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AbstractBovine serum albumin (BSA), a model protein was used to evaluate the binding behavior of nisoldipine and human serum albumin by a series of experiments and in silicoin this article. The outcomes suggested that nisoldipine and BSA formed the nisoldipine-BSA complex with a molar ratio of 1:1, caused the fluorescence quenching of BSA, which quenching mechanism was attributable to static quenching. The binding constant of the nisoldipine-BSA complex was (1.3–3.0) × 104 M−1at 298–310 K, indicating that nisoldipine on BSA protein had a moderate affinity. During the complexation of nisoldipine with BSA, nisoldipine can spontaneously insert into the site II (subdomain III A) of BSA and the distance of energy transfer from donor group in protein to acceptor group in nisoldipine was 3.21 nm, which led to the change in the hydrophobicity of the microenvironment surrounding Trp residues and in the secondary structure of BSA. Additionally, the findings also confirmed that the hydrogen bond and van der Waals force were responsible for forming the nisoldipine-BSA complex and the complexation process was a spontaneous exothermic process.Communicated by Ramaswamy H. Sarma

The demand for structural lightweight in a variety of industries, particularly the automobile industry, has driven the development of heat-free die-cast aluminum alloys with excellent properties. Utilizing lightweight materials, such as Al-Si alloys has several benefits, including higher overall performance in automobiles and other industries, increased heat resistance efficiency, decreased emissions, and reduced weight. The purpose of this study is to modify the microstructure and enhance the mechanical properties of high-pressure die-casting (HPDC) AlSi10MnMg foundry alloy by incorporation of TiB2 and Sc without any heat treatment. The results showed that the HPDC process significantly refines the grain structure and AlSiMnFe intermetallic compounds, transforming the eutectic morphology from sharp to rounded, and 93% enhancement in elongation at the optimum content (0.018 wt.%) of TiB2. While the hardness of the alloy was improved by 15.7% with the addition of 0.03wt.% TiB2. TiB2 incorporation refines the grain structure and AlSiMnFe phases, while depressing externally solidified crystals (ESCs). The HPDC process refines Al3Sc phases as well as AlSiMnFe phases while increasing yield strength due to Al3Sc strengthening effects. After 0.5wt.% Sc addition in 0.018wt.% TiB2-AlSi10MnMg alloy, the YS, and EL reached the maximum of 196MPa and 9.93% respectively.

AbstractDacomitinib (DAC), as a member of tyrosine kinase inhibitors is primarily used to treat non-small cell lung cancer. The intermolecular interaction between DAC and bovine serum albumin (BSA) was comprehended with the help of experiments and theoretical simulations. The outcomes indicated that DAC quenched the endogenous fluorescence of BSA through static quenching mode. In the binding process, DAC was preferentially inserted into the hydrophobic cavity of BSA subdomain IA (site III), and a fluorescence-free DAC-BSA complex with molar ratio of 1:1 was generated. The outcomes confirmed that DAC had a stronger affinity on BSA and the non-radiative energy transfer occurred in the combination process of two. And, it can be inferred from the outcomes of thermodynamic parameters and competition experiments with 8-aniline-1-naphthalenesulfonic acid (ANS) and D-(+)- sucrose that hydrogen bonds (H-bonds), van der Waals forces (vdW) and hydrophobic forces had a significant impact in inserting DAC into the hydrophobic cavity of BSA. The outcomes from multi-spectroscopic measurements that DAC could affect the secondary structure of BSA, that was, α-helix content decreased slightly from 51.0% to 49.7%. Moreover, the combination of DAC and BSA led to a reduction in the hydrophobicity of the microenvironment around tyrosine (Tyr) residues in BSA while had little influence on the microenvironment of around tryptophan (Trp) residues. The outcomes from molecular docking and molecular dynamics (MD) simulation further demonstrated the insertion of DAC into site III of BSA and hydrogen energy and van der Waals energy were the dominant energy of DAC-BSA stability. In addition, the influence of metal ions (Fe3+, Cu2+, Co2+, etc.) on the affinity of the system was explored.Communicated by Ramaswamy H. Sarma

The link between inflammation and the evolution of cancer is well established. Visualizing and tracking both tumor proliferation and the associated inflammatory response within a living organism are vital for dissecting the nexus between these two processes and for crafting precise treatment modalities. We report the creation and synthesis of an advanced NIR chemiluminescence probe that stands out for its exceptional selectivity, extraordinary sensitivity at nanomolar concentrations, swift detection capabilities, and broad application prospects. Crucially, this probe has been successfully utilized to image endogenous ONOO–across different inflammation models, including abdominal inflammation triggered by LPS, subcutaneous inflammatory conditions, and tumors grafted onto mice. These findings highlight the significant promise of chemiluminescence imaging in enhancing our grasp of the intricate interplay between cancer and inflammation and in steering the development of potent, targeted therapeutic strategies.

AbstractApatinib mesylate (APM), an oral tyrosine kinase inhibitor, has a good anti-tumor activity in the treatment of various cancers, particularly in advanced non-small cell lung cancer. In this study, the intermolecular binding mechanism between APM and human alpha-1-acid glycoprotein (HAG) was investigated by combining multi-spectroscopic approaches with in silicotechniques. The findings revealed that APM gave rise to the fluorescence quenching of HAG by forming a ground-state complex between APM and HAG with a stoichiometric ratio of 1:1, and APM has a moderate affinity for HAG as the binding constant of APM and HAG of approximately 105M−1, which was larger than the APM-HAG complex. The findings from thermodynamic parameter analysis indicated that the dominant driving forces for the formation of the APM-HAG complex were van der Waals forces, hydrogen bonding and hydrophobic interactions, which were also verified with site-probe studies and molecular docking. The findings from in silicostudy indicated that APM inserted into the opening of the hydrophobic cavity of HAG, leads to a slight conformational change in the HAG, which was verified by circular dichroism (CD) measurements, that was, the beta sheet level of HAG decreased. Additionally, the results of synchronous and 3D fluorescence spectroscopies confirmed the decline in hydrophobicity of the microenvironment around Trp and Tyr residues. Moreover, some common metal ions such as Cu2+, Mg2+, Fe3+, Ca2+, and Zn2+could cause the alteration in the binding constant of APM with HAG, leading to the change in the efficacy of APM. It will be expected that these study findings are to provide useful information for further understanding pharmacokinetic and structural modifications of APM.Communicated by Ramaswamy H. Sarma

AbstractTo investigate the binding characteristics of pesticide ethiprole (ETP) with serum albumin is of great significance for pathological analysis of pesticide poisoning, gene mutation, and clinical detection. In present work, the binding characteristics of ETP with a model protein BSA has been estimated by means of multi-spectroscopic approaches integrated with computer simulation. The outcomes testified that the intrinsic fluorescence of BSA was mainly quenched by ETP in a static quenching mode and the stable ETP-BSA complex with the stoichiometry of 1:1 and the binding constant of 6.81 × 103M−1(298 K) was produced. The outcomes revealed that ETP combined preferentially to the subdomain IIA (Site I) of BSA and caused the decline in the content of α-helix of BSA and the enhancement in the hydrophobicity of environment centered on Trp residues. The outcomes of experimental and theoretical studies provide the sufficient evidence about the driving forces for the complexation of ETP with BSA, which included van der Waals forces (vdW), hydrogen bonding (H-bonding) interaction, and hydrophobicity. Simultaneously, the theoretical calculation results also confirmed the existence of the significant changes in the physicochemical natures of ETP including molecular conformation, dipole moment, frontier orbital energy, and the atomic charge distribution, which was a responsible for the complexation with BSA.Communicated by Ramaswamy H. Sarma

The effect of Mn additions (up to 0.8 wt.%) into Al-7Si-0.3Mg alloy on the microstructure, mechanical properties and die soldering was firstly investigated in gravity die casting conditions, with the aim to obtain an optimized Mn addition level. Especially, the stirring testing on H13 die material was used to elucidate the effect of Mn additions on the Fe concentration in the Al melting as a function of melting temperature (690 °C) and holding time (up to 32 h), which can provide an indirect sign of die soldering. On this basis, the addition of 0.6wt.%Mn into Al-7Si-0.3Mg alloy was found to be beneficial for microstructure, strength and die soldering. Secondly, rheocasting of Al-7Si-0.3Mg alloy without (Mn-free alloy) and with 0.6 wt.% Mn (Mn-containing alloy) was performed. The addition of 0.6wt.%Mn into Al-7Si-0.3Mg alloy was found to have following effects: (i) solidification temperature of α-Al is increased and a higher (about 20 °C) rheocasting temperature is therefore needed, but no significant die soldering problem was observed even with increasing casting temperature, (ii) Mn-containing phase forms along grain boundaries and within Al matrix, which increases tensile and yield strength but decreases elongation in as-cast, T5 and T6 conditions, (iii) number density and volume fraction of pores increases, and (iv) die soldering slightly improves. This paper demonstrates that the addition of 0.6wt.%Mn into Al-7Si-0.3Mg alloy is beneficial for microstructure, strength and die soldering in both gravity die casting and rheocasting conditions.

In this paper, both thixocasting and rheocasting of Al-7Si-0.6Mg alloy (EN AC 42200) for the same part was performed. It was found that rheocasting of Al-7Si-0.6Mg alloy show a smaller primary Al grain size and significant improvement of cast defects compared with thixocasting of Al-7Si-0.6Mg alloy. This paper demonstrates that rheocasting of Al-7Si-0.6Mg alloy is more beneficial in terms of microstructure and cast defects compared with thixocasting of Al-7Si-0.6Mg alloy.

A wide range of food processing contaminants (FPCs) are usually formed while thermal processing of food products. Furan is a highly volatile compound among FPCs and could be formed in a variety of thermally processed foods. Therefore, identification of possible reasons of furan occurrence in different thermally processed foods, identification of the most consequential sources of furan exposure, factors impacting its formation, and its detection by specific analytical approaches are necessary to indicate gaps and challenges for future research findings. Furthermore, controlling furan formation in processed foods on a factory scale is also challenging, and research advancements are still ongoing in this context. Meanwhile, understanding adverse effects of furan on human health on a molecular level is necessary to gain insights into human risk assessment.

AbstractOlmutinib, the third-generation tyrosine kinase inhibitor, is applied in treating non-small cell lung cancer (NSCLC). The aim of this study is to elucidate the interaction mechanism of olmutinib with human α-1 acid glycoprotein (HAG), an important carrier protein, by mean of multi-spectroscopic and molecular simulation techniques. Fluorescence spectral results confirmed that the fluorescence of this carrier protein can be quenched by olmutinib in the static quenching mode, and this anticancer drug possesses a moderate binding affinity on HAG. The evidence from thermodynamic analysis, replacement interaction with ANS and sucrose, and computational simulation results showed that hydrogen bonding, hydrophobic interactions, and van der Waals forces involved the olmutinib-HAG complexation process. The results from UV-vis, 3D fluorescence and synchronous fluorescence spectroscopy proved that binding anticancer drug olmutinib caused the alteration in the microenvironment around Trp residues. And, circular dichroism spectral results provided the support for the conformational alterations in the carrier protein. The data also proved that olmutinib preferably bound to the hydrophobic cavity of HAG and the binding distance between the two was 2.21 nm. In addition, it can be found that the presence of some metal ions such as Zn2+, Ca2+, Ni2+and Cu2+would exert a certain extent effect on the olmutinib-HAG complexation process.Communicated by Ramaswamy H. Sarma

The Tibetan Plateau (TP) is characterized by heavily local dust activities, however, the mechanism of interannual variations of winter dust frequency over the TP remain poorly understood. Previous studies showed the autumn Arctic sea ice could significantly influence the winter climate over Eurasia. Whether autumn sea ice affects winter dust activity over the TP or not? Here, we used an integrated surface database to investigate possible mechanisms for interannual variability in the frequency of winter dust events above the TP. This variability, which is thought to be mainly caused by local dust emissions, shows significant correlations with sea ice concentration (SIC) in the Barents and Kara Seas during the preceding autumn. Low Barents–Kara SIC is accompanied by reduced snow depth over northern Eurasia between autumn and winter, which can enhance the Eurasian mid-latitude westerly jet stream. This strengthening increases the cyclogenesis and occurrence of strong surface wind speeds in winter, especially over the TP. In addition, a lower SIC is closely associated with reduced precipitation and snow cover in late autumn and winter over the TP, which in turn enhances warming of the land surface and reduces the area of frozen ground. These anomalies in atmospheric circulation patterns and local surface conditions promote dust events above the TP during winter. The ensemble means of Atmospheric Model Intercomparison Project experiments from Phase 6 of the Coupled Model Inter-comparison Project and the Community Atmosphere Model version 4 can generally reproduce the atmospheric circulation anomalies associated with decreased Barents–Kara SIC. This study reveals the crucial effect that SIC anomalies in the Barents and Kara Seas have on winter dust activities over the TP.

Vocal fold (VF) scarring results from injury to the unique layered structure and is one of the main reasons for long-lasting dysphonia. A minimally invasive procedure with injectable hydrogels is a promising method for therapy. However, current surgical techniques or standard injectable fillers do not yield satisfactory outcomes. In this work, an injectable hybrid hydrogel consisting of oxide hyaluronic acid and hydrazide-modified waterborne polyurethane emulsion was injected precisely into the injury site and cross-linked in situ by a dynamic hydrazone bond. The prepared hydrogel displays excellent injectability and self-healing ability, showing favorable biocompatibility and biodegradability to facilitate endogenous newborn cell migration and growth for tissue regeneration. With the aim of evaluating the antifibrosis and regeneration capacity of the hybrid hydrogel in the VF scarring model, the morphology and vibration characteristics of VFs, inflammatory response, and healing status were collected. The hybrid hydrogel can decrease the inflammation and increase the ratio of collagen III/collagen I to heal damaged scar-free tissue. Fascinatingly, the mucosal wave oscillations of healing VF by injecting the hybrid hydrogel were vibrated like the normal VF, achieving functional restoration. This work highlights the utility of hybrid hydrogels consisting of synthetic biodegradable waterborne polyurethane emulsions and natural hyaluronic acid as promising biomaterials for scarless healing of damaged VFs.

A 27-year-old man, with a history of non-Hodgkin lymphoma 8 years ago, was admitted due to 9 months of persistent sternal pain. Chest CT revealed a mass in the sternum. 18F-FDG PET/CT was performed, demonstrating a radioactive accumulation mass in the sternum, accompanied by massive osteogenesis and osteolysis. Histological and immunohistochemical analysis of ultrasound-guided fine-needle aspiration biopsy samples confirmed the diagnosis of aggressive osteoblastoma. We present a rare case of aggressive sternal osteoblastoma, instead of lymphoma recurrence, on 18F-FDG PET/CT in an adult with history of lymphoma.

AbstractThe binding behavior of ritonavir (RTV), a HIV/AIDS protease inhibitor, with ct-DNA was characterized through multiple testing technologies and theoretical calculation. The findings revealed that the RTV–DNA complex was formed through the noncovalent interaction mainly including conventional hydrogen bonds and carbon hydrogen bonds as well as hydrophobic interactions (pi–alkyl interactions). The stoichiometry and binding constant of the RTV–DNA complex were 1:1 and 1.87 × 103 M−1at 298 K, respectively, indicating that RTV has moderate affinity with ct-DNA. The findings confirmed that RTV binds to the minor groove of DNA. The outcomes of CD experiments showed that the binding with RTV changed the conformation of DNA slightly. However, the conformation of RTV had obvious changes after binding to DNA, meaning that the flexibility of RTV molecule played an important role in stabilizing the RTV–DNA complex. Meanwhile, the results of DFT calculation revealed that the RTV and DNA interaction caused the changes in the frontier molecular orbitals, dipole moment and atomic charge distribution of RTV, altering the chemical properties of RTV when it bound to DNA. Communicated by Ramaswamy H. Sarma

This study aimed to evaluate the feasibility and safety of a novel stent manufactured by metal injection molding (MIM) in clinical practice through animal experiments. Vessel stents were prepared using powder injection molding technology to considerably improve material utilization. The influence of MIM carbon impurity variation on the mechanical properties and corrosion resistance of 316L stainless steel was studied. In vitro cytotoxicity and animal transplantation tests were also carried out to evaluate the safety of MIM stents. The results showed that the performance of 316L stainless steel was very sensitive to the carbon content. Carbon fluctuations should be precisely controlled during MIM. All MIM stents were successfully implanted into the aortas of the dogs, and the MIM 316L stents had no significant cytotoxicity. The novel intravascular stent manufactured using MIM can maintain a stable form and structure with fast endothelialization of the luminal surface of the stent and ensure long-term patency in an animal model. The novel intravascular stent manufactured using MIM demonstrates favorable structural, physical, and chemical stability, as well as biocompatibility, offering promising application in clinical practice.

Posttranscriptional regulation has emerged as a driver for leukemia development and an avenue for therapeutic targeting. Among posttranscriptional processes, alternative polyadenylation (APA) is globally dysregulated across cancer types. However, limited studies have focused on the prevalence and role of APA in myeloid leukemia. Furthermore, it is poorly understood how altered poly(A) site usage of individual genes contributes to malignancy or whether targeting global APA patterns might alter oncogenic potential. In this study, we examined global APA dysregulation in patients with acute myeloid leukemia (AML) by performing 3' region extraction and deep sequencing (3'READS) on a subset of AML patient samples along with healthy hematopoietic stem and progenitor cells (HSPCs) and by analyzing publicly available data from a broad AML patient cohort. We show that patient cells exhibit global 3' untranslated region (UTR) shortening and coding sequence lengthening due to differences in poly(A) site (PAS) usage. Among APA regulators, expression of FIP1L1, one of the core cleavage and polyadenylation factors, correlated with the degree of APA dysregulation in our 3'READS data set. Targeting global APA by FIP1L1 knockdown reversed the global trends seen in patients. Importantly, FIP1L1 knockdown induced differentiation of t(8;21) cells by promoting 3'UTR lengthening and downregulation of the fusion oncoprotein AML1-ETO. In non-t(8;21) cells, FIP1L1 knockdown also promoted differentiation by attenuating mechanistic target of rapamycin complex 1 (mTORC1) signaling and reducing MYC protein levels. Our study provides mechanistic insights into the role of APA in AML pathogenesis and indicates that targeting global APA patterns can overcome the differentiation block in patients with AML.

Posttranscriptional regulation has emerged as a driver for leukemia development and an avenue for therapeutic targeting. Among posttranscriptional processes, alternative polyadenylation (APA) is globally dysregulated across cancer types. However, limited studies have focused on the prevalence and role of APA in myeloid leukemia. Furthermore, it is poorly understood how altered poly(A) site usage of individual genes contributes to malignancy or whether targeting global APA patterns might alter oncogenic potential. In this study, we examined global APA dysregulation in patients with acute myeloid leukemia (AML) by performing 3‘ region extraction and deep sequencing (3'READS) on a subset of AML patient samples along with healthy hematopoietic stem and progenitor cells (HSPCs) and by analyzing publicly available data from a broad AML patient cohort. We show that patient cells exhibit global 3‘ untranslated region (UTR) shortening and coding sequence lengthening due to differences in poly(A) site (PAS) usage. Among APA regulators, expression of FIP1L1, one of the core cleavage and polyadenylation factors, correlated with the degree of APA dysregulation in our 3'READS data set. Targeting global APA by FIP1L1 knockdown reversed the global trends seen in patients. Importantly, FIP1L1 knockdown induced differentiation of t(8;21) cells by promoting 3'UTR lengthening and downregulation of the fusion oncoprotein AML1-ETO. In non-t(8;21) cells, FIP1L1 knockdown also promoted differentiation by attenuating mechanistic target of rapamycin complex 1 (mTORC1) signaling and reducing MYC protein levels. Our study provides mechanistic insights into the role of APA in AML pathogenesis and indicates that targeting global APA patterns can overcome the differentiation block in patients with AML.

AbstractApatinib mesylate (APM), a novel tyrosine kinase inhibitor, has been applied in treating various cancers. In the present study, the binding mechanism of APM with bovine serum albumin (BSA) was studied by making use of various spectroscopic and theoretical calculation approaches to provide theoretical support for further studying its pharmacokinetics and metabolism. The results from fluorescence experiments showed that the quenching mechanism of BSA induced by APM was static quenching and the APM-BSA complex with the stoichiometry of 1:1 was formed during binding reaction. Moreover, the findings also showed that the binding process of APM to BSA was spontaneous and enthalpy-driven, and the mainly driving forces were hydrogen bonding, van der Waals as well as hydrophobic interactions. From the outcomes of the competitive experiments, it can be found that the binding site was primarily nestled in sub-domain IIIA of BSA (site II) which was in line with the results of molecular docking. An appreciable decline in α-helix content of BSA can be observed from the FT-IR data, meaning that the conformational change of BSA occurred after binding with APM, this phenomenon can be corroborated by the results of UV–vis, synchronous fluorescence and 3D fluorescence studies. Furthermore, the effect of some metal ions (e.g. K+, Co2+, Ni2+, Fe3+) on the binding constant of APM to BSA was explored.Communicated by Ramaswamy H. Sarma

A series of PEGylated active carbon nanoparticles were fabricated with improved dispersity in water and were explored for their ability for carrying drugs and potential application in lymphatic targeted tracing and chemotherapy of colorectal cancer. The active carbon nanoparticles were oxidized in a mild condition with 30% H2O2 solution and then mPEG-NH2 was grafted to the nanoparticles. Compared with the original carbon nanoparticles, the oxidized and PEGylated nanoparticles all present improved stability and initial solubility in water and the PEGylated nanoparticles perform best. Size of the nanoparticles was well controlled in a rational area which can fulfill the requirement for lymphatic targeting. The PEGylated nanoparticles have excellent drug loading properties and allow for sustained release under physiological conditions. The MTT results show the drug-loaded nanoparticles can effectively kill SW480 cells (Human Colon Cancer Cells). These characteristics make the PEGylated nanoparticles become a promising candidate for using as drug-loaded powder for both lymphatic targeted tracing and chemo-therapy without using suspending agent in tumor treatment.

A solidification model of coarsening coefficient for the criterion of secondary dendrite arm spacing has been established in this paper. When the model is applied to aluminum cast alloy, it is found that the model is in good agreement with the experiment results. Experiments and analysis show that addition of some chemical elements is conducive to the refinement of the secondary dendrite arm spacing under the same solidification condition. Different chemical elements have different refining effects, and Zr and Ti have better refining effect on A357 aluminum cast alloy than Cu.

AbstractThe binding characteristics of calf thymus DNA (ct-DNA) with dasatinib (DSTN), a tyrosine kinase inhibitor was assessed through multi-spectroscopic methodologies and viscosity measurement combined with molecular docking as well as DFT calculation to understand the binding mechanism, affinity of DSTN onto ct-DNA, effect of DSTN on ct-DNA conformation, and among others. The results confirmed DSTN bound onto ct-DNA, leading to forming the DSTN–ct-DNA complex with the binding constant of 4.82 × 103M−1at 310 K. DSTN preferentially inserted to the minor groove of ct-DNA with rich A-T region, that was the binding mode of DSTN onto ct-DNA was groove binding. The enthalpic change (ΔH0) and entropic change (ΔS0) during the binding process of DSTN with ct-DNA were 128.9 kJ mol−1and 489.2 J mol−1K−1, respectively, confirming clearly that the association of DSTN with ct-DNA was an endothermic process and the dominative driven-force was hydrophobic interaction. Meanwhile, the results also indicated that there was a certain extent of electrostatic force and hydrogen bonding, but they maybe play an auxiliary role. The CD measurement results confirmed the alteration in the helical configuration of ct-DNA but almost no change in the base stacking after binding DSTN. The results revealed that there was the obvious change in the conformation, the dipole moment, and the atomic charge distribution of DSTN in the B-DNA complexes, compared with free DSTN, to satisfy the conformational adaptation. From the obtained fronitier molecular orbitals of DSTN, it can be inferred that the nature of DSTN alters with the change of the environment around DSTN.Communicated by Ramaswamy H. Sarma

The present study discusses the expression and effect of the SOX17 gene in endometrioid adenocarcinoma. MTT assay is performed to determine the growth inhibition ratio of the DNA methyltransferase inhibitor 5-AZA for endometrial carcinoma cells, and the real-time fluorescence quantification PCR (qRT-PCR) was used to detect the mRNA expression of SOX17, β-catenin, and CyclinD1 in endometrial carcinoma tissues before and after using 5-AZA to treat the endometrial carcinoma cell line. There were 30 cases on endometrioid adenocarcinoma tissues and 10 cases on normal endometrial tissues. The results revealed that the expression of SOX17 in endometrioid adenocarcinoma tissues was downregulated (P< 0.05), the expression of β-catenin and CyclinD1 was upregulated (P< 0.05), and the expression of SOX17, CyclinD1, and β-catenin was negatively correlated (r= −0.353, P> 0.05; R= −0.463, P< 0.05). The higher the histological grade and FIGO staging were, the lower the expression level of SOX17 was (P< 0.05). After HEC1A cells were treated by 5-AZA, the cell growth inhibition was most obvious (IC50= 12.033) at 72 h, as determined by MTT assay. After cell treatment by 5-AZA, the genetic expression of SOX17 significantly increased, when compared with that before treatment (P< 0.05), while the genetic expression of β-catenin and CyclinD1 significantly declined (P< 0.05). These results indicate that the expression level of SOX17 in endometrioid adenocarcinoma declined, and the upregulated expression level of SOX17 in cells inhibited the growth of tumor cells.

Al-Mg-Si (AA6xxx) series alloys have been used widely in automotive industry for lightweight purpose. This work focuses on developing a short process for manufacturing Al-0.5Mg-1.3Si (wt.%) alloy sheets with good mechanical properties. Hereinto, a preparation route without homogenization was proposed on the basis of sub-rapid solidification (SRS) technique. The sample under SRS has fine microstructure and higher average partition coefficients of solute atoms, leading to weaker microsegregation owing to the higher cooling rate (160 °C/s) than conventional solidification (CS, 30 °C/s). Besides, Mg atoms tend to be trapped in Al matrix under SRS, inducing suppression of Mg 2 Si, and promoting generation of AlFeSi phase. After being solution heat treated (T4 state), samples following the SRS route have lower yield strength compared with that by CS route, indicating better formability in SRS sample. After undergoing pre-strain and artificial aging (T6 state), the SRS samples have comparable yield strength to CS samples, satisfying the service requirements. This work provides technological support to industrially manufacture high performance AA6xxx series alloys with competitive advantage by a novel, short and low-cost process, and open a door for the further development of twin-roll casting based on SRS technique in industries. [ABSTRACT FROM AUTHOR]

AbstractThe binding affinity between ritonavir (RTV) and model transport protein, BSA was assessed through multi-spectroscopic approaches and computer simulation. The findings revealed RTV statically quenched the fluorescence of BSA and formed the 1:1 RTV-BSA complex with the binding constant (Kb) of 1.06 × 103∼ 5.08 × 103M−1under the studied temperatures (298 ∼ 310 K). During the interaction of RTV with BSA, the hydrogen bonds and van der Waals forces acted as predominant function while the hydrophobicity played an assistant function. Molecular modeling further verified the result obtained from the competitive binding experiments, RTV preferentially fit into in the sub-domain IIIA of BSA. The perturbation in the secondary structures of BSA upon acting with RTV was observed from IR results, whereas synchronous and 3D fluorescence spectral findings unraveled the slight change in the hydrophobicity surrounding Tyr and Trp residues.Communicated by Ramaswamy H. Sarma

Objective This study aimed to investigate pelvic floor biometry of asymptomatic primiparous women compared with nulliparous women by using four-dimensional transperineal ultrasound (4D TPUS).Methods From July 2015 to February 2017, 722 women were enrolled and divided into the nulliparous group (n = 292), the vaginal delivery group (n = 272), and the elective cesarean section group (n = 158). The ultrasound parameters of 4D TPUS were compared among the groups.Results The vaginal delivery group had a significantly greater bladder neck descent (η2= 0.04), retrovesical angles on Valsalva maneuver (η2= 0.01), urethral rotation (η2= 0.01), levator hiatus area on Valsalva maneuver (η2= 0.02), urethral inclination angle (η2= 0.02), and funneling of the proximal urethra (η2= 0.11) than the other two groups. Comparison of the two modes of delivery (vaginal delivery and cesarean section) also showed significant differences in the above-mentioned ultrasound parameters.Conclusion There are significant differences in pelvic floor biometry between asymptomatic primiparous women and nulliparous women, as well as between women with vaginal delivery and those with elective cesarean section.

A 50-year-old woman underwent 18F-FDG PET/CT to evaluate possible abdominal malignancy, which was revealed by CT. The images showed a large cystic-solid lesion with peripherally increased FDG activity in the left mid-abdomen. Histopathology of the excised lesion confirmed a jejunal cavernous hemangioma. We reported a rare case of jejunal cavernous hemangioma with FDG accumulation on PET/CT, mimicking malignancy.

Invasive pulmonary Aspergillusinfection has the characteristics of high morbidity, difficult to be treated, poor prognosis and high mortality. This study aims to investigate the effects of cinnamaldehyde on 1,3-β-D-glucans in the pulmonary Aspergillus fumigatuscell wall to provide a basis for developing novel antifungal drugs.

Few effective treatments for chronic Keshan disease have been available till now. The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive. This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up. A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years. Of the 302 chronic Keshan disease patients, 170 (56.3%) were given selenium supplementation until the end point of follow-up. Cox proportional hazards regression models were used to identify the independent predictors of cardiac events. Our results showed that during the follow-up, there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group (101/170, 59.4%) and 98 in non-selenium supplementation group (98/132, 74.2%). Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death (HR 0.39, 95% CI 0.28–0.53) after adjustment for baseline age, sex, cigarette smoking, family history of Keshan disease, body mass index (BMI), heart rate, electrocardiogram (ECG) abnormalities, blood pressure, initial cardiothoracic ratio, left ventricular ejection fractions (LVEF) and whole-blood selenium concentration. Our ten-year follow-up analysis indicated that selenium supplementation, specifically combined with the use of angiotensin-converting enzyme inhibitor and beta blocker therapy, improved the survival of patients with chronic Keshan disease with congestive heart failure. BMI, selenium deficiency, male, combined ECG abnormalities, LVEF, and fast heart rate increased the risk of cardiac events.

Invasive pulmonary candidiasis is a disease with high incidence, difficult treatment, poor prognosis, and high mortality. The present study analyzed the influence of cinnamaldehyde on 1,3-β-D-glucans in the cell wall of Candida albicansin order to provide a theoretical basis for the research of antifungal drugs.

Molecular interaction of atenolol, a selective β1receptor antagonist with the major carrier protein, bovine serum albumin (BSA), was investigated under imitated physiological conditions (pH 7.4) by means of fluorescence spectroscopy, UV absorption spectroscopy, Fourier transform infrared spectroscopy (FT-IR), and molecular modeling studies. The steady-state fluorescence spectra manifested that static type, due to formation of the atenolol-BSA complex, was the dominant mechanism for fluorescence quenching. The characteristic information about the binding interaction of atenolol with BSA in terms of binding constant (Kb) were determined by the UV–vis absorption titration, and were found to be in the order of 103 M−1at different temperatures, indicating the existence of a weak binding in this system. Thermodynamic analysis revealed that the binding process was primarily mediated by van der Waals force and hydrogen bonds due to the negative sign for enthalpy change (ΔH0), entropy change (ΔS0). The molecular docking results elucidated that atenolol preferred binding on the site II of BSA according to the findings observed in competitive binding experiments. Moreover, via alterations in synchronous fluorescence, three-dimensional fluorescence and FT-IR spectral properties, it was concluded that atenolol could arouse slight configurational and micro-environmental changes of BSA.