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A novel series of imidazo[2,1-b]thiazole-sulfonyl piperazine conjugates (9aa-ee) has been synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory potency against four isoforms: The cytosolic isozyme hCA I, II and trans-membrane tumor-associated isoform hCA IX and hCA XII, taking acetazolamide (AAZ) as standard drug, using a stopped flow CO2 hydrase assay. The results revealed that most of the compounds showed selective activity against hCA II whereas none of them were active against hCA I, IX, XII (Ki > 100 µM). The physiologically dominant cytosolic isoform hCA II was inhibited by these molecules with inhibition constants in the range of 57.7–98.2 µM. This new derivative, thus, selectively inhibits hCA II over the hCA I, IX, XII isoforms, which may be used for further understanding the physiological roles of some of these isoforms in various pathologies.

Objective:Members of the Apiaceae family have many biological and pharmacological effects like anticancer, antidiabetic, antioxidant, anti-inflammatory, anti-hypertensive, anticoagulant, antimicrobial, and anticholinesterase. Also, some of them are consumed as vegetables, pickles, and spices. Carbonic anhydrase has a remarkable role in diseases like osteoporosis, glaucoma, edema, cancer, epilepsy, and obesity. The inhibition effects of methanol extracts and subextracts (n-hexane, dichloromethane, ethyl acetate, n-butanol, and aqueous residue) of Leiotulus dasyanthus and Ferulago pauciradiata roots on carbonic anhydrase I and II isoenzymes were investigated in this research.Methods:Leiotulus dasyanthus and Ferulago pauciradiata were collected in 2017 from Erzurum and in 2013 from Nevşehir (Turkey), respectively. The roots of L. dasyanthus and F. pauciradiata were macerated with methanol, dispersed with methanol: distilled water (1:9), and fractionated with n-hexane, dichloromethane, ethyl acetate, and n-butanol, in turn. The hCA I and II isoenzymes were isolated from erythrocytes of fresh human blood via Sepharose-4BL- Tyrosine-sulfanilamide affinity chromatography. The analysis of hCA I and II isoenzymes was actualized by the Verpoorte method.Results:The hCA I and II were influentially inhibited by the dichloromethane and ethyl acetate sub-extracts of F. pauciradiata root with IC50 values of 1.694 μg/mL towards hCA I and 1.677 μg/ mL towards hCA II, respectively. Whereas dichloromethane subextract and methanol extract of L. dasyanthus root inhibited hCA I and II isoenzymes with IC50 values of 1.828 μg/mL towards hCA I and 1.852 μg/mL towards hCA II, respectively.Conclusion:The hCA I and II were influentially inhibited by the dichloromethane and ethyl acetate sub-extracts of Ferulago pauciradiata root

Eight new bisbenzimidazolium halides were prepared from alkyl halides and 4,4′-bis[(benzimidazol-1-yl)methyl]-1,1′-biphenyl.The structures of the benzimidazole salts were characterized using elemental analysis techniques as well as 1 H, 13 C NMR, and FT-IR spectroscopic methods. The inhibitory effects of the benzimidazole derivatives were measured against human carbonic anhydrase I (hCA I), human carbonic anhydrase II (hCA II), and acetylcholinesterase (AChE) enzymes. All benzimidazolium halides exhibited significant enzyme inhibitory properties. They showed highly potent inhibitory effect on AChE and hCAs ( K i values are in the range of 15.7 ± 0.8 to 49.7 ± 10.1 nM, 14.6 ± 1.5 to 70.7 ± 2.7 nM, and 17.4 ± 2.8 to 38 ± 10 nM for AChE, hCA I, and hCA II, respectively). The binding orientation of the synthesized bisbenzimidazolium halides was evaluated by molecular docking studies, reflecting the importance of the p -methylbenzyl, m -methylbenzyl, p -nitrophenethyl, and 3-(1,3-dioxoisoindolin-2-yl)methyl) groups in protein–ligand interaction. The docking results support the K i values of the respective compounds in this study. The structure–activity relationships against the various targets are clearly shown in three dimensions at the atomic level by their interactions with the mentioned enzymes. Graphical abstract

Inter- and intra-subject variability pose a major challenge to decoding human brain activity in brain-computer interfaces (BCIs) based on non-invasive electroencephalogram (EEG). Conventionally, a time-consuming and laborious training procedure is performed on each new user to collect sufficient individualized data, hindering the applications of BCIs on monitoring brain states (e.g. drowsiness) in real-world settings. This study proposes applying hierarchical clustering to assess the inter- and intra-subject variability within a large-scale dataset of EEG collected in a simulated driving task, and validates the feasibility of transferring EEG-based drowsiness-detection models across subjects. A subject-transfer framework is thus developed for detecting drowsiness based on a large-scale model pool from other subjects and a small amount of alert baseline calibration data from a new user. The model pool ensures the availability of positive model transferring, whereas the alert baseline data serve as a selector of decoding models in the pool. Compared with the conventional within-subject approach, the proposed framework remarkably reduced the required calibration time for a new user by 90% (18.00 min–1.72 ± 0.36 min) without compromising performance (p = 0.0910) when sufficient existing data are available. These findings suggest a practical pathway toward plug-and-play drowsiness detection and can ignite numerous real-world BCI applications. •A novel subject-transfer framework for reducing calibration time in brain state decoding.•Feasibility of cross-subject model transferring inferred from hierarchical clustering.•Robust decoding performance supported by large-scale existing data.•Significant decrease in calibration time using baseline brain activity.

In this study, the aroma profile of 10 single origin Arabica coffees originating from eight different growing locations, from Central America to Indonesia, was analyzed using Headspace SPME-GC-MS as the analytical method. Their roasting was performed under temperature–time conditions, customized for each sample to reach specific sensory brew characteristics in an attempt to underline the customization of roast profiles and implementation of separate roastings followed by subsequent blending as a means to tailor cup quality. A total of 138 volatile compounds were identified in all coffee samples, mainly furan (~24–41%) and pyrazine (~25–39%) derivatives, many of which are recognized as coffee key odorants, while the main formation mechanism was the Maillard reaction. Volatile compounds’ composition data were also chemometrically processed using the HCA Heatmap, PCA and HCA aiming to explore if they meet the expected aroma quality attributes and if they can be an indicator of coffee origin. The desired brew characteristics of the samples were satisfactorily captured from the volatile compounds formed, contributing to the aroma potential of each sample. Furthermore, the volatile compounds presented a strong variation with the applied roasting conditions, meaning lighter roasted samples were efficiently differentiated from darker roasted samples, while roasting degree exceeded the geographical origin of the coffee. The coffee samples were distinguished into two groups, with the first two PCs accounting for 73.66% of the total variation, attributed mainly to the presence of higher quantities of furans and pyrazines, as well as to other chemical classes (e.g., dihydrofuranone and phenol derivatives), while HCA confirmed the above results rendering roasting conditions as the underlying criterion for differentiation.

Syzygium cumini L. is an evergreen tree belonging to family Myrtaceae, employed for different traditional uses like diabetes, inflammation, and fever. The current study aimed to compare the chemical compositions of the essential oils (EOs) isolated from different organs of Syzygium cumini (leaves (Scl), fruits (Scf), seeds (Scs), and bark (Scb)) using a GC/MS analysis. Also, a chemometric analysis was applied to explore the main similarities and differences among different organs using a Principal Component Analysis (PCA) and a hierarchal cluster analysis (HCA). Furthermore, in vitro antiaging activities were investigated via anti-collagenase, anti-elastase, and anti-hyaluronidase assays. The GC-MS analysis revealed 82 compounds representing 92.13%, 99.42%, 100%, and 92.97% in Scl, Scf, Scs, and Scb, respectively. The predominant components were α-pinene, β-pinene, (E)-β-caryophyllene, α-caryophyllene, caryophyllene oxide, and α-humulene epoxide II with variable percentages. All EOs were positioned on positive PC1, except for Scs, which was positioned on the negative side in a separate quadrant. The HCA dendrogram displayed the closeness of Scl and Scb, which was not clearly recognized in the PCA score plot. Moreover, the Scs oils were totally discriminated from other parts. The Scl and Scs oils showed superior anti-collagenase, anti-elastase, and anti-hyaluronidase activities. Thus, S. cumini oils should be considered for cosmetic preparations to retard skin aging manifestations.

Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L-FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard.

The present study aimed to assess the impact of anthropogenic stressors on the physico-chemical characteristics and water quality of the River Ganga employing a GIS-based approach in the middle Gangetic Plain at Patna, India. After the survey, sand mining, bridge construction, and disposal of untreated domestic and sewage wastes were selected as major anthropogenic stressors. A total of 48 samples were collected in pre-monsoon and post-monsoon seasons of 2022 and were analyzed for 16 physico-chemical parameters, namely water temperature (WT), pH, electrical conductivity (EC), total dissolved solids (TDS), turbidity, dissolved oxygen (DO), biological oxygen demand (BOD), total hardness (TH), Ca2+, Mg2+, Na+, K+, Cl- and SO42− ions, following standard protocols. The WQI was calculated using the Weighted Arithmetic Water Quality Index (WAQWI) method and spatial maps were created using ArcGIS software. The result revealed significant seasonal variation in several physico- chemical parameters except for Ca2+, K+ and TA (p > 0.05). ANOVA revealed significant variation for BOD and COD at Ghagha and Triveni, whereas for nitrate at Gai Ghat reference and impact sites, respectively. The Water Quality Index (WQI) revealed a deterioration in water quality by 60% in post-monsoon season. HCA revealed that the WQI was mostly governed by TDS, TH, TA, and EC.

Stroke is the main cause for acquired disabilities. Pharmaceutical or mechanical removal of the thrombus is the cornerstone of stroke treatment but can only be administered to a subset of patients and within a narrow time window. Novel treatment options are therefore required. Here we induced stroke by permanent occlusion of the distal medial cerebral artery of wild-type mice and knockout mice for the lactate receptor hydroxycarboxylic acid receptor 1 (HCA1). At 24 h and 48 h after stroke induction, we injected L-lactate intraperitoneal. The resulting atrophy was measured in Nissl-stained brain sections, and capillary density and neurogenesis were measured after immunolabeling and confocal imaging. In wild-type mice, L-lactate treatment resulted in an HCA1-dependent reduction in the lesion volume accompanied by enhanced angiogenesis. In HCA1 knockout mice, on the other hand, there was no increase in angiogenesis and no reduction in lesion volume in response to L-lactate treatment. Nevertheless, the lesion volumes in HCA1 knockout mice—regardless of L-lactate treatment—were smaller than in control mice, indicating a multifactorial role of HCA1 in stroke. Our findings suggest that L-lactate administered 24 h and 48 h after stroke is protective in stroke. This represents a time window where no effective treatment options are currently available.

Interest in medicinal plants and fruits has increased in recent years due to people beginning to consume natural foods. This study aims to investigate the total phenolic flavonoid content, antioxidant activity, condensed tannin content, oil content, and fatty acid compositions of five local breeds of Berberis spp. from Bayburt, Turkey, and their antioxidant and antimicrobial activities. The fatty acid composition of samples was performed with gas chromatography-mass spectrometry (GC-MS), and the total fatty acid content of samples was between 6.12% and 8.60%. The main fatty acids in Berberis spp. samples were α-linolenic acid (32.85–37.88%) and linoleic acid (30.98–34.28%) followed by oleic acid (12.85–19.56%). Two antioxidant assays produced similar results, demonstrating that extracts of wild B. vulgaris L. had the highest ferric reducing antioxidant power (FRAP) (621.02 μmol FeSO4.7H2O/g) and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (0.10 SC50 mg/mL) values. According to principal component analysis (PCA), four components were determined. In addition, two main groups were determined according to hierarchical cluster analysis (HCA), and wild and culture of B. vulgaris L. were in different subgroups. This is the first original report about the fatty acid composition and oil content of Berberis spp. grown in Bayburt, Turkey. The obtained results indicate that B. integerrima Bunge and B. vulgaris, which have especially remarkable fatty acid content, antioxidant, and antimicrobial activity, could be potential sources for these properties in different areas of use.