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Sensor Review ◽  
2022 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Amin Eidi ◽  
Mousa Shamsi ◽  
Habib Badri Ghavifekr

Purpose In this work, the sensing and actuating elements are designed with interdigitated capacitors away from the sensitive element on which the droplet is placed. This pattern helps to prevent interference of electrical elements with the droplet. Choosing shear resonance mode at this proposed structure minimizes the damping effect of droplet touch by the resonator structure. The glass-based standard fabrication method of the proposed biosensor is presented exactly. Design/methodology/approach Mechanical resonator sensors are extremely limited because of the high damping factor and the high electrical conductivity in the aqueous environment. In this work, a molecule detector biosensor is proposed for droplet analysis, which is possible to fabricate using micro-electro-mechanical systems (MEMS) technology. By electromechanical coupling of resonators as a mechanical resonator structure, a standing mechanical wave is formed at this structure by electrostatic actuating elements. Findings In this paper, a mechanical resonator structure as a biosensor is proposed for micro-droplet analysis that can be fabricated by MEMS technology. It is designed at a lower cost fabrication method using electrostatic technology and interdigitated capacitors. The response of the biosensor displacement frequency at the resonance frequency of the desired mode is reasonable for measuring the capacitive changes of its output. The mass sensitivity of the proposed biosensor is in the range of 1 ng, and it has a large sensitive area for capturing target molecules. Originality/value To evaluate the quality of the proposed design, the stimulated analysis is conducted by COMSOL and results are presented.


Crystals ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 99
Author(s):  
Ki Hyun Nam

Serial crystallography (SX) is an emerging technique to determine macromolecules at room temperature. SX with a pump–probe experiment provides the time-resolved dynamics of target molecules. SX has developed rapidly over the past decade as a technique that not only provides room-temperature structures with biomolecules, but also has the ability to time-resolve their molecular dynamics. The serial femtosecond crystallography (SFX) technique using an X-ray free electron laser (XFEL) has now been extended to serial synchrotron crystallography (SSX) using synchrotron X-rays. The development of a variety of sample delivery techniques and data processing programs is currently accelerating SX research, thereby increasing the research scope. In this editorial, I briefly review some of the experimental techniques that have contributed to advances in the field of SX research and recent major research achievements. This Special Issue will contribute to the field of SX research.


2022 ◽  
Vol 8 (1) ◽  
pp. 6
Author(s):  
Wei-Sheng Wu ◽  
Jordan S. Brown ◽  
Pin-Hao Chen ◽  
Sheng-Cian Shiue ◽  
Dong-En Lee ◽  
...  

Non-coding RNAs, such as miRNAs and piRNAs, play critical roles in gene regulation through base-pairing interactions with their target molecules. The recent development of the crosslinking, ligation, and sequencing of hybrids (CLASH) method has allowed scientists to map transcriptome-wide RNA–RNA interactions by identifying chimeric reads consisting of fragments from regulatory RNAs and their targets. However, analyzing CLASH data requires scientists to use advanced bioinformatics, and currently available tools are limited for users with little bioinformatic experience. In addition, many published CLASH studies do not show the full scope of RNA–RNA interactions that were captured, highlighting the importance of reanalyzing published data. Here, we present CLASH Analyst, a web server that can analyze raw CLASH data within a fully customizable and easy-to-use interface. CLASH Analyst accepts raw CLASH data as input and identifies the RNA chimeras containing the regulatory and target RNAs according to the user’s interest. Detailed annotation of the captured RNA–RNA interactions is then presented for the user to visualize within the server or download for further analysis. We demonstrate that CLASH Analyst can identify miRNA- and piRNA-targeting sites reported from published CLASH data and should be applicable to analyze other RNA–RNA interactions. CLASH Analyst is freely available for academic use.


Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 461
Author(s):  
Arthit Makarasen ◽  
Suwicha Patnin ◽  
Pongsit Vijitphan ◽  
Nanthawan Reukngam ◽  
Panita Khlaychan ◽  
...  

New target molecules, namely, 2-phenylamino-4-phenoxyquinoline derivatives, were designed using a molecular hybridization approach, which was accomplished by fusing the pharmacophore structures of three currently available drugs: nevirapine, efavirenz, and rilpivirine. The discovery of disubstituted quinoline indicated that the pyridinylamino substituent at the 2-position of quinoline plays an important role in its inhibitory activity against HIV-1 RT. The highly potent HIV-1 RT inhibitors, namely, 4-(2′,6′-dimethyl-4′-formylphenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6b) and 4-(2′,6′-dimethyl-4′-cyanophenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6d) exhibited half-maximal inhibitory concentrations (IC50) of 1.93 and 1.22 µM, respectively, which are similar to that of nevirapine (IC50 = 1.05 µM). The molecular docking results for these two compounds showed that both compounds interacted with Lys101, His235, and Pro236 residues through hydrogen bonding and interacted with Tyr188, Trp229, and Tyr318 residues through π–π stacking in HIV-1 RT. Interestingly, 6b was highly cytotoxic against MOLT-3 (acute lymphoblastic leukemia), HeLA (cervical carcinoma), and HL-60 (promyeloblast) cells with IC50 values of 12.7 ± 1.1, 25.7 ± 0.8, and 20.5 ± 2.1 µM, respectively. However, 6b and 6d had very low and no cytotoxicity, respectively, to-ward normal embryonic lung (MRC-5) cells. Therefore, the synthesis and biological evaluation of 2-phenylamino-4-phenoxyquinoline derivatives can serve as an excellent basis for the development of highly effective anti-HIV-1 and anticancer agents in the near future.


2022 ◽  
Vol 23 (2) ◽  
pp. 693
Author(s):  
Mirela Sarbu ◽  
Raluca Ica ◽  
Alina D. Zamfir

Gangliosides are effective biochemical markers of brain pathologies, being also in the focus of research as potential therapeutic targets. Accurate brain ganglioside mapping is an essential requirement for correlating the specificity of their composition with a certain pathological state and establishing a well-defined set of biomarkers. Among all bioanalytical methods conceived for this purpose, mass spectrometry (MS) has developed into one of the most valuable, due to the wealth and consistency of structural information provided. In this context, the present article reviews the achievements of MS in discovery and structural analysis of gangliosides associated with severe brain pathologies. The first part is dedicated to the contributions of MS in the assessment of ganglioside composition and role in the specific neurodegenerative disorders: Alzheimer’s and Parkinson’s diseases. A large subsequent section is devoted to cephalic disorders (CD), with an emphasis on the MS of gangliosides in anencephaly, the most common and severe disease in the CD spectrum. The last part is focused on the major accomplishments of MS-based methods in the discovery of ganglioside species, which are associated with primary and secondary brain tumors and may either facilitate an early diagnosis or represent target molecules for immunotherapy oriented against brain cancers.


2022 ◽  
Author(s):  
Sara G Dosil ◽  
Sheila Lopez-Cobo ◽  
Ana Rodriguez-Galan ◽  
Irene Fernandez-Delgado ◽  
Marta Ramirez-Huesca ◽  
...  

Natural killer (NK) cells recognise and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated NK cells and their secreted EVs led to the identification of a specific repertoire of NK-EV-associated microRNAs and their post-transcriptional modifications signature. Several microRNAs of NK-EVs, namely miR-10b-5p, miR-92a-3p and miR-155-5p, specifically target molecules involved in Th1 responses. NK-EVs promote the downregulation of GATA-3 mRNA in CD4+ T cells and subsequent T-bet de-repression that leads to Th1 polarization and IFN-γ and IL-2 production. NK-EVs also have an effect on monocyte and moDCs function, driving their activation and increased presentation and co-stimulatory functions. Nanoparticle-delivered NK-EV microRNAs partially recapitulate NK-EV effects in vivo. Our results provide new insights on the immunomodulatory roles of NK-EVs that may help to improve their use as immunotherapeutic tools.


Gene ◽  
2022 ◽  
pp. 146173
Author(s):  
YunQiang Zhang ◽  
MingYang Tang ◽  
Qiang Guo ◽  
HaoQiang Xu ◽  
ZhiYong Yang ◽  
...  

2022 ◽  
pp. 547-577
Author(s):  
Verónica E. Manzano ◽  
Custodiana A. Colmenarez Lobo ◽  
Evangelina Repetto

2022 ◽  
Author(s):  
Francisco G. Cirujano ◽  
Amarajothi Dhakshinamoorthy

Propargylamines are one of the aza-compounds very often observed in many drug molecules. Hence, considerable efforts have been made to obtain these target molecules in very high yields and selectivity....


Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 86
Author(s):  
Prabhat K. Mallik ◽  
Kimi Nishikawa ◽  
Pramit Mallik ◽  
Hua Shi

Unlike microbes that infect the human body, cancer cells are descended from normal cells and are not easily recognizable as “foreign” by the immune system of the host. However, if the malignant cells can be specifically earmarked for attack by a synthetic “designator”, the powerful effector mechanisms of the immune response can be conscripted to treat cancer. To implement this strategy, we have been developing aptamer-derived molecular adaptors to invoke synthetic immune responses against cancer cells. Here we describe multi-valent aptamers that simultaneously bind target molecules on the surface of cancer cells and an activated complement protein, which would tag the target molecules and their associated cells as “foreign” and trigger multiple effector mechanisms. Increased deposition of the complement proteins on the surface of cancer cells via aptamer binding to membrane targets could induce the formation of the membrane attack complex or cytotoxic degranulation by phagocytes and natural killer cells, thereby causing irreversible destruction of the targeted cells. Specifically, we designed and constructed a bi-functional aptamer linking EGFR and C3b/iC3b, and used it in a cell-based assay to cause lysis of MDA-MB-231 and BT-20 breast cancer cells, with either human or mouse serum as the source of complement factors.


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