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Neonatal jaundice is a common symptom that occurs in neonates during the first month of their life and is generally divided into physiological and pathological subtypes. In serious cases, pathological neonatal jaundice frequently shows complications including seizures, cerebral palsy, and kernicterus. However, due to the unclear pathogenesis of pathological neonatal jaundice, effective drugs for this disease remain unsatisfied. In the present study, we first estimated the protective effects of folic acid (FA) on phenylhydrazine (PHA) or homocysteine (Hcy)-injected neonatal rats (2-3 days aged). Intriguingly, we found that FA significantly decreased the elevated total bilirubin (TBIL) and direct bilirubin (DBIL) concentration, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activity in PHA- or Hcy-injected rats, indicating that FA improves liver functions. Meanwhile, our results also showed that the plasma Hcy level and N-homocysteinylation (N-Hcy) modification of albumin were significantly elevated in the jaundice rats, which were obviously reversed after FA administration. Furthermore, we identified a novel N-Hcy modification site K545 of human serum albumin (HSA) using LC-MS/MS, and the mutagenesis assay in HEK293 further validated these observations. Besides, we demonstrated that the N-Hcy modification of albumin functionally inhibits the bilirubin-binding ability of albumin without altering its protein level both in vitro and in vivo. Altogether, we highlight a mechanism that FA reduces the plasma Hcy level and thereby enhance the bilirubin-binding ability of albumin, which may provide a novel therapeutic strategy for the treatment of pathological neonatal jaundice.

China has gradually achieved a far leading position in the field of industrial robots. The application of robots in various fields has also been widely promoted. Therefore, the safety and reliability of robot work need to be further improved. This paper is mainly for the safety and reliability of the robot arm in the work. Based on Solidworks and ANSYS, the workbench performs a static analysis of a robotic arm with six degrees of freedom. Firstly, the three-dimensional model of the robot arm is established by Solidworks. And then, it is introduced into the ANSYS workbench to simulate the actual force situation to analyze the force of the robot arm and obtain the change law of the stress on each component and the deformation of the key structure during operation. According to the analysis results of ANSYS workbench software, the design of each component of the robot arm has a certain degree of reliability, which can lay the foundation for subsequent research such as motion control.

Background Integration of HBV DNA into the human genome could progressively contribute to hepatocarcinogenesis. Both intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC) are known to be associated with HBV infection. However, the integration of HBV and mechanism of HBV-induced carcinogenesis in ICC and CHC remains unclear. Methods 41 patients with ICC and 20 patients with CHC were recruited in the study. We conducted HIVID analysis on these 61 samples to identify HBV integration sites in both the tumor tissues and adjacent non-tumor liver tissues. To further explore the effect of HBV integration on gene alteration, we selected paired tumors and adjacent non-tumor liver tissues from 3 ICC and 4 CHC patients for RNA-seq and WGS. Results We detected 493 HBV integration sites in ICC patients, of which 417 were from tumor samples and 76 were from non-tumor samples. And 246 HBV integration sites were detected in CHC patients, of which 156 were located in the genome of tumor samples and 90 were in non-tumor samples. Recurrent HBV integration events were detected in ICC including TERT, ZMAT4, MET, ANKFN1, PLXNB2, and in CHC like TERT, ALKBH5. Together with our established data of HBV-infected hepatocellular carcinoma, we found that HBV preferentially integrates into the specific regions which may affect the gene expression and regulation in cells and involved in carcinogenesis. We further performed genomic and transcriptomic sequencing of three ICC and four CHC patients, and found that HBV fragments could integrate near some important oncogene like TERT, causing large-scale genome variations on nearby genomic sequences, and at the same time changing the expression level of the oncogenes. Conclusion Comparative analysis demonstrates numerous newly discovered mutational events in ICC and CHC resulting from HBV insertions in the host genome. Our study provides an in-depth biological and clinical insights into HBV-induced ICC and CHC.

Ubiquitin-specific Peptidase 13 (USP13) is a deubiquitinating enzyme that regulates the stability or function of its substrate. USP13 is highly amplified in human ovarian cancer, and elevated expression of USP13 promotes tumorigenesis and metastasis of ovarian cancer. However, there is little known about USP13 post-translational modifications and their role in ovarian cancer. Here, we found that USP13 is phosphorylated at Thr122 in ovarian cancer cells. Phosphorylated Thr122 (pT122) on endogenous USP13 was observed in most human ovarian cancer cells, and the abundance of this phosphorylation was correlated to the total level of USP13. We further demonstrated that Casein kinase 2 (CK2) directly interacts with and phosphorylates USP13 at Thr122, which promotes the stability of USP13 protein. Finally, we showed that Threonine 122 is important for cell proliferation of ovarian cancer cells. Our findings may reveal a novel regulatory mechanism for USP13, which may lead to novel therapeutic targeting of USP13 in ovarian cancer.

Small-scale robots have great potential in minimally invasive surgery (MIS). In this paper, we propose an untethered magnetic gripper with small scale and build a double-magnet model for it. The gripper is 4.3mm long and its maximum width is 4mm. It contains a spindle and two magnets, which can achieve precise control of orientation, position and open angle with external magnetic driven field. As a result, it can perform operations such as transporting medicines in confined and constrained environments. Modeling and analysis of the magnetic gripper have been carried out. Relationship between the open angle and external magnetic field has been established. Kinematics model of the gripper has been built. A 3-axis Helmholtz-Maxwell coil system has been established to generate the magnetic field, in which orientation and open angle can be controlled with uniform magnetic field while position can be controlled with gradient field. The proposed gripper have been validated with phantom experiments. An opened angle control error of 0.63° and direction control error of 1.1° have been obtained.

Objective: to understand the development level of digital inclusive finance in 31 provinces in China in recent years, so that the areas with poor development level can speed up the development. Methods: the data of Peking University Digital inclusive Financial Index from 2012 to 2018 were collected, and the optimal clustering number was determined, and then the cross-sectional data and multi-index panel data were clustered respectively. Conclusion: the level of digital inclusive finance in China shows an upward trend as a whole, but there are great differences in the development level of digital inclusive finance among 31 provinces in China, in which East China is the best, South China and Central China have a better overall development level, and North China, Northwest, Southwest and Northeast are poor in overall development level, but have provincial differences.

Based on the literature research, this paper collects and reads the theoretical literature related to strategic models and tries to find out the common points and shortcomings of the strategic models of the two major e-commerce platforms, Jingdong and Alibaba, in the process of development, and mainly conducts a comparative study on the logistics strategies and competitive strategies of Alibaba and Jingdong. Through the research and analysis, it is hoped that the two platforms can build on their strengths and avoid their weaknesses in the development and promote the further optimization of their respective platforms, and also have high reference value for other similar e-commerce platforms.

BackgroundCholestasis patients often suffer from pain desensitization, resulting in serious complications in perioperative period. This study was aim to investigate the mechanism of bilirubin in cholestasis mediating pain desensitization through 5-hydroxytryptamine 3A (5-HT3A) receptor activation in spinal dorsal horn (SDH).MethodsA cholestasis model was established by bile duct ligation (BDL) in rats. Pain thresholds of rats were measured after BDL or intrathecally injecting bilirubin in the presence or absence of agonist (mCPBG) and antagonists (ondansetron, bicuculline, or CGP55845). Expression of 5-HT3 receptors, and the affinity and binding mode of bilirubin to 5-HT3A receptor were determined. Effects of bilirubin on γ-aminobutyric acid (GABA) pathway and the interactions with 5-HT3A receptor were tested.ResultsBilirubin was elevated significantly in both serum and CSF in BDL rats, accompanied with the up-regulation of pain thresholds. Both of 5-HT3A receptor and GABAA receptor antagonists could reverse the increased pain threshold in BDL rats. Further, 5-HT3A and GABAA receptor expressions were increased in BDL rats or intervention with bilirubin. Molecular docking suggested that bilirubin entered the hydrophobic pocket pre-formed in 5-HT3A receptor with potential hydrogen bonding. Bilirubin also increased GABA concentrations in CSF and GABAergic spontaneous inhibitory postsynaptic current in spinal cord, and directly induced inward currents in HEK293 cells which were overexpressed 5-HT3A receptor by lentivirus.ConclusionIn conclusion, bilirubin induced pain desensitization in cholestasis by activating 5-HT3A receptor in spinal cord. The activation of 5-HT3A receptor might regulate pain threshold by acting on the GABA pathway.

The two-layer nanotubes consisted of carbon atoms on the outside layer and silicon atoms on the inside layer (CNT@SiNT) show a series of diversity in the shape transitions, for instance transforming from a circle through an oval to a rectangle. In this paper, we investigate this geometric change from three perspectives. In the first aspect, we stationary time, followed by quantize in the three-dimensional Z-axis of nanotubes. In the second aspect, we stationary Z-axis, followed by quantize in the time. Finally, we tracked distance of nanotubes flattest section and roundest section. At the stationary time, the overall image of different Z-axis distance distributions is similar to a plan view of multiple ice creams, regardless of whether CNT or SiNT are on the same Z-axis, their slice plans are circle or rectangle of the projection of the Z-axis section on the XOY plane. In the stationary Z-axis, the nanotubes periodically change from a circle to an oval, and then from an oval to a rectangle at different times. Most remarkably, the distance value of deformation which we track the flattest and roundest is a constant value, and in the same distance period, there is only one roundest circle and one longest rectangle at different section and different time. The geometric analysis provided theoretical reference for the preparation of various devices and semiconductor nano-heterojunctions.

In this paper, an improved LBP (Local Binary Patterns) feature extraction algorithm is proposed. According to the traditional LBP algorithm for noise sensitivity, an improved median filtering is adopted. For the LBP operator, the neighboring neighbor points are ignored when extracting feature information. The shortcomings of the relationship, the LBP algorithm is improved, firstly according to the distance between the neighborhood point and the central pixel point, the new field pixel value is obtained, and then the central pixel is compared with the new neighborhood pixel gray value. The operation takes its absolute value, and finally finds the average of all absolute values as an introduced threshold. The threshold improves the parameters of LBP encoding, and uses the improved algorithm to extract the railway fasteners features. Experiments show that the improved LBP algorithm extracts the railway fasteners. The effect is better.

Guanidinylated bioresponsive poly(amido amine)s polymers, CAR-CBA and CHL-CBA, were synthesized by Michael-type addition reaction between guanidine hydrochloride (CAR) or chlorhexidine (CHL) and N,N′-cystaminebisacrylamide (CBA). Previous studies have shown that both polymers had high transfection efficiencies as gene delivery carriers. In this study, we investigated the nucleolus localization abilities and cellular internalization pathways of these two polymers in gene delivery. Each polymer condensed plasmid DNA (pDNA) and formed nanoparticle complexes, and then their transfection studies were performed in MCF-7 cells. Both complexes were found enriched in nucleolus after cellular transfection, and their transfection efficiencies were significantly improved when transfection was performed on MCF-7 cells arrested at M phase. The transfection efficiency of CAR-CBA-pDNA was inhibited by chlorpromazine, and cell endosomes were disrupted after being exposed to CAR-CBA-pDNA. In regards to CHL-CBA-pDNA, its transfection efficiency was not affected by three types of endocytosis inhibitors used in the study, and CHL-CBA-pDNA showed no effect on endosomes. Cellular lactate dehydrogenase release and membrane morphology were changed after cells were transfected by the two complexes. The results indicated that both CAR-CBA and CHL-CBA polymers demonstrated good nucleolus localization abilities. It was beneficial for transfection when cells were arrested at M phase. CAR-CBA-pDNA cellular internalization was involved with clathrin-mediated endocytosis pathway, and escaping from endosomal entrapment, while the cellular uptake of CHL-CBA-pDNA occurs via clathrin- and caveolae-independent mechanism., Graphical abstract Each polymer condensed plasmid DNA and formed nanoparticle complexes, then the nucleolus localization abilities and cellular internalization pathways of these two polymers in gene delivery were investigated. Image, graphical abstract

Based on data from the World Health Organization, breast cancer is the most common type of cancer among women, accounting for about 15% of all cancer-related deaths. Thus, new treatment options are urgently needed to decrease this mortality rate. In recent years, mesoionic compounds have shown promising potential as anti-cancer agents due to their unique structure and reaction properties. We recently reported that a 1,3-thiazolium-5-thiolate mesoionic compound (MIH 2.4Bl) inhibited oxidative phosphorylation in the MCF-7 breast cancer cell line compared to normal human mammary epithelial cells. Furthermore, MIH 2.4Bl induced cytotoxicity by activating autography-related proteins (Beclin-1 and ATG5) and cell cycle arrest at the G2/M phase. Based on our previous findings, MIH 2.4BI is a promising candidate for treating breast cancer. However, a major challenge facing cancer therapeutics is tumor delivery in vivo for the selective destruction of malignant cells while sparing normal cells to preserve tissue integrity. The development and use of drug delivery systems is a recognized approach to improve the efficacy of chemotherapy agents. Nonetheless, drug delivery systems have been largely unexplored in the context of mesoionic compounds. Lipoproteins are ideal for carrying transporting lipophilic anti-cancer drugs and imaging agents as they circulate in the bloodstream for an extended period. In addition, the hydrophobic core of lipoprotein particles allows the incorporation of lipophilic components (including a number of anti-cancer agents). Reconstituted high-density lipoprotein (rHDL) mimics the structure and function of endogenous (i.e., human plasma) HDL and thus presents a potentially markedly improved therapeutic strategy for cancer drug delivery. Previous studies from our group have shown that a stable reconstituted synthetic rHDL-drug complex could be prepared by combining paclitaxel and other chemotherapy drugs using the natural lipid and protein components of circulating HDL via a novel procedure. In this preliminary work, we present an improved strategy of using a newly developed formulation of MIH 2.4BI compound with rHDL nanoparticles as the delivery agent. Also, physico-chemical characterization of the nanoparticles and cytotoxicity analyses using a panel of breast cancer cell lines were performed. These studies support the potential therapeutic use of MIH 2.4Bl in treating breast cancer. (D. Debnath and R.M. Petty contributed equally to this work) Citation Format: Dipti Debnath, R. Max Petty, Nirupama Sabnis, Jinmin Zhang, Andras G. Lacko, Helivaldo Diógenes Souza, Petrônio Filgueiras Filho, J. Michael Mathis, Rafal Fudala. An improved strategy for delivering the mesoionic compound MIH 2.4Bl utilizing reconstituted high density nanoparticles (rHDL) in treating breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 300.

To understand the photoluminescence mechanisms and optimize the design of Mg 2 Si-based light-emitting devices, Mg 2 Si films were fabricated on silicon (111) and glass substrates by magnetron sputtering technique, and the influences of different substrates on the photoelectric properties of Mg 2 Si films were investigated systematically. The crystal structure, cross-sectional morphology, composition ratios and temperature-dependent photoluminescence (PL) of the Mg 2 Si films were examined using X-ray diffraction (XRD), Scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDS) and PL measurement system, respectively. XRD results indicate that the Mg 2 Si film on Si (111) displays polycrystalline structure, whereas Mg 2 Si film on glass substrate is of like-monocrystalline structure.SEM results show that Mg 2 Si film on glass substrate is very compact with a typical dense columnar structure, and the film on Si substrate represents slight delamination phenomenon. EDS results suggest that the stoichiometry of Mg and Si is approximately 2:1. Photoluminescence (PL) of Mg 2 Si films was observed for the first time. The PL emission wavelengths of Mg 2 Si are almost independence on temperature in the range of 77–300 K. The PL intensity decreases gradually with increasing temperature. The PL intensity of Mg 2 Si films on glass substrate is much larger than that of Mg 2 Si film on Si (111) substrate. The activation energy of 18 meV is determined from the quenching of major luminescence peak(1342 nm) as a function of temperature in the Mg 2 Si film grown on Si (111) substrate, which is much smaller than that deduced in the sample grown on glass substrate (about 25meV). The small activation energy can be attributed to the additional nonradiative centers originated from relatively poor crystal quality.The physical mechanism responsible for the measured ∼1342 nm and other three longer wavelengths emissions may be respectively result from strong Mg i donor level to valence band transitions and other defect-related radiative recombination occurred in the Mg 2 Si films.

Melting refers to the phase transition from solid to liquid, which is a common physical phenomenon in nature. It is also a phase transformation process that the materials such as metals and semiconductors need to undergo in the process. It is closely related to the preparation and performance of materials. At present, it is difficult to trace the microstructure of the melting process, and computer simulation can get a lot of microstructure information of the melting process, which can well explain how the orderly arrangement of crystals becomes random liquid phase structure in the melting process. For the ternary semiconductor alloy In x Ga1 - x As, it has important application value in microelectronics and optoelectronic devices, because it can adjust its electrical parameters and optical band gap in a wide range composition. So the research of alloy structure has been paid more and more attentions for the ternary semiconductor. It is generally known that the macroscopic properties of the materials are mainly determined by their microstructures. However, most studies on the melting process are based on the dynamics, but the mechanism of the evolution of the microstructure during the melting process is lacking. Therefore, it is of great significance to study the evolution of microstructures during the melting process of InGaAs crystals in the development of novel optoelectronic materials and devices. At present, it is still difficult in the experiment to obtain the structural details of InGaAs system during the melting process. Molecular dynamics simulation is an efficient tool especially for such process. In this paper, the melting process of the ideal InGaAs crystal is simulated by using the molecular dynamics method, and the Tersoff potential function of the In x Ga1 - x As covalent bond system, which has been proved to be suitable for the simulation of complex structures. The structural evolution of the solid-liquid phase transition process was analyzed by using the radial distribution function, angular distribution function, coordination numbers and 3D visualization. From the results of our simulation, we find that the microstructures of the InGaAs phase change greatly during the solid-liquid phase transition, especially in the first-order phase transition. It shows significant variations in the average atomic energy and specific volume, the radial distribution function, angular distribution functions, coordination numbers and atomic cross-sections, local atomic distributions, and diamond structure analysis. In the melting process, covalent bonds the InGaAs atoms are broken, and the system changes from the four coordinated structure into the three coordinated structure. For the dominant three coordinated structure and a small amount of four coordinated structures, the three coordinated structure is connected with the three coordinated structure, and the three coordinated structure interpenetrated the four coordinated structure to form a disordered topological structure.

In this study, the epitaxial growth of the full-composition-graded AlxGa1-xN films has been demonstrated on the sapphire substrates by using metalorganic chemical vapor deposition (MOCVD). The aluminum composition in the AlxGa1-xN films has been precisely controlled from 0 to 100%, as confirmed by X-ray diffraction and energy-dispersive spectroscopy analyses. The pseudo-periodic AlxGa1-xN/AlyGa1-yN structures are spontaneously formed during the initial growth of the graded AlGaN layer, which facilitate the strain relaxation. In addition, the behavior of the bending dislocations has been investigated in detail, and the threading dislocation bending along the growth direction is noted to relax the strain further.

Purpose IR780 iodide, a promising near-infrared dye, is widely used to prepare nanoparticles as a theranostic agent for tumor imaging and therapy. However, there are no validated (bio)analytical methods to measure IR780 in nanoparticles and tissues in literature. The aim of this study is to develop and validate a new HPLC method to measure IR780 concentration in IR780 formulations as well as a new LC–MS/MS method to measure IR780 concentration in tissue samples, particularly in liver and lung. Materials and methods IR780 granules that produced IR780 in situ self-assembled nanoparticles upon contact with water were prepared at two drug loadings (0.2 % and 0.37 %). An HPLC method was developed and validated to measure IR780 concentrations in IR780 granules and nanoparticles. Furthermore, a validated LC–MS/MS method was developed to measure IR780 in mouse liver and lung. Both HPLC method and LC–MS/MS method were validated in terms of specificity, stability, linearity, limit of detection, limit of quantification, accuracy and precision. Results Both HPLC method and LC–MS/MS method achieved the criteria for method validation. The HPLC method was accurate in the concentration range of 0.5−25 μg/mL. The measured drug loadings were 95 % of the theoretical drug loadings. The validated LC–MS/MS method can quantitatively measure the concentrations of IR780 in liver and lung. The linear range of the LC–MS/MS method was 1−1000 ng/mL for both liver and lung samples. IR780 granules showed the lung selectivity compared to IR780 solution at 2 h after oral administration. Conclusion A validated HPLC method was developed to measure IR780 concentration in pharmaceutical formulations and a validated LC–MS/MS method was developed to measure IR780 concentration in tissues. These quantitative methods provide reliable measurements of IR780 in pharmaceutic formulations and biological samples, which will significantly facilitate the research of IR780 as a theranostic agent for cancer therapy and imaging.

Polymers of guanidinylated disulfide containing poly(amido amine)s (Gua-SS-PAAs), have shown high transfection efficiency and low cytotoxicity. Previously, we synthesized two Gua-SS-PAA polymers, using guanidino containing monomers (i.e., arginine and agmatine, denoted as ARG and AGM, respectively) and N,N'-cystaminebisacrylamide (CBA). In this study, these two polymers, AGM-CBA and ARG-CBA were complexed with plasmid DNA, and their uptake pathway was investigated. Complexes distribution in MCF-7 cells, and changes on cell endosomes/lysosomes and membrane after the cells were exposed to complexes were tested. In addition, how the transfection efficiency changed with the cell cycle status as well as endocytosis inhibitors were studied. The polymers of AGM-CBA and ARG-CBA can avoid endosomal/lysosomal trap, therefore, greatly delivering plasmid DNA (pDNA) to the cell nucleoli. It is the guanidine groups in the polymers that enhanced complexes' permeation through cell membrane with slight membrane damage, and targeting to the nucleoli. J. Cell. Biochem. 118: 903-913, 2017. © 2016 Wiley Periodicals, Inc.

Ternary photocatalyst, reduced graphene oxide-ZnFe 2 O 4 -polyaniline (RZP), has been successfully developed by the in-situ polymerization of aniline on the reduced graphene oxide-ZnFe 2 O 4 (RG/ZF) surface for sewage purification. The SEM, TEM and STEM images suggest that PANI has coated the RG/ZF composite well. The XRD, TG-DTG and FT-IR analysis confirm that there are some interactions between RG/ZF composite and PANI. Importantly, the decontamination performance of RZP composites has been investigated using RhB as a model organic in view of adsorption and photocatalysis. On one hand, thermodynamic researches indicate that the adsorption behaviors of RZP composites conform to the Langmuir model, and their adsorption mechanism can be well described by the second-order kinetic model. On the other hand, RZP composites with different mass ratios of PANI to RG/ZF ( m P/RZ ) present a better photocatalytic activity than that of RG/ZF composites, and their photocatalytic behaviors under different pH could be described by the first-order kinetic model. Furthermore, it can be observed that the RZP composite with m P/RZ = 0.4 has the excellent photocatalytic activity and photocatalytic stability under pH = 1. Finally, the possible photocatalytic degradation mechanisms of the RZP composite on RhB have been discussed. These results can unveil that the prepared RZP photocatalyst is very promising for application in water purification.

Color correction algorithm based on color space conversion is an essential part in color management system. Subject to the variation in conditions such as the limitations on imaging-forming principle, device performances and machining controls, the captured images usually contain certain color distortion compared to the actual images. Therefore, the paper proposes a mind evolutionary computation (MEC)-back propagation (BP)-adaboost algorithm (Adaboost) neural network-based color correction algorithm for color image collecting equipment. MEC-BP-Adaboost is utilized in training process to establish the color mapping model, with the captured samples of the color-targets under the color image acquisition equipments as input data and the standard color data as output data. MEC-BP-Adaboost neural network-based color correction algorithm not only can further the correction accuracy, but also can solve the problem that the color correction models obtained by using the neural network methods are not unique, and the difference among that color correction models is very big. Experimental results demonstrate that the proposed method achieves much better correction performance than the polynomial regression model, the conventional BP neural network, and the genetic algorithm (GA)-BP neural network.