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.

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.

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.

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.

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.

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.

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.

Chronic obstructive pulmonary disease does not impair responses to resistance training.

BACKGROUND: Subjects with chronic obstructive pulmonary disease (COPD) are prone to accelerated decay of muscle strength and mass with advancing age. This is believed to be driven by disease-inherent systemic pathophysiologies, which are also assumed to drive muscle cells into a state of anabolic resistance, leading to impaired abilities to adapt to resistance exercise training. Currently, this phenomenon remains largely unstudied. In this study, we aimed to investigate the assumed negative effects of COPD for health- and muscle-related responsiveness to resistance training using a healthy control-based translational approach. METHODS: Subjects with COPD (n = 20, GOLD II-III, FEV1predicted 57 ± 11%, age 69 ± 5) and healthy controls (Healthy, n = 58, FEV1predicted 112 ± 16%, age 67 ± 4) conducted identical whole-body resistance training interventions for 13 weeks, consisting of two weekly supervised training sessions. Leg exercises were performed unilaterally, with one leg conducting high-load training (10RM) and the contralateral leg conducting low-load training (30RM). Measurements included muscle strength (nvariables = 7), endurance performance (nvariables = 6), muscle mass (nvariables = 3), muscle quality, muscle biology (m. vastus lateralis; muscle fiber characteristics, RNA content including transcriptome) and health variables (body composition, blood). For core outcome domains, weighted combined factors were calculated from the range of singular assessments. RESULTS: COPD displayed well-known pathophysiologies at baseline, including elevated levels of systemic low-grade inflammation ([c-reactive protein]serum), reduced muscle mass and functionality, and muscle biological aberrancies. Despite this, resistance training led to improved lower-limb muscle strength (15 ± 8%), muscle mass (7 ± 5%), muscle quality (8 ± 8%) and lower-limb/whole-body endurance performance (26 ± 12%/8 ± 9%) in COPD, resembling or exceeding responses in Healthy, measured in both relative and numeric change terms. Within the COPD cluster, lower FEV1predicted was associated with larger numeric and relative increases in muscle mass and superior relative improvements in maximal muscle strength. This was accompanied by similar changes in hallmarks of muscle biology such as rRNA-content↑, muscle fiber cross-sectional area↑, type IIX proportions↓, and changes in mRNA transcriptomics. Neither of the core outcome domains were differentially affected by resistance training load. CONCLUSIONS: COPD showed hitherto largely unrecognized responsiveness to resistance training, rejecting the notion of disease-related impairments and rather advocating such training as a potent measure to relieve pathophysiologies. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02598830. Registered November 6th 2015, https://clinicaltrials.gov/ct2/show/NCT02598830.

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.

Increased biological relevance of transcriptome analyses in human skeletal muscle using a model-specific pipeline.

BACKGROUND: Human skeletal muscle responds to weight-bearing exercise with significant inter-individual differences. Investigation of transcriptome responses could improve our understanding of this variation. However, this requires bioinformatic pipelines to be established and evaluated in study-specific contexts. Skeletal muscle subjected to mechanical stress, such as through resistance training (RT), accumulates RNA due to increased ribosomal biogenesis. When a fixed amount of total-RNA is used for RNA-seq library preparations, mRNA counts are thus assessed in different amounts of tissue, potentially invalidating subsequent conclusions. The purpose of this study was to establish a bioinformatic pipeline specific for analysis of RNA-seq data from skeletal muscles, to explore the effects of different normalization strategies and to identify genes responding to RT in a volume-dependent manner (moderate vs. low volume). To this end, we analyzed RNA-seq data derived from a twelve-week RT intervention, wherein 25 participants performed both low- and moderate-volume leg RT, allocated to the two legs in a randomized manner. Bilateral muscle biopsies were sampled from m. vastus lateralis before and after the intervention, as well as before and after the fifth training session (Week 2). RESULT: Bioinformatic tools were selected based on read quality, observed gene counts, methodological variation between paired observations, and correlations between mRNA abundance and protein expression of myosin heavy chain family proteins. Different normalization strategies were compared to account for global changes in RNA to tissue ratio. After accounting for the amounts of muscle tissue used in library preparation, global mRNA expression increased by 43-53%. At Week 2, this was accompanied by dose-dependent increases for 21 genes in rested-state muscle, most of which were related to the extracellular matrix. In contrast, at Week 12, no readily explainable dose-dependencies were observed. Instead, traditional normalization and non-normalized models resulted in counterintuitive reverse dose-dependency for many genes. Overall, training led to robust transcriptome changes, with the number of differentially expressed genes ranging from 603 to 5110, varying with time point and normalization strategy. CONCLUSION: Optimized selection of bioinformatic tools increases the biological relevance of transcriptome analyses from resistance-trained skeletal muscle. Moreover, normalization procedures need to account for global changes in rRNA and mRNA abundance.

Evaluation of foraminal cross-sectional area in lumbar spondylolisthesis using kinematic MRI.

PURPOSE: To evaluate the kinematic change of cross-sectional area of lumbar intervertebral foramen in degenerative lumbar spondylolisthesis patients using multi-positional MRI. METHODS: Multi-positional MRI was performed on 31 patients diagnosed with single or multilevel degenerative lumbar spondylolisthesis and 31 control patients without degenerative lumbar spondylolisthesis. Foraminal area (FA) was measured at the lumbar spondylolisthesis level in degenerative lumbar spondylolisthesis group and at L3-4, L4-5, and L5-S1 level in the control group. FA was measured bilaterally in neutral, flexion, and extension positions. The difference in FA between the groups was analyzed using Mann-Whitney U test, and the difference between positions within groups was analyzed using Wilcoxon signed-rank test. RESULTS: Degenerative lumbar spondylolisthesis group showed significantly smaller FA on both sides and on average in all three positions compared to the control group (p < 0.05 all). From neutral to flexion position, the change in FA was significantly smaller in the degenerative lumbar spondylolisthesis group than in the control group on both sides and on average (p < 0.005 all). In degenerative lumbar spondylolisthesis group, the FA showed no significant change from neutral to flexion, but showed significant change from neutral to extension (p < 0.005 all). CONCLUSIONS: FA in the degenerative lumbar spondylolisthesis group was smaller than in the control group. There was no difference in FA in degenerative lumbar spondylolisthesis group from neutral to flexion, only from neutral to extension. Patients with degenerative lumbar spondylolisthesis have a higher chance of developing foraminal stenosis.

Microsphere-Based Scaffolds in Regenerative Engineering.

Microspheres have long been used in drug delivery applications because of their controlled release capabilities. They have increasingly served as the fundamental building block for fabricating scaffolds for regenerative engineering because of their ability to provide a porous network, offer high-resolution control over spatial organization, and deliver growth factors/drugs and/or nanophase materials. Because they provide physicochemical gradients via spatiotemporal release of bioactive factors and nanophase ceramics, microspheres are a desirable tool for engineering complex tissues and biological interfaces. In this review we describe various methods for microsphere fabrication and sintering, and elucidate how these methods influence both micro- and macroscopic scaffold properties, with a special focus on the nature of sintering. Furthermore, we review key applications of microsphere-based scaffolds in regenerating various tissues. We hope to inspire researchers to join a growing community of investigators using microspheres as tissue engineering scaffolds so that their full potential in regenerative engineering may be realized.

Dehydration-responsive miRNAs in foxtail millet: genome-wide identification, characterization and expression profiling.

MAIN CONCLUSION: A set of novel and known dehydration-responsive miRNAs have been identified in foxtail millet. These findings provide new insights into understanding the functional role of miRNAs and their respective targets in regulating plant response to dehydration stress. MicroRNAs perform significant regulatory roles in growth, development and stress response of plants. Though the miRNA-mediated gene regulatory networks under dehydration stress remain largely unexplored in plant including foxtail millet (Setaria italica), which is a natural abiotic stress tolerant crop. To find out the dehydration-responsive miRNAs at the global level, four small RNA libraries were constructed from control and dehydration stress treated seedlings of two foxtail millet cultivars showing contrasting tolerance behavior towards dehydration stress. Using Illumina sequencing technology, 55 known and 136 novel miRNAs were identified, representing 22 and 48 miRNA families, respectively. Eighteen known and 33 novel miRNAs were differentially expressed during dehydration stress. After the stress treatment, 32 dehydration-responsive miRNAs were up-regulated in tolerant cultivar and 22 miRNAs were down-regulated in sensitive cultivar, suggesting that miRNA-mediated molecular regulation might play important roles in providing contrasting characteristics to these cultivars. Predicted targets of identified miRNAs were found to encode various transcription factors and functional enzymes, indicating their involvement in broad spectrum regulatory functions and biological processes. Further, differential expression patterns of seven known miRNAs were validated by northern blot and expression of ten novel dehydration-responsive miRNAs were confirmed by SL-qRT PCR. Differential expression behavior of five miRNA-target genes was verified under dehydration stress treatment and two of them also validated by RLM RACE. Overall, the present study highlights the importance of dehydration stress-associated post-transcriptional regulation governed by miRNAs and their targets in a naturally stress-tolerant model crop.

C2H2 type of zinc finger transcription factors in foxtail millet define response to abiotic stresses.

C2H2 type of zinc finger transcription factors (TFs) play crucial roles in plant stress response and hormone signal transduction. Hence considering its importance, genome-wide investigation and characterization of C2H2 zinc finger proteins were performed in Arabidopsis, rice and poplar but no such study was conducted in foxtail millet which is a C4 Panicoid model crop well known for its abiotic stress tolerance. The present study identified 124 C2H2-type zinc finger TFs in foxtail millet (SiC2H2) and physically mapped them onto the genome. The gene duplication analysis revealed that SiC2H2s primarily expanded in the genome through tandem duplication. The phylogenetic tree classified these TFs into five groups (I-V). Further, miRNAs targeting SiC2H2 transcripts in foxtail millet were identified. Heat map demonstrated differential and tissue-specific expression patterns of these SiC2H2 genes. Comparative physical mapping between foxtail millet SiC2H2 genes and its orthologs of sorghum, maize and rice revealed the evolutionary relationships of C2H2 type of zinc finger TFs. The duplication and divergence data provided novel insight into the evolutionary aspects of these TFs in foxtail millet and related grass species. Expression profiling of candidate SiC2H2 genes in response to salinity, dehydration and cold stress showed differential expression pattern of these genes at different time points of stresses.

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-.

Synergy between psychological impact and biochemical manifestation of stress among the COVID-19 pandemic-affected population.

Objective: Due to the COVID-19 pandemic, many countries around the world experienced an unprecedented increase in stress in the general population. Even after normal life has been reestablished, the new normal is punctuated by severely impacted vulnerable groups. Stress-associated symptoms display an intricate relationship with biochemical modulations, which coordinate the stress response. Identifying these biochemical factors is inherent to deciphering the mode of treatment needed to diminish the health-care gap resulting from the pandemic. Methods: We applied psychological measures using the perceived stress (PS) and COVID-19 anxiety (CA) scales and preventive health behavior (PHB) to evaluate stress in the general population. Biochemical markers of stress, that is, total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), cortisol, and C-reactive protein (CRP) were tested in the serum samples of the participants. Statistical analysis was carried out using SPSS version 22.0. Results: Stress scores for PS, CA, and PHB indicate the prevalence of moderate-to-high stress among participants, and a correlation between psychological stress and biochemical correlates, TAC, TBARS, cortisol, and CRP. Serum concentrations of TBARS, Cortisol, and CRP were found to be significantly increased, while the TAC was decreased across all stress types and levels. Our findings demonstrate a positive correlation between PS, CA, PHB TBARS, cortisol, and CRP and a strong negative correlation with TAC. Conclusion: The results of this study will help in tailoring targeted interventions and preventive regimes to mitigate COVID-19-associated anxiety and stress disorders prevailing even after the actual pandemic has subsided.

Identification of mirtrons in rice using MirtronPred: a tool for predicting plant mirtrons.

Studies from flies and insects have reported the existence of a special class of miRNA, called mirtrons that are produced from spliced-out introns in a DROSHA-independent manner. The spliced-out lariat is debranched and refolded into a stem-loop structure resembling the pre-miRNA, which can then be processed by DICER into mature ~21 nt species. The mirtrons have not been reported from plants. In this study, we present MirtronPred, a web based server to predict mirtrons from intronic sequences. We have used the server to predict 70 mirtrons in rice introns that were put through a stringent selection filter to shortlist 16 best sequences. The prediction accuracy was subsequently validated by northern analysis and RT-PCR of a predicted Os-mirtron-109. The target sequences for this mirtron were also found in the rice degradome database. The possible role of the mirtron in rice regulon is discussed. The MirtronPred web server is available at http://bioinfo.icgeb.res.in/mirtronPred.

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.

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.

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.