Japanese encephalitis virus infection causes reactive oxygen species-mediated skeletal muscle damage.

Skeletal muscle wasting is a clinically proven pathology associated with Japanese encephalitis virus (JEV) infection; however, underlying factors that govern skeletal muscle damage are yet to be explored. The current study aims to investigate the pathobiology of skeletal muscle damage using a mouse model of JEV infection. Our study reveals a significant increment in viral copy number in skeletal muscle post-JEV infection, which is associated with enhanced skeletal muscle cell death. Molecular and biochemical analysis confirms NOX2-dependent generation of reactive oxygen species, leading to autophagy flux inhibition and cell apoptosis. Along with this, an alteration in mitochondrial dynamics (change in fusion and fission process) and a decrease in the total number of mitochondria copies were found during JEV disease progression. The study represents the initial evidence of skeletal muscle damage caused by JEV and provides insights into potential avenues for therapeutic advancement.

Targeting cellular plasticity: esculetin-driven reversion of stem cell-like characteristics and EMT phenotype in transforming cells with sequential p53/p73 knockdowns.

The intricate interplay of cancer stem cell plasticity, along with the bidirectional transformation between epithelial-mesenchymal states, introduces further intricacy to offer insights into newer therapeutic approaches. Differentiation therapy, while successful in targeting leukemic stem cells, has shown limited overall success, with only a few promising instances. Using colon carcinoma cell strains with sequential p53/p73 knockdowns, our study underscores the association between p53/p73 and the maintenance of cellular plasticity. Morphological alterations corresponding with cell surface marker expressions, transcriptome analysis and functional assays were performed to access stemness and EMT (Epithelial-Mesenchymal Transition) characteristics in the spectrum of cells exhibiting sequential p53 and p73 knockdowns. Notably, our investigation explores the effectiveness of esculetin in reversing the shift from an epithelial to a mesenchymal phenotype, characterized by stem cell-like traits. Esculetin significantly induces enterocyte differentiation and promotes epithelial cell polarity by altering Wnt axes in Cancer Stem Cell-like cells characterized by high mesenchymal features. These results align with our previous findings in leukemic blast cells, establishing esculetin as an effective differentiating agent in both Acute Myeloid Leukemia (AML) and solid tumor cells.

Next-generation therapeutics for rare genetic disorders.

The therapeutic potential of the human genome has been explored through the development of next-generation therapeutics, which have had a high impact on treating genetic disorders. Classical treatments have traditionally focused on common diseases that require repeated treatments. However, with the recent advancements in the development of nucleic acids, utilizing DNA and RNA to modify or correct gene expression in genetic disorders, there has been a paradigm shift in the treatment of rare diseases, offering more potential one-time cure options. Advanced technologies that use CRISPR-Cas 9, antisense oligonucleotides, siRNA, miRNA, and aptamers are promising tools that have achieved successful breakthroughs in the treatment of various genetic disorders. The advancement in the chemistry of these molecules has improved their efficacy, reduced toxicity, and expanded their clinical use across a wide range of tissues in various categories of human disorders. However, challenges persist regarding the safety and efficacy of these advanced technologies in translating into clinical practice. This review mainly focuses on the potential therapies for rare genetic diseases and considers how next-generation techniques enable drug development to achieve long-lasting curative effects through gene inhibition, replacement, and editing.

Modulation of various host cellular machinery during COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) emerged in December 2019, causing a range of respiratory infections from mild to severe. This resulted in the ongoing global COVID-19 pandemic, which has had a significant impact on public health. The World Health Organization declared COVID-19 as a global pandemic in March 2020. Viruses are intracellular pathogens that rely on the host's machinery to establish a successful infection. They exploit the gene expression machinery of host cells to facilitate their own replication. Gaining a better understanding of gene expression modulation in SARS-CoV2 is crucial for designing and developing effective antiviral strategies. Efforts are currently underway to understand the molecular-level interaction between the host and the pathogen. In this review, we describe how SARS-CoV2 infection modulates gene expression by interfering with cellular processes, including transcription, post-transcription, translation, post-translation, epigenetic modifications as well as processing and degradation pathways. Additionally, we emphasise the therapeutic implications of these findings in the development of new therapies to treat SARS-CoV2 infection.

Modern Clinical Mycobacterium tuberculosis Strains Leverage Type I IFN Pathway for a Proinflammatory Response in the Host.

Host phagocytes respond to infections by innate defense mechanisms through metabolic shuffling to restrict the invading pathogen. However, this very plasticity of the host provides an ideal platform for pathogen-mediated manipulation. In the human (THP1/THP1 dual/PBMC-derived monocyte-derived macrophages) and mouse (RAW264.7 and C57BL/6 bone marrow-derived) macrophage models of Mycobacterium tuberculosis infection, we have identified an important strategy employed by clinical lineages in regulating the host immune-metabolism axis. We show greater transit via the macrophage phagosomal compartments by Mycobacterium tuberculosis strains of lineage: M. tuberculosis lineage 3 is associated with an ability to elicit a strong and early type I IFN response dependent on DNA (in contrast with the protracted response to lineage: M. tuberculosis lineage 1). This augmented IFN signaling supported a positive regulatory loop for the enhanced expression of IL-6 consequent to an increase in the expression of 25-hydroxycholesterol in macrophages. This amplification of the macrophage innate response-metabolic axis incumbent on a heightened and early type I IFN signaling portrays yet another novel aspect of improved intracellular survival of clinical M. tuberculosis strains.

Exposure to thiourea during the early stages of development impedes the formation of the swim bladder in zebrafish larvae.

Thiourea, a widely used agrochemical, is known to inhibit the activity of thyroid peroxidase, a key enzyme in the biosynthetic pathway of thyroid hormones. Thyroid insufficiency compromises the basal metabolic rate in warm-blooded organisms and embryonic development in vertebrates. In this study, we looked for developmental defects by exposing the zebrafish embryos to an environmentally relevant dose of thiourea (3 mg/mL). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to validate thiourea's presence in the treated zebrafish embryos. Structural anomalies like bent tail and pericardial edema were noticed in 96-h post-fertilization (hpf) larvae. On histological examination, underdeveloped swim bladder was noticed in 96 hpf larvae exposed to 3 mg/mL thiourea. The treated larvae also failed to follow the characteristic swimming behavior in response to stimuli due to defective swim bladder. Swim bladder being homologous to the lung of tetrapod, the role of Bmp4, a major regulator of lung development, was studied along with the associated regulatory genes. Gene expression analysis revealed that thiourea administration led to the downregulation of bmp4, shh, pcna, anxa5, acta2, and the downstream effector snail3 but the upregulation of caspase3. The protein expression showed a similar trend, wherein Bmp4, Shh, and Pcna were downregulated, but Cleaved Caspase3 showed an increased expression in the treated group. Therefore, it is prudent to presume that exposure to thiourea significantly reduces the expression of Bmp4 and other key regulators; hence, the larvae fail to develop a swim bladder, a vital organ that regulates buoyancy.

Rice straw waste-based green synthesis and characterizations investigation of Fe-MoS2-derived nanohybrid.

In present work, synthesis of a nanohybrid material using Fe and MoS2 has been performed via a cost-effective and environmentally friendly route for sustainable manufacturing innovation. Rice straw extract was prepared and used as a reducing and chelating agent to synthesize the nanohybrid material by mixing it with molybdenum disulfide (MoS2) and ferric nitrate [Fe (NO3)3.9H2O], followed by heating and calcination. The X-ray diffraction (XRD) pattern confirms the formation of a nanohybrid consisting of monoclinic Fe2(MoO4)3, cubic Fe2.957O4, and orthorhombic FeS with 86% consisting of Fe2(MoO4)3. The properties were analyzed through Fourier-transformed infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results of the dynamic light scattering (DLS) study revealed a heterogeneous size distribution, with an average particle size of 48.42 nm for 18% of particles and 384.54 nm for 82% of particles. Additionally, the zeta potential was measured to be -18.88 mV, suggesting moderate stability. X-ray photoelectron spectroscopy (XPS) results confirmed the presence of both Fe2+ and Fe3+ oxidation states along with the presence of Molybdenum (Mo), oxygen (O), and Sulphur (S). The prepared nanohybrid material exhibited a band gap of 2.95 eV, and the photoluminescence intensity increased almost twice that of bare MoS2. The present work holds potential applications in photo luminescent nanoplatform for biomedical applications.

Exploring a facile preparation method for Co-Ni/MoS2-derived nanohybrid from wheat straw extract and its physicochemical properties.

This study presents a novel approach for the fabrication of a Co,Ni/MoS2-derived nanohybrid material using wheat straw extract. The facile synthesis method involves a sol-gel process, followed by calcination, showcasing the potential of agricultural waste as a sustainable reducing and chelating reagent. The as-prepared nanohybrid has been characterized using different techniques to analyse its physicochemical properties. X-ray diffraction analysis confirmed the successful synthesis of the nanohybrid material, identifying the presence of NiMoO4, CoSO4 and Mo17O47 as its components. Fourier-transform infrared spectroscopy differentiated the functional groups present in the wheat straw biomass and those in the nanohybrid material, highlighting the formation of metal-oxide and sulphide bonds. Scanning electron microscopy revealed a heterogeneous morphology with agglomerated structures and a grain size of around 70 nm in the nanohybrid. Energy-dispersive X-ray spectroscopy analysis shows the composition of elements with weight percentages of (Mo) 9.17%, (S) 6.21%, (Co) 12.48%, (Ni) 12.18% and (O) 50.46% contributing to its composition. Electrochemical analysis performed through cyclic voltammetry showcased the exceptional performance of the nanohybrid material as compared with MoS2, suggesting its possible applications for designing biosensors and related technologies. Thus, the research study presented herein underscores the efficient utilization of natural resources for the development of functional nanomaterials with promising applications in various fields. This study paves a way for manufacturing innovation along with advancement of novel synthesis method for sustainable nanomaterial for future technological developments.

Incidence of Different Characters of Neuropathic Pain in Cancer Patients Coming to Tertiary Care Centre in North India Over A Period of 1 Year - An Observational Study.

Objectives: Pain is classified as nociceptive, neuropathic, or nociplastic. Neuropathic pain presents as variable phenotypes (characters) based on specific aetiology and pathophysiology. This study aimed to find out among cancer patients the incidence of different phenotypes of neuropathic pain and form specific phenotypic clusters based on the underlying neurophysiology and association of sensory profile with various organ systems - A prospective observational study. Materials and methods: The Institutional Ethical Committee clearance (IEC code: 2020-49-MD-EXP-15) https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=44886&EncHid=88651.15716&userName=CTRI/2020/09/027964 approval was obtained. After written and informed consent, patients of age group 18-80 years, registering in the pain and palliative outpatient department or radiotherapy department with complaints of pain and not taking any anti-neuropathic pain medications, were enrolled. They were assessed using Leeds assessment of neuropathic symptoms and signs (LANSS) pain score, and a score of >12 was eligible for assessment of neuropathic pain phenotypes. Results: Out of 210 cancer patients complaining of pain, a neuropathic component with LANSS >12 was found in 73 (34.76%). The most predominant phenotypes, allodynia> tingling> pricking = burning, were found in 72.60%, 56.16%, and 43.84% of patients, respectively. Phenotypes were clustered into Nodes 1 and 2 based on clinically significant separation of phenotypes. Node 1 had neuropathic pain of spontaneous origin found predominantly in gastrointestinal tract (GIT) and genitourinary tract (GUT) cancers. Node 2 had stimulus-evoked negative and positive characters which occurred in head and neck, thoracic, and spinal metastatic cancers. Conclusion: Careful patient assessment reveals the incidence of neuropathic pain in 34.76%; allodynia and tingling astable the most prominent phenotypes. Broadly, sensory characters were clustered into spontaneous and stimulus-evoked sensations with GIT and GUT cancers presenting with Node 1 symptoms.

Applications of some advanced sequencing, analytical, and computational approaches in medicinal plant research: a review.

The potential active chemicals found in medicinal plants, which have long been employed as natural medicines, are abundant. Exploring the genes responsible for producing these compounds has given new insights into medicinal plant research. Previously, the authentication of medicinal plants was done via DNA marker sequencing. With the advancement of sequencing technology, several new techniques like next-generation sequencing, single molecule sequencing, and fourth-generation sequencing have emerged. These techniques enshrined the role of molecular approaches for medicinal plants because all the genes involved in the biosynthesis of medicinal compound(s) could be identified through RNA-seq analysis. In several research insights, transcriptome data have also been used for the identification of biosynthesis pathways. miRNAs in several medicinal plants and their role in the biosynthesis pathway as well as regulation of the disease-causing genes were also identified. In several research articles, an in silico study was also found to be effective in identifying the inhibitory effect of medicinal plant-based compounds against virus' gene(s). The use of advanced analytical methods like spectroscopy and chromatography in metabolite proofing of secondary metabolites has also been reported in several recent research findings. Furthermore, advancement in molecular and analytic methods will give new insight into studying the traditionally important medicinal plants that are still unexplored.

The Effect of Cadmium Tolerant Plant Growth Promoting Rhizobacteria on Plant Growth Promotion and Phytoremediation: A Review.

Cadmium (Cd) is a heavy metal of considerable toxicity with destructive impacts on plants, microbes and environments. Its toxicity is due to mishandling and manual hazards in plants and is primarily observed within the soil to cause decline of plants and microbial activity inside the rhizosphere. Cadmium accumulation in crops and the probability of Cd entering the food chain are grave for public health in the worldwide. Cadmium toxicity leads to depletion in seed germination, initial seedling growth, plant biomass, chlorosis, necrosis, hindrance of photosynthetic machinery and other physiological and biological activities in plants. Cadmium triggers the reactive oxygen species (ROS) that influences gene mutation and DNA damage that affects the cell cycle and cell division. Cd toxicity altered the levels of phenolic compounds, carbohydrates, glycine betaine, proline and organic acids in crops. Under stress conditions, the plant growth promoting rhizobacteria (PGPR) have various properties such as enzymatic activities, plant growth hormones production, phosphate solubilization, siderophores production and chelating agents that help the plants tolerate against Cd stress and also increase phenolic compound levels and osmolytes. Hence, this review highlights the crucial role of cadmium tolerant PGPR for crop production, declining metal phytoavailability and enhancing morphological and physiological boundaries of plants under stress conditions. It could be an environment friendly and cost effective technology under sustainable crop production.

Microfluidic Isolation of Disseminated Tumor Cells from the Bone Marrow of Breast Cancer Patients.

Disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer (BC) patients are putative precursors of metastatic disease, and their presence is associated with an adverse clinical outcome. To achieve the personalization of therapy on a clinical routine level, the characterization of DTCs and in vitro drug testing on DTCs are of great interest. Therefore, biobanking methods, as well as novel approaches to DTC isolation, need to be developed. In this study, we established a protocol for the biobanking of BM samples and evaluated a microfluidic-based separation system (Parsortix®) for the enrichment of cryopreserved DTCs. We were able to successfully isolate viable DTCs after the prior cryopreservation of BM samples. We calculated a significant increase of up to 90-fold in harvested DTCs with the proposed method compared to the current standard techniques, opening up new analysis possibilities for DTCs. Our advanced method further presents options for 3D DTC cultures, enabling the individualized testing of targeted therapies for BC patients. In conclusion, we present a novel approach for DTC enrichment, with possibilities for future clinical implications.

Opportunities and challenges for 2D heterostructures in battery applications: a computational perspective.

With an increasing demand for large-scale energy storage systems, there is a need for novel electrode materials to store energy in batteries efficiently. 2D materials are promising as electrode materials for battery applications. Despite their excellent properties, none of the available single-phase 2D materials offers a combination of properties required for maximizing energy density, power density, and cycle life. This article discusses how stacking distinct 2D materials into a 2D heterostructure may open up new possibilities for battery electrodes, combining favourable characteristics and overcoming the drawbacks of constituent 2D layers. Computational studies are crucial to advancing this field rapidly with first-principles simulations of various 2D heterostructures forming the basis for such investigations that offer insights into processes that are hard to determine otherwise. We present a perspective on the current methodology, along with a review of the known 2D heterostructures as anodes and their potential for Li and Na-ion battery applications. 2D heterostructures showcase excellent tunability with different compositions. However, each of them has distinct properties, with its own set of challenges and opportunities for application in batteries. We highlight the current status and prospects to stimulate research into designing new 2D heterostructures for battery applications.

Magneto-Optical Stark Effect in Fe-Doped CdS Nanocrystals.

Fe2+ doping in II-VI semiconductors, due to the absence of energetically accessible multiple spin state configurations, has not given rise to interesting spintronic applications. In this work, we demonstrate for the first time that the interaction of homogeneously doped Fe2+ ions with the host CdS nanocrystal with no clustering is different for the two spin states and produces two magnetically inequivalent excitonic states upon optical perturbation. We combine ultrafast transient absorption spectroscopy and density functional theoretical analysis within the ground and excited states to demonstrate the presence of the magneto-optical Stark effect (MOSE). The energy gap between the spin states arising due to MOSE does not decay within the time frame of observation, unlike optical and electrical Stark shifts. This demonstration provides a stepping-stone for spin-dependent applications.

Symmetry induced phonon renormalization in few layers of 2H-MoTe2 transistors: Raman and first-principles studies.

Understanding of electron-phonon coupling (EPC) in two-dimensional (2D) materials manifesting as phonon renormalization is essential to their possible applications in nanoelectronics. Here we report in situ Raman measurements of electrochemically top-gated 2, 3 and 7 layered 2H-MoTe2 channel based field-effect transistors. While the [Formula: see text] and B2g phonon modes exhibit frequency softening and linewidth broadening with hole doping concentration (p) up to ∼2.3 × 1013/cm2, A1g shows relatively small frequency hardening and linewidth sharpening. The dependence of frequency renormalization of the [Formula: see text] mode on the number of layers in these 2D crystals confirms that hole doping occurs primarily in the top two layers, in agreement with recent predictions. We present first-principles density functional theory analysis of bilayer MoTe2 that qualitatively captures our observations, and explain that a relatively stronger coupling of holes with [Formula: see text] or B2g modes as compared with the A1g mode originates from the in-plane orbital character and symmetry of the states at valence band maximum. The contrast between the manifestation of EPC in monolayer MoS2 and those observed here in a few-layered MoTe2 demonstrates the role of the symmetry of phonons and electronic states in determining the EPC in these isostructural systems.

Thrombotic complications with interruption of direct oral anticoagulants in dermatologic surgery.

BACKGROUND: Direct oral anticoagulants (DOACs), such as apixaban, rivaroxaban, and dabigatran, are increasingly being used to provide prophylaxis and treatment for arterial and venous thromboembolism. Multiple procedural subspecialties have implemented guidelines detailing time frames for perioperative DOAC interruption; however, the impact of perioperative DOAC interruption in patients undergoing dermatologic surgery is currently unknown, and evidence-based guidelines are lacking. OBJECTIVE: To assess the 30-day postoperative rate of thrombotic complications (ischemic stroke, transient ischemic attack, systemic embolism, deep vein thrombosis [DVT] and pulmonary embolism) in patients with nonvalvular atrial fibrillation (AF) or a history of DVT who underwent perioperative DOAC interruption during dermatologic surgery. METHODS: A retrospective medical record review was performed of all patients with AF or a history of DVT who underwent perioperative DOAC interruption during dermatologic surgery at Advanced Dermatologic Surgery and the University of Kansas Medical Center between January 1, 2016, and August 31, 2020. RESULTS: Among 806 operations, comprising 750 Mohs micrographic operations (93.1%) and 56 excisions (6.9%), 1 patient (0.14% of patients with AF) sustained a transient ischemic attack and 2 patients (0.25% of all patients) sustained minor bleeding complications during the 30-day postoperative period. CONCLUSION: Perioperative DOAC interruption appears to be safe and efficacious in dermatologic surgery.

The levels and trends of contraceptive use before first birth in India (2015-16): a cross-sectional analysis.

BACKGROUND: Indian women are more prone to first birth at a relatively younger age after marriage. Also, we do not have sufficient literature available that focuses on contraceptive use before first birth. The analysis of the present study was done using data from the fourth round of National Family Health Survey (2015-16), India. The objectives of the present study were to measure the levels and trends of contraceptive use before first birth among Indian ever married women, aged 15-34 years. METHODS: The study includes 279,896 ever married women aged 15-34 years at the time of the NFHS-4 survey. To identify the socio-demographic determinants governing the pioneering study behavior, multivariable techniques have been used in the analysis. The statistical significance of the relationship between socio-demographic factors and contraceptive use prior to first birth was tested using a chi-squared test for association. Hosmer Lemeshow statistics and Nagelkerke R square have been used to check how well the logistic regression model fits the data. Map of India showing different zonal classification is made using the ArcGIS software version 10.3. RESULT: The trends of contraceptive usage show a decline in use before first birth and the various socio-demographic factors affecting the use of contraceptive before first birth are religion, caste, education, wealth index, media exposure, age at marriage and the zonal classifications. CONCLUSION: The noticeable result in this study is the comparative decline in contraceptive use by women in India before first birth in NFHS-4 with respect to previous NFHS done in India. The likelihood of using contraception before first birth is significantly affected by factors like place of residence, religion, caste, current age of women, age at marriage, education level of women, wealth index, media exposure and zonal classification.

Mapping human health risk by geostatistical method: a case study of mercury in drinking groundwater resource of the central ganga alluvial plain, northern India.

Human health is "at risk" from exposure to sub-lethal elemental occurrences at a local and or regional scale. This is of global concern as good-quality drinking water is a basic need for our wellbeing. In the present study, the "probability kriging," a geostatistical method that has been used to predict the risk magnitude of the areas where the probability of dissolved mercury concentration (dHg) is higher than the World Health Organization (WHO) permissible limit. The method was applied to geochemical data of dHg concentration in 100 drinking groundwater samples of Lucknow monitoring area (1222 km2) located within the Ganga Alluvial Plain, India. Threefold (high to extreme risk) and twofold (moderate risk) higher dHg concentration values than the WHO permissible limit were observed in all of the groundwater samples. The generated prediction map using the probability kriging method shows that the probability of exceedance of dHg is the highest in the northwestern part of the Lucknow monitoring area due to anthropogenic interferences. The hotspots with high to very high probability are potentially alarming in the urban sector where 32.4% of the total population is residing in 6.8% of the total area. Interpolation of local estimates results in an easily readable and communicable human health risk map. It may help to consider substantial remediation measures for managing drinking water resources of the Ganga Alluvial Plain, which is among the anthropogenic mercury emission-dominated regions of the world.