Mitomycin C is an anticancer antibiotic agent that has the potential for broad-spectrum use against several cancers, including mammary cancers. Because its half-life is 17 min after a 30 mg ...intravenous bolus administration, the suitability of mitomycin C for wide use in the clinical setting is limited. Based on tumor pathophysiology, pH-sensitive liposomes could provide better tumor-targeted effects. The aim of this study was to investigate the possibility of diminishing the side effect of mitomycin C by using pH-sensitive liposomes.
pH-sensitive liposomes was employed to deliver mitomycin C and evaluate the characterization, release behaviors, cytotoxicity, in vivo pharmacokinetics and biochemical assay.
The results demonstrated that mitomycin C-loaded pH-sensitive liposomes had a particle diameter of 144.5±2.8 nm and an entrapment efficiency of 66.5%. The in vitro release study showed that the pH-sensitive liposome release percentages at pH 7.4 and pH 5.5 were approximately 47% and 93%, respectively. The cell viability of MCF-7 cells showed that both the solution and liposome group exhibited a concentration-dependent effect on cell viability. The MCF-7 cell uptake of pH-sensitive liposomes with a folate modification was higher which was indicated by an increased fluorescence intensity compared to that without a folate modification. The area under the concentration-time curve of mitomycin C-loaded pH-sensitive liposomes (18.82±0.51 µg·h/L) was significantly higher than that of the mitomycin C solution group (10.07±0.31 µg·h/L). The mean residence times of the mitomycin C-loaded and mitomycin C solution groups were 1.53±0.16 and 0.05 h, respectively. In addition, there was no significant difference in terms of V
(
>0.05). Moreover, the half-life of pH-sensitive liposomes and the mitomycin C solution was 1.35±0.15 and 1.60±0.04 h, respectively. In terms of safety, mitomycin C-loaded pH-sensitive liposomes did not affect the platelet count and the levels of blood urea nitrogen and aspartate aminotransferase.
The positive results of pH-sensitive liposomes demonstrated maintained the cytotoxicity and decrease the side effect.
Background and purpose
Huntington's disease is due to a CAG triplet repeat elongation in the huntingtin gene. Boundaries in CAG numbers have been found between healthy people with and without risk to ...pass the disorder to the next generation, and between people without, with a mild, or with a fully penetrant phenotype. These data have been generated in western populations and it is not clear whether they are also valid amongst Chinese.
Methods
In order to establish normative data in the huntingtin gene for Chinese people, 966 chromosomes from normal controls were tested. Further, the range of CAG repeats was examined in a cohort from six centres and a total of 368 patients with the disease were included.
Results
The CAG triplet repeat range in normal controls was between 9 and 35 (mean 18.9, SD 2.57). Triplets in the range between 26 and 35 were found in 2.5%. In the patient cohort, triplet repeats in the shorter allele were between 8 and 37 (mean 17.7, SD 1.6). In the longer allele, a range between 36 and 120 was found. There was a negative correlation (−0.65, r = 0.42) between age at onset and the number of triplet repeats in the larger allele. The mean age at onset was 38 years, with a range between 2 and 70 years. In 23 patients (6%) a childhood or juvenile onset was noted.
Conclusion
These data show comparable ranges of huntingtin gene CAG triplet repeats in normal people and in patients with Huntington's disease as in western populations.
Cigarette smoking is the leading preventable cause of death in the United States. Although smoking behavior has a significant genetic determination, the specific genes and associated mechanisms ...underlying the smoking behavior are largely unknown. Here, we carried out a genome-wide association study on smoking behavior in 840 Caucasians, including 417 males and 423 females, in which we examined approximately 380,000 single nucleotide polymorphisms (SNPs). We found that a cluster of nine SNPs upstream from the IL15 gene were associated with smoking status in males, with the most significant SNP, rs4956302, achieving a P-value (8.80 x 10(-8)) of genome-wide significance. Another SNP, rs17354547 that is highly conserved across multiple species achieved a P-value of 5.65 x 10(-5). These two SNPs, together with two additional SNPs (rs1402812 and rs4956396) were selected from the above nine SNPs for replication in an African-American sample containing 1251 subjects, including 412 males and 839 females. The SNP rs17354547 was replicated successfully in the male subgroup of the replication sample; it was associated with smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerstrom Test for Nicotine Dependence (FTND), with P-values of 0.031, 0.0046 and 0.019, respectively. In addition, a haplotype formed by rs17354547, rs1402812 and rs4956396 was also associated with SQ, HSI and FTND, achieving P-values of 0.039, 0.0093 and 0.0093, respectively. To further confirm our findings, we carried out an in silico replication study of the nine SNPs in a Framingham Heart Study sample containing 7623 Caucasians from 1731 families, among which, 3491 subjects were males and 4132 were females. Again, the male-specific association with smoking status was observed, for which seven of the nine SNPs achieved significant P-values (P<0.05) and two achieved marginally significant P-values (P<0.10) in males. Several of the nine SNPs, including the highly conserved one across species, rs17354547, are located at potential transcription factor binding sites, suggesting transcription regulation as a possible function for these SNPs. Through this function, the SNPs may modulate the gene expression of IL15, a key cytokine regulating immune function. As the immune system has long been recognized to influence drug addiction behavior, our association findings suggest a novel mechanism for smoking addiction involving immune modulation through the IL15 pathway.
Du LZ, Liu PY, Ge CY, et al. Neuropsychiatr Dis Treat. 2022;18:13091314. The authors have advised the affiliation on page 1309 is incorrect. The correct affiliation should read "Department of ...Clinical Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China". The authors apologize for this error.
CuS and Cu1.1Fe1.1S2 crystals have been synthesized by the hydrothermal decomposition of Cu or Cu/Fe diethyldithiocarbamate complex obtained by mixing sodium diethyldithiocarbamate, CuCl2 and FeCl3 ...in absolute ethanol. CuS crystals with a hexagonal structure exhibit irregular particles with an average size of less than 500nm and rod-shaped morphology with a diameter of less than 100nm. Cu1.1Fe1.1S2 crystals with a cubic structure contain irregular particles and some rod-shaped structures with length and diameter of about 1μm and less than 100nm, respectively. The electrochemical responses of the Cu1.1Fe1.1S2 crystal modified glassy carbon electrode in NaCl and PBS solution show the irreversible and semi-reversible electrochemical process, respectively, which may originate from the NaCl, PBS solution and ascorbic acid. The Cu1.1Fe1.1S2 crystal modified electrodes exhibit definite potential to be used as the electrochemical sensors for detecting cysteine and ascorbic acid.
► CuS and Cu1.1Fe1.1S2 crystals were prepared by the hydrothermal decomposition process. ► The Cu1.1Fe1.1S2 modified electrode exhibits potential for cysteine and ascorbic acid. ► The Cu1.1Fe1.1S2 modified electrode may be used as electrochemical sensors.
In this study, the subcellular localization, tissue distribution and response to grass carp reovirus (GCRV) infection and lipopolysaccharide (LPS) stimulation of four grass carp Ctenopharyngodon ...idellus toll‐like receptor 4 (tlr4) genes were investigated. All four genes were constitutively expressed in all tissues studied, but the subcellular localization and tissue exhibiting the highest expression differed for each protein. Following GCRV infection, all the four tlr4s were upregulated in all tissues examined, and stimulation of C. idellus kidney (CIK) cells with LPS resulted in downregulation of all four tlr4s. These results provide a foundation for further investigation of tlr4 genes in bony fishes.
Background There is increasing concern about the surgeon maintaining a static posture during laparoscopic surgery, which can contribute to musculoskeletal disorders. A series of studies are being ...conducted in Hong Kong examining the surgeons’ real-time movements and electromyography in the operating theater during different operations. The present paper examines the postures and movements of surgeons during real-time open and laparoscopic procedures. Materials and Methods Fourteen surgeons participated in the study (12 men, 2 women). Cervical spine movements were measured using a biaxial inclinometer attached to the surgeon’s head via a headband. Biaxial electrogoniometers were attached to the surgeon’s bilateral shoulder joints. Real-time joint movements in sagittal and coronal planes were recorded during open and laparoscopic surgeries for periods ranging from 30 to 80 min. Results Surgeons generally maintained a flexed neck posture during open surgery and a more extended neck posture during laparoscopic procedures. There were statistically significant differences in mean neck posture and mean left shoulder abduction posture between the two types of surgery. Laparoscopic procedures showed a trend for longer duration in static posture in the neck, while open procedures showed trends for higher frequencies of movements. Conclusions This study presented a novel approach to quantify the physical workload of surgeons using biomechanical parameters to describe duration of static posture and repetitiveness of movements. Results showed that long durations of static postures in laparoscopic surgery were closely associated with low-level muscle tension, which may contribute to an increased risk of surgeons developing musculoskeletal disorders.
The magnetoelectric (ME) effect originating from the effective coupling between electric field and magnetism is an exciting frontier in nanoscale science such as magnetic tunneling junction (MTJ), ...ferroelectric/piezoelectric heterojunctions etc. The realization of switchable ME effect under external electric field in d0
semiconducting materials of single composition is needed especially for all‐silicon spintronics applications because of its natural compatibility with current industry. We employ density functional theory (DFT) to reveal that the pristine Si(111)‐3×3
R30° (Si3
hereafter) reconstructed surfaces of thin films with a thickness smaller than eleven bilayers support a sizeable linear ME effect with switchable direction of magnetic moment under external electric field. This is achieved through the interlayer exchange coupling effect in the antiferromagnetic regime, where the spin‐up and spin‐down magnetized density is located on opposite surfaces of Si3
thin films. The obtained coefficient for the linear ME effect can be four times larger than that of ferromagnetic Fe films, which fail to have the reversal switching capabilities. The larger ME effect originates from the spin‐dependent screening of the spin‐polarized Dirac fermion. The prediction will promote the realization of well‐controlled and switchable data storage in all‐silicon electronics.
Switchable magnetoelectric effect: Silicon thin films with pristine Si(111)‐3×3
R30° reconstructed surfaces have antiferromagnetic magnetic structure. An external electric field can induce a variation in the total magnetic moment, which is known as the magnetoelectric effect. The effect originating from spin‐dependent screening is four times larger than that in ferromagnetic Fe films.
This paper describes a fuzzy modeling framework based on support vector machine, a rule-based framework that explicitly characterizes the representation in fuzzy inference procedure. The support ...vector learning mechanism provides an architecture to extract support vectors for generating fuzzy IF-THEN rules from the training data set, and a method to describe the fuzzy system in terms of kernel functions. Thus, it has the inherent advantage that the model does not have to determine the number of rules in advance, and the overall fuzzy inference system can be represented as series expansion of fuzzy basis functions. The performance of the proposed approach is compared to other fuzzy rule-based modeling methods using four data sets.
Four novel amicoumacins, namely lipoamicoumacins A-D (1-4), and one new bacilosarcin analog (5) were isolated from culture broth of a marine-derived bacterium Bacillus subtilis, together with six ...known amicoumacins. Their structures were elucidated on the basis of extensive spectroscopic (2D NNR, IR, CD and MS) analysis and in comparison with data in literature.
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