Bouncing Regimes of Supercooled Water Droplets Impacting Superhydrophobic Surfaces with Controlled Temperature and Humidity.

Superhydrophobic surfaces have shown significant potential for the passive anti-icing application due to their unique water repellency. Reducing the contact time between the impacting droplets and the underlying surfaces with certain textures, especially applying the pancake bouncing mechanism, is expected to eliminate droplet icing upon impingement. However, the anti-icing performance of such superhydrophobic surfaces against the impact of supercooled water droplets has not yet been examined. Therefore, we fabricated a typical post-array superhydrophobic surface (PSHS) and a flat superhydrophobic surface (FSHS), to study the droplet impact dynamics on them with controlled temperature and humidity. The contact time and the bouncing behavior on these surfaces and their dependence on the surface temperature, Weber number, and surface frost were systematically investigated. The conventional rebound and full adhesion were observed on the FSHS, and the adhesion is mainly induced by the penetration of the droplet into the surface micro/nanostructures and the consequent Cassie-to-Wenzel transition. On the PSHS, four distinct regimes including pancake rebound, conventional rebound, partial rebound, and full adhesion were observed, where the contact time increases correspondingly. Over a certain Weber number range, the pancake rebound regime where the droplet bounces off the surface with a dramatically shortened contact time benefits the anti-icing performance. By further decreasing the surface temperature, the pancake rebound turns into the conventional rebound, where the droplet is not levitated after the capillary emptying process. Our scale analysis indicates that the frost between the posts reduces the capillary energy stored during the downward penetration, resulting in the failure of the pancake bouncing. A droplet adheres onto the frosted surface at sufficiently low temperature, especially at larger Weber numbers, on account of the coupling influence of droplet nucleation and wetting transition.

Health insurance fraud detection by using an attributed heterogeneous information network with a hierarchical attention mechanism.

BACKGROUND: With the rapid growth of healthcare services, health insurance fraud detection has become an important measure to ensure efficient use of public funds. Traditional fraud detection methods have tended to focus on the attributes of a single visit and have ignored the behavioural relationships of multiple visits by patients. METHODS: We propose a health insurance fraud detection model based on a multilevel attention mechanism that we call MHAMFD. Specifically, we use an attributed heterogeneous information network (AHIN) to model different types of objects and their rich attributes and interactions in a healthcare scenario. MHAMFD selects appropriate neighbour nodes based on the behavioural relationships at different levels of a patient's visit. We also designed a hierarchical attention mechanism to aggregate complex semantic information from the interweaving of different levels of behavioural relationships of patients. This increases the feature representation of objects and makes the model interpretable by identifying the main factors of fraud. RESULTS: Experimental results using real datasets showed that MHAMFD detected health insurance fraud with better accuracy than existing methods. CONCLUSIONS: Experiment suggests that the behavioral relationships between patients' multiple visits can also be of great help to detect health care fraud. Subsequent research fraud detection methods can also take into account the different behavioral relationships between patients.

Novel short synthetic matrix attachment region for enhancing transgenic expression in recombinant Chinese hamster ovary cells.

Matrix attachment regions (MARs) are DNA fragments with specific motifs that enhance transgenic expression; however, the characteristics and functions of these elements remain unclear. In this study, we designed and synthesized three short chimeric MARs, namely, SM4, SM5, and SM6, with different numbers and orders of motifs on the basis of the features and motifs of previously reported MARs, namely, SM1, SM2, and SM3, respectively. Expression vectors with six synthetic MARs flanking the down or upstream of the expression cassette for enhanced green fluorescence protein (EGFP) were constructed and introduced into Chinese hamster ovary (CHO) cells. Results indicated that the EGFP expression of the CHO cells with transfection bySM4, SM5, or SM6-containing vectors was higher than that of those containing SM1, SM2, or SM3 regardless of the MAR insertion position. The improving effect of SM5 was particularly pronounced. Transgenic expression was further enhanced with the increasing SM5 copy number. Bioinformatics analysis indicated that several arrangements of the DNA-binding motifs for CEBP, FAST, Hox, glutathione, and NMP4 may help increase transgenic expression levels and the average population of highly expressed cells. Our findings on novel synthetic MARs will help establish stable expression systems in mammalian cells.

CRISPR/Cas9-mediated gene knockout for DNA methyltransferase Dnmt3a in CHO cells displays enhanced transgenic expression and long-term stability.

CHO cells are the preferred host for the production of complex pharmaceutical proteins in the biopharmaceutical industry, and genome engineering of CHO cells would benefit product yield and stability. Here, we demonstrated the efficacy of a Dnmt3a-deficient CHO cell line created by CRISPR/Cas9 genome editing technology through gene disruptions in Dnmt3a, which encode the proteins involved in DNA methyltransferases. The transgenes, which were driven by the 2 commonly used CMV and EF1α promoters, were evaluated for their expression level and stability. The methylation levels of CpG sites in the promoter regions and the global DNA were compared in the transfected cells. The Dnmt3a-deficent CHO cell line based on Dnmt3a KO displayed an enhanced long-term stability of transgene expression under the control of the CMV promoter in transfected cells in over 60 passages. Under the CMV promoter, the Dnmt3a-deficent cell line with a high transgene expression displayed a low methylation rate in the promoter region and global DNA. Under the EF1α promoter, the Dnmt3a-deficient and normal cell lines with low transgene expression exhibited high DNA methylation rates. These findings provide insight into cell line modification and design for improved recombinant protein production in CHO and other mammalian cells.

Health insurance fraud detection based on multi-channel heterogeneous graph structure learning.

Health insurance fraud is becoming more common and impacting the fairness and sustainability of the health insurance system. Traditional health insurance fraud detection primarily relies on recognizing established data patterns. However, with the ever-expanding and complex nature of health insurance data, it is difficult for these traditional methods to effectively capture evolving fraudulent activity and tactics and keep pace with the constant improvements and innovations of fraudsters. As a result, there is an urgent need for more accurate and flexible analytics to detect potential fraud. To address this, the Multi-channel Heterogeneous Graph Structured Learning-based health insurance fraud detection method (MHGSL) was proposed. MHGSL constructs a graph of health insurance data from various entities, such as patients, departments, and medicines, and employs graph structure learning to extract topological structure, features, and semantic information to construct multiple graphs that reflect the diversity and complexity of the data. We utilize deep learning methods such as heterogeneous graph neural networks and graph convolutional neural networks to combine multi-channel information transfer and feature fusion to detect anomalies in health insurance data. The results of extensive experiments on real health insurance data demonstrate that MHGSL achieves a high level of accuracy in detecting potential fraud, which is better than existing methods, and is able to quickly and accurately identify patients with fraudulent behaviors to avoid loss of health insurance funds. Experiments have shown that multi-channel heterogeneous graph structure learning in MHGSL can be very helpful for health insurance fraud detection. It provides a promising solution for detecting health insurance fraud and improving the fairness and sustainability of the health insurance system. Subsequent research on fraud detection methods can consider semantic information between patients and different types of entities.

Risk prediction of pulse wave for hypertensive target organ damage based on frequency-domain feature map.

The application of deep learning to the classification of pulse waves in Traditional Chinese Medicine (TCM) related to hypertensive target organ damage (TOD) is hindered by challenges such as low classification accuracy and inadequate generalization performance. To address these challenges, we introduce a lightweight transfer learning model named MobileNetV2SCP. This model transforms time-domain pulse waves into 36-dimensional frequency-domain waveform feature maps and establishes a dedicated pre-training network based on these maps to enhance the learning capability for small samples. To improve global feature correlation, we incorporate a novel fusion attention mechanism (SAS) into the inverted residual structure, along with the utilization of 3 × 3 convolutional layers and BatchNorm layers to mitigate model overfitting. The proposed model is evaluated using cross-validation results from 805 cases of pulse waves associated with hypertensive TOD. The assessment metrics, including Accuracy (92.74 %), F1-score (91.47 %), and Area Under Curve (AUC) (97.12 %), demonstrate superior classification accuracy and generalization performance compared to various state-of-the-art models. Furthermore, this study investigates the correlations between time-domain and frequency-domain features in pulse waves and their classification in hypertensive TOD. It analyzes key factors influencing pulse wave classification, providing valuable insights for the clinical diagnosis of TOD.

UBQLN1 links proteostasis and mitochondria function to telomere maintenance in human embryonic stem cells.

BACKGROUND: Telomeres consist of repetitive DNA sequences at the chromosome ends to protect chromosomal stability, and primarily maintained by telomerase or occasionally by alternative telomere lengthening of telomeres (ALT) through recombination-based mechanisms. Additional mechanisms that may regulate telomere maintenance remain to be explored. Simultaneous measurement of telomere length and transcriptome in the same human embryonic stem cell (hESC) revealed that mRNA expression levels of UBQLN1 exhibit linear relationship with telomere length. METHODS: In this study, we first generated UBQLN1-deficient hESCs and compared with the wild-type (WT) hESCs the telomere length and molecular change at RNA and protein level by RNA-seq and proteomics. Then we identified the potential interacting proteins with UBQLN1 using immunoprecipitation-mass spectrometry (IP-MS). Furthermore, the potential mechanisms underlying the shortened telomeres in UBQLN1-deficient hESCs were analyzed. RESULTS: We show that Ubiquilin1 (UBQLN1) is critical for telomere maintenance in human embryonic stem cells (hESCs) via promoting mitochondrial function. UBQLN1 deficiency leads to oxidative stress, loss of proteostasis, mitochondria dysfunction, DNA damage, and telomere attrition. Reducing oxidative damage and promoting mitochondria function by culture under hypoxia condition or supplementation with N-acetylcysteine partly attenuate the telomere attrition induced by UBQLN1 deficiency. Moreover, UBQLN1 deficiency/telomere shortening downregulates genes for neuro-ectoderm lineage differentiation. CONCLUSIONS: Altogether, UBQLN1 functions to scavenge ubiquitinated proteins, preventing their overloading mitochondria and elevated mitophagy. UBQLN1 maintains mitochondria and telomeres by regulating proteostasis and plays critical role in neuro-ectoderm differentiation.

Overexpression of YTHDF3 increases the specific productivity of the recombinant protein in CHO cells by promoting the translation process.

Due to their high-quality characteristics, Chinese hamster ovary (CHO) cells have become the most widely used and reliable host cells for the production of recombinant therapeutic proteins in the biomedical field. Previous studies have shown that the m6A reader YTHDF3, which contains the YTH domain, can affect a variety of biological processes by regulating the translation and stability of target mRNAs. This study investigates the effect of YTHDF3 on transgenic CHO cells. The results indicate that stable overexpression of YTHDF3 significantly enhances recombinant protein expression without affecting host cell growth. Transcriptome sequencing indicated that several genes, including translation initiation factor, translation extension factor, and ribosome assembly factor, were upregulated in CHO cells overexpressing YTHDF3. In addition, cycloheximide experiments confirmed that YTHDF3 enhanced transgene expression by promoting translation in CHO cells. In conclusion, the findings in this study provide a novel approach for mammalian cell engineering to increase protein productivity by regulating m6A.

Nanosecond pulsed laser damage characteristics of HfO2/SiO2 high reflection coatings irradiated from crystal-film interface.

The nano-precursors in the subsurface of Nd:YLF crystal were limiting factor that decreased the laser-induced damage threshold (LIDT) of HfO(2)/SiO(2) high reflection (HR) coatings irradiated from crystal-film interface. To investigate the contribution of electric-field (E-field) to laser damage originating from nano-precursors and then to probe the distribution of vulnerable nano-precursors in the direction of subsurface depth, two 1064 nm HfO(2)/SiO(2) HR coatings having different standing-wave (SW) E-field distributions in subsurface of Nd:YLF c5424181043036123rystal were designed and prepared. Artificial gold nano-particles were implanted into the crystal-film interface prior to deposition of HR coatings to study the damage behaviors in a more reliable way. The damage test results revealed that the SW E-field rather than the travelling-wave (TW) E-field contributed to laser damage. By comparing the SW E-field distributions and LIDTs of two HR coating designs, the most vulnerable nano-precursors were determined to be concentrated in a thin redeposition layer that is within 100 nm from the crystal-film interface.

Apilimod enhances specific productivity in recombinant CHO cells through cell cycle arrest and mediation of autophagy.

Chinese hamster ovary (CHO) cells are expected to acquire the ability to produce higher recombinant therapeutic protein levels using various strategies. Genetic engineering targeting the cell cycle and autophagy pathways in the regulation of cell death in CHO cell cultures has received attention for enhancing the production of therapeutic proteins. In this study, we examined the small-molecule compound apilimod, which was found to have a positive influence on recombinant protein expression in CHO cells. This was confirmed by selective blocking of the cell cycle at the G0/G1 phase. Apilimod treatment resulted in decreased expression of cyclin-dependent kinase 3 (CDK3) and Cyclin C and increased expression of cyclin-dependent kinase suppressor p27Kip1, which are critical regulators of G1 cell cycle progression and important targets controlling cell proliferation. Furthermore, total transcription factor EB (TFEB) was lower in apilimod-treated CHO cells than in control cells, resulting in decreased lysosome biogenesis and autophagy with apilimod treatment. These multiple effects demonstrate the potential of apilimod for development as a novel enhancer for the production of recombinant proteins in CHO cell engineering.

The complete chloroplast genome of Camellia leyeensis (theaceae).

Camellia leyeensis Chang ＆ Y. C. Zhong is a plant belonging to the genus Camellia. To determine its correct taxonomic status and better understand its molecular phylogenetic and genetic diversity, we studied the chloroplast genome of this species. Here, we report and characterize the complete chloroplast (cp) genome of C. leyeensis by using Illumina paired-end sequencing data. The chloroplast genome was determined to be 157,063 bp in length with a GC content of 37.30%. The genome contained 136 genes, including 91 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The sequence contained a large single-copy region (LSC, 86,661 bp), a small single-copy region (SSC, 18,284 bp), and two inverted repeat sequences (IRs, 26,059 bp, each). The GC content of the IR regions (42.96%) was higher than that of the SSC region (30.6%) and LSC region (35.31%). Phylogenetic analysis suggested that Camellia leyeensis is closely related to C. anlungensis with 96% bootstrap support. This chloroplast genome would be helpful for the phylogeny and conservation of Camellia.

MFDA: Multiview fusion based on dual-level attention for drug interaction prediction.

Drug-drug interaction prediction plays an important role in pharmacology and clinical applications. Most traditional methods predict drug interactions based on drug attributes or network structure. They usually have three limitations: 1) failing to integrate drug features and network structures well, resulting in less informative drug embeddings; 2) being restricted to a single view of drug interaction relationships; 3) ignoring the importance of different neighbors. To tackle these challenges, this paper proposed a multiview fusion based on dual-level attention to predict drug interactions (called MFDA). The MFDA first constructed multiple views for the drug interaction relationship, and then adopted a cross-fusion strategy to deeply fuse drug features with the drug interaction network under each view. To distinguish the importance of different neighbors and views, MFDA adopted a dual-level attention mechanism (node level and view level) to obtain the unified drug embedding for drug interaction prediction. Extensive experiments were conducted on real datasets, and the MFDA demonstrated superior performance compared to state-of-the-art baselines. In the multitask analysis of new drug reactions, MFDA obtained higher scores on multiple metrics. In addition, its prediction results corresponded to specific drug reaction events, which achieved more accurate predictions.

[Development of an APRT-deficient CHO cell line and its ability of expressing recombinant protein].

Chinese hamster ovary (CHO) cells are the preferred host cells for the production of complex recombinant therapeutic proteins. Adenine phosphoribosyltransferase (APRT) is a key enzyme in the purine biosynthesis step that catalyzes the condensation of adenine with phosphoribosylate to form adenosine phosphate AMP. In this study, the gene editing technique was used to knock out the aprt gene in CHO cells. Subsequently, the biological properties of APRT-KO CHO cell lines were investigated. A control vector expressed an enhanced green fluorescent protein (EGFP) and an attenuation vector (containing an aprt-attenuated expression cassette and EGFP) were constructed and transfected into APRT-deficient and wild-type CHO cells, respectively. The stable transfected cell pools were subcultured for 60 generations and the mean fluorescence intensity of EGFP in the recombinant CHO cells was detected by flow cytometry to analyze the EGFP expression stability. PCR amplification and sequencing showed that the aprt gene in CHO cell was successfully knocked out. The obtained APRT-deficient CHO cell line had no significant difference from the wild-type CHO cells in terms of cell morphology, growth, proliferation, and doubling time. The transient expression results indicated that compared with the wild-type CHO cells, the expression of EGFP in the APRT-deficient CHO cells transfected with the control vector and the attenuation vector increased by 42%±6% and 56%±9%, respectively. Especially, the EGFP expression levels in APRT-deficient cells transfected with the attenuation vector were significantly higher than those in wild-type CHO cells (P < 0.05). The findings suggest that the APRT-deficient CHO cell line can significantly improve the long-term expression stability of recombinant proteins. This may provide an effective cell engineering strategy for establishing an efficient and stable CHO cell expression system.

Salvianolic acid B inhibits the progression of liver fibrosis in rats via modulation of the Hedgehog signaling pathway.

Salvianolic acid B (Sal B) has previously reported anti-hepatic fibrosis effects, though it is not clear if it can inhibit hepatic fibrosis by regulating the hedgehog (Hh) signaling pathway. The aim of the present study was to explore the roles and mechanism of Sal B in preventing and treating liver fibrosis in rats. The study also aimed to determine the role of the Hh signaling pathway in this process. A rat model of liver fibrosis was induced through the subcutaneous injection of 50% carbon tetrachloride, followed by treatment with Sal B. After gavage, blood was collected to detect serum markers of liver injury. The degree of liver fibrosis and tissue damage was assessed using histopathological analysis. Western blotting and reverse transcription-quantitative PCR were used to detect the expression levels of TGF-ß1 and Hh signaling pathway-related genes, including Sonic hedgehog (Shh) protein, membrane protein receptor protein patched homolog 1 (Ptch1), membrane protein receptor Smoothened (Smo) and transcription factor glioma-associated oncogene homolog 1 (Gli1). Serum alanine aminotransferase, aspartate aminotransferase and total bilirubin levels were decreased, whilst levels of albumin were increased in rats with liver fibrosis that were treated with Sal B (P<0.05). Additionally, significant increases in TGF-ß1, Shh, Ptch1, Smo, Gli1 and α-smooth muscle actin expression levels were observed in the liver tissues of rats with hepatic fibrosis (P<0.05). However, Sal B treatment significantly reduced the expression levels of these proteins (P<0.05). In conclusion, the results of the present study suggested that the Hh signaling pathway may be activated during the process of rat liver fibrosis. Thus, Sal B may exert its anti-hepatic fibrosis effects, at least in part, by inhibiting the activation of the Hh signaling pathway.

Effects of substrate temperatures on the structure and properties of hafnium dioxide films.

Different HfO2 monolayers under different deposition conditions, such as substrate temperature and oxygen partial pressure, were prepared from metal hafnium using the reactive electron beam evaporation method. X-ray diffraction was applied to determine the crystalline phase of these films, the surface morphology of the samples was examined by atomic force microscopy, and the optical properties were analyzed using a spectrophotometer and the surface thermal lens technique. The relationship between substrate temperature and film characteristic was investigated, and the correlation between the observed film properties and the laser damage threshold was also discussed.

Laser damage study of nodules in electron-beam-evaporated HfO2/SiO2 high reflectors.

A reactive electron beam evaporation process was used to fabricate 1.064 µm HfO2/SiO2 high reflectors. The deposition process was optimized to reduce the nodular density. Cross-sectioning of nodular defects by a focused ion-beam milling instrument showed that the nodule seeds were the residual particles on the substrate and the particulates from the silica source "splitting." After optimizing the substrate preparation procedure and the evaporation process, a low nodular density of 2.7/mm2 was achieved. The laser damage test revealed that the ejection fluences and damage growth behaviors of nodules created from deep or shallow seeds were totally different. A mechanism based on directional plasma scald was proposed to interpret observed damage growth phenomenon.

Direct Numerical Simulation of Fluid Flow and Mass Transfer in Particle Clusters.

In this paper, an efficient ghost-cell based immersed boundary method is applied to perform direct numerical simulation (DNS) of mass transfer problems in particle clusters. To be specific, a nine-sphere cuboid cluster and a random-generated spherical cluster consisting of 100 spheres are studied. In both cases, the cluster is composed of active catalysts and inert particles, and the mutual influence of particles on their mass transfer performance is studied. To simulate active catalysts the Dirichlet boundary condition is imposed at the external surface of spheres, while the zero-flux Neumann boundary condition is applied for inert particles. Through our studies, clustering is found to have negative influence on the mass transfer performance, which can be then improved by dilution with inert particles and higher Reynolds numbers. The distribution of active/inert particles may lead to large variations of the cluster mass transfer performance, and individual particle deep inside the cluster may possess a high Sherwood number.

Direct Numerical Simulation of Reactive Fluid-Particle Systems Using an Immersed Boundary Method.

In this paper, direct numerical simulation (DNS) is performed to study coupled heat and mass-transfer problems in fluid-particle systems. On the particles, an exothermic surface reaction takes place. The heat and mass transport is coupled through the particle temperature, which offers a dynamic boundary condition for the thermal energy equation of the fluid phase. Following the case of the unsteady mass and heat diffusion in a large pool of static fluid, we consider a stationary spherical particle under forced convection. In both cases, the particle temperatures obtained from DNS show excellent agreement with established solutions. After that, we investigate the three-bead reactor, and finally a dense particle array composed of hundreds of particles distributed in a random fashion is studied. The concentration and temperature profiles are compared with a one-dimensional heterogeneous reactor model, and the heterogeneity inside the array is discussed.

[Effect of platelet lysate on chondrogenic differentiation of human umbilical cord derived mesenchymal stem cells in vitro].

OBJECTIVE: To study the effect of platelet lysate (PL) on chondrogenic differentiation of human umbilical cord derived mesenchymal stem cells (hUCMSCs) in vitro. METHODS: Umbilical cords were voluntarily donated by healthy mothers. The hUCMSCs were isolated by collagenase digestion and cultured in vitro. The surface markers of the cells were detected by flow cytometer. According to different components of inductive medium, the cultured hUCMSCs were divided into 3 groups: group A [H-DMEM medium, 10% fetal bovine serum (FBS), and 10%PL]; group B [H-DMEM medium, 10%FBS, 10 ng/mL transforming growth factor beta1 (TGF-beta1), 1 x 10(-7) mol/L dexamethasone, 50 microg/mL Vitamin C, and 1% insulin-transferrin-selenium (ITS)]; and group C (H-DMEM medium, 10%FBS, 10 ng/mL TGF-beta1, 1 x 10(-7) mol/L dexamethasone, 50 microg/mL vitamin C, 1%ITS, and 10%PL). The hUCMSCs were induced in the mediums for 2 weeks. Toluidine blue staining was used to detect the secretion of chondrocyte matrix. Immunofluorescence method was used to identify the existence of collagen type II. The expressions of Aggrecan and collagen type II were detected by semiquantitative RT-PCR. RESULTS: Flow cytometer results showed that the hUCMSCs did not express the surface markers of hematopoietic cell CD34, CD45, and human leukocyte antigen DR, but expressed the surface markers of adhesion molecule and mesenchymal stem cells CD44, CD105, and CD146. Toluidine blue staining and immunofluorescence showed positive results in group C, weak positive results in group B, and negative results in group A. Semiquantitative RT-PCR showed the expressions of Aggrecan and collagen type II at mRNA level in groups B and C, but no expression in group A. The mRNA expressions of Aggrecan and collagen type II were higher in group C than in group B (P < 0.05). CONCLUSION: Only 10%PL can not induce differentiation of hUCMSCs into chondrocytes, but it can be a supplement to the induced mediums. PL can improve hUCMSCs differentiating into chondrocytes obviously in vitro. This study provides new available conditions for constructing tissue engineered cartilage.