Preparation and evaluation of 2-methoxyestradiol-loaded pH-sensitive liposomes

The development and clinical application of 2-methoxyestradiol (2-ME) as a new type of antitumor drug are limited due to its poor solubility, rapid metabolism in vivo, and large oral dosage. 2-ME-loaded pHsensitive liposomes (2-ME-PSLs) was prepared containing the lipids, Lipoid E-80 (E-80), cholesteryl hemisuccinate (CHEMS), and cholesterol (CHOL) via thin-film ultrasonic dispersion. First, preparation conditions of 2-ME-PSLs were optimized by orthogonal test. Then 2-ME-PSL was characterized, and the release behavior and stability of 2-ME-PSL in vitro were evaluated. The optimal preparation conditions for 2-ME-PSLs were as follows: 2-ME : E-80+CHEMS 1:15; CHOL : E-80+CHEMS 1:5; ultrasonication time 20 minutes. The mean particle size, PDI, zeta potential, and entrapment efficiency (EE) of 2-MEPSLs were 116 ± 9 nm, 0.161 ± 0.025, −22.4 ± 1.7 mV, and 98.6 ± 0.5%, respectively. As viewed under a transmission electron microscope, 2-ME-PSLs were well dispersed and almost spherical. They exhibited significant pH-sensitive properties and were fairly stable when diluted with a physiological solution. In conclusion, 2-ME-PSLs were successfully prepared and possessed a favorable pH sensitivity and good dissolution stability with a normal solution

Advances in post-translational modifications of proteins and cancer immunotherapy

Protein post-translational modification (PTM) is a regulatory mechanism for protein activity modulation, localization, expression, and interactions with other cellular molecules. It involves the addition or removal of specific chemical groups on the amino acid residues of proteins. Its common forms include phosphorylation, ubiquitylation, methylation, and acetylation. Emerging research has highlighted lactylation, succinylation, and glycosylation. PTMs are involved in vital biological processes. The occurrence and development of diseases depends on protein abundance and is regulated by various PTMs. In addition, advancements in tumor immunotherapy have revealed that protein PTM is also involved in the proliferation, activation, and metabolic reprogramming of immune cells in tumor microenvironment. These PTMs play an important role in tumor immunotherapy. In this review, we comprehensively summarize the role of several types of PTMs in tumor immunotherapy. This review could provide new insights and future research directions for tumor immunotherapy

Causal association between lipid-lowering drugs and female reproductive endocrine diseases: a drug-targeted Mendelian randomization study

PurposeThe relationship between dyslipidemia and female reproductive endocrine diseases has been increasingly studied. The use of lipid-lowering drugs in treating various related diseases, including coronary heart disease, may affect female reproductive endocrine diseases. Therefore, our study aims to investigate the effects of lipid-lowering drugs on female reproductive endocrine diseases and provide a basis for the appropriate selection of drugs.MethodsIn this study, we focused on three drug targets of statins, namely HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase kexin 9 (PCSK9) inhibitors, and Niemann–Pick C1-Like 1 (NPC1L1) inhibitors. To identify potential inhibitors for these targets, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR, PCSK9, and NPC1L1 from published genome-wide association study statistics. Subsequently, we conducted a drug target Mendelian randomization (MR) analysis to investigate the effects of these inhibitors on reproductive endocrine diseases mediated by low-density lipoprotein cholesterol (LDL-C) levels. Alongside coronary heart disease as a positive control, our main outcomes of interest included the risk of polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), premenstrual syndrome (PMS), abnormal uterine bleeding (including menorrhagia and oligomenorrhea), and infertility.ResultsPCSK9 inhibitors significantly increased the risk of infertility in patients (OR [95%CI] = 1.14 [1.06, 1.23], p<0.05). In contrast, HMGCR inhibitors significantly reduced the risk of menorrhagia in female patients (OR [95%CI] = 0.85 [0.75, 0.97], p<0.05), but had no statistical impact on patients with oligomenorrhea.ConclusionThe findings suggest that PCSK9 inhibitors may significantly increase the risk of infertility in patients. On the other hand, HMGCR inhibitors could potentially offer protection against menorrhagia in women. However, no effects of lipid-lowering drugs have been observed on other reproductive endocrine disorders, such as PCOS, POF, PMS and oligomenorrhea

Lost calligraphy or reinvented motif : Chinese pictograms in Western fashion

This thesis investigates the complexity of cultural translation of visual language, considering writing systems both a profound shaping force and microcosmic reflection of the central elements of its culture. It focuses on the case of Chinese pictogram in Western everyday fashion; fashion is treated here as a site where the conceptual, aesthetic and cultural dynamics vividly interact with one another. This work probes what tensions are lost and added to the pictograms' cultural meaning in the process of translation, bearing in mind the two different aesthetic philosophies underlining Western and Chinese calligraphies. Seeing the complexity in the change of tensions, the thesis argues that nothing remains "authentic" in cultural translation, but the value of the encounter lies in the possibilities for each culture to reconsider itself in the corrective mirror of the Other

Optimal Placement of Virtual Masses for Structural Damage Identification

Adding virtual masses to a structure is an efficient way to generate a large number of natural frequencies for damage identification. The influence of a virtual mass can be expressed by Virtual Distortion Method (VDM) using the response measured by a sensor at the involved point. The proper placement of the virtual masses can improve the accuracy of damage identification, therefore the problem of their optimal placement is studied in this paper. Firstly, the damage sensitivity matrix of the structure with added virtual masses is built. The Volumetric Maximum Criterion of the sensitivity matrix is established to ensure the mutual independence of measurement points for the optimization of mass placement. Secondly, a method of sensitivity analysis and error analysis is proposed to determine the values of the virtual masses, and then an improved version of the Particle Swarm Optimization (PSO) algorithm is proposed for placement optimization of the virtual masses. Finally, the optimized placement is used to identify the damage of structures. The effectiveness of the proposed method is verified by a numerical simulation of a simply supported beam structure and a truss structure

Seismic damage mechanism of slope and lining in the mountain tunnel portal section

A series of numerical simulations were conducted to study the seismic response in the mountain tunnel portal section. The seismic damage mechanism, including slope cracking and landslide, rockfalls and collapse, and lining cracking were analyzed based on the seismic damage characteristics of the Longxi tunnel during the 2008 Wenchuan earthquake in China. The results show that slope cracking due to the huge horizontal seismic inertial force which exceeds the strength of slope; landslide is caused by the connected cracks where the oblique component of horizontal seismic inertia force exceeds the shear strength of slope; rockfalls and collapse are caused by the cumulative tensile stress in loose soil and rock which exceed the strength of slope; the transverse lining cracks due to the alternate tensile and compressive action of the seismic load along the axial direction, which makes the lining tensile strain accumulates and exceeds the concrete ultimate strength. As for the longitudinal lining cracking, the transverse seismic load makes the bending moment direction in lining alternates, leading to the strength reduction of concrete. Moreover, the circumferential penetrating rupture zone is caused by the large shear force resulting from the slope sliding, which leads to the stress concentration at vault and when the tensile stress exceeds the concrete tensile strength, the vault begins to crack, and then the cracks extend from the arch shoulder to foot

Siderophore (from Synechococcus sp. PCC 7002)-Chelated Iron Promotes Iron Uptake in Caco-2 Cells and Ameliorates Iron Deficiency in Rats

Siderophores are iron chelators with low molecular weight secreted by microorganisms. Siderophores have the potential to become natural iron fortifiers. To explore the feasibility of the application of Synechococcus sp. PCC7002-derived siderophores as iron fortifiers, Synechococcus sp. PCC7002, as a carrier, was fermented to produce siderophores. The absorption mechanism and anemia intervention effect of siderophores-chelated iron (SCI) were studied through the polarized Caco-2 Cell monolayers and the rat model of iron-deficiency anemia, respectively. The results indicated that siderophores (from Synechococcus sp. PCC7002) had an enhancing effect on iron absorption in polarized Caco-2 cell monolayers. The main absorption site of SCI was duodenum with pH 5.5, and the absorption methods included endocytosis and DMT1, with endocytosis being dominant. The effect of sodium phytate on SCI was less than that of ferrous sulfate. Therefore, SCI could resist inhibitory iron absorption factors in polarized Caco-2 cell monolayers. SCI showed significantly higher relative bioavailability (133.58 ± 15.42%) than ferrous sulfate (100 ± 14.84%) and ferric citrate (66.34 ± 8.715%) in the rat model. Food intake, hemoglobin concentration, and hematocrit and serum iron concentration of rats improved significantly after Fe-repletion. Overall, this study indicated that siderophores derived from Synechococcus sp. PCC7002 could be an effective and feasible iron nutritive fortifier