10/14/2024


Ovarian cancer is highly metastatic, with a high frequency of relapse, and is the most fatal gynecologic malignancy in women worldwide. It is important to elevate the drug susceptibility and cytotoxicity of ovarian cancer cells, thereby eliminating resident cancer cells for more effective therapeutic efficacy. Here, we developed a bispecific antibody (BsAb; mPEG × HER2) that can easily provide HER2+ tumor tropism to mPEGylated liposomal doxorubicin (PLD) and further increase the drug accumulation in cancer cells via receptor-mediated endocytosis, and improve the cytotoxicity and therapeutic efficacy of HER2+ ovarian tumors. The mPEG × HER2 can simultaneously bind to mPEG molecules on the surface of PLD and HER2 antigen on the surface of ovarian cancer cells. Simply mixing the mPEG × HER2 with PLD was able to confer HER2 specificity of PLD to HER2+ ovarian cancer cells and efficiently trigger endocytosis and enhance cytotoxicity by 5.4-fold as compared to non-targeted PLD. mPEG × HER2-modified PLD was able to significantly increase the targeting and accumulation of HER2+ ovarian tumor by 220% as compared with non-targeted PLD. It could also significantly improve the anti-tumor activity of PLD (P  less then  0.05) with minimal obvious toxicity in a tumor-bearing mouse model. We believe that the mPEG × HER2 can significantly improve the therapeutic efficacy, potentially reduce the relapse freqency and thereby achieve good prognosis in ovarian cancer patients.In this paper, we present a Kane-Mele model in the presence of magnetic field and next nearest neighbors hopping amplitudes for investigations of the spin susceptibilities of Germanene layer. Green's function approach has been implemented to find the behavior of dynamical spin susceptibilities of Germanene layer within linear response theoryand in the presence of magnetic field and spin-orbit coupling at finite temperature. Our results show the magnetic excitation mode for both longitudinal and transverse components of spin tends to higher frequencies with spin-orbit coupling strength. Moreover the frequency positions of sharp peaks in longitudinal dynamical spin susceptibility are not affected by variation of magnetic field while the peaks in transverse dynamical susceptibility moves to lower frequencies with magnetic field. The effects of electron doping on frequency behaviors of spin susceptibilities have been addressed in details. Finally the temperature dependence of static spin structure factors due to the effects of spin-orbit coupling, magnetic field and chemical potential has been studied.Grapheme-colour synesthesia occurs when letters or numbers elicit an abnormal colour sensation (e.g., printed black letters are perceived as coloured). This phenomenon is typically reported following explicit presentation of graphemes. Very few studies have investigated colour sensations in synesthesia in the absence of visual awareness. We took advantage of the dichoptic flash suppression paradigm to temporarily render a stimulus presented to one eye invisible. Synesthetic alphanumeric and non-synesthetic stimuli were presented to 21 participants (11 synesthetes) in achromatic and chromatic experimental conditions. The test stimulus was first displayed to one eye and then masked by a sudden presentation of visual noise in the other eye (flash suppression). The time for an image to be re-perceived following the onset of the suppressive noise was calculated. Trials where there was no flash suppression performed but instead mimicked the perceptual suppression of the flash were also tested. Results showed that target detection by synesthetes was significantly better than by controls in the absence of flash suppression. No difference was found between the groups in the flash suppression condition. Our findings suggest that synesthesia is associated with enhanced perception for overt recognition, but does not provide an advantage in recovering from a perceptual suppression. Further studies are needed to investigate synesthesia in relation to visual awareness.The drivers of organic carbon (OC) burial efficiency are still poorly understood despite their key role in reliable projections of future climate trends. Here, we provide insights on this issue by presenting a paleoclimate time series of sediments, including the OC contents, from Lake Veliko jezero, Croatia. The Sr/Ca ratios of the bulk sediment are mainly derived from the strontium (Sr) and calcium (Ca) concentrations of needle-like aragonite in Core M1-A and used as paleotemperature and paleohydrology indicators. Four major and six minor cold and dry events were detected in the interval from 8.3 to 2.6 calibrated kilo anno before present (cal ka BP). https://www.selleckchem.com/JNK.html The combined assessment of Sr/Ca ratios, OC content, carbon/nitrogen (C/N) ratios, stable carbon isotope (δ13C) ratios, and modeled geochemical proxies for paleoredox conditions and aeolian input revealed that cold and dry climate states promoted anoxic conditions in the lake, thereby enhancing organic matter preservation and increasing the OC burial efficiency. Our study shows that the projected future increase in temperature might play an important role in the OC burial efficiency of meromictic lakes.In quantitative PCR research, appropriate reference genes are key to determining accurate mRNA expression levels. In order to screen the reference genes suitable for detecting gene expression in tissues of the reproductive axis, a total of 420 (males and females = 15) 3-year-old Magang geese were selected and subjected to light treatment. The hypothalamus, pituitary and testicular tissues were subsequently collected at different stages. Ten genes including HPRT1, GAPDH, ACTB, LDHA, SDHA, B2M, TUBB4, TFRC, RPS2 and RPL4 were selected as candidate reference genes. The expression of these genes in goose reproductive axis tissues was detected by real-time fluorescent quantitative PCR. The ΔCT, geNorm, NormFinder and BestKeeper algorithms were applied to sort gene expression according to stability. The results showed that ACTB and TUBB4 were the most suitable reference genes for the hypothalamic tissue of Magang goose in the three breeding stages; HPRT1 and RPL4 for pituitary tissue; and HPRT1 and LDHA for testicular tissue.