Role of infrastructure and operation in disease prevalence in dairy farms: groundwork for disease prevention-based antibiotic stewardship.

Attempts at regulating misuse of antibiotics in the dairy industry have been ineffective, especially in low- and middle-income countries, who also typically have high burden of preventable infectious disease, we propose a disease prevention-based approach to minimize the need and in turn consumption of antibiotics in dairy farms. Since the immediate environment of the animals is key to disease prevalence, we targeted the infrastructure- and operation-related factors in dairy farms and their link with prevalence of most common diseases and symptoms. We conducted four focused group discussions and a cross-sectional survey in 378 dairy farms to investigate disease prevalence and associated infrastructural (housing system, and manger shape), and operational (waste management, feed management, and type of cleaning agent) parameters. The most common diseases (Mastitis and secondary infections related to Foot-and-mouth disease) and symptoms (fever and diarrhoea) in the focus area were linked with the infrastructural and operational factors on the dairy farm with higher disease prevalence reported in dairy farms, where the animals were exposed to variations in diurnal temperatures or were hard to clean. We further used ML classifiers - Neural Network (NN), k-Nearest Neighbour (kNN), Support Vector Machine (SVM), Decision Tree (DT), and Random Forest (RF) - to corroborate the relationship between infrastructure and operations of the dairy farms and disease prevalence- The DT classifier on randomly sampled data could predict the prevalence of the two most common diseases (accuracy = 92%, F1-score = 0.919) Our results open new avenues for cost-effective interventions such as use of curve-edged mangers, use of rubber mats on floors, not reusing leftover feed etc. in dairy farms to prevent the most common diseases and symptoms in dairy farms and reduce the need and consumption of antibiotics.

Invasion potential of the aquarium pet snail Planorbella trivolvis in India: impact of certain abiotic and biotic factors.

Planorbella trivolvis (ramshorn snail) is one of India's most extensively sold exotic aquarium pet snails. The unintentional or deliberate release of P. trivolvis may result in the colonisation and establishment as an invasive snail in freshwater ecosystems. However, the successful invasion of P. trivolvis will depend on several abiotic and biotic factors of the concerned freshwater ecosystem. We have assessed the possibility of overcoming the opposing factors in P. trivolvis invasion through laboratory-based experiments and examined the effects of household-derived pollutants on egg hatchability, adult survivability and fecundity, and temperature (15 to 35 °C) on growth, sexual maturity, and reproduction. Additionally, we have evaluated the potential of native predators as biotic resistance to invasion by prey-choice experiment. The results indicated that egg hatchability, adult survivability, and fecundity were reduced with increasing pollutant concentration. However, the same traits did not differ from a native freshwater snail, Indoplanorbis exustus. The fecundity of P. trivolvis increased with increasing body size, but no considerable differences at different temperature levels suggest a wide range of adaptation to temperature. Faster growth and the requirement of comparatively few days to attain sexual maturity were observed in the higher temperatures. The native predators, Glossiphonia weberi and Diplonychus rusticus, avoided P. trivolvis as prey over the alternative prey snails in most instances, suggesting the masking of biotic resistance against the colonisation. Our observations indicate that the chance dispersal of P. trivolvis from household or commercial aquaria may lead to a possible invasion of freshwater ecosystems under suitable conditions.

Progression and expansion of quinoline as bioactive moiety: a patent review.

Quinoline inhibitors are appealing medicinal products for a range of illnesses and problems. It is bicyclic heterocyclic scaffold has been intensively employed in pharmacological research and is well known for its wide range of biological purposes. Biological activities exhibited by quinoline derivatives, such as anti-inflammatory properties, antioxidant, antimicrobial, anti-tubercular, antidiabetic, anti-malarial and others are covered in detail in this review. The IC50 of patented inhibitors might range from nm to µM range, based on the experiments used. It presents an outline of patents file between 2002 and 2023 concerning to biological activities by quinoline derivatives. As a result, it is critical to develop additional chemical quinoline core alterations for novel chemical compounds and enhanced pharmacological impacts.

Cross-talk between the cytokinin, auxin, and gibberellin regulatory networks in determining parthenocarpy in cucumber.

Cucumber is a model plant for studying parthenocarpy with abundant slicing- and pickling-type germplasm. This study was undertaken to understand the role of the important cytokines (CKs), auxin (AUX) and gibberellin (GA) biosynthesis and degradation genes for the induction of parthenocarpy in slicing and pickling germplasm. Two genotypes of gynoecious parthenocarpic cucumber, PPC-6 and DG-8, along with an MABC-derived gynoecious non-parthenocarpic line, IMPU-1, were evaluated in this study. The slicing and pickling cucumber genotypes PPC-6 and DG-8 were strongly parthenocarpic in nature and set fruit normally without pollination. Endogenous auxin and gibberellin were significantly higher in parthenocarpic than non-parthenocarpic genotypes, whereas the concentration of cytokinins varied among the genotypes at different developmental stages. However, the exogenous application of Zeatin and IAA + Zeatin was effective in inducing parthenocarpic fruit in IMPU-1. Expression analysis with important CK, AUX, and GA biosynthesis-related genes was conducted in IMPU-1, PPC-6, and DG-8. The expression of the CK synthase, IPT, IPT3, PaO, LOG1, LOG2, CYP735A1, and CYP735A2 was up-regulated in the parthenocarpic genotypes. Among the transcription factor response regulators (RRs), positive regulation of CSRR8/9b, CSRR8/9d, CSRR8/9e, and CSRR16/17 and negative feedback of the CK signalling genes, such as CsRR3/4a, CsRR3/4b, CsRR8/9a, and CsRR8/9c, were recorded in the parthenocarpic lines. Homeostasis between cytokinin biosynthesis and degradation genes such as CK oxidases (CKXs) and CK dehydrogenase resulted in a non-significant difference in the endogenous CK concentration in the parthenocarpic and non-parthenocarpic genotypes. In addition, up-regulation of the key auxin-inducing proteins and GA biosynthesis genes indicated their crucial role in the parthenocarpic fruit set of cucumber. This study establishes the critical role of the CKs, AUX, and GA regulatory networks and their cross-talk in determining parthenocarpy in slicing and pickling cucumber genotypes.

Pralsetinib: chemical and therapeutic development with FDA authorization for the management of RET fusion-positive non-small-cell lung cancers.

Pralsetinib (PRL) is a selective Rearranged during Transfection (RET) inhibitor, developed by Blueprint Medicines Corporation for the treatment of RET fusion non-small-cell lung cancer (NSCLC), papillary thyroid cancer (PTC), and medullary thyroid carcinoma (MTC). RET is a known proto-oncogene found in NSCLC, PTC, and MTC. PRL was recently granted accelerated USFDA approval with the brand name GAVRETO™ on 4 September 2020 to treat metastatic RET fusion-positive NSCLC and was updated on 1 December 2020 with the addition of advanced and metastatic RET-altered MTC and PTC in the USA. On 19 November 2021, the European Commission granted conditional marketing authorization to PRL for use as a single agent in adult patients with RET fusion-positive advanced NSCLC. They were not previously treated with an RET inhibitor. This review article summarizes the milestones in the development of PRL, chemistry, chemical (synthesis) research and development, characterization and identification of PRL-resistant RET mutants, the structural basis of resistance to PRL, mechanism of action, pharmacokinetics, pharmacodynamic, adverse effects, and regulatory status, including ongoing clinical trial of PRL and other potential drug candidates, leading to this first approval of PRL for the treatment of various solid tumors (RET fusion NSCLC, MTC, and PTC).

Nanotechnology-based Medicinal Products and Patents: A Promising Way to Treat Psoriasis

Psoriasis is an autoimmune skin disorder that is characterised by chronic inflammation and erythematous scaly patches. It has a significant impact on the patient's quality of life and can cause psychological stress. There are several aspects that cause psoriasis, for instance, environmental issues, immune disorders, bacterial infections, and genetic issues. Plentiful therapeutic means or treatments are accessible, but not any of them can completely and effectively cure psoriasis without hindering patient compliance. Hence, it becomes challenging to discover a new drug moiety or any drug delivery method to cure psoriasis. Conventional treatment of psoriasis involves anti-inflammatory agents, immune suppressants, phototherapy, and biological treatment, which were given in different forms such as topical, oral, or systemic formulations, but these all were unsuccessful to accomplish complete reduction of psoriasis as well as causing adverse side effects. In terms of dose frequency, doses, efficacy, and side effects, nanotechnology-based new formulations are the most promising prospects for addressing the challenges and limits associated with present psoriasis formulations. Hence, our major goal of this review is to present various advanced nanotechnological approaches for the effective topical treatment of psoriasis. In short, nano-formulations continue to be formed as very promising modalities in the treatment of psoriasis as they suggest improved penetration, targeted delivery, increased safety, and efficacy.

Identification of a major QTL, Parth6.1 associated with parthenocarpic fruit development in slicing cucumber genotype, Pusa Parthenocarpic Cucumber-6.

Parthenocarpy is an extremely important trait that revolutionized the worldwide cultivation of cucumber under protected conditions. Pusa Parthenocarpic Cucumber-6 (PPC-6) is one of the important commercially cultivated varieties under protected conditions in India. Understanding the genetics of parthenocarpy, molecular mapping and the development of molecular markers closely associated with the trait will facilitate the introgression of parthenocarpic traits into non-conventional germplasm and elite varieties. The F1, F2 and back-crosses progenies with a non-parthenocarpic genotype, Pusa Uday indicated a single incomplete dominant gene controlling parthenocarpy in PPC-6. QTL-seq comprising of the early parthenocarpy and non-parthenocarpic bulks along with the parental lines identified two major genomic regions, one each in chromosome 3 and chromosome 6 spanning over a region of 2.7 Mb and 7.8 Mb, respectively. Conventional mapping using F2:3 population also identified two QTLs, Parth6.1 and Parth6.2 in chromosome 6 which indicated the presence of a major effect QTL in chromosome 6 determining parthenocarpy in PPC-6. The flanking markers, SSR01148 and SSR 01012 for Parth6.1 locus and SSR10476 and SSR 19174 for Parth6.2 locus were identified and can be used for introgression of parthenocarpy through the marker-assisted back-crossing programme. Functional annotation of the QTL-region identified two major genes, Csa_6G396640 and Csa_6G405890 designated as probable indole-3-pyruvate monooxygenase YUCCA11 and Auxin response factor 16, respectively associated with auxin biosynthesis as potential candidate genes. Csa_6G396640 showed only one insertion at position 2179 in the non-parthenocarpic parent. In the case of Csa_6G405890, more variations were observed between the two parents in the form of SNPs and InDels. The study provides insight about genomic regions, closely associated markers and possible candidate genes associated with parthenocarpy in PPC-6 which will be instrumental for functional genomics study and better understanding of parthenocarpy in cucumber.

Indole derivatives (2010-2020) as versatile tubulin inhibitors: synthesis and structure-activity relationships.

Tubulin inhibitors are conjugates that interfere with the dynamic equilibrium of the polymerization and depolymerization of microtubules. Among all the reported conjugates, indole moiety is one of the most significant classes for the development of new drug candidates for cancer therapy. Due to their presence in a wide range of natural as well as synthetic antitubulin agents, indole has become a versatile scaffold in research, and various synthetic and semisynthetic indole-based antitubulin agents have been identified and reported. The present article focuses on the reported indole-based tubulin inhibitors of synthetic origin from last the decade. Synthesis, structure-activity relationships and biological activities of synthetic indole derivatives along with brief updates on their antitubulin activity are presented.

Contemporary advances of cyclic molecules proposed for inflammation.

This review stretches insight about the advancement (2011-2021) of synthesized non-heterocyclic, heterocyclic and natural occurring cyclic molecules for inflammation. While inflammation is very significant in the abolition of pathogens and other causes of soreness, a protracted inflammatory procedure takes to outcomes in chronic disease that might finally affect in organ failure or damage. Thus, restraining the provocative process by the use of anti-inflammatory agents is chief in controlling this damage. It also reveals other pursuit along with their anti-inflammatory activity. Molecular docking studies represent most suitable PDB (Protein Data Bank) ID for the synthesized heterocyclic molecules with their selective inhibitor. It discusses the findings presented in recent research papers and provides understanding to researchers intended for the growth of newer combinations/molecules having littler side things.

Measurement of vapour-liquid equilibrium and e-NRTL model development of CO2 absorption in aqueous dipropylenetriamine.

Vapour-liquid equilibrium (VLE) of CO2 in aqueous dipropylenetriamine (DPTA) is investigated experimentally using a stirred equilibrium cell setup. Equilibrium solubility of CO2 is measured in the temperature and pressure range of (313-333) K and (1-100) kPa respectively. Composition of aqueous DPTA solvent used for the absorption study is in the range of (5-15) mass%. Experimental data shows higher CO2 loading capacity of this solvent compared to conventional solvents like monoethanolamine (MEA), 2-amino-2-methyl-1-propanol (AMP), and N-methyldiethanolamine (MDEA) as well as recently developed polyamine solvents like aminoethylethanolamine (AEEA), piperazine (PZ), and hexamethylenediamine (HMDA). Experimental VLE data is then correlated using the electrolyte non-random two-liquid (e-NRTL) theory which is an activity coefficient-based model for the electrolyte system. Data regression system (DRS) in Aspen Plus® (V8.8) is employed to fit the e-NRTL model equation with the experimental data by regressing the model parameters. Model-predicted data is found to be in good agreement with the experimental VLE data with an average absolute deviation of 22.3%. Performance of aqueous DPTA solvent is also analysed by predicting solvent capacity, equilibrium liquid-phase speciation, and heat of CO2 absorption using the newly developed e-NRTL model for the investigated system.

Free radical scavengers: An overview on heterocyclic advances and medicinal prospects.

In the present scenario, there has been a lot of consideration toward the field of free radical chemistry. Free radicals responsive oxygen species are produced by different endogenous frameworks, exposure to various physicochemical conditions, radiation, toxins, metabolized drug by-product, and pathological states. On the off chance that free radical overpowers the body's capacity, it generates a condition known as oxidative stress, which can alter physiological conditions of the body and results in several diseases. For appropriate physiological function, it is necessary to have a proper balance between free radicals and antioxidants. Antioxidants chemically inhibit the oxidation process; they are also known as free radical scavengers. For tackling the problem of oxidative stress application of an external source of antioxidant is helpful. A lot of antioxidants of natural, semi-synthetic and synthetic origin are in use, with time search of more effective, nontoxic, safe antioxidant is intensified. The present review, discuss different synthetic derivatives bearing various heterocyclic scaffolds as radical scavengers.

Aromatase inhibitors: Role in postmenopausal breast cancer.

Postmenopausal women are at high risk of developing breast cancer due to estrogen production in peripheral tissues of the body other than ovaries. Aromatase is present in breast tissue, leading to local estrogen production which can be inhibited by a variety of steroidal and nonsteroidal aromatase inhibitors. There are many aromatase inhibitors available in clinical practice like exemestane, formestane, anastrozole, letrozole, fadrozole, vorozole, and so forth, but the major challenge in anti-breast cancer therapy is the toxicity associated with aromatase inhibitors, especially the steroidal class of drugs. It is, therefore, urgently required to develop novel anticancer drugs having better safety and efficacy for the treatment of breast cancer. This study highlights the aromatase inhibitors reported in the current literature as well as the recent advances in the management of breast cancer.

Medicinal prospects of antioxidants: A review.

Free radicals generated due to exposure of radiation, environmental pollutants and as by-products of metabolised drugs. These free radicals are antagonized by molecules which are antioxidant in nature. Antioxidants are the substances which inhibit oxidation. They are moreover acknowledged as "free radical scavengers" as they form minor reactive species via radicals. Based on origin, they are categorised into two types: exogenous and endogenous antioxidants. An Antioxidant reduces the occurrence of different disorders like: aging, cancer, diabetes, inflammation, liver disease, cardiovascular disease, cataract and nephrotoxicity and neurodegenerative disorders. Dietary antioxidants are thought to have potential capacities to avert oxidative anxiety induced diseases. This review figures the various researches on pharmacological activity of natural along with synthetic antioxidant molecules.

Curcumin as a modulator of oxidative stress during storage: a study on plasma.

BACKGROUND: Plasma reflects the situations of oxidative stress in blood. Curcumin as an additive in storage solutions is not explored. MATERIALS AND METHODS: Blood was drawn from male Wistar rats (4 months old) and stored over a period of 20 days at 4 °C in CPDA-1. Plasma was isolated from stored blood at regular intervals. Oxidative stress markers were analyzed in controls and experimental samples (with curcumin 10mM, 30 mM and 60mM). RESULTS: Antioxidant enzymes and sulfhydryls ameliorated, while TBARS and protein carbonyls reduced in curcumin samples. However, curcumin could not protect the susceptible groups in proteins thereby leading to dityrosine linkages (AOPP). CONCLUSION: Curcumin was beneficial at higher concentrations as it reduced oxidative stress, therefore paving way for the further studies on curcumin as a component in storage solutions.