Intricate relationship between cancer stemness, metastasis, and drug resistance.

Cancer stem cells (CSCs) are widely acknowledged as the drivers of tumor initiation, epithelial-mesenchymal transition (EMT) progression, and metastasis. Originating from both hematologic and solid malignancies, CSCs exhibit quiescence, pluripotency, and self-renewal akin to normal stem cells, thus orchestrating tumor heterogeneity and growth. Through a dynamic interplay with the tumor microenvironment (TME) and intricate signaling cascades, CSCs undergo transitions from differentiated cancer cells, culminating in therapy resistance and disease recurrence. This review undertakes an in-depth analysis of the multifaceted mechanisms underlying cancer stemness and CSC-mediated resistance to therapy. Intrinsic factors encompassing the TME, hypoxic conditions, and oxidative stress, alongside extrinsic processes such as drug efflux mechanisms, collectively contribute to therapeutic resistance. An exploration into key signaling pathways, including JAK/STAT, WNT, NOTCH, and HEDGEHOG, sheds light on their pivotal roles in sustaining CSCs phenotypes. Insights gleaned from preclinical and clinical studies hold promise in refining drug discovery efforts and optimizing therapeutic interventions, especially chimeric antigen receptor (CAR)-T cell therapy, cytokine-induced killer (CIK) cell therapy, natural killer (NK) cell-mediated CSC-targeting and others. Ultimately use of cell sorting and single cell sequencing approaches for elucidating the fundamental characteristics and resistance mechanisms inherent in CSCs will enhance our comprehension of CSC and intratumor heterogeneity, which ultimately would inform about tailored and personalized interventions.

Sustainable solutions for direct TLC enantioseparation with in-home thought-out, prepared/modified chiral stationary phases.

TLC is used globally, yet less attention has been paid to TLC (in enantioseparation) despite its advantages. The present paper describes/reviews successfully practiced direct approaches of 'chiral additive in achiral stationary phase' (as an application of in-home thought out, prepared, tested, and modified chiral stationary phase), 'pre-mixing of chiral reagent with the enantiomeric mixture' (an approach using both achiral phases during chromatographic separation) and 'chiral additive in mobile phase', and chiral ligand exchange for enantioseparation of DL-amino acids, their derivatives, and some active pharmaceutical ingredients. It provided efficient enantioseparation, quantitative determination, and isolation of native forms via in-situ formation of non-covalent diastereomeric pair. The mechanism of enantioseparation in these approaches has been discussed along with the isolation and establishment of the structure of diastereomers. This may help chemists gain useful insights into fields outside their specialization and the experts get brief accounts of recent key developments, providing solutions for sustainable development of less expensive methods for control of enantiomeric purity and isolation of native enantiomers.

Exploring the promise of regulator of G Protein Signaling 20: insights into potential mechanisms and prospects across solid cancers and hematological malignancies.

RGS (Regulator of G protein signaling) proteins have long captured the fascination of researchers due to their intricate involvement across a wide array of signaling pathways within cellular systems. Their diverse and nuanced functions have positioned them as continual subjects of scientific inquiry, especially given the implications of certain family members in various cancer types. Of particular note in this context is RGS20, whose clinical relevance and molecular significance in hepatocellular carcinoma we have recently investigated. These investigations have prompted questions into the prevalence of pathogenic mutations within the RGS20 gene and the intricate network of interacting proteins that could contribute to the complex landscape of cancer biology. In our study, we aim to unravel the mutations within the RGS20 gene and the multifaceted interplay between RGS20 and other proteins within the context of cancer. Expanding on this line of inquiry, our research is dedicated to uncovering the intricate mechanisms of RGS20 in various cancers. In particular, we have redirected our attention to examining the role of RGS20 within hematological malignancies, with a specific focus on multiple myeloma and follicular lymphoma. These hematological cancers hold significant promise for further investigation, as understanding the involvement of RGS20 in their pathogenesis could unveil novel therapeutic strategies and treatment avenues. Furthermore, our exploration has extended to encompass the latest discoveries concerning the potential involvement of RGS20 in diseases affecting the central nervous system, thereby broadening the scope of its implications beyond oncology to encompass neurobiology and related fields.

Genetic variants related to insulin metabolism are associated with gestational diabetes mellitus.

The current study sought to investigate the associations of common genetic risk variants with gestational diabetes mellitus (GDM) risk in the north Indian population and to evaluate their utility in identifying GDM cases. A case-control study, including 300 pregnant women, was included, and clinical and pathological information was collected. The amplification-refractory mutation system (ARMS) was used for genotyping four single nucleotide polymorphisms (SNPs), namely FTO (rs9939609), PPARG2 (rs1801282), SLC30A8 (rs13266634), and TCF7L2 (rs12255372). The odds ratio and confidence interval were determined for each SNP in different genetic models. Further, attributable risk, population penetrance, and relative risk were also calculated. The risk allele A of FTO (rs9939609) poses a two times higher risk of GDM (p = 0.02, OR = 2.5). The CG and GG genotypes of PPARG2 (rs1801282) have half a lower risk of GDM. In SLC30A8 (rs13266634), the recessive model analysis showed a two times higher risk of having GDM, while the recessive model (TT vs. GG + GT) analysis in TCF7L2 (rs12255372) indicates a lower risk of GDM. Finally, the relative risk, population penetrance, and attributable risk for risk allele in all four variants was higher in GDM mothers. All four polymorphisms were found to be significantly associated with BMI, HbA1c, and insulin. Our study first time confirmed a significant association with GDM for four variants, FTO, PPARG2, SLC30A8, and TCF7L2, in the North Indian population.

Engineering circular RNA for molecular and metabolic reprogramming.

The role of messenger RNA (mRNA) in biological systems is extremely versatile. However, it's extremely short half-life poses a fundamental restriction on its application. Moreover, the translation efficiency of mRNA is also limited. On the contrary, circular RNAs, also known as circRNAs, are a common and stable form of RNA found in eukaryotic cells. These molecules are synthesized via back-splicing. Both synthetic circRNAs and certain endogenous circRNAs have the potential to encode proteins, hence suggesting the potential of circRNA as a gene expression machinery. Herein, we aim to summarize all engineering aspects that allow exogenous circular RNA (circRNA) to prolong the time that proteins are expressed from full-length RNA signals. This review presents a systematic engineering approach that have been devised to efficiently assemble circRNAs and evaluate several aspects that have an impact on protein production derived from. We have also reviewed how optimization of the key components of circRNAs, including the topology of vector, 5' and 3' untranslated sections, entrance site of the internal ribosome, and engineered aptamers could be efficiently impacting the translation machinery for molecular and metabolic reprogramming. Collectively, molecular and metabolic reprogramming present a novel way of regulating distinctive cellular features, for instance growth traits to neoplastic cells, and offer new possibilities for therapeutic inventions.

In silico analysis unveiling potential biomarkers in gallbladder carcinogenesis.

Gallbladder cancer (GBC) is a rare but very aggressive most common digestive tract cancer with a high mortality rate due to delayed diagnosis at the advanced stage. Moreover, GBC progression shows asymptomatic characteristics making it impossible to detect at an early stage. In these circumstances, conventional therapy like surgery, chemotherapy, and radiotherapy becomes refractive. However, few studies reported some molecular markers like KRAS (Kirsten Rat Sarcoma) mutation, upregulation of HER2/neu, EGFR (Epidermal Growth Factor Receptor), and microRNAs in GBC. However, the absence of some specific early diagnostic and prognostic markers is the biggest hurdle for the therapy of GBC to date. The present study has been designed to identify some specific molecular markers for precise diagnosis, and prognosis, for successful treatment of the GBC. By In Silico a network-centric analysis of two microarray datasets; (GSE202479) and (GSE13222) from the Gene Expression Omnibus (GEO) database, shows 50 differentially expressed genes (DEGs) associated with GBC. Further network analysis revealed that 12 genes are highly interconnected based on the highest MCODE (Molecular Complex Detection) value, among all three genes; TRIP13 (Thyroid Receptor Interacting Protein), NEK2 (Never in Mitosis gene-A related Kinase 2), and TPX2 (Targeting Protein for Xklp2) having highest network interaction with transcription factors and miRNA suggesting critically associated with GBC. Further survival analysis data corroborate the association of these genes; TRIP13, NEK2, and TPX2 with GBC. Thus, TRIP13, NEK2, and TPX2 genes are significantly correlated with a greater risk of mortality, transforming them from mere biomarkers of the GBC for early detections and may emerge as prognostic markers for treatment.

Generic pharmaceuticals, regulatory aspects, bioequivalence investigation, and perception.

INTRODUCTION: The objective and significance of the topic is to draw attention toward regulatory aspects (and pharmacopoeias) for bioequivalence investigation, and perception for generic pharmaceuticals, especially their stereoselective bioequivalence evaluation for understanding the performance of the racemic generic products available in the market. AREAS COVERED: The areas covered include bioequivalence studies (and related USP and FDA requirements) on certain generic APIs for comparison, examples of concern related to inspection of pharmaceuticals for export/import. Literature methodology includes search through USP monographs, MDPI.com, msn.com, WHO Drug Information, certain specific web links, PubMed Central®, PubMed®, NLM's advanced biomedical information services, and several pdf published in relevant journals in the field for related authentic information. EXPERT OPINION: The USP, the USFDA, and the units alike internationally should enforce pharmaceutical companies to perform stereoselective investigations on generic APIs to show that their PK/PD parameters are (nearly) equal to the standards set by such units for allowing marketing of that API. This should be provided to professionals in the areas of patient care and every country should enforce such regulations at the time of export and import of generics.

Contribution of fossil and biomass-derived secondary organic carbon to winter water-soluble organic aerosols in Delhi, India.

Delhi, among the world's most polluted megacities, is a hotspot of particulate matter emissions, with high contribution from organic aerosol (OA), affecting health and climate in the entire northern India. While the primary organic aerosol (POA) sources can be effectively identified, an incomplete source apportionment of secondary organic aerosol (SOA) causes significant ambiguity in the management of air quality and the assessment of climate change. Present study uses positive matrix factorization analysis on the water-soluble organic aerosol (WSOA) data from the offline-aerosol mass spectrometry (AMS). It revealed POA as the dominant source of WSOA, with biomass-burning OA (31-34 %) and solid fuel combustion OA (∼21 %) being two major contributors. Here we use water-solubility fingerprints to track the SOA precursors, such as oxalates or organic nitrates, instead of identifying them based on their O:C ratio. Non-fossil precursors dominate in more oxidized oxygenated organic carbon (MO-OOC) (∼90 %), a proxy for aged secondary organic carbon (SOC), by coupling offline-AMS with 14C measurements. On the contrary, the oxidation of fossil fuel emissions produces a large quantity of fresh fossil SOC, which accounts for ∼75 % of less oxidized oxygenated organic carbon (LO-OOC). Our study reveals that apart from major POA contributions, large fractions of fossil (10-14 %) and biomass-derived SOA (23-30 %) contribute significantly to the total WSOA load, having impact on climate and air quality of the Delhi megacity. Our study reveals that large-scale unregulated biomass burning was not only found to dominate in POA but was also observed to be a significant contributor to SOA with implications on human health, highlighting the need for effective control strategies.

Enantioselective and Chemoselective Optical Detection of Chiral Organic Compounds without Resorting to Chromatography.

Enantiorecognition and resolution are of essential importance in many diverse areas of science. Whenever there arises a need to analyze/investigate enantiomers in different situations chromatography stands up in our minds immediately. Nevertheless, chemoselective and enantioselective recognition/discrimination (without going for separation) constitutes a different perception and requirement. The techniques using chiroptical sensing cause detection based on molecular interactions induced in different manners. Enantioselective sensing of monosaccharides in γ-cyclodextrin assembly and by diboronic acid based fluorescent sensors, application of bi-naphthol and H8 BINOL based sensors and dendrimers, metal-to-ligand charge transfer transitions in CD, exciton-coupled circular dichroism, surface enhanced Raman spectroscopy, and enantioselective indicator displacement sensor arrays for enantioselective recognition/detection of chiral organic compounds, such as amines, amino acids/alcohols, and hydroxycarboxylic acids have been discussed in progressive manner with mechanistic explanations, wherever available. Besides, the chiroptical vs LC approach has been discussed. The present paper is focused on certain different non-chromatographic optical techniques and aims to extend an understanding and a view to consider such techniques which have been successful in selective detection, and determination of absolute configuration and enantiomeric excess, (without resorting to separation vis-à-vis LC) and that have potential use in high-throughput chiral assay and combinatorial search for asymmetric catalysts and reagents.

Uncommon Presentation of Leprosy: A Report of Two Cases.

Lazarine leprosy is an unusual expression of usually borderline tuberculoid (BT) form characterized by spontaneous ulceration of skin lesions. This is presumably the result of an exaggerated type 1 reaction. It commonly occurs in the BT, borderline lepromatous forms and rarely in the lepromatous forms of leprosy. We report two cases of lazarine leprosy in the BT and BT downgrading to borderline lepromatous spectrum in healthy and immunocompetent males.

Fabrication of thin Molybdenum backed target using rolling method.

A successful attempt was made to fabricate a thin foil of natural Mo target on a thick Au backing with Indium in between to improve adhesion between the foils. Rolling at elevated temperature was considered to fabricate Mo foil while gold foil was fabricated employing conventional rolling technique. The heating of Mo foil under natural environment lead to the oxidation or carbonization on foil surface which was confirmed through Energy Dispersive X-ray Spectroscopy (EDS) measurements. Indium of thickness ∼86µg/cm2 was evaporated on Mo foil to improve adhesion between Mo and Au foils. The characterization of fabricated thin Mo foil was done using the Energy Dispersive X-ray Spectroscopy (EDS) and the Scanning Electron microscope (SEM) techniques. Thickness measurement of the target (Mo-Au) was done using Energy Dispersive X-ray Fluorescence (EDXRF) technique, in the measurements the thickness of the Mo foil and of gold backing are found out to be 1.3 mg/cm2 and 9 mg/cm2 respectively.

Model based examination of radiocarbon contribution from Indonesian throughflow to the south-eastern tropical Indian Ocean.

Shallow seawater coral records from the south-eastern tropical Indian Ocean region can be investigated to study Indonesian throughflow (ITF). In this study, the radiocarbon records of Porites corals were used to estimate lateral transport via ITF and to understand the influence of ITF on radiocarbon levels of surface waters in the south-eastern tropical Indian Ocean. A simple box model based on radiocarbon was applied for this purpose. Model estimated a mean lateral transport via ITF to be 12.5 × 106 m3 s-1 towards the south-eastern tropical Indian Ocean region using pre-bomb radiocarbon records. The model was further used to reconstruct post-bomb radiocarbon level in the Cocos Island surface water and result was compared with the observed value. The box model result demonstrated that along with air-sea CO2 exchange, the ITF was also an important contributor of bomb radiocarbon to the surface water of the south-eastern tropical Indian Ocean. The box model showed that the ITF significantly contributed bomb radiocarbon to the surface water of the south-eastern tropical Indian Ocean after the rapid increase in bomb radiocarbon in the region.

Seasonal variation of surface seawater radiocarbon in the Andaman Sea as recorded in coral.

Corals provide high-resolution radiocarbon record of the surface ocean. These high-resolution records can provide understanding of the surface ocean conditions and processes regulating these conditions. A Porites coral from the Andaman Sea was investigated for its high-resolution radiocarbon record between 2007 and 2014. The radiocarbon measurement of the coral shows a post-bomb period decline trend (2.7‰ yr-1) along with seasonal variations. A positive correlation is observed between the seasonal radiocarbon changes and the stable oxygen isotope values of the coral. The coral registers the seasonal changes in mixed layer depth and sea surface temperature between the monsoon and non-monsoon periods. Recent radiocarbon values of the Andaman Sea surface water have been found to be higher compared to the contemporary atmospheric radiocarbon values.

MicroRNA-7 Regulates Insulin Signaling Pathway by Targeting IRS1, IRS2, and RAF1 Genes in Gestational Diabetes Mellitus.

BACKGROUND: Small non-coding micro RNAs (miRNAs) are indicated in various metabolic processes and play a critical role in disease pathology, including gestational diabetes mellitus (GDM). OBJECTIVE: The purpose of this study was to examine the altered expression of miRNAs and their target genes in placental tissue (PL), cord blood (CB), and maternal blood (MB) of matched non-glucose tolerant (NGT) and GDM mother. METHODS: In a case-control study, micro-RNA was quantified from forty-five serum (MB n = 15, CB n = 15, and PL n = 15) and matched placental tissue using stem-loop RT-qPCR followed by target prediction, network construction and functional and pathways enrichment analysis. Further, target genes were verified in-vitro through transfection and RT-qPCR. RESULTS: Five miRNAs, namely hsa-let 7a-5P, hsa-miR7-5P, hsa-miR9-5P, hsa-miR18a-5P, and hsamiR23a- 3P were significantly over-expressed (p < 0.05) in all three samples namely PL, CB, and MB of GDM patients. However, the sample-wise comparison reveals higher expression of miRNA 7 in MB while lowest in CB than control. Furthermore, a comparison of fold change expression of target genes discloses a lower expression of IRS1, IRS2, and RAF1 in MB while comparatively higher expression of NRAS in MB and CB. In-vitro validation reveals lower expression of IRS1/2 and RAF1 in response to overexpression of miR-7 and vice-versa. Thus it is evident that increased miRNA7 expression causes down-regulation of its target genes IRS1, IRS2, and RAF1 in GDM mother compared to control. Further, target prediction, pathway enrichment, and hormone analysis (significantly higher FSH & LH in MB of GDM compared to NGT) revealed insulin signaling, inflammatory and GnRH signaling as major pathways regulated by miRNA7. CONCLUSION: Thus, an elevated level of miRNA7 may be associated with the progression of GDM by altering the multiple pathways like insulin, GnRH, and inflammatory signaling pathways via targeting IRS1, IRS2, and RAF1, implicating a new therapeutic target for GDM.

'Ab Ovo' Chiral Phases and Chiral Reagents for Liquid Chromatographic Separation and Isolation of Enantiomers.

The de-novo approach of mixing chirally pure reagents or Cu(II)-L-amino acid complexes in the slurry of silica gel for preparing TLC plates was reported from author's laboratory and was successful for separation and isolation of enantiomers. Using high molar absorptivity molecules, e. g., 1,5-difluoro-2,4-dinitrobenzene and cyanuric chloride, more than 38 new chiral derivatizing reagents were synthesized in our laboratory by straightforward nucleophilic substitution with simple chiral auxiliaries. Besides, (S)-naproxen, (S)-ketoprofen, and (S)-levofloxacin were used as chiral platforms. A conceptual approach using both achiral phases in chromatography for enantioseparation was also adopted. 1 H NMR and DFT based software were used to explain structures of non-covalent and covalent diastereomeric pairs and determination of configuration and separation mechanism. The methods can be easily used to determine and control enantiomeric purity with advantages over a variety of commercial chiral phases.

10Be depositional flux variation in the central Indian Ocean during the last 43 ka.

The advent of Accelerator Mass Spectrometer (AMS) enhanced the application of meteoric 10Be (half-life of 1.39 Ma) as a tracer for understanding earth surface processes on thousand to million-year time scales. However, for the majority of applications, an adequate understanding of the 10Be depositional flux is a prerequisite. A number of efforts have been made to understand both spatial and temporal variation of 10Be depositional flux. Yet, due to the limited globally distributed dataset and modulation of the 10Be signal by local processes, a significant offset is observed between model-derived and measured deposition rates of 10Be. In this study, an attempt has been made to determine the 10Be depositional flux from a marine sediment core from the central Indian Ocean chronologically constrained with the AMS radiocarbon dating and 10Be concentration measured with AMS. The 10Be depositional flux estimates using weak leaching method are found to be nearly 44% lower compared to the strong leaching method. The calculated 10Be depositional flux during the Holocene varies between 9.63 and 13.01 × 105 atoms/cm2/yr, which is 2-28% lower compared to the modeled depositional flux for the region. The difference observed in 10Be depositional flux could be due to the local processes (such as boundary scavenging, changing rate of sediment deposition at the location) affecting 10Be deposition into the sediment column or offset associated with the model estimations. The changes in 10Be depositional flux and the 10Be/9Be ratio have been reconstructed up to 43 ka. An increase in the 10Be/9Be ratio during 28 to 43 ka is observed due to the lower geomagnetic field intensity during the period. A high-resolution 10Be/9Be ratio reconstruction shows a peak at 41.2 ka, which can be attributed to the Laschamp event.

Tofacitinib for the Treatment of Twenty-Nail Dystrophy: A Single Case Report.

Twenty nail dystrophy refers to the condition of trachyonychia affecting all the twenty nails. The term trachyonychia is used to describe thin brittle nails with excessive longitudinal ridging. Treatment of twenty nail dystrophy is difficult due to poor bioavailability of drugs in nails. Tofacitinib is novel JAK-STAT inhibitor that has been used successfully for the treatment of nail dystrophy with alopecia areata suggests the possibility of the drug being used for twenty nail dystrophy.

Zinc-Responsive Acral Hyperkeratosis: A Report of a Rare Entity.

Chronic acral hyperkeratotic dermatosis includes several conditions such as lichen simplex chronicus (LSC), hypertrophic lichen planus (HLP), psoriasis vulgaris (Ps), acral acanthosis nigricans, acquired zinc deficiency, and necrolytic acral erythema (NAE). LSC, Ps, and HLP respond to conventional treatments such as topical corticosteroids, immuno-modulators such as tacrolimus, and oral methotrexate. Zinc-responsive acral hyperkeratosis is a novel entity that resembles the above mentioned diagnoses clinically but fails to respond to the above treatment options. NAE is a rare condition, commonly associated with hepatitis C virus infection and manifest similar clinical features of zinc-responsive acral hyperkeratosis, but differs histopathologically. Both conditions show a good response to oral zinc supplementation. As there is a paucity of literature on zinc-responsive acral hyperkeratosis, we are highlighting the case.

Clinical Spectrum of Cutaneous Malignancies in Central India: A Retrospective Study.

INTRODUCTION: Cutaneous malignancies account for 1%-2% of all the diagnosed cancers in India. Nonmelanoma skin cancers (NMSCs) include basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). Others include melanoma, cutaneous lymphomas, and sarcomas. Exposure to ultraviolet (UV) rays is the most important risk factor associated with skin malignancies, although various other factors are also implicated. AIMS AND OBJECTIVES: The aims of this work were to study clinical spectrum with age and sex distribution of cutaneous malignancies and metastasis; to study clinicopathological variants of each type of cutaneous malignancies; and to study the risk factors associated with cutaneous malignancies. PATIENTS AND METHODS: It was a retrospective analysis of clinically and biopsy proven cases of cutaneous malignancies from January 1, 2016 to January 31, 2018. Medical records of patients were assessed with respect to demographic information, clinical examination, dermoscopy, and histopathology. Statistical analysis was done using mean, proportion, and percentage. RESULTS: Sixty-six cases with cutaneous malignancies were recruited. There was female preponderance. The most common age group affected was 60-70 years. BCC was the most common malignancy (41%) followed by SCC (30%), malignant melanoma (9%), and cutaneous T-cell lymphoma (1.5%). Head and neck was the most common site involved. The most common clinical type of both BCC and SCC was the nodular type. Acral lentiginous was the most frequent subtype of melanoma reported. The most common predisposing for NMSCs was prolonged sun exposure (46%). CONCLUSION: This study highlights an increasing trend of NMSCs with female preponderance. Head and neck is the most common site involved. Increased risk of NMSCs is seen with increased sun exposure and predisposed genetic conditions. T-cell lymphoma was common than B-cell type. The most common internal malignancy to cause cutaneous metastasis was breast carcinoma.

Reversed-phase-HPLC enantioseparation and control of enantiomeric purity of duloxetine using a new chiral reagent and recovery of enantiomers.

This study reports a rapid and low-cost LC method for control of enantiomeric purity of duloxetine. Though duloxetine, as marketed and administered, is expected to be a single (S)-enantiomer, the analysis of a few commercial branded samples by the method developed and presented here showed that they contain a relatively high percentage of (R)-enantiomer (e.g., 2.71-5.42%, which is undesirable in drug formulations). A new chiral derivatizing reagent [isatinyl-(S)-naproxen amide] was synthesized on (S)-naproxen platform. Diastereomeric derivatives were synthesized under microwave irradiation and were separated using reversed-phase-HPLC on a C18 column. A combination of acetonitrile and triethylammonium phosphate buffer (9 mM, pH 4) as the mobile phase and detection at 273 nm were found successful. The diastereomeric derivatives at preparative scale were separated using open column chromatography, and the native enantiomers were obtained and characterized. The HPLC separation method was validated for detection limit, linearity, accuracy, and precision. The limits of detection of (S,R)-diastereomer and (S,S)-diastereomer were found to be 12 and 16 pg/mL, respectively, for the 20-µL injected volume. The method so developed has a practical significance and greater societal impact in establishing the control of enantiomeric purity and in ensuring the enantiomeric purity of the drug meant for human consumption.