Targeting AFP-RARß complex formation: a potential strategy for treating AFP-positive hepatocellular carcinoma.

Alpha-fetoprotein (AFP) is a glycoprotein primarily expressed during embryogenesis, with declining levels postnatally. Elevated AFP levels correlate with pathological conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Recent investigations underscore AFP's intracellular role in HCC progression, wherein it forms complexes with proteins like Phosphatase and tensin homolog (PTEN), Caspase 3 (CASP3), and Retinoic acid receptors and Retinoid X receptors (RAR/RXR). RAR and RXR regulate gene expression linked to cell death and tumorigenesis in normal physiology. AFP impedes RAR/RXR dimerization, nuclear translocation, and function, promoting gene expression favoring cancer progression in HCC that provoked us to target AFP as a drug candidate. Despite extensive studies, inhibitors targeting AFP to disrupt complex formation and activities remain scarce. In this study, employing protein-protein docking, amino acid residues involved in AFP-RARß interaction were identified, guiding the definition of AFP's active site for potential inhibitor screening. Currently, kinase inhibitors play a significant role in cancer treatment and, the present study explores the potential of repurposing FDA-approved protein kinase inhibitors to target AFP. Molecular docking with kinase inhibitors revealed Lapatinib as a candidate drug of the AFP-RARß complex. Molecular dynamics simulations and binding energy calculations, employing Mechanic/Poisson-Boltzmann Surface Area (MM-PBSA), confirmed Lapatinib's stability with AFP. The study suggests Lapatinib's potential in disrupting the AFP-RARß complex, providing a promising avenue for treating molecularly stratified AFP-positive HCC or its early stages.

Clinical Profile and Outcome of Severe Acute Respiratory Illness (SARI) in Children Amidst the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES:  Beginning in December 2019, COVID-19 rapidly emerged as a global pandemic. Though its severity in children was reported to be less than that in adults, data on its epidemiology in relation to severe acute respiratory illness (SARI) caused by other microbes needed to be generated. This study compares the clinical profile and outcome of children hospitalized with COVID-19-positive and negative SARI. METHODS:  This is a prospective observational analytical study involving children 1 month to 18 years old, hospitalized with COVID-19-positive and negative SARI during the pandemic. All eligible patients were enrolled after obtaining informed parental consent. Their clinical manifestations, investigations, and outcomes were documented on a predesigned case record form. A nasopharyngeal swab sample for COVID-19 reverse transcription polymerase chain reaction was sent, and results were noted. RESULTS:  From May 2020 to July 2021, 267 children were hospitalized with a diagnosis of SARI. Out of these, 146 (54.7%) were boys and 78.7% were under five years of age. Other presentations included fever and cough, breathlessness, nausea, vomiting, diarrhea, rash, seizures, and altered sensorium. Twenty-eight patients (10.5%) tested positive for COVID-19. COVID-19 patients were similar in terms of demographic characteristics and presenting symptoms to non-COVID-19 patients but had a lower absolute lymphocyte count (p = 0.019) and higher serum alanine transaminase levels (p = 0.013). Acute respiratory distress syndrome (OR, 4.3; 95% CI, 1.8-10.0), shock (OR, 3.9; 95% CI, 1.9-7.9), and need for intensive care unit admission (OR, 9.9; 95% CI, 6.9-14) were more common in COVID-19 SARI patients. Death occurred in 18% of COVID-19 and 9% of non-COVID-19 patients (p = 0.07). SARI nonsurvivors had significantly lower blood pH and platelet counts than survivors. CONCLUSIONS: Comparison of COVID-19-positive and negative SARI patients showed subtle differences between the two groups, with COVID-19-positive children having an increased severity of illness. Also, laboratory evidence of multiorgan dysfunction at admission was associated with higher mortality.

Concomitant Tricuspid Valve Ring Annuloplasty During Mitral Valve Surgery Versus Mitral Valve Surgery Alone: A Systematic Review and Meta-Analysis.

AIM: Although current guidelines recommend concomitant tricuspid annuloplasty for moderate or greater tricuspid regurgitation (TR) and/or dilated annulus, there remains significant variation in undertaking concomitant tricuspid valve surgery (TVA) across different centres. This meta-analysis aimed to compare the clinical outcomes of concomitant tricuspid valve surgery for patients with moderate or greater TR and/or dilated annulus at the time of mitral valve (MV) surgery. METHOD: A systematic review of the literature using six databases. Eligible studies include comparative studies on TVA concomitant with MV surgery versus MV surgery alone. A meta-analysis was performed on studies reporting outcomes of interest to quantify the effects of concomitant tricuspid ring annuloplasty. RESULTS: Two randomised controlled trials and six cohort studies were included in the analysis. 1,941 patients were included in the analysis, of whom, 1,090 underwent concomitant TVA and 851 underwent MV surgery alone. Pooled analysis demonstrated that there was less progression of moderate/severe TR in the concomitant group (3.0% vs 9.6%; odds ratio [OR] 0.29; 95% confidence interval [CI] 0.13-0.55; p=0.0001). There was no significant difference in in-hospital mortality (3.0% vs 3.8%; OR 0.79; 95% CI 0.47-1.34; p=0.38). The rate of permanent pacemaker implantation was higher in the concomitant group although this did not reach statistical significance (7.6% vs 5.3%; OR 1.30; 95% CI 0.85-1.98; p=0.23). Cardiopulmonary bypass was longer in the concomitant TVA group by 20 minutes (mean difference 13.9-26.0; p<0.00001). CONCLUSIONS: Our study demonstrated that concomitant tricuspid ring annuloplasty at the time of MV surgery is associated with a significantly lower rate of TR progression without increasing the operative mortality. There is a trend towards a higher permanent pacemaker implantation rate although this did not reach statistical significance.

Acid-catalyzed Transformation of Nitrite to Nitric Oxide on Copper(II)-Cobalt(II) Centers in a Bimetallic Complex.

Nitrite (NO2-) serves as a pool of nitric oxide (NO) in biological systems under hypoxic conditions, and it is transformed to NO by nitrite reductase (NiR) enzyme in the presence of acid. However, NO synthases generate NO in normoxic conditions. Previously, acid-induced NO2- reduction chemistry was modeled on mono-metallic 3d-metals, generating metal-nitrosyls or NO(g) with H2O or H2O2 products. Herein, to understand the relative potency of a bimetallic system, we report the acid-induced reductive conversion of η2-bound NO2- to NO on CuII-CoII centers of a hetero-bimetallic CuII­nitrito-CoII complex, [(LN8H)CuII­NO2-­CoII]3+ (CuII-NO2--CoII, 2) bearing an octadentate N8-cryptand ligand (LN8H). The CuII-NO2--CoII generates [CuII(LN8H)CoII]4+ (1) upon reaction with one equiv. acid (HClO4, H+ ions source) with NO(g) via a presumed transient nitrousacid (ONOH) intermediate species. Likewise, this NO2- reduction was found to form H2O, which is believed to be from the decomposition of H2O2, an intermediate species. In addition, complex 2, in the presence of more than one equiv. H+ ions also showed the formation of NO(g) with H2O. Mechanistic investigations, using 15N-labeled-15NO2-, 18O-labeled-18O14N16O- and 2H-labeled-DClO4 (D+ source), revealed that the N-atom and O-atom in the 14/15NO and 14N18O gases are derived from NO2- ligand and H-atom in H2O derived from H+-source, respectively.

Delineating dengue risk zones in Jaipur: An interdisciplinary approach to inform public health strategies.

Dengue fever (DF) is a pervasive public health concern in tropical climates, with densely populated regions, such as India, disproportionately affected. Addressing this issue requires a multifaceted understanding of the environmental and sociocultural factors that contribute to the risk of dengue infection. This study aimed to identify high-risk zones for DF in Jaipur, Rajasthan, India, by integrating physical, demographic, and epidemiological data in a comprehensive risk analysis framework. We investigated environmental variables, such as soil type and plant cover, to characterize the potential habitats of Aedes aegypti, the primary dengue vector. Concurrently, demographic metrics were evaluated to assess the population's susceptibility to dengue outbreaks. High-risk areas were systematically identified through a comparative analysis that integrated population density and incidence rates per ward. The results revealed a significant correlation between high population density and an increased risk of dengue, predominantly facilitated by vertical transmission. Spatially, these high-risk zones are concentrated in the northern and southern sectors of Jaipur, with the northern and southwestern wards exhibiting the most acute risk profiles. This study underscores the importance of targeted public health interventions and vaccination campaigns in vulnerable areas. It further lays the groundwork for future research to evaluate the effectiveness of such interventions, thereby contributing to the development of robust evidence-based strategies for dengue risk mitigation.

Medicinal plants traditionally used in health care practices by inhabitants of Paddar region of Jammu and Kashmir, India.

ETHNOPHARMACOLOGICAL RELEVANCE: The present study is the first quantitative assessment of ethno-medicinal plants of Paddar region of Jammu and Kashmir. AIM OF THE STUDY: The study aimed to document the relative importance of medicinal plants used in human ailments by the villagers in the Paddar region of Jammu and Kashmir, India. MATERIAL AND METHODS: Data were collected from 132 informants (72 male and 60 female) through semi structured interviews and group discussions. Use report (UR) and Informant consensus factor (ICF) were employed to quantitatively examine the data. RESULTS: The inhabitants of Paddar reported the use of 98 plants species of 55 families to treat 63 ailments. Rosaceae (10 spp.) was the most frequently used family in the study area. Herbs were dominantly (66 spp., 50%) utilized in herbal preparation and leaves the mostly used plant parts (25%). The highest informant consensus factor (ICF = 0.96) was obtained for parasitic problems. Important new uses for species stated by informants to treat human diseases were; Viburnum grandiflorum Wall. ex DC., Sium latijugum C.B.Clarke, Corylus jacquemontii Decne., Capsella bursa-pastoris (L.) Medik., Cannabis sativa L., Taraxacum campylodes G.E.Haglund, Euphorbia helioscopia L., Juglans regia L., Cotoneaster acuminatus Lindl., Ficus palmata Forssk., Plantago lanceolata L., and Eleusine coracana (L.) Gaertn. CONCLUSIONS: The current study contributes towards the preservation of indigenous plants' based knowledge. Although the therapeutic value of most of the preferred medicinal plants has already been validated, some medicinal plants lack proper scientific validation. We recommend further phytochemical investigations and pharmacological validations of Viburnum grandiflorum, C. jacquemontii, F. palmata, Viola pilosa, Cotoneaster acuminatus, Eleucine coracana, Sium latijugum, Aquilegia pubiflora, Euphorbia helioscopia, Plantago lanceolata and Pinus gerardiana.

Turn-on detection of Al3+ ions using quinoline-based tripodal probe: mechanistic investigation and live cell imaging applications.

In this study, an easily synthesizable Schiff base probe TQSB having a quinoline fluorophore is demonstrated as a fluorescent and colorimetric turn-on sensor for Al3+ ions in a semi-aqueous medium (CH3CN/water; 4 : 1; v/v). Absorption, emission and colorimetric studies clearly indicated that TQSB exhibited a high selectivity toward Al3+, as observed from its excellent binding constant (Kb = 3.8 × 106 M-1) and detection limit (7.0 nM) values. TQSB alone was almost non-fluorescent in nature; however, addition of Al3+ induced intense fluorescence at 414 nm most probably due to combined CHEF (chelation-enhanced fluorescence) and restricted PET effects. The sensing mechanism was established via Job's plot, NMR spectroscopy, ESI-mass spectrometry, and density functional theory (DFT) analyses. Furthermore, to evaluate the applied potential of probe TQSB, its sensing ability was studied in real samples such as soil samples and Al3+-containing Digene gastric tablets as well as on low-cost filter paper strips. Fluorescence microscopy imaging experiments further revealed that TQSB can be used as an effective probe to detect intracellular Al3+ in live cells with no cytotoxicity.

Dithiophosphonate-Protected Eight-Electron Superatomic Ag21 Nanocluster: Synthesis, Isomerism, Luminescence, and Catalytic Activity.

The structure-property relationship considering isomerism-tuned photoluminescence and efficient catalytic activity of silver nanoclusters (NCs) is exclusive. Asymmetrical dithiophosphonate NH4[S2P(OR)(p-C6H4OCH3)] ligated first atomically precise silver NCs [Ag21{S2P(OR)(p-C6H4OCH3)}12]PF6 {where, R = nPr (1), Et (2)} were established by single-crystal X-ray diffraction and characterized by electrospray ionization mass spectrometry, NMR (31P, 1H, 2H), X-ray photoelectron spectroscopy, UV-visible, energy-dispersive X-ray spectroscopy, Fourier transforms infrared, thermogravimetric analysis, etc. NCs 1 and 2 consist of eight silver atoms in a cubic framework and enclose an Ag@Ag12-centered icosahedron to constitute an Ag21 core of Th symmetry, which is concentrically inscribed within the S24 snub-cube, P12 cuboctahedron, and the O12 truncated tetrahedron formed by 12 dithiophosphonate ligands. These NCs facilitate to be an eight-electron superatom (1S21P6), in which eight capping Ag atoms exhibit structural isomerism with documented isoelectronic [Ag21{S2P(OiPr)2}12]PF6, 3. In contrast to 3, the stapling of dithiophosphonates in 1 and 2 triggered bluish emission within the 400 to 500 nm region at room temperature. The density functional theory study rationalized isomerization and optical properties of 1, 2, and 3. Both (1, and 2) clusters catalyzed a decarboxylative acylarylation reaction for rapid oxindole synthesis in 99% yield under ambient conditions and proposed a multistep reaction pathway. Ultimately, this study links nanostructures to their physical and catalytic properties.

Peroral Endoscopic Myotomy: Short Versus Long Esophageal Myotomy for Achalasia Cardia: A Randomized Controlled Noninferiority Trial.

BACKGROUND AND AIMS: The appropriate length of esophageal myotomy in peroral endoscopic myotomy (POEM) for achalasia cardia remains unclear. This study aimed to compare the outcome of short (≤3 cm) and long (≥6 cm) esophageal myotomy in patients with type I and II achalasia cardia. METHODS: This single-blinded, randomized controlled noninferiority trial was conducted at a tertiary center between July 2021 and December 2021. Patients with achalasia types I and II were randomized into short (≤3 cm) and long (≥6 cm) esophageal myotomy groups. The primary outcome of the study was clinical success (Eckardt score ≤3) 1 year after the procedure. The secondary outcomes included a comparison of technical success, operating duration, occurrence of intraoperative adverse events, alterations in integrated relaxation pressure (IRP), change in barium column height after 5 minutes (1 mo), and gastroesophageal reflux disease (3 mo) between the groups. RESULTS: Fifty-four patients were randomized into the short (n=27) or long (n=27) esophageal myotomy groups. Technical success rates were 100% (27/27) and 96.3% (26/27) in short myotomy (SM) and long myotomy (LM) groups, respectively. The clinical success rates were 96.3% (26/27) and 96.2% (25/26) in the SM and LM groups, respectively (P=0.998). The mean (±SD) length of the esophageal myotomy was 2.75±0.36 cm in the SM and 6.69±1.35 cm in the LM groups (P<0.001). The mean (±SD) procedure time for the SM and LM groups was 61.22±8.44 and 82.42±14.70 minutes (P<0.001), respectively. The mean integrated relaxation pressure (IRP), Eckardt score, adverse events, reflux esophagitis, symptomatic gastroesophageal reflux disease, and esophageal acid exposure (>6%) did not differ significantly between the 2 groups following POEM treatment. CONCLUSIONS: Short myotomy is noninferior to long myotomy in terms of clinical success, gastroesophageal reflux disease, and intraoperative adverse events at the short-term follow-up (P>0.05). Short myotomy resulted in a reduced operative time (P<0.05).

Bioinspired Diiron Complex with Proton Shuttling and Redox-Active Ligand for Electrocatalytic Hydrogen Evolution.

A µ-oxo diiron complex, featuring the pyridine-2,6-dicarboxamide-based thiazoline-derived redox-active ligand, H2L (H2L = N2,N6-bis(4,5-dihydrothiazol-2-yl)pyridine-2,6-dicarboxamide), was synthesized and thoroughly characterized. [FeIII-(µ-O)-FeIII] showed electrocatalytic hydrogen evolution reaction activity in the presence of different organic acids of varying pKa values in dimethylformamide. Through electrochemical analysis, we found that [FeIII-(µ-O)-FeIII] is a precatalyst that undergoes concerted two-electron reduction to generate an active catalyst. Fourier transform infrared spectrum of reduced species and density functional theory (DFT) investigation indicate that the active catalyst contains a bridged hydroxo unit which serves as a local proton source for the Fe(III) hydride intermediate to release H2. We propose that in this active catalyst, the thiazolinium moiety acts as a proton-transferring group. Additionally, under sufficiently strong acidic conditions, bridged oxygen gets protonated before two-electron reduction. In the presence of exogenous acids of varying strengths, it displays electro-assisted catalytic response at a distinct applied potential. Stepwise electron-transfer and protonation reactions on the metal center and the ligand were studied through DFT to understand the thermodynamically favorable pathways. An ECEC or EECC mechanism is proposed depending on the acid strength and applied potential.

Nitric oxide mediated kisspeptin regulation of steroidogenesis and gametogenesis in the catfish, Clarias batrachus.

Nitric oxide (NO) is a gaseous molecule that regulates various reproductive functions. It is a well-recognized regulator of GnRH-FSH/LH-sex steroid secretion in vertebrates including fish. Kisspeptin is a recently discovered neuropeptide which also regulates GnRH secretion. Nitrergic and kisspeptin neurons are reported in close physical contact in the mammalian brain suggesting their interactive role in the release of GnRH. The existence of kisspeptin and NOS is also demonstrated in vertebrate gonads, but information on their reciprocal relation in gonads, if any, is obscure. Therefore, attempts were made to evaluate the functional reciprocal relation between nitric oxide and kisspeptin in the catfish gonads, if any, by administering the nitric oxide synthase (NOS) inhibitor, L-NAME {N(G)-nitro-L-arginine methyl ester}, which reduces NO production, and kisspeptin agonist (KP-10) and assessing their impacts on the expressions of kisspeptin1, different NOS isoforms, NO and steroid production in the gonadal tissue. The results revealed that L-NAME suppressed the expression of kiss1 in gonads of the catfish establishing the role of NO in kisspeptin expression. However, KP-10 increased the expression of all the isoforms of NOSs (iNOS, eNOS, nNOS) and concurrently NO and steroids in the ovary and testis. In vitro studies also indicate that kisspeptin stimulates the production of NO and estradiol and testosterone levels in the gonadal explants and medium. Thus, in vivo results clearly suggest a reciprocal interaction between kisspeptin and NO to regulate the gonadal activity of the catfish. The in vitro findings further substantiate our contention regarding the interactive role of kisspeptin and NO in gonadal steroidogenesis.

Anatomical correlates for the newly discovered meningeal layer in the existing literature: A systematic review.

The existence of a previously unrecognized subarachnoid lymphatic-like membrane (SLYM) was reported in a recent study. SLYM is described as an intermediate leptomeningeal layer between the arachnoid and pia mater in mouse and human brains, which divides the subarachnoid space (SAS) into two functional compartments. Being a macroscopic structure, having missed detection in previous studies is surprising. We systematically reviewed the published reports in animals and humans to explore whether prior descriptions of this meningeal layer were reported in some way. A comprehensive search was conducted in PubMed/Medline, EMBASE, Google Scholar, Science Direct, and Web of Science databases using combinations of MeSH terms and keywords with Boolean operators from inception until 31 December 2023. We found at least eight studies that provided structural evidence of an intermediate leptomeningeal layer in the brain or spinal cord. However, unequivocal descriptions for this layer all along the central nervous system were scarce. Obscure names like the epipial, intermediate meningeal, outer pial layers, or intermediate lamella were used to describe it. Its microscopic/ultrastructural details closely resemble the recently reported SLYM. We further examined the counterarguments in current literature that are skeptical of the existence of this layer. The potential physiological and clinical implications of this new meningeal layer are significant, underscoring the urgent need for further exploration of its structural and functional details.

Unraveling the enigma of root-knot nematodes: from origins to advanced management strategies in agriculture.

MAIN CONCLUSION: Integrated management strategies, including novel nematicides and resilient cultivars, offer sustainable solutions to combat root-knot nematodes, crucial for safeguarding global agriculture against persistent threats. Root-knot nematodes (RKN) pose a significant threat to a diverse range of host plants, with their obligatory endoparasitic nature leading to substantial agricultural losses. RKN spend much of their lives inside or in contact by secreting plant cell wall-modifying enzymes resulting in the giant cell development for establishing host-parasite relationships. Additionally, inflicting physical harm to host plants, RKN also contributes to disease complexes creation with fungi and bacteria. This review comprehensively explores the origin, history, distribution, and physiological races of RKN, emphasizing their economic impact on plants through gall formation. Management strategies, ranging from cultural and physical to biological and chemical controls, along with resistance mechanisms and marker-assisted selection, are explored. While recognizing the limitations of traditional nematicides, recent breakthroughs in non-fumigant alternatives like fluensulfone, spirotetramat, and fluopyram offer promising avenues for sustainable RKN management. Despite the success of resistance mechanisms like the Mi gene, challenges persist, prompting the need for integrative approaches to tackle Mi-virulent isolates. In conclusion, the review stresses the importance of innovative and resilient control measures for sustainable agriculture, emphasizing ongoing research to address evolving challenges posed by RKN. The integration of botanicals, resistant cultivars, and biological controls, alongside advancements in non-fumigant nematicides, contributes novel insights to the field, laying the ground work for future research directions to ensure the long-term sustainability of agriculture in the face of persistent RKN threats.

Paleoseismological evidence for segmentation of the Main Himalayan Thrust in the Darjeeling-Sikkim Himalaya.

Whether the Main Himalayan Thrust can host a single surface-rupturing event in the Himalaya with a rupture length of > 700 km remains controversial. Previous paleoseismological studies in the Darjeeling-Sikkim Himalaya (DSH) suggested medieval surface-rupturing earthquakes, correlating them with the eleventh-thirteenth century events from Nepal and Bhutan and extending the coseismic rupture length > 700 km. Conversely, there is no rupture evidence of the 1714 Bhutan and 1934 Bihar-Nepal earthquakes in the DSH, resulting in a discrepancy in the rupture extent of the great earthquakes. Consequently, we conducted a paleoseismological investigation across a ~ 10 m-high fault scarp on the Himalayan Frontal Thrust at Chenga village, DSH, revealing a surface-faulting event during 1313-395 BCE. We suggest that the DSH is a 150 km-long independent segment bounded by a transverse ridge and fault and has a recurrence interval of ~ 949-1963 years, which is significantly larger than Nepal (~ 700-900 years) and Bhutan Himalaya (~ 339-761 years).

Persistent dysbiosis of duodenal microbiota in patients with controlled pediatric Crohn's disease after resolution of inflammation.

Crohn's disease is an inflammatory condition of the intestine characterized by largely unknown etiology and a relapse remission cycle of disease control. While possible triggers have been identified, research is inconsistent on the precise cause of these relapses, especially in the under-researched pediatric population. We hypothesized that patients in remission would have persistent microbial and inflammatory changes in small intestinal tissue that might trigger relapse. To this end, we analyzed intestinal biopsy samples from six patients with pediatric Crohn's disease in remission and a control group of 16 pediatric patients with no evident pathogenic abnormality. We identified compositional microbiota differences, including decreases in the genera Streptococcus and Actinobacillus as well as increases in Oribacterium and Prevotella in patients with controlled Crohn's disease compared to controls. Further, a histologic analysis found that patients with controlled Crohn's disease had increased epithelial integrity, and decreased intraepithelial lymphocytes compared with controls. Additionally, we observed increased peripheral CD4+ T cells in patients with pediatric Crohn's disease. These results indicate that markers of intestinal inflammation are responsive to Crohn's disease treatment, however the interventions may not resolve the underlying dysbiosis. These findings suggest that persistent dysbiosis may increase vulnerability to relapse of pediatric Crohn's disease. This study used a nested cohort of patients from the Bangladesh Environmental Enteric Dysfunction (BEED) study (ClinicalTrials.gov ID: NCT02812615 Date of first registration: 24/06/2016).

Multifaceted role of erlotinib in various cancer: nanotechnology intervention, patent landscape, and advancements in clinical trials.

Erlotinib (ELB) is a tyrosine kinase inhibitor that targets the activity of Epidermal Growth Factor Receptor (EGFR) protein found in both healthy and cancerous cells. It binds reversibly to the ATP-binding site of the EGFR tyrosine kinase. ELB was approved by the US Food and Drug Administration (FDA) in 2004 for advanced non-small cell lung cancer (NSCLC) treatment in patients who relapsed after at least one other therapy. It was authorized for use with gemcitabine in 2005 for the treatment of advanced pancreatic cancer. In addition to lung cancer, ELB has shown promising results in the treatment of other cancers, including breast, prostate, colon, pancreatic, cervical, ovarian, and head and neck cancers. However, its limited water solubility, as a BCS class II drug, presents biopharmaceutical problems. Nanoformulations have been developed to overcome these issues, including increased solubility, controlled release, enhanced stability, tumor accumulation, reduced toxicity, and overcoming drug resistance. In older patients, ELB management should involve individualized dosing based on age-related changes in drug metabolism and close monitoring for adverse effects. Regular assessments of renal and hepatic functions are essential. This review provides an overview of ELB's role of ELB in treating various cancers, its associated biopharmaceutical issues, and the latest developments in ELB-related nanotechnology interventions. It also covers ELB patents granted in previous years and the ongoing clinical trials.

Impact of titanium dioxide (TiO2) nanoparticle and liquid leachate of mushroom compost on agronomic and biochemical response of marigold (Tagetes erecta L.) under saline stress.

The cultivation of ornamental horticultural crops under salinity stress has been a challenge for growers all over the world. In this study, an attempt was made for pot cultivation of Marigold (Tagetes erecta L. var. Pusa Basanti Gainda) in salt-stressed (SS) soil (150 mM) with the combined use of mushroom compost leachate (CL) and foliar application of titanium dioxide nanoparticles (TiO2-NPs). For this purpose, a total of six pot treatments, i.e., borewell water (BW; control), T1 (BW with SS), T2 (BW with SS and TiO2-NPs), T3 (CL supplemented), T4 (CL with SS), and T5 (CL with SS and TiO2-NPs) were conducted in triplicate. The results of this study showed that CL supplementation significantly (p < 0.05) improved the physicochemical i.e., pH (14.5%), electrical conductivity (32.9%), total nitrogen (27.4%), total phosphorus (247.6%)), and nutrient (organic matter: 119.6%) profiles of soil which later helped in higher growth (30-35%) and yield (5.4-40.7%) of T. erecta. In CL-based treatments, the biochemical constituents were significantly (p < 0.05) higher than those in BW-irrigated ones. Also, the levels of selected stress defense enzymes were significantly increased under SS treatment but reduced under TiO2-NP application. Overall, it was observed that the combined application of CL and TiO2-NPs (T5 treatment) was the most helpful treatment for enhanced germination, growth, yield, biochemical parameters, and better plant enzymatic activities to cope with saline stress. This study provides a mechanistic understanding of T. erecta plants under saline stress which is crucial for the development of targeted interventions aimed at improving plant tolerance to saline conditions.

Glaucarubinone from Simarouba glauca DC. as a potential biocontrol agent for mosquito vector management.

The study explored Simarouba glauca DC. for mosquito larvicidal potential by performing bioactivity-guided chemical investigation of its root extract resulting in isolation of the known bioactive metabolite glaucarubinone (1). Mosquito larvicidal activity of glaucarubinone (1) against the three vector species viz. Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus was determined using a modified WHO 2005 protocol. It was observed that Culex quinquefasciatus larvae were the most susceptible species with LC50 13.88 ppm and LC90 70.01 ppm followed by Aedes aegypti and Anopheles stephensi at 24 h of exposure. The mode of action as observed microscopically is the lysis of midgut and thorax cells of the third instar larvae. The crystal structure of the glaucarubinone (1) is reported for the first time using X-ray crystallography. This phytochemical product has the potential to act as a green alternative to existing chemical-based insecticides for integrated vector management.