The pharmaceutical industry has been desperately searching for efficient drug discovery methods. Organ-on-a-Chip, a cutting-edge technology that can emulate the physiological environment and ...functionality of human organs on a chip for disease modeling and drug testing, shows great potential for revolutionizing the drug development pipeline. However, successful translation of this novel engineering platform into routine pharmacological and medical scenarios remains to be realized. In this review, we discuss how the Organ-on-a-Chip technology can have critical roles in different preclinical stages of drug development and highlight the current challenges in translation and commercialization of this technology for the pharmacological and medical end-users. Moreover, this review sheds light on the future developmental trends and need for a next-generation Organ-on-a-Chip platform to bridge the gap between animal studies and clinical trials for the pharmaceutical industry.
Organ-on-a-Chip is a promising interdisciplinary technique emulating in vivo physiology and pathology for in vitro disease modeling, drug screening, and precision medicine.The Organ-on-a-Chip technology can be organically incorporated into the drug development pipeline from early drug discovery to preclinical screening, testing, and translation of new drugs, which bridges the gap between animal studies and clinical trials involving human subjects.The future development of personalized Organ-on-a-Chip and continuous integration of novel engineering tools (e.g., automation handling, 3D printing. and in situ multisensors) and biological concepts (e.g., patient-specific induced pluripotent stem cells and organoids) into Organ-on-a-Chip platform will unprecedentedly promote its biomedical applications.
This paper presents generalized logic-based methods for intelligent fault diagnosis in power electronic converters based on correlation between faults and basic measurements. Fault recovery is then ...applied based on this correlation by using necessary signals and quantities from existing measurements. The main purpose of the proposed fault diagnosis methods is for power electronic systems to survive from fault conditions that could occur in various components, to cope with the notion of a smart grid and extend their lifetime. The proposed methods are online, i.e., real-time or near-real-time, and can be applied to any power electronic system. Existing intelligent control of power electronic systems along with various short- and open-circuit faults in major power electronic components are reviewed. Two methods are established to diagnose faults and engage redundancy for fault recovery with one method using combinational logic and another using fuzzy logic. In both methods, two quantities are observed for each of the measured signals: 1) the signal's average value and 2) the signal's RMS value. Total harmonic distortion is also used in some simulations but is not required in experimental implementation. A systematic methodology to reduce the number of measured quantities while maintaining effective diagnosis is introduced. A solar PV microinverter in standalone mode is used as an example testing platform for the proposed methods. A simulation model is experimentally validated and the effect of each fault on different voltage and current measurements are observed, then both methods are tested in simulation and hardware. Results show the ability of both methods to diagnose several faults in the inverter's power stage along with their ability to engage redundancy for fault recovery.
Circulating tumor cells (CTCs) escape from primary or metastatic lesions and enter into circulation, carrying significant information of cancer progression and metastasis. Capture of CTCs from the ...bloodstream and the characterization of these cells hold great significance for the detection, characterization, and monitoring of cancer. Despite the urgent need from clinics, it remains a major challenge to capture and retain these rare cells from human blood with high specificity and yield. Recent exciting advances in micro/nanotechnology, microfluidics, and materials science have enable versatile, robust, and efficient cell isolation and processing through the development of new micro/nanoengineered devices and biomaterials. This review provides a summary of recent progress along this direction, with a focus on emerging methods for CTC capture and processing, and their application in cancer research. Furthermore, classical as well as emerging cellular characterization methods are reviewed to reveal the role of CTCs in cancer progression and metastasis, and hypotheses are proposed in regard to the potential emerging research directions most desired in CTC‐related cancer research.
Capturing circulating tumor cells (CTCs) from the bloodstream and characterizing these cells hold great significance for the detection, characterization, and monitoring of cancer. This review provides a summary of emerging micro/nanotechnologies for CTC capture, characterization, and application, as well as future directions in cancer research.
Long noncoding RNAs (lncRNAs) are RNAs whose transcripts are longer than 200nt in length and lack the ability to encode proteins due to lack of specific open reading frames. lncRNAs were once thought ...to represent transcriptome noise or garbage sequences and a byproduct of RNA polymerase II (Pol II), and thereby ignored by researchers. In fact, lncRNA was involved in a wide variety of physiological and pathological processes in organisms. Comprehensive study of lncRNA does not only provide explanations to the physiological and pathological processes of living organisms, but also gives us new perspectives to the diagnosis, prevention and treatment of some clinical diseases. Therefore, the study of lncRNA is a very broad field of great research value and significance.
This article reviews the function of lncRNAs and their role in major human diseases.
Numerous studies show that lncRNA might serve as a biomarker for diagnosis and prognosis of various diseases. Compared to conventional biomarkers, lncRNA seems to have a higher diagnostic and prognostic values, not only because of their tissue and disease specific expression patterns, but also due to their highly stable physical and chemical properties.
Due to the close links between quality of life standards and level of regional development, it is important to gain an improved understanding of the factors that contribute to unequal spatial ...accessibility of medical and health services in China. This study analyzed 2859 counties using the average shortest distance traveled from settlements to medical facilities to calculate spatial accessibility. The Theil index at three levels (three partitions, eight economic zones and provinces) was used to assess the inequality between regions. Then, a method of spatial autocorrelation was used to assess the spatial agglomeration characteristics of spatial accessibility. To explore the underlying reasons for the imbalance in spatial accessibility, a total of eight indicators in three aspects (nature, society, and economy) were collected and geographically weighted regression (GWR) was employed to investigate spatial heterogeneity. We observed marked disparities in spatial accessibility to medical facilities at the national level. In particular, there appears to be improved spatial accessibility and lesser regional inequality in eastern and central regions as opposed to western Chinese regions; in coastal regions instead of inland regions; and in municipalities such as Beijing, Tianjin, and Shanghai, but not in other provinces and autonomous regions. Besides, significant global autocorrelation and obvious clusters were revealed in a spatial pattern analysis. A wide range of hot-spot areas (clusters of poor spatial accessibility) mainly concentrated in Tibet and other areas with complex terrain and lagging social and economic development. A number of cold-spot areas (clusters of good spatial accessibility) mostly scattered in built-up areas especially municipalities and well-developed urban agglomeration such as the Yangtze River Delta, the Pearl River Delta, and the Wuhan 1 + 8 city circle. Furthermore, the relationships between influencing factors and spatial accessibility were also investigated. The influence of altitude on spatial accessibility gradually decreased from the West to the East, while the influence of slope decreased from the South to the North with prominent provinces of Qinghai and Gansu. Population density exerted a higher impact on the distance in the southwest region whereas the urbanization rate influenced the northeast and southeast coastal region more intensively. In contrast, the pattern of educational level was relatively discrete. The influencing pattern of economic factors in both per area GDP and tertiary industry output share of accessibility showed apparent regional characteristics in the southeast coastal areas, as well as in the northwestern and northeastern parts. Outcomes from this study can be used to provide important information to aid policy making, while also facilitating future research aimed at improving the understanding of equality and sustainable development of medical facilities.
•This study provides data of medical facility accessibility for 2859 counties in China.•Disparities were found in spatial accessibility to medical facilities at three scales.•A significant global autocorrelation and obvious clusters were revealed.•Prominent counties with significant disparity to their neighbors were identified.•The aspects nature, society, and economy and eight influencing factors were analyzed.
Radiotherapy is one of the major therapeutic strategies for cancer treatment. In the past decade, there has been growing interest in using high Z (atomic number) elements (materials) as ...radiosensitizers. New strategies in nanomedicine could help to improve cancer diagnosis and therapy at cellular and molecular levels. Metal-based nanoparticles usually exhibit chemical inertness in cellular and subcellular systems and may play a role in radiosensitization and synergistic cell-killing effects for radiation therapy. This review summarizes the efficacy of metal-based
against cancers in both
and
systems for a range of ionizing radiations including gamma-rays, X-rays, and charged particles. The potential of translating preclinical studies on metal-based nanoparticles-enhanced radiation therapy into clinical practice is also discussed using examples of several metal-based
(such as CYT-6091, AGuIX, and NBTXR3). Also, a few general examples of theranostic multimetallic nanocomposites are presented, and the related biological mechanisms are discussed.
•Synthetic nanotopographical surfaces for stem cell fate control.•Emerging nanotechnologies for generation of nanotopographical surfaces.•Cellular mechano-sensing and -transduction mechanisms for ...nanotopography sensing.
During embryogenesis and tissue maintenance and repair in an adult organism, a myriad of stem cells are regulated by their surrounding extracellular matrix (ECM) enriched with tissue/organ-specific nanoscale topographical cues to adopt different fates and functions. Attributed to their capability of self-renewal and differentiation into most types of somatic cells, stem cells also hold tremendous promise for regenerative medicine and drug screening. However, a major challenge remains as to achieve fate control of stem cells in vitro with high specificity and yield. Recent exciting advances in nanotechnology and materials science have enabled versatile, robust, and large-scale stem cell engineering in vitro through developments of synthetic nanotopographical surfaces mimicking topological features of stem cell niches. In addition to generating new insights for stem cell biology and embryonic development, this effort opens up unlimited opportunities for innovations in stem cell-based applications. This review is therefore to provide a summary of recent progress along this research direction, with perspectives focusing on emerging methods for generating nanotopographical surfaces and their applications in stem cell research. Furthermore, we provide a review of classical as well as emerging cellular mechano-sensing and -transduction mechanisms underlying stem cell nanotopography sensitivity and also give some hypotheses in regard to how a multitude of signaling events in cellular mechanotransduction may converge and be integrated into core pathways controlling stem cell fate in response to extracellular nanotopography.
White blood cells (WBCs) constitute about 0.1% of the blood cells, yet they play a critical role in innate and adaptive immune responses against pathogenic infections, allergic conditions, and ...malignancies and thus contain rich information about the immune status of the body. Rapid isolation of WBCs directly from whole blood is a prerequisite for any integrated immunoassay platform designed for examining WBC phenotypes and functions; however, such functionality is still challenging for blood-on-a-chip systems, as existing microfluidic cell sorting techniques are inadequate for efficiently processing unprocessed whole blood on chip with concurrent high throughput and cell purity. Herein we report a microfluidic chip for continuous-flow isolation and sorting of WBCs from whole blood with high throughput and separation efficiency. The microfluidic cell sorting chip leveraged the crossflow filtration scheme in conjunction with a surface-micromachined poly(dimethylsiloxane) (PDMS) microfiltration membrane (PMM) with high porosity. With a sample throughput of 1 mL h(-1), the microfluidic cell sorting chip could recover 27.4 ± 4.9% WBCs with a purity of 93.5 ± 0.5%. By virtue of its separation efficiency, ease of sample recovery, and high throughput enabled by its continuous-flow operation, the microfluidic cell sorting chip holds promise as an upstream component for blood sample preparation and analysis in integrated blood-on-a-chip systems.
Radiotherapy (RT) is considered an important therapeutic strategy in the fight against colorectal cancer (CRC). However, the existence of some radioresistance factors becomes the main challenge for ...the RT. Recently, non-coding RNAs (ncRNAs) have shown an important role in modulating cancer cell responses to ionizing radiation (IR). It is therefore of great significance to elucidate the exact mechanisms of ncRNAs in IR-mediated responses to CRC.
Microarrays were used to identify specific miRNAs that may be altered in response to IR. Bioinformatics, luciferase reporter analyses were used to explore the targets of miR-6778-5p. CircRNA CBL.11 was identified to bind with miR-6778-5p by bioinformatic analysis, AGO2 immunoprecipitation and biotinylated RNA pull-down assay. Functional experiments, including CCK-8 assay, cell colony formation assay and EdU incorporation were conducted to investigate the biological roles of miR-6778-5p and circular RNA CBL.11.
MiR-6778-5p was suppressed in CRC cells after irradiation. Results of functional experiments indicated that miR-6778-5p promoted the proliferation of CRC cells. Luciferase reporter analyses showed that YWHAE was a target of miR-6778-5p, which mediated the function of miR-6778-5p in the proliferation of CRC cells via the p53 pathway. Furthermore, we have noticed that after carbon ion irradiation, circRNA CBL.11 was increased in CRC cells and could function as a competing endogenous RNA (ceRNA) to regulate YWHAE expression by sponging miR-6778-5p, resulting in regulation the proliferation of CRC cells.
CircRNA CBL.11 may play an important role in improving the efficacy of carbon ion RT against CRC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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