Synthesis, DFT, Molecular Docking, and Antimicrobial Studies of New Indole-Thiosemicarbazone Ligand and Their Complexes with Fe(III), Co(II), Ni(II), Cu(II).

Indole-3-carbaldehyde based novel ligand (E)-2-((1-benzyl-1H-indol-3-yl)methylene)-N-methylhydrazine-1-carbothioamide (MBIHC) and their complexes [(MBIHC)2FeCl2]Cl(C1), [(MBIHC-)2Co] (C2), [(MBIHC-)2Ni] (C3), and [(MBIHC-)2Cu] (C4) have been synthesized. All compounds have been characterized by spectroanalytical techniques. The structure of MBIHC was confirmed by single-crystal X-ray data. The geometry of complexes was determined by spectroscopic and computational studies. In the case of iron complex, ligand MBIHC coordinated to the metal ion in bidentate mode (N and S) while in the case of cobalt, nickel, and copper complexes ligand act as a tridentate ligand (N, S and C). In vitro,antifungal and antibacterial studies of ligand and metal complexes were assayed against C. albicans, C. glabrata, E. coli, and K. pneumoniae pathogens. In antifungal activity, complex C1 exhibited a greater inhibition zone than the other compounds for the both examined fungi C. albicans (24±0.32 mm) and C. glabrata (20±0.16 mm).. However, the antifungal activities of complex C2has shown better activity against both E. coli (25±0.24 mm) and K. pneumoniae (16±0.80 mm) pathogens than the other examined compound.. Complex C2 has found even better than the benchmark drug Ampiciline in case of E. coli. Further, the DFT calculations and molecular docking studies also validate the experimental bioactivity results of examined compounds.

Comparative Analysis of Clinicopathologic Characteristics and Outcomes of Urothelial Bladder Cancer Between Young and Older Adults-Experience from a Tertiary Care Center.

The evidence on bladder cancer in the young population remains fragmented due to lack of literature and conflicting results from the existing studies. We aim to elucidate such conflicting data and define the clinicopathologic characteristics, management trends, and outcomes of urothelial bladder carcinoma in young adults as compared to their older counterparts. This was a retrospective, single-center study involving patients with primary urothelial bladder cancer who underwent treatment at our center from March 2017 to March 2022. For analysis, patients were stratified into three subgroups based on age: group A, 18-40 years; group B, > 40 years; and group C, > 60 years. Group A with younger patients was compared with groups B and C. A total of 471 eligible patients (422 males and 49 females) were included in the study with a median age of 44 years. Group A had significantly lower recurrence and progression rates as compared to group B (31% vs 57.1%, p = 0.002 and 9.5% vs 19.2%, p = 0.04, respectively). Group A had significantly more recurrence-free survival (RFS) than group B (5-year-RFS = 68.03% vs 32.58%, p = 0.01). Similarly, group A also had lower recurrence (31% vs 62.6%, p < 0.001) and progression (9.5% vs 28.6%, p = 0.015) rates as compared to group C as well as better RFS (5-year-RFS = 68.03% vs 19.00%, p = 0.04) and progression-free survival (5-year-PFS = 83.1% vs 62.8%, p = 0.03) in comparison to group C. Age and tumor grade were found to be independent predictors of recurrence-free and progression-free survival. We concluded that high-grade disease is more common than low-grade disease both in younger and older patients. Younger patients fare better in terms of recurrence and progression when compared to their older counterparts.

Phyllodes Tumors of the Breast-Experience in a Tertiary Care Center.

Phyllodes tumors (PTs) are rare neoplasms of the breast that are a challenge in clinical practice. Though mostly benign, they are notorious for local recurrence, requiring adjuvant treatments. This study was planned to report the clinicopathological features and outcomes of patients with PT treated at our center. Details of all patients who underwent surgery for PT in the last 6 years (December 2017-December 2023) were obtained from our prospectively maintained database. The demographic, clinical, radiological, pathological, and follow-up details were recorded and analyzed. Statistical analyses were carried out with Jamovi version 2.3.18. Out of 61 suspected PTs by triple assessment, 9 were excluded due to a non-phyllodes diagnosis on histopathology. We included 52 women with a mean age of 38.2 ± 11.0 years, most of whom were premenopausal (57.7%). BI-RADS 4 was the most common finding on radiological assessment (65.4%). Core needle biopsy (CNB) was the most frequently employed modality for histological diagnosis preoperatively (65.4% of cases). Wide local excisions (WLE) and mastectomies were done in 63.5% and 36.5% of patients, respectively. Benign, borderline, and malignant phyllodes constituted 67.3%, 15.4%, and 17.3% of tumors, respectively. Patients undergoing breast conservation surgery (BCS) had a significantly smaller mean tumor diameter than those who underwent a mastectomy (p < 0.001). Overall, the margin positivity rate was 34.6%. Patients undergoing mastectomy developed more local recurrence compared to WLE, although the difference was not significant (p = 0.400). The outcome following surgical excisions of large PTs in terms of margin positivity and local recurrence is the same, irrespective of whether BCS or mastectomy is done. A negative pathological margin width of > 1 mm appears acceptable. Malignant phyllodes with positive margins are associated with a higher rate of recurrence but positive margins in patients with other subtypes may not translate into recurrence, at least in the short term.

A review on the use of composites of a natural protein, silk fibroin with Mxene/carbonaceous materials in biomedical science.

Silk fibroin (SF), a natural biodegradable and biocompatible protein, has garnered significant attention in biomedical applications due to its impressive properties, including excellent biocompatibility, biodegradability, and mechanical resilience. Nevertheless, its broader usage faces obstacles by its insufficient mechanical strength and electrical conductivity. In order to address these constraints, recent studies have concentrated on combining SF with cutting-edge nanomaterials like MXene and carbon-based materials. This review comprehensively examines the applications and potential of silk fibroin-MXene/carbon-based nanocomposites in biomedical fields. The unique properties of SF, MXene, and carbon-based materials are explored, emphasizing how their combination enhances mechanical strength, conductivity, and biocompatibility. These composites show substantial enhancements in performance for several biomedical applications by utilising the excellent conductivity and mechanical capabilities of MXene and carbonaceous elements. The innovative potential of these nanocomposites is highlighted by critically discussing key applications such as tissue engineering, drug delivery, and biosensing. In addition, the work discusses the latest research progress, difficulties, and future prospects in the sector, providing valuable insights into possible breakthroughs and uses. This review seeks to comprehensively analyse the existing information on silk fibroin-MXene/carbon based nanocomposites in healthcare.

Two new species of Dulcicalothrix (Nostocales, Cyanobacteria) from India and erection of Brunnivagina gen. nov., with observations on the problem of using multiple ribosomal operons in cyanobacterial taxonomy.

Two new species of Dulcicalothrix, D. adhikaryi sp. nov. and D. iyengarii sp. nov., were discovered in India and are characterized and described in accordance with the rules of the International Code of Nomenclature for algae, fungi, and plants (ICN). As a result of phylogenetic analysis, Calothrix elsteri is reassigned to Brunnivagina gen. nov. During comparison with all Dulcicalothrix for which sequence data were available, we observed that the genus has six ribosomal operons in three orthologous types. Each of the three orthologs could be identified based upon indels occurring in the D1-D1' helix sequence in the ITS rRNA region between the 16S and 23S rRNA genes, and in these three types, there were operons containing ITS rRNA regions with and without tRNA genes. Examination of complete genomes in Dulcicalothrix revealed that, at least in the three strains for which complete genomes are available, there are five ribosomal operons, two with tRNA genes and three with no tRNA genes in the ITS rRNA region. Internal transcribed spacer rRNA regions have been consistently used to differentiate species, both on the basis of secondary structure and percent dissimilarity. Our findings call into question the use of ITS rRNA regions to differentiate species in the absence of efforts to obtain multiple operons of the ITS rRNA region through cloning or targeted PCR amplicons. The ITS rRNA region data for Dulcicalothrix is woefully incomplete, but we provide herein a means for dealing with incomplete data using the polyphasic approach to analyze diverse molecular character sets. Caution is urged in using ITS rRNA data, but a way forward through the complexity is also proposed.

An updated view of bacterial endophytes as antimicrobial agents against plant and human pathogens.

Bacterial endophytes are a crucial component of the phytomicrobiome, playing an essential role in agriculture and industries. Endophytes are a rich source of bioactive compounds, serving as natural antibiotics that can be effective in combating antibiotic resistance in pathogens. These bacteria interact with host plants through various processes such as quorum sensing, chemotaxis, antibiosis, and enzymatic activity. The current paper focuses on how plants benefit extensively from endophytic bacteria and their symbiotic relationship in which the microbes enhance plant growth, nitrogen fixation, increase nutrient uptake, improve defense mechanisms, and act as antimicrobial agents against pathogens. Moreover, it highlights some of the bioactive compounds produced by endophytes.

Computational Insights for interactions between NsP2 and NsP3 of CHIKV and Hormones through DFT computations and Molecular Dynamics Simulations.

The non-structural protein (nsP2 & nsP3) of the CHIKV is responsible for the transmission of viral infection. The main role of nsp is involved in the transcription process at an early stage of the infection. In this work, authors have studied the impact of nsP2 and nsP3 of CHIKV on hormones present in the human body using a computational approach. The ten hormones of chemical properties such as 4-Androsterone-2,17-dione, aldosterone, androsterone, corticosterone, cortisol, cortisone, estradiol, estrone, progesterone and testosterone were taken as a potency. From the molecular docking, the binding energy of the complexes is estimated, and cortisone was found to be the highest negative binding energy (-6.57 kcal/mol) with the nsP2 protease and corticosterone with the nsP3 protease (-6.47 kcal/mol). This is based on the interactions between hormones and NsP2/NsP3, which are types of noncovalent intermolecular interactions categorized into three types: electrostatic interactions, van der Waals interactions, and hydrogen-bonding. To validate the docking results, molecular dynamics simulations and MM-GBSA methods were performed. The change in enthalpy, entropy, and free energy were calculated using MM-GBSA methods. The nsP2 and nsP3 protease of CHIKV interact strongly with the cortisone and corticosterone with free energy changes of -20.55 & -36.08 kcal/mol, respectively.

Plant growth promoting bacteria (PGPB)-induced plant adaptations to stresses: an updated review.

Plants and bacteria are co-evolving and interact with one another in a continuous process. This interaction enables the plant to assimilate the nutrients and acquire protection with the help of beneficial bacteria known as plant growth-promoting bacteria (PGPB). These beneficial bacteria naturally produce bioactive compounds that can assist plants' stress tolerance. Moreover, they employ various direct and indirect processes to induce plant growth and protect plants against pathogens. The direct mechanisms involve phytohormone production, phosphate solubilization, zinc solubilization, potassium solubilization, ammonia production, and nitrogen fixation while, the production of siderophores, lytic enzymes, hydrogen cyanide, and antibiotics are included under indirect mechanisms. This property can be exploited to prepare bioformulants for biofertilizers, biopesticides, and biofungicides, which are convenient alternatives for chemical-based products to achieve sustainable agricultural practices. However, the application and importance of PGPB in sustainable agriculture are still debatable despite its immense diversity and plant growth-supporting activities. Moreover, the performance of PGPB varies greatly and is dictated by the environmental factors affecting plant growth and development. This review emphasizes the role of PGPB in plant growth-promoting activities (stress tolerance, production of bioactive compounds and phytohormones) and summarises new formulations and opportunities.

Sentinel lymph node biopsy in early breast carcinoma using fluorescein sodium and methylene blue dye: A validation study.

The availability of radioisotopes for sentinel lymph node biopsy (SLNB) in breast carcinoma is limited in low- and middle-income countries and thus the need for other reliable tracers exists. We aimed to validate the effectiveness of fluorescein sodium (FS) together with methylene blue dye (MBD) for patients with node-negative early breast carcinoma in a prospective cross-sectional study. Patients underwent SLNB using FS and MBD followed by axillary dissection to validate results. Sentinel lymph node (SLN) identification rate and false negative rate were assessed for all three tracers/combinations (MBD, FS, and MBD + FS). We concluded that SLNB using a combination of FS and MBD has an acceptable rate of SLN identification but the addition of FS provided no additional benefit.

Digital PCR assay for the specific detection and estimation of Salmonella contamination levels in poultry rinse.

Strains of Salmonella are a frequent cause of foodborne illness and are known to contaminate poultry products. Most Salmonella testing methods can qualitatively detect Salmonella and cannot quantify or estimate the Salmonella load in samples. Therefore, the aim of this study was to standardize and validate a partitioned-based digital PCR (dPCR) assay for the detection and estimation of Salmonella contamination levels in poultry rinses. Pure culture Salmonella strains were cultured, enumerated, cold-stressed for 48 h, and used to inoculate whole carcass chicken rinse (WCCR) at 1-4 log CFU/30 mL and enriched at 37 °C for 5 h. Undiluted DNA samples with primer and probes targeting the Salmonella-specific invA gene were used for the dPCR assay. The dPCR assay was highly specific, with a limit of detection of 0.001 ng/µL and a limit of quantification of 0.01 ng/µL. The dPCR assay further showed no PCR reaction inhibition up to 5 µg of crude DNA extract. The assays accurately detected all cold-stressed Salmonella in inoculated WCCR samples following a 5-h enrichment. Most importantly, when converted to log, the dPCR copies/µL values accurately estimated the inoculated Salmonella levels. The dPCR assay standardized in this study is a robust method for the detection and estimation of Salmonella concentration in contaminated food samples. This approach can allow same-day decision-making for poultry processors attempting to maintain limits and controls on Salmonella contamination.

In vitro larvicidal efficacy of Lantana camara essential oil and its nanoemulsion and enzyme inhibition kinetics against Anopheles culicifacies.

Mosquitoes are important vectors for the transmission of several infectious diseases that lead to huge morbidity and mortality. The exhaustive use of synthetic insecticides has led to widespread resistance and environmental pollution. Using essential oils and nano-emulsions as novel insecticides is a promising alternative approach for controlling vector borne diseases. In the current study, Lantana camara EO and NE were evaluated for their larvicidal and pupicidal activities against Anopheles culicifacies. The inhibitory effect of EO and NE on AChE, NSE (α/ß), and GST was also evaluated and compared. GC-MS analysis of oil displayed 61 major peaks. The stable nano-emulsion with an observed hydrodynamic diameter of 147.62 nm was formed using the o/w method. The nano-emulsion exhibited good larvicidal (LC50 50.35 ppm and LC90 222.84 ppm) and pupicidal (LC50 54.82 ppm and LC90 174.58 ppm) activities. Biochemical evaluations revealed that LCEO and LCNE inhibited AChE, NSE (α/ß), and GST, displaying LCNE to be a potent binder to AChE and NSE enzyme, whereas LCEO showed higher binding potency towards GST. The nano-emulsion provides us with novel opportunities to target different mosquito enzymes with improved insecticidal efficacy. Due to its natural origin, it can be further developed as a safer and more potent larvicide/insecticide capable of combating emerging insecticide resistance.

An updated review on 1,2,3-/1,2,4-triazoles: synthesis and diverse range of biological potential.

The synthesis of triazoles has attracted a lot of interest in the field of organic chemistry because of its versatile chemical characteristics and possible biological uses. This review offers an extensive overview of the different pathways used in the production of triazoles. A detailed analysis of recent research indicates that triazole compounds have a potential range of pharmacological activities, including the ability to inhibit enzymes, and have antibacterial, anticancer, and antifungal activities. The integration of computational and experimental methods provides a thorough understanding of the structure-activity connection, promoting sensible drug design and optimization. By including triazoles as essential components in drug discovery, researchers can further explore and innovate in the synthesis, biological assessment, and computational studies of triazoles as drugs, exploring the potential therapeutic significance of triazoles.

Pyrazoline Spiro-oxindole tethered 1,2,3-triazole hybrids: Design, synthesis, antimicrobial efficacy and molecular modelling studies.

Inspired from the important applications of spirocyclic compounds in medicinal chemistry, a new series of pyrazoline Spiro-oxindole tethered 1,2,3-triazole hybrids was reported via Cu(I)-catalyzed click reaction from isatin-pyrazoline linked terminal alkynes with in situ derived benzyl azides. Antimicrobial evaluation data showed that all hybrids exhibited promising efficacy towards the tested microbial strains. Antimicrobial screening as well as docking studies suggested that hybrid 6a was found to be most potent towards Aspergillus niger (MIC = 0.0122 µmol/mL) and Escherichia coli (MIC = 0.0061 µmol/mL). Molecular docking studies of 6a within the binding pockets of antibacterial and antifungal targets revealed good interactions with the binding energies of - 144.544 kcal/mol and - 154.364 kcal/mol against 1KZN (E. coli) and 3D3Z (A. niger), respectively. Further, MD simulations were performed to study the stability of the complexes formed at 300 K. Based on the RMSD trajectories, it is evident that 3D3Z-6a complex exhibits minimal deviation, whereas the 1KZN-6a complex displayed little more deviation compared to the protein but, both are in acceptable range. Moreover, 3D3Z-6a and 1KZN-6a showed maximum number of hydrogen bonds at 50 ns and 70 ns, respectively, thereby complementing the stability of these complexes.

Flanking Effect on the Structure and Stability of Human Telomeric G-Quadruplex in Varying Salt Concentrations.

The stability of the human telomere G-quadruplex (G4) is directly linked to cancer disease. The human telomere is mostly associated with the flanking nucleobases, which can affect the stability of G4. Hence, in this study, the effect of the flanking nucleobases in the context of their chemical nature, number, and position on the structure and stability of G4 has been investigated in varying concentrations of KCl mimicking the normal and cancer KCl microenvironments. The addition of flanking nucleobases does not alter the G4 topology. However, the presence of merely a single flanking nucleobase destabilizes the telomeric G4. This destabilizing effect is more prominent for thymine than adenine flanking nucleobase, probably due to the formation of the intermolecular G4 topology by thymine. Interestingly, the change in the stability of the telomeric G4 in the presence of thymine flanking nucleobase is sensitive to the concentration of KCl relevant to the normal and cancerous microenvironments, in contrast to adenine. Flanking nucleobases have a greater impact at the 5' end compared to the 3' end, particularly noticeable in KCl concentrations resembling the normal microenvironment rather than the cancerous one. These findings indicate that the effect of the flanking nucleobases on telomeric G4 is different in the KCl salt relevant to normal and cancerous microenvironments. This study may be helpful in attaining molecular-level insight into the role of G4 in telomeric length regulation under normal and cancerous KCl salt conditions.

Investigating the Potential of 2-Ethylbutyl-(Phenoxy)phosphoryl-D-Alaninate Against RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2.

There was an emergency call globally when COVID-19 was detected in December 2019. The SARS-CoV-2 virus, a modified virus, is what causes this contagious disease. Although research is being conducted throughout the world, the main target is still to find the promising candidate to target RNA-dependent RNA polymerase (RdRp) to provide possible drug against COVID-19. Aim of this work is to find a molecule to inhibit the translational process of viral protein synthesis. Density Functional Theory calculations revealed information about the formation of the desired ligand (RD). Molecular docking of RD with RdRp was performed and compared with some reported molecules and the data revealed that RD had the best docking score with RdRp (-6.7 kcal/mol). Further, molecular dynamics (MD) simulations of RD with RdRp of SARS-CoV-2 revealed the formation of stable complex with a maximum number of seven hydrogen bonds. Root mean square deviations values are in acceptable range and root mean square fluctuations has less fluctuation indicate stable complex formation. Further, based on MM-GBSA calculation, RD formed a stable complex with RdRp of nCoV with ΔG° of -12.28 kcal·mol-1.

Box-Behnken Design for Mitigation of Cadmium Bivalent Ions from Aqueous Medium.

Statistical analysis is essential for minimizing the time, cost, and number of experiments needed to get the maximum output. In this work, the removal of cadmium bivalent (Cd (II)) ions was optimized using Box-Behnken design methodology. The effects of pH, concentration, time, and temperature were investigated for the removal of cadmium. Maximum removal (85.70%) was achieved at pH of 5.34, initial Cd(II) ions concentration 46.61,contact time 166.09 (min), and at 59.40 oC temperature on Punica Granatum carpellary membrane powder (PGCMP) and 88.61% removal was achieved on its modified forms (MPGCMP) at pH of 5.79, initial Cd(II) ions concentration 65.70,contact time 178.96, and at 59.91 oC temperature. The model was validated by analyzing variance (ANOVA). The practical data was well fitted to the quadratic model. PGCMP and MPGCMP were found to be naturally occurring, environmentally friendly adsorbents for the mitigation of Cd (II) ions as well as other toxic heavy metals from drinkable or wastewater.

Unveiling the impact of dyes on aquatic ecosystems through zebrafish - A comprehensive review.

Dye industry plays an essential role in industrial development, contributing significantly to economic growth and progress. However, its rapid expansion has led to significant environmental concerns, especially water pollution and ecosystem degradation due to the discharge of untreated or inadequately treated dye effluents. The effluents introduce various harmful chemicals altering water quality, depleting oxygen levels, harming aquatic organisms, and disrupting food chains. Dye contamination can also persist in the environment for extended periods, leading to long-term ecological damage and threatening biodiversity. Therefore, the complex effects of dye pollutants on aquatic ecosystems have been comprehensively studied. Recently, zebrafish (Danio rerio) has proved to be an effective biomedical model for this study due to its transparent embryos allowing real-time observation of developmental processes and genetic proximity (approx. 87%) to humans for studying diverse biological responses. This review highlights the various toxicological effects of industrial dyes, including cardiovascular toxicity, neurotoxicity, genotoxicity, hepatotoxicity, and developmental toxicity. These effects have been observed at different developmental stages and dye concentrations in zebrafish. The review underscores that the structure, stability and chemical composition of dyes significantly influence toxicological impact, emphasizing the need for detailed investigation into dye degradation to better understand and mitigate the environmental and health risks posed by dye pollutants.

Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells.

Understanding prostate response to castration and androgen receptor signaling inhibitors (ARSI) is critical to improving long-term prostate cancer (PCa) patient survival. Here, we use a multi-omics approach on 229,794 single cells to create a mouse single-cell reference atlas for interpreting mouse prostate biology and castration response. Our reference atlas refines single-cell annotations and provides a chromatin context, which, when coupled with mouse lineage tracing, demonstrates that castration-resistant luminal cells are distinct from the pre-existent urethra-proximal stem/progenitor cells. Molecular pathway analysis and therapeutic studies further implicate AP1 (JUN/FOS), WNT/ß-catenin, FOXQ1, NF-κB, and JAK/STAT pathways as major drivers of castration-resistant luminal populations with relevance to human PCa. Our datasets, which can be explored through an interactive portal (https://visportal.roswellpark.org/data/tang/), can aid in developing combination treatments with ARSI for advanced PCa patients.