Morin Inhibits Proliferation of SW480 Colorectal Cancer Cells by Inducing Apoptosis Mediated by Reactive Oxygen Species Formation and Uncoupling of Warburg Effect

The study under investigation focuses on in vitro antiproliferative efficacy of the flavonoid morin and the mechanisms by which it inhibits the growth of colon cancer using SW480 colon cancer cells with emphasis on Warburg effect. It was found that the cell proliferation was significantly inhibited by morin in a dose and time dependent manner. Morin induced apoptosis that was correlated with increased levels of reactive oxygen species formation and loss of mitochondrial membrane potential of the cells. In addition, an increase in cleaved PARP, cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and Bax as well as a decrease in Bcl 2 was observed, indicating morin is inducing both intrinsic as well as extrinsic pathway of apoptosis. This was further confirmed by using downstream caspase 3 inhibitor which indicated that caspase 3 inhibition reduces morin induced cell death. Moreover, the impact of morin on over all energy status when determined in terms of total cellular ATP level showed a decline with low level of glucose uptake and Glut1 expression. The results indicate that morin exerts antiproliferative activity by inducing apoptosis and by reducing Warburg effect in the evaluated cell lines and provide preliminary evidence for its anticancer activity

Single molecule force measurements of perlecan/HSPG2: A key component of the osteocyte pericellular matrix

Perlecan/HSPG2, a large, monomeric heparan sulfate proteoglycan (HSPG), is a key component of the lacunar canalicular system (LCS) of cortical bone, where it is part of the mechanosensing pericellular matrix (PCM) surrounding the osteocytic processes and serves as a tethering element that connects the osteocyte cell body to the bone matrix. Within the pericellular space surrounding the osteocyte cell body, perlecan can experience physiological fluid flow drag force and in that capacity function as a sensor to relay external stimuli to the osteocyte cell membrane. We previously showed that a reduction in perlecan secretion alters the PCM fiber composition and interferes with bone's response to a mechanical loading in vivo. To test our hypothesis that perlecan core protein can sustain tensile forces without unfolding under physiological loading conditions, atomic force microscopy (AFM) was used to capture images of perlecan monomers at nanoscale resolution and to perform single molecule force measurement (SMFMs). We found that the core protein of purified full-length human perlecan is of suitable size to span the pericellular space of the LCS, with a measured end-to-end length of 170 ± 20 nm and a diameter of 2–4 nm. Force pulling revealed a strong protein core that can withstand over 100 pN of tension well over the drag forces that are estimated to be exerted on the individual osteocyte tethers. Data fitting with an extensible worm-like chain model showed that the perlecan protein core has a mean elastic constant of 890 pN and a corresponding Young's modulus of 71 MPa. We conclude that perlecan has physical properties that would allow it to act as a strong but elastic tether in the LCS

Time Based Self-Destruction System for Secure Data Sharing in Cloud

Abstract -Cloud computing is often touted as the future of business and enterprise technology where people are subjected to post their personal information like passwords, account number and different vital data. The shared data in a dynamic environment remains in cloud for indefinite period of time and the sensitive information stored may be misused by a miscreant or even by service providers. As a result sensitive and confidential data is at risk from outsider and insider attacks. Thus security and privacy becomes a major issue. In our proposed system, a self-destructing module can be used to automatically clear the data and their copies after a user-specified time. After time expiration, the multicloud feature enables the user to retain the shared data from the user cloud while it is deleted from the shared cloud. By using AES-256 and triple DES algorithm such a system can be developed and hence it reduces the time taken to upload and download file as compared to the native system

Beyond the marrow:insights from comprehensive next-generation sequencing of extramedullary multiple myeloma tumors

Extramedullary multiple myeloma (EMM) is an aggressive form of multiple myeloma (MM). This study represents the most comprehensive next-generation sequencing analysis of EMM tumors (N = 14) to date, uncovering key molecular features and describing the tumor microenvironment. We observed the co-occurrence of 1q21 gain/amplification and MAPK pathway mutations in 79% of EMM samples, suggesting that these are crucial mutational events in EMM development. We also demonstrated that patients with mutated KRAS and 1q21 gain/amplification at the time of diagnosis have a significantly higher risk of EMM development (HR = 2.4, p = 0.011) using data from a large CoMMpass dataset. We identified downregulation of CXCR4 and enhanced cell proliferation, along with reduced expression of therapeutic targets (CD38, SLAMF7, GPRC5D, FCRH5), potentially explaining diminished efficacy of immunotherapy. Conversely, we identified significantly upregulated EZH2 and CD70 as potential future therapeutic options. For the first time, we report on the tumor microenvironment of EMM, revealing CD8+ T cells and NK cells as predominant immune effector cells using single-cell sequencing. Finally, this is the first longitudinal study in EMM revealing the molecular changes from the time of diagnosis to EMM relapse.</p

Automated Speckle Interferometry of Known Binaries

Astronomers have been measuring the separations and position angles between the two components of binary stars since William Herschel began his observations in 1781. In 1970, Anton Labeyrie pioneered a method, speckle interferometry, that overcomes the usual resolution limits induced by atmospheric turbulence by taking hundreds or thousands of short exposures and reducing them in Fourier space. Our 2022 automation of speckle interferometry allowed us to use a fully robotic 1.0-meter PlaneWave Instruments telescope, located at the El Sauce Observatory in the Atacama Desert of Chile, to obtain observations of many known binaries with established orbits. The long-term objective of these observations is to establish the precision, accuracy, and limitations of this telescope's automated speckle interferometry measurements. This paper provides an early overview of the Known Binaries Project and provide example results on a small-separation (0.27") binary, WDS 12274-2843 B 228

Surface Functionalized MXenes for Wastewater Treatment-A Comprehensive Review.

Funder: European Regional Development Fund; Id: http://dx.doi.org/10.13039/501100008530Over 80% of wastewater worldwide is released into the environment without proper treatment. Whilst environmental pollution continues to intensify due to the increase in the number of polluting industries, conventional techniques employed to clean the environment are poorly effective and are expensive. MXenes are a new class of 2D materials that have received a lot of attention for an extensive range of applications due to their tuneable interlayer spacing and tailorable surface chemistry. Several MXene-based nanomaterials with remarkable properties have been proposed, synthesized, and used in environmental remediation applications. In this work, a comprehensive review of the state-of-the-art research progress on the promising potential of surface functionalized MXenes as photocatalysts, adsorbents, and membranes for wastewater treatment is presented. The sources, composition, and effects of wastewater on human health and the environment are displayed. Furthermore, the synthesis, surface functionalization, and characterization techniques of merit used in the study of MXenes are discussed, detailing the effects of a range of factors (e.g., PH, temperature, precursor, etc.) on the synthesis, surface functionalization, and performance of the resulting MXenes. Finally, the limits of MXenes and MXene-based materials as well as their potential future research directions, especially for wastewater treatment applications are highlighted

Surface Functionalized MXenes for Wastewater Treatment-A Comprehensive Review.

Funder: European Regional Development Fund; Id: http://dx.doi.org/10.13039/501100008530Over 80% of wastewater worldwide is released into the environment without proper treatment. Whilst environmental pollution continues to intensify due to the increase in the number of polluting industries, conventional techniques employed to clean the environment are poorly effective and are expensive. MXenes are a new class of 2D materials that have received a lot of attention for an extensive range of applications due to their tuneable interlayer spacing and tailorable surface chemistry. Several MXene-based nanomaterials with remarkable properties have been proposed, synthesized, and used in environmental remediation applications. In this work, a comprehensive review of the state-of-the-art research progress on the promising potential of surface functionalized MXenes as photocatalysts, adsorbents, and membranes for wastewater treatment is presented. The sources, composition, and effects of wastewater on human health and the environment are displayed. Furthermore, the synthesis, surface functionalization, and characterization techniques of merit used in the study of MXenes are discussed, detailing the effects of a range of factors (e.g., PH, temperature, precursor, etc.) on the synthesis, surface functionalization, and performance of the resulting MXenes. Finally, the limits of MXenes and MXene-based materials as well as their potential future research directions, especially for wastewater treatment applications are highlighted

Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study

Background: The spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in hospitalised children and adolescents. Methods: We did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group. Paediatric neurologists were invited to notify any children and adolescents (age <18 years) admitted to hospital with neurological or psychiatric disorders in whom they considered SARS-CoV-2 infection to be relevant to the presentation. Patients were excluded if they did not have a neurological consultation or neurological investigations or both, or did not meet the definition for confirmed SARS-CoV-2 infection (a positive PCR of respiratory or spinal fluid samples, serology for anti-SARS-CoV-2 IgG, or both), or the Royal College of Paediatrics and Child Health criteria for paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Individuals were classified as having either a primary neurological disorder associated with COVID-19 (COVID-19 neurology group) or PIMS-TS with neurological features (PIMS-TS neurology group). The denominator of all hospitalised children and adolescents with COVID-19 was collated from National Health Service England data. Findings: Between April 2, 2020, and Feb 1, 2021, 52 cases were identified; in England, there were 51 cases among 1334 children and adolescents hospitalised with COVID-19, giving an estimated prevalence of 3·8 (95% CI 2·9–5·0) cases per 100 paediatric patients. 22 (42%) patients were female and 30 (58%) were male; the median age was 9 years (range 1–17). 36 (69%) patients were Black or Asian, 16 (31%) were White. 27 (52%) of 52 patients were classified into the COVID-19 neurology group and 25 (48%) were classified into the PIMS-TS neurology group. In the COVID-19 neurology group, diagnoses included status epilepticus (n=7), encephalitis (n=5), Guillain-Barré syndrome (n=5), acute demyelinating syndrome (n=3), chorea (n=2), psychosis (n=2), isolated encephalopathy (n=2), and transient ischaemic attack (n=1). The PIMS-TS neurology group more often had multiple features, which included encephalopathy (n=22 [88%]), peripheral nervous system involvement (n=10 [40%]), behavioural change (n=9 [36%]), and hallucinations at presentation (n=6 [24%]). Recognised neuroimmune disorders were more common in the COVID-19 neurology group than in the PIMS-TS neurology group (13 [48%] of 27 patients vs 1 [<1%] of 25 patients, p=0·0003). Compared with the COVID-19 neurology group, more patients in the PIMS-TS neurology group were admitted to intensive care (20 [80%] of 25 patients vs six [22%] of 27 patients, p=0·0001) and received immunomodulatory treatment (22 [88%] patients vs 12 [44%] patients, p=0·045). 17 (33%) patients (10 [37%] in the COVID-19 neurology group and 7 [28%] in the PIMS-TS neurology group) were discharged with disability; one (2%) died (who had stroke, in the PIMS-TS neurology group). Interpretation: This study identified key differences between those with a primary neurological disorder versus those with PIMS-TS. Compared with patients with a primary neurological disorder, more patients with PIMS-TS needed intensive care, but outcomes were similar overall. Further studies should investigate underlying mechanisms for neurological involvement in COVID-19 and the longer-term outcomes. Funding: UK Research and Innovation, Medical Research Council, Wellcome Trust, National Institute for Health Research

Economical synthesis of silver nanoparticles using leaf extract of Acalypha hispida and its application in the detection of Mn(II) ions

This study was focused on the synthesis of silver nanoparticles using Acalypha hispida leaf extract and the characterization of the particles using UV–Vis spectroscopy, XRD, FT-IR, and TEM. The results showed the formation of silver nanoparticles, crystalline in nature, with an average size of 20–50 nm. The leaf extract components were analyzed with GC–MS and exhibited a high content of Phytol (40.52%), n-Hexadecanoic acid (9.67%), 1,2,3-Benzenetriol (7.04%), α-d-Mannofuranoside methyl (6.22%), and d-Allose (4.45%). The optimization and statistical investigation of reaction parameters were studied and maximum yield with suitable properties of silver nanoparticles was obtained at leaf extract volume (0.5 mL), the concentration of silver nitrate (1.75 mM), and reaction temperature (50 °C). The method of detecting Mn2+ ions using the colloidal silver nanoparticles was discussed. The minimum and maximum detection limit were found to be 50 and 200 µM of Mn(II) ions, respectively. Thus, the obtained results encourage the use of economical synthesis of silver nanoparticles in the development of nanosensors to detect the pollutants present in industrial effluents