Development of chromone-thiazolidine-2,4-dione Knoevenagel conjugates as apoptosis inducing agents.

Overexpression of Bcl-2 protein is a predominant hallmark of disturbed apoptotic pathway in most of the cancers. Herein, chromone-linked thiazolidinediones were designed and synthesized to target Bcl-2 for regulating anti-apoptotic proteins. The study on in vitro cancer cell lines revealed the presence of compounds 8a, 8k, 8l, and 8n, which were found to have good to moderate anti-proliferative activity (with an IC50 concentration less than 10 µM). Among them, 8l depicted the highest cytotoxicity on the A549 cell line with an IC50 of 6.1 ± 0.02 µM. Aberrantly, the compounds displayed less toxicity towards human embryonic kidney HEK cells underlining its selectivity. The DCFDA study revealed a gradual increase in the ROS generation of 8l, followed by its quantification by flow analysis. Similarly, the studies including DAPI, AO/EtBr and Annexin-V binding clearly elucidated the DNA damage, membrane integrity prospects, and insights for early and late apoptotic phases. Markedly, the Bcl-2-FITC anti-body study revealed that compound 8l reduced the expression of anti-apoptotic proteins by 79.1 % compared to the control at 9 µM concentration. In addition, the molecular docking study provided the impending scope of these hybrids, showing promising interaction with the Mcl-1 target (member of the Bcl-2 family) with comparable binding affinities.

Brown-top millet: an overview of breeding, genetic, and genomic resources development for crop improvement.

MAIN CONCLUSION: Brown-top millet is a lesser-known millet with a high grain nutrient value, early maturation, and drought tolerance that needs basic research to understand and conserve food security. Brown-top millet [Urochloa ramosa (L.)] is currently cultivated in some developing countries (especially in India) for food and fodder, although it is less known among the small millets. Like other millets, it contains macro- and micronutrients, vitamins, minerals, proteins, and fiber, all of which have rich health benefits. The nutritional importance and health benefits of brown-top millet are still unknown to many people due to a lack of awareness, wide cultivation, and research. Hence, this millet is currently overshadowed by other major cereals. This review article aims to present the nutritional, breeding, genetic, and genomic resources of brown-top millet to inform millet and other plant researchers. It is important to note that genetic and genomic resources have not yet been created for this millet. To date, there are no genomic and transcriptomic resources for brown-top millet to develop single nucleotide polymorphisms (SNP) and insertion/Deletions (InDels) for breeding studies. Furthermore, studies regarding nutritional significance and health benefits are required to investigate the exact nutritional contents and health benefits of the brown-top millet. The present review delves into the nutritional value and health advantages of brown-top millet, as supported by the available literature. The limitations of producing brown-top millet have been enumerated. We also cover the status of marker-assisted breeding and functional genomics research on closely related species. Lastly, we draw insights for further research such as developing omics resources and applying genome editing to study and improve brown-top millet. This review will help to start breeding and other molecular studies to increase the growth and development of this cereal.

Rh(III)-catalysed C-H annulation of cis-stilbene acids with 2-diazo-1,3-diketones: facile access to 6,7-dihydrobenzofuran-4(5H)-one and α-pyrone scaffolds.

An efficient Rh(III)-catalysed C-H functionalization, tandem annulation of cis-stilbene acids using 2-diazo-1,3-diketones was devised. This protocol solely afforded 6,7-dihydrobenzofuran-4(5H)-ones using alicyclic diazocarbonyls via decarbonylation and α-pyrones with aliphatic diazo compounds. The chameleonic nature of cis-stilbene acid was observed with various diazo compounds by altering the additives. This synthetic method furnished good atom-economy and wide functional group tolerance, and also explained the use of carboxylic acids as a directing group. In addition, a mechanistic investigation of the catalysed reaction using ESI-MS, and the fluorescence properties of α-pyrones were well explored.

Digital Health Literacy: Evaluating the Readability and Reliability of Cochlear Implant Patient Information on the Web.

Hearing aids and implants are used to treat hearing loss, with cochlear implants being the most successful option for severe sensorineural hearing loss. Patients frequently use the internet as a trusted source of clinical information before committing to any therapeutic procedure, including receiving a cochlear implant. A health resource's readability and dependability influence its value to patients. Readability refers to how easily language can be understood, whereas reliability refers to the correctness and consistency of the information presented. JAMA standards and the DISCERN tool were used to assess the reliability of the websites listed. For readability analysis, the FRE, FKG and GFI were chosen. The acceptable readability level was set to < 7 for the FKG, GF score over 17 as the equivalent of college-level education and ≥ 80.0 for the FRE. The readability scores vary across the sources, suggesting a range of comprehension levels required for understanding the cochlear implant patient information found on Google. There was a statistical difference detected in Discern score between the groups (p = 0.008). The mean discern score was significantly higher in hospital generated sources when compared to industry (3.13 ± 0.69 vs. 2.11 ± 0.78, p = 0.03).

Copper and Silver Nanoparticle Seed Priming and Foliar Spray Modulate Plant Growth and Thrips Infestation in Capsicum spp.

Nanoparticles (NPs) have the potential to improve plant health and secondary metabolite production. In the present study, three different NPs, i.e., Ag, Cu, and Cu-Ag NPs were produced in the range from 25 to 86 nm, with zeta potentials ranging from -28.8 to -38.5 mV. The synthesized NPs were used for seed priming and foliar spray on three varieties of Capsicum annuum. L, i.e., Arka Sweta (AS), Arka Meghana (AM), and Arka Harita (AH) plants grown under greenhouse conditions. Seed priming at various concentrations of NPs (1, 10, 20 ppm) enhanced the seed germination (96%), seedling vigor index (2494-3112.66), seedling length (6-49%), and biomass (46%) of 45 days old Arka Meghana seedlings. Additionally, all plant tissues accumulated significantly higher amounts of chlorophyll (51-142%), carotenoids (23-94.2%), total phenolic content (73%), and total flavonoid content (57%), compared with the control (p ≤ 0.05). The foliar spray of NPs (20-100 ppm) has a protective effect on the chili plants against thrips infestation (30-76%). The foliar spray enhanced chlorophyll (15-62%), carotenoids (15-50%), total phenolic content (20-62%), total flavonoid content (64-99%), reducing sugars (15-97%), total antioxidant activity (15-142%), ferric reducing antioxidant power assay (15-109%), DPPH (129-54 mg mL-1), and capsaicinoids (capsaicin and dihydrocapsaicin) (82-128%). This study illustrates that Ag, Cu, and Cu-Ag NPs suppress thrips infestation and proliferation with enhanced plant growth and biochemical activity, which is inversely proportional to the NP size. Chemical NPs play a crucial role in the economic significance of chili plants, offering a promising avenue for developing pesticides to effectively combat thrips infestation. This advancement holds great potential in enhancing the overall agronomic productivity of the chili crops.

Miniature inverted-repeat transposable elements (MITEs), derived insertional polymorphism as a tool of marker systems for molecular plant breeding.

Plant molecular breeding is expected to give significant gains in cultivar development through development and utilization of suitable molecular marker systems for genetic diversity analysis, rapid DNA fingerprinting, identification of true hybrids, trait mapping and marker-assisted selection. Transposable elements (TEs) are the most abundant component in a genome and being used as genetic markers in the plant molecular breeding. Here, we review on the high copious transposable element belonging to class-II DNA TEs called "miniature inverted-repeat transposable elements" (MITEs). MITEs are ubiquitous, short and non-autonomous DNA transposable elements which have a tendency to insert into genes and genic regions have paved a way for the development of functional DNA marker systems in plant genomes. This review summarises the characteristics of MITEs, principles and methodologies for development of MITEs based DNA markers, bioinformatics tools and resources for plant MITE discovery and their utilization in crop improvement.

Truncated Thioredoxin Peptides Serves as an Efficient Fusion Tag for Production of Proinsulin.

BACKGROUND: Insulin is a peptide hormone used for regulating blood glucose levels. Human insulin market is projected to grow at a rate of 12.5% annually. To meet the needs of patients, a cost effective insulin manufacturing strategy has to be developed. This can be achieved by selecting a competent host, ideal fusion tag and streamlined downstream process. OBJECTIVE: In this article, we have demonstrated that selecting a right fusion partner for expression of toxic proteins like insulin, plays a major role in increasing the recombinant protein yield. METHODS: In this article, we have focused on identifying a peptide tag fusion partner for expressing proinsulin by truncating thioredoxin tag. Truncations were carried out from both Amino and Carboxy terminus of the protein and efficiency of truncated sequences was evaluated by expressing it with proinsulin gene. FCTRX (1-15) sequence fused to proinsulin was processed further to establish downstream protocol for purification. RESULTS: Thioredoxin tag was truncated appropriately by considering the fusion tag: protein ratio. A couple of sequences ranging 10 - 15 amino acids were identified based on its in silico properties. Of these FCTRX (1-15) showed increased expression and stability of fusion protein. 156 mg of purified insulin was generated from 1g of inclusion body after enzymatic conversion and chromatographic steps. CONCLUSION: As a result of the current study, it was concluded that FCTRX (1-15) peptide has advantageous attributes to be considered as an ideal fusion tag for expression of proinsulin. This can be further explored by expressing it with other proteins.

Add-on Effect Of Hot Sand Fomentation To Yoga On Pain, Disability, And Quality Of Life In Chronic Neck Pain Patients.

BACKGROUND: Neck pain is one of the commonest complaints and an important public health problem across the globe. Yoga has reported to be useful for neck pain and hot sand has reported to be useful for chronic rheumatism. The present study was conducted to evaluate the add-on effect of hot sand fomentation (HSF) to yoga on pain, disability, quality of sleep (QOS) and quality of life (QOL) of the patients with non-specific neck pain. MATERIALS AND METHODS: A total of 60 subjects with non-specific or common neck pain were recruited and randomly divided into either study group or control group. Both the groups have received yoga and sesame seed oil (Sesamum Indicum L.) application. In addition to yoga and sesame seed oil, study group received HSF for 15 min per day for 5-days. Assessments were taken prior to and after the intervention. RESULTS: Results of the study showed a significant reduction in the scores of visual analogue scale for pain, neck disability index (NDI), The Pittsburgh Sleep Quality Index (PSQI), and a significant increase in physical function, physical health, emotional problem, pain, and general health both in study and control groups. However, reductions in pain and NDI along with improvement in social functions were better in the study group as compared with control group. CONCLUSION: Results of this study suggest that addition of HSF to yoga provides a better reduction in pain and disability along with improvement in the social functioning of the patients with non-specific neck pain than yoga alone.

Asymptomatic CMV infections in long-term renal transplant recipients are associated with the loss of FcRγ from LIR-1+ NK cells.

While it is established that cytomegalovirus (CMV) disease affects NK-cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here, we characterize NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age-matched controls (n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR-1, NKp30, NKp46, and FcRγ, a signaling adaptor molecule, on CD56dim NK cells. Phenotypic changes ascribed to CMV were clearer in RTRs than in control subjects and affected NK-cell function as assessed by TNF-α and CD107a expression. The most active NK cells were FcRγ- LIR-1+ NKG2C- and displayed high antibody-dependent cell cytotoxicity responses in the presence of immobilized CMV glycoprotein B reactive antibody. However, perforin levels in supernatants from RTRs with active CMV replication were low. Overall we demonstrate that CMV can be reactivated in symptom-free renal transplant recipients, affecting the phenotypic, and functional profiles of NK cells. Continuous exposure to CMV may maintain and expand NK cells that lack FcRγ but express LIR-1.

Prospects of molecular markers in Fusarium species diversity.

Recent developments in genomics have opened up for newer opportunities to study the diversity and classification of fungi. The genus Fusarium contains many plant pathogens that attack diverse agricultural crops. Fusarium spp. are not only pathogenic to plants but are also known as toxin producers that negatively affect animal and human health. The identification of Fusarium species still remains one of the most critical issues in fungal taxonomy, given that the number of species recognized in the genus has been constantly changing in the last century due to the different taxonomic systems. This review focuses of various molecular-based techniques employed to study the diversity of Fusarium species causing diseases in major food crops. An introduction of fusarial diseases and their mycotoxins and molecular-marker-based methods for detection introduce the concept of marker application. Various well-known molecular techniques such as random amplified polymorphic DNA, amplification fragment length polymorphism, etc. to more modern ones such as DNA microarrays, DNA barcoding, and pyrosequencing and their application form the core of the review. Target regions in the genome which can be potential candidates for generation of probes and their use in phylogeny of Fusarium spp. are also presented. The concluding part emphasizes the value of molecular markers for assessing genetic variability and reveals that molecular tools are indispensable for providing information not only of one Fusarium species but on whole fungal community. This will be of extreme value for diagnosticians and researchers concerned with fungal biology, ecology, and genetics.

Treatment of class II division 1 malocclusion with myofunctional trainer system in early mixed dentition period.

Dentofacial growth interferences, caused by abnormal lip and tongue function in the mixed dentition period are a common clinical condition. The main purpose of the treatment in such cases is to eliminate oral dysfunction, establish muscular balance and correct or diminish maxillary incisor protrusion. The position of the teeth is determined by the lip and tongue pressure. Lip function may have been the cause of forcing teeth in to malposition they occupy. The case report is presented where the myofunctional trainer T4K is used during growth phase.

Production and characterization of alpha-amylase from Aspergillus niger JGI 24 isolated in Bangalore.

Five fungal isolates were screened for the production of alpha-amylase using both solid-state and submerged fermentations. The best amylase producer among them, Aspergillus niger JGI 24, was selected for enzyme production by solid-state fermentation (SSF) on wheat bran. Different carbon and nitrogen supplements were used to enhance enzyme production and maximum amount of enzyme was obtained when SSF was carried out with soluble starch and beef extract (1% each) as supplements. Further attempts to enhance enzyme production by UV induced mutagenesis were carried out. Survival rate decreased with increase in duration of UV exposure. Partial purification of the enzyme using ammonium sulphate fractionation resulted in 1.49 fold increase in the enzyme activity. The enzyme showed a molecular weight of 43 kDa by SDS-PAGE. Metal ions Ca2+ and Co2+ increased the enzyme activity. The enzyme was optimally active at 30 degrees C and pH 9.5.