Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study.

Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR's, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1ß) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.

An unprecedented roll-off ratio in high-performing red TADF OLED emitters featuring 2,3-indole-annulated naphthalene imide and auxiliary donors.

The capability of organic emitters to harvest triplet excitons via a thermally activated delayed fluorescence (TADF) process has opened a new era in organic optoelectronics. Nevertheless, low brightness, and consequently an insufficient roll-off ratio, constitutes a bottleneck for their practical applications in the domain of organic light-emitting diodes (OLEDs). To address this formidable challenge, we developed a new design of desymmetrized naphthalimide (NMI) featuring an annulated indole with a set of auxiliary donors on its periphery. Their perpendicular arrangement led to minimized HOMO-LUMO overlap, resulting in a low energy gap (ΔE ST = 0.05-0.015 eV) and efficient TADF emission with a photoluminescence quantum yield (PLQY) ranging from 82.8% to 95.3%. Notably, the entire set of dyes (NMI-Ind-TBCBz, NMI-Ind-DMAc, NMI-Ind-PXZ, and NMI-Ind-PTZ) was utilized to fabricate TADF OLED devices, exhibiting yellow to red electroluminescence. Among them, red-emissive NMI-Ind-PTZ, containing phenothiazine as an electron-rich component, revealed predominant performance with a maximum external quantum efficiency (EQE) of 23.6%, accompanied by a persistent luminance of 38 000 cd m-2. This results in a unique roll-off ratio (EQE10 000 = 21.6%), delineating a straightforward path for their commercial use in lighting and display technologies.

Micro and nanoplastics pollution: Sources, distribution, uptake in plants, toxicological effects, and innovative remediation strategies for environmental sustainability.

Microplastics and nanoplastics (MNPs), are minute particles resulting from plastic fragmentation, have raised concerns due to their widespread presence in the environment. This study investigates sources and distribution of MNPs and their impact on plants, elucidating the intricate mechanisms of toxicity. Through a comprehensive analysis, it reveals that these tiny plastic particles infiltrate plant tissues, disrupting vital physiological processes. Micro and nanoplastics impair root development, hinder water and nutrient uptake, photosynthesis, and induce oxidative stress and cyto-genotoxicity leading to stunted growth and diminished crop yields. Moreover, they interfere with plant-microbe interactions essential for nutrient cycling and soil health. The research also explores the translocation of these particles within plants, raising concerns about their potential entry into the food chain and subsequent human health risks. The study underscores the urgency of understanding MNPs toxicity on plants, emphasizing the need for innovative remediation strategies such as bioremediation by algae, fungi, bacteria, and plants and eco-friendly plastic alternatives. Addressing this issue is pivotal not only for environmental conservation but also for ensuring sustainable agriculture and global food security in the face of escalating plastic pollution.

Antiproliferative, apoptotic and anti-inflammatory potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues: Novel series of anticancer compounds.

Lung cancer (LC) is the most common cancer in males. As per GLOBOCAN 2020, 8.1 % of deaths and 5.9 % of cases of LC were reported in India. Our laboratory has previously reported the significant anticancer potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues. In this study, we have explored the anticancer potential of 7A {4-(6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-7-yl)phenol} and 9A {7-(4-chlorophenyl)-9-methyl-6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazoline}by using in-vitro and in-vivo models of LC. In this study, we investigated the antiproliferative potential of quinazoline analogues using A549 cell line to identify the best compound of the series. The in-vitro and molecular docking studies revealed 7A and 9A compounds as potential analogues. We also performed acute toxicity study to determine the dose. After that, in-vivo studies using urethane-induced LC in male albino Wistar rats carried out further physiological, biochemical, and morphological evaluation (SEM and H&E) of the lung tissue. We have also evaluated the antioxidant level, inflammatory, and apoptotic marker expressions. 7A and 9A did not demonstrate any signs of acute toxicity. Animals treated with urethane showed a significant upregulation of oxidative stress. However, treatment with 7A and 9A restored antioxidant markers near-normal levels. SEM and H&E staining of the lung tissue demonstrated recovered architecture after treatment with 7A and 9A. Both analogues significantly restore inflammatory markers to normal level and upregulate the intrinsic apoptosis protein expression in the lung tissue. These experimental findings demonstrated the antiproliferative potential of the synthetic analogues 7A and 9A, potentially due to their anti-inflammatory and apoptotic properties.

Role of Serum Micro-RNA-122-5p Expression as a Circulatory Biomarker in People Having Both Knee Osteoarthritis and Osteoporosis: A Case-Control Study.

Background Although knee osteoarthritis (KOA) and osteoporosis (OP) manifest distinct pathophysiologies, they share numerous similarities. These health conditions are commonly found in older individuals, particularly among women. The objective of this study is to explore the expression of micro-RNA (miRNA) 122-5p (miR-122-5p) in people affected by both KOA and OP. The main aim is to identify diagnostic biomarkers and potential therapeutic targets, which could help develop personalized treatment approaches. Methods As part of the study, a total of 268 serum samples were collected from the participants, who were divided into four groups: KOA, OP, KOA and OP, and controls, with 67 subjects per group. The miRNA species-containing total RNA was isolated from the serum samples using an miRNeasy serum/plasma kit by QIAGEN (Hilden, Germany). The expression of miR-122-5p was examined in each group using real-time quantitative polymerase chain reaction. Results Expression of miR-122-5p in all three groups (KOA, OP, and common group of KOA and OP) was significantly upregulated, and the fold change value was much higher in the group having both diseases. Conclusions These results might contribute to the identification of cases at risk, early diagnosis, and development, and might also contribute to the development of therapeutic targets in subjects having both KOA and OP.

Long-term Outcome of Coronavirus Disease-associated Mucormycosis: 1-year Follow-up Study from India.

IMPORTANCE: Invasive fungal infections have recently become a public health problem, particularly in India following the second wave of coronavirus disease 2019 (COVID-19). India harbors the world's largest population of patients suffering from diabetes. What prompted the sudden spike of mucormycosis infections in the COVID pandemic needs investigation. OBJECTIVE: To determine if COVID-19 infection prompted the spike in invasive fungal infections in diabetic population. To determine the long-term outcome of COVID-associated mucormycosis. To determine if COVID-19 infection causes diabetes mellitus transiently. DESIGN: The study was a prospective cohort study comprising patients suffering from mucormycosis. The study was planned from 20 May 2021, until 30 November 2022, to investigate the long-term follow-up (1 year) of mucormycosis patients. SETTING: The study setting was a referral hospital. PARTICIPANTS: All the consecutive patients admitted to this hospital for treatment of mucormycosis were included in the study who consented to it. Intervention(s) (for clinical trials) or exposure(s) (for observational studies): All patients suffering with mucormycosis underwent treatment at this hospital with surgery and injectable systemic antifungal drugs alongside diabetes management. MAIN OUTCOME(S) AND MEASURE(S): Primary outcome measurement was in the form of survival with cure of mucormycosis. Hypothesis being tested was formulated during data collection. RESULTS: The data of 98 participants was collected, but analysis was done after excluding the case of cutaneous mucormycosis (infant patient). Mean age for patients was 55.5 years, varying from 28 to 88 years. In our study, 63.3% of patients with mucormycosis were males and 37.8% were females, of which 55.7% (34) and 58.3% (21) were known diabetics, respectively. Previous history of diabetes mellitus was identified as an underlying comorbid condition in 56.7% of patients, while the rest were diagnosed with new-onset diabetes mellitus. Sugar levels ranged (on admission) from 112 to 494 mg/dL (median 212 mg/dL) for known diabetics and from 132 to 356 mg/dL (median 204 mg/dL) for newly diagnosed diabetics. Other comorbidities included hypertension (19.5%), ischemic heart disease (8.2%), chronic renal illness (3.09%), and one case (1.03%) of postoperative renal cell carcinoma (disease-free). The majority of cases (91.8%) were not vaccinated for COVID-19, while only two patients reported a history of vaccination with two doses, and six others had received only a single dose. At the 1-year follow-up, 57.7% of cases were disease-free, 30.9% had expired, and 11.3% were lost to follow-up. The mean glycated hemoglobin (HbA1c) at the time of admission was found to be statistically significant when compared between known diabetics and newly diagnosed ones [confidence interval (CI)-95%, p ≤ 0.01]. A total of seven patients from the newly diagnosed diabetic group no longer required medicines for diabetes at the end of 1 year (CI-95%, p ≤ 0.01). CONCLUSIONS AND RELEVANCE: Diabetes mellitus, particularly with poor glycemic control, was the single most important factor associated with and predictor of outcome. Contrary to the popular hypothesis, industrial oxygen and oxygen masks were not the reasons for the mucormycosis pandemic. Additionally, immunization against COVID provided protection not only from severe COVID but also from COVID-associated mucormycosis. It is recommended that patients with mucormycosis be followed for longer periods as a few patients could be suffering from transient diabetes, particularly against the backdrop of a pandemic.

Facile access to C-substituted piperazin-2-ones and mianserin derivative enabled by chemoselective carbene insertion and cyclization cascade.

The chemoselective N-H insertion of unsymmetrical diamines into carbene is a longstanding challenge. A simple copper-catalyzed strategy for synthesizing C-substituted piperazinones is described, employing easily accessible diazo compounds and 1,2-diamines. The reaction proceeded via chemo-selective carbene insertion at the comparatively less nucleophilic amine, followed by instantaneous cyclization. The protocol was further extended to access NH-free piperazinone, and the synthesis of a Mianserin derivative.

Comparative investigation on chemical and green synthesized titanium dioxide nanoparticles against chromium (VI) stress eliciting differential physiological, biochemical, and cellular attributes in Helianthus annuus L.

Nanotechnology is a new scientific area that promotes unique concepts to comprehend the optimal mechanics of nanoparticles (NPs) in plants under heavy metal stress. The present investigation focuses on effects of synthetic and green synthesized titanium dioxide nanoparticles (TiO2 NPs and gTiO2 NPs) against Cr(VI). Green TiO2 NPs have been produced from plant leaf extract (Ricinus communis L.). Synthesis was confirmed employing an array of optical spectroscopic and electron microscopic techniques. Chromium strongly accelerated H2O2 and MDA productions by 227 % and 266 % at highest chromium concentration (60 mg/kg of soil), respectively, and also caused DNA damage, and decline in photosynthesis. Additionally, anomalies were observed in stomatal cells with gradual increment in chromium concentrations. Conversely, foliar applications of TiO2 NPs and gTiO2 NPs considerably mitigated chromium stress. Sunflower plants treated with modest amounts of green TiO2 NPs had significantly better growth index compared to chemically synthesized ones. Principal component analysis highlighted the variations among photosynthetic attributes, oxidative stress markers, and antioxidant defense systems. Notably, gTiO2 supplementation to the Cr(VI) strained plants minimized PC3 production which is a rare report so far. Conclusively, gTiO2 NPs have been identified to be promising nano-based nutrition resource for farming applications.

Does Lake Louise questionnaire interpret high-altitude headache as acute mountain sickness? Experience in the western Himalayas.

BACKGROUND OBJECTIVES: High-altitude headache (HAH) and headache in acute mountain sickness (AMS) are common among lowlanders ascending to the high altitude and are often confused with one another. A pilot study was undertaken to analyze HAH and AMS cases in Indian lowlanders ascending to Leh city (3500 m) in western Himalayas. METHODS: A total number of 1228 Indian lowlanders, who ascended (fresh and re-inductees) by air and acclimatized, participated in this pilot study. The intensity of headache was assessed by the Visual Analogue Score. The parameters of HAH as per the International Classification of Headache Disorders-3 and 2018 Revised Lake Louise Questionnaire (LLQ) were used to differentiate HAH and AMS. RESULTS: Out of 1228 cases, 78 (6.4%) cases had headache, of which 24 (1.95%) cases were HAH only, 40 (3.25%) cases AMS only and 14 (1.14%) cases were defined as both HAH and AMS. There was a significant difference in heart rate [F (2,51) = (4.756), P =0.01] between these groups. It also showed a difference in the correlation between the parameters within the groups. The Odd's Ratio of AMS in fresh and re-inductees was found to be 4.5 and for HAH it was 4.33. INTERPRETATION CONCLUSIONS: The findings of this study suggest that LLQ has a tendency of overestimating AMS by including HAH cases. Furthermore differential parameters exhibit differences when AMS and HAH are considered separately. Re-inductees showed a lower incidence of HAH and AMS.

Functional Outcomes and Gait Analysis of Total Hip Arthroplasty Through Lateral Hardinge Approach and Gluteus Medius-Sparing Approach: A Prospective Study.

Background and objective Hip degenerative joint disease is a common and debilitating musculoskeletal disorder. Total hip arthroplasty (THA) is a reconstructive hip procedure to relieve this condition through various surgical approaches. This study aimed to compare the functional outcomes between patients undergoing THA using the lateral Hardinge approach and the lateral gluteus medius-sparing approach. Material and methods This prospective study was carried out at a tertiary care institution. Thirty patients with arthritic hip joints were managed with total hip replacement (THR). The patients were allocated into two treatment groups; in group A, 14 patients received a THR by the lateral Hardinge approach, whereas in group B, 16 patients were managed by the lateral gluteus medius-sparing approach. Functional outcomes were assessed by the Harris Hip Score (HHS), and gait analysis was performed. Results The mean age of group A was 39.79 ±14.01 years and that of group B was 37.00 ±14.81 years. The mean length of incision was significantly lower in group B (p=0.001), whereas the mean duration of surgery (p=0.018) and mean contralateral pelvic tilt were found to be significantly lower in group A (p=0.009). No significant difference was found in abductor muscle strength, limb length discrepancy, HHS, pelvic obliquity, and pelvic rotation. Conclusion While functional outcomes were similar in both groups, the group that underwent THA with the gluteus medius-sparing approach had better gait based on lower pelvic tilt.

Functional outcome of total hip arthroplasty in tubercular hip arthritis: A prospective study.

Background: Total hip arthroplasty (THA) is a well-established procedure to cure tubercular hip arthritis in patients with healed tuberculosis while its role in active tuberculosis is still debatable. The aim of the study is to investigate the functional outcomes of THA in active tuberculosis with advanced hip arthritis. The reactivation of tuberculosis and complications postoperatively has also been assessed. Materials and methods: The current open-ended prospective cohort study was carried out at a tertiary center from 2018 to 2020. Twenty patients of active tubercular hip arthritis (8 females and 12 males) were taken with a follow-up period ranging from 1 year to 3 years, with a mean of 14 months.Biochemical investigations were done both preoperatively and postoperatively. Preoperative anti-tubercular therapy (ATT) regimen was administered, as per standard norms, to patients for a minimum period of 6 weeks, and postoperatively for 6 months-12 months. Postero-lateral and Hardinge approaches were employed in all cases. Clinical and radiological parameters were assessed and functional outcomes were evaluated using the Harris Hip score (HHS). Results: The mean age of patients was 37.6 ± 11.38 years. Biochemical parameters were also found to improve postoperatively (p < 0.0001). The mean flexion, extension, abduction, external and internal rotation were found to increase postoperatively (p < 0.001). The mean flexion deformity in the preoperative period was 12.35 ± 4.716, whereas none of the patients had flexion deformities post operatively. The mean shortening was 2.12 ± 0.60 and 1 ± 0 at preoperative and postoperative respectively. The Total hip arthroplasty implant was found stable in all patients. The mean Harris score increased subsequently throughout the follow-up interval and differences were statistically significant (p < 0.0001). None of the patients had reactivation of tuberculosis infection postoperatively. Conclusion: Total hip arthroplasty is a reliable option to treat active advanced tubercular hip arthritis and gives good functional outcome with proper preoperative and postoperative ATT regimen.

Role of Phytoconstituents in Cancer Treatment: A Review.

Over the years, natural compounds have become a significant advancement in cancer treatment, primarily due to their effectiveness, safety, bio-functionality, and wide range of molecular structures. They are now increasingly preferred in drug discovery due to these attributes. These compounds, whether occurring naturally or with synthetic modifications, find applications in various fields like biology, medicine, and engineering. While chemotherapy has been a successful method for treating cancer, it comes with systemic toxicity. To address this issue, researchers and medical practitioners are exploring the concept of combinational chemotherapy. This approach aims to reduce toxicity by using a mix of natural substances and their derivatives in clinical trials and prescription medications. Among the most extensively studied natural anticancer compounds are quercetin, curcumin, vincristine, and vinblastine. These compounds play crucial roles as immunotherapeutics and chemosensitizers, both as standalone treatments and in combination therapies with specific mechanisms. This review article provides a concise overview of the functions, potentials, and combinations of natural anticancer compounds in cancer treatment, along with their mechanisms of action and clinical applications.

Antitumor efficacy of synthesized Ag-Au nanocomposite loaded with PEG and ascorbic acid in human lung cancer stem cells.

Lung cancer is the leading cause of mortality worldwide of which non-small cell lung carcinoma constitutes majority of the cases. High mortality is attributed to early metastasis, late diagnosis, ineffective treatment and tumor relapse. Chemotherapy and radiotherapy form the mainstay of its treatment. However, their associated side effects involving kidneys, nervous system, gastrointestinal tract, and liver further adds to dismal outcome. These disadvantages of conventional treatment can be circumvented by use of engineered nanoparticles for improved effectiveness with minimal side effects. In this study we have synthesized silver gold nanocomposite (Ag-Au NC) using polyethylene glycol and l-ascorbic acid as surfactant and reducing agent respectively. Synthesized nanocomposite was characterized by ultraviolet-visible absorption, dynamic light scattering, scanning and transmission electron microscopy. Compositional analysis was carried out by energy dispersive X-ray analysis and average pore diameter was estimated using Barrett-Joyner-Halenda method. In-silico molecular docking analysis of the synthesized NC against active regions of epidermal growth factor receptor revealed good binding energy. Subsequently, we investigated the effect of NC on growth and stem cell attributes of A549 lung cancer cells. Results showed that NC was effective in inhibiting A549 cell proliferation, induced DNA damage, G2/M phase arrest and apoptosis. Further, tumor cell migration and spheroid formation were also negatively affected. NC also enhanced reactive oxygen species generation and mitochondrial depolarization. In addition, the effect of NC on putative cancer stem cells in A549 cells was evaluated. We found that Ag-Au NC at IC50 targeted CD44, CD24, CD166, CD133 and CD326 positive cancer stem cells and induced apoptosis. CD166 positive cells were relatively resistance to apoptosis. Together our results demonstrate the anticancer efficacy of Ag-Au NC mediated by a mechanism involving cell cycle arrest and mitochondrial derangement.

Induced Pluripotent Stem Cells in the Era of Precise Genome Editing.

Genome editing has enhanced our ability to understand the role of genetics in a number of diseases by facilitating the development of more precise cellular and animal models to study pathophysiological processes. These advances have shown extraordinary promise in a multitude of areas, from basic research to applied bioengineering and biomedical research. Induced pluripotent stem cells (iPSCs) are known for their high replicative capacity and are excellent targets for genetic manipulation as they can be clonally expanded from a single cell without compromising their pluripotency. Clustered, regularly interspaced short palindromic repeats (CRISPR) and CRISPR/Cas RNA-guided nucleases have rapidly become the method of choice for gene editing due to their high specificity, simplicity, low cost, and versatility. Coupling the cellular versatility of iPSCs differentiation with CRISPR/Cas9-mediated genome editing technology can be an effective experimental technique for providing new insights into the therapeutic use of this technology. However, before using these techniques for gene therapy, their therapeutic safety and efficacy following models need to be assessed. In this review, we cover the remarkable progress that has been made in the use of genome editing tools in iPSCs, their applications in disease research and gene therapy as well as the hurdles that remain in the actual implementation of CRISPR/Cas systems.

Mito-Q supplementation of in vitro maturation or in vitro culture medium improves maturation of buffalo oocytes and developmental competence of cloned embryos by reducing ROS production.

Mito-Q is a well-known mitochondria-specific superoxide scavenger. To our knowledge, the effect of Mito-Q on buffalo oocyte maturation and developmental competency of cloned embryos has not been examined. To investigate the effects of Mito-Q on the in vitro maturation (IVM) of buffalo oocytes and the developmental competence of cloned embryos, different concentration of Mito-Q were supplemented with IVM (0, 0.1, 0.5, 1, 2 µM) and in vitro culture (IVC) medium (0, 0.1 µM). Supplementation of IVM medium with 0.1 µM Mito-Q significantly (P ≤ 0.05) increased the cumulus expansion, nuclear maturation, mitochondrial membrane potential (MMP) and antioxidants genes (GPX1 and SOD2) expression and effectively reduced ROS production leading to a significant improvement in the maturation rate of buffalo oocytes. Further, the supplementation of 0.1 µM Mito-Q in IVC medium promotes the cleavage and blastocyst rate significantly over the control. Mito-Q supplementation improves (P ≤ 0.05) MMP, antioxidant gene (GPX1) expression and reduced the ROS level and apoptosis related genes (caspase 9) expression in cloned blastocysts. In conclusion, the present study demonstrated that the supplementation of 0.1 µM Mito-Q in IVM and IVC media exerts a protective role against oxidative stress by reducing ROS production and improving MMP, fostering improved maturation of buffalo oocytes and enhanced developmental competence of cloned embryos. These findings contribute valuable insights into the optimization of assisted reproductive technologies protocols for buffalo breeding and potentially offer novel strategies to enhance reproductive outcomes in livestock species.

Review on interactions between nanomaterials and phytohormones: Novel perspectives and opportunities for mitigating environmental challenges.

Nanotechnology offers the potential to provide innovative solutions for sustainable crop production as plants are exposed to a combination of climate change factors (CO2, temperature, UV radiation, ozone), abiotic (heavy metals, salinity, drought), and biotic (virus, bacteria, fungi, nematode, and insects) stresses. The application of particular sizes, shapes, and concentration of nanomaterials (NMs) potentially mitigate the negative impacts in plants by modulation of photosynthetic rate, redox homeostasis, hormonal balance, and nutrient assimilation through upregulation of anti-stress metabolites, antioxidant defense pathways, and genes and genes network. The present review inculcates recent advances in uptake, translocation, and accumulation mechanisms of NMs in plants. The critical theme of this review provides detailed insights into different physiological, biochemical, molecular, and stress tolerance mechanism(s) of NMs action and their cross-talk with different phytohormones. The role of NMs as a double-edged sword for climate change factors, abiotic, and biotic stresses for nutrients uptake, hormones synthesis, cytotoxic, and genotoxic effects including chromosomal aberration, and micronuclei synthesis have been extensively studied. Importantly, this review aims to provide an in-depth understanding of the hormesis effect at low and toxicity at higher doses of NMs under different stressors to develop innovative approaches and design smart NMs for sustainable crop production.

Wound Healing, Anti-inflammatory and Antioxidant Potential of Quercetin Loaded Banana Starch Nanoparticles.

BACKGROUND: Quercetin belongs to the BCS Class IV of drugs, which means it exhibits low solubility and low permeability. Quercetin is a potent antioxidant drug candidate, but it has several drawbacks, such as a short half-life, poor stability, bioavailability, and solubility. These factors affect its reliability as a good wound-healing, anti-inflammatory, and antioxidant agent. Quercetin nanoparticles resolved these problems and offered high stability, high encapsulation efficacy, sustained and prolonged release, and enhanced accumulation at target sites with high therapeutic efficacy. METHODS: Banana starch and quercetin were used to formulate a new composition of nanoparticles. Formulated QBSN were evaluated for their antioxidant, wound healing, and anti-inflammatory potential. RESULTS: QBSN showed a good antioxidant effect against the DPPH free radical scavenging model. Inhibition of DPPH free radicals reached up to 98 percent at 40 µl. Histopathological studies of treated tissues (wound and paw edema) confirmed the potential of QBSN. CONCLUSION: In the future, prepared nanoparticles may be the choice of drug formulation for wound healing, anti-inflammatory therapy, and antioxidant therapy.

Knowledge and perception regarding adverse drug reactions among undergraduate medical students of Bihar, Eastern India.

Background: Adverse drug reactions (ADRs) have national and international monitoring and are part of teaching-learning of undergraduate medical course and curriculum. Objectives: To find the knowledge and perception of ADRs among undergraduate medical students in a tertiary care teaching institute in eastern India. Materials and Methods: This was an observational cross-sectional study conducted among the MBBS medical students by administration of pre-designed, pre-tested, semi-structured questionnaires. The data on their knowledge and candid reflections on ADRs were analyzed question by question using software and compared with peers. Results: The responses from the participants on knowledge and perception of ADRs varied widely. Final-year students had the most precise response on classification, filing an ADR report, national reporting centers, and the first step in monitoring ADRs; the majority accepted their first- hand experience and legal and professional responsibilities on ADRs. Third-year students responded well on objectives, methods, and scope of patients on direct reporting or drug overdose and monitoring; respect patient confidentiality while reporting; and expect feedback from monitoring centers, with special training on ADR. Second-year students responded well on definitions, pharmacovigilance programs in India, alertness of banned drugs because of ADR, and related capacity building. Conclusions: The awareness and insight on ADRs of the undergraduate medical students were quite reasonable. However, further reinforcement is needed in future to be updated to relevant issues to their practice as primary care physicians.

Electroporation-based CRISPR gene editing in adult buffalo fibroblast cells.

Electroporation is a widely used method for delivering CRISPR components into cells; however, it presents challenges when applied to difficult-to-transfect cells like adult buffalo fibroblasts. In this study, the ITGB2 gene (encoding the CD18 protein), plays vital for cellular adhesion and immune responses, was selected for editing experiments. To optimize electroporation conditions, we investigated parameters such as electric field strength, pulse duration, plasmid DNA amount, cuvette type, and cell type. The best transfection rates were obtained in a 4 mm gap cuvette with a single 20-millisecond pulse of 300 V using a 10 µg of all-in-one CRISPR plasmid for 106 cells in 100 µL of electroporation buffer. Increasing DNA quantity enhanced transfection rates but compromised cell viability. The 4 mm cuvette gap had high transfection rates than the 2 mm gap, and newborn cells exhibited higher transfection rates than adult cells. We achieved transfection rates of 10-12% with a cell viability of 25-30% for adult fibroblast cells. Subsequently, successfully edited the ITGB2 gene with a 30% editing efficiency, confirmed through various analysis methods, including T7E1 assay, TIDE and ICE analysis, and TA cloning. In conclusion, electroporation conditions reported here can edit buffalo gene(s) for various biotechnological research applications.

Facile Functionalization of Ambipolar, Nitrogen-Doped PAHs toward Highly Efficient TADF OLED Emitters.

Despite promising optoelectronic features of N-doped polycyclic aromatic hydrocarbons (PAHs), their use as functional materials remains underdeveloped due to their limited post-functionalization. Facing this challenge, a novel design of N-doped PAHs with D-A-D electronic structure for thermally activated delayed fluorescence (TADF) emitters was performed. Implementing a set of auxiliary donors at the meta position of the protruding phenyl ring of quinoxaline triggers an increase in the charge-transfer property simultaneously decreasing the delayed fluorescence lifetime. This, in turn, contributes to a narrow (0.04-0.28 eV) singlet-triplet exchange energy split (ΔEST) and promotes a reverse intersystem crossing transition that is pivotal for an efficient TADF process. Boosting the electron-donating ability of our N-PAH scaffold leads to excellent photoluminescence quantum yield that was found in a solid-state matrix up to 96% (for phenoxazine-substituted derivatives, under air) with yellow or orange-red emission, depending on the specific compound. Organic light-emitting diodes (OLEDs) utilizing six, (D-A)-D, N-PAH emitters demonstrate a significant throughput with a maximum external quantum efficiency of 21.9% which is accompanied by remarkable luminance values which were found for all investigated devices in the range of 20,000-30,100 cd/m2 which is the highest reported to date for N-doped PAHs investigated in the OLED domain.