Osteoarticular tuberculosis infection in spine, hip, and knee is the most common bone and joint extrapulmonary tuberculosis (EPTB), accounting for 10-15% of all EPTB cases. The urgent need for new treatment strategies arises from the severe clinical consequences of delayed or misdiagnosed osteoarticular TB infections, compounded by the inadequacies of current antibiotic therapies. Local antibiotic delivery approaches using advanced biomimetic biomaterials as a carrier system provide an efficient alternative. Herein, we develop an injectable, biocompatible nanohydroxyapatite-based carrier system (Nanocement; NC), compositionally similar to natural bone mineral, to deliver two first-line anti-tuberculosis antibiotics, isoniazid and rifampicin locally. The NC carrier was characterised for physicochemical properties, in vitro biocompatibility and anti-mycobacterial activities using a virulent H37Rv strain of Mycobacterium tuberculosis. The antibiotic-loaded NC was finally implanted in the spine and tibia TB infection model developed in guinea pigs for 8 weeks, using oral antibiotic therapy as a control. The results showed that the antibiotic carrier system has enormous potential to provide an promising alternative to oral antibiotic therapy or could be more beneficial if combined with an oral regime. During the surgical debridement, an irregular dead space is created that require local infection control and support for early bone healing, rather than immediate structural restoration. As an injectable cement, NC is optimized to conform to these cavities, deliver sustained local anti-tubercular therapy, and provide an osteoconductive microenvironment that supports gradual bone regeneration. While its intrinsic mechanical properties may limit its use in large, critical defects requiring structural support, NC can be effectively applied in combination with fixation devices or secondary grafting strategies. STATEMENT OF SIGNIFICANCE: Osteoarticular tuberculosis remains a debilitating global health challenge, where delayed diagnosis and limited efficacy of systemic antibiotics often result in irreversible skeletal damage. This study explores the potential of an indigenously developed injectable nanohydroxyapatite-based "Nanocement" that locally co-delivers isoniazid and rifampicin while simultaneously acting as an osteoconductive bone filler. By directly targeting infectious bone lesions, this biomimetic carrier achieves potent and sustained anti-mycobacterial activity against virulent M. tuberculosis in vivo, while promoting bone healing in infectious lesions. This dual-action strategy offers a transformative alternative to conventional oral regimens and highlights a clinically translatable approach for treating complex bone infections.
Herein, we report the design, synthesis, and molecular characterization of a highly oxidative Ru(II)-based photocatalyst: [Ru(TPA)(qdppz)]PF6 [Ru1], where TPA is tris(2-pyridylmethyl)amine and qdppz represents 12,17-dihydronaphtho-[2,3-h]dipyrido[3,2-a:2',3'-c]-phenazine-12,17-dione. The MLCT band of [Ru1] complex at 485 nm enabled a green-light-induced photocatalytic chemotherapeutic modality. The conjugation of the quinone moiety to the [Ru(TPA)] core significantly enhances the lipophilicity of [Ru1], facilitating its cellular uptake. The photostable complex demonstrated good photocytotoxicity under green light irradiation with a high selectivity index (SI) against HepG2 cancer cells, with an IC50 of 16.34 μM (SI = 7) in normoxia and an IC50 of 45.68 μM (SI = 3) under hypoxic conditions. Furthermore, the [Ru1] complex also presents anticlonogenic activity, as evidenced by the colony formation assay. ROS generation was identified in the HepG2 cell lines in the presence of green light and the [Ru1] complex, which was verified using an in vivo DCFDA assay. Mechanistic investigations reveal that, under green light irradiation, the [Ru1] complex exhibits synergistic Type I/II photosensitization and photocatalytically oxidizes NADH and NADPH to NAD+/NADP+ in biological media (PBS) with high turnover frequencies (TOF) of 104.73 h-1 and 136.79 h-1, respectively. Overall, [Ru1] represents a promising new approach for developing efficient Ru(II)-based complexes for cancer photochemotherapy by inducing intracellular redox imbalance.
Due to increasing population, consumption of vegetables is also increasing know days and to increase production, fertilizers of different types are being used and fertilizers contain heavy metals which cause soil and water pollution. Water pollution and soil pollution are increasing due to industrialization and urbanization. Due to which the concentration of heavy metal (lead) in the environment, living organisms and vegetables is also increasing. Vegetables is used for nutrient values. But apart from nutrients, these vegetables also contain heavy metals which cause health issues in humans. The aim was to analyze the concentration of heavy metal (lead) in selected vegetables grown in the area around Kishangarh using wet acid digestion and analysis using Atomic Absorption Spectroscopy. We observed that the concentration of heavy metal (lead) in most of the vegetables was higher than the limits issued by WHO/EU/FSSAI. We should pay attention to this and think about the coming generation.
Highly sensitive, nonenzymatic electrochemical sensor has been developed for the detection of Ferrum Metallicum, a homeopathic iron formulation. The sensor architecture integrates a nickel foam functionalized with an activated graphene-carbon nanotube (NAG-CNT) composite, yielding a defect-rich, graphitic nanostructure as confirmed by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), Raman spectroscopies, and X-ray diffraction. Enhanced electroactive surface area facilitates rapid charge transfer, as validated through cyclic voltammetry and chronocoulometry. Electrochemical characterization using differential pulse voltammetry within a three-electrode system demonstrated a broad linear detection range (50 nM-200 mM), a low detection limit similar to 13.12 nM, and high sensitivity (25 mA mM(-1) cm(-2)). Mechanistic studies revealed an oxidation process governed by diffusion and proton transfer. The sensor exhibited remarkable selectivity against common interferents and achieved quantitative recovery (>97%) with excellent reproducibility (<= 5% RSD) in spiked serum samples. These findings underscore its potential for pharmaceutical quality control and point-of-care diagnostic applications.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a progressive liver disorder with complex pathogenesis and no approved treatments beyond lifestyle changes. Here, we report a sprayable and biodegradable bioadhesive hydrogel loaded with exosomes derived from human mesenchymal stromal cells that provides sustained therapy localized to the liver. In a rat model of chronic MAFLD, a single application of the spray markedly improved liver pathology and systemic metabolic indices over the effects of lifestyle interventions. Specifically, collagen deposition, liver-enzyme levels, insulin resistance, and chronic inflammation were all attenuated. Furthermore, the spray led to an increase in markers of gut-barrier integrity and gut bacterial diversity and modulated key pathways of lipid metabolism, inflammation, and fibrosis, as we show via multi-omics profiling of liver tissue. Our findings strongly suggest that exosomes delivered to the liver via a sprayable anti-inflammatory hydrogel can address the multifactorial pathology of MAFLD, yielding improvements in liver histology and function, and inducing systemic metabolic homeostasis.
Naturally derived biopolymers have attracted significant attention due to their biocompatibility but the innately poor mechanical properties of pristine biopolymer films obstruct their utility as wound dressings. To address this issue, herein we have synthesised a mechanically robust polysaccharide-based hydrogel patch with intrinsic antibacterial activity and haemostatic abilities. Sodium alginate and carboxymethyl cellulose were integrated with corn waste-derived natural fibre utilising a dual crosslinking approach through carbon dots (CD) and Zn2+ ion. The introduction of CD brought flexibility into Zn2+ ion crosslinked hydrogel, which enhanced the mechanical property. Variation in CD content, polymer ratio or metal ion concentration endowed the importance of synergistic interaction of both the crosslinker on the mechanical property of the patch. At optimum conditions, the patch exhibited a tensile strength up to similar to 51 MPa. The patch released 72.52 % CD and 39.21 % Zn2+ ions within 12 h, which endowed a zone of inhibition of 40 mm against E. coli and 30 mm against S. aureus. Furthermore, the patches displayed remarkable biocompatibility with L929 cells, haemocompatible and promoted coagulation, effectively absorbing blood within 20 min. Therefore, this study represents a sustainable, high-strength, antibacterial, biopolymer-based patch, ideal for wound dressing applications.
In this study, we measured both the pre-scission and post-scission neutron multiplicities for the 31P + 170Er reaction at excitation energies in the range of 62-84 MeV, using the National Array of Neutron Detectors (NAND) at Inter University Accelerator Centre (IUAC), New Delhi. Theoretical calculations to reproduce the measured neutron multiplicities have been performed using the dynamical model code VECLAN. These calculations show that the dissipation strength parameter (beta) increases with excitation energy. Dynamical model calculations also have been performed using HICOL code to understand the fusion dynamics and formation time. It has been observed that transitioning from an asymmetric to a symmetric entrance channel leads to a gradual increase in the compound nucleus formation time, accompanied by more emission of neutrons during its formation.
The recent IceCube detection of TeV neutrino emission from the nearby active galaxy NGC 1068 suggests that active galactic nuclei (AGNs) could make a sizable contribution to the diffuse flux of astrophysical neutrinos. The absence of TeV γ -rays from NGC 1068 indicates neutrino production in the vicinity of the supermassive black hole, where the high radiation density leads to γ -ray attenuation. Therefore, any potential neutrino emission from similar sources is not expected to correlate with high-energy γ -rays. Disk-corona models predict neutrino emission from Seyfert galaxies to correlate with keV X-rays because they are tracers of coronal activity. Using through-going track events from the Northern Sky recorded by IceCube between 2011 and 2021, we report results from a search for individual and aggregated neutrino signals from 27 additional Seyfert galaxies that are contained in the Swift's Burst Alert Telescope AGN Spectroscopic Survey. Besides the generic single power law, we evaluate the spectra predicted by the disk-corona model assuming stochastic acceleration parameters that match the measured flux from NGC 1068. Assuming all sources to be intrinsically similar to NGC 1068, our findings constrain the collective neutrino emission from X-ray bright Seyfert galaxies in the northern sky, but, at the same time, show excesses of neutrinos that could be associated with the objects NGC 4151 and CGCG 420-015. These excesses result in a 2.7 σ significance with respect to background expectations.
MoS2 has elicited notable interest as a promising material for gas sensing applications. The pristine MoS2 is still encumbered by drawbacks such as low response, large response time, and a propensity for weak adsorption of target gases, which can impede its effectiveness in practical applications. To address these challenges, this study investigates the functionalization of nitrogen-doped MoS2 with silver nanoparticles to improve its sensing performance for NO2 gas. MoS2 nanosheets were synthesized through chemical vapor deposition and subsequently subjected to nitrogen plasma treatment to facilitate doping. We evaluated the gas sensing performance of pristine MoS2, Ag-decorated MoS2, nitrogen-doped MoS2, and Ag-decorated nitrogen-doped MoS2 (Ag-N-MoS2) specifically for NO2 gas sensing. The Ag-N-MoS2 configuration demonstrated a response that was nearly double that of pristine MoS2 at 100 degrees C, demonstrating the benefits of this dual enhancement strategy. Additionally, selectivity tests revealed the sensor's capacity to distinguish NO2 from other gases. To reinforce our experimental results, density functional theory (DFT) calculations were conducted, confirming the improved electronic properties achieved through nitrogen doping and Ag NP functionalization. This research underscores the potential of Ag-NMoS2 as a formidable platform for sophisticated gas sensors, addressing crucial environmental monitoring requirements while surmounting the intrinsic limitations of pristine MoS2.
Thin, durable and uniform self-supporting isotopic targets of 170 Er and 185 Re targets with carbon backing have been fabricated by using cold-rolling and high vacuum evaporative deposition techniques respectively at Inter University Accelerator Centre (IUAC) target laboratory, New Delhi. For the fabrication of 185 Re, e-Gun (electron-Gun) evaporation technique was used. The thickness obtained for 170 Er was around 2.1 mg/cm2 and for 185 Re, it was 200 mu g/cm 2 with a carbon backing of 50 mu g/cm 2 . Using characterization techniques such as energy dispersive X-ray spectroscopy (EDX), Rutherford backscattering spectroscopy (RBS), alpha energy loss technique, and X-ray diffraction, the thickness and elemental composition of the targets were analyzed. These measurements essentially exhibited no contamination, indicating their excellent purity and durability. Both the targets were used in nuclear experiment performed at NAND (National Array of Neutron Detectors) facility, IUAC, New Delhi to study the nuclear reaction dynamics. For such kind of study, one needs pure targets without any contamination to ensure that the neutron data is coming only from the reaction of interest. For mass distribution measurements, thin target (100-200 mu g/cm 2 ) is the requirement.
The researchers have paid considerable attention to the nanocomposites of rare-earth and metal-oxide nanostructures because of their excellent optical, attractive, and catalytic properties. The alpha-Fe2O3/Gd2O3 nanocomposites were synthesized utilizing a simple and cost-effective chemical co-precipitation method. The variation in the crystallite size and lattice parameter of synthesized nanocomposites was confirmed by XRD measurements. To get their valence states, surfaces and interfacing of materials, XPS measurement is utilized. The band gap of the materials lies in the range of 2.01 eV-2.64 eV and the estimated particle size lies in the range from 42 nm to 10 nm. Moreover, most elevated attraction appeared by the nanocomposites is 5.877 emu/g. In 90 min, the photocatalytic degradation of alpha-Fe2O3/Gd2O3 nanocomposites for Rose Bengal dye reaches up to 97.91 %. The synergistic commitment of alpha-Fe2O3 and Gd2O3, avoids photo-generated charge carrier recombination and the generation of exceedingly dynamic radical species (OH center dot and O2 center dot radicals), which is capable of the progressed photocatalytic action.
Active galactic nuclei (AGN) are promising candidate sources of high-energy astrophysical neutrinos, since they provide environments rich in matter and photon targets where cosmic-ray interactions may lead to the production of gamma rays and neutrinos. We searched for high-energy neutrino emission from AGN using the Swift-BAT Spectroscopic Survey catalog of hard X-ray sources and 12 yr of IceCube muon track data. First, upon performing a stacked search, no significant emission was found. Second, we searched for neutrinos from a list of 43 candidate sources and found an excess from the direction of two sources, the Seyfert galaxies NGC 1068 and NGC 4151. We observed NGC 1068 at flux ϕ ν μ + ν ¯ μ = 4.0 2 − 1.52 + 1.58 × 1 0 − 11 TeV −1 cm −2 s −1 normalized at 1 TeV, with a power-law spectral index γ = 3.10 − 0.22 + 0.26 , consistent with previous IceCube results. The observation of a neutrino excess from the direction of NGC 4151 is at a posttrial significance of 2.9 σ . If interpreted as an astrophysical signal, the excess observed from NGC 4151 corresponds to a flux ϕ ν μ + ν ¯ μ = 1.5 1 − 0.81 + 0.99 × 1 0 − 11 TeV −1 cm −2 s −1 normalized at 1 TeV and γ = 2.83 − 0.28 + 0.35 .
Measuring observables to constrain models using maximum-likelihood estimation is fundamental to many physics experiments. Wilks' theorem provides a simple way to construct confidence intervals on model parameters, but it only applies under certain conditions. These conditions, such as nested hypotheses and unbounded parameters, are often violated in neutrino oscillation measurements and other experimental scenarios. Monte Carlo methods can address these issues, albeit at increased computational cost. In the presence of nuisance parameters, however, the best way to implement a Monte Carlo method is ambiguous. This paper documents the method selected by the NOvA experiment, the profile construction. It presents the toy studies that informed the choice of method, details of its implementation, and tests performed to validate it. It also includes some practical considerations which may be of use to others choosing to use the profile construction.
The cholinergic deficits and deposition of β-amyloid (Aβ) species are regarded as the key events contributing to the progression of Alzheimer's disease (AD). Herein, a series of novel donor-acceptor architecture-type potential theranostic agents were designed, synthesized, and evaluated for their potential against cholinesterase (ChE) enzymes and detection of Aβ species, which are primary targets in the development of therapeutics for AD. The optimal compound/probe 18 containing a benzothiazolium fluorophore with a bifunctional electron-donating N-aryl piperazine scaffold exhibited potent inhibitory activities against acetylcholinesterase (AChE; IC50 = 0.172 ± 0.011 μM) and butyrylcholinesterase (BuChE; IC50 = 1.376 ± 0.141 μM). Measurement of fluorescence properties showed that probe 18 exhibited emission maxima (λem) of >610 nm in dimethyl sulfoxide (DMSO) and >590 nm in PBS, suitable for the fluorescence imaging. In vitro studies demonstrated a change in fluorescence characteristics and high binding affinities (18; Kd = 0.731 μM) upon binding with Aβ aggregates. The affinity of probe 18 toward Aβ aggregates was further observed in elavGAL4 > UAS Aβ, the Drosophila larval brain sections, using a fluorescence imaging technique. The in vivo acute oral toxicity evaluation indicated a safety profile of the lead probe 18. Moreover, in vivo behavioral studies including Y-maze and novel object recognition tests signified that the administration of compound 18 improved cognitive and spatial memory impairment at a dose of 10 and 20 mg/kg in the scopolamine-induced cognitive deficit model.
Lifetimes of excited states of positive and negative parity Δ I = 2 bands of ^106 Cd have been measured using the Doppler Shift Attenuation Method (DSAM). The electric quadrupole reduced transition probability rates, B(E2), show a significant decreasing trend with increasing spin along with large observed ^(2) /B(E2) values. The experimental observations, interpreted in the framework of semiclassical particle-rotor model (SCM) calculations, suggest that these bands have the character of twin-shears type anti-magnetic rotational bands resulting from the coupling of g _9/2 proton holes with h _11/2 , g _9/2 and d _5/2 neutron particles. Another negative-parity band in the same nucleus has been studied using SCM, which also interprets it to be an anti-magnetic rotational band.
This work systematically investigates the stability and electronic and thermoelectric characteristics of newly discovered 2D Janus monolayers BiYZ (Y not equal Z = Te, Se and S) according to the first-principles theory. Janus BiYZ monolayers are stable based on the AIMD simulations, positive phonon spectra plots and the evaluation of elastic strain tensor. These monolayers show a high carrier mobility (similar to 103 cm2 V-1 s-1) and an indirect bandgap nature. The Janus monolayers BiTeSe, BiTeS and BiSeS show an ultralow lattice thermal conductivity of 0.04 W m-1 K-1, 0.20 W m-1 K-1 and 0.02 W m-1 K-1, respectively, at room temperature. Low lattice thermal conductivity is obtained due to a small phonon group velocity, high Gr & uuml;neisen parameter, small phonon relaxation time and significantly reduced phonon transport. The maximum ZT values at 500 K reach up to 0.97, 0.60 and 1.78 for BiTeSe, BiSeS, and BiTeS monolayers, respectively. Our results suggest Janus BiYZ monolayers to be promising thermoelectric candidates due to their superior thermal and electrical transport characteristics and subsequent strong thermoelectric performance.
This study presents a phyto-nanoengineered bone regenerative platform that addresses the clinical challenges of critical-sized bone defects, which often fail to heal due to impaired regenerative capacity compounded by oxidative stress and chronic inflammation. Traditional interventions, including autografts and synthetic drugs, are limited by poor bioactivity, insufficient tissue integration, and systemic side effects. To overcome these limitations, biologically reduced trans-resveratrol-loaded gold nanoparticles (tRGNPs) were incorporated into a macroporous cryogel scaffold composed of gelatin, chitosan, and nano-hydroxyapatite, forming the tRGCH nano-scaffold. The tRGNPs, synthesized to preserve the bioactive trans-form of resveratrol, exhibited spherical morphology (similar to 22 nm), high crystallinity, and excellent colloidal stability. They demonstrated potent antioxidant and anti-inflammatory activities by upregulating M2 markers (Arg-1, IL-10) in macrophages while downregulating M1 markers (iNOS, IL-1 beta). In vitro, tRGNPs significantly enhanced pre-osteoblast proliferation (similar to 1.5-fold vs. control), migration (95.6 +/- 0.3 % wound closure vs. 67.1 +/- 0.9 % in control; 1002.7 +/- 20.6 migrating cells/mm(2) vs. 132.3 +/- 21.2 in control), and osteogenic differentiation, achieving ALP activity and calcium deposition comparable to osteogenic induction medium, while mitigating oxidative stress-induced damage. Furthermore, the pre-synthesis incorporation of tRGNPs ensured homogeneous nanoparticle distribution, improved mechanical integrity, and sustained biomolecular release, effectively addressing issues such as polyphenol instability and burst release. The resulting tRGCH scaffolds exhibited optimal swelling, biodegradability, and porosity, closely mimicking native bone matrix architecture. In a rat tibial defect model, tRGCH scaffolds significantly enhanced bone regeneration, inducing collagen formation (similar to 36 % trichrome-positive area compared to control), mineral deposition, and trabecular organization. This nanoengineered system offers a promising, cost-effective approach for bone regeneration under inflammatory conditions.
Non-alcoholic fatty liver disease (NAFLD) is a complex metabolic disorder, where the underlying molecular mechanisms are mostly not well-understood and therefore, warrants the need for therapeutic interventions targeting several metabolic pathways as a unified response. Of late, promising outcomes have been observed with mesenchymal stem cell-derived exosomes. However, reduced bioavailability due to systemic delivery and the need for repeated fresh isolation hinders their feasibility for clinical applications. In this regard, an 'off-the-shelf' 3D bioprinted hyaluronic acid-based hepatic patch to deliver encapsulated exosomes alone/or with hepatocytes (as dual-therapy) is developed as a holistic approach for ameliorating the disease condition and promoting tissue regeneration. The bioprinted hepatic patch demonstrated sustained and localized release of exosomes (similar to 82 % in 21 days), and healthy liver tissue-like mechanical properties while being biocompatible and biodegradable. Assessment in NAFLD rat models displayed alleviation of the altered biochemical parameters such as fat deposition, deranged liver functions, disrupted lipid, glucose, and insulin metabolism along with a reduction in localized inflammation, and associated liver fibrosis. The study suggests that a synergistic effect between the miRNA population of released exosomes, cell therapy, and the bioprinted matrix materials is crucial in targeting multiple complex metabolic pathways associated with the severity of the disease.