Molecular Analysis Research Articles

A novel inhibitor of class IIa histone deacetylases attenuates collagen-induced arthritis.

Most inhibitors of histone deacetylases (HDACs) are not selective and are cytotoxic. Some have anti-inflammatory activity in disease models, but cytotoxicity prevents long-term uses in non-fatal diseases. Inhibitors selective for class IIa HDACs are much less cytotoxic and may have applications in management of chronic inflammatory diseases. LL87 is a novel HDAC inhibitor examined here for HDAC enzyme selectivity. It was also investigated in macrophages for cytotoxicity and for inhibition of lipopolysaccharide (LPS)-stimulated cytokine secretion. In a rat model of collagen-induced arthritis, LL87 was investigated for effects on joint inflammation in Dark Agouti rats. Histological, immunohistochemical, micro-computed tomography and molecular analyses characterise developing arthritis and anti-inflammatory efficacy. LL87 was significantly more inhibitory against class IIa than class I or IIb HDAC enzymes. In macrophages, LL87 was not cytotoxic and reduced both LPS-induced secretion of pro-inflammatory cytokines, and IL6-induced class IIa HDAC activity. In rats, LL87 attenuated paw swelling and clinical signs of arthritis, reducing collagen loss and histological damage in ankle joints. LL87 decreased immune cell infiltration, especially pro-inflammatory macrophages and osteoclasts, into synovial joints and significantly reduced expression of pro-inflammatory cytokines and tissue-degrading proteases. A novel inhibitor of class IIa HDACs has been shown to have an anti-inflammatory and anti-arthritic profile distinct from current therapies. It is efficacious in reducing macrophage infiltration and joint inflammation in a chronic model of rat arthritis.

Aneuploidy in neoplasia: Single-cell data on 83,862 tumors.

Chromosomal aneuploidy, that is, numerical chromosome aberrations, is one of the molecular hallmarks of cancer. However, when neoplasms are studied with sequencing- and array-based approaches, chromosome numbers and ploidy states are typically inferred from bulk DNA data. Furthermore, published molecular estimates of neoplasia-associated aneuploidy often also include genomic imbalances resulting from various types of structural rearrangement, which likely result from other mechanisms than numerical chromosome aberrations. We thus analyzed chromosome numbers using single-cell cytogenetic data from 83,862 tumors, and show that both benign and malignant tumors are highly heterogeneous with regard to deviations from the normal, diploid state. Focusing on the chromosome numbers in 112 specific tumor types, defined by both exact morphologic diagnosis and organ location and from which data from ≥50 cases were available, we found two major clusters: one predominated by near-diploid neoplasms and one by neoplasms with extensive aneuploidy and one or more whole genome doublings. The former cluster included most benign solid tumors, myeloid neoplasms, and malignant gene fusion-associated solid tumors, whereas the latter was predominated by malignant solid tumors and lymphomas. For 16 malignant tumor types, the distribution of chromosome numbers could be compared to TCGA ploidy level data. Cytogenetic and molecular data correlated well, but the former indicates a higher level of clonal heterogeneity. The results presented here suggest shared pathogenetic mechanisms in certain tumor types and provide a reference for molecular analyses.

Molecular analysis of changes in DNA binding affinity and bending extent induced by the mutations on the aromatic amino residues in Cren7.

Proteins from Crenarchaeal organisms exhibit remarkable thermal stability. The aromatic amino acids in Cren7, a Crenarchaeal protein, regulate protein stability and further modulate DNA binding and its compaction. Specific aromatic amino acids were mutated, and using spectroscopic and theoretical approaches, we have examined the structure, DNA binding affinity, and DNA bending ability of mutants. and compared with wild-type (WT) Cren7. The reverse titration profiles were analysed by a noncooperativeMcGhee-von Hippel model to estimate affinity constant (Ka) and site size (n) associated with binding to the DNA. Biolayer interferometry (BLI) measurements showed that the binding affinity decreased at higher salt concentrations. For theoretical analysis of extent of DNA bending, radius of gyration and bending angle were compared for WT and mutants. Time evolution of order parameters based on translational and rotational motion of tryptophan residue (W26) was used for qualitative detection of stacking interactions between W26 of Cren7 and DNA nucleobases. It was observed that orientation of W26 in F41A favoredformation of a new lone pair-lone pair interaction between DNA and Cren7. Consequently, in thermostable proteins, the aromatic residues at the terminus maintain structural stability, whereas the residues at the core optimize the degree of DNA bending and compaction.

Assessing Species-Level Identification of Some Cryptic Frog Species of Bangladesh Using 16s and 12s Rrna Genes

In recent years, a number of new and undescribed anuran species are being discovered at a very fast rate in South and Southeast Asia. With the revelation of more and more species that were previously considered to be some other species, accurate identification of these morphologically cryptic anurans based on morphology alone have become difficult. In this study, we attempted specieslevel identification of 15 frog specimens belonging to the families Dicroglossidae and Microhylidae of Bangladesh by analyzing their 16S and 12S rRNA gene sequences. The collected specimens were successfully identified to be belonging to eight different species, namely Fejervarya dhaka, F. asmati, F. pierri and F. orissaensis; Euphlyctis kalasgramensis and Euphlyctis sp.; Microhyla berdmorei and M. mymensinghensis using BLAST and maximum likelihood analyses. In some cases the frog samples showed morphological resemblance but after molecular analysis they were found to be different and in another case morphologically distant samples were found to be molecularly similar. For example, two of the specimens (ESP 01, ESP 02) turned out to be E. kalasgramensis at molecular analysis, however, did not match with the morphological and morphometric descriptions (specially snout-vent length) described previously. Moreover, a species is suspected to be still undescribed and another species namely M. berdmorei was thought to be absent in Bangladesh which has been recorded in our study. Thus, morphological ambiguity strengthens the urge for molecular analysis for proper identification. Dhaka Univ. J. Biol. Sci. 33(2): 27-52, 2024 (July)

Mechanism of American Ginseng Against Type 2 Diabetes Mellitus Based on Network Pharmacology & Molecular Docking

Background: Ginseng is one of the top-selling natural products worldwide and has been shown to have significant effects. Nonetheless, there is limited research on American ginseng when compared to Asian ginseng. A small number of studies have demonstrated the therapeutic benefits of American ginseng, which include antioxidant, anti-inflammatory, and immune-stimulating activities. Objective: The objective of our research is to predict the molecular mechanism by which American ginseng combats Type 2 diabetes mellitus (T2DM) using Network Pharmacology and Molecular Docking techniques. By doing so, we aim to reveal one of the comprehensive mechanisms through which American ginseng exerts its therapeutic effects. Methods: We conducted a search for related compounds in American ginseng using the TCMSP database, which we then utilized to classify potential targets for the major ingredients. We obtained targets associated with T2DM from various databases, including PharmGKB, OMIM, TTD, GeneCards, and DrugBank. Using STRING and Cytoscape software, we constructed PPI networks. We subsequently performed GO and KEGG analysis on the targets using the R programming language. Ligand and target structures were acquired from PubChem and PDB databases, respectively. Chem3D and AutoDock software was used to process the structures, while PyMoL was employed for molecular docking analysis. Results: Several investigations have indicated that PTGS2, NFKBIA, PRKCA, IL1B, NCOA2, and LPL targets are significantly associated with American ginseng's effectiveness in treating T2DM. Molecular docking analysis further validated these findings. We discovered three active components with highaffinity, namely papaverine, ginsenoside-rh2, and beta-sitosterol. Conclusion: The outcomes of our predictions could contribute to the development of American ginseng or its active constituents as an alternative therapy for T2DM.

Thelazia callipaeda Eyeworms in American Black Bear, Pennsylvania, USA, 2023.

We identified a Thelazia callipaeda eyeworm in an American black bear in Pennsylvania, USA, on the basis of its morphological features and molecular analysis. Our finding highlights emergence of a T. callipaeda worm sylvatic transmission cycle in the United States.

First Molecular Diagnosis of Oestrus ovis (Linnaeus, 1758) Larvae Causing Conjunctival Ophthalmomyiasis in Mexico City, Mexico.

Human ophthalmomyiasis is a rare ocular parasitosis that results from the accidental infestation of dipteran larvae of several species, including Oestrus ovis (Linnaeus, 1758). This study aims to present the fourth documented human case of ophthalmomyiasis in Mexico, identifying the etiological agent through morphological and molecular analyses. Additionally, we investigated the phylogenetic position and genetic distances among different specimens globally characterized based on mitochondrial Cox1 sequences. A total of five larval specimens were extracted from the patient's eye, with two specimens allocated for identification based on morphological features using a stereomicroscope, and the remaining three preserved in absolute ethanol, one of them used for subsequent analysis using molecular methods. The mitochondrial Cox1 region was amplified and sequenced using automated Sanger sequencing. The resulting sequence was deposited in GenBank under accession number OR440699 and subjected to BlastN analysis against 35 other Cox1 sequences of O. ovis from GenBank. The identity and phylogenetic position of the strains were further explored using parsimony and maximum likelihood phylogenetic methods. Morphological examination of the larval specimens extracted from the patient's eye unequivocally identified them as O. ovis species. BlastN analysis and comprehensive phylogenetic investigations involving a total of 36 Cox1 sequences confirmed the taxonomic identity of the larvae. Notably, our sequence was positioned within the cluster formed by the Brazilian and two Iranian samples. This finding underscores a shared genetic ancestry among these distinct geographical isolates and provides valuable insights into the evolutionary relationships within O. ovis populations. The presence of O. ovis infestation in Mexico City suggests potential shifts in environmental conditions favoring fly proliferation, highlighting the need for vigilance in urban healthcare settings.

Unraveling the molecular landscape of UTROSCT: Insights from a clinicopathological, morphological, immunohistochemical, and molecular analysis of 35 cases.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor of uncertain lineage and low malignant potential. Most tumors behave in a benign fashion, but a subset of UTROSCT exhibit an aggressive clinical course with recurrences and metastases. The recurrent molecular alterations in UTROSCT mostly represent gene fusions involving NCOA1-3. We performed a comprehensive clinicopathological, morphological, immunohistochemical, and molecular analysis on a cohort of 35 UTROSCT. The tumors exhibited various architectural patterns (diffuse, corded/trabecular, tubular, sertoliform, fascicular, whorled, nested, microfollicular, and pseudoglandular), often in combination. The immunohistochemical analysis confirmed the polyphenotypic immunoprofile, often with co-expression of sex cord-stromal, smooth muscle, and epithelial markers, as well as hormone receptors. NGS RNA analysis revealed recurrent NCOA1-3 gene fusions in 22/32 analyzed cases (69%), including ESR1::NCOA3 (11/22), GREB1::NCOA2 (7/22), ESR1::NCOA2 (3/22), and GREB1::NCOA1 (1/22). Tumor mutation burden was low in all cases. The fusion-positive cases exhibited statistically significant association with whorled architecture, conversely necrosis was associated with fusion-negative status. We did not find a significant relationship between any architectural pattern and GREB1-alterations, but the NCOA2-altered tumors were associated with pseudoglandular architecture. The GREB1-altered cases occurred in older patients and tended to be more often intramural masses compared to ESR1-altered cases. On the contrary, the ESR1-altered cases presented more often like submucosal or polypoid tumors. Two tumors exhibited aggressive behavior with recurrent disease. Both of these cases harbored a GREB1::NCOA2 fusion. Unsupervised hierarchical cluster analysis of our cohort revealed two main clusters. The tumors with GREB1 or NCOA2 fusion cluster together, suggesting that there are underlying molecular differences between these cases and cases with ESR1::NCOA3 fusion or without fusion. Our findings contribute to the growing knowledge about a rare neoplasm with currently uncertain biological behavior.

Risk assessment of heavy metals in wild mushroom from Mizoram, India

Heavy metals (HMs) contaminate the environment and pose serious health risks to humans by accumulating in ecosystems, leading to toxicity and various diseases. In Mizoram, HMs pollution is a growing concern, with increasing research on contamination in various environmental sources. Present study aim to evaluate the HMs content in wild mushrooms collected from two different districts in Mizoram, India. Trichaptum biforme and Polyporus philippinensis were collected from Dampa Tiger Reserve (DTR), Mamit and Cantharellus tropicalis and Coprinellus disseminatus were collected from Lalsavunga Park (LP), Aizawl. The collected samples were identified based on standard mycotaxonomical methods and molecular analysis. Four species were evaluated for their cadmium (Cd), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) content and two species were assessed for their health risk associated with consumption of HMs. The ranges of element contents for cadmium (Cd), manganese (Mn), nickel (Ni), lead (Pb) and zinc (Zn) were found to be 0.19 - 0.92, 4.77 - 24, 0.24 - 1.61, 0.23 - 1.84, 9.5 - 30.9 µg/ g dried weight, respectively. The amount of Cd content was found to be over the safety limits values and can cause adverse health effects when consumed regularly. Wild edible mushrooms are valuable nutraceutical foods, but careful collection is essential to avoid health risks from HM contamination.

SENECA study: staging endometrial cancer based on molecular classification

ObjectiveManagement of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement...

Characterization of volatile profiles and markers prediction of eleven popular edible boletes using SDE-GC–MS and FT-NIR combined with chemometric analysis

Wild edible boletes mushrooms are regarded as a delicacy in many countries and regions due to their rich nutritional contents and strong aromatic compounds. This study aimed to identify 445 samples of 11 boletes species collected from Yunnan and Sichuan provinces through molecular analysis. Using simultaneous distillation–extraction (SDE) combined with gas chromatography-mass spectrometry (GC–MS), 97 volatile compounds were identified. Chemometric methods were then applied to analyze the heterogeneity of these volatile compounds among the different species. The results showed that, 22 and 21 volatile compounds were selected using variable importance in projection (VIP > 1) and relative odor activity values (ROAV > 0.1), respectively. Partial least squares discrimnatint analysis (PLS-DA) was then employed to develop pattern recognition models for 11 species, which demonstrated strong identification performance. Furthermore, correlation heat maps, volcano plots, and Fisher linear discriminant analysis identified five volatile organic compounds, including methyl (9E)-9-octadecenoate, 2, 6-dimethylpyrazine, 1-decen-3-one, furfural, and methional as markers for distinguishing 11 boletes species. Ultimately, the rapid content prediction models of partial least squares regression (PLSR) were established by combining Fourier Transform Near-Infrared Spectroscopy (FT-NIR) with the concentrations of these five marker compounds. These findings provide a methodological strategy for the effective species identification of wild edible mushrooms and the rapid prediction of their characteristic aroma compounds.

Dietary oxygenated water mitigates type 2 diabetes mellitus by modulating gut microbiota and enhancing glucose metabolism in skeletal muscle

Type 2 diabetes mellitus (T2DM) is a significant health concern resulting from dysregulation of glucose metabolism, emphasizing the need for effective dietary interventions. Emerging evidence suggests a correlation between diabetes and hypoxia, indicating that oxygenated water (ORW) may hold promise in mitigating T2DM. This study employed a multifaceted approach involving physiological, genomic, metabolomic, transcriptomic, and molecular biological analyses to investigate the effects of ORW on T2DM and its underlying mechanisms. The results demonstrated that ORW effectively ameliorated key symptoms of T2DM by improving polydipsia and polyphagia, reducing fasting blood glucose, enhancing glucose tolerance, and increasing insulin levels. Notably, the beneficial effects of ORW appeared to be mediated through modulation of gut-muscle interactions by influencing gut microbiota composition and metabolite profiles. Transcriptomic and molecular analyses revealed that ORW activated the Akt signaling pathway and upregulated key genes involved in glucose uptake and utilization in skeletal muscle, as evidenced by increased p-AKT/AKT ratio and upregulation of Irs1, Glut4, Hk2, and Pfk. Collectively, these findings demonstrate that ORW alleviates T2DM by modulating gut microbiota while enhancing glucose uptake/utilization in skeletal muscle, supporting its potential use as an effective adjuvant strategy for targeted regulation of T2DM.

Diversity, toxicity, and distribution of potentially toxic diatoms in Antarctic waters – with description of Pseudo-nitzschia meridionalis sp. nov. and P. glacialis sp. nov.

Diatoms of the genus Pseudo-nitzschia, known for their potential toxicity, are integral to the phytoplankton community of the Southern Ocean, which surrounds Antarctica. Despite their ecological importance, the diversity and toxicity of Pseudo-nitzschia in this region remain underexplored. Globally, these diatoms are notorious for forming harmful algal blooms in temperate and tropical waters, causing significant impacts on marine life, ecosystems, and coastal economies. However, detailed information on the diversity, morphology, and toxicity of Pseudo-nitzschia species in Antarctic waters is limited, with molecular characterizations of these species being particularly scarce.During three research expeditions to the Southern Ocean, monoclonal strains of Pseudo-nitzschia were isolated and cultivated. Stored samples from a fourth expedition, the Brategg expedition, were used to complete the description of particularly P. turgidula. Through electron microscopy and molecular analysis, two novel species were identified—Pseudo-nitzschia meridionalis sp. nov. and Pseudo-nitzschia glacialis sp. nov.—alongside the previously described species P. subcurvata, P. turgiduloides, and P. turgidula. Toxin assays revealed no detectable levels of domoic acid in P. turgiduloides, P. turgidula, P. meridionalis sp. nov. and P. glacialis sp. nov. Conversely, P. subcurvata was reported in a related study to produce domoic acid and its isomer, iso-domoic acid C.These findings emphasize the need for comprehensive research on the phytoplankton of Antarctic waters, which is currently a largely uncharted domain. With the looming threat of climate change, understanding the dynamics of potentially harmful algal populations in this region is becoming increasingly critical.

Klinefelter syndrome in a patient with double Y-autosomal translocation

Klinefelter syndrome is one of the most common chromosomal abnormalities and the most common genetic cause of male infertility. About 85 % of patients have 47,XXY karyotype, other patients have other non-mosaic and mosaic Klinefelter syndrome variants. We report a unique clinical case — Klinefelter syndrome patient with double Y autosomal translocation. The proband is a 15-year-old male patient (height 180 cm, weight 50 kg, normal IQ) who was admitted for cytogenetic examination and genetic counseling due to delayed puberty. He was diagnosed with testicular hypoplasia, hypergonadotropic hypogonadism, pituitary microadenoma and left-sided varicocele. The proband was born in a nonconsanguineous marriage after in vitro fertilization due to paternal male factor infertility. Cytogenetic analysis was performed on cultured peripheral blood lymphocytes using standard chromosome analysis with GTG staining and FISH analysis. Molecular analysis of the Y chromosome was performed by multiplex PCR. Complex cytogenetic examination revealed a 46,XX,der(Y) t(Y;15)(q12;q11.1),der(13)t(Y;13)(q12;p11.2),-15 karyotype in the proband. Molecular analysis showed that the proband is SRY positive; no microdeletion of the Y chromosome was found. The detected double Y autosomal translocation is a chromosomal abnormality independent of KS. The father of the proband is an oligozoospermic man with robertsonian translocation 13;15 — 45,XY,der(13;15)(q10;q10), the mother has a normal karyotype 46,XX. Apparently, the der(13) and der(Y) chromosomes result from abnormal meiotic recombination in paternal meiosis between the heterochromatic region Yq12 and the centromeric/pericentromeric heterochromatin of chromosomes 13 and 15 involved in the paternal robertsonian translocation, and Klinefelter syndrome is due to the presence of two X chromosomes in the karyotype in the presence of a derivative Y chromosome. The detected double Y-autosomal translocation is a chromosomal abnormality unrelated to Klinefelter syndrome, arising on the background of the paternal robertsonian translocation.

Network pharmacology prediction and molecular docking analysis on the mechanism of eugenol as a candidate against estrogen receptor-positive breast cancer

Context: Breast cancer therapy currently presents several uncomfortable side effects in patients, including effects on non-malignant tissues, recurrence, and resistance, which restrict their utilization. Consequently, researchers have directed their attention toward studying plant-derived anticancer compounds that exhibit high efficacy and safety profiles. Eugenol, a major component found in clove plants, demonstrates promising potential as a therapeutic agent for both estrogen receptor-positive and estrogen receptor-negative breast cancer. Aims: To predict the target of eugenol in estrogen receptor–positive breast cancer using network pharmacology and molecular docking analyses. Methods: Network pharmacology analysis was performed using the Chemical Toxigenomic Database, STITCH, GeneCards, Cytoscape, Enrichr, and Stringdb. Subsequently, molecular docking was performed using protein targets obtained from the RCSB-PDB and analyzed using AutoDock software. Results: Network pharmacology study and molecular docking revealed the anticancer effect of eugenol against breast cancer estrogen receptor–positive, especially in cancer and apoptotic pathways, by acting on caspase-3 (CASP3), epidermal growth factor receptor (EGFR), and poly [ADP-ribose] polymerase 1 (PARP1) signaling pathways. The docking results between the protein targets and eugenol showed that eugenol has the strongest binding with CASP3 (ligand binding energy: -5.78 kcal/mol), followed by eugenol binding with EGFR (ligand binding energy: -5.58 kcal/mol), and eugenol binding with PARP1 (ligand binding energy: -5.58 kcal/mol). Conclusions: Eugenol is a potential candidate for breast cancer therapy, especially for apoptosis mediated by CASP3 in breast cancer luminal A.

Identification of Potential Inhibitors against Corynebacterium diphtheriae MtrA Response Regulator Protein; An in-silico Drug Discovery Approach

Corynebacterium diphtheriae is a multi-drug resistant bacteria responsible for the life-threatening respiratory illness, diphtheria which can lead to severe Nervous system disorders, mainly infecting the lungs, heart, and kidneys if left untreated. In the current study, Corynebacterium diphtheriae MtrA response regulator protein was targeted, which regulates a two-component system of bacterial pathogenesis, and initiates DNA replication and cell division. In the current study a computational approach have been described for drug development against C. diphtheriae infections by inhibiting MtrA protein by small molecules acting as potential inhibitors against it. Molecular docking analysis of the equilibrated MtrA protein revealed compound-0.2970, compound-0.3029, and compound-0.3016 from Asinex Library as the promising inhibitors based on their lowest binding energies (-9.8 KJ/mol, -9.2 KJ/mol, and -8.9 KJ/mol), highest gold scores (40.53, 47.41, and 48.41), drug-likeness and pharmacokinetic properties. The MD simulation studies of the identified top-ranked inhibitors at 100 ns elucidated the system stability and fluctuations in the binding pocket of MtrA protein. Molecular Dynamics Simulations of the top three docked complexes further revealed that the standard binding pocket was retained ensuring the system stability. The rearrangements of H-bonds, van der Waals, pi-pi, and solid hydrophobic interactions were also observed. The binding free energy calculations (MM/PBSA and MM/GBSA) suggested a fundamental binding capability of the ligand to the target receptor MtrA. Therefore, the current study has provided excellent candidates acting as potent inhibitors for developing therapeutic drugs against C. diphtheria infections. However, in vivo and in vitro animal experiments and accurate clinical trials are needed to validate the potential inhibitory effect of these compounds.

Molecular characterisation and expression analysis of an interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) homologue from Asian seabass (Lates calcarifer)

The interferon-induced protein with tetratricopeptide repeats 1(IFIT1) is an interferon-inducible protein that acts downstream of the interferon pathway in response to viral infection or an interferon-stimulation. Our study describes the isolation and characterization of a IFIT1 homologue from Lates calcarifer (named LcIFIT1), as well as its expression profile in response to viral mimetic poly(I:C) and Red-spotted grouper nervous necrosis virus (RGNNV). The complete ORF of LcIFIT1 encodes a 441 amino acid protein with nine tetratricopeptide repeat (TPR) domains. The protein-coding region of the LcIFIT1 gene was encoded by two exons separated by a small 157 bp intron. The phylogenetic analysis revealed that LcIFIT1 is evolutionarily conserved and forms a distinct clade with homologues from other teleost. LcIFIT1 mRNA was constitutively expressed in all tissues examined, with predominant expression in blood. LcIFIT1 expression was upregulated following poly(I:C) and RGNNV challenges in different tissues examined. These results shed light on the antiviral role of LcIFIT1 in the host immune response against nodaviral infection.

Synthesis, structural characterization, molecular docking analysis and Carbonic Anhydrase IX inhibitory evaluations of novel Cerium(III)-based MOF constructed from 1,10-phenanthroline and fumaric acid.

In this study, a novel Cerium-based MOFs with 1,10-phenanthroline (phen) and fumaric acid (H2fum) has been hydrothermally synthesized as single crystal structurally characterized by X-ray diffraction, IR spectroscopy and ATG measurements. This compound corresponds to the formula: [Ce2(phen)2(fum)3(H2O)2]n(I), it crystallizes in the triclinic system with space group P1¯, with the following parameters: a = 9.062(1) Å, b = 10.0608(5) Å, c = 10.603(1) Å, α = 72.545(6) °, β = 77.57(1) °, γ = 69.959(6) °, V = 859.49(14) Å3, Z = 2.The structure revealed 2D bridged polymeric chains where the adjacent Ce(III) atoms are bridged by fumarate linkers with a mean intermetallic distance of about 9.36 Å. H···O bonds link the 2D sheets leading to a pseudo 3D network, while the stability of the structure is assured by a weak π-π stacking between parallel and opposed phen ligands.The Ce3+ cation is nona-coordinated and it is in a distorted tricapped trigonal prism geometry.Hirshfeld surface analysis was used to investigate the non-covalent intermolecular interactions and the dominant H···O, H···C and H···H contacts were quantified. The thermal properties of the considered coordination polymer (I) are also discussed and disclose that (I) is stable up to 300°C. Besides, this study explores the potential of (I) as an inhibitor of the carbonic anhydrase IX enzyme (CA IX), a critical player in tumor microenvironment regulation. Through molecular docking simulations, we elucidate the binding interactions between (I) and CA IX, the results suggest the efficiency of (I) as a CA IX inhibitor. Moreover, we assessed the drug-likeness properties and ADMET characteristics of (I), providing valuable insights for its potential as a therapeutic agent.

A miniaturized microfluidic nanoplasmonic sensor with cavity reflection enhancement for ultrasensitive molecular interaction analysis

Molecular binding kinetics quantification is pivotal in the design of antibodies, small-molecule drugs, and early diagnosis of complex disease. This study presents a portable microfluidic system, featuring a nanoplasmonic sensor with cavity reflection enhancement (NSCRE), designed for the ultrasensitive detection and analysis of molecular interactions. This device comprises liquid flow paths, generic fiber spectrometers, a versatile NSCRE sensor chip, and a novel data analysis system. Furthermore, a neural network data processing system is developed based on a deep learning model to decrease significant data fluctuations caused by air segments. This “all-in-one” platform, integrating multifunctional, easy-to-use, and renewable NSCRE biosensors, boasts detection capabilities for both slow and rapid kinetics. It can automatically monitor interactions between molecules across a broad range of molecular weights (0.259–150 kDa), allowing for real-time, ultra-sensitive, and highly selective analysis. In addition, the platform with CRE effect facilitates a 7.2-fold increase in reflection intensity signals compared to that of a sensor without CRE. The immunoglobulin G detection with a limit of detection of 73 pM based on this device, showing a 50-fold increase in sensitivity compared to previously reported values. The miniaturized automatic detection system paves a new path for the use of molecular interaction analysis in life science research, drug discovery, early diagnosis, and other fields.

Palladium catalysed cross coupling reactions on 2,3-isoxazol-17α-ethynyltestosterone, their anti-cancer activity, molecular docking studies and ADMET analysis

Palladium catalysed cross coupling reactions on 2,3-isoxazol-17α-ethynyltestosterone, their anti-cancer activity, molecular docking studies and ADMET analysis