Arylazo-3,5-diphenylpyrazole Derivatives: Molecular Probes Exhibiting Reversible Light-induced Phase Transitions for Energy Storage and Direct Photolithographic Patterning.

We report azopyrazole photoswitches decorated with variable N-alkyl and alkoxy chains (for hydrophobic interactions) and phenyl substituents on the pyrazoles (enabling π-π stacking), showing efficient bidirectional photoswitching and reversible light-induced phase transition (LIPT). Extensive spectroscopic, microscopic, and diffraction studies and computations confirmed the manifestation of molecular-level interactions and photoisomerization into macroscopic changes leading to the LIPT phenomena. Using differential scanning calorimetric (DSC) studies, the energetics associated with those accompanying processes were estimated. The long half-lives of Z isomers, high energy contents for isomerization and phase transitions, and the stability of phases over an extended temperature range (-60 to 80 oC) make them excellent candidates for energy storage and release applications. Remarkably, the difference in the solubility of the distinct phases in one of the derivatives allowed us to utilize it as a photoresist in photolithography applications on diverse substrates.

Recent Advances in Nanomaterials Based Optical Sensors for the Detection of Melatonin and Serotonin.

In this review paper we discussed the detection of melatonin and serotonin by using various optical methods. Melatonin and serotonin are very necessary body hormones these are also called neuroregulatory hormones secreted by pineal gland in brain by pinealocytes and shape of pineal gland is cone like. Sensitive detection of melatonin and serotonin in pharmacological samples and human serum is crucial for human beings, lots of research publications available in literature for melatonin and serotonin and we overviewed these papers. We have deeply reviewed many research papers where sensitively sensing of melatonin and serotonin occurs, by using of various interfering agents and nanomaterials. This review aims presenting colorimetry, fluorometry and spectrophotometric detection of melatonin (MEL) and serotonin (SER) by using different metal oxides, carbon nanomaterials (nanosheets, nanorods, nanofibers) and many other agents. Nanomaterials typically possess favourable optical, electrical and mechanical characteristics, they provide up new avenues for enhancing the efficacy of sensors. It is crucial to provide an optical sensors platform that is dependable, sensitive and low price. The development of sensors and biosensors to use nanomaterials for neurotransmitters has advanced significantly in recent years. There are currently many developing biomarkers in biological fluids, and bionanomaterial-based biosensor systems, as well as clinical and pharmacological settings, have garnered significant interest. Biomarkers have been found using optical devices in a quick, selective and sensitive manner. Our aim is to compile all the data that already published on MEL, SER sensing and comparison of each method, we mainly focused on principle, observations, sensitivity, selectivity, limit of detection, mechanism behind the reaction, effect of temperature, pH and concentration. In the last of this paper, we discuss some challenges of these methods and future projects.

Highly Sensitive and Selective Fluorescence and Smartphone-Based Sensor for Detection of Rutin Using Boron Nitrogen Co-doped Graphene Quantum Dots.

This research explores the fluorescence properties and photostability of boron nitrogen co-doped graphene quantum dots (BN-GQDs), evaluating their effectiveness as sensors for rutin (RU). BN-GQDs are biocompatible and exhibit notable absorbance and fluorescence characteristics, making them suitable for sensing applications. The study utilized various analytical techniques to investigate the chemical composition, structure, morphology, optical attributes, elemental composition, and particle size of BN-GQDs. Techniques included X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The average particle size of the BN-GQDs was determined to be approximately 3.5 ± 0.3 nm. A clear correlation between the emission intensity ratio and RU concentration was identified across the range of 0.42 to 4.1 µM, featuring an impressively low detection limit (LOD) of 1.23 nM. The application of BN-GQDs as fluorescent probes has facilitated the development of a highly sensitive and selective RU detection method based on Förster resonance energy transfer (FRET) principles. This technique leverages emission at 465 nm. Density Functional Theory (DFT) analyses confirm that FRET is the primary mechanism behind fluorescence quenching, as indicated by the energy levels of the lowest unoccupied molecular orbitals (LUMOs) of BN-GQDs and RU. The method's effectiveness has been validated by measuring RU concentrations in human serum samples, showing a recovery range between 97.8% and 103.31%. Additionally, a smartphone-based detection method utilizing BN-GQDs has been successfully implemented, achieving a detection limit (LOD) of 49 nM.

Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by deficits in communication and behavior. Increasing evidence suggests that the microbiota-gut-brain axis and the likely related immune imbalance may play a role in the development of this disorder. Gastrointestinal deficits and gut microbiota dysfunction have been linked to the development or severity of autistic behavior. Therefore, treatments that focus on specific diets may improve gastrointestinal function and aberrant behavior in individuals with ASD. In this study, we investigated whether a diet containing specific prebiotic fibers, namely, 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1), can mitigate the adverse effects of in utero exposure to valproic acid (VPA) in mice. Pregnant BALB/cByJ dams were injected with VPA (600 mg/kg, sc.) or phosphate-buffered saline (PBS) on gestational day 11 (G11). Male offspring were divided into four groups: (1) in utero PBS-exposed with a control diet, (2) in utero PBS-exposed with GOS/FOS diet, (3) in utero VPA-exposed with a control diet, and (4) in utero VPA-exposed with GOS/FOS diet. Dietary intervention started from birth and continued throughout the duration of the experiment. We showed that the prebiotic diet normalized VPA-induced alterations in male offspring, including restoration of key microbial taxa, intestinal permeability, peripheral immune homeostasis, reduction of neuroinflammation in the cerebellum, and impairments in social behavior and cognition in mice. Overall, our research provides valuable insights into the gut-brain axis involvement in ASD development. In addition, dietary interventions might correct the disbalance in gut microbiota and immune responses and, ultimately, might improve detrimental behavioral outcomes in ASD.

FusionGDB 2.0: fusion gene annotation updates aided by deep learning.

A knowledgebase of the systematic functional annotation of fusion genes is critical for understanding genomic breakage context and developing therapeutic strategies. FusionGDB is a unique functional annotation database of human fusion genes and has been widely used for studies with diverse aims. In this study, we report fusion gene annotation updates aided by deep learning (FusionGDB 2.0) available at https://compbio.uth.edu/FusionGDB2/. FusionGDB 2.0 has substantial updates of contents such as up-to-date human fusion genes, fusion gene breakage tendency score with FusionAI deep learning model based on 20 kb DNA sequence around BP, investigation of overlapping between fusion breakpoints with 44 human genomic features across five cellular role's categories, transcribed chimeric sequence and following open reading frame analysis with coding potential based on deep learning approach with Ribo-seq read features, and rigorous investigation of the protein feature retention of individual fusion partner genes in the protein level. Among ∼102k fusion genes, about 15k kept their ORF as In-frames, which is two times compared to the previous version, FusionGDB. FusionGDB 2.0 will be used as the reference knowledgebase of fusion gene annotations. FusionGDB 2.0 provides eight categories of annotations and it will be helpful for diverse human genomic studies.

Bistable Aryl Azopyrazolium Ionic Photoswitches in Water.

We report a new class of arylazopyrazolium-based ionic photoswitches (AAPIPs). These AAPIPs with different counter ions have been accessed through a modular synthetic approach in high yields. More importantly, the AAPIPs exhibit excellent reversible photoswitching and exceptional thermal stability in water. The effects of solvents, counter ions, substitutions, concentration, pH, and glutathione (GSH) have been evaluated using spectroscopic investigations. The results revealed that the bistability of studied AAPIPs is robust and near quantitative. The thermal half-life of Z isomers is extremely high in water (up to years), and it can be lowered electronically by the electron-withdrawing groups or highly basic pH.

Machine learning-driven blood transcriptome-based discovery of SARS-CoV-2 specific severity biomarkers.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by rapidly evolving variants of severe acute respiratory syndrome coronavirus (SARS-CoV-2), continues to be a global health threat. SARS-CoV-2 infection symptoms often intersect with other nonsevere respiratory infections, making early diagnosis challenging. There is an urgent need for early diagnostic and prognostic biomarkers to predict severity and reduce mortality when a sudden outbreak occurs. This study implemented a novel approach of integrating bioinformatics and machine learning algorithms over publicly available clinical COVID-19 transcriptome data sets. The robust 7-gene biomarker identified through this analysis can not only discriminate SARS-CoV-2 associated acute respiratory illness (ARI) from other types of ARIs but also can discriminate severe COVID-19 patients from nonsevere COVID-19 patients. Validation of the 7-gene biomarker in an independent blood transcriptome data set of longitudinal analysis of COVID-19 patients across various stages of the disease showed that the dysregulation of the identified biomarkers during severe disease is restored during recovery, showing their prognostic potential. The blood biomarkers identified in this study can serve as potential diagnostic candidates and help reduce COVID-19-associated mortality.

Host and viral non-coding RNAs in dengue pathogenesis.

Dengue virus (DENV) is a mosquito-borne flavivirus that causes frequent outbreaks in tropical countries. Due to the four different serotypes and ever-mutating RNA genome, it is challenging to develop efficient therapeutics. Early diagnosis is crucial to prevent the severe form of dengue, leading to mortality. In the past decade, rapid advancement in the high throughput sequencing technologies has shed light on the crucial regulating role of non-coding RNAs (ncRNAs), also known as the "dark matter" of the genome, in various pathological processes. In addition to the human host ncRNAs like microRNAs and circular RNAs, DENV also produces ncRNAs such as subgenomic flaviviral RNAs that can modulate the virus life cycle and regulate disease outcomes. This review outlines the advances in understanding the interplay between the human host and DENV ncRNAs, their regulation of the innate immune system of the host, and the prospects of the ncRNAs in clinical applications such as dengue diagnosis and promising therapeutics.

Alterations in the Stool Microbiome in Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is associated with brain injury in newborns and may lead to disability or death. Mild therapeutic hypothermia (TH) is an effective neuroprotective intervention and an established standard of care in western countries. The gut microbiome, the genomic and physicochemical contribution of the gut microbiota, serves important functions and is increasingly recognized as a major influencer on development. The impact of HIE and TH on the evolving gut microbiota of the newborn remains to be elucidated. OBJECTIVE: The objective of this study was to carry out an exploratory study on the effects of HIE and TH on the gut microbiome in term neonates. METHODS AND RESULTS: Stool samples were obtained from 28 newborns with HIE (median age 68 h) undergoing TH on the neonatal unit (HIE TH group), with a follow-on stool sample available for 20 of these babies (median age 151 h). For comparison, a single stool specimen was obtained from 19 healthy newborns on the postnatal ward (median age 34 h). The microbiota composition was determined using established microbial DNA extraction and 16S rRNA gene sequencing methodology. There was no difference in the mode of delivery or the method of feeding the newborns, once established, between the 2 groups. All the infants in the HIE TH group had received antibiotics compared to only one of the controls. A lower α-diversity, quantified by the Shannon diversity index, was noted in the microbiota of the HIE TH group in comparison to the control group. The HIE TH group had a higher mean relative abundance (MRA) of facultative anaerobes and aerobes such as Staphylococcus species and a lower MRA of strict anaerobes, such as members of the Bacteroides genus, compared to the control. Also, there was a significant reduction in the MRA of the genus Bifidobacterium in the HIE TH group. Although the mode of delivery exerts a profound influence on the gut microbiota of the newborn, distance-based redundancy analysis showed that TH may exert an independent influence. This study could not determine the independent contribution of the use of antibiotics or the neonatal intensive care unit environment. CONCLUSION: In this study, we demonstrate an alteration in the microbiota composition in newborns undergoing TH for HIE.

Poly IC triggers a cathepsin D- and IPS-1-dependent pathway to enhance cytokine production and mediate dendritic cell necroptosis.

RIG-I-like receptors (RLRs) sense virus-derived RNA or polyinosinic-polycytidylic acid (poly IC) to exert antiviral immune responses. Here, we examine the mechanisms underlying the adjuvant effects of poly IC. Poly IC was taken up by dendritic cells (DCs), and it induced lysosomal destabilization, which, in turn, activated an RLR-dependent signaling pathway. Upon poly IC stimulation, cathepsin D was released into the cytoplasm from the lysosome to interact with IPS-1, an adaptor molecule for RLRs. This interaction facilitated cathepsin D cleavage of caspase 8 and the activation of the transcription factor NF-κB, resulting in enhanced cytokine production. Further recruitment of the kinase RIP-1 to this complex initiated the necroptosis of a small number of DCs. HMGB1 released by dying cells enhanced IFN-ß production in concert with poly IC. Collectively, these findings suggest that cathepsin D-triggered, IPS-1-dependent necroptosis is a mechanism that propagates the adjuvant efficacy of poly IC.

Structure-Property Relationship for Visible Light Bidirectional Photoswitchable Azoheteroarenes and Thermal Stability of Z-Isomers.

A modular approach has been adopted to synthesize a wide range of visible light-driven photoswitchable azoheteroarenes. In this regard, we considered ortho substitution of cyclic amines in the aryl ring and varied substitution patterns. Using detailed spectroscopic studies, we established a relationship between structure and photoswitching ability and also half-lives of the Z-isomers. Through this, we envision tunable and bidirectional longer wavelength photoswitches.

Tuning of Bistability, Thermal Stability of the Metastable States, and Application Prospects in the C3 -Symmetric Designs of Multiple Azo(hetero)arenes Systems.

Light-responsive molecular systems with multiple photoswitches in C3 -symmetric designs have enormous application potential. The design part of such molecular systems is critical due to its influence in several properties associated with the photoswitches. In order to tune, and in the evaluation of the design-property relationship, we synthesized 18 tripodal systems with variations in the core, linkers, connectivity, and azo(hetero)arene photoswitches. Through extensive spectroscopic and computational studies, we envisaged the factors controlling near-quantitative photoisomerization in both the directions (bistability) and the thermal stability of the metastable states. Furthermore, we also evaluated the impact of designs in obtaining reversible photo-responsive sol-gel phase transitions, solvatochromism, photo- and thermochromism.

Cross-amplification of ungulate microsatellite markers in the endemic Indian antelope or blackbuck (Antilope cervicapra) for population monitoring and conservation genetics studies in south Asia.

The Indian antelope or blackbuck (Antilope cervicapra) is endemic to the Indian subcontinent, inhabiting scrublands and dry grasslands. Most of the blackbuck populations are small, isolated, and threatened by habitat fragmentation and degradation. Management of such disjunct populations requires genetic characterization, which is critical for assessing hazards of stochastic events and inbreeding. Addressing the scarcity of such information on the blackbuck, we describe a novel panel of microsatellite markers that could be used to monitor blackbuck demography and population genetic parameters using non-invasive faecal sampling. We screened microsatellites (n = 40) that had been reported to amplify in bovid and cervid species using faecal samples of the blackbuck collected from Kaimoor Wildlife Sanctuary, Uttar Pradesh, India and its vicinities. We selected 12 markers for amplification using faecal DNA extracts (n = 140) in three multiplex reactions. We observed a mean amplification success rate of 72.4% across loci (92.1-25.7%) with high allele diversity (mean number of alleles/locus = 8.67 ± 1.03). Mean genotyping error rates across the markers were low to moderate (allelic drop-out rate = 0.09; false allele rate = 0.11). The proportions of first- and second-order relatives in the study population were 0.69% and 6.21%, respectively. Based on amplification success, genotyping error rates and the probability of identity (PID), we suggest (i) a panel of five microsatellite markers (cumulative PID = 1.24 × 10-5) for individual identification and population monitoring and (ii) seven additional markers for conservation genetics studies. This study provides essential tools capable of augmenting blackbuck conservation strategies at the landscape level, integral to protecting the scrubland-grassland ecosystem.

Sonographic pattern of median nerve enlargement in Hansen's neuropathy.

OBJECTIVES: Median nerve enlargement in leprosy seems to be more proximal than in carpal tunnel syndrome (CTS), but this feature has not been studied systematically. The aim of the study was to compare the sites of median nerve enlargement in patients with leprosy with that of patients with CTS. MATERIALS AND METHODS: Transverse sections of the median nerve were recorded from wrist to the mid-forearm (at distal wrist crease and at 2-cm: M1, 4-cm: M2, 6-cm: M3, 8-cm: M4 and 10-cm: M5, proximal to the distal wrist crease in the forearm) in patients with leprosy, CTS and healthy subjects using high-resolution ultrasound. RESULTS: Twenty-six patients each with leprosy and CTS were compared with healthy controls. Patients with leprosy included 6 (23.1%), 7 (26.9%), 7 (26.9%) and 6 (23.1%) patients with borderline tuberculoid, borderline-borderline, borderline lepromatous and lepromatous leprosy, respectively. Cross-sectional area (CSA) of median nerve was increased in all patients with leprosy as compared to healthy controls at all points of measurement. CSA was higher among patients with leprosy as compared to CTS at all points except at the wrist. In patients with leprosy, the maximal enlargement was noted 2-cm (M1) proximal to the wrist crease with gradual tapering of the CSA proximally (p < .05). In contrast, in patients with CTS the median nerve was maximally enlarged at the distal wrist crease (p<.05). CONCLUSIONS: Median nerve enlargement 2-cm proximal to the distal wrist crease distinguishes leprosy from CTS. This important discriminating sign can be used at point-of-care to identify patients with leprosy.

Emotion Recognition Using Electrodermal Activity Signals and Multiscale Deep Convolutional Neural Network.

In this work, an attempt has been made to classify emotional states using electrodermal activity (EDA) signals and multiscale convolutional neural networks. For this, EDA signals are considered from a publicly available "A Dataset for Emotion Analysis using Physiological Signals" (DEAP) database. These signals are decomposed into multiple-scales using the coarse-grained method. The multiscale signals are applied to the Multiscale Convolutional Neural Network (MSCNN) to automatically learn robust features directly from the raw signals. Experiments are performed with the MSCNN approach to evaluate the hypothesis (i) improved classification with electrodermal activity signals, and (ii) multiscale learning captures robust complementary features at a different scale. Results show that the proposed approach is able to differentiate various emotional states. The proposed approach yields a classification accuracy of 69.33% and 71.43% for valence and arousal states, respectively. It is observed that the number of layers and the signal length are the determinants for the classifier performance. The performance of the proposed approach outperforms the single-layer convolutional neural network. The MSCNN approach provides end-to-end learning and classification of emotional states without additional signal processing. Thus, it appears that the proposed method could be a useful tool to assess the difference in emotional states for automated decision making.

RelB suppresses type I Interferon signaling in dendritic cells.

Type I Interferon (IFN) signaling plays a critical role in dendritic cell (DC) development and functions. Inhibition of hyper type I IFN signaling promotes cDC2 subtype development. Relb is essential to development of cDC2 subtype and here we analyzed its effect on type I IFN signaling in DCs. We show that Relb suppresses the homeostatic type I IFN signaling in cDC2 cultures. TLR stimulation of FL-DCs led to RelB induction coinciding with fall in IFN signatures; conforming with the observation Relb expression reduced TLR stimulated IFN induction along with decrease in ISGs. Towards understanding mechanism, we show that effects of RelB are mediated by increased levels of IκBα. We demonstrate that RelB dampened antiviral responses by lowering ISG levels and the defect in cDC2 development in RelB null mice can be rescued in Ifnar1-/- background. Overall, we propose a novel role of RelB as a negative regulator of the type I IFN signaling pathway; fine tuning development of cDC2 subtype.

dropClust: efficient clustering of ultra-large scRNA-seq data.

Droplet based single cell transcriptomics has recently enabled parallel screening of tens of thousands of single cells. Clustering methods that scale for such high dimensional data without compromising accuracy are scarce. We exploit Locality Sensitive Hashing, an approximate nearest neighbour search technique to develop a de novo clustering algorithm for large-scale single cell data. On a number of real datasets, dropClust outperformed the existing best practice methods in terms of execution time, clustering accuracy and detectability of minor cell sub-types.

Prediction and analysis of COVID-19 positive cases using deep learning models: A descriptive case study of India.

In this paper, Deep Learning-based models are used for predicting the number of novel coronavirus (COVID-19) positive reported cases for 32 states and union territories of India. Recurrent neural network (RNN) based long-short term memory (LSTM) variants such as Deep LSTM, Convolutional LSTM and Bi-directional LSTM are applied on Indian dataset to predict the number of positive cases. LSTM model with minimum error is chosen for predicting daily and weekly cases. It is observed that the proposed method yields high accuracy for short term prediction with error less than 3% for daily predictions and less than 8% for weekly predictions. Indian states are categorised into different zones based on the spread of positive cases and daily growth rate for easy identification of novel coronavirus hot-spots. Preventive measures to reduce the spread in respective zones are also suggested. A website is created where the state-wise predictions are updated using the proposed model for authorities,researchers and planners. This study can be applied by other countries for predicting COVID-19 cases at the state or national level.

MicroRNA hsa-miR-324-5p Suppresses H5N1 Virus Replication by Targeting the Viral PB1 and Host CUEDC2.

MicroRNAs (miRNAs) are small noncoding RNAs that are crucial posttranscriptional regulators for host mRNAs. Recent studies indicate that miRNAs may modulate host response during RNA virus infection. However, the role of miRNAs in immune response against H5N1 infection is not clearly understood. In this study, we showed that expression of cellular miRNA miR-324-5p was downregulated in A549 cells in response to infection with RNA viruses H5N1, A/PR8/H1N1, and Newcastle disease virus (NDV) and transfection with poly(I·C). We found that miR-324-5p inhibited H5N1 replication by targeting the PB1 viral RNA of H5N1 in host cells. In addition, transcriptome analysis revealed that miR-324-5p enhanced the expression of type I interferon, type III interferon, and interferon-inducible genes (ISGs) by targeting CUEDC2, the negative regulator of the JAK1-STAT3 pathway. Together, these findings highlight that the miR-324-5p plays a crucial role in host defense against H5N1 by targeting viral PB1 and host CUEDC2 to inhibit H5N1 replication.IMPORTANCE Highly pathogenic influenza A virus (HPAIV) continues to pose a pandemic threat globally. From 2003 to 2017, H5N1 HPAIV caused 453 human deaths, giving it a high mortality rate (52.74%). This work shows that miR-324-5p suppresses H5N1 HPAIV replication by directly targeting the viral genome (thereby inhibiting viral gene expression) and cellular CUEDC2 gene, the negative regulator of the interferon pathway (thereby enhancing antiviral genes). Our study enhances the knowledge of the role of microRNAs in the cellular response to viral infection. Also, the study provides help in understanding how the host cells utilize small RNAs in controlling the viral burden.

IL-10 suppresses TNF-α-induced expression of human aromatase gene in mammary adipose tissue.

White adipose tissue inflammation is linked with increased aromatase gene expression and estrogen production, a major risk factor for breast cancer in obese postmenopausal women. TNF-α, a proinflammatory cytokine, is a key driver of aromatase promoter I.4-mediated expression in adipose tissue. In this study, we have shown that IL-10, an anti-inflammatory cytokine, suppressed both TNF-α-stimulated human aromatase reporter-luciferase (hARO-Luc) expression in mouse bone marrow mesenchymal stromal cells and aromatase gene expression in human breast adipose stromal cells (ASCs). IL-10 blocked TNF-α-stimulated ERK1/2 activation in ASCs, suggesting an inhibitory effect through the MAPK signaling pathway. The links among obesity, IL-10, and aromatase were confirmed in ovariectomized (OVX) hARO-Luc mice, where increased adiposity was associated with upregulation of aromatase reporter activity and reduced IL-10 level in the mammary fat pad. OVX mice also exhibited changes in gut microbiota, similar to that in obese women, indicating altered immune function. In summary, our results suggest that increased adiposity, induced by the lack of ovarian hormones, results in enhanced expression of aromatase in mammary adipose tissue, mediated by reduction in local IL-10. These findings may bring new insights into the mechanisms involved in the development of postmenopausal breast cancer, as well as novel approaches for prevention.-Martínez-Chacón, G., Brown, K. A., Docanto, M. M., Kumar, H., Salminen, S., Saarinen, N., Mäkelä, S. IL-10 suppresses TNF-α-induced expression of human aromatase gene in mammary adipose tissue.