Apigenin Provides Structural Protection to Human Fibrinogen against Nitrosative Stress: Biochemical and Molecular Insights.

BACKGROUND: Peroxynitrite (ONOO-) is an oxidant linked with several human pathologies. Apigenin, a natural flavonoid known for its health benefits, remains unexplored in relation to ONOO- effects. This study investigated the potential of apigenin to structurally protect fibrinogen, an essential blood clotting factor, from ONOO--induced damage. METHODS: Multi-approach analyses were carried out where fibrinogen was exposed to ONOO- generation while testing the efficacy of apigenin. The role of apigenin against ONOO--induced modifications in fibrinogen was investigated using UV spectroscopy, tryptophan or tyrosine fluorescence, protein hydrophobicity, carbonylation, and electrophoretic analyses. RESULTS: The findings demonstrate that apigenin significantly inhibits ONOO--induced oxidative damage in fibrinogen. ONOO- caused reduced UV absorption, which was reversed by apigenin treatment. Moreover, ONOO- diminished tryptophan and tyrosine fluorescence, which was effectively restored by apigenin treatment. Apigenin also reduced the hydrophobicity of ONOO--damaged fibrinogen. Moreover, apigenin exhibited protective effects against ONOO--induced protein carbonylation. SDS-PAGE analyses revealed that ONOO-treatment eliminated bands corresponding to fibrinogen polypeptide chains Aα and γ, while apigenin preserved these changes. CONCLUSIONS: This study highlights, for the first time, the role of apigenin in structural protection of human fibrinogen against peroxynitrite-induced nitrosative damage. Our data indicate that apigenin offers structural protection to all three polypeptide chains (Aα, Bß, and γ) of human fibrinogen. Specifically, apigenin prevents the dislocation or breakdown of the amino acids tryptophan, tyrosine, lysine, arginine, proline, and threonine and also prevents the exposure of hydrophobic sites in fibrinogen induced by ONOO-.

Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells.

MicroRNAs (miRNAs) are involved in the modulation of pathogenic genes by binding to their mRNA sequences' 3' untranslated regions (3'UTR). Interleukin-6 (IL-6) is known to promote cancer progression and treatment resistance. In this study, we aimed to explore the therapeutic effects of gold nanoparticles (GNP) against IL-6 overexpression and the modulation of miRNA-26a-5p in breast cancer (BC) cells. GNP were synthesized using the trisodium citrate method and characterized through UV-Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). To predict the binding of miR-26a-5p in the IL-6 mRNA's 3'UTR, we utilized bioinformatics algorithms. Luciferase reporter clone assays and anti-miRNA-26a-5p transfection were employed to validate the binding of miR26a-5p in the IL-6 mRNA's 3'UTR. The activity of RelA and NF-κBp50 was assessed and confirmed using Bay 11-7082. The synthesized GNP were spherical with a mean size of 28.3 nm, exhibiting high stability, and were suitable for BC cell treatment. We found that miR-26a-5p directly regulated IL-6 overexpression in MCF-7 cells activated with PMA. Treatment of MCF-7 cells with GNP resulted in the inhibition of IL-6 overexpression and secretion through the increase of miR26a-5p. Furthermore, GNP deactivated NF-κBp65/NF-κBp50 transcription activity. The newly engineered GNP demonstrated safety and showed promise as a therapeutic approach for reducing IL-6 overexpression. The GNP suppressed IL-6 overexpression and secretion by deactivating NF-κBp65/NF-κBp50 transcription activity and upregulating miR-26a-5p expression in activated BC cells. These findings suggest that GNP have potential as a therapeutic intervention for BC by targeting IL-6 expression and associated pathways.

The potential role of mechanotransduction in the management of pediatric calvarial bone flap repair.

Pediatric patients suffering traumatic brain injuries may require a decompressive craniectomy to accommodate brain swelling by removing a portion of the skull. Once the brain swelling subsides, the preserved calvarial bone flap is ideally replaced as an autograft during a cranioplasty to restore protection of the brain, as it can reintegrate and grow with the patient during immature skeletal development. However, pediatric patients exhibit a high prevalence of calvarial bone flap resorption post-cranioplasty, causing functional and cosmetic morbidity. This review examines possible solutions for mitigating pediatric calvarial bone flap resorption by delineating methods of stimulating mechanosensitive cell populations with mechanical forces. Mechanotransduction plays a critical role in three main cell types involved with calvarial bone repair, including mesenchymal stem cells, osteoblasts, and dural cells, through mechanisms that could be exploited to promote osteogenesis. In particular, physiologically relevant mechanical forces, including substrate deformation, external forces, and ultrasound, can be used as tools to stimulate bone repair in both in vitro and in vivo systems. Ultimately, combating pediatric calvarial flap resorption may require a combinatorial approach using both cell therapy and bioengineering strategies.

Efficacy of Clear Aligners in Treating Class III Malocclusion With Mandibular Molar Distalization: A Systematic Review.

The primary goal of orthodontic therapy in pseudo-class III is to restore the proper dental connection by rectifying the canine and molar relationship to Class I through lower molar and premolar visualization, as well as providing normal anterior overjet. The purpose of this systematic study was to determine the efficacy of clear aligners in treating class III malocclusion with mandibular molar distalization. A wide range of searches were done on various search engines like Cochrane, Web of Science, Embase, PubMed, Scopus, and Google Scholar to collect relevant articles related to our study. This review's article selection was guided by the PRISMA flowchart. The electronic findings provided numerous articles with nearly 78 articles regarding clear aligners in class III malocclusion with molar distalization. From this, seven full-text papers were evaluated for eligibility criteria, with two articles being rejected with justification and five articles being elaborated in the current systematic review. The current evidence of this review suggested that the clear aligners were effective in correcting class III malocclusion with molar distalization. The amount of molar distalization is about 2 to 3 mm, which helps in achieving molar and canine relationship in class I, with a high compliance level and also improvement of the facial profile.

Discovery of a three-proton insertion mechanism in α-molybdenum trioxide leading to enhanced charge storage capacity.

The α-molybdenum trioxide has attracted much attention for proton storage owing to its easily modified bilayer structure, fast proton insertion kinetics, and high theoretical specific capacity. However, the fundamental science of the proton insertion mechanism in α-molybdenum trioxide has not been fully understood. Herein, we uncover a three-proton intercalation mechanism in α-molybdenum trioxide using a specially designed phosphoric acid based liquid crystalline electrolyte. The semiconductor-to-metal transition behavior and the expansion of the lattice interlayers of α-molybdenum trioxide after trapping one mole of protons are verified experimentally and theoretically. Further investigation of the morphology of α-molybdenum trioxide indicates its fracture behavior upon the proton intercalation process, which creates diffusion channels for hydronium ions. Notably, the observation of an additional redox behavior at low potential endows α-molybdenum trioxide with an improved specific discharge capacity of 362 mAh g-1.

Phytoconstituents as potential therapeutic agents against COVID-19: a computational study on inhibition of SARS-CoV-2 main protease.

The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) has become a global health crisis, and the urgent need for effective treatments is evident. One potential target for COVID-19 therapeutics is the main protease (Mpro) of SARS­CoV­2, an essential enzyme for viral replication. Natural compounds have been explored as a source of potential inhibitors for Mpro due to their safety and availability. In this study, we employed a computational approach to screen a library of phytoconstituents and identified potential Mpro inhibitors based on their binding affinities and molecular interactions. The top-ranking compounds were further validated through molecular dynamics simulations (MDS) and free energy calculations. As a result of the above procedures, we identified two phytoconstituents, Khelmarin B and Neogitogenin, with appreciable binding affinity and specificity towards the Mpro binding pocket. Our results suggest that Khelmarin B and Neogitogenin could potentially serve as Mpro inhibitors and have the potential to be developed as COVID-19 therapeutics. Further experimental studies are required to confirm the efficacy and safety of these compounds.Communicated by Ramaswamy H. Sarma.

Cancer Bioenergetics and Tumor Microenvironments-Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems.

Cancer is an impending bottleneck in the advanced scientific workflow to achieve diagnostic, prognostic, and therapeutic success. Most cancers are refractory to conventional diagnostic and chemotherapeutics due to their limited targetability, specificity, solubility, and side effects. The inherent ability of each cancer to evolve through various genetic and epigenetic transformations and metabolic reprogramming underlies therapeutic limitations. Though tumor microenvironments (TMEs) are quite well understood in some cancers, each microenvironment differs from the other in internal perturbations and metabolic skew thereby impeding the development of appropriate diagnostics, drugs, vaccines, and therapies. Cancer associated bioenergetics modulations regulate TME, angiogenesis, immune evasion, generation of resistant niches and tumor progression, and a thorough understanding is crucial to the development of metabolic therapies. However, this remains a missing element in cancer theranostics, necessitating the development of modalities that can be adapted for targetability, diagnostics and therapeutics. In this challenging scenario, nanomaterials are modular platforms for understanding TME and achieving successful theranostics. Several nanoscale particles have been successfully researched in animal models, quite a few have reached clinical trials, and some have achieved clinical success. Nanoparticles exhibit an intrinsic capability to interact with diverse biomolecules and modulate their functions. Furthermore, nanoparticles can be functionalized with receptors, modulators, and drugs to facilitate specific targeting with reduced toxicity. This review discusses the current understanding of different theranostic nanosystems, their synthesis, functionalization, and targetability for therapeutic modulation of bioenergetics, and metabolic reprogramming of the cancer microenvironment. We highlight the potential of nanosystems for enhanced chemotherapeutic success emphasizing the questions that remain unanswered.

Gold Nanoparticles Inhibit PMA-Induced MMP-9 Expression via microRNA-204-5p Upregulation and Deactivation of NF-κBp65 in Breast Cancer Cells.

OBJECTIVE: Breast cancer (BC) is the most common malignancy in females globally. Matrix metalloproteinase-9 (MMP-9) is crucial to the invasion, progression and spread of BC. Gold nanoparticles (AuNPs) have an anti-tumorigenic role, but their therapeutic role in microRNAs (miRNAs) regulation has not been explored. This study determined the potential of AuNPs against MMP-9 overexpression/production and miRNA-204-5p regulation in BC cells. METHODS: AuNPs were newly engineered, and their stability was analyzed using the zeta potential, polydispersity index, surface-plasmon-resonance peak and transmission electron microscopy. A bioinformatics algorithm was used to predict the pairing of miRNA in the 3'untranslated-region (3'UTR) of MMP-9 mRNA. TaqMan assays were carried out to quantify miRNA and mRNA, whereas MMP-9-specific immunoassays and gelatin zymography were used to determine protein secretion and activity. The binding of miRNA in MMP-9 mRNA 3'UTR was verified by luciferase reporter clone assays and transfection with anti-miRNAs. In addition, NF-κBp65 activity was determined and confirmed with parthenolide treatment. RESULTS: Engineered AuNPs were highly stable and spherical in shape, with a mean size of 28.3 nm. Tested in MCF-7 BC cells, microRNA-204-5p directly regulates MMP-9. AuNPs inhibit PMA-induced MMP-9 mRNA and protein via hsa-miR-204-5p upregulation. Anti-miR-204 transfected MCF-7 cells demonstrated enhanced MMP-9 expression (p < 0.001), while AuNPs treatment attenuated MMP-9 expression in a dose-dependent manner (p < 0.05). Moreover, AuNPs also inhibit PMA-induced NF-κBp65 activation in anti-hsa-miR-204 transfected MCF-7 cells. CONCLUSION: Engineered AuNPs were stable and non-toxic to BC cells. AuNPs inhibit PMA-induced MMP-9 expression, production and activation via NF-κBp65 deactivation and hsa-miR-204-5p upregulation. These novel therapeutic potentials of AuNPs on stimulated BC cells provide novel suggestions that AuNPs inhibit carcinogenic activity via inverse regulation of microRNAs.

A Laser-Induced Mo2 CTx MXene Hybrid Anode for High-Performance Li-Ion Batteries.

MXenes, a fast-growing family of two-dimensional (2D) transition metal carbides/nitrides, are promising for electronics and energy storage applications. Mo2 CTx MXene, in particular, has demonstrated a higher capacity than other MXenes as an anode for Li-ion batteries. Yet, such enhanced capacity is accompanied by slow kinetics and poor cycling stability. Herein, it is revealed that the unstable cycling performance of Mo2 CTx is attributed to the partial oxidation into MoOx with structural degradation. A laser-induced Mo2 CTx /Mo2 C (LS-Mo2 CTx ) hybrid anode has been developed, of which the Mo2 C nanodots boost redox kinetics, and the laser-reduced oxygen content prevents the structural degradation caused by oxidation. Meanwhile, the strong connections between the laser-induced Mo2 C nanodots and Mo2 CTx nanosheets enhance conductivity and stabilize the structure during charge-discharge cycling. The as-prepared LS-Mo2 CTx anode exhibits an enhanced capacity of 340 mAh g-1 vs 83 mAh g-1 (for pristine) and an improved cycling stability (capacity retention of 106.2% vs 80.6% for pristine) over 1000 cycles. The laser-induced synthesis approach underlines the potential of MXene-based hybrid materials for high-performance energy storage applications.

Balloon mitral valvuloplasty: a re-emerging technique enhanced with real-time, three-dimensional transoesophageal cardiac ultrasound/echocardiography (3D-TOE).

We describe the case of a woman in her 60s with mitral stenosis, rate-controlled atrial fibrillation and a history of childhood rheumatic fever. She successfully underwent elective percutaneous transvenous mitral commissurotomy (PTMC), also described as balloon mitral valvuloplasty, for severe, symptomatic mitral stenosis. This was completed via right femoral vein access, trans-septal puncture and commissural separation guided by real-time three-dimensional (3D) transoesophageal echocardiography under general anaesthesia.Balloon mitral valvuloplasty is being completed more frequently in the UK due to the population having a higher incidence of mitral valve disease as a result of migration and as a palliative measure in those considered too high risk for mitral valve replacement cardiothoracic surgery.Rheumatic mitral stenosis is known to be a disease prevalent in countries of low and middle income and with increased migration to the UK, resulting in an increased prevalence of rheumatic mitral valve disease in the UK. It is estimated that within the UK, one in seven persons are migrants, and as such, we believe it is important to pay attention to diseases which affect the evolving population of the UK.Technological advancements, including availability and use of 3D transoesophageal cardiac ultrasound/echocardiography, have made PTMC much safer and more effective than previously. Additionally, the multidisciplinary team approach to PTMC is very important to its success. The procedure was completed successfully, with no complications.

Artificial Intelligence Based Approach for Classification of Human Activities Using MEMS Sensors Data.

The integration of Micro Electronic Mechanical Systems (MEMS) sensor technology in smartphones has greatly improved the capability for Human Activity Recognition (HAR). By utilizing Machine Learning (ML) techniques and data from these sensors, various human motion activities can be classified. This study performed experiments and compiled a large dataset of nine daily activities, including Laying Down, Stationary, Walking, Brisk Walking, Running, Stairs-Up, Stairs-Down, Squatting, and Cycling. Several ML models, such as Decision Tree Classifier, Random Forest Classifier, K Neighbors Classifier, Multinomial Logistic Regression, Gaussian Naive Bayes, and Support Vector Machine, were trained on sensor data collected from accelerometer, gyroscope, and magnetometer embedded in smartphones and wearable devices. The highest test accuracy of 95% was achieved using the random forest algorithm. Additionally, a custom-built Bidirectional Long-Short-Term Memory (Bi-LSTM) model, a type of Recurrent Neural Network (RNN), was proposed and yielded an improved test accuracy of 98.1%. This approach differs from traditional algorithmic-based human activity detection used in current wearable technologies, resulting in improved accuracy.

Ultrasound-derived mechanical stimulation of cell-laden collagen hydrogels for bone repair.

Cell therapy is emerging as an effective treatment strategy for many diseases. Here we describe a novel approach to bone tissue repair that combines hydrogel-based cell therapy with low intensity pulsed ultrasound (LIPUS), an FDA approved treatment for fracture repair. Bone marrow-derived stromal cells (BMSCs) have been encapsulated in type I collagen hydrogels and mechanically stimulated using LIPUS-derived acoustic radiation force (ARF). We observed the expression and upward trend of load-sensitive, osteoblast-specific markers and determined that the extent of cell response is dependent on an optimal combination of both hydrogel stiffness and ARF intensity. Specifically, cells encapsulated in hydrogels of optimal stiffness respond at the onset of ultrasound by upregulating early bone-sensitive markers such as calcium, cyclooxygenase-2, and prostaglandin E2 , and later by supporting mineralized tissue formation after 21 days of culture. In vivo evaluation of a critical size calvarial defect in NOD scid gamma (NSG) mice indicated that the implantation of BMSC-laden hydrogels of optimal stiffness improved healing of calvarial defects after daily administration of ARF over 4 weeks. Collectively, these findings validate the efficacy of our system of localized cell delivery for treating bone defects where undifferentiated BMSCs are induced to the osteoblastic lineage. Further, in vivo healing may be enhanced via non-invasive transdermal mechanical stimulation of implanted cells using ARF.

Revolutionizing Dental Imaging: A Comprehensive Study on the Integration of Artificial Intelligence in Dental and Maxillofacial Radiology.

Recent advancements in deep learning and artificial intelligence (AI) have profoundly impacted various fields, including diagnostic imaging. Integrating AI technologies such as deep learning and convolutional neural networks has the potential to drastically improve diagnostic methods in the field of dentistry and maxillofacial radiography. A systematic study that adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards was carried out to examine the efficacy and uses of AI in dentistry and maxillofacial radiography. Incorporating cohort studies, case-control studies, and randomized clinical trials, the study used an interdisciplinary methodology. A thorough search spanning peer-reviewed research papers from 2009 to 2023 was done in databases including MEDLINE/PubMed and EMBASE. The inclusion criteria were original clinical research in English that employed AI models to recognize anatomical components in oral and maxillofacial pictures, identify anomalies, and diagnose disorders. The study looked at numerous research that used cutting-edge technology to show how accurate and dependable dental imaging is. Among the tasks covered by these investigations were age estimation, periapical lesion detection, segmentation of maxillary structures, assessment of dentofacial abnormalities, and segmentation of the mandibular canal. The study revealed important developments in the precise definition of anatomical structures and the identification of diseases. The use of AI technology in dental imaging marks a revolutionary development that will usher in a time of unmatched accuracy and effectiveness. These technologies have not only improved diagnostic accuracy and enabled early disease detection but have also streamlined intricate procedures, significantly enhancing patient outcomes. The symbiotic collaboration between human expertise and machine intelligence promises a future of more sophisticated and empathetic oral healthcare.

A 2.75†V ammonium-based dual-ion battery.

The popular metal-ion batteries (MIBs) suffer from environmental and economic issues because of their heavy dependency on nonrenewable metals. Here, we propose a metal-free ammonium (NH4 + )-based dual-ion battery with a record-breaking operation voltage of 2.75 V. The working mechanism of this sustainable battery involves the reversible anion (PF6 - ) intercalation chemistry in graphite cathode and NH4 + intercalation behavior in PTCDI (3,4,9,10-perylenetetracarboxylic diimide) anode. This new battery configuration successfully circumvented the reduction susceptibility of NH4 + and the lack of mature NH4 + -rich cathodes for NH4 + ion batteries (AIBs). The customized organic NH4 + electrolyte endows the graphite||PTCDI full battery with durable longevity (over 1000 cycles) and a high energy density (200 Wh kg-1 ). We show that the development of AIBs should be high-voltage-oriented while circumventing low operation potential to avoid NH4 + reduction.

In silico Prediction of Deleterious Single Nucleotide Polymorphism in S100A4 Metastatic Gene: Potential Early Diagnostic Marker.

S100A4 protein overexpression has been reported in different types of cancer and plays a key role by interacting with the tumor suppressor protein Tp53. Single nucleotide polymorphisms (SNP) in S100A4 could directly influence the biomolecular interaction with the tumor suppressor protein Tp53 due to their aberrant conformations. Hence, the study was designed to predict the deleterious SNP and its effect on the S100A4 protein structure and function. Twenty-one SNP data sets were screened for nonsynonymous mutations and subsequently subjected to deleterious mutation prediction using different computational tools. The screened deleterious mutations were analyzed for their changes in functionality and their interaction with the tumor suppressor protein Tp53 by protein-protein docking analysis. The structural effects were studied using the 3DMissense mutation tool to estimate the solvation energy and torsion angle of the screened mutations on the predicted structures. In our study, 21 deleterious nonsynonymous mutations were screened, including F72V, E74G, L5P, D25E, N65S, A28V, A8D, S20L, L58P, and K26N were found to be remarkably conserved by exhibiting the interaction either with the EF-hand 1 or EF-hand 2 domain. The solvation and torsion values significantly deviated for the mutant-type structures with S20L, N65S, and F72L mutations and showed a marked reduction in their binding affinity with the Tp53 protein. Hence, these deleterious mutations might serve as prospective targets for diagnosing and developing personalized treatments for cancer and other related diseases.

Normalization of gene expression data revisited: the three viewpoints of the transcriptome in human skeletal muscle undergoing load-induced hypertrophy and why they matter.

BACKGROUND: The biological relevance and accuracy of gene expression data depend on the adequacy of data normalization. This is both due to its role in resolving and accounting for technical variation and errors, and its defining role in shaping the viewpoint of biological interpretations. Still, the choice of the normalization method is often not explicitly motivated although this choice may be particularly decisive for conclusions in studies involving pronounced cellular plasticity. In this study, we highlight the consequences of using three fundamentally different modes of normalization for interpreting RNA-seq data from human skeletal muscle undergoing exercise-training-induced growth. Briefly, 25 participants conducted 12 weeks of high-load resistance training. Muscle biopsy specimens were sampled from m. vastus lateralis before, after two weeks of training (week 2) and after the intervention (week 12), and were subsequently analyzed using RNA-seq. Transcript counts were modeled as (1) per-library-size, (2) per-total-RNA, and (3) per-sample-size (per-mg-tissue). RESULT: Initially, the three modes of transcript modeling led to the identification of three unique sets of stable genes, which displayed differential expression profiles. Specifically, genes showing stable expression across samples in the per-library-size dataset displayed training-associated increases in per-total-RNA and per-sample-size datasets. These gene sets were then used for normalization of the entire dataset, providing transcript abundance estimates corresponding to each of the three biological viewpoints (i.e., per-library-size, per-total-RNA, and per-sample-size). The different normalization modes led to different conclusions, measured as training-associated changes in transcript expression. Briefly, for 27% and 20% of the transcripts, training was associated with changes in expression in per-total-RNA and per-sample-size scenarios, but not in the per-library-size scenario. At week 2, this led to opposite conclusions for 4% of the transcripts between per-library-size and per-sample-size datasets (↑ vs. ↓, respectively). CONCLUSION: Scientists should be explicit with their choice of normalization strategies and should interpret the results of gene expression analyses with caution. This is particularly important for data sets involving a limited number of genes or involving growing or differentiating cellular models, where the risk of biased conclusions is pronounced.

Camptothecin Encapsulated in ß-Cyclodextrin-EDTA-Fe3O4 Nanoparticles Induce Metabolic Reprogramming Repair in HT29 Cancer Cells through Epigenetic Modulation: A Bioinformatics Approach.

Cancer progresses through a distinctive reprogramming of metabolic pathways directed by genetic and epigenetic modifications. The hardwired changes induced by genetic mutations are resilient, while epigenetic modifications are softwired and more vulnerable to therapeutic intervention. Colon cancer is no different. This gives us the need to explore the mechanism as an attractive therapeutic target to combat colon cancer cells. We have previously established the enhanced therapeutic efficacy of a newly formulated camptothecin encapsulated in ß-cyclodextrin-EDTA-Fe3O4 nanoparticles (CPT-CEF) in colon cancer cells. We furthered this study by carrying out RNA sequencing (RNA-seq) to underscore specific regulatory signatures in the CPT-CEF treated versus untreated HT29 cells. In the study, we identified 95 upregulated and 146 downregulated genes spanning cellular components and molecular and metabolic functions. We carried out extensive bioinformatics analysis to harness genes potentially involved in epigenetic modulation as either the cause or effect of metabolic rewiring exerted by CPT-CEF. Significant downregulation of 13 genes involved in the epigenetic modulation and 40 genes from core metabolism was identified. Three genes, namely, DNMT-1, POLE3, and PKM-2, were identified as the regulatory overlap between epigenetic drivers and metabolic reprogramming in HT29 cells. Based on our results, we propose a possible mechanism that intercepts the two functional axes, namely epigenetic control, and metabolic modulation via CPT-CEF in colon cancer cells, which could skew cancer-induced metabolic deregulation towards metabolic repair. Thus, the study provides avenues for further validation of transcriptomic changes affected by these deregulated genes at epigenetic level, and ultimately may be harnessed as targets for regenerating normal metabolism in colon cancer with better treatment potential, thereby providing new avenues for colon cancer therapy.

Self-Reported Academic Misconduct among Medical Students: Perception and Prevalence.

Academic integrity is the basis of an education system and must be taught as an ethical behavior during academic training. Students who reflect honesty and truthfulness during the academic years are more likely to follow this path, develop professional integrity, and thus become responsible and dependable professionals. Here, we determine the prevalence of academic lapses among medical students by a cross-sectional descriptive survey based on a self-assessment questionnaire. Students' perception of 37 behaviors comprising five domains, plagiarism, indolence, cheating, disruptive behavior, and falsifying data, were explored. A high percentage of students (83%) indicated that all 37 behaviors constitute misconduct. Approximately 65% of students thought that their fellow students were involved in dishonest behaviors, and 34% answered that they were indulged in some form of misconduct. Content analysis identified some prevalent behaviors such as doing work for another student (82.5%), getting information from the students who already took the exam (82.5%), copying the answer from neighbors (79%), and marking attendance for absent friends (74.5%). Multiple regression analysis points out that future indulgence in a behavior is significantly (p ≤ 0.5) correlated with understanding a behavior as wrong, perceiving that others do it and whether one has already indulged in it. This study can serve as a diagnostic tool to analyze the prevalence of misconduct and a foothold to develop the medical school system's ethical guidelines.

The Sw5a gene confers resistance to ToLCNDV and triggers an HR response after direct AC4 effector recognition.

Several attempts have been made to identify antiviral genes against Tomato leaf curl New Delhi virus (ToLCNDV) and related viruses. This has led to the recognition of Ty genes (Ty1-Ty6), which have been successful in developing virus-resistant crops to some extent. Owing to the regular appearance of resistance-breaking strains of these viruses, it is important to identify genes related to resistance. In the present study, we identified a ToLCNDV resistance (R) gene, SlSw5a, in a ToLCNDV-resistant tomato cultivar, H-88-78-1, which lacks the known Ty genes. The expression of SlSw5a is controlled by the transcription factor SlMyb33, which in turn is regulated by microRNA159 (sly-miR159). Virus-induced gene silencing of either SlSw5a or SlMyb33 severely increases the disease symptoms and viral titer in leaves of resistant cultivar. Moreover, in SlMyb33-silenced plants, the relative messenger RNA level of SlSw5a was reduced, suggesting SlSw5a is downstream of the sly-miR159-SlMyb33 module. We also demonstrate that SlSw5a interacts physically with ToLCNDV-AC4 (viral suppressor of RNA silencing) to trigger a hypersensitive response (HR) and generate reactive oxygen species at infection sites to limit the spread of the virus. The "RTSK" motif in the AC4 C terminus is important for the interaction, and its mutation completely abolishes the interaction with Sw5a and HR elicitation. Overall, our research reports an R gene against ToLCNDV and establishes a connection between the upstream miR159-Myb33 module and its downstream target Sw5a to activate HR in the tomato, resulting in geminivirus resistance.