MicroRNA-22-3p displaces critical host factors from the 5' UTR and inhibits the translation of Coxsackievirus B3 RNA.

Coxsackievirus B3 (CVB3) is known to cause acute myocarditis and pancreatitis in humans. We investigated the microRNAs (miRNAs) that can potentially govern the viral life cycle by binding to the untranslated regions (UTRs) of CVB3 RNA. MicroRNA-22-3p was short-listed, as its potential binding site overlapped with the region crucial for recruiting internal ribosome entry site trans-acting factors (ITAFs) and ribosomes. We demonstrate that miR-22-3p binds CVB3 5' UTR, hinders recruitment of key ITAFs on viral mRNA, disrupts the spatial structure required for ribosome recruitment, and ultimately blocks translation. Likewise, cells lacking miR-22-3p exhibited heightened CVB3 infection compared to wild type, confirming its role in controlling infection. Interestingly, miR-22-3p level was found to be increased at 4 hours post-infection, potentially due to the accumulation of viral 2A protease in the early phase of infection. 2Apro enhances the miR-22-3p level to dislodge the ITAFs from the SD-like sequence, rendering the viral RNA accessible for binding of replication factors to switch to replication. Furthermore, one of the cellular targets of miR-22-3p, protocadherin-1 (PCDH1), was significantly downregulated during CVB3 infection. Partial silencing of PCDH1 reduced viral replication, demonstrating its proviral role. Interestingly, upon CVB3 infection in mice, miR-22-3p level was found to be downregulated only in the small intestine, the primary target organ, indicating its possible role in influencing tissue tropism. It appears miR-22-3p plays a dual role during infection by binding viral RNA to aid its life cycle as a viral strategy and by targeting a proviral protein to restrict viral replication as a host response.IMPORTANCECVB3 infection is associated with the development of end-stage heart diseases. Lack of effective anti-viral treatments and vaccines for CVB3 necessitates comprehensive understanding of the molecular players during CVB3 infection. miRNAs have emerged as promising targets for anti-viral strategies. Here, we demonstrate that miR-22-3p binds to 5' UTR and inhibits viral RNA translation at the later stage of infection to promote viral RNA replication. Conversely, as host response, it targets PCDH1, a proviral factor, to discourage viral propagation. miR-22-3p also influences CVB3 tissue tropism. Deciphering the multifaced role of miR-22-3p during CVB3 infection unravels the necessary molecular insights, which can be exploited for novel intervening strategies to curb infection and restrict viral pathogenesis.

Structural, material and antibacterial properties of quercetin incorporated soy protein isolate films and its binding behavior through molecular docking.

This study aimed to investigate the three different methods for the fabrication of quercetin (1%-3% w/w of protein) incorporated soy protein isolate (SPI) films and their effect on material properties. The quercetin incorporated SPI films prepared by these methods were characterized by Fourier transform infrared (FTIR) spectroscopy, UV-Vis spectrophotometer, tensile properties, and water uptake and leaching properties. The cross-linking pattern was revealed by the FTIR spectrum that showed formation of an ester group because of interaction between the quercetin hydroxyl group and the carboxyl side chain of SPI amino acids. The tensile strength of SPI films were enhanced with the addition of quercetin as it increased to a maximum of 6.17 MPa while neat SPI film had tensile strength 4.13 MPa. The prepared films exhibit significant antibacterial activity against Listeria monocytogenes and Escherichia coli. The In-silico docking analysis demonstrates that covalent and non-covalent forces play crucial roles in binding interaction. It shows the formation of four hydrogen bonds, two salt bridges along with one pi-alkyl interaction. The simulation studies reflect the crucial amino acid residues involved in SPI-quercetin binding. The effect of quercetin binding with SPI on its stability and compactness is revealed by Root mean square deviation (RMSD) and radius of gyration studies.

FDA approved fezolinetant (Veozah): a critical evaluation of its efficacy and safety for menopausal vasomotor symptoms, calling for prospective research.

Women going through menopause frequently experience vasomotor symptoms such as hot flashes, night sweats, and sleep disturbances, significantly influencing their quality of life. Hormonal therapy has been demonstrated to be beneficial in treating VMS. However, due to specific restrictions, it is not recommended for every woman. Fezolinetant, a neurokinin 3 antagonist and non-hormonal treatment for severe to moderate VMS, functions by inhibiting neuronal impulses originating from the hypothalamic thermoregulatory center. Current Skylight 2 and 4 trials statistically demonstrate the safety and acceptability of fezolinetant, with relatively few adverse effects reported. Fezolinetant has been shown great potential for treating menopausal-related VMS, supporting its further advancement. However, further investigation is required to thoroughly evaluate its safety, effectiveness, and its impact on sleep patterns.

Cellular Protein HuR Regulates the Switching of Genomic RNA Templates for Differential Functions during the Coxsackievirus B3 Life Cycle.

Coxsackievirus B3 (CVB3) is an enterovirus belonging to the family Picornaviridae. Its 5' untranslated region (UTR) contains a cloverleaf structure followed by an internal ribosome entry site (IRES). The cloverleaf forms an RNA-protein complex known to regulate virus replication, translation, and stability of the genome, and the IRES regulates virus RNA translation. For positive-strand RNA-containing viruses, such as members of the flaviviruses or enteroviruses, the genomic RNA is used for translation, replication, and encapsidation. Only a few regulatory mechanisms which govern the accessibility of genomic RNA templates for translation or replication have been reported. Here, we report the role of human antigen R (HuR) in regulating the fate of CVB3 positive-strand RNA into the replication cycle or translation cycle. We have observed that synthesis of HuR is induced during CVB3 infection, and it suppresses viral replication by displacing PCBP-2 (a positive regulator of virus replication) at the cloverleaf RNA. Silencing of HuR increases viral RNA replication and consequently reduces viral RNA translation in a replication-dependent manner. Furthermore, we have shown that HuR level is upregulated upon CVB3 infection. Moreover, HuR limits virus replication and can coordinate the availability of genomic RNA templates for translation, replication, or encapsidation. Our study highlights the fact that the relative abundance of translation factors and replication factors in the cell decides the outcome of viral infection. IMPORTANCE A positive-strand RNA virus must balance the availability of its genomic template for different viral processes at different stages of its life cycle. A few host proteins are shown to be important to help the virus in switching the usage of a template between these processes. These proteins inhibit translation either by displacing a stimulator of translation or by binding to an alternative site. Both mechanisms lead to ribosome clearance and availability of the genomic strand for replication. We have shown that HuR also helps in maintaining this balance by inhibiting replication and subsequently promoting translation and packaging.

Tuning the properties of graphene quantum dots by passivation.

The electronic and optical properties of graphene quantum dots (GQDs) of size less than 10 nm are different from those of graphene sheets due to quantum confinement effects. For analyzing their use in optoelectronic applications, it is very crucial to optimally tune the bandgap and engineer the controlling parameters. In the present work, a systematic investigation of the band gap of hexagonal GQDs has been carried out by examining their HOMO and LUMO energies. Passivation of dangling bonds of these GQDs has been carried out with the help of electron-withdrawing substituents in order to tune the band gap and engineer their optical properties such as absorption and emission spectra by carrying out the simulation with Density Functional Theory formalism using Gaussian 09 software. Carrying out passivation with electronegative element fluorine (F) effectively decreases the band gap of these QDs resulting in a redshift in the absorption spectra. The HOMO and LUMO topographical surfaces have been used to understand the absorption spectra. These surfaces show some σ-bond characteristics along with π-bond properties on passivating GQDs with the F-atom which further results in alteration of their energies and a corresponding decrease in their band gap. Here, the absorption is found to be dependent on the size of GQDs and the type of passivating atoms (H or F). The results thus obtained are found to be in good consonance with those reported in the literature engaging different methods. The present analysis may prove to be useful in improving the working of solar cells and other optoelectronic devices.

The mammalian host protein DAP5 facilitates the initial round of translation of Coxsackievirus B3 RNA.

During enteroviral infections, the canonical translation factor eukaryotic translation initiation factor 4 γ I (eIF4GI) is cleaved by viral protease 2A. The resulting C-terminal fragment is recruited by the viral internal ribosome entry site (IRES) for efficient translation of the viral RNA. However, the 2A protease is not present in the viral capsid and is synthesized only after the initial round of translation. This presents the conundrum of how the initial round of translation occurs in the absence of the C-terminal eIF4GI fragment. Interestingly, the host protein DAP5 (also known as p97, eIF4GIII, and eIF4G2), an isoform of eIF4GI, closely resembles the eIF4GI C-terminal fragment produced after 2A protease-mediated cleavage. Using the Coxsackievirus B3 (CVB3) IRES as a model system, here we demonstrate that DAP5, but not the full-length eIF4GI, is required for CVB3 IRES activity for translation of input viral RNA. Additionally, we show that DAP5 is specifically required by type I IRES but not by type II or type III IRES, in which cleavage of eIF4GI has not been observed. We observed that both DAP5 and C-terminal eIF4GI interact with CVB3 IRES in the same region, but DAP5 exhibits a lower affinity for CVB3 IRES compared with the C-terminal eIF4GI fragment. It appears that DAP5 is required for the initial round of viral RNA translation by sustaining a basal level of CVB3 IRES activity. This activity leads to expression of 2A protease and consequent robust CVB3 IRES-mediated translation by the C-terminal eIF4GI fragment.

Assessment of Palatal Rugae to Aid in Gender Identification in Hazaribag Population-A Cross-Sectional Study.

Background: This research paper aims to investigate the effectiveness of gender identification utilizing palatal rugae. Materials and Methods: The size of the sample that was selected included 100 people. They were made up of 50 men and 50 women, all in between the ages of 18 and 25. To examine their palatal rugae patterns, casts were made after taking maxillary impressions. Based on the size and rugae amount found on the left as well as the right sides, the palatal rugae patterns were investigated. Rugae patterns have been recognized based on the categorization provided by Thomas and Kotze (1983). Statistical Analysis: Chi-square analysis has been used. Results: There were comparative variations in the shape of rugae patterns among male and female individuals. The study revealed that the circular pattern was higher in males (P < 0.01) as compared to females and the unification pattern was comparatively greater in females (P < 0.05) as compared to males. The most predominant pattern that was seen in both genders was the wavy pattern that was seen to be present in 57.17% of males and 53.42% of females. The rugae number on the right and left sides did not exhibit any significant variations. Conclusions: This research thus exhibits a relevant difference in patterns of rugae and also confirms the uniqueness of patterns in each individual. Hence, it could be utilized as an adjunct to other tools for identification in the forensic sciences.

Analysis of the Microstructural and Mechanical Properties of 3D-Printed Removable Partial Denture Base Materials.

Background: Recent advancements in three-dimensional (3D) printing have introduced novel materials for removable partial dentures (RPD) base fabrication, promising improved mechanical properties, and biocompatibility. Materials and Methods: In this study, three different RPD base materials were evaluated: conventional heat-cured acrylic resin (Control), biocompatible 3D-printed resin (Test Group A), and a novel nanocomposite 3D-printed resin (Test Group B). A total of 30 standardized RPD base specimens (n = 10 per group) were fabricated according to established protocols. Microstructural analysis was performed using scanning electron microscopy (SEM), and the mechanical properties, including flexural strength and modulus, were determined using a universal testing machine. Results: Microstructural analysis revealed distinct differences among the materials. SEM images showed a well-defined and homogeneous microstructure in Test Group B, while Test Group A exhibited fewer voids compared to the Control group. Mechanical testing results indicated that Test Group B had the highest flexural strength (120 ± 5 MPa), followed by Test Group A (90 ± 4 MPa), and the Control group (75 ± 3 MPa). Similarly, Test Group B demonstrated the highest flexural modulus (3.5 ± 0.2 GPa), followed by Test Group A (2.8 ± 0.1 GPa), and the Control group (2.1 ± 0.1 GPa). Conclusion: These findings suggest that 3D-printed RPD base materials, particularly nanocomposite resins, hold promise for improving the overall quality and durability of removable partial dentures.

A Preliminary Report of Maximum Voluntary Bite Force of Young Indian Population.

Introduction: The measurement of bite force is increasingly gaining importance in dentistry. This preliminary report evaluates the maximum voluntary bite force (MVBF) of young healthy individuals with normal occlusion and correlates the effect of age and gender with the maximum bite force (MBF). Materials and Methods: 405 participants in the age group of 18 to 40 years were selected from the outpatient department meeting inclusion and exclusion criteria. MVBF was measured with the help of a digital device called "Byte" at incisors, right first molar, and left first molar region. Results: There was a strong correlation between age with bite force. Bite force increased with age. Males had more bite force than females. The posterior region had higher bite force than the anterior region. Conclusion: Measurement of bite force is very important for every patient undergoing restorative treatment. The "Byte" device was found to be very efficient.

Assessment of the Capability to Accurately Capture the Vertical Relationship by the Various Bite Registration Materials.

Background: This research study aimed to evaluate and compare the capability of four various bite registration materials to reproduce precise interocclusal relationships in the vertical dimension. Materials and Methods: Ideal maxillary and mandibular casts were mounted on the semi-adjustable articulator in maximum intercuspation after mock tooth preparation on 46, 47, and 48. Models were scanned by the Medit T500 Dental Lab Scanner, and initial reading was noted at the predetermined points. Ten interocclusal bite registrations were made using four materials (CADbite, Jet Bite, Ramitec, and Aluwax). The mandibular model was demounted and again remounted using the interocclusal records, and the final reading was noted after scanning. Results: Ramitec showed superior results when compared to polyvinyl bite registration material and Aluwax, but the differences between Ramitec, CADbite, and Jet Bite were nonsignificant. Conclusions: Although all four materials are suitable for clinical use, elastomeric materials showed superior results. In that, polyether was found to be the best.

Maxillary Cast Partial Denture and Mandibular Implant-Supported Metal-Ceramic Prosthesis With a Split Framework to Compensate for Mandibular Flexure: A Case Report.

The goal of modern dentistry is to restore optimum oral health, function, and comfort for a patient. For an implant-supported fixed prosthesis, these goals cannot be met if the biomechanical factors governing the success of the prosthesis are overlooked. Mandibular flexure is one such factor that needs to be considered, especially when implants are being placed posterior to the interforaminal region. If not, it can lead to problems like increased stress, bone resorption, poor fit of the prosthesis, screw loosening, and patient discomfort. The use of a split-framework prosthesis is one of the measures that could be taken to decrease the stress, ensure a passive fit of the framework, and long-term maintenance of patient comfort and function. This case report describes the oral rehabilitation of a patient using a maxillary cast partial denture and mandibular split framework fixed prosthesis to compensate for mandibular flexure.

Evaluation of Impact Strength and Flexural Strength of Polyether Ether Ketone vs. Computer-Aided Design/Computer-Aided Manufacturing Polymethyl Methacrylate Denture Base Materials: An In-Vitro Study.

OBJECTIVE: The objective is to comparatively assess the impact strength and flexural strength of polyether ether ketone (PEEK) vs. computer-aided design/computer-aided manufacturing (CAD/CAM) polymethyl methacrylate denture base material. METHODS: A total of 90 samples were fabricated with traditional heat cure PMMA, PEEK, and CAD/CAM PMMA and divided into three groups of 30 samples each. The impact strength of all the samples was measured using an Izod impact tester with a pendulum in the air at 23±2°C. A three-point bending test was used in a Universal Testing Machine to assess the flexural strength of all the samples. The impact strength and flexural strength mean values were computed using a one-way ANOVA test. RESULT: Impact strength and flexural strength of PEEK (IS=10.22±1.25 kJ/m2 and FS=120±8.0 MPa) is almost identical to CAD/CAM PMMA sample (IS=9.595±3.313 kJ/m2 and FS=118.11±5.00 MPa) whereas for conventional heat cure PMMA (IS=4.00±.011 kJ/m2 and FS=75.4±4.50 MPa) the values are least among the three. CONCLUSION:  PEEK or CAD/CAM PMMA share almost identical and superior mechanical properties, and both can be used as better alternatives for complete denture fabrication rather than using conventional heat cure PMMA.

Attention-augmented U-Net (AA-U-Net) for semantic segmentation.

Deep learning-based image segmentation models rely strongly on capturing sufficient spatial context without requiring complex models that are hard to train with limited labeled data. For COVID-19 infection segmentation on CT images, training data are currently scarce. Attention models, in particular the most recent self-attention methods, have shown to help gather contextual information within deep networks and benefit semantic segmentation tasks. The recent attention-augmented convolution model aims to capture long range interactions by concatenating self-attention and convolution feature maps. This work proposes a novel attention-augmented convolution U-Net (AA-U-Net) that enables a more accurate spatial aggregation of contextual information by integrating attention-augmented convolution in the bottleneck of an encoder-decoder segmentation architecture. A deep segmentation network (U-Net) with this attention mechanism significantly improves the performance of semantic segmentation tasks on challenging COVID-19 lesion segmentation. The validation experiments show that the performance gain of the attention-augmented U-Net comes from their ability to capture dynamic and precise (wider) attention context. The AA-U-Net achieves Dice scores of 72.3% and 61.4% for ground-glass opacity and consolidation lesions for COVID-19 segmentation and improves the accuracy by 4.2% points against a baseline U-Net and 3.09% points compared to a baseline U-Net with matched parameters. Supplementary Information: The online version contains supplementary material available at 10.1007/s11760-022-02302-3.

p53 and RNA viruses: The tug of war.

Host factors play essential roles in viral infection, and their interactions with viral proteins are necessary for establishing effective pathogenesis. p53 is a host factor that maintains genomic integrity by controlling cell-cycle progression and cell survival. It is a well-known tumor suppressor protein that gets activated by various stress signals, thereby regulating cellular pathways. The cellular outcomes from different stresses are tightly related to p53 dynamics, including its alterations at gene, mRNA, or protein levels. p53 also contributes to immune responses leading to the abolition of viral pathogens. In turn, the viruses have evolved strategies to subvert p53-mediated host responses to improve their life cycle and pathogenesis. Some viruses attenuate wild-type p53 (WT-p53) function for successful pathogenesis, including degradation and sequestration of p53. In contrast, some others exploit the WT-p53 function through regulation at the transcriptional/translational level to spread infection. One area in which the importance of such host factors is increasingly emerging is the positive-strand RNA viruses that cause fatal viral infections. In this review, we provide insight into all the possible mechanisms of p53 modulation exploited by the positive-strand RNA viruses to establish infection. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications Translation > Regulation RNA in Disease and Development > RNA in Disease.

Automated Emotion Recognition System Using Blood Volume Pulse and XGBoost Learning.

In this study, a new method for detecting emotions using Blood Volume Pulse (BVP) signals and machine learning was presented. The BVP of 30 subjects from the publicly available CASE dataset was pre-processed, and 39 features were extracted from various emotional states, such as amusing, boring, relaxing, and scary. The features were categorized into time, frequency, and time-frequency domains and used to build an emotion detection model with XGBoost. The model achieved the highest classification accuracy of 71.88% using the top 10 features. The most significant features of the model were computed from time (5 features), time-frequency (4 features), and frequency (1 feature) domains. The skewness calculated from the time-frequency representation of the BVP was ranked highest and played a crucial role in the classification. Our study suggests the potential of using BVP recorded from wearable devices to detect emotions in healthcare applications.

A Comparison of the Wetting Ability of Three Artificial Saliva Substitutes on Heat-Cured Denture Base Resin - An In vitro Study.

Introduction: Salivary substitutes are gaining popularity these days because of the increase in patients with dry mouth. These substitutes must satisfy certain criteria to fulfill the patient's needs. One of these is wettability. Materials and Methods: One hundred fifty rectangular specimens of heat-cured denture base acrylic resin were prepared. A drop of test liquids (human saliva, distilled water, aqwet, saleva, and wet mouth) was placed over the test specimen and right and left contact angles were measured using optical contact angle machine. Results: All test liquids performed better than distilled water. Human saliva has the least contact angle followed by aqwet. Conclusion: Carboxymethyl cellulose base aqwet saliva substitute was found to be best having similar contact angle values to human saliva.

Prosthodontic Rehabilitation With Kennedy's Class I and Class II Using an Extended Precision Attachment: A Report of Two Cases.

Satisfactory restorations can be difficult in partially edentulous patients, especially those with unilateral or bilateral posterior ocular defects. With traditional and modern treatment options, recovery can be successful. Partial dentures with attachments are such a treatment. An implant-supported prosthesis is another option for therapy in these circumstances. Precision extracoronary attachments are the preferred treatment option when implant treatment does not give good results. This research offers two examples of partial cast prosthetic rehabilitation for distal extension utilizing precise attachments.

Prevalence of Oral Submucous Fibrosis, Its Correlation of Clinical Grading to Various Habit Factors among Patients of Bihar: A Cross Sectional Study.

Aim: To find out the prevalence of OSMF and its Co-relation of clinical grading to various habit factors (time span of habit practiced in years, repetition of habit practiced per day, time of habit practiced in minutes per use). Method: This descriptive, cross-sectional survey was carried out and close ended questionnaire was used for data collection. Demographic details like gender & age and different tissue exploiting habits like, chewing gutkha, chewing areca nut, chewing panmasala with or without tobacco, plain tobacco, mawa, smoking, alcohol was recorded. Also, duration of habit in years, repetition of habit per day, time of habit per use & site of involvement was recorded. Results: Among 5297 patients examined at OPD, 120 were diagnosed with OSMF. The present study found no statistical relation between age, gender & OSMF. The present study concluded that majority 83 (69.17%) of the OSMF patients are guthka user and buccal mucosa was most affected site. OSMF was more prevalent in patients who practiced the habit for more than 15 years. Conclusion: Among the OSMF patients, guthka was most commonly practiced & buccal mucosa was most commonly involved. Duration and frequency of consumption were significantly associated with severity of OSMF.

Root Canal Configurations and Morphological Variations in Maxillary and Mandibular Second Molars in a Pakistani Population.

OBJECTIVE: To determine the dental morphology and root canal anatomy of maxillary and mandibular second molars in Pakistani population living in Hyderabad. STUDY DESIGN: Retrospective, cross-sectional study. Place and Duration of the Study: Department of Operative Dentistry and Endodontics, Liaquat University of Medical and Health Sciences (LUMHS), Jamshoro, from April to May 2023. METHODOLOGY: This study analysed the number of roots, root canal configurations, and frequency of C-shaped root canals and their configuration assessment. The data was obtained from Cone Beam Computerised Tomography (CBCT) records sourced from the Department of Radiology at Advanced Dental Care Centre of LUMHS. RESULTS: Two-rooted maxillary second molar was present in 10.6% of teeth, while 5.3% were single-rooted. Among mandibular second molars, 6.8% had one root, while 2.3% had three. The maxillary second molar mesiobuccal roots were Type I in 47.7% cases. The maxillary second molars had C1-shaped canals in 3.8% of cases. The study revealed that 10.6% of mandibular second molars had C-shaped canals, 3.0% were C1, 6.8% C3a, and 0.8% C4. A minority of patients had palatal morphology with two roots (MP and DP) and Type 1 canal structure, while a subset had both MP and DP canals. CONCLUSION: The prevalence of radix in mandibular second molars was found to be relatively infrequent. The prevalent root canal configurations were Type I in the mesiobuccal and palatal roots and Type IV in the mesial root of mandibular second molars. A noteworthy correlation was detected between the molar type characterised by a single root and the existence of a C-shaped canal in the female population. KEY WORDS: CBCT, Dental anatomy, Gender, Root canal, Morphology, Pakistani population.

Picolinic acid is a broad-spectrum inhibitor of enveloped virus entry that restricts SARS-CoV-2 and influenza A virus in vivo.

The COVID-19 pandemic highlights an urgent need for effective antivirals. Targeting host processes co-opted by viruses is an attractive antiviral strategy with a high resistance barrier. Picolinic acid (PA) is a tryptophan metabolite endogenously produced in mammals. Here, we report the broad-spectrum antiviral activity of PA against enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), flaviviruses, herpes simplex virus, and parainfluenza virus. Mechanistic studies reveal that PA inhibits enveloped virus entry by compromising viral membrane integrity, inhibiting virus-cellular membrane fusion, and interfering with cellular endocytosis. More importantly, in pre-clinical animal models, PA exhibits promising antiviral efficacy against SARS-CoV-2 and IAV. Overall, our data establish PA as a broad-spectrum antiviral with promising pre-clinical efficacy against pandemic viruses SARS-CoV-2 and IAV.