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The Cagsao mangrove is a thriving young forest along the San Miguel Bay (SMB), Camarines Sur. To establish the Spatio-temporal Water Quality mapping, data from the Chesapeake Bay, an estuary in the United States of America (USA), was sourced as the train set for this study. Spatio-temporal maps of chlorophyll and dissolved oxygen were generated using Linear Regression (LR) models which were derived from the train set and satellite images of the SMB. GNU (GNU’s not UNIX) Octave was used for the image processing, computing, and analysis. There were three phases in the image processing conducted in this study, 1) extraction of image data of the corresponding measure points from the train area, 2) conversion of the satellite study area to a two-color raster image, and 3) generation of the spatio-temporal maps from the analysis. The study found that the SMB is in the range of Mesotrophic to Moderate Eutrophic classification. The decay from two other point sources (Manga River and Libmanan River) was compared to that of Tigman River, an adjacent river to the Cagsao mangrove forest to determine variations and impact of the mangrove forest in the water quality of the SMB. The presence of Cagsao mangrove forest was found to affect the gap of increasing chlorophyll levels from shore toward the bay center in the adjacent Tigman River unlike Manga River and Libmanan River, which have both no adjacent mangrove forest in the river mouth area. The corresponding satellite images for the dataset taken during and near the date of the train area measurements were also extracted.

A novel approach in the field, a range of new azothiazole dyes substituted with different hydrophobic groups, was utilized as colorants for dyeing polyester fabrics in a supercritical carbon dioxide environment. The innovative dyes were analyzed using standard spectroscopy techniques and elemental analysis. The dyeing process was assessed for its dyeing ability, color strength, and color fastness for twelve different dyes. The polyester fabrics dyed with these dyes appeared in various shades, between red and magenta. Using the AATCC method, the antibacterial assessment revealed that some dyes exhibited significant antibacterial properties against both positive and negative bacteria. All 12 dyes showed outstanding resistance to washing, rubbing, and light, with staining and color change ratings of 4–5. The results indicate that the synthesized dyes could be employed for large-scale, energy-efficient, and environmentally friendly polyester fabric dyeing utilizing supercritical carbon dioxide. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica spectrum disorder (NMOSD) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. We report a casewith paraneoplastic NMOSD that improved after immunosuppressive therapy, surgical resection, and chemotherapy. A 48-year-old woman initially presented with gradual binocular visual loss over the course of one week. The patient was evaluated usingmagnetic resonance imaging (MRI), computed tomography (CT), visual evoked potential (VEP), pathological biopsy, immunohistochemistry, and autoimmune antibody testing. The brain MRI findings were normal. The VEP revealed prolonged P100 latencies in the right eye and an absence of significant waves in the left eye. Positive serum AQP4-IgG antibodies were found. The patient was diagnosed as NMOSD. Then the patient responded well to treatment with methylprednisolone. An ovarian tumor was found in the patient using abdominal MRI and CT. The tumor was surgically resected, and a pathological biopsy revealed that it was ovarian dysgerminoma. The patient received four rounds of chemotherapy after surgery. Onemonth after the final chemotherapy treatment, a positron emission tomography (PET) scan revealed no tumor. The vision of the patient gradually recovered and serum AQP4 was negative. Furthermore, we summarized the characteristics of patients diagnosed with paraneoplastic NMOSD associated with ovarian neoplasms in previous studies. This is a characteristic case of overlapping NMOSD and ovarian dysgerminoma, demonstrating the importance of tumor therapy in cases of paraneoplastic NMOSD. [ABSTRACT FROM AUTHOR]

Certain diseases such as Multiple Sclerosis (MS), a chronic demyelinating disease, affect more women than men, despite males appearing to be predisposed to infections and malignancies. X-linked genes contribute to increased MS susceptibility. Currently, an immense body of research exists that explores the complexity surrounding underlying risk factors for MS development including X-chromosome-linked inflammatory processes. Female–male disparities in disease susceptibility have been found at both the gene and chromosomal level. Genes such as CXORF21 and DDX3X can escape X-chromosome inactivation (XCI) and contribute to various disease pathogenesis. Additionally, blocking immune cell entry to the central nervous system (CNS) can have a major impact on MS. Prior research on MS has shown that immune cells such as T cells and dendritic cells (DCs) infiltrate the CNS. Due to persistent tissue stress, these cells may induce local inflammation and autoimmunity, subsequent neurodegeneration, and both the onset and progression of MS. Chemokines are signaling proteins which regulate leukocyte trafficking to the site of injury, contributing to cell recruitment, CNS inflammation, and disease severity. Some chemokine receptors (CXCR3) are X-linked and may escape XCI. This review provides an account of the contribution of x-linked genes in MS in relation to the chemotaxis of myeloid cells into CNS and subsequent neuroinflammation. The impact of the X-chromosome on autoimmunity, including XCI and the expression of X-linked genes is evaluated. Collectively, the analyses from this review seek to advance both our understanding of MS and advocate for more patient-specific therapies. [ABSTRACT FROM AUTHOR]

Objective: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy with evidence of neuroinflammation and demyelination that affects the central nervous system and is mediated by aquaporin-4 (AQP4) immunoglobulin (IgG). AQP4-IgG may also be present in paraneoplastic syndromes secondary to malignancy such as breast cancer. Methods: A systematic review and meta-analysis of the literature were completed using PubMed, Scopus, and ScienceDirect databases (CRD42022352109). Results: A total of 12 publications, which included 19 cases, met the inclusion criteria and were assessed in both the qualitative and quantitative synthesis. The mean age was 51.26 years (SD: 13.12, SEM: 3.01), and 100% of the cases were reported in women. Speech abnormalities and symptoms of myelopathy were the most observed neurological manifestations. MRI often revealed longitudinally extensive transverse myelitis (LETM) involving the cervical spine. Three of 19 (15.9%) cases were diagnosed with NMOSD and breast cancer within the same month. Five of 19 (26.1%) cases had a diagnosis of breast cancer preceding that of NMOSD. Eight of 19 (42.1%) cases were diagnosed with breast cancer after NMOSD. The median time of breast cancer diagnosis was 1.0 months (range 216 months) after NMOSD. Conclusions: The diagnosis of breast cancer most often occurs after the onset of the paraneoplastic NMOSD symptoms. However, a wide time range for the diagnosis of breast cancer was observed both before and after the onset of neurological symptoms. Older women with a new diagnosis of NMOSD should be considered for frequent breast cancer screening. [ABSTRACT FROM AUTHOR]

In this present communication, four component, one pot synthesis of benzyl pyrazolyl coumarin (5a-m) derivatives achieved from the condensation of phenyl hydrazine (1), ethyl acetoacetate (EAA, 2), various substituted benzaldehyde (3), and 4-hydroxy coumarin (4) in EtOH/H2O using metal-free chitosan supported ionic liquid carbon nanotubes (CSIL@CNTs, 10 mol%) as heterogeneous catalyst reflux at 50 °C for 25–30 min. The optimized conditions and excellent yields of the products were reported. All the synthesized compounds were charecterized by the spectroscopic methods. The main advantages of this reported method using CSIL@CNTs. leads to effective conversions were achieved under reflux conditions without the need of an inert atmosphere. In adition, shorter reaction time, simple work up procedure, easy preparation of the catalyst, and chemoselectivity were siginificantly recorded. [ABSTRACT FROM AUTHOR]

During pregnancy, hormonal and immune adaptations are vital for supporting the genetically distinct fetus during elevated infection risks. The global prevalence of HPV necessitates its consideration during pregnancy. Despite a seemingly mild immune response, historical gestational viral infections underscore its significance. Acknowledging the established HPV infection risks during pregnancy, our review explores the unfolding immunological changes in pregnant women with HPV. Our analysis aims to uncover strategies for safely modulating the immune system, mitigating adverse pregnancy consequences, and enhancing maternal and child health. This comprehensive narrative review delves into the existing knowledge and studies on this topic. [ABSTRACT FROM AUTHOR]

Mendelian randomization (MR) is a powerful approach for assessing the causal effect of putative risk factors on an outcome, using genetic variants as instrumental variables. The methodology and application developed in the framework of MR have been dramatically improved, taking advantage of the many public genome‐wide association study (GWAS) data. The availability of summary‐level data allowed to perform numerous MR studies especially for complex diseases, pinpointing modifiable exposures causally related to increased or decreased disease risk. Multiple sclerosis (MS) is a complex multifactorial disease whose aetiology involves both genetic and non‐genetic risk factors and their interplay. Previous observational studies have revealed associations between candidate modifiable exposures and MS risk; although being prone to confounding, and reverse causation, these studies were unable to draw causal conclusions. MR analysis addresses the limitations of observational studies and allows to establish reliable and accurate causal conclusions. Here, we systematically reviewed the studies evaluating the causal effect, through MR, of genetic and non‐genetic exposures on MS risk. Among 107 papers found, only 42 were eligible for final evaluation and qualitative synthesis. We found that, above all, low vitamin D levels and high adult body mass index (BMI) appear to be uncontested risk factors for increased MS risk. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD4+ T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4+ T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus. This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4+ T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF. [ABSTRACT FROM AUTHOR]

Some new hemorphin-4 analogs with structures of Xxx-Pro-Trp-Thr-NH 2 and Tyr-Yyy-Trp-Thr-NH 2 , where Xxx is 2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoic acid or 2-amino-3-(4-dibenzylamino-2,6-dimethylphenyl)propanoic acid, and Yyy is (2S,4S)-4-amino-pyrrolidine-2-carboxylic acid, were synthesized and characterized by electrochemical and spectral analyses. In vivo anticonvulsant and antinociceptive activities of peptide derivatives were studied after intracerebroventricular injection in mice. The therapeutic effects of the modified peptides on seizures and pain in mice were evaluated to provide valuable insights into the potential applications of the novel compounds. Electrochemical characterization showed that the compounds behave as weak protolytes and that they are in a soluble, stable molecular form at physiological pH values. The antioxidant activity of the peptides was evaluated with voltammetric analyses, which were confirmed by applying the 2,2-Diphenyl-1-picrylhydrazyl method. The compounds showed satisfactory results regarding their structural stability, reaching the desired centers for the manifestation of biological activity without hydrolysis processes at 37°C and physiological pH. Dm-H4 and H4-P1 exhibited 100% and 83% potency to suppress the psychomotor seizures in the 6-Hz test compared to 67% activity of H4. Notably, only the H4-P1 had efficacy in blocking the tonic component in the maximal electroshock test with a potency comparable to H4. All investigated peptides containing unnatural conformationally restricted amino acids showed antinociceptive effects. The analogs Db-H4 and H4-P1 showed the most pronounced and long-lasting effect in both experimental models of pain induced by thermal and chemical stimuli. Dm-H4 produced a dose-dependent thermal antinociception and H4-P2 inhibited only formalin-induced pain behavior., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

The mechanism of brain aging is not fully understood. Few studies have attempted to identify molecular changes using bioinformatics at the subregional level in the aging brain. This study aimed to identify the molecular signatures and key genes involved in aging, depending on the brain region. Differentially expressed genes (DEGs) associated with aging of the cerebral cortex (CX), hippocampus (HC), and cerebellum (CB) were identified based on five datasets from the Gene Expression Omnibus (GEO). The molecular signatures of aging were explored using functional and pathway analyses. Hub genes of each brain region were determined by protein– protein interaction network analysis, and commonly expressed DEGs (co-DEGs) were also found. Gene–microRNAs (miRNAs) and gene–disease interactions were constructed using online databases. The expression levels and regional specificity of the hub genes and co-DEGs were validated using animal experiments. In total, 32, 293, and 141 DEGs were identified in aging CX, HC, and CB, respectively. Enrichment analysis indicated molecular changes related to leukocyte invasion, abnormal neurotransmission, and impaired neurogenesis due to inflammation as the major signatures of the CX, HC, and CB. Itgax is a hub gene of cortical aging. Zfp51 and Zfp62 were identified as hub genes involved in hippocampal aging. Itgax and Cxcl10 were identified as hub genes involved in cerebellar aging. S100a8 was the only co- DEG in all three regions. In addition, a series of molecular changes associated with inflammation was observed in all three brain regions. Several miRNAs interact with hub genes and S100a8. The change in gene levels was further validated in an animal experiment. Only the upregulation of Zfp51 and Zfp62 was restricted to the HC. The molecular signatures of aging exhibit regional differences in the brain and seem to be closely related to neuroinflammation. Itgax, Zfp51, Zfp62, Cxcl10, and S100a8 may be key genes and potential targets for the prevention of brain aging. [ABSTRACT FROM AUTHOR]

We present a taxonomic treatment for the monospecific genus Koernickanthe (Marantaceae) based on morphology and previous phylogenetic studies. We return K. orbiculata to Maranta once more and have located the last remnant syntype for its basionym, Ischnosiphon orbiculatus, deposited at the Komarov Botanical Institute of RAS herbarium (LE), designating it as lectotype. Nomenclature and taxonomic novelties include the acceptance of the name Maranta orbiculata and its correct application, and also provide lectotypification for its basionym and that of its synonym, Calathea cardenasii. [ABSTRACT FROM AUTHOR]

A facile, catalyst‐ and solvent‐ free, three‐component reaction was developed for the synthesis of tetrasubstituted pyrroles at room temperature and under white light. The reaction proceeds via enamine formation between primary amines with 1,3‐dicarbonyl compounds followed by Michael addition with β‐nitro styrene and subsequent intramolecular cyclization and aromatization to yield 1,2,3,4‐tetrasubstituted pyrroles in good to excellent yields. Further, the present strategy is highly atom‐economical and environmentally benign. The preliminary in vitro cytotoxic studies on a set of compounds were performed against Hepatocellular carcinoma cells (HepG2) and one of the compounds 4 ac showed significant activity with an IC50 value of 17.82 μM. [ABSTRACT FROM AUTHOR]

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The incidence of nontuberculous mycobacterial (NTM) infection has been increasing globally. Further, it has been reported that early NTM infection diagnosis and treatment can considerably improve patient prognosis. However, traditional methods for detecting pathogenic microorganisms are associated with several limitations, and optimal treatment regimens for several NTM infections have not yet been established. Here, we report the case of a 22-year-old woman with renal and lymph node Mycobacterium xenopi infection. This patient presented with repeated fever and systemic lymphadenopathy events for more than 2 years, but the etiology of the disease was unclear. We performed metagenomic next-generation sequencing (mNGS) using tissue sections from the patient’s left kidney and successfully identified M. xenopi. Thereafter, the patient’s condition was effectively controlled via treatment with rifampicin, clarithromycin, and ethambutol hydrochloride (orally administered after hemodialysis). Further, this case showed that the clinical symptoms of NTM infection are atypical and highly occult, especially for extrapulmonary NTM infections, which are difficult to diagnose. Therefore, mNGS may be a powerful tool for diagnosing NTM infections. The combination therapy used showed efficacy and thus could serve as a reference treatment for kidney and lymph node M. xenopi infection. [ABSTRACT FROM AUTHOR]

Background: Aquaporin‐4 IgG seropositive neuromyelitis optica spectrum disorder (AQP4‐IgG NMOSD) might occur in association with cancer. According to diagnostic criteria, a probable paraneoplastic NMOSD can be diagnosed only in patients with isolated myelitis and adenocarcinoma or tumors expressing AQP4. The aim of this study was to explore the features of paraneoplastic NMOSD through a data‐driven approach. Methods: A systematic literature review was performed. Patients with AQP4‐IgG positivity in association with tumor in the absence of history of checkpoint inhibitors administration/central nervous system metastases were included. Demographic, clinical, and oncological data were collected. A hierarchical cluster analysis (HCA) was performed and data were compared between resulting clusters. Results: A total of 1333 records were screened; 46 studies (72 patients) fulfilled inclusion criteria. Median age was 54 (14–87) years; adenocarcinoma occurred in 41.7% of patients, and 44% of cases had multifocal index events. Cancer and NMOSD usually co‐occurred. HCA classified patients in three clusters that differed in terms of isolated/multifocal attacks, optic neuritis, pediatric onset, and type of underlying tumor. Age, time from neoplasm to NMOSD onset, and tumor AQP4 staining did not differ between clusters. Conclusions: Our data‐driven approach reveals that paraneoplastic NMOSD does not present a homogeneous phenotype nor peculiar features. Accordingly, cancer screening may be useful in AQP4‐IgG NMOSD regardless of age and clinical presentation. [ABSTRACT FROM AUTHOR]

A tertiary amine-catalyzed asymmetric [3+2] spiroannulation reaction of pyrazolone-derived Morita–Baylis–Hillman carbonates with alkynyl ketones was achieved under mild conditions. This protocol offers a facile approach to chiral spiro[cyclopentadiene-pyrazolone] scaffolds in good to high yields (up to 92%) with good degrees of enantiocontrol (up to 98% ee). In addition, scale-up reaction and transformation of the products were performed to show the synthetic utility of this protocol. [ABSTRACT FROM AUTHOR]

This work aimed at estimating narrow-sense heritability, defined as the proportion of the phenotypic variance explained by the sum of additive genetic effects, via Haseman–Elston regression for a subset of 56 plasma protein levels related to Multiple Sclerosis (MS). These were measured in 212 related individuals (with 69 MS cases and 143 healthy controls) obtained from 20 Sardinian families with MS history. Using pedigree information, we found seven statistically significant heritable plasma protein levels (after multiple testing correction), i.e., Gc ( h 2 = 0.77; 95%CI: 0.36, 1.00), Plat ( h 2 = 0.70; 95%CI: 0.27, 0.95), Anxa1 ( h 2 = 0.68; 95%CI: 0.27, 1.00), Sod1 ( h 2 = 0.58; 95%CI: 0.18, 0.96), Irf8 ( h 2 = 0.56; 95%CI: 0.19, 0.99), Ptger4 ( h 2 = 0.45; 95%CI: 0.10, 0.96), and Fadd ( h 2 = 0.41; 95%CI: 0.06, 0.84). A subsequent analysis was performed on these statistically significant heritable plasma protein levels employing Immunochip genotyping data obtained in 155 healthy controls (92 related and 63 unrelated); we found a meaningful proportion of heritable plasma protein levels' variability explained by a small set of SNPs. Overall, the results obtained, for these seven MS-related proteins, emphasized a high additive genetic variance component explaining plasma levels' variability. [ABSTRACT FROM AUTHOR]

Diversely functionalised pyrazolone analogues have been reported to display a wide range of biological activities. In this paper, we report the synthesis of a series of novel analogues based on piperidine fused pyrazolone core and explore its potential as novel antibacterial agents. The synthesised compounds were analysed using spectroscopic techniques such as 1H NMR, LC-MS, and FT-IR. The major highlight involves the cyclisation reaction of tert-butyl-4-methyl 3-oxopiperidine-1,4-dicarboxylate with the hydrazine component to access the privileged piperdine fused pyrazolone scaffold. This scaffold was further treated with HCl to remove the amine protecting group and subsequently reacted with acid chlorides to deliver the final products in excellent yields. Density functional theory (DFT) calculations were performed to determine the various molecular properties of the synthesised compounds. Based on the reactive sites explored by the molecular electrostatic potential maps, the compounds were screened against two gram positive bacterial strains namely S. aureus, and M. luteus, and a gram negative bacterial strain namely E.coli. Highlights A Series of novel pyrazole derivatives were synthesised using bicyclisation strategy. Computational methods were used to determine various quantum chemical properties. All molecules were screened against S. aureus, M. luteus, and E. coli bacterial strains. [ABSTRACT FROM AUTHOR]

4-Benzylidene pyrazolones are valuable scaffolds of numerous bioactive molecules, building blocks, ligands, dyes, and pigments. Therefore, the construction of 4-benzylidene pyrazolones with diverse substitution patterns is a desirable target of organic synthesis. We developed a (5+1) benzannulation strategy for the practical synthesis of multisubstituted 4-benzylidene pyrazolones, which are challenging to prepare through conventional condensation reactions. This organocatalytic cycloaddition of Morita–Baylis–Hillman carbonate undergoes an unprecedented α-double deprotonation pathway to de novo assemble the benzene ring, avoiding the use of a metal catalyst, large amount of base, and oxidant. This green approach features the use of a cheap catalyst (triethylenediamine), metal-free and mild conditions, readily available starting materials, and broad substrate scope. Moreover, several highly efficient one-pot approaches based on the (5+1) benzannulation reaction were developed, enabling the construction of diverse, interesting multisubstituted oxindole derivatives, which are also challenging to synthesize via existing methods. [ABSTRACT FROM AUTHOR]

Background. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. MS pathogenesis is closely related to the environment, genetic, and immune system, but the underlying interactions have not been clearly elucidated. This study aims to unveil the genetic basis and immune landscape of MS pathogenesis with bioinformatics. Methods. Gene matrix was retrieved from the gene expression database NCBI-GEO. Then, bioinformatics was used to standardize the samples and obtain differentially expressed genes (DEGs). The protein-protein interaction network was constructed with DEGs on the STRING website. Cytohubba plug-in and MCODE plug-in were used to mine hub genes. Meanwhile, the CIBERSORTX algorithm was used to explore the characteristics of immune cell infiltration in MS brain tissues. Spearman correlation analysis was performed between genes and immune cells, and the correlation between genes and different types of brain tissues was also analyzed using the WGCNA method. Results. A total of 90 samples from 2 datasets were included, and 882 DEGs and 10 hub genes closely related to MS were extracted. Functional enrichment analysis suggested the role of immune response in MS. Besides, CIBERSORTX algorithm results showed that MS brain tissues contained a variety of infiltrating immune cells. Correlation analysis suggested that the hub genes were highly relevant to chronic active white matter lesions. Certain hub genes played a role in the activation of immune cells such as macrophages and natural killer cells. Conclusions. Our study shall provide guidance for the further study of the genetic basis and immune infiltration mechanism of MS. [ABSTRACT FROM AUTHOR]

Anti- N -methyl-d-aspartate receptor encephalitis (NMDARe), a common autoimmune encephalitis, can be accompanied by demyelinating disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). To compare the clinical characteristics of patients with different overlapping syndromes, we searched the PubMed database and performed a systematic review. Of the 79 patients with overlapping syndromes, 15 had MS, 18 had aquaporin-4-antibody-positive NMOSD (AQP4-Ab-positive NMOSD), and 46 had MOGAD. Compared with classical NMDARe, overlapping syndromes showed atypical symptoms, such as limb weakness, sensory disturbance, and visual impairments in addition to the main symptoms of NMDARe and a lower ratio of ovarian teratoma. Patients with MOGAD overlap were the youngest, while patients with MS and AQP4-Ab-positive NMOSD overlap tended to be older than patients with classical NMDARe. A majority of patients with NMDARe who overlapped with MS or AQP4-Ab-positive NMOSD were female, but this was not the case for patients overlapped with MOGAD. When NMDARe and demyelinating diseases occurred sequentially, the interval was the longest in patients with NMDARe overlapped with MS. A favorable outcome was observed in patients overlapping with MOGAD, but no robust comparison can be drawn with the patients overlapping with AQP4-Ab-positive NMOSD and MS regarding the small number of available data. The long-term prognosis of overlapping syndromes needs further investigation. [ABSTRACT FROM AUTHOR]

The development of inhibitors of anti-apoptotic proteins, such as Mcl-1, is currently a very active area in the field of cancer research. One of the very first reported inhibitors of Mcl-1 was the MIM1 molecule, but we have recently demonstrated that the structure of this compound had to be revised from 2 to the derivative 1 (FJ-809). In this paper we first develop a strategy to unambiguously prepare molecules such as 1 with a thiazol-3(2H)-yl)imino core, instead of the [2(3H)-thiazolylidene]hydrazine previously found in MIM1 (2). Next a series of biological studies have been performed on 1, using IGROV1-R10 ovarian cancer cells as models, and they have been complemented by fluorescence polarisation assays. These studies demonstrated that the new compound FJ-809 (1) was devoid of any significant activity on Mcl-1, in contrast to 2. Then molecular modelling and molecular dynamics studies have been performed in order to elucidate the differences between FJ-809 and MIM1 in their interaction with the Mcl-1 protein. [ABSTRACT FROM AUTHOR]