A mild and greener protocol was developed to synthesize substituted quinazolinones and dihydroquinazolinones via deep eutectic solvent (DES) mediated cyclization with a series of aliphatic, aromatic, ...and heteroaromatic aldehydes in good to excellent yields. This greener strategy was further utilised to synthesize various quinazolinone natural products and drugs.
The microtubule-associated protein tau (MAPT, tau) forms neurotoxic aggregates that promote cognitive deficits in tauopathies, the most common of which is Alzheimer’s disease (AD). The 90-kDa heat ...shock protein (Hsp90) chaperone system affects the accumulation of these toxic tau species, which can be modulated with Hsp90 inhibitors. However, many Hsp90 inhibitors are not blood–brain barrier-permeable, and several present associated toxicities. Here, we find that the cochaperone, activator of Hsp90 ATPase homolog 1 (Aha1), dramatically increased the production of aggregated tau. Treatment with an Aha1 inhibitor, KU-177, dramatically reduced the accumulation of insoluble tau. Aha1 colocalized with tau pathology in human brain tissue, and this association positively correlated with AD progression. Aha1 overexpression in the rTg4510 tau transgenic mouse model promoted insoluble and oligomeric tau accumulation leading to a physiological deficit in cognitive function. Overall, these data demonstrate that Aha1 contributes to tau fibril formation and neurotoxicity through Hsp90. This suggests that therapeutics targeting Aha1 may reduce toxic tau oligomers and slow or prevent neurodegenerative disease progression.
A novel route to synthesize the biologically active benzimidazolopyrazine core is outlined. The reaction proceeds via tandem benzimidazole formation/annulations of indole, pyrrole and aliphatic ...δ-alkynyl aldehydes in the presence of copper salts and green solvents with moderate to good yields.
In the present investigation, machining performance of Ti6Al4V is studied under dry environment, pressurized air supply and distilled water based Minimum Quantity Lubrication (MQL). Machining ...(turning) performance is assessed in purview of cutting force (tangential component) magnitude, tool-tip temperature, width of tool flank wear progression, morphology of evolved chips and severity of vibrations at varied cutting speeds as well as cooling media. Characteristic features of spatial temperature distribution profile (at the vicinity of tool-tip) as influenced by varied cooling media are studied with the help of thermographs of the cutting zone. Mechanisms of cutting tool wear are studied as well. It is experienced that amongst three cutting environments tested, application of water-MQL is beneficial for machining of Ti6Al4V at low cutting speed. Severity of vibrations gets 50.39% reduced during machining under water-MQL than dry condition. Consequently, as compared to dry machining, water-MQL causes 79% reduced tool flank wear and 82% reduced crater wear at low cutting speed. Under water-MQL, reduced tool-tip temperature (66% reduced than dry condition) suppresses severity of tool wear. In comparison with high cutting speed, performance of water-MQL is found much better at low cutting speed. ‘
Unaffected zones
’ are identified at the worn-out tool rake face under water-MQL. High amplitude of vibration (maximum absolute mean value) causes low chip-segmentation ratio. On the contrary, chip reduction coefficient gets truncated with decrement in vibration amplitude. Vibration amplitude has positive influence on degree of chip-curl.
Introduction: Colorectal Carcinoma (CRC) is a multi-step process that occurs due to the accumulation of several genetic alterations. The most important alterations are related to the rat sarcoma ...viral oncogene homolog (RAS) and Rapidly Accelerated Fibrosarcoma (RAF), which have been implicated as key intermediates in the RAS-mediated signalling cascade. However, the levels of Kristen Rat Sarcoma Virus (KRAS) and v-raf Murine Sarcoma Viral Oncogene Homolog (BRAF) protein expression and their prognostic evaluation in CRC patients remain unknown. Aim: To investigate the immunohistochemical expression of KRAS and BRAF proteins in CRC. Materials and Methods: The present institutional-based cross-sectional observational study was conducted in a tertiary care centre in West Bengal, specifically in the Department of Pathology in collaboration with the Department of Surgery at Murshidabad Medical College and Hospital, Berhampore, West Bengal, India. A total of 26 CRC cases were enrolled in the present study, received over a period of one and a half years from January 2021 to June 2022. The parameters studied included demographic and clinical information of the patients, histopathological findings, pathological grade and stage of carcinoma, and immunohistochemical findings for KRAS and BRAF. For statistical analysis, data were entered into Microsoft (MS) Excel. Descriptive measures such as mean±Standard Deviation (SD), range, and percentage were used. The Chi-square test was used to determine the significance of the study. Results: A total of biopsy-proven CRC specimens were studied, consisting of 17 male patients (65.38%) with a male-to-female ratio of 1.9:1. The most common age group involved was 51-60 years (38%). Conventional adenocarcinoma accounted for the majority of cases (85%), with mucinous carcinoma comprising the remaining 15%. Among the 26 cases, 15 (58%) showed KRAS positivity, which was significantly associated with tumour grade and stage. Most of the cases were BRAF-negative. Out of the 21 cases where either KRAS or BRAF or both were positive, 20 cases showed high T stage (T3 and T4) and/or metastatic lesions (p-value 0.001). All four cases that were negative for both BRAF and KRAS belonged to the low T stage. Conclusion: A significant correlation was observed between the expression of KRAS and high-grade, high pathological Tumour, Node, Metastasis (TNM) T stage (T3 and T4) CRC. Therefore, KRAS Immunohistochemistry (IHC) biomarkers should be included in the standard diagnostic protocol for colorectal cancer, as they help identify KRAS-positive CRC cases that are resistant to targeted immunotherapy.
Introduction: Breast carcinoma is the most common malignant tumour and is the leading cause of carcinoma death in women. Assessing Vascular Endothelial Growth Factor-C (VEGF-C) is important because ...the expression of VEGF-C is one of the factors determining the aggressiveness of breast carcinoma. Aim: To evaluate the expression of VEGF-C in breast carcinoma and its association with HER2/neu and Oestrogen Receptors (ER)/Progesterone Receptors (PR). Materials and Methods: A cross-sectional observational study was carried out in Department of Pathology of a tertiary care center of Burdwan Medical College and Hospital, West Bengal from 1st January 2018 to 30th June 2019. Patients attending Outpatient Department (OPD) and were diagnosed clinically as having breast cancer, operated upon, and subsequently sent for Histopathological Examination (HPE) in Pathology. The samples which were positive for breast carcinoma by histopathology were further studied with Immunohistochemical (IHC) markers and the positivity of IHC expression was reported using standard procedure and scoring pattern. The assosciation of VEGF-C expression with respect to histological type, grade, and stage of cancer as well as the HER2/neu and ER/PR status was studied. Using the Statistical Package for Social Sciences (SPSS) version 18.0, Chi-square was applied for the significance of p-value and the significance level was considered at a p-value <0.05. Results: This study consisted of 44 cases of malignant breast lesions and of which 27 cases were associated with axillary lymph nodes. After IHC staining, 25 (56.82%) were VEGF-C positive and the rest 19 (43.18%) were VEGF-C negative. There was a significant association between VEGF-C and histologic grades of breast carcinoma. VEGF-C expression was significantly associated with lymph node metastasis and with HER2/neu. VEGF-C seems to be significantly associated with ER status of breast carcinoma and was not associated with the PR status of breast carcinoma. Conclusion: Assessment of VEGF-C is recommended because expression of VEGF-C is one of the factors determining the aggressiveness of breast carcinoma. If VEGF-C is positive in node- negative breast carcinoma, then it may help in targeted therapy of breast carcinoma before lymphatic metastasis develops.
Present work investigates the effect on heat conduction due to the intrusion in a homogeneous bulk and proposes models to detect its position from the temperature distribution on the surface. Finite ...volume-based, automated numerical simulations are performed for obtaining the temperature history along/across the bulk surface having different positions of the intrusion. Two approaches are developed to predict the intrusion-position from temperature data. In approach 1, a multi-layer feed-forward neural network (NN) with back-propagation (BP) algorithm is used, whereas the NN parameters are determined through a thorough sequential parametric study. In approach 2, again a NN with BP algorithm is used, but a global evolutionary optimizer, namely genetic algorithm (GA) is employed to optimize the NN parameters. NN with BP algorithm and GA are indigenously developed using 'C' programming language in 'linux' operating system. NN and GA are indigenously combined in a common monolithic platform using some specially designed system commands so that data transfer take place seamlessly in a fully automated way. The performances of the developed approaches are tested and validated in several ways. After comparison, approach 2 is found to have higher prediction capability.
Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model ...identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylgliotoxin and a derivative of hyalodendrin. The abundance of fungal secondary metabolites indentified in this screen prompted further studies investigating the interaction between opportunistic pathogenic fungi and Aspergillus fumigatus, because of the ability of the fungus to produce a plethora of secondary metabolites, including the well studied ETP gliotoxin. We found that cell-free supernatant of A. fumigatus was able to inhibit the growth of Candida albicans through the production of a secreted product. Comparative studies between a wild-type and an A. fumigatus ΔgliP strain unable to synthesize gliotoxin demonstrate that this secondary metabolite is the major factor responsible for the inhibition. Although toxic to organisms, gliotoxin conferred an increase in survival to C. albicans-infected C. elegans in a dose dependent manner. As A. fumigatus produces gliotoxin in vivo, we propose that in addition to being a virulence factor, gliotoxin may also provide an advantage to A. fumigatus when infecting a host that harbors other opportunistic fungi.
Some host-guest complexes of cucurbit
n
uril (CB
n
) host molecules act as supramolecular amphiphiles (SAs), which hierarchically self-assemble into various nanomaterials such as vesicles, micelles, ...nanorods, and nanosheets in water. The structures and functions of the nanomaterials can be controlled by supramolecular engineering of the host-guest complexes. In addition, functionalization at the periphery of CB6 and CB7 generates CB
n
-based molecular amphiphiles (MAs) that can also self-assemble into vesicles or micelle-like nanoparticles in water. Taking advantage of the molecular cavities of CBs and their strong guest recognition properties, the surface of the self-assembled nanomaterials can be easily decorated with various functional tags in a non-covalent manner. In this feature article, the two types (SAs and MAs) of CB-based amphiphiles, their self-assemblies and their applications for nanotherapeutics and theranostics are presented with future perspectives.
In this feature article, the two types (molecular amphiphile and supramolecular amphiphile) of CB-based amphiphiles, their self-assemblies and their applications for useful nanotherapeutics and theranostics are presented with future perspectives.
Phentermine is a sympathomimetic amine used for the short-term weight loss that has been associated with ischemic and hemorrhagic strokes in adults. The effects of this medication on a developing ...fetus are not well studied. We present the case of a woman who was taking phentermine during the first two trimesters of pregnancy and subsequently delivered a child with bilateral porencephalic cysts likely due to a prenatal stroke.
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![Cucurbit[]uril-based amphip...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1359-7345/small "Cucurbit[]uril-based amphiphiles that self-assemble into functional nanomaterials for therapeutics")
