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Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enhancing its clinical translation. The momentum of cfDNA liquid biopsy technologies in recent years has propelled epigenetics to the forefront of molecular biology. We have only begun to reveal the true potential of epigenetics in both our understanding of disease and leveraging epigenetics in the diagnostic and therapeutic domains. Recent clinical applications of epigenetics-based cfDNA liquid biopsy revolve around DNA methylation in screening and early cancer detection, leading to the development of multi-cancer early detection tests and the capability to pinpoint tissues of origin. The clinical application of epigenetics in cfDNA liquid biopsy in minimal residual disease, monitoring, and surveillance are at their initial stages. A notable advancement in fragmentation patterns analysis has created a new avenue for epigenetic biomarkers. However, the widespread application of cfDNA liquid biopsy has many challenges, including biomarker sensitivity, specificity, logistics including infrastructure and personnel, data processing, handling, results interpretation, accessibility, and cost effectiveness. Exploring and translating epigenetics in cfDNA liquid biopsy technology can transform our understanding and perception of cancer prevention and management. cfDNA liquid biopsy has great potential in precision oncology to revolutionize conventional ways of early cancer detection, monitoring residual disease, treatment response, surveillance, and drug development. Adapting the implementation of liquid biopsy workflow to the local policy worldwide and developing point-of-care testing holds great potential to overcome global cancer disparity and improve cancer outcomes.

Abstract Diabetic kidney disease (DKD) is a devastating kidney disease and lacks effective therapeutic interventions. The present study was aimed to determine whether reconstituted high‐density lipoprotein (rHDL) ameliorated renal injury in eNOS−/− dbdb mice, a mouse model of DKD. Three groups of mice, wild type C57BLKS/J (non‐diabetes), eNOS−/− dbdb (diabetes), and eNOS−/− dbdb treated with rHDL (diabetes+rHDL) with both males and females were used. The rHDL nanoparticles were administered to eNOS−/− dbdb mice at Week 16 at 5 μg/g body weight in ~100 μL of saline solution twice per week for 4 weeks via retroorbital injection. We found that rHDL treatment significantly blunted progression of albuminuria and GFR decline observed in DKD mice. Histological examinations showed that the rHDLs significantly alleviated glomerular injury and renal fibrosis, and inhibited podocyte loss. Western blots and immunohistochemical examinations showed that increased protein abundances of fibronectin and collagen IV in the renal cortex of eNOS−/− dbdb mice were significantly reduced by the rHDLs. Taken together, the present study suggests a renoprotective effect of rHDLs on DKD.

This article examines a distinctive and debated social group called the “Baboos” in late colonial India, particularly in Bengal. The Baboos represented the Western-educated, aspiring middle class who were integral to the British administration. They were often viewed skeptically for adopting the English language and Western lifestyle. This study delves into the quotidian lives of the Baboos, particularly their interactions with the colonial rulers in public transport, which became a crucial contact zone. Despite facing racial conflicts and discrimination in these shared spaces, the Baboos were not passive victims. They used diverse strategies to combat injustices and voice their grievances publicly. Within this larger narrative of discriminating treatment, another power narrative was played out by the Baboos among their own population. Conscious of their distinct functional status, the Baboos sought to distance themselves from those Indians who did not match their ideas of “respect”. Everyday experiences formed the basis of the public outrage reflected continually in regional newspapers and, subsequently, in the larger narratives of resistance and nationalism. How the Baboos negotiated their position in the public spaces sheds light on their claims of civil rights and their ways of using the colonizer’s tropes of equality, justice, and fairness back at them.

The figure of the 'kīrtimukha' or ‘glory- face’ is an artistic motif that appears on early Indian art and architecture, initially as a sacred symbol and then more commonly as a decorative element. In Assam, the motif of 'kīrtimukha' is seen crowning the stele of the stray icons of the early medieval period. The motif also appeared in the structural components of the ancient and early medieval temples of Assam. The Kapili-Jamuna valley, situated in the districts of Nagaon, Marigaon and Hojai in central Assam houses innumerable rich archaeological remains, especially temple ruins and sculptures, both stone and terracotta. Many such architectural components are adorned by the 'kīrtimukha' figures, usually carved in low relief. It is proposed to discuss the iconographic features of the 'kīrtimukha' motif in the art of the Kapili-Jamuna valley of Assam and also examine whether the iconographic depictions of the 'kīrtimukha' as prescribed in canonical texts, such as the 'Śilpaśāstras' are reflected in the art of the valley. Pan Asian linkages of the 'kīrtimukha' motif will also be examined.

TERI (The Energy and Resources Institute) has recently developed a novel wastewater treatment technology called TERI Advanced Oxidation Technology (TADOX), which provides an end-to-end treatment of textile and dyeing industry wastewater within a few hours without any kind of bioremediation in the treatment trail. It involves UV/n-TiO2 Photocatalysis during secondary treatment; Photocatalysis, is a promising approach for treating difficult wastewater, however there is always effort to reduce cost and electrical energy consumption. In this pursuit, TiO2 was modified using Bagasse Fly Ash (BFA) to form a nanocomposite BFA-TiO2, which led to increased surface area and higher adsorptive capacity as compared to Bare TiO2. Both nanomaterials and BFA alone were characterized using X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR) and BET (Brunauer-Emmet-Teller) surface area analysis. These nanomaterials acted as photocatalysts in TADOX treatment of synthetic dye bath and real textile & dyeing wastewater and the overall performance of both materials was evaluated based on % Chemical Oxygen Demand (COD) removal, Electrical energy per Order (EEO) and Electrical energy consumption per unit wastewater treatment (EEvolume). Further, the cost of treatment per kg COD removed and overall cost of treatment per unit wastewater treated were also calculated. Results indicate that modification of TiO2 with BFA appears to be a promising approach towards higher % COD removal, lower EEO and lower cost of treatment per kg COD.

Tailless is a committed transcriptional repressor and principal regulator of the brain and eye development in Drosophila. Rpd3, the histone deacetylase, is an established repressor that interacts with co-repressors like Sin3a, Prospero, Brakeless and Atrophin. This study aims at deciphering the role of Rpd3 in embryonic segmentation and larval brain development in Drosophila. It delineates the mechanism of Tailless regulation by Rpd3, along with its interacting partners. There was a significant reduction in Tailless in Rpd3 heteroallelic mutant embryos, substantiating that Rpd3 is indispensable for the normal Tailless expression. The expression of the primary readout, Tailless was correlative to the expression of the neural cell adhesion molecule homologue, Fascilin2 (Fas2). Rpd3 also aids in the proper development of the mushroom body. Both Tailless and Fas2 expression are reported to be antagonistic to the epidermal growth factor receptor (EGFR) expression. The decrease in Tailless and Fas2 expression highlights that EGFR is upregulated in the larval mutants, hindering brain development. This study outlines the axis comprising Rpd3, dEGFR, Tailless and Fas2, which interact to fine-tune the early segmentation and larval brain development. Therefore, Rpd3 along with Tailless has immense significance in early embryogenesis and development of the larval brain.

Cessation of one-week oral administration of the benzodiazepine flurazepam (FZP) to rats results in withdrawal anxiety after 1 day of withdrawal. FZP withdrawal is correlated with synaptic incorporation of homomeric GluA1-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) in the proximal stratum radiatum of CA1 neurons. After 2 days of withdrawal, Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylates GluA1 subunits at Ser831, increasing channel conductance. Secondary to AMPAR potentiation, GluN2B-containing N-methyl-D-aspartate receptors (NMDARs), known binding partners of CaMKII, are selectively removed from the postsynaptic density (PSD). While activation of synaptic CaMKII is known to involve translocation to the PSD, CaMKII bound to NMDARs may be removed from the PSD. To distinguish these possibilities, the current studies used postembedding immunogold electron microscopy to investigate alterations in CaMKII signaling at CA1 stratum radiatum synapses after 2 days of FZP withdrawal. These studies revealed decreased total, but not autophosphorylated (Thr286) CaMKIIα expression in CA1 PSDs. The removal of CaMKII-GluN2B complexes from the PSD during drug withdrawal may serve as a homeostatic mechanism to limit AMPAR-mediated CA1 neuron hyperexcitability and benzodiazepine withdrawal anxiety.

Long-term BZ (benzodiazepine) anxiolytic therapy increases the risk of physical dependence manifested as withdrawal anxiety. BZ-induced potentiation of GABAAR (γ-aminobutyric acid type-A receptor) function by 1-week oral administration of FZP (flurazepam) bi-directionally modulates excitatory glutamatergic synaptic transmission in hippocampal CA1 neurons during drug withdrawal. Previous electrophysiological studies on acutely isolated and intact CA1 neurons, as well as immunofluorescence and post-embedding immunogold electron microscopy studies, suggest increased synaptic insertion of GluR (glutamate receptor) 2-lacking AMPARs (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors) in 2-day FZP-withdrawn rats. Preliminary studies indicated a similar increase in GluR1, then phospho-Ser831-GluR1, as well as CaMKIIα (Ca2+/calmodulin-dependent protein kinase IIα), but not phospho-Thr286-CaMKII levels at the same time point. In our studies, whole-cell recordings in hippocampal slices revealed that AMPAR mEPSC [miniature EPSC (excitatory postsynaptic current)] amplitude was increased in 1-day FZP-withdrawn rats followed by an increase in estimated single-channel conductance in 2-day-FZP-withdrawn rats. Enhanced conductance was no longer observed in slices pre-incubated for 2 h in the CaMKII inhibitor KN-93, but not the inactive analogue KN-92. To evaluate whether CaMKII-mediated AMPA potentiation could occlude LTP (long-term potentiation), LTP was induced by TBS (theta burst stimulation) and recorded using whole-cell and extracellular techniques. LTP was induced in both groups, but only maintained for <15 min in 2-day FZP-withdrawn rats. LTP was fully restored after 7-day withdrawal. Despite the lack of LTP maintenance, impairment of object recognition, place and context was not observed in 2-day-FZP-withdrawn rats. Since L-VGCC (L-type voltage-gated calcium channel) current density was doubled on drug withdrawal and up to 2 days, Ca2+entry through L-VGCCs and perhaps subsequently through Ca2+-permeable AMPARs are proposed to be responsible for enhanced CaMKIIα levels and AMPAR potentiation. Mechanisms associated with several different models of activity-dependent plasticity may underlie BZ physical dependence. [ABSTRACT FROM AUTHOR]

Curcumin and curcumin containing polyherbal preparations have demonstrated anti-microbial and anti- viral properties in pre-clinical studies. Till date no therapeutic intervention has been proved to be effective and safe in clearing established cervical human papillomavirus (HPV) infection. The present study evaluated the efficacy of Basant polyherbal vaginal cream (containing extracts of curcumin, reetha, amla and aloe vera) and of curcumin vaginal capsules to eliminate HPV infection from cervix. Women were screened by Pap smear and HPV DNA test by PCR. HPV positive women without high grade cervical neoplasias (N=287) were randomized to four intervention arms to be treated with vaginal Basant cream, vaginal placebo cream, curcumin vaginal capsules and placebo vaginal capsules respectively. All subjects were instructed to use one application of the assigned formulation daily for 30 consecutive days except during menstruation and recalled within seven days of the last application for repeat HPV test, cytology and colposcopy. HPV clearance rate in Basant arm (87.7%) was significantly higher than the combined placebo arms (73.3%). Curcumin caused higher rate of clearance (81.3%) than placebo though the difference was not statistically significant. Vaginal irritation and itching, mostly mild to moderate, was significantly higher after Basant application. No serious adverse events were noted.