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Pancreatic ductal adenocarcinoma rapidly acquires resistance to chemotherapy, remaining a fatal disease. Immunotherapy is one of the breakthroughs in cancer treatment, which includes immune checkpoint inhibitors, chimeric antigen receptor T‐cell immunotherapy, and neoantigen vaccines. However, immunotherapy has not achieved satisfactory results in the treatment of pancreatic cancer. Immunogenic death comprises proinflammatory cell death, which provides a way to enhance tumor immunogenicity and promote an immune response in solid tumors. Herein, an ionic liquid ablation agent (LAA), synthesized from choline and geranic acid, which triggers necrosis‐induced immunotherapy by remodeling an immunosuppressive "cold" tumor to an immune activated "hot" tumor is described. The results indicate that LAA‐treated tumor cells can enhance immunogenicity, inducing dendritic cell maturation, macrophage M1 polarization, and cytotoxic T lymphocyte infiltration. The results of the present study provide a novel strategy for solid tumor immunotherapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Drug-in-cyclodextrin-in-liposome (DCL) was used to encapsulated limonene (Lim). • Complexation ratio of 1:1 of Lim/HP-β-CD complex was analyzed by molecular dynamics simulation. • The average size was 147.5 nm, and zeta potential was 48.7 mv. • DCL formulation improved the stability and enhanced the antioxidant activity of Lim. • DCL can be used as a nanocarrier of food matrix for volatile and hydrophobic compounds. Drug-in-cyclodextrin-in-liposome (DCL) combines advantages of cyclodextrin and liposome. Here, DCL formulation was successfully prepared to encapsulate limonene (Lim), whose characterization revealed that particle size was 147.5 ± 1.3 nm and zeta potential was −48.7 ± 0.8 mV. And the complexation mechanism of Lim/HP-β-CD inclusion complex (the intermediate of DCL) was analyzed by molecular dynamics simulation, showing that Lim was entrapped into the cavity of HP-β-CD through electrostatic and hydrophobic interaction with a molar ratio of 1:1. Notably, DCL formulation not only reduced Lim volatilization in 25℃, but also enhanced the free radical (DPPH· and ABTS·+) scavenging ability of Lim. In summary, Lim-DCL formulation improved the stability and enhanced the antioxidant activity of Lim. DCL nanocarrier system is suitable to preserve volatile and hydrophobic compounds, enlarging their application in pharmaceutics industries. [ABSTRACT FROM AUTHOR]

There are many conflicting theories about the relationship between media reports and public opinion, but few of them are supported by empirical work on large data sets. We use sentiment results on over 260,000 China-related articles in The New York Times to show that events in international relations affect media sentiment which, in turn, affects public opinion. We find that sudden shifts in US-China relations are accompanied by changes in how The New York Times covers China and that the news reporting on China leads public opinion on China by 1 year. Our work illustrates how The New York Times, a prestigious mass media institution, propagates international relation signals to shape American views of the Chinese state and the Chinese people. [ABSTRACT FROM AUTHOR]

Background: Situs inversus totalis (SIT) is a rare genetic congenital disease, characterized with complete right-to-left inversion of all the internal organs. We herein describe a meaningful case which was diagnosed as gallbladder adenosquamous carcinoma, a rare histology type of gallbladder cancer, with SIT. Case Presentation: A 59-year-old Chinese woman was admitted for persistent epigastric distention and intermittent abdominal pain. The abdominal CT scan revealed a huge mass at the gallbladder bottom, involving the adjacent transverse colon and liver. En-bloc radical resection of the gallbladder cancer, including partial colectomy and hepatectomy with regional node dissection, followed by colocolostomy and Roux-en-Y choledochojejunostomy, was successfully performed. Pathology analysis indicated an adenosquamous carcinoma with positive adenocarcinoma markers (CK7, CK19) and squamous carcinoma markers (CK5/6, P63). Conclusion: The SIT anomaly might increase the risk of malignancies by sharing genome mutations, suggesting the importance of surveillance in the SIT settings. [ABSTRACT FROM AUTHOR]

Objective: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play key roles in cancer. This study aims to clarify role of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in non-small cell lung cancer (NSCLC) and uncover the underlying mechanisms. Materials and Methods: In this experimental study, MALAT1 and miR-202 expression in tissues and cell lines were detected using quantitative real time polymerase chain reaction (qRT-PCR) assay. Cell transfection was conducted using Lipofectamine 3000. Cell proliferation was determined with CCK-8 assay. MMP2 and MMP9 expressions were measured with Western blot. Cell invasive ability was evaluated by Transwell assay. Starbase 2.0 tool was used to predict targets of MALAT1. Dual luciferase reporter assay, RNA-binding protein immunoprecipitation assay and RNA pull-down assay were conducted to confirm the potential direct interaction between MALAT1 and miR-202. Results: MALAT1 was overexpressed in NSCLC samples and cell lines. High expression of MALAT1 was related to large tumor size (>3 cm), poor histological grade, advanced cancer and tumor metastasis in NSCLC. In vitro assays exhibited that knockdown of MALAT1 remarkably decreased A549 cell growth and invasion capacity, while overexpression of MALAT1 significantly enhanced NCI-H292 cell proliferation and invasion ability. Next, we verified that MALAT1 could act as a competing endogenous RNA (ceRNA) by sponging miR-202 in NSCLC and there is a negative correlation between MALAT1 and miR-202. Besides, overexpression of miR-202 inhibited cell proliferation and invasive ability in MALAT1-overexpressed cells. Conclusion: This study demonstrated that lncRNA-MALAT1 gets involved in NSCLC progression by targeting miR- 202, indicating that MALAT1 may serve as a novel therapeutic target for NSCLC treatment. [ABSTRACT FROM AUTHOR]

The use of pooled data from different repeated survey series to study long-term trends is handicapped by a measurement difficulty: different survey series often use different scales to measure the same attitude and thus generate scale-incomparable data. In this article, the authors propose the latent attitude method (LAM) to address this scale-incomparability problem, on the basis of the assumption that attitudes measured by ordinal categories reflect a latent attitude with cut points. The method extends the latent variable method in the case of a single survey series to the case of multiple survey series and leverages overlapping years for identification. The authors first assess the validity of the method with simulated data. The results show that the method yields accurate estimates of mean attitudes and cut point values. The authors then apply the method to an empirical study of Americans' attitudes toward China from 1974 to 2019. [ABSTRACT FROM AUTHOR]

Swine are the main host of the H1N1 swine influenza virus (SIV), however, H1N1 can also infect humans and occasionally cause serious respiratory disease. To trace the evolution of the SIV in Guangdong, China, we performed an epidemic investigation during the period of 2016–2017. Nine H1N1 influenza viruses were isolated from swine nasal swabs. Antigenic analysis revealed that these viruses belonged to two distinct antigenic groups, represented by A/Swine/Guangdong/101/2016 and A/Swine/Guangdong/52/2017. Additionally, three genotypes, known as GD52/17-like, GD493/17-like and GD101/16-like, were identified by phylogenetic analysis. Importantly, the genotypes including a minimum of 4 pdm/09-origin internal genes have become prevalent in China in recent years. A total of 2966 swine serum samples were used to perform hemagglutination inhibition (HI) tests, and the results showed that the seroprevalence values of SW/GD/101/16 (32.2% in 2016, 32.1% in 2017) were significantly higher than the seroprevalence values of SW/GD/52/17 (18.0% in 2016, 16.7% in 2017). Our study showed that the three reassortant genotypes of H1N1 SIV currently circulating in China are stable, but H1N1pdm09 poses challenges to human health by the introduction of internal genes into these reassortant genotypes. Strengthening SIV surveillance is therefore critical for SIV control and minimizing its potential threat to public health. [ABSTRACT FROM AUTHOR]

Food occupies a central position in every culture and it is therefore of great interest to understand the evolution of food culture. The advent of the World Wide Web and online recipe repositories have begun to provide unprecedented opportunities for data-driven, quantitative study of food culture. Here we harness an online database documenting recipes from various Chinese regional cuisines and investigate the similarity of regional cuisines in terms of geography and climate. We find that geographical proximity, rather than climate proximity, is a crucial factor that determines the similarity of regional cuisines. We develop a model of regional cuisine evolution that provides helpful clues for understanding the evolution of cuisines and cultures. [ABSTRACT FROM AUTHOR]

In the sustainability concept framework, wastewater highly loaded with acid is considered as a valuable resource, rather than a waste. Diffusion dialysis employing anion exchange membranes is a feasible solution to extracting acid from this waste stream. However, conventional anion exchange membranes have dense spatial structures with no observable pores even at nanoscale, which limits the transfer of protons. Porous anion exchange membranes provide a practical avenue to enhance the proton transfer due to their unique spatial structure. In this study, novel porous anion exchange membranes were designed by one-step crosslinking and quaternization of porous brominated poly (phenylene oxide) membrane substrate by 1, 4-diazabicyclo [2.2.2] octane. The resultant porous anion exchange membranes showed a high performance in acid recovery by diffusion dialysis, due to their uniquely tailored microstructures including an extremely thin selective layer and high free space volume. Specifically, the optimal anion exchange membrane possessed an acid dialysis coefficient of 0.066 ± 0.003 m h−1 and an acid/salt separation factor of 96.9 ± 2.5 in the HCl/FeCl 2 mixture solution, outperforming the commercial anion exchange membrane (i.e., DF-120, acid dialysis coefficient of 0.0085 m h−1 and acid/salt separation factor of 18.5). This study demonstrates the great potential in constructing advanced anion exchange membranes at large scale for efficient acid recovery from highly acidic wastewater to support environment sustainability. Image 1 • Novel porous anion exchange membranes (AEMs) are prepared by a facile one-step method. • The tailor-made AEMs show superior performance for acid recovery by diffusion dialysis. • The optimal AEM has an acid dialysis coefficient of 0.066 ± 0.003 m h−1 and an acid/salt separation factor of 96.9 ± 2.5. • Great potential of the porous AEMs in industrial acidic wastewater treatment can be expected. [ABSTRACT FROM AUTHOR]

Background LINC00152, a novel long noncoding RNA (lncRNA), was identified as an oncogene involved various cancers. This study was designed to explore the clinical significance and prognosis role of LINC00152. Methods Eligible studies were recruited by a systematic search in PubMed, Web of Science, and Embase up to August 23, 2017. Odds ratios (ORs), hazard ratios (HRs) and 95% confidence interval (95% CI) were pooled using Review Manager 5.3 and STATA 12.0. Result A total of 10 studies with 913 patients were included to evaluate the association between LINC00152 expression and clinicopathological factors, overall survival (OS) and disease-free survivals (DFS). The results indicated that the expression level of LINC00152 was positively correlated with tumor size (OR = 5.19, 95% CI: 2.33–11.52, p  < .0001), TNM stage (OR = 3.12, 95% CI: 1.77–5.51, p  < .0001) and lymph node metastasis (OR = 3.41, 95% CI: 2.13–5.48, p  < .00001). Moreover, elevated LINC00152 could predict unfavorable OS with pooled HR of 1.66 (95% CI: 1.29–2.13, p  < .0001) and poor DFS (HR = 2.13, 95% CI: 1.39–3.25, p  = .0005) in cancer patients. Conclusion LINC00152 was correlated with advanced clinicopathological features and poor prognosis as a novel predictive biomarker in various cancers. [ABSTRACT FROM AUTHOR]

Gemcitabine (GEM), as a first‐line chemotherapeutics for pancreatic ductal adenocarcinoma (PDAC) treatment, still faces several clinical challenges, restricted by instability in blood circulations, low tumor selectivity, and acquired nature characteristics of chemo‐resistance. To solve these challenges, the rational design of combination therapy with GEM and other therapy modalities is imperative. Herein, a small molecular self‐assembly nano‐prodrug is developed, which can achieve the co‐delivery of GEM, Ferrocene and nutlin‐3a on the achievement of GEM‐induced apoptosis with ferroptosis. In this nano‐prodrug, the disulfide linkage not only acts as a GSH‐responsive trigger but also plays an important role in self‐assembly behavior of nanoparticle that can load nutlin‐3a. Interestingly, nutlin‐3a plays an important role in both ferroptosis and apoptosis, one is effectively sensitized cells to ferroptosis by inhibiting cystine uptake, and the other is promoted apoptosis by elevating p53 expression. To further enhance the drug tumor accumulation and maintain stability in systemic circulations, this nano‐prodrug is then encapsulated into plectin1 receptor‐targeting phospholipid micelles (DSPE‐PEG‐PTP), which displays high selective tumor inhibition and good biosafety on different mice models, especially in orthotopic and patient‐derived xenograft (PDX) models. The findings provide new insights into the combination therapy of GEM with ferroptosis for reduced chemo‐resistance on PDAC treatment. [ABSTRACT FROM AUTHOR]

Micro-blogging systems have become one of the most important ways for information sharing. Network structure and users’ interactions such as forwarding behaviors have aroused considerable research attention, while mention, as a key feature in micro-blogging platforms which can improve the visibility of a message and direct it to a particular user beyond the underlying social structure, is seldom studied in previous works. In this paper, we empirically study the mention effect in information diffusion, using the dataset from a population-scale social media website. We find that users with high number of followers would receive much more mentions than others. We further investigate the effect of mention in information diffusion by examining the response probability with respect to the number of mentions in a message and observe a saturation at around 5 mentions. Furthermore, we find that the response probability is the highest when a reciprocal followship exists between users, and one is more likely to receive a target user’s response if they have similar social status. To illustrate these findings, we propose the response prediction task and formulate it as a binary classification problem. Extensive evaluation demonstrates the effectiveness of discovered factors. Our results have consequences for the understanding of human dynamics on the social network, and potential implications for viral marketing and public opinion monitoring. [ABSTRACT FROM AUTHOR]

The decline in vascular capacity within the meniscus is a well-documented phenomenon during both development and degeneration. Maintaining vascular integrity has been proposed as a potential therapeutic strategy for osteoarthritis. Therefore, our study aims to investigate the characteristics of endothelial cells and blood vessels in embryonic and degenerated meniscus tissues. Human embryonic and mature menisci were used for histological analyses. Single-cell RNA sequencing was used to identify cell clusters and their significant genes in embryo meniscus to uncover characteristic of endothelial cells. Computer analysis and various staining techniques were used to characterize vessels in development and osteoarthritis meniscus. Vessels structure first observed in E12w and increasing in E14w. Vessels were veins majorly and arteries growth in E35w. Endothelial cells located not only perivascular but also in the surface of meniscus. The expression of DLL1 was observed to be significantly altered in endothelial cells within the vascular network that failed to form. Meniscus tissues affected by osteoarthritis, characterized by diminished vascular capacity, displayed reduced levels of DLL1 expression. Experiment in vitro confirmed DLL1/NOTCH1 be vital to angiogenesis. Lack of DLL1/NOTCH1 signaling pathway was mechanism of vascular declination in development and degenerated meniscus. [ABSTRACT FROM AUTHOR]

A capillary electrophoresis (CE) with chemiluminescence (CL) detection method was developed for the simultaneous quantification of 5-hydroxyindoleacetic acid (5-HIAA) and 5-hydroxytryptamine (5-HT). In this method, CdTe quantum dot (QD) and horseradish peroxidase (HRP) were used as enhancing reagents to co-catalyze the post-column CL reaction between luminol and hydrogen peroxide, achieving highly efficient CL emission. 5-HIAA and 5-HT inhibit the CL emission resulting to the formation of negative peaks in electropherogram. The degree of CL suppression is proportional to the concentration of 5-HT and 5-HIAA. The linear ranges for the determination of 5-HIAA and 5-HT were 2.5 × 10 −8 –2.5 × 10 −6 M and 2.5 × 10 −8 –5.0 × 10 −6 M with detection limits (signal/noise = 3) of 7.0 × 10 −9 M and 6.0 × 10 −9 M, respectively. Intraday precision do not exceed 5.0%. The accuracy was confirmed by the recoveries ranged from 98% to 104%. The present method was successfully applied for the quantification of 5-HIAA and 5-HT in human urine. The concentrations of 5-HT and 5-HIAA in human urine were found to be in the range of 0.78–1.2 μM and 3.2–5.1 μM, respectively. [ABSTRACT FROM AUTHOR]

Abstract: A sensitive method based on quantum dot (QD)-enhanced capillary electrophoresis–chemiluminescence (CE–CL) detection was developed for simultaneous determination of dopamine (DA) and epinephrine (E). In this work, CdTe QD was added into the running buffer of CE to catalyze the post-column CL reaction between luminol and hydrogen peroxide, achieving higher CL emission. Negative peaks were produced due to the inhibitory effects on CL emission from DA and E eluted from the electrophoretic capillary. The decrease in CL intensity was proportional to the concentration of DA and E in the range of 8.0×10−8–5.0×10−6 M and 4.0×10−8–5.0×10−6 M, respectively. Detection limits for DA and E were 2.3×10−8 M and 9.3×10−9 M, respectively. Using this method, the levels of DA and E in human urine from healthy donors were determined. [Copyright &y& Elsevier]

Introduction: Although the fall protection net installed at the end of the truck escape ramp has a protective effect on trucks and drivers, but lacks sufficient theoretical basis and verification method. Objectives: The primary objective of this paper was to design a fall protection net that meets the regulations and research its protection performance. Methods: The finite-element method was used to design the overall size, material, mesh length, mesh type, shape, and supporting structure of the fall protection net installed at the end of truck escape ramp, then dummy and truck models were used to impact the fall protection net to verify the rationality of the design. After the design completed, the truck model was used to impact the fall protection net twice to research the cumulative protection performance. Results: A fall protection net with a width of 6000 mm, a span of 6000 mm, a depth of 5196 mm, a mesh length of 150 mm, a mesh type of diamond mesh, a shape of 60-degree V-shaped, a supporting structure of steel pipe supporting has a better effect on energy absorption and protection. Within the two consecutive impacts, the residual plastic deformation and stress of the fall protection net generated in the first impact severely affect the protection performance in the second impact. Conclusion: It is feasible to use the finite-element method to design and research the fall prevention net installed at the end of the truck escape ramp, and the fall protection net can indeed protect the trucks and drivers, and it should be inspected and maintained after impact to ensure the protective performance in subsequent use. [ABSTRACT FROM AUTHOR]

Background and Aim: Clinically significant serrated polyps are precursors of colorectal cancers, with features considered high risk including size ≥10 mm, dysplasia, and presence of synchronous conventional adenoma. While these features have been described in cohorts undergoing screening colonoscopy, there is little information regarding the prevalence and patient characteristics associated with high‐risk sessile serrated polyps (SSPs) in those undergoing surveillance colonoscopy. Methods: Polyp pathology at the index and first follow‐up colonoscopy performed between 2004 and 2019 were examined in patients enrolled in a surveillance program because of an index finding of adenoma and/or SSP. Demographics and pathology features for SSP were compared between the colonoscopies. Results: Of 6297 patients undergoing index colonoscopy, 2035 underwent follow‐up colonoscopy after 3.3 years (interquartile range 2.1–4.8 years). The proportion with SSP decreased from 7.6% at index to 5.0% at follow‐up (P < 0.001); however, the proportion of SSPs that were considered high risk was not different between the colonoscopies (62.8% vs 62.4%). Female gender was associated with the presence of high‐risk SSP at index colonoscopy (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.28–2.06), while age ≥75 years (OR 3.38, 95% CI 1.67–6.81) and previous high‐risk SSP (OR 9.40, 95% CI 4.23–20.88) were independently associated with high‐risk SSP at follow‐up. Conclusions: The prevalence of SSP falls by one‐third at first follow‐up colonoscopy although the proportion of SSP with high‐risk features remains the same. While females were more likely to have a high‐risk SSP at the index colonoscopy, those at greatest risk for high‐risk SSP at follow‐up colonoscopy were age >75 years and an index high‐risk SSP. [ABSTRACT FROM AUTHOR]

Background: An autologous bone-cage made from the spinous process and laminae might provide a stability in posterior lumbar interbody fusion (PLIF) close that of the traditional-cage made of polyetheretherketone (PEEK) or titanium. The biomechanical effect of autologous bone-cages on cage stability, stress, and strains, and on the facet contact force has not been fully described. This study aimed to verify whether autologous bone-cages can achieve similar performance as that of PEEK cages in PLIF by using a finite element analysis.Methods: The finite element models of PLIF with an autologous bone-cage, a titanium cage, and a PEEK cage were constructed. The autologous bone-cage was compared with the titanium and PEEK cages. The mechanical properties of the autologous bone-cage were obtained through mechanical tests. The four motion modes were simulated. The range of motion (ROM), the stress in the cage-end plate interface, and the facet joint force (FJF) were compared.Results: The ROM was increased at adjacent levels but decreased over 97% at the treated levels, and the intradiscal pressure at adjacent levels was increased under all conditions in all models. The FJF disappeared at treated levels and increased under extension, lateral bending, and lateral rotation in all models. The maximum stress of the cage-endplate interface was much lower in the autologous bone-cage model than those in the PEEK and titanium cage models.Conclusions: In a finite model of PLIF, the autologous bone-cage model could achieve stability close that of traditional titanium or PEEK cages, reducing the risk of subsidence. [ABSTRACT FROM AUTHOR]

Malignancies treated by insoluble targeted agents show low dose exposure and therapeutic responses, therefore easily develop drug resistance. Nanoparticle-modified drugs might disrupt chemoresistance by increasing dose exposure and altering resistance pathways, as administrated via the intravenous route to maximize efficacy. Herein, we proposed a self-assembled nanocapsulation strategy to construct a nanocomplex with multiarm polymer and novel dendrimer series (MAP-mG3) for encapsulating insoluble inhibitors by nucleotide lock. MAP-mG3 delivering the mammalian target of rapamycin (mTOR) inhibitor OSI-027 (MAP-mG3/OSI-027) showed higher loading capacity, enhanced solubility, controlled release, and increased intracellular tumoral accumulation. MAP-mG3/OSI-027, more efficiently than the free targeted agents, attenuated mTOR phosphorylation and inhibited growth of pancreatic cancer cells. In addition, MAP-mG3/OSI-027 reverted chemoresistance to OSI-027 in drug resistance pancreatic cancer by increasing intracellular dose exposure, as well as regulating ABCB1 expression and compensatory pathways. The optimized nanocapsulation design provides an effective strategy to engineer and reactivate insoluble targeted agents for chemoresistant applications. Unlabelled Image [ABSTRACT FROM AUTHOR]

We developed a biodegradable, oncosensitive, megamer-based delivery system for miRNA therapy. The miRNA nanotherapeutics, activatable by stepwise stimulation of acidity and reduction mimicking tumor microenvironment, efficiently improve liver-specific miR-122 expression, increasing the possibility of translational application of miR-122 therapy against liver cancer. [ABSTRACT FROM AUTHOR]

Southern China is considered an important source of influenza virus pandemics because of the large, diverse viral reservoirs in poultry and swine. To examine the trend in influenza A virus of swine (IAV-S), an active surveillance program has been conducted from 2013 to 2015 in Guangdong, China. The phylogenetic analyses showed that the external genes of the isolates were assigned to the Eurasian avian-like swine (EA) H1N1 and/or human-like H3N2 lineages with multiple substitutions, indicating a notable genetic shift. Moreover, the internal genes derived from different origins (PB2, PB1, PA, NP: pdm/09 (pandemic influenza virus 2009)-origin, M: pdm/09- or EA-origin, NS: North American Triple Reassortant (TR)-origin have become the dominant backbone of IAV-S in southern China. According to the origins of the eight gene segments, the isolates can be categorized into five genotypes. The results of mice experiment showed that the YJ4 (genotype 1) and DG2 (genotype 4) are the most pathogenic to mice, and the viruses are observed in kidneys and brains, indicating the systemic infection. The alterations of the IAV-S gene composition supported the continued implementation of the intensive surveillance of IAV-S and the greater attention focused on potential shifts toward transmission to humans. [ABSTRACT FROM AUTHOR]

Epiphyseal growth plate is highly dynamic tissue which is controlled by a variety of endocrine, paracrine hormones, and by complex local signaling loops and mechanical loading. Mechano growth factor (MGF), the splice variant of the IGF-I gene, has been discovered to play important roles in tissue growth and repair. However, the effect of MGF on the growth plate remains unclear. In the present study, we found that MGF mRNA expression of growth plate chondrocytes was upregulated in response to mechanical stimuli. Treatment of MGF had no effect on growth plate chondrocytes proliferation and differentiation. But it could inhibit growth plate chondrocytes apoptosis and inflammation under mechanical overload. Moreover, both wound healing and transwell assay indicated that MGF could significantly enhance growth plate chondrocytes migration which was accompanied with YAP activation and nucleus translocation. Knockdown of YAP with YAP siRNA suppressed migration induced by MGF, indicating the essential role of YAP in MGF promoting growth plate chondrocytes migration. Furthermore, MGF promoted YAP activation through RhoA GTPase mediated cytoskeleton reorganization, RhoA inhibition using C3 toxin abrogated MGF induced YAP activation. Importantly, we found that MGF promoted focal adhesion(FA) formation and knockdown of YAP with YAP siRNA partially suppressed the activation of FA kinase, implying that YAP is associated with FA formation. In conclusion, MGF is an autocrine growth factor which is regulated by mechanical stimuli. MGF could not only protect growth plate chondrocytes against damage by mechanical overload, but also promote migration through activation of RhoA/YAP signaling axis. Most importantly, our findings indicate that MGF promote cell migration through YAP mediated FA formation to determine the FA-cytoskeleton remodeling. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the effects of Prunella Vulgaris (P. vulgaris) on the immune function in mice. The mice were randomly divided into one control group and three treatment groups of 10 mice each. The control group received pure water and the treatment groups received P. vulgaris extract at concentrations of 0.15, 0.30 and 0.90 g/kg BW orally for 30 days, respectively. Changes in cell immune function, non-specific immunity and humoral immunity function were evaluated. Active lymphocytes and T lymphocyte subsets were determined by fluorescence-activated cell sorting (FACS). Certain Serum concentrations of cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that, for cell immune function, compared with the control group, foot pad thickness in high dose group increased significantly (p<0.01), whereas no significant difference in the proliferative ability of splenic lymphocytes was observed among all groups (p>0.05). For non-specific immunity, NK cell activity increased significantly in a dose-dependent manner in P. vulgaris treated mice (p<0.01), mononuclear-macrophage function in medium and high dose P. vulgaris treated mice were significantly higher than that of the control group (p<0.05). For humoral immunity, no significant differences were observed in terms of the half value of hemolysis (HC50), number of hemolytic plaques and serum IgG level (p>0.05). The percentage of active T and Th lymphocytes of mice peripheral blood in high dose group were significantly higher than that of the control group (p<0.01). There was no significant difference in serum levels of IL-1β, IL-4, IL-10 and IFN-γ among all of the four groups (p>0.05). The data indicated that 0.90 g/kg BW P. vulgaris extract (equivalent to 7.5 g/kg BW crude drug) had some effect on cellular immune function and non-specific immune function in mice. [ABSTRACT FROM AUTHOR]

Abstract: A microchip electrophoresis (MCE) method with chemiluminescence (CL) detection was developed for the determination of carnosine-related peptides, including carnosine, homocarnosine, and anserine, in biological samples. A simple integrated MCE–CL system was built to perform the assays. The highly sensitive CL detection was achieved by means of the CL reaction between hydrogen peroxide and N-(4-aminobutyl)-N-ethylisoluminol-tagged peptides in the presence of adenine as a CL enhancer and Co2+ as a catalyst. Experimental conditions for analyte labeling, MCE separation, and CL detection were studied. MCE separation of the above-mentioned three peptides took less than 120s. Detection limits (signal/noise ratio [S/N]=3) of 3.0×10−8, 2.8×10−8, and 3.4×10−8 M were obtained for carnosine, anserine, and homocarnosine, respectively. The current MCE–CL method was applied for the determination of carnosine, anserine, and homocarnosine in human cerebrospinal fluid (CSF) and canine plasma. Homocarnosine was detected at the micromolar (μM) level in the CSF samples analyzed, whereas the levels of carnosine and anserine in these samples were below the detection limit of the assay. Interestingly, both carnosine and anserine were detected in the canine plasma samples, whereas homocarnosine was not. [Copyright &y& Elsevier]

• We identify a natural Ser-Leu substitution in the HA cleavage site of EA H1N2 virus. • Ser-Leu substitution at the P2 position reduces viral replication and HA cleavage. • Ser-Leu also affects survival rates in mice infected with reassortant viruses. • This amino acid change may be valuable for influenza vaccine development. Swine influenza viruses not only constitute a potential economic problem for livestock, but also pose a substantial threat to human health. Mutation in the proteolytic cleavage site of hemagglutinin (HA) is recognized as an essential factor of tissue tropism and viral pathogenicity. However, the molecular properties of the cleavage site of Eurasian avian-like swine (EA) H1N2 virus remain largely unknown. In this study, we found a serine-leucine (Ser-Leu) substitution at the P2 position of the HA cleavage site (S328 L) in naturally occurring EA H1N2 virus. To study the effect of this substitution, we used reverse genetics to generate recombinant wild-type and mutant viruses containing a single amino acid mutation at the P2 position in A/swine/Guangdong/YJ28/2014 (YJ28) or A/swine/Guangdong/DG2/2015 (DG2) background. In vitro experiments showed that the Ser-Leu substitution at the P2 position attenuated the viral replication and HA cleavage efficiency. In vivo analyses revealed that, while all mice inoculated with r/DG2-S328 L or r/YJ28 viruses survived, the survival rates of r/DG2- and r/YJ28-L328S-inoculated animals were 20 % and 40 %, respectively. Furthermore, the Ser-Leu substitution at the P2 position attenuated the replication in nasal turbinate and lungs. In summary, this amino acid change may be useful to understand the molecular properties of the cleavage site and be valuable for vaccine development. [ABSTRACT FROM AUTHOR]

Magnesium and Mg-based alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. However, the drawbacks of these materials include high hydrogen gas production, unexpected corrosion resistance, and insufficient mechanical strength duration. Surface modification can protect these biomaterials and induce osteogenesis. In this work, a SrHPO 4 coating was developed for our patented biodegradable Mg–Nd–Zn–Zr alloy (abbr. JDBM) through a chemical deposition method. The coating was characterized by in vitro immersion, ion release, and cytotoxicity tests, which showed a slower corrosion behavior and excellent cell viability. RNA sequencing of MC3T3E1 cells treated with SrHPO 4 -coated JDBM ion release test extract showed increased Tlr4 , followed by the activation of the downstream PI3K/Akt signaling pathway, causing proliferation and growth of pre-osteoblasts. An intramedullary nail (IMN) was implanted in a femoral fracture rat model. Mechanical test, radiological and histological analysis suggested that SrHPO 4 -coated JDBM has superior mechanical properties, induces more bone formation, and decreases the degradation rate compared with uncoated JDBM and the administration of TLR4 inhibitor attenuated the new bone formation for fracture healing. SrHPO 4 is a promising coating for JDBM implants, particularly for long-bone fractures. • SrHPO 4 reduces the in vivo corrosion rate of Mg–Nd–Zn–Zr implants. • Release of Sr2+ and Mg2+ ions induces a biochemical response in rat femur fracture model. • Osteogenic response is stimulated by the TLR4/PI3K/Akt signaling pathway. • Improved mechanical stability and osteogenic induction enhances fracture healing. [ABSTRACT FROM AUTHOR]

Magnesium and Mg-based alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. However, the drawbacks of these materials include high hydrogen gas production, unexpected corrosion resistance, and insufficient mechanical strength duration. Surface modification can protect these biomaterials and induce osteogenesis. In this work, a SrHPO 4 coating was developed for our patented biodegradable Mg–Nd–Zn–Zr alloy (abbr. JDBM) through a chemical deposition method. The coating was characterized by in vitro immersion, ion release, and cytotoxicity tests, which showed a slower corrosion behavior and excellent cell viability. RNA sequencing of MC3T3E1 cells treated with SrHPO 4 -coated JDBM ion release test extract showed increased Tlr4 , followed by the activation of the downstream PI3K/Akt signaling pathway, causing proliferation and growth of pre-osteoblasts. An intramedullary nail (IMN) was implanted in a femoral fracture rat model. Mechanical test, radiological and histological analysis suggested that SrHPO 4 -coated JDBM has superior mechanical properties, induces more bone formation, and decreases the degradation rate compared with uncoated JDBM and the administration of TLR4 inhibitor attenuated the new bone formation for fracture healing. SrHPO 4 is a promising coating for JDBM implants, particularly for long-bone fractures. • SrHPO 4 reduces the in vivo corrosion rate of Mg–Nd–Zn–Zr implants. • Release of Sr2+ and Mg2+ ions induces a biochemical response in rat femur fracture model. • Osteogenic response is stimulated by the TLR4/PI3K/Akt signaling pathway. • Improved mechanical stability and osteogenic induction enhances fracture healing. [ABSTRACT FROM AUTHOR]