A review on structure-function mechanism and signaling pathway of serine/threonine protein PIM kinases as a therapeutic target.

The proviral integration for the Moloney murine leukemia virus (PIM) kinases, belonging to serine/threonine kinase family, have been found to be overexpressed in various types of cancers, such as prostate, breast, colon, endometrial, gastric, and pancreatic cancer. The three isoforms PIM kinases i.e., PIM1, PIM2, and PIM3 share a high degree of sequence and structural similarity and phosphorylate substrates controlling tumorigenic phenotypes like proliferation and cell survival. Targeting short-lived PIM kinases presents an intriguing strategy as in vivo knock-down studies result in non-lethal phenotypes, indicating that clinical inhibition of PIM might have fewer adverse effects. The ATP binding site (hinge region) possesses distinctive attributes, which led to the development of novel small molecule scaffolds that target either one or all three PIM isoforms. Machine learning and structure-based approaches have been at the forefront of developing novel and effective chemical therapeutics against PIM in preclinical and clinical settings, and none have yet received approval for cancer treatment. The stability of PIM isoforms is maintained by PIM kinase activity, which leads to resistance against PIM inhibitors and chemotherapy; thus, to overcome such effects, PIM proteolysis targeting chimeras (PROTACs) are now being developed that specifically degrade PIM proteins. In this review, we recapitulate an overview of the oncogenic functions of PIM kinases, their structure, function, and crucial signaling network in different types of cancer, and the potential of pharmacological small-molecule inhibitors. Further, our comprehensive review also provides valuable insights for developing novel antitumor drugs that specifically target PIM kinases in the future. In conclusion, we provide insights into the benefits of degrading PIM kinases as opposed to blocking their catalytic activity to address the oncogenic potential of PIM kinases.

Metagenomic landscape of sediments of river Ganga reveals microbial diversity, potential plastic and xenobiotic degradation enzymes.

The Ganga is the largest river in India, serves as a lifeline for agriculture, drinking water, and religious rites. However, it became highly polluted due to the influx of industrial wastes and untreated sewages, leading to the decline of aquatic biodiversity. This study investigated the microbial diversity and plastic-xenobiotic degrading enzymes of six sediment metagenomes of river Ganga at Prayagraj (RDG, TSG, SDG) and Devprayag (KRG, BNG, BRG). The water quality parameters, higher values of BOD (1.8-3.7 ppm), COD (23-29.2 ppm) and organic carbon (0.18-0.51%) were recorded at Prayagraj. Comparative analysis of microbial community structure between Prayagraj and Devprayag revealed significant differences between Bacteroidetes and Firmicutes, which emerging as the predominant bacterial phyla across six sediment samples. Notably, their prevalence was highest in the BRG samples. Furthermore, 25 OTUs at genus level were consistent across all six samples. Alpha diversity exhibited minimal variation among samples, while beta diversity indicated an inverse relationship between species richness and diversity. Co-occurrence network analysis established that genera from the same and different groups of phyla show positive co-relations with each other. Thirteen plastic degrading enzymes, including Laccase, Alkane-1 monooxygenase and Alkane monooxygenase, were identified from six sediment metagenomes of river Ganga, which can degrade non-biodegradable plastic viz. Polyethylene, Polystyrene and Low-density Polyethelene. Further, 18 xenobiotic degradation enzymes were identified for the degradation of Bisphenol, Xylene, Toluene, Polycyclic aromatic hydrocarbon, Styrene, Atrazene and Dioxin etc. This is the first report on the identification of non-biodegradable plastic degrading enzymes from sediment metagenomes of river Ganga, India. The findings of this study would help in pollution abatement and sustainable management of riverine ecosystem.

Submammary Approach for Harvesting Pectoralis Major Myocutaneous Flap in Females with Oral Cavity Cancers: Report of Technique and Our Experience.

Background: Oral squamous cell carcinoma is one of the most common types of cancers affecting both male and female population worldwide. Currently gold standard for reconstruction of oral cavity defects is free flap reconstruction. However, in developing countries due to large case load, infrastructural and resource constraints, Pectoralis major myocutaneous flap is still widely being used. Harvesting PMMC flap in females is challenging due to thick fat and breast tissue affecting its reliability and also increased donor site morbidity. This article aims at highlighting our experience with harvesting PMMC flap in female patients by submammary approach and its outcomes. Methods: A total of 23 female patients who underwent wide local excision of oral cavity cancers and reconstruction with PMMC flap were included. Data was analysed as mean, median, mode, percentages and statistical averages. Results: Majority of patients belonged to 40-60 years of age group (60.86%). Buccal mucosa was the most common site of primary lesion in 16 patients (69.56%). Out of the 23 patients who underwent PMMC flap reconstruction, recipient site complications were seen in 4 patients including total flap loss in 2 patients (8.69%), minor complications, e.g. infection in 2 patients (8.69%). Donor site morbidity in the form of axillary seroma was seen in only 1 patient (4.34%). Conclusion: In our experience, PMMC flap is still a viable option for reconstruction especially in resource constraint settings. Submammary approach to PMMC flap harvest is a safe technique as it is associated with minimum recipient site complications whilst preserving donor site anatomy and thereby reducing donor site morbidities to minimum.

Analysis for optimized prerequisites of modified solar stills.

This research portrayed the analysis of performance enhancement through a relative optimization approach of novel solar still models based on energetic-exergetic performances and energy matrices with environs-economic breakthroughs and is an extension of the existing research done by Singh & Samsher, and Singh & Gautam in the year 2022. The existing solar distiller models haven't shown relative influence on the performance of variable number of vacuum tubes, fully/partially illuminated and with/without the augmentation of parabolic concentrators among different schemes of solar still models. The present research bridges the above gaps to identify the analytical observations for the optimized results for the novel arrangement of the solar distillers compared to others. The dual slope solar still (DSS) with parabolic solar receiver (PSR) and evacuated annual tubes (EATC) found superior among other schemes and the DSS-EATC-PSR arrangement is advanced and enhanced with basin mass temperature (11.4 %) in observance with 30° inclined glaze cover and vacuum tubes altogether. A natural circulated thermo siphon shows increment (28.1 % & 0.1 %) to DSS-EATC-PSR relative to SSS with EATC & PSR, respectively. Further, the daily overall efficiencies (energy and exergy) have a marginal decrement of 8.4 % and 4.7 %, respectively, than the single-face solar still scheme (SSS). The daily yielding improvement is 4.6 % than the SSS scheme with nominal promotional cost (0.07 $/l) at a noticeable production cost. The CO2 mitigates, and environmental revenue is better than the SSS scheme by 5.9 % & 14.6 %. The concern price of the DSS coordination is lower by 6.6 %, and the productivity of the systems was found to be more than 100 % which assures the viability of the projected scheme.

Evaluation of biocontrol efficacy of rhizosphere dwelling bacteria for management of Fusarium wilt and Botrytis gray mold of chickpea.

BACKGROUND: Chickpea (Cicer arietinum L.) production is affected by many biotic factors, among them Fusarium wilt caused by Fusarium oxysporum f. sp. ciceri and Botrytis gray mold caused by Botrytis cinerea led to severe losses. As fungicide application is not advisable, biological management is the best alternative for plant protection. The rhizosphere-dwelling antagonistic bacteria are one of the important successful alternative strategy to manage these diseases of chickpea. Rhizosphere dwelling bacteria serve as biocontrol agents by different mechanisms like producing antibiotics, different enzymes, siderophores against pathogens and thereby reducing the growth of pathogens. RESULTS: The present study aimed to isolate rhizospheric bacteria from the soils of different chickpea fields to evaluate biocontrol efficacy of the isolated bacteria to manage Fusarium wilt and Botrytis gray mold in chickpea. A total of 67 bacteria were isolated from chickpea rhizosphere from Bundelkhand region of India. Study revealed the isolated bacteria could reduce the Fusarium oxysporum f. sp. ciceris and Botrytis cinerea infection in chickpea between 17.29 and 75.29%. After screening of all the bacteria for their biocontrol efficacy, 13 most promising bacterial isolates were considered for further study out of which, three bacterial isolates (15d, 9c and 14a) have shown the maximum in vitro antagonistic effects against Fusarium oxysporum f. sp. ciceri and Botrytis cinerea comparable to in vivo effects. However, Isolate (15d) showed highest 87.5% and 82.69% reduction in disease against Fusarium wilt and Botrytis gray mold respectively, under pot condition. Three most potential isolates were characterized at molecular level using 16S rRNA gene and found to be Priestia megaterium (9c and 14a) and Serratia marcescens (15d). CONCLUSION: This study identified two native biocontrol agents Priestia megaterium and Serratia marcescens from the rhizospheric soils of Bundelkhand region of India for control of Fusarium wilt, Botrytis gray mold. In future, efforts should be made to further validate the biocontrol agents in conjugation with nanomaterials for enhancing the synergistic effects in managing the fungal diseases in chickpea. This study will definitely enhance our understanding of these bioagents, and to increase their performance by developing effective formulations, application methods, and integrated strategies.

Fine mapping of qBK1.2, a major QTL governing resistance to bakanae disease in rice.

Bakanae disease caused by Fusarium fujikuroi is an emerging disease of rice causing losses in all rice-growing regions around the world. A BC2F2 population was developed by backcrossing the recurrent parent Pusa Basmati 1121 (PB1121) with the recombinant inbred line RIL28, which harbors a major quantitative trait locus (QTL) governing resistance to bakanae, qBK1.2. MassARRAY-based single-nucleotide polymorphism (SNP) assays targeting the genomic region of qBK1.2 helped in fine mapping the QTL to a region of 130 kb between the SNP markers rs3164311 and rs3295562 using 24 recombinants. In-silico mining of the fine-mapped region identified 11 putative candidate genes with functions related to defense. The expression analysis identified two significantly differentially expressed genes, that is, LOC_Os01g06750 and LOC_Os01g06870, between the susceptible genotype PB1121 and the resistant genotypes Pusa1342 and R-NIL4. Furthermore, the SNPs identified in LOC_Os01g06750 produced minor substitutions of amino acids with no major effect on the resistance-related functional motifs. However, LOC_Os01g06870 had 21 amino acid substitutions, which led to the creation of the leucine-rich repeat (LRR) domain in the resistant genotype Pusa1342, thereby making it a potential candidate underlying the major bakanae-resistant QTL qBK1.2. The markers used in the fine mapping program are of immense utility in marker-assisted breeding for bakanae resistance in rice.

Genetic Enhancement for Biotic Stress Resistance in Basmati Rice through Marker-Assisted Backcross Breeding.

Pusa Basmati 1509 (PB1509) is one of the major foreign-exchange-earning varieties of Basmati rice; it is semi-dwarf and early maturing with exceptional cooking quality and strong aroma. However, it is highly susceptible to various biotic stresses including bacterial blight and blast. Therefore, bacterial blight resistance genes, namely, xa13 + Xa21 and Xa38, and fungal blast resistance genes Pi9 + Pib and Pita were incorporated into the genetic background of recurrent parent (RP) PB1509 using donor parents, namely, Pusa Basmati 1718 (PB1718), Pusa 1927 (P1927), Pusa 1929 (P1929) and Tetep, respectively. Foreground selection was carried out with respective gene-linked markers, stringent phenotypic selection for recurrent parent phenotype, early generation background selection with Simple sequence repeat (SSR) markers, and background analysis at advanced generations with Rice Pan Genome Array comprising 80K SNPs. This has led to the development of Near isogenic lines (NILs), namely, Pusa 3037, Pusa 3054, Pusa 3060 and Pusa 3066 carrying genes xa13 + Xa21, Xa38, Pi9 + Pib and Pita with genomic similarity of 98.25%, 98.92%, 97.38% and 97.69%, respectively, as compared to the RP. Based on GGE-biplot analysis, Pusa 3037-1-44-3-164-20-249-2 carrying xa13 + Xa21, Pusa 3054-2-47-7-166-24-261-3 carrying Xa38, Pusa 3060-3-55-17-157-4-124-1 carrying Pi9 + Pib, and Pusa 3066-4-56-20-159-8-174-1 carrying Pita were identified to be relatively stable and better-performing individuals in the tested environments. Intercrossing between the best BC3F1s has led to the generation of Pusa 3122 (xa13 + Xa21 + Xa38), Pusa 3124 (Xa38 + Pi9 + Pib) and Pusa 3123 (Pi9 + Pib + Pita) with agronomy, grain and cooking quality parameters at par with PB1509. Cultivation of such improved varieties will help farmers reduce the cost of cultivation with decreased pesticide use and improve productivity with ensured safety to consumers.

Visual field indices in children and adults with comparable retinal nerve fiber layer thickness.

PURPOSE: To compare visual field indices in normal children and adults with similar retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT). METHODS: This cross-sectional study included 59 eyes of 59 normal children 6-18 years of age compared to normal adults. The children underwent visual field testing on the Humphrey Field Analyzer (HFA) and RNFL thickness measurement on OCT. Normal adults who had undergone OCT and visual field testing were retrieved from the OCT database. The mean deviation (MD) in each child was compared with the MD in RNFL thickness-matched eyes of normal adults. Children 6-11 years and 12-18 years were analyzed separately. RESULTS: Overall, the MD of children was significantly less than that of the normal adults despite having the same RNFL thickness (-2.42 ± 1.42 dB vs -1.61 ± 1.47 dB [P = 0.006]). When stratified by age, the difference in MD of children <12 years was significantly less than normal adults (-2.72 ± 1.5dB vs -1.53 ± 1.2 dB [P = 0.003) while in children >12 years, the difference did not reach statistical significance (-2.18 ± 1.2 vs -1.51 ± 1.32 [P = 0.12]). CONCLUSIONS: In our study cohort, children <12 years had lower visual field indices than adults. Their visual fields may appear worse than they would for an adult with the same RNFL thickness. Normal children >12 years of age seem to have a retinal sensitivity comparable to the adult normative database. It is worthwhile to consider the development of a separate pediatric normative database for the visual field assessment of children <12 years of age.

Fluticasone Furoate/Vilanterol Use Trends and Characteristics in Patients With Obstructive Airway Disease: A Real-World Study of 10,374 Patients From India.

Introduction Obstructive Airway Diseases (OADs) are the leading cause of death among chronic respiratory diseases worldwide, and novel therapies are direly needed. Fluticasone furoate/vilanterol (FF/Vi) (100/25 µg) is the first once-daily ICS/uLABA marketed in India for COPD since 2021. Considering its limited real-world experience in OAD patients in Indian clinical settings, a large drug utilization study (DUS) was planned. Methodology We conducted a cross-sectional, observational DUS at 1900 outpatient clinics in India from October 2021 to March 2022. Prescription data and medical history of patients who were prescribed the FF/Vi combination were collected. Results It was observed that FF/Vi was prescribed in an almost equal number of patients with COPD (44.2%) and asthma (42.9%). The majority of the patients (74%) were switched from previous ICS/LABA to this ICS/uLABA, while 26% of patients were treatment naïve. The average CAT score was 19.5±7.8 (43.2% GOLD Group C and 32.2% GOLD Group B) in COPD patients, while the average ACQ-5 score was 2.6±1.3 (33.1% GINA Step 3, 29.5% GINA Step 2) in asthmatic patients. Most of the patients (63.9%) had raised biomarkers (Blood eosinophil count >300 cells/µl). Prior history of exacerbation was present in 65% of patients with annual exacerbation rates of 1.2 in COPD, 1.1 in asthma, and 1.2 in asthma-COPD overlap syndrome (ACOS). Leukotriene inhibitors (42%) and LAMAs (30.8%) were common add-on medications. Conclusion We observed a trend towards a shift to once-daily ICS/uLABA (FF/Vi) by physicians, especially in symptomatic and exacerbating OAD patients with underlying comorbidities.

Topical Steroid-Induced Cushing's Syndrome in a Newborn Following Goniotomy for Glaucoma.

Iatrogenic Cushing's syndrome is a life-threatening condition which requires an early diagnosis multidisciplinary approach. Despite reports of iatrogenic Cushing's syndrome following nasal or inhaled steroids, its development after topical betamethasone eye drops for a short duration is a less frequently reported or anticipated condition. We describe a 6-week-old infant who developed exogenous Cushing's syndrome following topical steroids after bilateral goniotomy for newborn glaucoma. The child was kept under observation and managed with a physiological dose of hydrocortisone. Parental counselling regarding the proper method of eye drop instillation and signs of steroid toxicity is of vital importance in all cases of pediatric ocular surgeries, especially where bilateral surgeries are undertaken.

From farm to plate: Spatio-temporal characterization revealed compositional changes and reduced retention of γ-oryzanol upon processing in rice.

Background: Antioxidants detain the development and proliferation of various non-communicable diseases (NCDs). γ-oryzanol, a group of steryl ferulates and caffeates, is a major antioxidant present in rice grain with proven health benefits. The present study evaluated the distribution and dynamics of γ-oryzanol and its components in spatial and temporal scales and also delineated the effect of processing and cooking on its retention. Methods: Six rice varieties (four Basmati and two non-Basmati) belonging to indica group were analyzed at spatial scale in four different tissues (leaf blades, leaf sheaths, peduncle and spikelets) and temporal scale at three developmental stages (booting, milky and dough). Additionally, the matured grains were fractioned into husk, embryo, bran, and endosperm to assess differential accumulation in these tissues. Further, milling and cooking of the samples was done to assess the retention upon processing. After extraction of γ-oryzanol by solvent extraction method, individual components were identified by UPLC-QToF-ESI-MS and quantified by RP-HPLC. Results: The non-seed tissues were significantly different from the seed tissues for composition and quantitative variation of γ-oryzanol. Cycloartenyl caffeate was predominant in all the non-seed tissues during the three developmental stages while it showed significant reduction during the growth progression toward maturity and was totally absent in the matured grains. In contrary, the 24-methylenecycloartanyl ferulate, campesteryl ferulate and ß-sitosteryl ferulate showed significant increment toward the growth progression to maturity. Milling caused significant reduction, retaining only an average of 58.77% γ-oryzanol. Cooking of brown rice in excess water showed relatively lower average retention (43.31%) to samples cooked in minimal water (54.42%). Cooked milled rice showed least mean retention of 21.66%. Conclusion: The results demonstrate prominent compositional variation of γ-oryzanol during different growth stages. For the first time, the study demonstrated that ferulate esters of γ-oryzanol were predominant in the seed tissues while caffeate esters were dominant in non-seed tissues. Basmati cultivars show differential expression of γ-oryzanol and its components compared to non-Basmati cultivars. Cooking in excess water causes maximum degradation of γ-oryzanol. Post-harvest losses due to milling and cooking indicate the necessity of biofortification for γ-oryzanol content in rice grain.

Genome-wide association study reveals novel genomic regions governing agronomic and grain quality traits and superior allelic combinations for Basmati rice improvement.

Background: Basmati is a speciality segment in the rice genepool characterised by explicit grain quality. For the want of suitable populations, genome-wide association study (GWAS) in Basmati rice has not been attempted. Materials: To address this gap, we have performed a GWAS on a panel of 172 elite Basmati multiparent population comprising of potential restorers and maintainers. Phenotypic data was generated for various agronomic and grain quality traits across seven different environments during two consecutive crop seasons. Based on the observed phenotypic variation, three agronomic traits namely, days to fifty per cent flowering, plant height and panicle length, and three grain quality traits namely, kernel length before cooking, length breadth ratio and kernel length after cooking were subjected to GWAS. Genotyped with 80K SNP array, the population was subjected to principal component analysis to stratify the underlying substructure and subjected to the association analysis using Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model. Results: We identified 32 unique MTAs including 11 robust MTAs for the agronomic traits and 25 unique MTAs including two robust MTAs for the grain quality traits. Six out of 13 robust MTAs were novel. By genome annotation, six candidate genes associated with the robust MTAs were identified. Further analysis of the allelic combinations of the robust MTAs enabled the identification of superior allelic combinations in the population. This information was utilized in selecting 77 elite Basmati rice genotypes from the panel. Conclusion: This is the first ever GWAS study in Basmati rice which could generate valuable information usable for further breeding through marker assisted selection, including enhancing of heterosis.

Estimation of serum immunoglobulin G and immunoglobulin A levels in oral submucous fibrosis patients.

Background: Oral submucous fibrosis (OSMF) is a disabling, chronic, insidious potentially malignant condition of the oral cavity seen predominantly in the Indian subcontinent. Due to the idiopathic nature and various immunological changes seen in some OSMF patients, it can be considered an autoimmune disorder. Hyperimmunoglobulinemia is often seen with OSMF. Aim and Objectives: (i) To estimate the serum immunoglobulin G (IgG) and immunoglobulin A (IgA) levels in OSMF patients; (ii) to correlate the serum IgG and IgA levels with age and gender of OSMF patients; (iii) to correlate the serum IgG and IgA levels with clinical stages of OSMF; (iv) to correlate the serum IgG and IgA levels with the content of the habit in OSMF patients. Materials and Methods: Serum samples were collected from a total of 50 patients (25 OSMF cases and 25 controls) of both genders and IgG and IgA levels were estimated by NEPHELOMETRY. Results: As compared to the control group, the mean serum IgG level was marginally increased among the OSMF patients and the mean serum IgA level was marginally decreased among the OSMF patients, but this was not statistically significant. Furthermore, there was only a weak correlation between serum immunoglobulins and content of the habit and no significant correlation was found between the serum IgG and IgA levels and age and sex of the OSMF patients. Serum IgG was increased and IgA was decreased with increasing stages of OSMF. Conclusion: The results of the present study suggested that there is an alteration in serum immunoglobulin levels in OSMF patients as compared to the control group.

Unilateral advanced glaucoma in isolated congenital ectropion uveae with ipsilateral ptosis: A pictorial description of five children.

Aim: To report the cases of five children with unilateral advanced glaucoma in isolated congenital ectropion uveae (CEU) with ipsilateral ptosis and myopia. Methods: This is an ambispective observational case series. After diagnosing one patient with CEU and glaucoma, consecutive patients presenting with unilateral ptosis, congenital iris anomaly, and glaucoma between 2014 to 2020, and had completed a minimum one-year postoperative follow-up, were analyzed. Results: Of the 1421 newly registered pediatric glaucoma patients in the period under review, five children were diagnosed with CEU. All patients presented with gradual painless diminution of vision in the left eye in early adolescence. The left eye of all patients had peculiar clinical features: mild congenital ptosis, high iris insertion, crypt-less smooth iris surface, congenital ectropion uveae, pigments over anterior lens capsule, high myopia, advanced glaucomatous optic disc cupping, and very high intraocular pressure (IOP), which was > 45 mmHg in all cases. The right eye showed signs of angle dysgenesis with mild anterior iris insertion and numerous fine iris processes. Antiglaucoma medications and angle surgery failed to control the IOP, and all children required glaucoma filtration surgery, resulting in reasonable IOP control. Despite the older age, postoperative strict amblyopia treatment resulted in significant improvement in vision. Conclusions: Although ectropion uveae and ptosis have been present since birth, unilaterality, and the asymptomatic nature of the disease led to the late presentation with irreversible damage. Early surgical management and amblyopia therapy are the cornerstones of management. Abbreviations: CEU = Congenital ectropion uvea, CIES = Congenital Iris Ectropion Syndrome, ASD = Anterior segment dysgenesis syndrome, BCVA = Best-corrected visual acuity, IOP = Intraocular pressure.

Population Dynamics of Wide Compatibility System and Evaluation of Intersubspecific Hybrids by indica-japonica Hybridization in Rice.

The exploitation of heterosis through intersubspecific hybridisation between indica and japonica has been a major breeding target in rice, but is marred by the cross incompatibility between the genomes. Wide compatibility (WC) is a triallelic system at the S5 locus on chromosome 6 that ensures the specificity of hybridisation within and between indica and japonica. The S5n allele that favours intercrossing is sparsely distributed in the rice gene pool and therefore warrants identification of diverse WC sources to develop superior intersubspecific hybrids. In this study, we have identified several novel WC sources through the marker-assisted screening of a large set of 950 rice genotypes. Seventeen percent of the genotypes carried S5n, which fell into two subpopulations. The WC genotypes showed wide phenotypic and genotypic variability, including both indica and japonica lines. Based on phenotypic performance, the WC varieties were grouped into three clusters. A subset of 41 WC varieties was used to develop 164 hybrids, of which WC/japonica hybrids showed relative superiority over WC/indica hybrids. The multilocation evaluation of hybrids indicated that hybrids derived from WC varieties, such as IRG137, IRG143, OYR128, and IRGC10658, were higher yielding across all the three different locations. Most of the hybrids showed the stability of performance across locations. The identified diverse set of wide compatible varieties (WCVs) can be used in the development of intersubspecific hybrids and also for parental line development in hybrid rice breeding.