab/nmd-wf.

Bulk-flow composites in paediatric dentistry: long term survival of posterior restorations. A retrospective study.

Dental decay is a prevalent bacterial disease affecting a significant percentage of children globally. In paediatric dentistry, various materials are available for restoring deciduous teeth, addressing both functional and aesthetic concerns. However, paediatric dentists encounter challenges related to patient compliance, limited working time, and material handling. This study aims to observe the survival rate of bulk-fill composite restorations in paediatric patients over a five-year follow-up. A total of 198 patients aged 0 to 12 years underwent 673 class II restorations on deciduous first molars (1M) and second molars (2M). All restorations were conducted performed by 1 Pediatric DDS resident students from the Paediatric Dentistry Department (Padova University), utilizing using different isolation techniques. Bulk-fill composite restorations were evaluated over a five-year follow-up, and data were collected by a single investigator. After five years, 177 patients and 611 restorations were assessed. The retention rate was higher in primary second molars than in first molars, with fewer marginal dyschromies and less formation of secondary caries. The overall failure rate was higher in primary first molars and primary lower second molars. Bulk-fill composites demonstrated significantly positive performance in terms of retention, maintenance, and marginal dyschromies. Bulk-fill composites are promising materials of choice in paediatric dentistry due to their easy handling and favorable properties. Further research is necessary to compare high and low viscosity bulk-fill composites and assess the impact of different variables on restoration success.