Enhancing Agricultural Sustainability Through Rhizomicrobiome: A Review.

Sustainable agriculture represents the responsible utilization of natural resources while safeguarding the well-being of the natural environment. It encompasses the objectives of preserving the environment, fostering economic growth, and promoting socioeconomic equality. To achieve sustainable development for humanity, it is imperative to prioritize sustainable agriculture. One significant approach to achieving this transition is the extensive utilization of microbes, which play a crucial role due to the genetic reliance of plants on the beneficial functions provided by symbiotic microbes. This review focuses on the significance of rhizospheric microbial communities, also known as the rhizomicrobiome (RM). It is a complex community of microorganisms that live in the rhizosphere and influence the plant's growth and health. It provides its host plant with various benefits related to plant growth, including biocontrol, biofertilization, phytostimulation, rhizoremediation, stress resistance, and other advantageous properties. Yet, the mechanisms by which the RM contributes to sustainable agriculture remain largely unknown. Investigating this microbial population presents a significant opportunity to advance toward sustainable agriculture. Hence, this study aims to provide an overview of the diversity and applications of RM in sustainable agriculture practices. Lately, there has been growing momentum in various areas related to rhizobiome research and its application in agriculture. This includes rhizosphere engineering, synthetic microbiome application, agent-based modeling of the rhizobiome, and metagenomic studies. So, developing bioformulations of these beneficial microorganisms that support plant growth could serve as a promising solution for future strategies aimed at achieving a new green revolution.

Identification of new hit to lead magmas inhibitors as potential therapeutics for glioblastoma.

In continuation of our previous efforts for the development of potent small molecules against brain cancer, herein we synthesized seventeen new compounds and tested their anti-gliomapotential against established glioblastoma cell lines, namely, D54MG, U251, and LN-229 as well as patient derived cell lines (DB70 and DB93). Among them, the carboxamide derivatives, BT-851 and BT-892 were found to be the most active leads in comparison to our established hit compound BT#9.The SAR studies of our hit BT#9 compound resulted in the development of two new lead compounds by hit to lead strategy. The detailed biological studies are currently underway. The active compounds could possibly act as template for the future development of newer anti-glioma agents.

Stimuli-Responsive Boron-Based Materials in Drug Delivery.

Drug delivery systems, which use components at the nanoscale level as diagnostic tools or to release therapeutic drugs to particular target areas in a regulated manner, are a fast-evolving field of science. The active pharmaceutical substance can be released via the drug delivery system to produce the desired therapeutic effect. The poor bioavailability and irregular plasma drug levels of conventional drug delivery systems (tablets, capsules, syrups, etc.) prevent them from achieving sustained delivery. The entire therapy process may be ineffective without a reliable delivery system. To achieve optimal safety and effectiveness, the drug must also be administered at a precision-controlled rate and the targeted spot. The issues with traditional drug delivery are overcome by the development of stimuli-responsive controlled drug release. Over the past decades, regulated drug delivery has evolved considerably, progressing from large- and nanoscale to smart-controlled drug delivery for several diseases. The current review provides an updated overview of recent developments in the field of stimuli-responsive boron-based materials in drug delivery for various diseases. Boron-containing compounds such as boron nitride, boronic acid, and boron dipyrromethene have been developed as a moving field of research in drug delivery. Due to their ability to achieve precise control over drug release through the response to particular stimuli (pH, light, glutathione, glucose or temperature), stimuli-responsive nanoscale drug delivery systems are attracting a lot of attention. The potential of developing their capabilities to a wide range of nanoscale systems, such as nanoparticles, nanosheets/nanospheres, nanotubes, nanocarriers, microneedles, nanocapsules, hydrogel, nanoassembly, etc., is also addressed and examined. This review also provides overall design principles to include stimuli-responsive boron nanomaterial-based drug delivery systems, which might inspire new concepts and applications.

Development of a New Methodology for Dearomative Borylation of Coumarins and Chromenes and Its Applications to Synthesize Boron-Containing Retinoids.

Dearomative borylation of coumarins and chromenes via conjugate addition represents a relatively unexplored and challenging task. To address this issue, herein, we report a new and general copper (I) catalyzed dearomative borylation process to synthesize boron-containing oxacycles. In this report, the borylation of coumarins, chromones, and chromenes comprising functional groups, such as esters, nitriles, carbonyls, and amides, has been achieved. In addition, the method generates different classes of potential boron-based retinoids, including the ones with oxadiazole and anthocyanin motifs. The borylated oxacycles can serve as suitable intermediates to generate a library of compounds.

Cocaine Modulates the Neuronal Endosomal System and Extracellular Vesicles in a Sex-Dependent Manner.

In multiple neurodevelopmental and neurodegenerative disorders, endosomal changes correlate with changes in exosomes. We examined this linkage in the brain of mice that received cocaine injections for two weeks starting at 2.5 months of age. Cocaine caused a decrease in the number of both neuronal early and late endosomes and exosomes in the brains of male but not female mice. The response to cocaine in ovariectomized females mirrored male, demonstrating that these sex-differences in response to cocaine are driven by hormonal differences. Moreover, cocaine increased the amount of α-synuclein per exosome in the brain of females but did not affect exosomal α-synuclein content in the brain of males, a sex-difference eliminated by ovariectomy. Enhanced packaging of α-synuclein into female brain exosomes with the potential for propagation of pathology throughout the brain suggests a mechanism for the different response of females to chronic cocaine exposure as compared to males.

Boron-Containing heterocycles as promising pharmacological agents.

The incorporation of the "magic" boron atom has been established as an important new strategy in the field of medicinal chemistry as boron compounds have been shown to form various bonds with their biological targets. Currently, a number of boron-based drugs (e.g. bortezomib, crisaborole, and tavaborole) have been FDA approved and are in the clinic, and several other boron-containing compounds are in clinical trials. Boron-based heterocycles have an incredible potential in the ongoing quest for new therapeutic agents owing to their plethora of biological activities and useful pharmacokinetic profiles. The present perspective is intended to review the pharmacological applications of boron-based heterocycles that have been published. We have classified these compounds into groups exhibiting shared pharmacological activities and discussed their corresponding biological targets focusing mainly on the most potent therapeutic compounds.

Synthesis of a boron-containing amidoxime reagent and its application to synthesize functionalized oxadiazole and quinazolinone derivatives.

Herein, we report the design, synthesis and application of a borylated amidoxime reagent for the direct synthesis of functionalized oxadiazole and quinazolinone derivatives. This reagent exhibits broad synthetic utility to obtain a variety of biologically relevant drug-like molecules. It can be easily prepared at large scale from relatively inexpensive reagents, and can undergo facile transformations to obtain target compounds. The developed amidoxime reagent was synthesized from 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile and hydroxyl amine hydrochloride using N,N-diisopropylethylamine as a base in ethanol under reflux conditions. Overall advantages include a metal-free route to boronated oxadiazoles, quinazolinone derivatives, and restriction of the multistep sequences. Importantly, the boron-rich pharmacophore derived compounds were obtained through an efficient and inexpensive strategy.

The Role of Microbiome in Brain Development and Neurodegenerative Diseases.

Hundreds of billions of commensal microorganisms live in and on our bodies, most of which colonize the gut shortly after birth and stay there for the rest of our lives. In animal models, bidirectional communications between the central nervous system and gut microbiota (Gut-Brain Axis) have been extensively studied, and it is clear that changes in microbiota composition play a vital role in the pathogenesis of various neurodevelopmental and neurodegenerative disorders, such as Autism Spectrum Disorder, Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, anxiety, stress, and so on. The makeup of the microbiome is impacted by a variety of factors, such as genetics, health status, method of delivery, environment, nutrition, and exercise, and the present understanding of the role of gut microbiota and its metabolites in the preservation of brain functioning and the development of the aforementioned neurological illnesses is summarized in this review article. Furthermore, we discuss current breakthroughs in the use of probiotics, prebiotics, and synbiotics to address neurological illnesses. Moreover, we also discussed the role of boron-based diet in memory, boron and microbiome relation, boron as anti-inflammatory agents, and boron in neurodegenerative diseases. In addition, in the coming years, boron reagents will play a significant role to improve dysbiosis and will open new areas for researchers.

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboranes, and BODIPY, for the treatment of different human diseases.In addition, we also describe the synthesis, key structure-activity relationship, and associated biological activities, such as antimicrobial, antituberculosis, antitumor, antiparasitic, antiprotozoal, anti-inflammatory, antifolate, antidepressant, antiallergic, anesthetic, and anti-Alzheimer's agents, as well as proteasome and lipogenic inhibitors. This compilation could be very useful in the exploration of novel boron-derived compounds against different diseases, with promising efficacy and lesser side effects.

Retinoic acid signaling pathways in development and diseases.

Retinoids comprise a group of compounds each composed of three basic parts: a trimethylated cyclohexene ring that is a bulky hydrophobic group, a conjugated tetraene side chain that functions as a linker unit, and a polar carbon-oxygen functional group. Biochemical conversion of carotenoid or other retinoids to retinoic acid (RA) is essential for normal regulation of a wide range of biological processes including development, differentiation, proliferation, and apoptosis. Retinoids regulate various physiological outputs by binding to nuclear receptors called retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which themselves are DNA-binding transcriptional regulators. The functional response of RA and their receptors are modulated by a host of coactivators and corepressors. Retinoids are essential in the development and function of several organ systems; however, deregulated retinoid signaling can contribute to serious diseases. Several natural and synthetic retinoids are in clinical use or undergoing trials for treating specific diseases including cancer. In this review, we provide a broad overview on the importance of retinoids in development and various diseases, highlighting various retinoids in the drug discovery process, ranging all the way from retinoid chemistry to clinical uses and imaging.

Bacterial chromate reductase, a potential enzyme for bioremediation of hexavalent chromium: a review.

Hexavalent chromium is mobile, highly toxic and considered as a priority environmental pollutant. Chromate reductases, found in chromium resistant bacteria are known to catalyse the reduction of Cr(VI) to Cr(III) and have recently received particular attention for their potential use in bioremediation process. Different chromate reductases such as ChrR, YieF, NemA and LpDH, have been identified from bacterial sources which are located either in soluble fractions (cytoplasm) or bound to the membrane of the bacterial cell. The reducing conditions under which these enzymes are functional can either be aerobic or anaerobic or sometimes both. Enzymatic reduction of Cr(VI) to Cr(III) involves transfer of electrons from electron donors like NAD(P)H to Cr(VI) and simultaneous generation of reactive oxygen species (ROS). Based on the steps involved in electron transfer to Cr(VI) and the subsequent amount of ROS generated, two reaction mechanisms, namely, Class I "tight" and Class II "semi tight" have been proposed. The present review discusses on the types of chromate reductases found in different bacteria, their mode of action and potential applications in bioremediation of hexavalent chromium both under free and immobilize conditions. Besides, techniques used in characterization of the Cr (VI) reduced products were also discussed.

Decline in unmet needs for cataract surgery among the ageing population in India: findings from LASI, wave-1.

Introduction: Cataracts are the leading cause of blindness among older people, but they can be treated with corrective surgery. India boasts the oldest blindness control programme in the world. We aimed to assess the prevalence of cataract surgery, and we compared the determinants of undergoing cataract surgery and identified the unmet needs for cataract surgery among older adults in India. Methods: We included 52,380 individuals aged ≥50 years from the Longitudinal Ageing Study in India, wave-1. The primary outcome measures of our study were the prevalence of cataract surgery and the unmet need for cataract surgery. Multivariate analysis was executed to investigate the association between socio-demographic variables and outcomes, expressing the results as adjusted odds ratios with 95% confidence intervals (CIs). Results: The overall prevalence of cataracts was 14.85%. The coverage of cataract surgery was 76.95%, with 23% having unmet needs for cataract surgery. Notably, cataract surgery coverage was higher at 78.30% (95% CI: 76.88-79.48) among participants aged 66-80 years, while the percentage of those who did not undergo cataract surgery was higher at 24.62% (95% CI: 23.09-26.20) among participants aged 50-60 years. The most deprived group had a higher odds ratio [adjusted odds ratio: 1.20 (95% CI: 1.00-1.44)] (p < 0.05) of having unmet needs for cataract surgery. Conclusions: There is a considerable burden of age-related cataracts in India. While the coverage of cataract surgery is high, the unmet need for cataract surgery cannot be overlooked. The existing blindness control programme has contributed significantly to increasing the coverage of cataract surgery, but it still needs to be strengthened, especially to reach the most deprived sections of society.

Netarsudil monotherapy as the initial treatment for open-angle glaucoma and ocular hypertension in Indian patients: A real-world evaluation of efficacy and safety.

Purpose: Glaucoma is the second leading cause of blindness worldwide, affecting more than 64 million people aged 40-80. The best way to manage primary open-angle glaucoma (POAG) is by lowering the intraocular pressure (IOP). Netarsudil is a Rho kinase inhibitor, the only class of antiglaucoma medications that reorganizes the extracellular matrix to improve the aqueous outflow through the trabecular pathway. Methods: An open-label, real-world, multicentric, observation-based 3-month study was performed for assessing the safety and ocular hypotensive efficacy of netarsudil ophthalmic solution (0.02% w/v) in patients with elevated IOP. Patients were given netarsudil ophthalmic solution (0.02% w/v) as a first-line therapy. Diurnal IOP measurements, best-corrected visual acuity, and adverse event assessments were recorded at each of the five visits (Day-1: screening day and first dosing day; subsequent observations were taken at 2 weeks, 4 weeks, 6 weeks, and 3 months). Results: Four hundred and sixty-nine patients from 39 centers throughout India completed the study. The mean IOP at baseline of the affected eyes was 24.84 ± 6.39 mmHg (mean ± standard deviation). After the first dose, the IOP was measured after 2, 4, and 6 weeks, with the final measurement taken at 3 months. The percentage reduction in IOP in glaucoma patients after 3 months of once-daily netarsudil 0.02% w/v solution use was 33.34%. The adverse effects experienced by patients were not severe in the majority of cases. Some adverse effects observed were redness, irritation, itching, and others, but only a small number of patients experienced severe reactions, as reported in a decreasing order: redness > irritation > watering > itching > stinging > blurring. Conclusion: We found that netarsudil 0.02% w/v solution monotherapy when used as the first-line treatment in primary open-angle glaucoma and ocular hypertension was both safe and effective.

A novel procedure for the synthesis of borylated quinolines and its application in the development of potential boron-based homeodomain interacting protein kinase 2 (HIPK2) inhibitors.

Herein, we demonstrate a Pd catalyzed C-4 borylation of structurally complex chloroquinolines with bis(pinacolato)diboron under relatively simple and efficient conditions. Moreover, the borylated quinolines were converted into oxaborole, trifluoroborate salt and boronic acid and also rendered in the Suzuki reaction successfully. The method was also applied for the synthesis of potential boron-based homeodomain interacting protein kinase 2 (HIPK2) inhibitors. The strategy opens up new avenues for the functionalization of quinolines as potential probes and pharmacological agents for future biomedical research.

Magmas Inhibition in Prostate Cancer: A Novel Target for Treatment-Resistant Disease.

The purpose of our study was to evaluate Magmas as a potential target in prostate cancer. In addition, we evaluated our synthetic Magmas inhibitor (BT#9) effects on prostate cancer and examined the molecular mechanism of BT#9. A cell viability assay showed that treatment with BT#9 caused a significant decrease in the viability of DU145 and PC3 prostate cancer cells with little effect on the viability of WPMY-1 normal prostate cells. Western blot proved that BT#9 downregulated the Magmas protein and caspase-3 activation. Flow cytometry studies demonstrated increased apoptosis and disturbed mitochondrial membrane potential. However, the main mode of cell death was caspase-independent necrosis, which was correlated with the accumulation of mitochondrial and intra-cellular Reactive Oxygen Species (ROS). Taken together, our data suggest Magmas is a potential molecular target for the treatment of prostate cancer and that Magmas inhibition results in ROS-dependent and caspase-independent necrotic cell death.

Experiences of Urban Slum-Dwelling Women With Maternal and Child Health Services During COVID-19 Pandemic: A Multi-City Qualitative Study From India.

Objectives: The COVID-19 pandemic containment necessitated the diversion of substantial health care resources thus affecting the routine essential care, and posing barriers to achieving the Sustainable Development Goals (SDGs). We explored the experiences of vulnerable communities-urban-slum-dwelling women regarding maternal and child health services during COVID-19. Methods: We conducted 48 in-depth interviews in four Indian states-12 in each state among urban-slum antenatal, intra-natal, and postnatal women. We used framework analysis. Results: Amidst the implementation of the mandatory stay-at-home, many women acknowledged that routine immunization services and antenatal check-ups remained uninterrupted, and were mostly provided at the community level. To prevent transmission, the family members and relatives had restricted visits to the health facility during labor or post-delivery. Women preferred to have a shorter hospital stay post-delivery and reduced routine postnatal check-ups for fear of infection. Conclusion: India has a variety of national and state-level programs focused on improving MCH indicators to achieve the SDGs. COVID-19 inadvertently interrupted some components of health services, insinuating the need for a disaster or pandemic-resilient MCH services delivery system.

Reduction of hexavalent chromium by Exiguobacterium mexicanum isolated from chromite mines soil.

Hexavalent chromium is a highly toxic element generated due to indiscriminate chromite mining in Sukinda, Odisha. In the present research investigation a relatively higher Cr(VI) resistant (900 mg L-1) bacterium CWB-54 was isolated from the chromite mine water. Based on the biochemical and molecular analysis the strain (CWB-54) was identified as Exiguobacterium mexicanum. When this bacterium was grown at 35 °C, 100 rpm, pH~8.0, and fructose as an electron donor, it could reduce the total hexavalent chromium (100 mg L-1) supplemented in the medium within 33 h of incubation period. Though experiment was carried out to study the effect of Mn, Ni, Cd, Hg and Zn on Cr(VI) reduction by the strain E. mexicanum it has been observed that in the presence of Cd and Hg, Cr(VI) reduction drastically decreased. Characterization of Cr(VI) reduced product by SEM-EDX and TEM analysis revealed intracellular and extracellular Cr(III) deposition in the bacterium, which is assumed to be Cr(OH)3 precipitate in nanometric size. But the extracellular chromate reductase enzyme production is found to be negligible as compared to the intracellular enzyme production. The increased concentration of Cr(VI) above (1000 mg L-1) also showed the genotoxic effect on the DNA. Several reports have been published on Exiguobacterium sp. on different scientific aspect but the current report on the reduction of toxic Cr(VI) by a new species E. mexicanum is a novel one which established the potentiality of this microorganism for a broad area of application.

5-ureidobenzofuranone indoles as potent and efficacious inhibitors of PI3 kinase-alpha and mTOR for the treatment of breast cancer.

A series of 5-ureidobenzofuran-3-one indoles as potent inhibitors of PI3Kalpha and mTOR has been developed. The best potency in cells was obtained when the urea group was extended to a 4-[2-(dimethylamino)ethyl]methylamino amidophenyl group. A 7-fluoro group on the indole ring also enhanced cellular potency. Compound 18i, incorporating the optimal functional groups, showed high potency in cellular lines and was further studied in vivo. It was able to inhibit the biomarker phosphorylation for 8h when dosed at 25 mg/kg iv. In the MDA-MB-361 breast cancer model, it shrank the tumor size remarkably when dosed at 25 mg/kg iv on days 1, 5, and 9.

Novel N9-arenethenyl purines as potent dual Src/Abl tyrosine kinase inhibitors.

Novel N(9)-arenethenyl purines, optimized potent dual Src/Abl tyrosine kinase inhibitors, are described. The key structural feature is a trans vinyl linkage at N(9) on the purine core which projects hydrophobic substituents into the selectivity pocket at the rear of the ATP site. Their synthesis was achieved through a Horner-Wadsworth-Emmons reaction of N(9)-phosphorylmethylpurines and substituted benzaldehydes or Heck reactions between 9-vinyl purines and aryl halides. Most compounds are potent inhibitors of both Src and Abl kinase, and several possess good oral bioavailability.

The relationship of abdominal girth with blood pressure, blood sugar and lipid profile among cardiac patients.

OBJECTIVES: This study aimed to characterize and identify the relationship of abdominal girth with blood pressure, blood sugar and lipid profile among cardiac patients. METHODS: A total of 100 patients with diagnosed cardiac problems were recruited from the outpatient clinic of a multi-speciality hospital. For data collection, a self-administered questionnaire was used to gather information about patients' demographics and socio-economic status. In addition, an assessment tool on the Physical and Laboratory Characteristics was employed. The data were analysed using t tests, Pearson correlations and chi squared tests. RESULTS: The findings of the study showed that there was a significant positive correlation of abdominal girth with blood pressure, blood sugar and lipid profile, as the R-values were reported to be 0.32, 0.28, 0.02, 0.32, 0.32, 0.28 and 0.18. There was no significant association of the selected demographic variables with abdominal girth, blood pressure, blood sugar or lipid profile among the selected cohort of patients. CONCLUSION: Lifestyle factors contribute significant risk in the development of abdominal obesity, metabolic syndrome and cardiovascular diseases. This study recommends a careful monitoring of risk factors at an early age, which would go a long way towards reducing the burden of abdominal obesity and obesity related cardio metabolic risk.