Trifluoromethyl-ß-dicarbonyls as Versatile Synthons in Synthesis of Heterocycles.

Trifluoromethyl group relishes a privileged position in the realm of medicinal chemistry because its incorporation into organic molecules often enhances the bioactivity by altering pharmacological profile of molecule. Trifluoromethyl-ß-dicarbonyls have emerged as pivotal building blocks in synthetic organic chemistry due to their facile accessibility, stability and remarkable versatility. Owing to presence of nucleophilic and electrophilic sites, they offer multifunctional sites for the reaction. This review covers a meticulous exploration of their multifaceted role, encompassing an in-depth analysis of mechanism, extensive scope, limitations and wide-ranging applications in diverse organic synthesis, covering the literature from the 21st century. This comprehensive review encapsulates the applications of trifluoromethyl-ß-dicarbonyls and their synthetic equivalents as precursors of complex and diverse heterocyclic scaffolds, fused heterocycles and spirocyclic compounds having medicinal and material importance. Their potent synthetic utility in cyclocondensation reactions with binucleophiles, cycloaddition reactions, C-C bond formations, asymmetric multicomponent reactions using classical/solvent-free/catalytic synthesis have been presented. Influence of unsymmetrical trifluoromethyl-ß-diketones on regioselectivity of transformation is also reviewed. This review will benefit the synthetic and pharmaceutical communities to explore trifluoromethyl-ß-dicarbonyls as trifluoromethyl building blocks for fabrication of heterocyclic scaffolds having implementation into drug discovery programs in the imminent future.

A perspective on varied fungal virulence factors causing infection in host plants.

Pathogenic fungi and their spores are ubiquitously present and invade the tissues of higher living plants causing pathogenesis and inevitably death or retarded growth. A group of fungi kills its hosts and consume the dead tissues (necrotrophs), while others feed on living tissue (biotrophs) or combination of two (hemibiotrophs). A number of virulent factors is used by fungal pathogens to inhabit new hosts and cause illness. Fungal pathogens develop specialized structures for complete invasion into plant organs to regulate pathogenic growth. Virulence factors like effectors, mycotoxins, cell wall degrading enzymes and organic acids have varied roles depending on the infection strategy and assist the pathogens to possess control on living tissues of the plants. Infection strategies employed by fungi generally masks the plant defense mechanism, however necrotrophs are best known to harm plant tissues with their poisonous secretion. Interestingly, the effector chemicals released by Biotrophs reduce plant cell growth and regulate plant metabolism in their advantage causing no direct death. All these virulence tools cause huge loss to the agricultural product of pre- harvest crops and post-harvest yields causing low output leading to huge economic losses. This review focusses on comprehensive study of range of virulence factors of the pathogenic fungi responsible for their invasion inside the healthy tissues of plants. The compiled information would influence researchers to design antidote against all virulence factors of fungi relevant to their area of research which could pave way for protection against plant pathogenesis.

Mapping of on-field soil nutrient variabilities as a guiding force for smart farming: a case study from FarmerZone sentinel-1 from three potato agroecological zones of India.

Mapping of soil nutrient parameters using experimental measurements and geostatistical approaches to assist site-specific fertiliser advisories is anticipated to play a significant role in Smart Agriculture. FarmerZone is a cloud service envisioned by the Department of Biotechnology, Government of India, to provide advisories to assist smallholder farmers in India in enhancing their overall farm production. As a part of the project, we evaluated the soil spatial variability of three potato agroecological zones in India and provided soil health cards along with field-specific fertiliser recommendations for potato cultivation to farmers. Specifically, 705 surface samples were collected from three representative potato-growing districts of Indian states (Meerut, UP; Jalandhar, Punjab and Lahaul and Spiti, HP) and analysed for soil parameters such as organic carbon, macronutrients (NPK), micronutrients (Zn, Fe, Mn, and Cu), pH, and EC. The soil parameters were integrated into a geodatabase and subjected to kriging interpolation to create spatial soil maps of the targeted potato agroecological zones through best-fit experimental semivariograms. The spatial distribution showed a deficiency of soil organic carbon in two studied zones and available nitrogen among all studied zones. The available phosphorus and potassium varied among the agroecological zones. The micronutrient levels were largely sufficient in all the zones except at a few specific sites where nutrient advisories are recommended to replenish. The general management strategies were recommended based on the nutrient status in the studied area. This study clearly supports the significance of site-specific soil analytics and interpolated spatial soil mapping over any targeted agroecological zones as a promising strategy to deliver reliable advisories of fertiliser recommendations for smart farming.

An expeditious on-water regioselective synthesis of novel arylidene-hydrazinyl-thiazoles as DNA targeting agents.

A series of twenty novel (E)-arylidene-hydrazinyl-thiazole derivatives has been synthesized employing α-bromo-ß-diketones, thiosemicarbazide, and aromatic/heteroaromatic aldehydes with a simple and facile one-pot multicomponent reaction passageway. This organic transformation proceeds efficiently in aqueous media and demonstrated a large functional group tolerance. The structures and stereochemistry of the regioisomeric product were rigorously characterized using heteronuclear 2D NMR experiments. The binding potential of the synthesized analogs with B-DNA dodecamer d(CGCGAATTCGCG)2 was primarily screened using molecular modeling tools and further, mechanistic investigations (either groove or intercalation) were performed using various spectroscopic techniques such as UV-Visible, Fluorescence, and Circular dichroism. The absorption spectra showed a hyperchromic shift in the absorption maxima of ctDNA with successive addition of thiazole derivatives, implying groove binding mode of interactions, further supported by displacement assay and circular dichroism analysis. Furthermore, steady-state fluorescence analysis revealed the static mode of quenching and moderate bindings between the ligand and DNA biomolecule. The competitive studies showed that the derivatives having a pyridinyl (heteroaromatic) group in their structure, bind with the nucleic acid of calf-thymus (ctDNA) more effectively in the minor groove region as compared with the aromatic substitutions.

Cardiovascular diseases display etiological and seasonal trend in human population: Evidence from seasonal cardiovascular comorbid diseases (SCCD) index.

Seasonal changes in the human cardiovascular system are known to play an important role in the onset of many diseases. Confounding variables include behavioral and environmental factors; failing to address such variables makes measuring the true temporal impact of these diseases difficult. On the other hand, numerous clinical studies imply that only specific groups of people are more seasonal sensitive and that their maladaptation might contribute to various illnesses. As a result, it is critical to evaluate the etiological and seasonal sensitive patterns of cardiovascular diseases (CVD), which impact the majority of the human population. The hypothesis for this study formulated that cardiovascular and associated illnesses had substantial connections with seasonal and etiological variations. Thus in the present study, 4519 systematic screen-eligible studies were analyzed using data mining to uncover 852 disease association relationships between cardiovascular and associated disorders. A disease ontology-based semantic similarity network (DSN) analysis was performed to narrow down the identified CVDs. Further, topological analysis was used to predict the seven CVDs, including myocardial infarction (MI), in three clusters. Following that, Mann-Kendall and Cox-Stuart analyses were used to investigate the seasonal sensitivity and temporal relationship of these seven CVDs. Finally, temporal relationships were confirmed using LOESS and TBATS, as well as seasonal breakdown utilizing autocorrelation and fast Fourier transform results. The study provides indirect evidence of a severe etiological association among the three cardiovascular diseases, including MI, atrial fibrillation, and atherosclerosis, which are winter season sensitive in most of the world population. Hypertension has two seasonal falls and peaks due to its seasonal nature, that is, summer and winter hypertension. While, heart failure was also identified, with minor temporal trends. Hence, all five diseases could be classified as seasonal cardiovascular comorbid diseases (SCCD). Furthermore, these diseases could be studied for potential common risk factors such as biochemical, genetic, and physiological factors.

miRNA dysregulation in traumatic brain injury and epilepsy: a systematic review to identify putative biomarkers for post-traumatic epilepsy.

Traumatic brain injury (TBI) leads to post-traumatic epilepsy (PTE); hence, both TBI and PTE share various similar molecular mechanisms. MicroRNA (miRNA) is a small noncoding RNA that acts as a gene-silencing molecule. Notably, the dysregulation of miRNAs in various neurological diseases, including TBI and epilepsy, has been reported in several studies. However, studies on commonly dysregulated miRNAs and the regulation of shared pathways in both TBI and epilepsy that can identify potential biomarkers of PTE are still lacking. This systematic review covers the peer-review publications of TBI and database studies of epilepsy-dysregulated miRNAs of clinical studies. For TBI, 290 research articles were identified after screening, and 12 provided data for dysregulated miRNAs in humans. The compiled data suggest that 85 and 222 miRNAs are consecutively dysregulated in TBI and epilepsy. In both, 10 miRNAs were found to be commonly dysregulated, implying that they are potentially dysregulated miRNAs for PTE. Furthermore, the targets and involvement of each putative miRNA in different pathways were identified and evaluated. Additionally, clusters of predicted miRNAs were analyzed. Each miRNA's regulatory role was linked with apoptosis, inflammation, and cell cycle regulation pathways. Hence, these findings provide insight for future diagnostic biomarkers.

Bulldog Scalp Syndrome.

Bulldog scalp syndrome or cutis verticis gyrata (CVG) is a rare cutaneous disorder with an incidence of just 0.026 to 1 per 100,000 population and cosmetic problems should not be ignored as they can affect the quality of life of patients in social and psychological aspects. In CVG the scalp thickens to form folds resembling sulci and gyri just as the skin fold of bulldog. It is a clinical diagnosis with various etiologies. It is classified as primary essential or nonessential and secondary CVG. It can manifest with symptoms ranging from mild to severe intensity. Cosmetic problems are the major concern that can affect patients' social and psychological health. If the folds are heavy, they can cause mass symptoms. Thus, surgery remains the definitive treatment option for improving the cosmetic appearance. Both our cases have different etiologies, however, were managed surgically with removal of skin folds (gyrae) and scoring of aponeuroses of the scalp followed by stretching of the scalp and closure to improve appearance. The surgical team as well as patients were satisfied with the appearance of the scalp after healing. CVG though a rare disease with various etiologies is a benign condition with good prognosis with no reports of malignant transformation so far.

Visible-Light-Prompted Synthesis and Binding Studies of 5,6-Dihydroimidazo[2,1-b]thiazoles with BSA and DNA Using Biophysical and Computational Methods.

Fused heterocyclic systems containing a bridgehead nitrogen atom have emerged as imperative pharmacophores in the design and development of new drugs. Among these heterocyclic moieties, the imidazothiazole scaffold has long been used in medicinal chemistry for the treatment of various diseases. In this study, we have established a simplistic and environmentally safe regioselective protocol for the synthesis of 5,6-dihydroimidazo[2,1-b]thiazole derivatives from easily available reactants. The reaction proceeds through in situ formation of the α-bromodiketones ensuing trap with imidazolidine-2-thione to provide these versatile bicyclic heterocycles in excellent yields. The synthesized compounds were screened through the molecular docking approach for the most stable complex formation with bovine serum albumin (BSA) and calf thymus deoxyribonucleic acid (ctDNA). The selected compound was further studied using ex vivo binding studies, which revealed moderate interactions with BSA and ctDNA. The binding studies were performed using biophysical approaches including UV-visible spectroscopy, steady-state fluorescence, circular dichroism (CD), and viscosity parameters.

Visible-light-mediated regioselective synthesis of novel thiazolo[3,2-b][1,2,4]triazoles: advantageous synthetic application of aqueous conditions.

From a green chemistry perspective, sustainable irradiation as the power source and water as the solvent have certainly grabbed the attention of chemists in recent times because their use helps reduce the hazardous ecological footprints of organic synthesis. In the present work, we have established an efficient, straightforward and green protocol for the regioselective synthesis of novel functionalized thiazolo[3,2-b][1,2,4]triazoles. The visible-light-mediated catalyst-free reaction of diversely substituted α-bromodiketones, generated in situ by the reaction of NBS and 1,3-diketones, with 3-mercapto[1,2,4]triazoles under aqueous conditions afforded thiazolo[3,2-b][1,2,4]triazole derivatives in excellent yields. The structure of the regioisomer has been confirmed explicitly by heteronuclear 2D-NMR [(1H-13C) HMBC, (1H-13C) HMQC] spectroscopic and X-ray crystallographic studies. Radical initiating and trapping experiments supported the free radical mechanism for the cyclization.

Ameliorative effect of curcumin on altered expression of CACNA1A and GABRD in the pathogenesis of FeCl3-induced epilepsy.

The pivotal role played by ion-channel dysregulations in the pathogenesis of epilepsy has always garnered much attention. Since mutation of ion-channel proteins CACNA1A and GABRD have been associated with epilepsy, it is important to determine the post-traumatic epilepsy-associated changes in expression levels of these ion channel proteins. Additionally, curcumin is already known for its antiepileptic and neuroprotective potential in FeCl3-induced model of post-traumatic epilepsy. Thus, we investigated FeCl3-induced epilepsy mediated differential expression of CACNA1A and GABRD in the cortical region of the rat brain. Furthermore, we investigated the effect of curcumin on the expression of both proteins. For this, epilepsy was induced by intracortical FeCl3 injection (5 µl of 100 mM). Additionally, curcumin (conc. 1000 ppm; 75 mg/kg of b.wt.; for 14 and 28 days) was administered, mixed with normal food pellets. Results obtained from EEG-MUA and Morris water maze assay demonstrate the progression of epilepsy after FeCl3 injection. Additionally, western blotting and histological studies show the downregulation of CACNA1A and GABRD during epileptogenesis. It was observed that epilepsy-associated decline in learning and memory of animals might be linked with the dysregulation of both proteins. Results also demonstrated that curcumin administration ameliorated epilepsy-associated change in expression of both CACNA1A and GABRD proteins. In conclusion, the neuroprotective effect of curcumin against iron-induced epilepsy might be accompanied by the alleviated upregulation of these channel proteins.

Evaluation and Comparison of the Effect of Different Border Molding Materials on Complete Denture Retention: An in vivo Study.

AIM: Different border molding materials have different qualities which help in recording fine details of tissues. The present study was conducted to evaluate and compare the effect of different border molding materials on complete denture retention. MATERIALS AND METHODS: The present study was conducted on 10 completely edentulous patients in the age group of 50 to 70 years. On each patient, three different border moldings were completed. In group I, border molding was done with green stick impression compound. In group II, border molding was done with putty consistency addition silicone. In group III, border molding and final impression were done by polyether impression material in a single step. Permanent denture bases were fabricated with wire loop at the center. Retention was assessed in all three groups using a digital force gauge. RESULTS: Upon data compilation and preparation of spread sheets for concerned groups, it was subjected to statistical analysis using Statistical Package for the Social Sciences (SPSS) software version 21.0 for Windows. Mean age ± standard deviation (SD) was 57.40 ± 8.46 in group I, 57.40 ± 8.46 in group II, and 57.40 ± 8.46 in group III. The difference was nonsignificant (p > 0.05). The overall mean value for the group I was 4.59 ± 0.81. For group II, it was 4.7 ± 0.81. For group III, it was 6.72 ± 0.81. The difference was significant (p < 0.05). CONCLUSION: Green stick compound with light body final wash showed the lowest mean values of complete denture retention. Dentures made using polyether final impression material showed the highest mean values of complete denture retention followed by putty rubber base border molding with light body final wash. CLINICAL SIGNIFICANCE: In this study, polyether showed the highest mean retentive value compared with other tested materials; therefore, it could possibly provide some future innovative means in achieving optimal denture retention.

In vitro Assessment of Clasps of Cobalt-Chromium and Nickel-titanium Alloys in Removable Prosthesis.

BACKGROUND: It has been since a long time that the use of base-metal alloys has significantly increased in the area of prosthetic science. One of the factors contributing for the increasing use of base-metal alloys is the increasing and high cost factor of noble metals. Although numerous materials have been tried since the recent past, Cobalt-Chromium (CoCr) alloys still form the most commonly used ones because of the numerous advantages they offer. Titanium alloys are also significantly being used in this field because of their high resistance strength and high corrosion resistance. Therefore, we aimed to evaluate the flexure strength and fatigue resistance of clasps made up of CoCr alloys and Nickel-titanium (NiTi) alloys. MATERIALS AND METHODS: We evaluated the retentive forces of CoCr and NiTi clasps two different sizes engaging retentive undercuts of different depths (0.25 and 0.50 mm). Mandibluar second premolar was prepared to frame the prosthesis for missing mandibular first and second molar. A total of 50 clasps were included in the study out of which 30 were NiTi clasps and 30 CoCr clasps. We evaluated the loading of the force at the rate of half Newton(N)/second at the central part of the specimen until fracturing of the specimen occurred and finally measurement of the modulus of elasticity was also done. Statistical analysis was carried out; unpaired "t" test was used for evaluating the level of significance. RESULTS: The mean load needed for CoCr clasps was 0.7450 and for NiTi clasp was 0.6140 Kgf for producing a deflection of 0.25 mm. As far as flexibility is concerned, more value was seen in NiTi group than CoCr group. For deflecting the clasp up to 0.50 mm, the mean load needed for CoCr clasps was 1.4102 and for NiTi clasp was 0.8260 Kgf. The results were statistically significant. While measuring the flexibility, more value (p < 0.05) was seen in NiTi group than in CoCr group. NiTi alloy clasps had mean flexural strength of 1640 MPa and modulus of elasticity of 32 GPa. CONCLUSION: For producing deflection of 0.25 and 0.50 mm, the mean loading force was higher for NiTi alloys. Although being increasingly used these days, NiTi alloys have limited use as compared with CoCr alloys due to high cost of titanium and certain other limitations.

Anomaly detection technique for securing microgrid against false data attacks.

The development of microgrid automation depends on information and communication technologies, which are vulnerable to cyber-attacks. Recent advancements in MGs enhance power systems' efficacy and reliability, but cybersecurity remains a significant concern, especially with false data injection attacks (FDIAs) posing serious threats. FDIAs can compromise measurement devices and tamper with State Estimation (SE), risking the seamless operation of MGs. To address this, this paper proposes an efficient Iterative Free Detection of False Data (IFDFD) scheme for detecting FDIAs in microgrid state estimation. The IFDFD scheme uses complex Micro Phasor Measurement Unit (µPMU) measurements and computes nodal power injections to detect FDIAs. Furthermore, the proposed scheme integrates an S-Estimator to eliminate noise errors caused by environmental factors and the component lifespan, making IFDFD robust against sophisticated attackers. The proposed IFDFD scheme has been tested and validated on the modified IEEE 14 bus test system, integrating Distributed Generations (DGs). False data was injected into the measurements to test the scheme's effectiveness. The efficacy of proposed IFDFD scheme has been validated by comparing it to existing method of FDIAs. The obtained result clearly validates the efficacy of the proposed IFDFD scheme.

Serendipitous N,S-difunctionalization of triazoles with trifluoromethyl-ß-diketones: access to regioisomeric 1-trifluoroacetyl-3-aryl-5-(2-oxo-2-arylethylthio)-1,2,4-triazoles as DNA-groove binders.

In the present research work, a serendipitous regioselective synthesis of DNA targeting agents, 1-trifluoroacetyl-3-aryl-5-(2-oxo-2-arylethylthio)-1,2,4-triazoles, has been achieved through the one-pot cascade reaction of 3-mercapto[1,2,4]triazoles with trifluoromethyl-ß-diktetones in presence of NBS instead of the cyclized thiazolo[3,2-b][1,2,4]triazole. The present protocol offered a unique approach for functionalizing both N-acylation and S-alkylation in a concerted fashion. The structures of the regioisomeric products were thoroughly characterized by heteronuclear 2D NMR experiments. Facile scalability and excellent atom economy through easily available starting reactants are the notable features of the present sustainable protocol. Targeting tumor cell DNA with minor groove-binding small molecules has proven highly effective in the recent past, drawing significant attention for combating tumor-related afflictions. In this context, the synthesized analogs were primarily screened for their ability to bind with the DNA duplex d(CGCGAATTCGCG)2 using molecular modeling tools. Additionally, the most promising compound 14m was deployed as a probe for DNA sensing and interaction mechanisms with calf thymus (ct)DNA through various spectral techniques at a physiologic temperature of 37 °C. It has been found that the compound demonstrated a strong binding affinity (Kb = 1 × 105 M-1) with double-helical DNA, particularly within the minor groove, resulting in the formation of a stable complex through static quenching (Kq = 5.86 ± 0.11 × 1012 M-1 s-1). The fluorescent displacement assay confirmed that the quencher binds to the minor groove of ctDNA, further supported by circular dichroism and viscosity studies.

Identification, management and pecuniary impact of major carbon footprint contributor in potato production system of north-west India.

Assessment of carbon footprint of a crop is an important component of sustainable crop production, as it helps in framing effectual and viable crop management strategies to minimize ecosystem tampering. Thus, in present investigation carbon footprint of potato production system in different agro-climatic zones viz. undulating plain zone, central plain zone and western plain zone of North-west India were estimated, and compared with the recommended practices of these zones. The carbon footprint was higher in undulating plain zone followed by central plain zone and western plain zone with values being 343, 296 and 220 kg CO2 eq./t tuber yield (TY), sequentially, whereas same were 198 kg CO2 eq./t tuber yield (TY) in case of recommended practices. The social cost of carbon (SCC), that represents economic damage from the CO2 emissions, was also estimated. The integrated net economic balance (net return from yield - SCC) was also better in case of recommended practices. The major sources of emission from potato production system were fertilizer (NPK) application (42 %), irrigation (20 %), seed (14 %), fertilizer production (13 %) and energy use (excluding Irrigation) (5 %). Top most in the list of carbon footprint contributors was fertilizer application which was due to imbalanced application of these, and for getting the clear picture of this imbalance as well as its impact, a new and exclusive index- Relative Imbalance Fertilization Index (RIFIcf) was developed and tested. Carbon footprints were also related to tuber yield and an empirical model was developed that can be used to predict tuber yield on the basis of carbon footprint of potato production system. An increase in tuber yield with increasing carbon footprint was noticed, which became somewhat static at higher emissions. The findings of this investigation provide a clear picture of quantitative GHG emissions due to imbalanced inputs that can be plummeted to some extent if already existing recommendations are followed.

Enhancing milk quality assessment with watermelon (Citrullus lanatus) urease immobilized on VS2-chitosan nanocomposite beads using response surface methodology.

An eco-friendly hydrothermal method synthesized VS2 nanosheets. Several spectroscopic and microscopic approaches (TEM) were used to characterize the produced VS2 nanosheet microstructure. VS2, Chitosan, and nanocomposite were used to immobilize watermelon (Citrullus lanatus) urease. Optimization using the Response Surface Methodology and the Box-Behnken design yielded immobilization efficiencies of 65.23 %, 72.52 %, and 87.68 % for chitosan, VS2, and nanocomposite, respectively. The analysis of variance confirmed the mathematical model's validity, enabling additional research. AFM, SEM, FTIR, Fluorescence microscopy, and Cary Eclipse Fluorescence Spectrometer showed urease conjugation to the matrix. During and after immobilization, FTIR spectra showed a dynamic connectivity of chemical processes and bonding. The nanocomposite outperformed VS2 and chitosan in pH and temperature. Chitosan and VS2-immobilized urease were more thermally stable than soluble urease, but the nanocomposite-urease system was even more resilient. The nanocomposite retained 60 % of its residual activity after three months of storage. It retains 91.8 % of its initial activity after 12 reuse cycles. Nanocomposite-immobilized urease measured milk urea at 23.62 mg/dl. This result was compared favorably to the gold standard p-dimethylaminobenzaldehyde spectrophotometric result of 20 mg/dl. The linear range is 5 to 70 mg/dl, with a LOD of 1.07 (±0.05) mg/dl and SD of less than 5 %. The nanocomposite's ksel coefficient for interferents was exceptionally low (ksel < 0.07), indicating urea detection sensitivity. Watermelon urease is suitable for dairy sector applications due to its availability, immobilization on nanocomposite, and reuse.

Watermelon Derived Urease Immobilized Gold Nanoparticles-Graphene Oxide Transducer for Direct Detection of Urea in Milk Samples.

Urea contamination in milk poses significant health risks, including kidney failure, urinary tract obstruction, fluid loss, shock, and gastrointestinal bleeding. This highlights the need for sensitive, rapid, and reliable methods to detect traces amount of urea in milk. In this study, we designed an electrochemical transducer for urea detection by utilizing purified watermelon urease (Urs), gold nanoparticles (AuNPs), and graphene oxide (GO). The nanomaterials and biosensor probe were characterized using UV-vis spectroscopy, XPS, TEM, XRD, FTIR, AFM, CV, EIS, and DPV. The engineered probe (GCE/AuNPs/GO/Urs) demonstrated a broad linear detection range of 5 to 90 mg/dL and a low limit of detection (LOD) of 0.037 (±0.012) mg/dL (RSD < 3.7%). The biosensor was tested for potential interferents that may be present in adulterated milk and an exceptionally low coefficient of selectivity (ksel <0.1) was obtained. Evaluation of milk samples from a local dairy farm showed good recovery rates from 93.13% to. 98.79% (RSD < 4.28%, n = 3), indicating reliable detection capabilities. Stability tests confirmed the sensor's reproducibility and consistent performance. Additionally, a comparison study of the system was carried out using the purified watermelon urease and the commercially available urease. Herein, the results obtained using the sensor probe was finally validated with the gold standard method.

In Silico Structural and Functional Insight into the Binding Interactions of the Modeled Structure of Watermelon Urease with Urea.

Urease (EC 3.5.1.5) is an amidohydrolase. This nickel-dependent metalloenzyme converts urea into NH3 and CO2. Despite their vital role in plants, the structure and function of watermelon (Citrullus lanatus) urease are unknown. We used third- and fourth-generation gene prediction algorithms to annotate the C. lanatus urease sequence in this investigation. The solved urease structure from Canavalia ensiformis (PDB ID: 4GY7) was utilized as a template model to identify the target 3-D model structure of the unknown C. lanatus urease for the first time. Cluretox, the C. lanatus urease intrinsic disordered area identical to Jaburetox, was also found. The C. lanatus urease structure was docked with urea to study atom interaction, amino acid interactions, and binding analyses in the urease-urea complex at 3.5 Å. This study found that amino acids His517, Gly548, Asp631, Ala634, Thr569, His543, Met635, His407, His490, and Ala438 of C. lanatus urease bind urea. To study the molecular basis and mode of action of C. lanatus urease, molecular dynamics simulation was performed and RMSD, RMSF, Rg, SAS, and H-bond analyses were done. The calculated binding free energy (ΔG) for the urea-urease complex at 100 ns using the MM/PBSA method is -7.61 kJ/mol. Understanding its catalytic principles helps scientists construct more efficient enzymes, tailor fertilization to boost agricultural output, and create sustainable waste management solutions.

Design, Synthesis, and In Vitro Cytotoxic Studies of Some Novel Arylidene-Hydrazinyl-Thiazoles as Anticancer and Apoptosis-Inducing Agents.

Cancer, defined by uncontrolled cell growth, poses a significant global health challenge, necessitating the development of new anticancer drugs crucial to address drug resistance, side effects, and the need for combination therapies. The study presents the design, synthesis, and anticancer screening of a series of novel functionalized arylidene-hydrazinyl-thiazoles against various human cancer cell lines. The environmentally benign synthetic protocol involves the visible-light prompted, NBS-mediated domino reaction of thiosemicarbazide, heteroaryl aldehydes, and unsymmetrical 1,3-diketones. The regioselective organic transformation delivered the single regioisomeric product, characterized unambiguously through detailed 2D NMR spectral studies. In vitro cytotoxic studies revealed that the synthesized derivatives exhibited excellent cytotoxic potential against BxPC-3, MOLT-4, and MCF-7 cancer cell lines. Notably, compounds 4m, 4n, and 4r showed significant cytotoxicity, reducing cell survival to 23.85-26.45% for BxPC-3, 30.08-33.30% for MOLT-4, and 44.40-47.63% for MCF-7 at a concentration of 10 µM. These compounds profoundly induced apoptosis, evidenced by increased caspase-3/7 activity, loss of mitochondrial membrane potential, and modulation of Bcl2 and Bax gene expression. Additionally, these compounds caused robust cell cycle arrest at the G2/M phase by inhibiting tubulin polymerization, indicating their multifaceted impact on cancer cells.