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This study utilized faradaic and non-faradaic electrochemical impedance spectroscopy to detect alpha synuclein amyloid fibrils on gold interdigitated tetraelectrodes (AuIDTE), providing valuable insights into electrochemical reactions for clinical use. AuIDE was purchased, modified with zinc oxide for increased hydrophobicity. Functionalization was conducted with hexacyanidoferrate and carbonyldiimidazole. Faradaic electrochemical impedance spectroscopy has been extensively explored in clinical diagnostics and biomedical research, providing information on the performance and stability of electrochemical biosensors. This understanding can help develop more sensitive, selective, and reliable biosensing platforms for the detection of clinically relevant analytes like biomarkers, proteins, and nucleic acids. Non-faradaic electrochemical impedance spectroscopy measures the interfacial capacitance at the electrode-electrolyte interface, eliminating the need for redox-active species and simplifying experimental setups. It has practical implications in clinical settings, like real-time detection and monitoring of biomolecules and biomarkers by tracking changes in interfacial capacitance. The limit of detection (LOD) for normal alpha synuclein in faradaic mode is 2.39-fM, The LOD for aggregated alpha synuclein detection is 1.82-fM. The LOD for non-faradaic detection of normal alpha synuclein is 2.22-fM, and the LOD for nonfaradaic detection of aggregated alpha synuclein is 2.40-fM. The proposed EIS-based AuIDTEs sensor detects alpha synuclein amyloid fibrils and it is highly sensitive., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polyalthia longifolia is well-known for its abundance of polyphenol content and traditional medicinal uses. Previous research has demonstrated that the methanolic extract of P. longifolia leaves (PLME, 1 mg/mL) possesses anti-aging properties in Saccharomyces cerevisiae BY611 yeast cells. Building on these findings, this study delves deeper into the potential antiaging mechanism of PLME, by analyzing the transcriptional responses of BY611 cells treated with PLME using RNA-sequencing (RNA-seq) technology. The RNA-seq analysis results identified 1691 significantly (padj < 0.05) differentially expressed genes, with 947 upregulated and 744 downregulated genes. Notably, the expression of three important aging-related genes, SIR2, SOD1, and SOD2, showed a significant difference following PLME treatment. The subsequent integration of these targeted genes with GO and KEGG pathway analysis revealed the multifaceted nature of PLME's anti-aging effects in BY611 yeast cells. Enriched GO and KEGG analysis showed that PLME treatment promotes the upregulation of SIR2, SOD1, and SOD2 genes, leading to a boosted cellular antioxidant defense system, reduced oxidative stress, regulated cell metabolism, and maintain genome stability. These collectively increased longevities in PLME-treated BY611 yeast cells and indicate the potential anti-aging action of PLME through the modulation of SIR2 and SOD genes. The present study provided novel insights into the roles of SIR2, SOD1, and SOD2 genes in the anti-aging effects of PLME treatment, offering promising interventions for promoting healthy aging., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Irrespective of medical technology improvements, cancer ranks among the leading causes of mortality worldwide. Although numerous cures and treatments exist, creating alternative cancer therapies with fewer adverse side effects is vital. Since ancient times, plant bioactive compounds have already been used as a remedy to heal cancer. These plant bioactive compounds and their anticancer activity can also deregulate the microRNAs (miRNAs) in the cancerous cells. Therefore, the deregulation of miRNAs in cancer cells by plant bioactive compounds and the usage of the related miRNA could be a promising approach for cancer cure, mainly to prevent cancer and overcome chemotherapeutic side effect problems. Hence, this review highlights the function of plant bioactive compounds as an anticancer agent through the underlying mechanism that alters the miRNA expression in cancer cells, ultimately leading to apoptosis. Moreover, this review provides insight into using plant bioactive compounds -driven miRNAs as an anticancer agent to develop miRNA-based cancer gene therapy. They can be the potential resource for gene therapy and novel strategies targeting cancer therapeutics., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Maintaining the proteome is crucial to retaining cell functionality and response to multiple intrinsic and extrinsic stressors. Protein misfolding increased the endoplasmic reticulum (ER) stress and activated the adaptive unfolded protein response (UPR) to restore cell homeostasis. Apoptosis occurs when ER stress is prolonged or the adaptive response fails. In healthy young cells, the ratio of protein folding machinery to quantities of misfolded proteins is balanced under normal circumstances. However, the age-related deterioration of the complex systems for handling protein misfolding is accompanied by ageing-related disruption of protein homeostasis, which results in the build-up of misfolded and aggregated proteins. This ultimately results in decreased cell viability and forms the basis of common age-related diseases called protein misfolding diseases. Proteins or protein fragments convert from their ordinarily soluble forms to insoluble fibrils or plaques in many of these disorders, which build up in various organs such as the liver, brain, or spleen. Alzheimer's, Parkinson's, type II diabetes, and cancer are diseases in this group commonly manifest in later life. Thus, protein misfolding and its prevention by chaperones and different degradation paths are becoming understood from molecular perspectives. Proteodynamics information will likely affect future interventional techniques to combat cellular stress and support healthy ageing by avoiding and treating protein conformational disorders. This review provides an overview of the diverse proteostasis machinery, protein misfolding, and ER stress involvement, which activates the UPR sensors. Here, we will discuss the crosstalk between protein misfolding and ER stress and their role in developing age-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Background: MiR-484, implicated in various carcinomas, holds promise as a prognostic marker, yet its relevance to cervical cancer (CC) remains unclear. Our prior study demonstrated the Polyalthia longifolia downregulation of miR-484, inhibiting HeLa cells. This study investigates miR-484's potential as a biomarker and therapeutic target in CC through integrated bioinformatics and an in vitro analysis., Methods: MiR-484 levels were analyzed across cancers, including CC, from The Cancer Genome Atlas. The limma R package identified differentially expressed genes (DEGs) between high- and low-miR-484 CC cohorts. We assessed biological functions, tumor microenvironment (TME), immunotherapy, stemness, hypoxia, RNA methylation, and chemosensitivity differences. Prognostic genes relevant to miR-484 were identified through Cox regression and Kaplan-Meier analyses, and a prognostic model was captured via multivariate Cox regression. Single-cell RNA sequencing determined cell populations related to prognostic genes. qRT-PCR validated key genes, and the miR-484 effect on CC proliferation was assessed via an MTT assay., Results: MiR-484 was upregulated in most tumors, including CC, with DEGs enriched in skin development, PI3K signaling, and immune processes. High miR-484 expression correlated with specific immune cell infiltration, hypoxia, and drug sensitivity. Prognostic genes identified were predominantly epidermal and stratified patients with CC into risk groups, with the low-risk group showing enhanced survival and immunotherapeutic responses. qRT-PCR confirmed FGFR3 upregulation in CC cells, and an miR-484 mimic reversed the P. longifolia inhibitory effect on HeLa proliferation., Conclusion: MiR-484 plays a crucial role in the CC progression and prognosis, suggesting its potential as a biomarker for targeted therapy.

Polyalthia longifolia var. angustifolia Thw. (Annonaceae), is a famous traditional medicinal plant in Asia. Ample data specifies that the medicinal plant P. longifolia has anticancer activity; however, the detailed mechanisms of action still need to be well studied. Recent studies have revealed the cytotoxicity potential of P. longifolia leaf against HeLa cells. Therefore, the current study was conducted to examine the regulation of miRNAs in HeLa cancer cells treated with the standardized P. longifolia methanolic leaf extract (PLME). The regulation of miRNAs in HeLa cancer cells treated with the standardized PLME extract was studied through Illumina, Hi-Seq. 2000 platform of Next-Generation Sequencing (NGS) and various in silico bioinformatics tools. The PLME treatment regulated a subset of miRNAs in HeLa cells. Interestingly, the PLME treatment against HeLa cancer cells identified 10 upregulated and 43 downregulated ( p < 0.05) miRNAs associated with apoptosis induction. Gene ontology (GO) term analysis indicated that PLME induces cell death in HeLa cells by inducing the pro-apoptotic genes. Moreover, the downregulated oncomiRs modulated by PLME treatment in HeLa cells were identified, targeting apoptosis-related genes through gene ontology and pathway analysis. The LC-ESI-MS/MS analysis identified the presence of Vidarabine and Anandamide compounds that were previously reported to exhibit anticancer activity. The findings of this study obviously linked the cell cytotoxicity effect of PLME treatment against the HeLa cells with regulating various miRNAs expression related to apoptosis induction in the HeLa cells. PLME treatment induced apoptotic HeLa cell death mechanism by regulating multiple miRNAs. The identified miRNAs regulated by PLME may provide further insight into the mechanisms that play a critical role in cervical cancer, as well as novel ideas regarding gene therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vijayarathna, Oon, Al-Zahrani, Abualreesh, Chen, Kanwar, Sahreen, Ghazanfar, Adnan and Sasidharan.)

Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck cancer, ranked as the sixth most common cancer worldwide, accounting for approximately 300,000 new cases and 145,000 deaths annually. Early detection using biomarkers significantly increases the 5-year survival rate of OSCC by up to 80-90%. Clusterin (CLU), also known as apolipoprotein J, is a sulfated chaperonic glycoprotein expressed in all tissues and human fluids and has been reported to be a potential biomarker of OSCC. CLU has been implicated as playing a vital role in many biological processes such as apoptosis, cell cycle, etc. Abnormal CLU expression has been linked with the development and progression of cancers. Despite the fact that there are many studies that have reported the involvement of CLU and its isoforms in OSCC, the exact roles of CLU and its isoforms in OSCC carcinogenesis have not been fully explored. This article aims to provide a comprehensive review of the current understanding of CLU structure and genetics and its correlation with OSCC tumorigenesis to better understand potential diagnostic and prognostic biomarker development. The relationship between CLU and chemotherapy resistance in cancer will also be discussed to explore the therapeutic application of CLU and its isoforms in OSCC., Competing Interests: The authors declare no conflicts of interest.

Myocardial infarction (MI) is highly related to cardiac arrest leading to death and organ damage. Radiological techniques and electrocardiography have been used as preliminary tests to diagnose MI; however, these techniques are not sensitive enough for early-stage detection. A blood biomarker-based diagnosis is an immediate solution, and due to the high correlation of troponin with MI, it has been considered to be a gold-standard biomarker. In the present research, the cardiac biomarker troponin I (cTnI) was detected on an interdigitated electrode sensor with various surface interfaces. To detect cTnI, a capture aptamer-conjugated gold nanoparticle probe and detection antibody probe were utilized and compared through an alternating sandwich pattern. The surface metal oxide morphology of the developed sensor was proven by microscopic assessments. The limit of detection with the aptamer-gold-cTnI-antibody sandwich pattern was 100 aM, while it was 1 fM with antibody-gold-cTnI-aptamer, representing 10-fold differences. Further, the high performance of the sensor was confirmed by selective cTnI determination in serum, exhibiting superior nonfouling. These methods of determination provide options for generating novel assays for diagnosing MI., (© 2022 International Union of Biochemistry and Molecular Biology, Inc.)

Mycoplasma pneumoniae is a highly infectious bacterium and the major cause of pneumonia especially in school-going children. Mycoplasma pneumoniae affects the respiratory tract, and 25% of patients experience health-related problems. It is important to have a suitable method to detect M. pneumoniae, and gold nanoparticle (GNP)-based colorimetric biosensing was used in this study to identify the specific target DNA for M. pneumoniae. The color of GNPs changes due to negatively charged GNPs in the presence of positively charged monovalent (Na + ) ions from NaCl. This condition is reversed in the presence of a single-stranded oligonucleotide, as it attracts GNPs but not in the presence of double-stranded DNA. Single standard capture DNA was mixed with optimal target DNA that cannot be adsorbed by GNPs; under this condition, GNPs are not stabilized and aggregate at high ionic strength (from 100 mM). Without capture DNA, the GNPs that were stabilized by capture DNA (from 1 μM) became more stable under high ionic conditions and retaining their red color. The GNPs turned blue in the presence of target DNA at concentrations of 1 pM, and the GNPs retained a red color when there was no target in the solution. This method is useful for the simple, easy, and accurate identification of M. pneumoniae target DNA at higher discrimination and without involving sophisticated equipment, and this method provides a diagnostic for M. pneumoniae., (© 2022 International Union of Biochemistry and Molecular Biology, Inc.)

Medicinal plants are an essential source of traditional curatives for numerous skin diseases. Polyalthia longifolia (Sonn.) Thwaites (Annonaceae family) is a medicinal plant used to cure skin illnesses. P. longifolia is usually applied in folkloric therapeutical systems to treat skin diseases. The methicillin-resistant Staphylococcus aureus (MRSA) bacteria is among the essential bacteria contributing to skin diseases. Hence, to verify the traditional medicinal claim of P. longifolia usage in skin disease treatment, the current research was performed to study the synergistic antibacterial activity of standardized Polyalthia longifolia methanol leaf extract (MEPL) against MRSA bacteria. The synergistic antimicrobial activity result of ceftriaxone, when mixed with MEPL, against MRSA was investigated by the disc diffusion method, broth microdilution method, checkerboard dilution test, and modulation of mecA gene expression by multiplex polymerase chain reaction (multiplex PCR). The MEPL extract exhibited good synergistic antimicrobial activity against MRSA. Using the checkerboard method, we confirmed the synergistic effect of MEPL from P. longifolia and ceftriaxone (2:1) for MRSA with a marked reduction of the MIC value of the ceftriaxone from 8000 µg/mL to 1000 µg/mL. Moreover, the combination of MEPL with ceftriaxone significantly ( p < 0.05) inhibited the presence of the resistant mecA gene in the tested strain. The LC-ESI-MS/MS analysis identified compounds that were reported to exhibit antimicrobial activity. Conclusively, the MEPL extract, an important etiological agent for skin diseases, showed worthy synergistic antimicrobial action against MRSA bacteria, thus supporting the traditional use of P. longifolia .

Carbon dots (CDs) are a new category of crystalline, quasi-spherical fluorescence, "zero-dimensional" carbon nanomaterials with a spatial size between 1 nm to 10 nm and have gained widespread attention in recent years. Green CDs are carbon dots synthesised from renewable biomass such as agro-waste, plants or medicinal plants and other organic biomaterials. Plant-mediated synthesis of CDs is a green chemistry approach that connects nanotechnology with the green synthesis of CDs. Notably, CDs made with green technology are economical and far superior to those manufactured with physicochemical methods due to their exclusive benefits, such as being affordable, having high stability, having a simple protocol, and being safer and eco-benign. Green CDs can be synthesized by using ultrasonic strategy, chemical oxidation, carbonization, solvothermal and hydrothermal processes, and microwave irradiation using various plant-based organic resources. CDs made by green technology have diverse applications in biomedical fields such as bioimaging, biosensing and nanomedicine, which are ascribed to their unique properties, including excellent luminescence effect, strong stability and good biocompatibility. This review mainly focuses on green CDs synthesis, characterization techniques, beneficial properties of plant resource-based green CDs and their biomedical applications. This review article also looks at the research gaps and future research directions for the continuous deepening of the exploration of green CDs.

We investigate flow-induced structural organization in a dilute suspension of tumbling red blood cells (RBCs) under confined shear flow. For small Reynolds ( Re = 0.1) and capillary numbers ( Ca ), with fully coupled hydrodynamic interaction (HI) and without interparticle adhesion, we find that HI between the biconcave discoid particles prompts the formation of layered RBC chains and synchronized rotating RBC pairs, referred here as "waltzing doublets." As the volume fraction ϕ increases, more waltzing doublets appear in RBC files. Stronger shear stress disrupts structural arrangements at higher Ca . We find that the flow-induced organization of waltzing doublets changes how the suspension viscosity varies with ϕ qualitatively. The intrinsic viscosity is particularly sensitive to microstructural rearrangement, increasing (decreasing) with ϕ at low (high) Ca that correlates with the change in the fraction of doublets. We verified flow-induced collective motion with comparison to two-cell simulations in which the cell volume fraction is controlled by varying the domain volume.

Structural variants of α-galactosylceramide (α-GalCer) that stimulate invariant natural killer T (iNKT) cells constitute an emerging class of immunomodulatory agents in development for numerous biological applications. Variations in lipid chain length and/or fatty acids in these glycoceramides selectively trigger specific pro-inflammatory responses. Studies that would link a specific function to a structurally distinct α-GalCer rely heavily on the availability of homogeneous and pure materials. To address this need, we report herein a general route to the diversification of the ceramide portion of α-GalCer glycolipids. Our convergent synthesis commences from common building blocks and relies on the Julia-Kocienski olefination as a key step. A cleavable fluorous tag is introduced at the non-reducing end of the sugar that facilitates quick purification of products by standard fluorous solid-phase extraction. The strategy enabled the rapid generation of a focused library of 61 α-GalCer analogs by efficiently assembling various lipids and fatty acids. Furthermore, when compared against parent α-GalCer in murine cells, many of these glycolipid variants were found to have iNKT cell stimulating activity similar to or greater than KRN7000. ELISA assaying indicated that glycolipids carrying short fatty N -acyl chains ( 1fc and 1ga ), an unsubstituted ( 1fh and 1fi ) or CF 3 -substituted phenyl ring at the lipid tail, and a flexible, shorter fatty acyl chain with an aromatic ring ( 1ge , 1gf , and 1gg ) strongly affected the activation of iNKT cells by the glycolipid-loaded antigen-presenting molecule, CD1d. This indicates that the method may benefit the design of structural modifications to potent iNKT cell-binding glycolipids.

The Young-Laplace equation suggests that nanosized gas clusters would dissolve under the effects of perturbation. The fact that nanobubbles are observed raises questions as to the mechanism underlying their stability. In the current study, we used all-atom molecular dynamics simulations to investigate the gas-water interfacial properties of gas clusters. We employed the instantaneous coarse-graining method to define the fluctuating boundaries and analyze the deformation of gas clusters. Fourier transform analysis of the cluster morphology revealed that the radius and morphology deformation variations exhibit power law relationships with the vibrational frequency, indicating that the surface energy dissipated through morphology variations. Increasing pressure in the liquid region was found to alter the network of water molecules at the interface, whereas increasing pressure in the gas region did not exhibit this effect. The overall gas concentration was oversaturated and proportional to the gas density inside the clusters. However, the result of comparison with Henry's law reveals that the gas pressure at the interface reduced by the interfacial effects is much lower than that inside the gas region, thus reducing the demanding degree of oversaturation. Originating from the interfacial charge allocation, the magnitude of the electrostatic stress is greater than that of the gas pressure inside the cluster. However, the magnitude of the reversed tension induced by electrostatic stress is far below the value of interfacial tension. The potential of mean force (PMF) profiles revealed that a barrier potential at the interface hindered gas particles from escaping the cluster. Several effects contribute to stabilizing the gas clusters in water, including high-frequency morphological deformation, electrostatic stress, reduced interfacial tension, and gas oversaturation conditions. Our results suggest that gas clusters can exist in water under gas oversaturation conditions in the absence of hydrophobic contaminants or pinning charges at interfaces.

We investigate the enzymatic self-catalyzed gelation process in aiyu gel, a natural ion crosslinked polysaccharide gel. The gelation process depends on the concentration ratio ( R max ) of the crosslinking calcium ions and all galacturonic acid binding sites. The physical gel network formation relies on the assembly of calcium-polysaccharide crosslink bonds. The crosslinks are initially transient and through break-up/rebinding gradually re-organizing into long, stable junction zones. Our previous study formulated a reaction kinetics model to describe enzymatic activation, crosslinker binding, and crosslink microstructural reorganization, in order to model the complex growth of elasticity. In this study, we extend the theory for the time-dependent profile of complex moduli and examine the interplay of enzyme conversion, crosslink formation, and crosslink re-organization. The adjusted model captures how the gelation and structural rearrangement characteristic times vary with the polymer and calcium concentrations. Furthermore, we find that calcium ions act as both crosslinkers and dopants in the excess calcium ion scenario and the binding dynamics is determined by R max . This study provides perspectives on the dynamic binding behaviors of aiyu pectin gel system and the theoretical approach can be generalized to enzyme-catalyzed ionic gel systems.

Nanomaterial on the sensing area elevates the biomolecular immobilization by its right orientation with a proper alignment, and zeolite is one of the suitable materials. In this research, the zeolite nanoparticles were synthesized using rice hush ash as the basic source and the prepared zeolite by the addition of sodium silicate was utilized to attach antibody as a probe on a gap-fingered dielectrode surface to identify the colon cancer biomarker, "colon cancer-secreted protein-2" (CCSP-2). Field Emission Scanning Electron Microscopy and Field Emission Transmission Electron Microscopy images confirmed the size of the nanoparticle to be ∼15 nm and the occurrence of silica and alumina. Zeolite was modified on the electrode surface through the amine linker, and then anti-CCSP-2 was attached by an aldehyde linker. On this surface, CCSP-2 was detected and attained the detection limit to be 3 nM on the linear regression curve with 3-5 nM of CCSP-2. Estimated by the determination coefficient of y = 2.3952x - 4.4869 and R 2 = 9041 with 3δ (n = 3). In addition, control proteins did not produce the notable current response representing the specific sensing of CCSP-2. This research is suitable to identify CCSP-2 at a lower level in the bloodstream under the physiological condition of a colon cancer patient., (© 2021 International Union of Biochemistry and Molecular Biology, Inc.)

Nanoscale iron oxide-based nanostructures are among the most apparent metallic nanostructures, having great potential and attracting substantial interest due to their unique superparamagnetic properties. The green production of nanostructures has received abundant attention and been actively explored recently because of their various beneficial applications and properties across different fields. The biosynthesis of the nanostructure using green technology by the manipulation of a wide variety of plant materials has been the focus because it is biocompatible, non-toxic, and does not include any harmful substances. Biological methods using agro-wastes under green synthesis have been found to be simple, environmentally friendly, and cost-effective in generating iron oxide-based nanostructures instead of physical and chemical methods. Polysaccharides and biomolecules in agro-wastes could be utilized as stabilizers and reducing agents for the green production of nanostructured iron oxide towards a wide range of benefits. This review discusses the green production of iron oxide-based nanostructures through a simple and eco-friendly method and its potential applications in medical and sustainable agro-environments. This overview provides different ways to expand the usage of iron oxide nanomaterials in different sectors. Further, provided the options to select an appropriate plant towards the specific applications in agriculture and other sectors with the recommended future directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Poh Yan, Gopinath, Subramaniam, Chen, Velusamy, Chinni, Gobinath and Lebaka.)

Pectin polymers are considered for lithium-ion battery electrodes. To understand the performance of pectin as an applied buffer layer, the electrical, magnetic, and optical properties of pectin films are investigated. This work describes a methodology for creating pectin films, including both pristine pectin and Fe-doped pectin, which are optically translucent, and explores their potential for lithium-ion battery application. The transmission response is found extended in optimally Fe-doped pectin, and prominent modes for cation bonding are identified. Fe doping enhances the conductivity observed in electrochemical impedance spectroscopy, and from the magnetic response of pectin evidence for Fe 3+ is identified. The Li-ion half-cell prepared with pectin as binder for anode materials such as graphite shows stable charge capacity over long cycle life, and with slightly higher specific capacity compare with the cell prepared using polyvinylidene fluoride (PVDF) as binder. A novel enhanced charging specific capacity at a high C-rate is observed in cells with pectin binder, suggesting that within a certain rate (∼5 C), pectin has higher capacity at faster charge rates. The pectin system is found as a viable base material for organic-inorganic synthesis studies., (© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.)

Carcinoembryonic antigen (CEA) is a glycoprotein, one of the common tumor biomarkers, found at low levels in body fluids. Generally, overexpression of CEA is found in various cancers, including ovarian, breast, lung, colorectal, gastric, and pancreatic cancers. Since CEA is an important tumor biomarker, the quantification of CEA is helpful for diagnosing cancer, monitoring tumor progression, and the follow-up treatment. This research develops a highly sensitive sandwich aptasensor for CEA identification on an interdigitated electrode sensor. Carbon-based material was used to attach a higher anti-CEA capture aptamer onto the sensor surface through a chemical linker, and then, CEA was quantified by the aptamer. Furthermore, CEA-spiked serum was tested by using the immobilized aptamer, which was found to not affect the target validation. The limit of detection for CEA in PBS and serum is calculated from a linear regression graph to be 0.5 ng/mL with R 2 values of 0.9593 and 0.9657, respectively, over a linear range from 0.5 to 500 ng/mL. This CEA quantification by the aptasensor can help diagnose various surgical tumors and monitor their progression., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Renyuan Ma et al.)

17β-Estradiol-E2 (17β-E2) is a steroid hormone that plays a major role in the reproductive endocrine system and is involved in various processes, such as pregnancy, fertility, and menopause. In this study, the performance of an enzyme-linked immunosorbent assay (ELISA) for 17β-E2 quantification was enhanced by using a gold nanoparticle (GNP)-conjugated aptamer. An anti-17β-E2-aptamer-GNP antibody was immobilized on an amine-modified ELISA surface. Then, 17β-E2 was allowed to interact with and be sandwiched by antibodies. Aptamer-GNP conjugation was confirmed by colorimetric assays via the naked eye and UV-visible light spectroscopy. The detection limit based on a signal-to-noise ratio (S/N) of 3 was estimated to be 1.5 nM (400 pg/mL), and the linear range was 1.5-50 nM. Control experiments (without 17β-E2/with a complementary aptamer sequence/with a nonimmune antibody) confirmed the specific detection of 17β-E2. Moreover, 17β-E2 spiking of human serum did not interrupt the interaction between 17β-E2 and its antibody and aptamer. Thus, the developed ELISA can be used as an alternate assay for quantification of 17β-E2 and assessment of endocrine-related gynecological problems., (© 2020 International Union of Biochemistry and Molecular Biology, Inc.)

Background: Oral squamous cell carcinoma (OSCC) has increased in incidence from 1990 to 2017, especially in South and Southeast Asia. It is often diagnosed at an advanced stage with a poor prognosis. Therefore, early detection of OSCC is essential to improve the prognosis of OSCC. This study aims to identify the differentially expressed serum proteins as potential biomarkers for oral squamous cell carcinoma (OSCC)., Methods: Comparative proteomics profiling of serum samples from OSCC patients, oral potentially malignant disorder (OPMD) patients, and healthy individuals were performed using two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS) ( n  = 60) and bioinformatics analysis. The enzyme-linked immunosorbent assay (ELISA) ( n  = 120) and immunohistochemistry (IHC) ( n  = 70) were used to confirm our findings., Results: The 2-DE analysis revealed that 20 differentially expressed proteins were detected in OPMD and OSCC ( p  < 0.05). Bioinformatics analysis indicated that the activation of classical complement, liver X receptor/retinoid X receptor (LXR/RXR) activation, and acute phase response signaling pathway are associated with the development and progression of OSCC. Most of the detected proteins are acute-phase proteins and were related to inflammation and immune responses, including apolipoprotein A-I (APOA1), complement C3 (C3), clusterin (CLU), and haptoglobin (HP). The expression levels of CLU and HP in ELISA are consistent with the findings from the 2-DE analysis, except for the mean serum level of HP in OPMD, whereby it was slightly higher than that in control. IHC results demonstrated that CLU and HP are significantly decreased in OSCC tissues., Conclusion: Decreased expression of CLU and HP could serve as complementary biomarkers of OSCC. These proteins may assist in predicting the outcomes of OSCC patients. However, a larger cohort is needed for further investigation., Competing Interests: The authors declared that they have no competing interests., (©2021 Wong et al.)

Gas aggregation and formation of interfacial nanobubbles (INBs) provide challenges and opportunities in the operation of micro-/nanofluidic devices. In the current study, we used molecular dynamics(MD) simulations to investigate the effects of hydrophobicity and various homogeneous surface conditions on gas aggregation and INB stability with a series of 3D argon-water-solid and water-solid systems. Among various signatures of surface hydrophobicity, the potential of mean force (PMF) minima exhibited the strongest correlation with the water molecular orientation at the liquid-solid interface, compared to the depletion layer width and the droplet contact angle. Our results indicated that argon aggregation on the substrate was a function of hydrophobicity as well as competition between gas-solid and water-solid PMFs. Thus, one precondition for gas aggregation on a surface is that the free energy minima of gas induced by the surface be much lower than that induced by water. We found that although the presence of gas molecules had little effect on the measures of wettability, it enhanced density fluctuations near liquid-solid interfaces. The PMF of gas along the surface tangential plane exhibited a small energy barrier between the epitaxial gas layer (EGL) in the bubble and the gas enrichment layer (GEL) in the liquid, which may benefit nanobubble stability. Much lower PMF in the EGL compared to that in the GEL indicated that gas molecules could migrate from the GEL to the nanobubble basement. However, density fluctuations enhanced by the GEL could reduce the energy barrier, thus reducing the stability of INBs.

Highly sensitive and easy detection method for Alzheimer's disease (AD) with a suitable biomarker is mandatory for preventing the factors resulting from AD. This research reports a modified ELISA with graphene for the detection of AD biomarker amyloid beta (Aβ) oligomer. Gold nanoparticle (AuNP) conjugated aptamer was used as the capture probe and attached on ELISA-graphene oxide surface through the amine linker. Antibody was used as the detection molecule to reach the maximum detection of Aβ oligomer. Suitable level of APTMS (2%), size of AuNP (30 nm) and aptamer concentration (2 μM) were optimized. This sandwich pattern of aptamer-Aβ oligomer-antibody helps to reach the detection at 50 pM on the optimized ELISA surface and the control experiments in the absence of Aβ oligomer or anti-Aβ oligomer antibody did not show the significant optical detection at 492 nm, indicting the specific detection. Further, Aβ oligomer spiked artificial cerebrospinal fluid did not interfere the detection of Aβ oligomer, confirming the selective detection. This new and modified ELISA surface helps to reach the lower detection of Aβ oligomer and diagnose AD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The prevalence of oral squamous cell carcinoma (OSCC) is high in South and Southeast Asia regions. Most OSCC patients are detected at advanced stages low 5-year survival rates. Aberrant expression of glycosylated proteins was found to be associated with malignant transformation and cancer progression. Hence, identification of cancer-associated glycoproteins could be used as potential biomarkers that are beneficial for diagnosis or clinical management of patients. This study aims to identify the differentially expressed glycoproteins using lectin-based glycoproteomics approaches. Serum samples of 40 patients with OSCC, 10 patients with oral potentially malignant disorder (OPMD), and 10 healthy individuals as control group were subjected to two-dimensional gel electrophoresis (2-DE) coupled with lectin Concanavalin A and Jacalin that specifically bind to N- and O-glycosylated proteins, respectively. Five differentially expressed N- and O-glycoproteins with various potential glycosylation sites were identified, namely N-glycosylated α1-antitrypsin (AAT), α2-HS-glycoprotein (AHSG), apolipoprotein A-I (APOA1), and haptoglobin (HP); as well as O-glycosylated AHSG and clusterin (CLU). Among them, AAT and APOA1 were further validated using enzyme-linked immunosorbent assay (ELISA) (n = 120). It was found that AAT and APOA1 are significantly upregulated in OSCC and these glycoproteins are independent risk factors of OSCC. The clinical utility of AAT and APOA1 as potential biomarkers of OSCC is needed for further evaluation.

We investigate the rich phase behavior of strongly confined semi-flexible (SFC) polymer-nanoparticle (NP) systems using the graphics processing unit accelerated Langevin dynamics simulation. Hard nanoparticles (HNP) that repel each other and ideal nanoparticles (INP) that do not interact with the same species are used as model additives to a strongly confined semiflexible polymer fluid. Both types of NPs exclude the monomer beads in the same way, but they have qualitatively different effects on the SFC isotropic-nematic (I-N) transition. For the total volume fraction ϕ tot < 0.16, adding a low volume fraction of HNPs (ϕ p ) disrupts the long range nematic order of the polymers, whereas adding HNPs in a moderately packed system (0.16 < ϕ tot < 0.32) facilitates polymer alignment due to the restricted polymer orientational degree of freedom. For dense packing (ϕ tot > 0.32), polymers and NPs separate into layers along the slit height and the NPs form crystalline microdomains. In contrast, INP additives always promote inter-polymer alignment for low to moderate monomer volume fractions (ϕ m ). Furthermore, we found that INPs form a droplet-like fluid domain in dense nematic polymer systems.

Cervical, ovarian, and endometrial cancers are common in the female reproductive system. Cervical cancer starts from the cervix, while ovarian cancer develops when abnormal cells grow in the ovary. Endometrial or uterine cancer starts from the lining of the womb in the endometrium. Approximately 12,000 women are affected every year by cervical cancer in the United States. Squamous cell carcinoma antigen (SCC-Ag) is a well-established biomarker in serum for diagnosing gynecological cancers, and its levels were observed to be elevated in cervical, ovarian, and endometrial cancer patients. Moreover, SCC-Ag was used to identify the tumor size and progression stages. Various biosensing systems have been proposed to identify SCC-Ag; herein, enhanced interdigitated electrode sensing is presented with the use of gold nanoparticles (GNPs) to conjugate an antigen/antibody. It was proved that the limit of detection is 62.5 fM in the case of antibody-GNP, which is 2-fold higher than that by SCC-Ag-GNP. Furthermore, the antibody-GNP-modified surface displays greater current increases with concomitant dose-dependent SCC-Ag levels. High analytical performance was shown by the discrimination against α -fetoprotein and CYFRA 21-1 at 1 pM. An enhanced sensing system is established for gynecological tumors, representing an advance from the earlier detection methods., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Xinmei Liu et al.)

Background: Polyalthia longifolia is a popular medicinal plant and has been widely used as a traditional remedy for centuries in curing of various ailments. The purpose of this study was conducted to determine the in situ antimicrobial synergistic effects between Polyalthia longifolia leaf ethyl acetate fraction (PLEAF) and ampicillin against MRSA local isolate by using modern microscopy technique., Methods: Hence, the evaluation of the synergistic activity of PLEAF and ampicillin against MRSA local isolate was conducted with scanning electron microscopy (SEM)., Results: The combinational effect of PLEAF fraction and ampicillin exhibited significant antibacterial activity against MRSA. Bacterial cells observations showed invagination, impaired cell division, extensive wrinkles, cell shrinkage, the appearance of a rougher cell with fibrous matrix and clustered cells which confirmed the synergistic effect of PLEAF and ampicillin against MRSA local isolate by SEM., Conclusion: Conclusively, the in situ SEM observation proved the synergistic antimicrobial activity between PLEAF fraction and ampicillin to destroy the MRSA resistance bacteria which is an important aspect of PLEAF fraction to be used in the future combinational therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Human papilloma virus (HPV) affects predominantly the genital area, which includes vagina, cervix, penis, vulva scrotum, rectum and anus. Among 100 types of HPV, 14 types are considered to cause the risky cancer. The gene HPV-16 E7 is responsible for the development of cancer with the infected women. Earlier identification of this gene sequence avoids the cancer progression. The targeted HPV-16 E7 sequence was sandwiched by capture and reporter sequences on the carbodiimidazole-modified interdigitated electrode (IDE) surface. Target sequence at 100 f. was paired to the capture sequence immobilized on IDE sensing surface. To this surface, different concentrations of reporter sequence with and without gold rod (GNR) were evaluated. In both cases the detections were attained 1 aM by the reporter sequence pairing and with GNR increments in current were found. This enhancement was found to be 1000 folds, considering the condition was revealed in the absence of reporter. This sandwich detection strategy of capture-target-reporter sequences for HPV-16 detection on the IDE sensing surface helps to diagnose the association of cervical cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The cell-free layer thickness of an aggregating red blood cell (RBC) suspension in a rectangular microchannel is investigated by hybrid fluid-particle numerical modeling. Several factors affect the suspension viscosity, cell-free layer thickness, and the cell aggregate distribution. These include the hematocrit, vessel size, red cell stiffness, aggregation interaction, and shear rate. In particular, the effect of the shear rate on the cell-free layer thickness is controversial. We found that the suspension viscosity increases along with a decrease in the cell-free layer thickness as the shear rate increases for aggregating model RBCs at low shear rates. At moderate to high shear rates, the cell-free layer thickness increases with the increasing shear rate from medium to strong shear flow for both 10% and 20% red blood cell suspensions., (Copyright © 2019 Author(s).)

Gestational hypertension is one of the complicated disorders during pregnancy; it causes the significant risks, such as placental abruption, neonatal deaths, and maternal deaths. Hypertension is also responsible for the metabolic and cardiovascular issues to the mother after the years of pregnancy. Identifying and treating gestational hypertension during pregnancy by a suitable biomarker is mandatory for the healthy mother and foetus development. Cortisol has been found as a steroid hormone that is secreted by the adrenal gland and plays a pivotal role in gestational hypertension. A normal circulating level of cortisol is involved in the regulation of blood pressure, and it is necessary to monitor the changes in the level of cortisol during pregnancy. In this work, aptamer-based colorimetric assay is demonstrated as a model with gold nanorod to quantify the level of cortisol using the coordinated aggregation (at 500 mM of NaCl) and dispersion (with 10  μ M of aptamer), evidenced by the scanning electron microscopy observation and UV-visible spectroscopy analysis. This colorimetric assay is an easier visual detection and reached the limit of detection of cortisol at 0.25 mg/mL. This method is reliable to identify the condition of gestational hypertension during the pregnancy period., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Xiucui Bao et al.)

Background: Gestational diabetes mellitus is a commonly occurring metabolic disorder during pregnancy, affecting >4% of pregnant women. It is generally defined as the intolerance of glucose with the onset or initial diagnosis during pregnancy. This illness affects the placenta and poses a threat to the baby as it affects the supply of proper oxygen and nutrients., Purpose: Due to the high percentage of affected pregnant women, it should be mandatory to evaluate glucose levels during pregnancy and there is a need for a continuous monitoring system., Methods: Herein, the investigators modified the interdigitated (di)electrodes (IDE) sensing surface to detect the glucose on covalently immobilized glucose oxidase (GOx) with the graphene. The characterization of graphene and gold nanoparticle (GNP) was performed by high-resolution microscopy., Results: Sensitivity was found to be 0.06 mg/mL and to enhance the detection, GOx was complexed with GNP. GNP-GOx was improved the sensitive detection twofold from 0.06 to 0.03 mg/mL, and it also displayed higher levels of current changes at all the concentrations of glucose that were tested. High-performance of the above IDE sensing system was attested by the specificity, reproducibility and higher sensitivity detections. Further, the linear regression analysis indicated the limit of detection to be between 0.02 and 0.03 mg/mL., Conclusion: This study demonstrated the potential strategy with nanocomposite for diagnosing gestational diabetes mellitus., Competing Interests: There are no conflicts of interest reported by the authors regarding this work., (© 2019 Ge et al.)

Cervical cancer is a life-threatening complication, appearing as the uncontrolled growth of abnormal cells in the lining of the cervix. Every year, increasing numbers of cervical cancer cases are reported worldwide. Different identification strategies were proposed to detect cervical cancer at the earlier stages using various biomarkers. Squamous cell carcinoma antigen (SCC-Ag) is one of the potential biomarkers for this diagnosis. Nanomaterial-based detection systems were shown to be efficient with different clinical biomarkers. In this study, we have demonstrated strontium oxide-modified interdigitated electrode (IDE) fabrication by the sol-gel method and characterized by scanning electron microscopy and high-power microscopy. Analysis of the bare devices indicated the reproducibility with the fabrication, and further pH scouting on the device revealed that the reliability of the working pH ranges from 3 to 9. The sensing surface was tested to detect SCC-Ag against its specific antibody; the detection limit was found to be 10 pM, and the sensitivity was in the range between 1 and 10 pM as calculated by 3 σ . The specificity experiment was carried out using major proteins from human serum, such as albumin and globulin. SCC-Ag was shown to be selectively detected on the strontium oxide-modified IDE surface.

We investigated how the stability of aqueous argon surface nanobubbles on hydrophobic surfaces depends on gas adsorption, solid-gas interaction energy, and the bulk gas concentration using molecular dynamics simulation with the SPC/E water solvent. We observed stable surface nanobubbles without surface pinning sites for longer than 160 ns, contrary to previous findings using monoatomic Lennard-Jones solvent. In addition, the hydrophobicity of a substrate has an effect to reduce the requirement degree of oversaturation on water bulk. We found that the gas enrichment layer, gas adsorption monolayer on the hydrophobic substrate, and water hydrogen bonding near the interface are likely necessary conditions for nanobubble stability. We concluded that gas nanobubble stability does not necessarily require three-phase pinning sites.

Recent studies indicate that changing the physical properties of lipid bilayers may profoundly change the function of membrane proteins. Here, the effects of dissolved nitrogen and oxygen molecules on the mechanical properties and stability of lipid bilayers are investigated using differential confocal microscopy, atomic force microscopy, and molecular dynamics simulations. All experiments evidence the presence of dissolved air gas in lipid bilayers prepared without gas control. The lipid bilayers in degassed solutions are softer and less stable than those in ambient solutions. High concentrations of nitrogen increase the bending moduli and stability of the lipid bilayers and impede phase separation in ternary lipid bilayers. The effect of oxygen is less prominent. Molecular dynamics simulations indicate that higher nitrogen affinity accounts for increased rigidity. These findings have fundamental and wide implications for phenomena related to lipid bilayers and cell membranes, including the origin of life., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We investigated the nematic to smectic phase transition for strongly confined semiflexible polymer solutions in slit-like confinements using GPU-accelerated Langevin dynamics. We characterized the phase transitions from the nematic to smectic phases for semi-flexible polymer solutions as the polymer density increased. The dependence for the lyotropic nematic to smectic transition can be collapsed by scaling exponents between 0.2 and 0.3. The smectic C phase is found for all the cases with the polymer orientation director tilted with respect to smectic layer lateral alignment. As the chain rigidity increases, the transition density decreases for systems in which the polymer persistence length (P) to slit height (H) ratios are 1.25, 2.5, 3.75, 5 and 25. We also characterized the polymer dynamics for the isotropic-nematic-smectic transitions. The overall polymer diffusivity decreased steadily as the polymer density increased. We observed anomalous polymer diffusion along the nematic director near the isotropic-nematic transition, similar to previously reported behavior for nematic-forming ellipsoids. Polymer diffusivity decreased sharply by two orders of magnitude upon the nematic-smectic transition.

The motile characteristics and mechanisms that drive the dissemination of diffuse large B-cell lymphoma (DLBCL) are elusive. Here, we show that DLBCL initiates dissemination through activating STAT3-mediated amoeboid migration. Mechanistically, STAT3 activates RHOH transcription, which competes with the RhoGDP dissociation inhibitor RhoGDIγ to activate RhoA. In addition, activated STAT3 regulates microtubule dynamics and releases ARHGEF2 to activate RhoA. Both the JAK inhibitor ruxolitinib and the microtubule stabilizer Taxol suppress DLBCL cell dissemination in vivo. A clinical DLBCL sample analysis shows that STAT3-driven amoeboid movement is particularly important for the transition from stage I to stage II. This study elucidates the mechanism of DLBCL dissemination and progression and highlights the potential of combating advanced DLBCL with a JAK/STAT inhibitor or microtubule stabilizer to reduce DLBCL motility; these findings may have a great impact on the development of patient-tailored treatments for DLBCL.

Open heart surgeries are common for treating ischemic and heart valve disease. During cardiac surgery, cardiopulmonary bypass (CPB) can temporarily take over the function of heart and lungs. However, elevated red blood cell (RBC) aggregation may lead to the common side-effects such as microinfarction. We investigated blood physical properties changes and the correlation between blood microstructure, viscoelastic response and biochemical changes following surgery with CPB. We examined shear-rate dependent blood viscosity, elasticity and RBC aggregate size in the pre-surgery disease state, post-surgery state and long-term recovery state of cardiac surgical patients. Within a week following surgery, the patient hematocrit was significantly lower due to CPB. Despite lower RBC concentration, the RBC aggregate shape became larger and more rounded, which is correlated to the elevated plasma fibrinogen related to systemic inflammatory response. During the same period, the hematocrit-adjusted low shear rate viscosity increased significantly, as did the yield stress, indicating more solid-like behavior for blood. Six months to one year later, all the physical and biochemical properties measured returned to baseline.

Enzyme hydrolysates (trypsin, papain, pepsin, α-chymotrypsin, and pepsin-pancreatin) of Tinospora cordifolia stem proteins were analyzed for antioxidant efficacy by measuring (1) 1,1-diphenyl-2-picrylhydrazyl (DPPH•) radical scavenging activity, (2) 2,20-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radical scavenging capacity, and (3) Fe2+ chelation. Trypsin hydrolysate showed the strongest DPPH• scavenging, while α-chymotrypsin hydrolysate exhibited the highest ABTS+ scavenging and Fe2+ chelation. Undigested protein strongly inhibited the gastrointestinal enzymes, trypsin (50% inhibition at enzyme/substrate ratio = 1:6.9) and α-chymotrypsin (50% inhibition at enzyme/substrate ratio = 1:1.82), indicating the prolonged antioxidant effect after ingestion. Furthermore, gel filtration purified peptide fractions of papain hydrolysates exhibited a significantly higher ABTS+ and superoxide radical scavenging as compared to non-purified digests. Active fraction 9 showing the highest radical scavenging ability was further purified and confirmed by MALDI-TOF MS followed by MS/MS with probable dominant peptide sequences identified are VLYSTPVKMWEPGR, VITVVATAGSETMR, and HIGININSR. The obtained results revealed that free radical scavenging capacity of papain hydrolysates might be related to its consistently low molecular weight hydrophobic peptides.

Ethnopharmacological Relevance: Phaleria macrocarpa (Scheff) Boerl, is a famous traditional medicinal plant which exhibited cytotoxicity against various cancerous cells. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and heart disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases., Aim of the Study: Recent studies have demonstrated a potent anticancer potential of P. macrocarpa, especially against HeLa cell. The objective of this study was to investigate the regulation of miRNAs on MDA-MB-231 treated with P. macrocarpa ethyl acetate fraction (PMEAF)., Materials and Methods: The regulation of miRNAs on MDA-MB-231 cells treated with PMEAF was studied through IIlumina, Hi-Seq. 2000 platform of Next Generation Sequencing (NGS) and various in silico bioinformatics tools., Results: The PMEAF treatment against MDA-MB-231 cells identified 10 upregulated and 10 downregulated miRNAs. A set of 606 target genes of 10 upregulated miRNAs and 517 target genes of 10 downregulated miRNAs were predicted based on computational and validated databases by using miRGate DB Query. Meanwhile, results from DAVID Bioinformatics Resources 6.8 specified the functional annotation of the upregulated miRNAs involvement in cancer pathway by suppressing the oncogenes and downregulating miRNAs by expressing the tumour suppressor genes in the regulation of apoptosis pathway., Conclusion: In conclusion, the results of this study proved that PMEAF is a promising anticancer agent with high cytotoxicity against MDA-MB-231 breast cancer cells and it induced apoptotic cell death mechanism through the regulation of miRNAs. PMEAF might be the best candidate for developing more potent anticancer drugs or chemo preventive supplements., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We present a biogenic method for the synthesis of palladium nanoparticle (PdNP)-modified by reducing graphene oxide sheets (rGO) in a one-pot strategy using Ficus carica fruit juice as the reducing agent. The synthesized material was well characterized by morphological and structural analyses, including, Ultraviolet-Visible spectroscopy (UV-Vis), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and Transmission Electron Microscopy (TEM) and Raman spectroscopy. The results revealed that the PdNP modified GO are spherical in shape and estimated to be a dimension of ~0.16 nm. The PdNP/graphene exhibits a great catalytic activity in Suzuki cross-coupling reactions for the synthesis of biaryl compounds with various substrates under both aqueous and aerobic conditions. The catalyst can be recovered easily and is suitable for repeated use because it retains its original catalytic activity. The PdNP/rGO catalyst synthesized by an eco-friendly protocol was used for the Suzuki coupling reactions. The method offers a mild and effective substitute to the existing methods and may significantly contribute to green chemistry.

This paper reports a microfluidic viscometer with an integrated pressure sensor based on electrofluidic circuits, which are electrical circuits constructed by ionic liquid-filled microfluidic channels. The electrofluidic circuit provides a pressure-sensing scheme with great long-term and thermal stability. The viscosity of the tested fluidic sample is estimated by its flow resistance, which is a function of pressure drop, flow rate, and the geometry of the microfluidic channel. The viscometer can be exploited to measure viscosity of either Newtonian or non-Newtonian power-law fluid under various shear rates (3-500 1/s) and temperatures (4-70 °C) with small sample volume (less than 400 μL). The developed sensor-integrated microfluidic viscometer is made of poly(dimethylsiloxane) (PDMS) with transparent electrofluidic circuit, which makes it feasible to simultaneously image samples under tests. In addition, the entire device is disposable to prevent cross-contamination between samples, which is desired for various chemical and biomedical applications. In the experiments, viscosities of Newtonian fluids, glycerol water solutions with different concentrations and a mixture of pyrogallol and sodium hydroxide (NaOH), and non-Newtonian fluids, xanthan gum solutions and human blood samples, have been characterized. The results demonstrate that the developed microfluidic viscometer provides a convenient and useful platform for practical viscosity characterization of fluidic samples for a wide variety of applications.

Circular RNAs characterize a class of widespread and diverse endogenous RNAs which are non-coding RNAs that are made by back-splicing events and have covalently closed loops with no polyadenylated tails. Various indications specify that circular RNAs (circRNAs) are plentiful in the human transcriptome. However, their participation in biological processes remains mostly undescribed. To date thousands of circRNAs have been revealed in organisms ranging from Drosophila melanogaster to Homo sapiens. Functional studies specify that these transcripts control expression of protein-coding linear transcripts and thus encompass a key component of gene expression regulation. This chapter provide a comprehensive overview on functional validation of circRNAs. Furthermore, we discuss the recent modern methodologies for the functional validation of circRNAs such as RNA interference (RNAi) gene silencing assay, luciferase reporter assays, circRNA gain-of-function investigation via overexpression of circular transcript assay, RT-q-PCR quantification, and other latest applicable assays. The methods described in this chapter are demonstrated on the cellular model.

We apply the lattice Boltzmann method and the bead-spring network model of deformable particles (DPs) to study shear-induced particle ordering and deformation and the corresponding rheological behavior for dense DP suspensions confined in a narrow gap under steady external shear. The particle configuration is characterized with small-angle scattering intensity, the real-space 2D local order parameter, and the particle shape factors including deformation, stretching and tilt angles. We investigate how particle ordering and deformation vary with the particle volume fraction ϕ (=0.45-0.65) and the external shear rate characterized with the capillary number Ca (=0.003-0.191). The degree of particle deformation increases mildly with ϕ but significantly with Ca. Under moderate shear rate (Ca  =  0.105), the inter-particle structure evolves from string-like ordering to layered hexagonal close packing (HCP) as ϕ increases. A long wavelength particle slithering motion emerges for sufficiently large ϕ. For ϕ  =  0.61, the structure maintains layered HCP for Ca  =  0.031-0.143 but gradually becomes disordered for larger and smaller Ca. The correlation in particle zigzag movements depends sensitively on ϕ and particle ordering. Layer-by-layer analysis reveals how the non-slippery hard walls affect particle ordering and deformation. The shear-induced reconfiguration of DPs observed in the simulation agrees qualitatively with experimental results of sheared uniform emulsions. The apparent suspension viscosity increases with ϕ but exhibits much weaker dependence compared to hard-sphere suspensions, indicating that particle deformation and unjamming under shear can significantly reduce the viscous stress. Furthermore, the suspension shear-thins, corresponding to increased inter-DP ordering and particle deformation with Ca. This work provides useful insights into the microstructure-rheology relationship of concentrated deformable particle suspensions.

This study was conducted to investigate the anticancer effects and mechanism of Calophyllum inophyllum fruit extract against MCF-7 cells. C. inophyllum fruit extract was found to have markedly cytotoxic effect against MCF-7 cells in a dose-dependent manner with the IC 50 for 24 h of 23.59 µg/mL. Flow cytometry analysis revealed that C. inophyllum fruit extract mediated cell cycle at G 0 /G 1 and G 2 /M phases, and MCF-7 cells entered the early phase of apoptosis. The expression of anti-apoptotic proteins Bcl-2 was decreased whereas the expression of the pro-apoptotic protein Bax, cytochrome C and p53 were increased after treatment. C. inophyllum fruit extract led to apoptosis in MCF-7 cells via the mitochondrial pathway in a dose dependent manner. This is evidenced by the elevation of intracellular ROS, the loss of mitochondria membrane potential (Δψm), and activation of caspase-3. Meanwhile, dose-dependent genomic DNA fragmentation was observed after C. inophyllum fruits extract treatment by comet assay. This study shows that C. inophyllum fruits extract-induced apoptosis is primarily p53 dependent and mediated through the activation of caspase-3. C. inophyllum fruit extract could be an excellent source of chemopreventive agent in the treatment of breast cancer and has potential to be explored as green anticancer agent.

We investigate the conformation and dynamics of a semi-flexible polymer near an attractive plane or a cylindrical post using Langevin dynamics. We characterize the transition from the desorbed to absorbed state and quantify how absorption depends on the attraction interaction, polymer molecular weight, polymer flexibility, intra-polymer interaction, and micro-confinement. We find that the critical point of adsorption for ideal flexible polymers only weakly depends on confinement. However, the critical point of adsorption increases significantly for self-avoiding flexible polymers and under confinement, deviating from scaling theory predictions. These findings provide insights into DNA surface adsorption in nanoslits and nanochannels.

Over the years a number of microscopy methods have been developed to assess the changes in cells. Some non-invasive techniques such as holographic digital microscopy (HDM), which although does not destroy the cells, but helps to monitor the events that leads to initiation of apoptotic cell death. In this study, the apoptogenic property and the cytotoxic effect of P. longifolia leaf methanolic extract (PLME) against the human cervical carcinoma cells (HeLa) was studied using light microscope (LM), holographic digital microscopy (HDM), scanning electron microscope (SEM) and transmission electron microscope (TEM). The average IC 50 value of PLME against HeLa cells obtained by MTT and CyQuant assay was 22.00μg/mL at 24h. However, noncancerous Vero cells tested with PLME exhibited no cytotoxicity with the IC 50 value of 51.07μg/mL at 24h by using MTT assay. Cytological observations showed nuclear condensation, cell shrinkage, multinucleation, abnormalities of mitochondrial cristae, membrane blebbing, disappearance of microvilli and filopodia, narrowing of lamellipodia, holes, formation of numerous smaller vacuoles, cytoplasmic extrusions and formation of apoptotic bodies as confirmed collectively by HDM, LM, SEM and TEM. In conclusion, PLME was able to produce distinctive morphological features of HeLa cell death that corresponds to apoptosis., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Our study of DNA dynamics in weakly attractive nanofabricated post arrays revealed crowding enhances polymer transport, contrary to hindered transport in repulsive medium. The coupling of DNA diffusion and adsorption to the microposts results in more frequent cross-post hopping and increased long-term diffusivity with increased crowding density. We performed Langevin dynamics simulations and found maximum long-term diffusivity in post arrays with gap sizes comparable to the polymer radius of gyration. We found that macromolecular transport in weakly attractive post arrays is faster than in non-attractive dense medium. Furthermore, we employed hidden Markov analysis to determine the transition of macromolecular adsorption-desorption on posts and hopping between posts. The apparent free energy barriers are comparable to theoretical estimates determined from polymer conformational fluctuations.

Medicinal plants have been accepted as a gold mine, with respect to the diversity of their phytochemicals. Many medicinal plants extracts are potential anticancer agents. Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is one of the most significant native medicinal plants and is found throughout Malaysia. Hence, the present study was intended to assess the anticancer properties of P. longifolia leaf methanolic extract (PLME) and its underlying mechanisms. The Annexin V/PI flow cytometry analysis showed that PLME induces apoptosis in HeLa cells in dose-dependent manner whereas the PI flow cytometric analysis for cell cycle demonstrated the accumulation of cells at sub G0/G1, G0/G1 and G2/M phases. Investigation with JC-1 flow cytometry analysis indicated increase in mitochondria membrane potential depolarisation corresponding to increase in PLME concentrations. PLME was also shown to influence intracellular reactive oxygen species (ROS) by exerting anti-oxidant (half IC 50 ) and pro-oxidant (IC 50 and double IC 50 ) affect against HeLa cells. PLME treatment also displayed DNA damage in HeLa cells in concentration depended fashion. The proteomic profiling array exposed the expression of pro-apoptotic and anti-apoptotic proteins upon PLME treatment at IC 50 concentration in HeLa cells. Pro-apoptotic proteins; BAX, BAD, cytochrome c, caspase-3, p21, p27 and p53 were found to be significantly up-regulated while anti-apoptotic proteins; BCL-2 and BCL-w were found to be significantly down-regulated. This investigation postulated the role of p53 into mediating apoptosis, cell cycle arrest and mitochondrial potential depolarisation by modulating the redox status of HeLa cells., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Ethnopharmacological Relevance: Phaleria macrocarpa (Scheff) Boerl, is a well-known folk medicinal plant in Indonesia. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and hearth disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases., Aim of the Study: The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death., Materials and Methods: MDA-MB-231 cells were incubated with PMEAF for 24h. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the Annexin V assay and also by fluorescence microscopy. Apoptosis protein profiling was detected by RayBio® Human Apoptosis Array., Results: The AO/PI staining and flow cytometric analysis of MDA-MB-231 cells treated with PMEAF were showed apoptotic cell death. The cell cycle analysis by flow cytometry analysis revealed that the accumulation of PMEAF treated MDA-MB-231 cells in G 0 /G 1 and G 2 /M-phase of the cell cycle. Moreover, the PMEAF exert cytotoxicity by increased the ROS production in MDA-MB-231 cells consistently stimulated the loss of mitochondrial membrane potential (∆ Ψm ) and induced apoptosis cell death by activation of numerous signalling proteins. The results from apoptosis protein profiling array evidenced that PMEAF stimulated the expression of 9 pro-apoptotic proteins (Bax, Bid, caspase 3, caspase 8, cytochrome c, p21, p27, p53 and SMAC) and suppressed the 4 anti-apoptotic proteins (Bcl-2, Bcl-w, XIAP and survivin) in MDA-MB-231 cells., Conclusion: The results indicated that PMEAF treatment induced apoptosis in MDA-MB-231 cells through intrinsic mitochondrial related pathway with the participation of pro and anti-apoptotic proteins, caspases, G 0 /G 1 and G 2 /M-phases cell cycle arrest by p53-mediated mechanism., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)