Key Matrix Research Articles

Fibronectin regulates the self-renewal of rabbit limbal epithelial stem cells by stimulating the Wnt11/Fzd7/ROCK non-canonical Wnt pathway

Microenvironmental factors regulate stem cell fate. Fibronectin (FN), a key extracellular matrix component of the microenvironment, has been linked to various stem cell behaviors. However, how FN controls self-renewal, proliferation, and homeostasis of limbal stem cells remains unclear. Our study investigated the roles of FN in the self-renewal of rabbit limbal epithelial stem cells (rLESCs) by assessing rLESC proliferation and stemness in the presence and absence of FN. We further examined the effect of FN on non-canonical Wnt signaling during rLESC proliferation by evaluating the expression of cell cycle regulators. We found that rLESC proliferation increased after FN treatment and that 12.5 μg/cm2 FN maintained rLESC stemness. FN facilitated rLESC self-renewal by promoting Wnt11 and Fzd7 interaction. Furthermore, FN modulated cell cycle regulators to enhance rLESC proliferation via the upregulation of ROCK1 and ROCK2. Our study provides new insights into the mechanism through which FN regulates the self-renewal of rLESCs; specifically, this occurs via stimulation of the Wnt11/Fzd7/ROCK non-canonical Wnt pathway. The roles of FN in the self-renewal of limbal epithelial stem cells should be further investigated for the potential treatment of limbal deficiency.

Treatment with the Pseudomonas aeruginosa Glycoside Hydrolase PslG Combats Wound Infection by Improving Antibiotic Efficacy and Host Innate Immune Activity.

Pseudomonas aeruginosa is an opportunistic, nosocomial bacterial pathogen that forms persistent infections due to the formation of protective communities, known as biofilms. Once the biofilm is formed, the bacteria embedded within it are recalcitrant to antimicrobial treatment and host immune defenses. Moreover, the presence of biofilms in wounds is correlated with chronic infection and delayed healing. The current standard of care for chronic wound infections typically involves physical disruption of the biofilm via debridement and subsequent antimicrobial treatment. The glycoside hydrolases PelAh and PslGh have been demonstrated in vitro to disrupt biofilm integrity through degradation of the key biofilm matrix exopolysaccharides Pel and Psl, respectively. Herein, we demonstrate that PslGh hydrolase therapy is a promising strategy for controlling P. aeruginosa wound infections. Hydrolase treatment of P. aeruginosa biofilms resulted in increased antibiotic efficacy and penetration into the biofilm. PslGh treatment of P. aeruginosa biofilms also improved innate immune activity leading to greater complement deposition, neutrophil phagocytosis, and neutrophil reactive oxygen species production. Furthermore, when P. aeruginosa-infected wounds were treated with a combination of PslGh and tobramycin, we observed an additive effect leading to greater bacterial clearance than treatments of tobramycin or PslGh alone. This study demonstrates that PelAh and PslGh have promising therapeutic potential and that PslGh may aid in the treatment of P. aeruginosa wound infections.

Identification and quantification of sites of nitration and oxidation in the key matrix protein laminin and the structural consequences of these modifications

Laminin is a major protein of the basement membrane (BM), a specialized extracellular matrix (ECM) of the artery wall. The potent oxidizing and nitrating agent peroxynitrous acid (ONOOH) is formed at sites of inflammation, and data implicate ONOOH in ECM damage and cardiovascular disease. Co-localization of 3-nitrotyrosine, a product of ONOOH-mediated tyrosine (Tyr) modification, and laminin has been reported in human atherosclerotic lesions. The sites and consequences of 3-nitrotyrosine (and related nitrated tryptophan) formation on laminin, it's self-assembly and cell interactions are poorly understood. In this study murine laminin-111 was exposed to ONOOH (1–500-fold molar excess). Nitration sites were mapped and quantified using LC-MS/MS. Mono-nitration was detected at 148 sites (126 Tyr, 22 Trp), and di-nitration at 14 sites. Label-free quantification showed enhanced nitration with increasing oxidant doses. Tyr nitration was ∼10-fold greater than at Trp. CO2 modulated damage in a site-specific manner, with most sites less extensively nitrated. 119 mono-nitration sites were identified with CO2 present, and no unique sites were detected. 23 di-nitration sites were detected, with 15 unique to the presence of CO2. Extensive modification was detected at sites involved in cell adhesion, protein-protein interactions and self-polymerization. Tyr-145 on the γ1 chain was extensively nitrated, and endothelial cells exhibited decreased adhesion to a nitrated peptide modelling this site. Modification of residues involved in self-polymerization interfered with the formation of ordered polymers as detected by scanning electron microscopy. These laminin modifications may contribute to endothelial cell dysfunction and modulate ECM structure and assembly, and thereby contribute to atherogenesis.

A Novel Method for Identifying the Potential Cancer Driver Genes Based on Molecular Data Integration.

The identification of the cancer driver genes is essential for personalized therapy. The mutation frequency of most driver genes is in the middle (2-20%) or even lower range, which makes it difficult to find the driver genes with low-frequency mutations. Other forms of genomic aberrations, such as copy number variations (CNVs) and epigenetic changes, may also reflect cancer progression. In this work, a method for identifying the potential cancer driver genes (iPDG) based on molecular data integration is proposed. DNA copy number variation, somatic mutation, and gene expression data of matched cancer samples are integrated. In combination with the method of iKEEG, the "key genes" of cancer are identified, and the change in their expression levels is used for auxiliary evaluation of whether the mutated genes are potential drivers. For a mutated gene, the concept of mutational effect is defined, which takes into account the effects of copy number variation, mutation gene itself, and its neighbor genes. The method mainly includes two steps: the first step is data preprocessing. First, DNA copy number variation and somatic mutation data are integrated. Then, the integrated data are mapped to a given interaction network, and the diffusion kernel is used to form the mutation effect matrix. The second step is to obtain the key genes by using the iKGGE method, and construct the connection matrix by means of the gene expression data of the key genes and mutation impact matrix of the mutated genes. Experiments on TCGA breast cancer and Glioblastoma multiforme datasets demonstrate that iPDG is effective not only to identify the known cancer driver genes but also to discover the rare potential driver genes. When measured by functional enrichment analysis, we find that these genes are clearly associated with these two types of cancers.

An image cryptosystem based on pseudorandomly enhanced chaotic DNA and random permutation

We propose an image encryption scheme based on pseudorandomly enhanced logistic map, random permutation and deoxyribonucleic acid coding in this paper. The scheme consists of two main phases: permutation and diffusion. Firstly, a random pixel permutation phase is carried out by a random permutation function to enhance the diffusion and statistical performance. Secondly, a DNA-based diffusion is performed via randomly selected DNA algebraic operations between the randomly permuted image matrix and a chaotic key matrix to produce the cipher image. Pseudorandomly enhanced logistic map is used to produce the key matrix while the direct logistic map is used to select DNA encoding/decoding rules and DNA algebraic operations. The chaos maps are driven by a SHA-256 hash value of the plain image. Experimental results based on several analyses including statistical, differential, key analyses, etc. show that the proposed scheme achieves robust encryption and provides sufficient resistance to various forms of attacks.

The Pseudomonas aeruginosa lectin LecB binds to the exopolysaccharide Psl and stabilizes the biofilm matrix

Pseudomonas aeruginosa biofilms are composed of exopolysaccharides (EPS), exogenous DNA, and proteins that hold these communities together. P. aeruginosa produces lectins LecA and LecB, which possess affinities towards sugars found in matrix EPS and mediate adherence of P. aeruginosa to target host cells. Here, we demonstrate that LecB binds to Psl, a key matrix EPS, and this leads to increased retention of both cells and EPS in a growing biofilm. This interaction is predicted to occur between the lectin and the branched side chains present on Psl. Finally, we show that LecB coordinates Psl localization in the biofilm. This constitutes a unique function for LecB and identifies it as a matrix protein that contributes to biofilm structure through EPS interactions.

Inflammatory biomarkers do not distinguish between patients with sciatica and referred leg pain within a primary care population: results from a nested study within the ATLAS cohort

BackgroundThere is increasing interest in the role of pro-inflammatory cytokines in the pathogenesis of sciatica and whether these could be potential targets for treatment. We sought to investigate serum biomarker levels in patients with low back-related leg pain, including sciatica.MethodsPrimary care consulters aged > 18 with low back-related leg pain were recruited to a cohort study (ATLAS). Participants underwent a standardised clinical assessment, lumbar spine MRI and a subsample (n = 119) had samples taken for biomarker analysis. Participants were classified having: a) clinically confirmed sciatica or referred leg pain, and then subdivided into those with (or without) MRI confirmed nerve root compression due to disc prolapse. Seventeen key cytokines, chemokines and matrix metalloproteinases (MMPs) implicated in sciatica pathogenesis including TNFα and IL-6, were assayed in duplicate using commercial multiplex detection kits and measured using a Luminex suspension array system. Median biomarker levels were compared between the groups using a Mann Whitney U test. Multivariate logistic regression analysis was used to investigate the association between clinical measures and biomarker levels adjusted for possible confounders such as age, sex, and symptom duration.ResultsNo difference was found in the serum level of any of the 17 biomarkers tested in patients with (n = 93) or without (n = 26) clinically confirmed sciatica, nor between those with (n = 44) or without (n = 49) sciatica and MRI confirmed nerve root compression.ConclusionIn this cohort, no significant differences in serum levels of TNFα, IL-6 or any other biomarkers were seen between patients with sciatica and those with back pain with referred leg pain. These results suggest that in patients with low back-related leg pain, serum markers associated with inflammation do not discriminate between patients with or without clinically confirmed sciatica or between those with or without evidence of nerve root compression on MRI.

The advance of assembly of exopolysaccharide Psl biosynthesis machinery in Pseudomonas aeruginosa.

Biofilms are microbial communities embedded in extracellular matrix. Exopolysaccharide Psl (ePsl) is a key biofilm matrix component that initiates attachment, maintains biofilms architecture, and protects bacteria within biofilms of Pseudomonas aeruginosa, an opportunistic pathogen. There are at least 12 Psl proteins involved in the biosynthesis of this exopolysaccharide. However, it remains unclear about the function of each Psl protein and how these proteins work together during the biosynthesis of ePsl. PslG has been characterized as a degrader of ePsl in extracellular or periplasm and PslD is predicted to be a transporter. In this study, we found that PslG and its glycoside hydrolytic activity were also involved in the biosynthesis of ePsl. PslG localized mainly in the inner membrane and some in the periplasm. The inner membrane association of PslG was critical for the biosynthesis of ePsl. The expression of PslA, PslD, and PslE helped PslG remain in the inner membrane. The bacterial two‐hybrid results suggested that PslE could interacted with either PslA, PslD, or PslG. The strongest interaction was found between PslE and PslD. Consistently, PslD was disabled to localize on the outer membrane in the ΔpslE strain, suggesting that the PslE‐PslD interaction affected the localization of PslD. Our results shed light on the assembly of ePsl biosynthesis machinery and suggested that the membrane‐associated PslG was a part of ePsl biosynthesis proteins complex.

Hill Cipher Cryptosystem over Complex Numbers

The Hill Cipher cryptosystem is a symmetry key cryptosystem. This cryptosystem uses the concept of integer over modulo p. This cryptosystem uses a matrix K as a secret key. We must choose the key matrix K which has an inverse in modulo p. This secret key matrix will be used by the sender and recipient of the message to encrypt and descript the message. For this reason, this paper will discuss the generalization of Hill Cipher using matrices over complex numbers. Calculation of determinants and inverses of the matrix K will adopt a system of determinant and inverse calculations on Hill Cipher. The results show that the proposed cryptosystem scrambles the plaintext.

Assessing the knowledge index of the region

Economy of knowledge is an economic formation, where today’s generation of young people will work. It is quite good that many scientists try to forecast what it will be like. The article studies different approaches to assessment of regional knowledge index. The authors put forward a new methodology of its estimation on the basis of key matrix determinant and its logarithming. To assess the knowledge index 16 indicators divided into 4 groups are used and they gave an opportunity to build a four-dimensional matrix. According to the author, this approach is more objective and can eliminate some inaccuracy of methods designed by other authors. On the basis of this methodology the knowledge index was estimated, which shows conditions for shaping economy of knowledge in Russian regions. The rating of federal districts and regions-leaders was built and regions-outsiders in respect of economy of knowledge shaping were identified. Indicators that exert the most serious effect (positive and negative) on the knowledge index of regions were found. More detailed results for the whole period of analysis – 2000–2015 – for all regions of the Russian Federation can be found in the Situational Center of the Russian Plekhanov University of Economics.

The first species of Cotithene Voss (Coleoptera: Curculionidae: Curculioninae) from Amazonian Brazil, with notes on its role as a pollinator of Evodianthus funifer (Poit.) Lindm. (Cyclanthaceae).

Cotithene gorayebi Valente, da Silva de Medeiros, sp. nov. is the first species of Cotithene Voss, 1940 described from the Amazonian forest in Brazil. The new species differs from other described species of Cotithene by its integument color pattern dissimilar between sexes and by the procoxal cavities separated by only a narrow septum in both male and female. It furthers differs by the unique morphology of male and female genitalia. A previously published key and phylogenetic matrix to Cotithene species were each modified to include the new species. The historical trajectory of host associations (inflorescences of Cyclanthaceae) in Cotithene is reanalyzed with the inclusion of the host of the new species. Previously known species are believed to be non-pollinators of various Cyclanthaceae; however, field observations of adults of the new species on inflorescences in anthesis of Evodianthus funifer (Cyclanthaceae) strongly suggest that this may be the first species of Cotithene known to play a role as a pollinator of Cyclanthaceae.

Confocal Laser Scanning Microscopy for Analysis of Pseudomonas aeruginosa Biofilm Architecture and Matrix Localization.

Most microbes can produce surface-associated or suspended aggregates called biofilms, which are encased within a biopolymer-rich matrix. The biofilm matrix provides structural integrity to the aggregates and shields the resident cells against environmental stressors, including antibiotic treatment. Microscopy permits examination of biofilm structure in relation to the spatial localization of important biofilm matrix components. This review highlights microscopic approaches to investigate bacterial biofilm assembly, matrix composition, and localization using Pseudomonas aeruginosa as a model organism. Initial microscopic investigations provided information about the role key matrix components play in elaborating biofilm aggregate structures. Additionally, staining of matrix components using specific labels revealed distinct positioning of matrix components within the aggregates relative to the resident cells. In some cases, it was found that individual matrix components co-localize within aggregates. The methodologies for studying the biofilm matrix are continuing to develop as our studies reveal novel aspects of its composition and function. We additionally describe some outstanding questions and how microscopy might be used to identify the functional aspects of biofilm matrix components.

Effects of Oxygen Concentration and Culture Time on Porcine Nucleus Pulposus Cell Metabolism: An in vitro Study.

Low back pain is a common ailment that affects millions of individuals each year and is linked to degeneration of the intervertebral discs in the spine. Intervertebral disc degeneration is known to result from an imbalance in anabolic and catabolic activity by disc cells. Due to the avascular nature of the intervertebral disc, oxygen deficiency may occur in the central nucleus pulposus (NP). The resulting hypoxia affects matrix regulation and energy metabolism of disc cells, although the mechanisms are not fully understood. This study investigates in vitro glucose consumption and gene expression by NP cells over time under varying oxygen tensions. Notochordal porcine NP cells were cultured in agarose discs at 21, 5, or 1% oxygen tension for 1, 5, or 10 days. The expression of 10 key matrix genes, as well as Brachyury (T), by NP cells was analyzed using RT-PCR. Glucose consumption was measured using a two-point method. Results show that culture time and oxygen tension significantly affect glucose consumption rates by porcine NP cells. There were also significant changes in T expression based on oxygen level and culture time. The 1% oxygen tension had a significantly higher T expression on day 10 than the other two groups, which may indicate a better maintenance of the notochordal phenotype. MMP 1 and 13 expression increased over time for all groups, while only the 5% group showed an increase over time for MMP 3. TIMP expression followed the direction of MMPs but to a lesser magnitude. Five percent and twenty-one percent oxygen tensions led to decreases in anabolic gene expression while 1% led to increases. Oxygen concentration and culture time significantly impacted glucose consumption rate and the gene expression of matrix regulatory genes with hypoxic conditions most accurately maintaining the proper NP phenotype. This information is valuable not only for understanding disc pathophysiology, but also for harnessing the potential of notochordal NP cells in therapeutic applications.

Cyclosporine‐A Enhances Mitochondrial Calcium Buffering to Delay mPTP Opening

Regulation of intra‐mitochondrial (matrix) free calcium ([Ca2+]m) is critical for cellular Ca2+ homeostasis. While mitochondria have the capacity to store a large amount of Ca2+, the availability of [Ca2+]m is maintained within a sub‐micro molar range at steady‐state by the dynamic balance between Ca2+ uptake, buffering, and efflux. Excessive matrix Ca2+ with oxidative stress induces permanent opening of a nonselective inner membrane pore, the mitochondrial permeability transition pore (mPTP), which leads to cell death. Cyclosporine A (CsA), a well‐known inhibitor of the mPTP, is thought to suppress pore opening, in part, by binding to cyclophilin D (CypD) and inhibiting its peptidyl‐prolyl cis‐trans isomerase (PPIase) activity in the presence of high [Ca2+]m. It is not known if the CsA mediated delay in mPTP opening involves regulation of [Ca2+]m as a potential mechanism for mPTP inhibition. In the present study, we tested a novel hypothesis that CsA enhances matrix Ca2+ buffering and consequently modulates the [Ca2+]m threshold for mPTP opening. To test this hypothesis, we investigated the effects of CsA on mitochondrial Ca2+ handling and bioenergetics in K+ pyruvate energized mitochondria isolated from the guinea pig hearts. We quantitatively determined mitochondrial Ca2+ uptake by monitoring both the disappearance of the extra‐matrix ([Ca2+]e) and the increase in [Ca2+]m, using the fluorescent dyes Fura‐4 penta‐K+ salt and Fura‐4 AM, respectively. Mitochondria suspended in Na+ free buffer, to obviate mitochondrial Na+/Ca2+ exchanger, containing 40 μM EGTA, were challenged with repeated boluses of CaCl2 (20 μM) every 5 minutes until mitochondria could not take up or retain the additional Ca2+. Key mitochondrial bioenergetics variables, membrane potential (ΔΨm), matrix pH and NADH (redox state), were also monitored using specific fluorescent dyes. We found that treatment of mitochondria with CsA, before adding boluses of CaCl2, significantly increased the amount of Ca2+ uptake and sequestration, maintained [Ca2+]m at a steady‐state level, and markedly delayed mPTP opening. The extent of matrix Ca2+ buffering, as determined by the bound/free Ca2+ ratio, was strikingly higher for CsA treated mitochondria vs. control. In addition, by enhancing matrix Ca2+ buffering, CsA preserved ΔΨm, matrix pH, and redox state. Interestingly, when CsA was added to mitochondrial suspension just before the onset of mPTP opening, it inhibited pore opening, in part, by promoting the buffering of [Ca2+]m, which reduced the [Ca2+]m and rescued bioenergetics variables to normal values. Since inorganic phosphate (Pi) is vital for Ca2+ sequestration in the matrix, we conducted experiments in Pi‐depleted mitochondria and in Pi free buffer condition. We found that in the absence of Pi, the CsA mediated buffering of [Ca2+]m was abrogated, and mitochondrial bioenergetics were compromised. These results suggest that CsA delays mPTP opening by a novel mechanism that involves enhanced matrix Ca2+ buffering primarily by induction of a PO43− ‐dependent matrix Ca2+ sequestration system.Support or Funding InformationNational Institutes of Health (R01 HL131673‐01A1) and the Veterans Administration (BX‐002539‐01).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

An in vitro model mimics the contact of biomaterials to blood components and the reaction of surrounding soft tissue

The therapeutic efficacy of a medical product after implantation depends strongly on the host-initiated fibrotic response (foreign body reaction). For novel biomaterials, it is of high relevance to understand this fibrotic process. As an alternative to in vivo studies, in vitro models mimic parts of the whole foreign body reaction. Aim of this study was to develop a wound model with key cells and matrix proteins in coculture. This approach combined blood components such as primary macrophages in a plasma-derived fibrin hydrogel, directly exposed to reference biomaterials (PTFE, glass, titanium). The soft tissue reaction is resembled by integrating fibroblasts in a collagen or a fibrin matrix. Those two experimental setups were conducted to show whether a long-term in vitro culture of 13 days is feasible. The response to reference biomaterials was assessed by multi-parametric analyses, comprising molecular profiling (cytokines, collagen I and ß-actin) and tissue remodeling (cell adherence, histological structure, tissue deposition). Polytetrafluorethylene (PTFE) and titanium were tested as references to correlate the in vitro evaluation to previous in vivo studies. Most striking, both model setups evaluated references’ fibrotic characteristics as previously reported by in vivo studies. Statement of SignificanceWe present a test platform applied for assessments on the foreign body reaction to biomaterials. This test system consists of blood components – macrophages and plasma-derived fibrin - as well as fibroblasts and collagen, generating a three-dimensional wound microenvironment. By this modular approach, we achieved a suitable test for long-term studies and overcame the limited short-term stability of whole blood tests. In contrast to previous models, macrophages’ viability is maintained during the extended culture period and excels the quality of the model. The potential to evaluate a foreign body reaction in vitro was demonstrated with defined reference materials. This model system might be of high potential as a screening platform to identify novel biomaterial candidates.

Conflicting Logics of Public Relations in the English NHS: A Qualitative Study of Communications and Engagement

Since the formation of the National Health Service (NHS), all UK citizens have been entitled to access a universal health service, but radical changes to the NHS are now occurring. Although recent NHS policy claims that ‘the NHS belongs to us all’ and ‘the NHS is a social movement’, these collectivist rhetorical claims appear when such communitarian discourse is under threat, as NHS’s Five Year Forward View tries to square the circle of efficiency, quality, and equity. Historically, patients and user-groups have formed support networks and social movements, and collectively campaigned for their voices to be heard by policymakers, clinicians, and managers. In contrast to the discourse of user movements, the field of marketing and public relations generally relies on the idea of the public as consumers rather than citizens. As complex governance arrangements blur the lines between public and private, concerns have been raised about how ‘spin’ associated with public relations might contravene accountability, communicative rationality, and deliberative or participatory democracy. Using qualitative methods, we conducted empirical research in two localities to explore the role of communications and engagement staff as they worked to ‘transform’ the NHS in line with the vision of the Five Year Forward View. We gathered documentary data and interview data from people whose roles required them to ‘do engagement’. These staff came from a range of backgrounds, including professional marketing backgrounds, and many were unaware of emancipatory goals or user-led involvement and activism. Our analysis examines the competing logics of marketing and patient empowerment within a key stakeholder matrix document and that surfaced in participants’ accounts of their engagement practices.

Glycosyltransferase-Mediated Biofilm Matrix Dynamics and Virulence of Streptococcus mutans.

Streptococcus mutans is a key cariogenic bacterium responsible for the initiation of tooth decay. Biofilm formation is a crucial virulence property. We discovered a putative glycosyltransferase, SMU_833, in S. mutans capable of modulating dynamic interactions between two key biofilm matrix components, glucan and extracellular DNA (eDNA). The deletion of smu_833 decreases glucan and increases eDNA but maintains the overall biofilm biomass. The decrease in glucan is caused by a reduction in GtfB and GtfC, two key enzymes responsible for the synthesis of glucan. The increase in eDNA was accompanied by an elevated production of membrane vesicles, suggesting that SMU_833 modulates the release of eDNA via the membrane vesicles, thereby altering biofilm matrix constituents. Furthermore, glucan and eDNA were colocalized. The complete deletion of gtfBC from the smu_833 mutant significantly reduced the biofilm biomass despite the elevated eDNA, suggesting the requirement of minimal glucans as a binding substrate for eDNA within the biofilm. Despite no changes in overall biofilm biomass, the mutant biofilm was altered in biofilm architecture and was less acidic in vitro Concurrently, the mutant was less virulent in an in vivo rat model of dental caries, demonstrating that SMU_833 is a new virulence factor. Taken together, we conclude that SMU_833 is required for optimal biofilm development and virulence of S. mutans by modulating extracellular matrix components. Our study of SMU_833-modulated biofilm matrix dynamics uncovered a new target that can be used to develop potential therapeutics that prevent and treat dental caries.IMPORTANCE Tooth decay, a costly and painful disease affecting the vast majority of people worldwide, is caused by the bacterium Streptococcus mutans The bacteria utilize dietary sugars to build and strengthen biofilms, trapping acids onto the tooth's surface and causing demineralization and decay of teeth. As knowledge of our body's microbiomes increases, the need for developing therapeutics targeted to disease-causing bacteria has arisen. The significance of our research is in studying and identifying a novel therapeutic target, a dynamic biofilm matrix that is mediated by a new virulence factor and membrane vesicles. The study increases our understanding of S. mutans virulence and also offers a new opportunity to develop effective therapeutics targeting S. mutans In addition, the mechanisms of membrane vesicle-mediated biofilm matrix dynamics are also applicable to other biofilm-driven infectious diseases.

Antifibrotic Therapy Disrupts Stromal Barriers and Modulates the Immune Landscape in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) remains one of the deadliest forms of cancer, in part, because it is largely refractory to current therapies. The failure of most standard therapies in PDA, as well as promising immune therapies, may be largely ascribed to highly unique and protective stromal microenvironments that present significant biophysical barriers to effective drug delivery, that are immunosuppressive, and that can limit the distribution and function of antitumor immune cells. Here, we utilized stromal reengineering to disrupt these barriers and move the stroma toward normalization using a potent antifibrotic agent, halofuginone. In an autochthonous genetically engineered mouse model of PDA, halofuginone disrupted physical barriers to effective drug distribution by decreasing fibroblast activation and reducing key extracellular matrix elements that drive stromal resistance. Concomitantly, halofuginone treatment altered the immune landscape in PDA, with greater immune infiltrate into regions of low hylauronan, which resulted in increased number and distribution of both classically activated inflammatory macrophages and cytotoxic T cells. In concert with a direct effect on carcinoma cells, this led to widespread intratumoral necrosis and reduced tumor volume. These data point to the multifunctional and critical role of the stroma in tumor protection and survival and demonstrate how compromising tumor integrity to move toward a more normal physiologic state through stroma-targeting therapy will likely be an instrumental component in treating PDA. SIGNIFICANCE: This work demonstrates how focused stromal re-engineering approaches to move toward normalization of the stroma disrupt physical barriers to effective drug delivery and promote antitumor immunity.See related commentary by Huang and Brekken, p. 328.

Color image chaos encryption algorithm combining CRC and nine palace map

The color image encryption algorithm based on the chaos theory is not strong enough. In this paper, we proposed a color image chaos encryption algorithm combining Cyclic Redundancy Check (CRC) and nine palace map. Firstly, the pixel data of the plain image were moved and shuffled based on the theory of nine palace map. And the R, G and B components were extracted and converted into a binary sequence matrix that was then cyclically shifted based on the technology of generating CRC code. Finally, the encrypted image was derived from the XOR operation with random key matrix. The average entropy of encrypted image by our algorithm is 7.9993, which is slight improved compared with the coupled hyper chaotic Lorenz algorithm in previous studies. In addition, the algorithm has the advantages of large key space, high key sensitivity, anti-robust attack, and feasible encryption efficiency.

Research on Big Data Security Storage Based on Compressed Sensing

Big data have the characteristics of volume and variety, which causes huge storage and communication overhead. The traditional encryption system has a high computational complexity and cannot effectively implement the secure storage for the big data. In order to solve these problems, a big data secure storage scheme based on compressed sensing (CS-BDCSS) is proposed. First, the primary encryption of plaintext data is realized by the Data Combined Crossover Random Permutation method, and then, the security-enhanced CS is used to compress and re-encrypt the data to reduce the space overhead and achieve secure storage. Aiming at the problem that the key matrix of the traditional CS algorithm is vulnerable to attack, a Hierarchical Security Key Matrix Generation Scheme is proposed; by expanding the secret key space, the hierarchical security protection for sensitive data of different levels is realized. The concept of pseudo-homomorphism encryption is proposed, and the computation based on ciphertext is realized by using the pseudo-homomorphism encryption, which can improve the efficiency of the data analysis on the basis of security. An adaptive secret key-updating mechanism is designed to automatically update the key in CS-BDCSS system so as to avoid the security risk caused by the repeated use of the same key. The experimental results show that the proposed scheme can achieve efficient data compression and secure encryption storage.