Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy

Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of current clinically approved liposome-based drugs with free drugs, and to also determine the clinical effect via liposomal variations in lipid composition. Furthermore, the major preclinical and clinical data related to the principal liposomal formulations are also summarized

The correlation between the capacity fade of LiFePO4 batteries and cycle life

A new model is developed by fitting the capacity of LiFePO$_4$ batteries, which can be used to investigate the relationship between capacity fade, state of health (SoH), electrochemical reactions and the number of cycles. The equation for the proposed model based on modified Thevenin circuit, Butler-Volmer kinetics and regression analysis consists of a constant term, a sine-exponential term and an exponential term. The constant term represents the rated capacity of a battery, while the sine-exponential term represents the variation in capacity in the active status and the exponential term represents the variation in capacity in the stable status. The model is divided into two parts. The first part is represented by the sine-exponential term, responsive to the activation of electrolyte and electrodes in the first 180 cycles; the second part can be described by the exponential term, estimating the capacity from cycle 180 to cycle 2000. In addition, the comparison between the model and mean absolute percentage error (mape) is able to predict the serious decay of capacity. The MAPE is only 0.47% for the tested battery. The proposed model also successfully estimates the capacity of a tested battery where the number of cycles is 2000 with the error of 0.90%. The results mean that the model is able to closely describe the correlation between capacity and the cycle numbers. References M. Zhao, G. Huang, W. Zhang, H. Zhang and X. Song, Electrochemical behaviors of limn1-xfexpo4$/$c cathode materials in an aqueous electrolyte with/without dissolved oxygen, Energy and Fuels 27 (2013), 2:1162-1167. doi:10.1021/ef301893b Y.-C. Wang, F.-M. Ni and T.-L. Lee, Hybrid modulation of bidirectional three-phase dual-active-bridge dc converters for electric vehicles, Energies 9 (2016), no. 7, 492. doi:10.3390/en9070492 A. H. N. Galapitage and P. Pudney, Scheduling electric vehicles with shared charging stations, ANZIAM Journal 57 (2016), 208. doi:10.21914/anziamj.v57i0.10443 T. Zhu, H. T. Min, Y. B. Yu, Z. M. Zhao, T. Xu, Y. Chen, X. Y. Li and C. Zhang, An optimized energy management strategy for preheating vehicle-mounted li-ion batteries at subzero temperatures, Energies 10 (2017), no. 2. doi:24310.3390/en10020243 K. M. Tsang and W. L. Chan, State of health detection for lithium ion batteries in photovoltaic system, Energ Convers Manage 65 (2013), 7-12. doi:10.1016/j.enconman.2012.07.006 Z. Rao, S. Wang, M. Wu, Z. Lin and F. Li, Experimental investigation on thermal management of electric vehicle battery with heat pipe, Energ Convers Manage 65 (2013), 92-97. doi:0.1016/j.enconman.2012.08.014 A. Nikolian, Y. Firouz, R. Gopalakrishnan, J.-M. Timmermans, N. Omar, P. van den Bossche and J. van Mierlo, Lithium ion batteries-development of advanced electrical equivalent circuit models for nickel manganese cobalt lithium-ion, Energies 9 (2016), no. 5, 360. doi:10.3390/en9050360 Z. Gao, C. Chin, W. Woo and J. Jia, Integrated equivalent circuit and thermal model for simulation of temperature-dependent lifepo_4 battery in actual embedded application, Energies 10 (2017), no. 1, 85. doi:10.3390/en10010085 S.-Y. Lee, W.-L. Chiu, Y.-S. Liao, K.-Y. Lee, J.-H. Chen, H.-J. Lin and K. Li, Modified empirical fitting of the discharge behavior of lifepo_4 batteries under various conditions, ANZIAM Journal textbf55 (2014), 368. doi:10.21914/anziamj.v55i0.8182 C.-Y. Chung, K.-Y. Lee, T.-J. Kuo, Z.-Y. Lin, S.-D. Wu, C. Fu, Mathematical fitting for the variation in capacity of lithium iron phosphate batteries corresponding to cycles, ANZIAM Journal 57 (2016), 291. doi:10.21914/anziamj.v57i0.10436 T. Zahid and W. Li, A comparative study based on the least square parameter identification method for state of charge estimation of a lifepo_4 battery pack using three model-based algorithms for electric vehicles, Energies 9 (2016), no. 9, 720. doi:10.3390/en9090720 T. Sasaki, Y. Ukyo and P. Novak, Memory effect in a lithium-ion battery, Nat Mater 12 (2013), no. 6, 569-575. doi:10.1038/nmat3623 B. R. Tiwari and M. M. Ghangrekar, Enhancing electrogenesis by pretreatment of mixed anaerobic sludge to be used as inoculum in microbial fuel cells, Energy $and$ Fuels 29 (2015), no. 5, 3518-3524. doi:10.1021/ef5028197 P. Bai and M. Z. Bazant, Charge transfer kinetics at the solid-solid interface in porous electrodes, Nat Commun 5 (2014), 3585. doi:10.1021/ef990039t A. Eddahech, O. Briat and J.-M. Vinassa, Determination of lithium-ion battery state-of-health based on constant-voltage charge phase, Journal of Power Sources 258 (2014), 218-227. doi:10.1016/j.jpowsour.2014.02.020 R. Castaing, Y. Reynier, N. Dupre, D. Schleich, S. J. S. Larbi, D. Guyomard and P. Moreau Degradation diagnosis of aged li4ti5012-lifepo_4 batteries, Journal of Power Sources 267 (2014), 744-752. doi:10.1016/jpowsour.2014.06.002 H. Bulter, F. Peters, J. Schwenzel and G. Wittstock, In situ quantification of the swelling of graphite composite electrodes by scanning electrochemical microscopy, J Electrochem Soc 163 (2016), no. 2, A27-A34. doi:10.1149/2.1061514je

The long noncoding RNA THRIL regulates TNFalpha expression through its interaction with hnRNPL

Thousands of large intergenic noncoding RNAs (lincRNAs) have been identified in the mammalian genome, many of which have important roles in regulating a variety of biological processes. Here, we used a custom microarray to identify lincRNAs associated with activation of the innate immune response. A panel of 159 lincRNAs was found to be differentially expressed following innate activation of THP1 macrophages. Among them, linc1992 was shown to be expressed in many human tissues and was required for induction of TNFalpha expression. Linc1992 bound specifically to heterogenous nuclear ribonucleoprotein L (hnRNPL) and formed a functional linc1992-hnRNPL complex that regulated transcription of the TNFalpha gene by binding to its promoter. Transcriptome analysis revealed that linc1992 was required for expression of many immune-response genes, including other cytokines and transcriptional and posttranscriptional regulators of TNFalpha expression, and that knockdown of linc1992 caused dysregulation of these genes during innate activation of THP1 macrophages. Therefore, we named linc1992 THRIL (TNFalpha and hnRNPL related immunoregulatory LincRNA). Finally, THRIL expression was correlated with the severity of symptoms in patients with Kawasaki disease, an acute inflammatory disease of childhood. Collectively, our data provide evidence that lincRNAs and their binding proteins can regulate TNFalpha expression and may play important roles in the innate immune response and inflammatory diseases in humans

Survival analysis of Stage IIA1 and IIA2 cervical cancer patients

AbstractObjectiveThe aim of this study was to assess the benefits of the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system for survival of patients with Stage IIA1 and IIA2 cervical cancer (Cx Ca).Materials and MethodsA study cohort of 51 patients with Stage IIA Cx Ca was retrospectively collected from the 2004–2009 hospital-based, long-form Cx Ca data registry at Mackay Memorial Hospital (Taipei, Taiwan). The survivorship and overall survival were compared between these two groups (Stages IIA1 and IIA2) using log-rank test.ResultsThirty-six and 15 patients were classified into Stages IIA1 and IIA2, respectively. Stage IIA2 patients were younger than those with Stage IIA1 disease (mean age, 47.4 vs. 55.1 years, p = 0.008), but no significant difference was observed in confirmed pelvic lymph node status (21.4% vs. 38.5%, p = 0.280) between them. Although the 2-year and 5-year overall survival was better among Stage IIA1 patients, there was no significant difference in survival between Stage IIA1 and IIA2 groups (2-year, 90.6% vs. 77.8%; 5-year, 86.3% vs. 51.9%, p = 0.218).ConclusionAlthough there was a trend in survival difference between Stage IIA1 and IIA2 patients, the difference was not statistically significant. The revised FIGO 2009 staging system for Cx Ca defines a group of Stage IIA patients with bulky tumor (Stage IIA2) that are generally younger than Stage IIA1 patients. It is sensible to investigate an alternate or enhanced treatment scheme for Stage IIA2 patients. Ideally, the treatment scheme should prevent unnecessary radical surgery if a patient can be exposed to either chemotherapy or radiotherapy, alone or in combination

Analysis of Surgically Treated Intraspinal Tumors in Southern Taiwan

The medical records of 117 patients with spinal tumors who underwent surgery with pathologic confirmation from January 1999 to April 2004 at Kaohsiung Medical University Hospital were reviewed. Data from this review were compared with those obtained from the same institution 10 years earlier (covering the period 1988-1995) and from other reported series. There were 69 male and 48 female patients aged from 13 to 87 years old (mean age, 51.9). The most common pathologic findings were metastasis in 45.3% (53/117), nerve sheath tumors in 28.2% (33/117), menin-giomas in 12% (14/117) and neuroepithelial tumors in 6% (7/117). The peak ages at diagnosis were 41-50 years and 61–70 years. A slight male predominance was noted for all tumors, except meningiomas. Motor weakness, even paralysis, was the major clinical presentation (64–86%), followed by sensory deficits (50%) and pain (42%). The location of tumors was most often in the thoracic (50.4%; 59/117), lumbosacral (27.4%; 32/117) and cervical spine (22.2%; 26/117) segments. Among the metastatic tumors, the lung (22.6%) and breast (15.1%) were the most common primary sites of origin, followed by unknown origin, the liver (hepatocellular carcinoma), the gastrointestinal tract and the nasopharynx (nasopharyngeal cancer)

Ultrasmall all-optical plasmonic switch and its application to superresolution imaging

Because of their exceptional local-field enhancement and ultrasmall mode volume, plasmonic components can integrate photonics and electronics at nanoscale, and active control of plasmons is the key. However, all-optical modulation of plasmonic response with nanometer mode volume and unity modulation depth is still lacking. Here we show that scattering from a plasmonic nanoparticle, whose volume is smaller than 0.001 μm3, can be optically switched off with less than 100 μW power. Over 80% modulation depth is observed, and shows no degradation after repetitive switching. The spectral bandwidth approaches 100 nm. The underlying mechanism is suggested to be photothermal effects, and the effective single-particle nonlinearity reaches nearly 10−9 m2/W, which is to our knowledge the largest record of metallic materials to date. As a novel application, the non-bleaching and unlimitedly switchable scattering is used to enhance optical resolution to λ/5 (λ/9 after deconvolution), with 100-fold less intensity requirement compared to similar superresolution techniques. Our work not only opens up a new field of ultrasmall all-optical control based on scattering from a single nanoparticle, but also facilitates superresolution imaging for long-term observation

Photothermal responsivity of van der Waals material-based nanomechanical resonators

Nanomechanical resonators made from van der Waals materials (vdW NMRs) provide a new tool for sensing absorbed laser power. The photothermal response of vdW NMRs, quantified from the resonant frequency shifts induced by optical absorption, is enhanced when incorporated in a Fabry-Perot (FP) interferometer. Along with the enhancement comes the dependence of the photothermal response on NMR displacement, which lacks investigation. Here, we address the knowledge gap by studying electromotively driven niobium diselenide drumheads fabricated on highly reflective substrates. We use a FP-mediated absorptive heating model to explain the measured variations of the photothermal response. The model predicts a higher magnitude and tuning range of photothermal responses on few-layer and monolayer NbSe$_{2}$ drumheads, which outperform other clamped vdW drum-type NMRs at a laser wavelength of $532\,$nm. Further analysis of the model shows that both the magnitude and tuning range of NbSe$_{2}$ drumheads scale with thickness, establishing a displacement-based framework for building bolometers using FP-mediated vdW NMRs.Comment: 7 pages, 4 figure

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities