Symmetry Engineering of Epitaxial Hf0.5Zr0.5O2 Ultrathin Films.

Robust ferroelectricity in HfO2-based ultrathin films has the potential to revolutionize nonvolatile memory applications in nanoscale electronic devices because of their compatibility with the existing Si technology. However, to fully exploit the potential of ferroelectric HfO2-based thin films, it is crucial to develop strategies for the controlled stabilization of various HfO2-based polymorphs in nanoscale heterostructures. This study demonstrates how substrate-orientation-induced anisotropic strain can engineer the crystal symmetry, structural domain morphology, and growth orientation of ultrathin Hf0.5Zr0.5O2 (HZO) films. Epitaxial ultrathin HZO films were grown on the heterostructures of (001)- and (110)-oriented La2/3Sr1/3MnO3/SrTiO3 (LSMO/STO) substrate. Various structural analyses revealed that the (110)-oriented substrate promotes a higher degree of structural order (crystallinity) with improved stability of the (111)-oriented orthorhombic phase (Pca21) of HZO. Conversely, the (001)-oriented substrate not only induces a distorted orthorhombic structure but also facilitates the partial stabilization of nonpolar phases. Electrical measurements revealed robust ferroelectric properties in epitaxial thin films without any wake-up effect, where the well-ordered crystal symmetry stabilized by STO(110) facilitated better ferroelectric characteristics. This study suggests that tuning the epitaxial growth of ferroelectric HZO through substrate orientation can improve the stability of the metastable ferroelectric orthorhombic phase and thereby offer a better understanding of device applications.

Fenestration: Integrating Wings Into the Atrial Septal Occluder for Navigating a Challenging Terrain.

Background Atrial septal defect (ASD) closure with significant left-to-right shunt and concurrent comorbidities poses challenges for intervention. A fenestrated atrial septal defect (FASD) device is a viable option for patients who cannot undergo complete occlusion due to hemodynamic and medical reasons. This study explores the use of FASD occluders in patients with secundum ASD and associated comorbidities where complete occlusion is difficult. Methodology This retrospective study collected the details of patients recommended for FASD closure diagnosed with significant secundum ASD and who had additional comorbidities between July 2015 and July 2023 in a tertiary cardiac center in eastern India. Among this cohort, patients who underwent FASD device placement were subjected to a comprehensive analysis. Results In total, 16 patients diagnosed with secundum ASD, characterized by significant left-to-right shunt and concurrent comorbidities, were considered for FASD closure during the study period. Ultimately, 13 patients (first group) underwent fenestrated atrial septal occluder implantation. The average age was 45.07 years, with the majority being females (n = 9). Comorbidities among this cohort included substantial left ventricular diastolic dysfunction (n = 7), left ventricular diastolic dysfunction coupled with moderate pulmonary hypertension (n = 1), severe pulmonary hypertension (n = 1), severe pulmonary valvular stenosis with right ventricular diastolic dysfunction (n = 2), and systemic lupus erythematosus (SLE) (n = 2). From this cohort, three patients did not undergo the intervention. The second group consisted of an elderly patient with severe left ventricular diastolic dysfunction, a young adult with a history of left atrial arrhythmia, and a child with Duchenne muscular dystrophy (DMD). The average ASD size among patients who underwent the intervention was 26.38 mm, with a thick-to-thick dimension measuring 31.15 mm. The procedure was successful in all 13 patients, with the most frequently used device being a 34 mm occluder (range = 28-40 mm). All devices, excluding the initial one, were custom-made atrial septal occluders (Lifetech Scientific). Among the patients, 12 exhibited left-to-right fenestration flow, while one patient experienced fenestration constriction, likely due to occluder overcrowding. The first patient had a handmade 5 mm fenestration in a 40 mm Amplatzer septal occluder, which got closed off at the one-year follow-up. The procedure was well-tolerated hemodynamically in all patients, with no major complications during the peri-procedural period. Short-term follow-up indicated favorable patient progress. Conclusions FASD closure emerges as a pivotal alternative for intricate scenarios involving secundum ASD coupled with concurrent comorbidities, offering individualized tailored solutions. Alongside the conventional associated comorbidities, such as left ventricular diastolic dysfunction and pulmonary hypertension, FASD devices hold the potential to extend their benefits to patients grappling with other complexities, including severe pulmonary valvular stenosis, SLE, predisposition to left atrial arrhythmia, and conditions like DMD. Ensuring meticulous evaluation of patient suitability and providing ongoing vigilant care becomes paramount for achieving optimal outcomes. The validation of these findings and the broadening of the comprehension of this approach necessitate further comprehensive investigations.

Unexpected stormy course after uneventful device closure of atrial septal defect - Possibly due to post-COVID-19 inflammatory state.

COVID-19 infection has myriad manifestations from self-limiting illness to stormy multi-organ failure. A 28-year-old woman negative for COVID reverse transcription-polymerase chain reaction underwent an uneventful elective device closure of atrial septal defect on intubation anesthesia. While a brief postprocedural endotracheal bleed was noted, significant hypoxia and respiratory distress ensued after extubation with biventricular dysfunction, pleural effusion, and radiographic evidence of acute respiratory distress syndrome. COVID antibodies were positive, and inflammatory markers were elevated. After a conservative multipronged medical management including anticoagulation, antibiotics, aspirin, beta-blocker, diuretics, and sildenafil, she improved in 1 week. The clinical course during this pandemic era gives a possibility of a post-COVID inflammatory syndrome as a potential etiology.

Optical temperature sensing by tuning photoluminescence in a wide (visible to near infrared) wavelength range in a Eu3+-doped Bi-based relaxor ferroelectric.

The prevalent material design principles for optical thermometry primarily rely on thermally driven changes in the relative intensities of the thermally coupled levels (TCLs) of rare-earth-doped phosphor materials, where the maximum achievable sensitivity is limited by the energy gap between the TCLs. In this work, a new, to the best of our knowledge, approach to thermometric material design is proposed, which is based on temperature tuning of PL emission from the visible to the NIR region. We demonstrate a model ferroelectric phosphor, Eu3+-doped 0.94(Na1/2Bi1/2TiO3)-0.06(BaTiO3) (NBT-6BT), which, by virtue of the contrasting effects of temperature on PL signals from the host and Eu3+ intraband transitions, can achieve a relative thermal sensitivity as high as 3.05% K-1. This model system provides a promising alternative route for developing self-referencing optical thermometers with high thermal sensitivity and good signal discriminability.

Challenges in Device Closure of Secundum Atrial Septal Defect in Older Patients in Their Fifth Decade and Beyond.

Objective Transcatheter atrial septal defect (ASD) device closure in the older population presents a greater challenge due to the long-standing effect of atrial left-to-right shunt. This study analyzes the challenges encountered in transcatheter ASD device closure in older patients in their fifth decade and beyond. Methods Adults aged 40 years and above with significant secundum ASD who underwent transcatheter ASD device closure between June 2015 and April 2021 were analyzed. Challenges were classified as major and minor challenges based on their impact on the alteration of the treatment protocol. Patients were categorized into three subgroups according to age. Group 1 consisted of patients aged 40-49 years (n = 13), Group 2 consisted of patients aged 50-59 years (n = 16), and Group 3 consisted of patients aged 60 years and above (n = 8). Results A total of 37 patients were analyzed. The challenges encountered were arrhythmia, pulmonary hypertension, left ventricular diastolic dysfunction, bleeding, stroke, coronary artery disease (CAD), hypertension, and airway disease. Thirteen percent of challenges were seen in pre-procedure time, whereas 79% of challenges during the procedure and 8% of challenges during post-procedure were seen. Thirty-five patients (94.6%) underwent transcatheter ASD device closure. Two patients (5.4%) did not undergo transcatheter ASD device closure due to severe diastolic dysfunction and associated CAD, respectively. Eleven major challenges were encountered in 10 patients in which one patient had a dual challenge of bleeding and arrhythmia. Thirteen patients (35.1%) had smooth procedures without any challenges encountered. Twenty-seven minor challenges were encountered in 20 patients with some patients having an overlap of multiple major and minor challenges. The patients were doing well at the mean follow-up of 28 months. Conclusions Transcatheter ASD device closure in older patients who are 40 years and above is safe and effective. Such high-risk patients are prone to various challenges that can be effectively managed if optimally monitored on the basis of a proper understanding of the altered physiology and anticipation of the deviated course at various stages of the procedure.

Spatial wake transition past a thin pitching plate.

The spatial transition of the wake behind a thin pitching plate in the thrust regime is studied. The drag-to-thrust transition is seen to occur at a threshold pitching frequency which becomes smaller for higher pitching angle and aspect ratio. The reverse von Kármán wake shows deflected asymmetric vortex pairing in two dimensions, while a bifurcated wake with a swirling ring is the signature in three dimensions, both resulting in nearly the same scaling for the power coefficient. The wake transition in the thrust regime occurs through three spatial regions comprising the reverse von Kármán vortex street, transitional zone, and twin jet region. Near the trailing edge, reverse von Kármán shedding is marked by linear decay of the spanwise wake width and growth of secondary instability. A large volume of fluid resulting from inward horizontal acceleration renders a weak form drag in the subsequent transition zone which is followed by vertical bifurcation into twin jet formation in the far wake. The spanwise pressure gradient is seen to guide the wake compression, with a streamwise adverse pressure gradient aiding it in the near wake.

Antimicrobial loaded gum odina - gelatin based biomimetic spongy scaffold for accelerated wound healing with complete cutaneous texture.

The main objective of this study was to assess the therapeutic activity of gum odina and gelatin based biomimetic scaffold which was previously established as an excellent wound dressing material. In the accelerated stability study, the changes in physicochemical properties were found to be negligible. The cytotoxicity studies were carried out in-vitro and the results showed that upto 90% of the cells remained viable in presence of the scaffold, confirming its biocompatibility. Moreover, results depicted the superior ability of the scaffold to promote cutaneous healing by increasing the rate of wound contraction (about 98%), granulation formation, collagen deposition and formation of an intact epidermis within 18 days. A satisfactory amount of hydroxyproline (240.2 ± 6.67 µg/100 mg tissue) in scaffold treated groups at 21 days ensured the significant deposition of collagen to re-epithelialization. Further it can be hypothesized that the controlled levels of antioxidant enzymes (SOD, CAT) to diminish the oxidative stress in the wounded sites were due to the innate antioxidant properties of both blank and drug loaded scaffold. These results strongly indicated that the prepared scaffolds have strong potential for biomedical applications and it may serve as promising candidate for the next generation of wound treatment systems.

Radiofrequency ablation for fascicular ventricular tachycardia causing tachycardiomyopathy and brief literature review.

A 10-years-old boy presented with a history of effort intolerance and palpitations for 4 months. His electrocardiogram showed wide complex tachycardia suggestive of fascicular ventricular tachycardia (VT). The echocardiogram showed moderate-to-severe left ventricular systolic dysfunction without any structural lesion. The tachycardia was unresponsive to adenosine and direct current cardioversion. It responded to oral verapamil. The electrophysiology study confirmed the tachycardia as left posterior fascicular VT. The tachycardia was successfully ablated guided by Purkinje potential on three-dimensional mappings. He showed improvement in ventricular functions before discharge. He is doing well on short-term follow-up.

Percutaneous closure of large pulmonary artery to left atrial fistula.

Pulmonary artery to the left atrial fistula is a rare anomaly. Two young males presented with effort intolerance and cyanosis and had large pulmonary artery to left atrial fistula from right and left pulmonary artery, respectively. The right-sided fistula was closed with a large duct occluder device in transseptal approach whereas the left-sided fistula was closed with a large muscular ventricular septal device. Complete occlusion and symptomatic relief was achieved in both cases. In the follow up the patients were doing well.

Characterization of an arabinogalactan isolated from gum exudate of Odina wodier Roxb.: Rheology, AFM, Raman and CD spectroscopy.

Purified gum odina (PGO) from Odina wodier Roxb. was characterized by rheology, AFM, Raman and CD spectroscopy, in vitro antioxidant activity against hydroxyl radical and superoxide radical, and total antioxidant capacity. The PGO dispersions exhibited pseudoplastic behaviour. The viscosity of dispersion increased with increasing PGO concentration, but decreased with increasing temperature and added salt concentration. The loss modulus was higher than storage modulus indicating prevalently viscous characteristics. AFM analysis showed irregular spherical lumps due to inter- and intramolecular interactions. The Raman spectrum of PGO was similar to that of gum arabic. Circular dichroism revealed partial adoption of polyproline II type conformation, suggesting a less compact structure. The PGO was found to scavenge hydroxyl radical (IC50 517.68 ± 3.60 µg/mL) and superoxide radical (IC50 586.21 ± 3.41 µg/mL), and possess total antioxidant capacity (9.64 ± 0.23 mg gallic acid equivalent/g). Overall, this work would exploit PGO as a new hydrocolloid source in the food and pharmaceutical industries.

Aluminium accumulation in excess and related anti-oxidation responses in C4 weed (Amaranthus viridis L.).

C4 species, Amaranthus viridis L. exhibited a significant bioaccumulation of aluminium (Al) through the duration of 3- and 5-days exposure. As compared to control, Amaranthus appeared as excess-accumulator with maximum 5.85-fold bioaccumulation of Al in root. Cellular responses to Al tolerance initially scored tissue specific distribution of metal through cortical layers revealed by electron microscopy. The affected cells changed an oxidative status as read by histochemical stains, particularly, for hydrogen peroxide. Osmotic stress and its stability were scored by maximum proline and free amino acids accumulation with 1.53 and 1.59-fold increase over control. The accumulation of phenolics and flavonoids were over expressed in the ranges of 2.48-2.50-fold and 2.00-1.5-fold at 3- and 5-days respectively against control. Anti-oxidation to detoxify Al stress was facilitated by variants of peroxidases. For exclusion mechanism of metal, esterase activity significantly over expressed with maximum value of 1.80-fold at 5-days. The polymorphism of esterase exhibited few significant over produced bands, varied in numbers as detected by densitometric scanning. Moreover, plant extract was satisfactorily potential under in vitro anti-oxidation systems through assay of 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), ferric chelation activity etc. Therefore, weeds like Amaranthus would be a bioprospecting in role likely involved in phytoremediation of metal.

Novel use of Konar-multifunctional occluder.

INTRODUCTION: Lifetech Konar-multifunctional occluder is a novel device which is primarily used for the closure of ventricular septal defects. Being "multifunctional", the occluder has the potential to be useful in various structural cardiac defects. MATERIALS AND METHODS: We share our retrospective review from two centres regarding non-conventional usage of multifunctional occluders in CHD. Eight patients who underwent interventions using multifunctional occluders for lesions other than ventricular septal defects between March 2019 to September 2019 were included in the study. The patients were analysed based on demography, the size and type of lesion, procedural success, and development of complications. All patients were followed up in the outpatient department for a minimum period of 6 months. RESULTS: The median age and weight of the cohort were 3.2 years and 9 kg, respectively. Six patients had patent ductus arteriosus, while one patient had aorto-pulmonary window and one had a coronary arterio-venous fistula. The sizing of the occluders and the procedural approach were based on the underlying pathology. The most commonly used occluder was 6 × 4 mm variant. One patient had successful implantation but had significant intra-device residual flow and was thus replaced by a different occluder. There were no major complications, nor any incidences of device embolisation or malposition. On follow-up, all patients had uneventful course. CONCLUSION: Konar-multifunctional occluder can be safely used in lesions other than ventricular septal defects, when needed under specific circumstances. Its unique characteristics make it a versatile choice in a variety of cardiac lesions.

Silver Can Induce Oxidative Stress in Parallel to Other Chemical Elicitors to Modulate the Ripening of Chili Cultivars.

Two chili cultivars, i.e., cv. Bullet and cv. Tejaswini, were evaluated on postharvest related ripening characteristics with varying durations under hydrogen peroxide, putrescine and silver treatments. The reducing sugar was inversely related to the maximum values at 7 days of ripening. Silver and putrescine were the most regulatory in terms of changing of the total carbohydrate content as compared to hydrolysis of the total reducing sugar. Regarding pectin methylesterase activity, both chilies were consistent, regardless of the number of days of incubation. Still, putrescine and silver were significant contributors to variations in cv. Bullet and cv. Tejaswani. For the pigment content, lycopene and chlorophyll increased in a linear manner, although these treatments significantly varied over time. Hydrogen peroxide and putrescine were responsible for the maximum accumulation of lycopene for both the cultivars, whereas, only cv. Tejaswani displayed maximum carotenoid for putrescine. Silver for both chili varieties was the most inhibitory for lycopene and carotenoid content. Superoxide had a good impact on the accumulation of lipid peroxides, irrespective of the chili variety. The maximum accumulation of lipid peroxide was recorded at seven days of treatment. Phenolics and flavonoids were in decreasing order for both the chili varieties, progressing through the days of the study period in a similar manner. Silver was the main contributor to variations in the phenolics and flavonoid contents in cv. Tejaswani. The solubilization of total carbohydrate into reducing sugar was in an inverse relationship, with the maximum values being reached at 7 days of ripening.

Metabolite profiling and in-vitro colon cancer protective activity of Cycas revoluta cone extract.

The methanolic extract of Cycas revoluta cone (MECR) was analyzed by GC-MS and UHPLC for metabolite profiling and was evaluated for anti-colon cancer property by using in vitro assays like Cell Viability Assay, Colony Formation Assay, ROS Determination, Flowcytometry, DAPI staining assay, Tunel assay. GC-MS and HPLC analysis confirmed the presence of different phytochemicals in the extract of Cycas revoluta cone. In-vitro studies showed MECR extract showed significant anti-colon cancer activity by reducing proliferation and inducing apoptosis in colon cancer cell (HCT-8) line, but no such activity was seen in normal colon cell (CCD-18Co) line. The investigation confirms that MECR may be a promising candidate in colon cancer protection.

Abscisic acid induced cellular responses of sub1A QTL to aluminium toxicity in rice (Oryza sativa L.).

Involvement of abscisic acid (ABA) was studied for aluminium (Al) sensitivity through functioning of sub1A quantitative trait loci in rice cultivars. sub1A quantitative trait loci bearing cv. Swarna Sub1 was found almost compatible with non sub1A quantitative trait loci bearing cv. Swarna for abscisic acid accumulation all through the aluminium concentrations. However, abscisic acid was self inductive by over expression of its biosynthetic gene in nine-cis-epoxycarotenoid dioxygenase 3 (NCED3) more in cv. Swarna than other. The effect of abscisic acid pretreatment was variable for specific leaf weight, leaf mass ratio and others for the cultivars. Bio-accumulation of aluminium had revealed the sensitivity of toxicity more in cv. Swarna than other. In connection to oxidative stress generation of reactive oxygen species was detected by both histochemical and in vitro assays through hematoxylin, Evans blue and schiff's reactions. Abscisic acid pretreatment had significantly reversed the effects of aluminium toxicity for reactive oxygen species generation. Regardless of varieties sensitivity of aluminium was more prone in shoot than root as detected by nitro blue tetrazolium and 3,3'-diaminobenzidine mediated signalling. Activity in metal chelation in extra cellular spaces monitored through esterase activity and that also established independence of abscisic acid pretreatment for cv. Swarna Sub1. The specific polymorphism of esterase at protein level strengthened the bio-monitoring of aluminium through the rice varieties as well its modulation with abscisic acid. Abscisic acid has been discussed an important effectors to modulate the tolerance pathway of rice cultivars through intrusion of sub1A quantitative trait loci.

Seasonal Variation of Phyto-Constituents of Tea Leaves Affects Antiproliferative Potential.

Objective: Tea (Camellia sinensis Linn.; family: Theaceae) is popular as a stimulant beverage across the globe and is also utilized as a functional antioxidant in alternative medicine. This study has evaluated the impact of seasonal variation on phyto-constituents of tea. Method: The antiproliferative potential of methanolic extracts of tea leaves collected in the rainy season (MECR) was compared with the extract of tea leaves collected in the autumn season (MECA) of the same mother plant. Evaluation of in vivo antitumor activity was carried out in adult female Swiss albino mice groups inoculated with Ehrlich ascites carcinoma (EAC) cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to compare efficacy of MECR with that of MECA in the EAC cell line. Both qualitative and quantitative tests for phytochemical constituents present in MECA and MECR were performed. Antitumor efficacy of both the extracts was determined by evaluating different tumor markers showing dose-dependent cytotoxicity. Results: Statistically significant reduction in EAC-induced tumor was observed in MECR treated mice compared to MECA treated ones. Cell decimation was significantly higher with MECR treatment, where restoration of different parameters including tissue structures returned to normal. Moreover, gas chromatography-mass spectrometry (GC-MS) study revealed the presence of cyclobarbital and benzazulene derivative in MECR, which is thought to be a novel source of these chemicals. Conclusions: To our knowledge, there is no report that has attempted to reveal nutritional changes in terms of efficacy and variation in anticancer constituents in tea leaves, plucked in two seasons. This study revealed a novel source of barbital and benzazulene derivative. The unique presence of cyclobarbital and benzazulene, as revealed from GC-MS data, in methanolic extract of tea leaves collected during the rainy season (MECR) may have contributed to its enhanced in vitro (adopting MTT assay) and in vivo (on EAC-infected Swiss albino mice) cytotoxicity vis-à-vis antiproliferative properties compared to methanolic extract of tea leaves collected during the autumn season (MECA). The nature of plucking leaves in the two selected seasons is different.

Moderation of physiological responses in rice plants with Azolla under 2,4-Dichlorophenoxy acetic acid stress.

The present work highlights some preliminary observations on metabolism in rice (Oryza sativa Linn.) when an aquatic fern Azolla pinnata R.Br. was co-cultured under 2,4-Dichlorophenoxy acetic acid toxicity. We have observed the effects of Azolla in both fresh and dried forms. This work signifies the possible physiological changes of a crop plant by using Azolla as a bioremediator. In brief the herbicide 2,4-D is considered as stressor to rice plants and by applying the fresh and dried Azolla we investigate the changes occurred. The activities of different nitrogen metabolizing enzymes and reactive oxygen species were observed. On the other hand chlorophyll and carotenoids synthesis were retrieved by addition of fresh and dried Azolla mass over 2,4-D toxicity. Thus, the efficiency of fresh and dried Azolla mass was evaluated under herbicidal toxicity in rice. We evaluate the bio remediating role of Azolla plants against 2,4-D stress and conclude this species would also be supporting in supplementation of major nutrients to rice plants.

Effect of Morphology and Concentration on Crossover between Antioxidant and Pro-oxidant Activity of MgO Nanostructures.

The toxicity of nanomaterials can sometimes be attributed to photogenerated reactive oxygen species (ROS), but these ROS can also be scavenged by nanomaterials, yielding opportunities for crossover between the properties. The morphology of nanomaterials also influences such features due to defect-induced properties. Here we report morphology-induced crossover between pro-oxidant activity (ROS generation) and antioxidant activity (ROS scavenging) of MgO. To study this process in detail, we prepared three different nanostructures of MgO (nanoparticles, nanoplates, and nanorods) and characterized them by HRTEM. These three nanostructures effectively generate superoxide anions (O2•-) and hydroxyl radicals (•OH) at higher concentrations (>500 µg/mL) but scavenge O2•- at lower concentrations (40 µg/mL) with successful crossover at 200 µg/mL. Nanorods of MgO generate the highest levels of O2•-, whereas nanoparticles scavenge O2•- to the highest extent (60%). Photoluminescence studies reveal that such crossover is based on the suppression of F2+ and the evolution of F+, F2+, and F23+ defect centers. The evolution of these defect centers reflects the antibacterial activity of MgO nanostructures which is initiated at 200 µg/mL against Gram-positive S. aureus ATCC 29737 and among different bacterial strains including Gram-positive B. subtilis ATCC 6633 and M. luteus ATCC 10240 and Gram-negative E. coli ATCC K88 and K. pneumoniae ATCC 10031. Nanoparticles exhibited the highest antibacterial (92%) and antibiofilm activity (17%) against B. subtilis ATCC 6633 in the dark. Interestingly, the nitrogen-centered free radical DPPH is scavenged (100%) by nanoplates due to its large surface area (342.2 m2/g) and the presence of the F2+ defect state. The concentration-dependent interaction with an antioxidant defense system (ascorbic acid (AA)) highlights nanoparticles as potent scavengers of O2•- in the dark. Thus, our findings establish guidelines for the selection of MgO nanostructures for diverse therapeutic applications.

Modulation of physiological responses with TiO2 nano-particle in Azolla pinnata R.Br. under 2,4-D toxicity.

The present work is emphasised with the herbicidal tolerance of Azolla pinnata R.Br. and its modulation with TiO2 nano-particle. Both carbohydrate and nitrogen metabolism were effected with 2,4-D as herbicide and in few cases TiO2-NP had recovered few detrimental effects. From the nutrient status in Azolla it recorded the recovery of nitrogen as well as potassium by TiO2-NP but not in case of phosphorus. However, a conversion of nitrate to ammonium was more induced by TiO2-NP under herbicidal toxicity. Similar results were obtained for inter-conversion of amino acid-nitrate pool, but no changes with glutamine synthase activity with TiO2-NP. Initially, the effects of 2,4-D was monitored with changes of chlorophyll content but had not been recovered with nanoparticle. Photosynthetic reserves expressed as both total and reducing sugar were insensitive to TiO2-NP interference but activity of soluble and wall bound invertase was in reverse trend as compared to control. The 2,4-D mediated changes of redox and its oxidative stress was ameliorated in plants with over expressed ADH activity. As a whole the Azolla bio system with TiO2 supplementation may be useful in sustenance against 2,4-D toxicity through recovery of nitrogen metabolism. Thus, Azolla-TiO2-NP bio system would be realised to monitor the herbicidal toxicity in soil and its possible bioremediation.

Novel fused oxazepino-indoles (FOIs) attenuate liver carcinogenesis via IL-6/JAK2/STAT3 signaling blockade as evidenced through data-based mathematical modeling.

AIMS: To potentiate the well-documented tumor protecting ability of paullones, literatures demand for rational modifications in paullone ring structure and exploration of a precise mechanism underlying their antitumor effects. Thus, recently we synthesized novel paullone-like scaffold, 5H-benzo [2, 3][1,4]oxazepino[5,6-b]indoles, where compounds 13a and 14a attenuated the growth of liver cancer specific Hep-G2 cells in vitro and formed stable binding complex with IL-6. Henceforth, we hypothesized that this action is probably due to the blockade of IL-6 mediated JAK2/STAT3 signaling cascade. MAIN METHODS: A preclinical study was conducted using NDEA-induced HCC rat model by oral administration of FOIs at 10 mg/kg dose for 15 days. The molecular insights were confirmed through ELISA, qRT-PCR, western blot analyses. The study was further confirmed by data-based mathematical modeling using the quantitative data obtained from western blot analysis. 1H NMR based metabolomics study was also performed to unveil metabolite discriminations among various studied groups. KEY FINDINGS: We identified that the HCC condition was produced due to the IL-6 induced activation of JAK2 and STAT3 which, in turn, was due to enhanced phosphorylation of JAK2 and STAT3. The treatment with FOIs led to the significant blockade of the IL-6 mediated JAK2/STAT3 signaling pathway. Besides, FOIs showed their potential ability in restoring perturbed metabolites linked to HCC. In particular, the anticancer efficacy of compound 13a was comparable or somewhat better than marketed chemotherapeutics, 5-flurouracil. SIGNIFICANCE: These findings altogether opened up possibilities of developing fused oxazepino-indoles (FOIs) as new candidate molecule for plausible alternative of paullones to treat liver cancer.