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Abstract Background Epithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies worldwide. The aim of this retrospective study was to create a predictive scoring model based on simple immunological and inflammatory parameters to predict overall survival (OS) and progression-free survival (PFS) in patients with EOC. Methods We obtained 576 EOC patients and randomly assigned them to the training set (n = 405) and the validation set (n = 171) in a ratio of 7:3. We retrospectively evaluated the association between PIV and OS and PFS using a novel immunoinflammatory marker, according to the optihmal treshold of PIV, we divided the patients into two different subgroups, high PIV (PIV > 254.9) and low PIV (PIV ≤ 254.9). Pan-immune Inflammatory Value (PIV) was computed as follows: neutrophil count (109/L) × platelet count (109/L) × monocyte count (109/L)/lymphocyte count (109/L). Then developed a simple score prediction model based on several independent prognostic parameters using Cox regression analysis. We used receiver operator characteristic (ROC) curves, calibration plots, and decision analysis (DCA) curves to evaluate the performance of the model. Finally, we used Kaplan-Meier curves to ensure that the model could distinguish well between low- and high-risk groups. Results There was a significant difference in survival outcomes between high PIV (PIV > 310.2) and low PIV (PIV ≤ PIV310.2) (3-year survival rates of 61.34% and 76.71%, respectively); 5-year OS, 25.21% and 51.14%, respectively; 3-year PFS, 40.90% and 65.30%; 5-year PFS, 19.33% and 39.73%, respectively). Column plots of OS and PFS were constructed using independent prognostic factors. In the training module, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.713, 0.796, 0.839, and 0.730, 0.799, 0.826, respectively.In the validation cohort, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.676, 0.803, 0.685, and 0.700, respectively, 0.754, 0.727. The calibration curves showed good agreement between predicted survival and actual observations. The decision analysis curves also showed that the current model has good accuracy and clinical applicability. 3-year OS was 61.34% and 76.71%, respectively; 5-year OS was 25.21% and 51.14%, respectively; 3-year PFS was 40.90% and 65.30%, respectively; 5-year PFS was 19.33% and 39.73%, respectively. Conclusions We constructed and validated a PIV-based nomogram to predict OS and PFS in EOC patients, with a view to helping gynaecologists converge on oncologists in their treatment and follow-up expertise in epithelial ovarian cancer.

Abstract Background and purpose PD-1/PD-L1 inhibitors have become a promising therapy. However, the response rate is lower than 30% in patients with cervical cancer (CC), which is related to immunosuppressive components in tumor microenvironment (TME). Tumor-associated macrophages (TAMs), as one of the most important immune cells, are involved in the formation of tumor suppressive microenvironment. Therefore, it will provide a theoretical basis for curative effect improvement about the regulatory mechanism of TAMs on PD-L1 expression. Methods The clinical data and pathological tissues of CC patients were collected, and the expressions of PD-L1, CD68 and CD163 were detected by immunohistochemistry. Bioinformatics was used to analyze the macrophage subtypes involved in PD-L1 regulation. A co-culture model was established to observe the effects of TAMs on the morphology, migration and invasion function of CC cells, and the regulatory mechanism of TAMs on PD-L1. Results PD-L1 expression on tumor cells could predict the poor prognosis of patients. And there was a strong correlation between PD-L1 expression with CD163+TAMs infiltration. Similarly, PD-L1 expression was associated with M1/M2-type TAMs infiltration in bioinformatics analysis. The results of cell co-culture showed that M1/M2-type TAMs could upregulate PD-L1 expression, especially M2-type TAMs may elevate the PD-L1 expression via PI3K/AKT pathway. Meanwhile, M1/M2-type TAMs can affect the morphological changes, and enhance migration and invasion abilities of CC cells. Conclusions PD-L1 expression in tumor cells can be used as a prognostic factor and is closely related to CD163+TAMs infiltration. In addition, M2-type TAMs can upregulate PD-L1 expression in CC cells through PI3K/AKT pathway, enhance the migration and invasion capabilities, and affect the tumor progression.

Abstract Background Serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) have been reported to be associated with outcomes in acute ischemic stroke (AIS). However, whether UA is related to the prognosis of AIS patients undergoing intravenous thrombolysis (IVT) remains inconclusive. We sought to explore the combined effect of UA and NLR on the prognosis of AIS treated with IVT. Methods A total of 555 AIS patients receiving IVT treatment were enrolled. Patients were categorized into four groups according to the levels of UA and NLR: LNNU (low NLR and normal UA), LNHU (low NLR and high UA), HNNU (high NLR and normal UA), and HNHU (high NLR and high UA). Multivariable logistic regression analysis was used to evaluate the value of serum UA level and NLR in predicting prognosis. The primary outcomes were major disability (modified Rankin scale (mRS) score 3–5) and death within 3 months. Results After multivariate adjustment, a high NLR (≥ 3.94) increased the risk of 3-month death or major disability (OR, 2.23; 95% CI, 1.42 to 3.55, p

The Total Focusing Method (TFM) technique is an advanced Non-Destructive Testing (NDT) Ultrasonic Testing (UT) technique well known for its representative images of high resolution. It was firstly developed together with Full Matrix Capture (FMC) acquisition which can be substituted later by Plane Wave Imaging (PWI) acquisition for its improved acquisition speed and gain reserve without lowering the image quality. For these advantages, the PWI/TFM technique is tending to be more and more widely implemented. This article presents some results of the related study on PWI/TFM technique. Starting by PWI/TFM reconstruction principles, mainly on the influences of beam steering settings and corresponding inspection coverage in predefined Region of Interest (ROI), it focuses on the comparison on the indication amplitudes of planar discontinuities between classical Phased Array (PA) technique and PWI/TFM technique.

Abstract Background Cervical cancer (CC) is a potential clinical application of PD-1/PD-L1 inhibitor. We aimed to study the mechanism of DNA mismatch repair (MMR) system regulating the expression of PD-L1 in CC through DNA methyltransferase (DNMTs). Methods We collected pathological specimens from 118 cases of CC to analyze the relationship between PD-L1 expression and DNMTs in different MMR states. RNA interference (RNAi) technique was used to simulate the formation of CC cell line with MMR deficiency (dMMR) state, and subcutaneous tumor formation experiment was carried out in nude mice to verify the relationship between PD-L1 expression and DNMTs in MMR state. Results The PD-L1 positive rate in 118 cases of CC was 58.47%, while the microsatellite instability (MSI) status accounted for 5.93%. There was a significant difference in the expression of PD-L1 between patients within the dMMR and MMR proficient (pMMR) groups (χ2 = 21.405, P

The Total Focusing Method (TFM) technique is an advanced Non-Destructive Testing (NDT) Ultrasonic Testing (UT) technique. It is usually used together with special acquisition configurations such as Full Matrix Capture (FMC) or Plane Wave Imaging (PWI) and can supply synthetic post-processing results based on a quantity of ultrasonic signals. It is believed that it will accelerate the UT technique revolution toward the artificial intelligence era. Compared to the conventional UT technique, or even advanced UT techniques, such like Time of Flight Diffraction (TOFD) and Phased Array (PA) techniques, this advanced UT technique is well known for its easy-to-interpret and high-resolution representative images. For these reasons, it is used more and more in the flaw sizing and characterization assessment. Following the publication of the standard ISO 23864, TFM technique become a member among all standardized weld inspection techniques. This article presents some related study results toward a code-compliant weld inspection regarding the related standards, dealing especially with the sensitivity calibration which is a key point for the applicability of amplitude-based acceptance criteria.

Grapholita molesta (Busck) is a pest of rosaceous fruit plants worldwide. Due to a combination of monandry and promiscuity in G. molesta, the age and mating history of both sexes significantly affected the mating and reproductive success. In this study, the interactions of different ages (3, 5, or 7 days) and mating history (unmated or mated) in each sex on the mating selection, reproductive system, and offspring production were investigated in the laboratory. The results showed that these differences mainly occurred in young females or males, associated with unmated or mated state. Especially, the 3-day-old unmated females were preferred by the 7-day-old males but discriminated against by the 3- or 5-day-old unmated males, whereas the 3-day-old mated males were preferred by the 3-day-old mated or 7-day-old females but discriminated against by the 3- or 5-day-old unmated females. The lengths of the ovarian ducts were affected by age in the unmated females, with the greatest length being found at 7 days old. The size of testes varied with age in the unmated males, being the largest at 3 days old. At 3 days old, the testes size of the unmated males was larger than that of the mated males. The pairing of 5-day-old unmated females × 3-day-old mated males maximized the successful matings. The least productive pairing was 7-day-old unmated females × 5-day-old mated males. The pairing of 5-day-old mated males × 3-day-old mated females had the lowest number of matings and the highest number of offspring. The pairing of 3-day-old mated females × 3-day-old mated males had a high rate of mating success and the most offspring. These results revealed the different roles between females and males because of physiological states in terms of the reproductive biology in G. molesta.

Hyperuricemia is an important metabolic disease of humans. Limited clinical drugs such as allopurinol can alleviate hyperuricemia. Wild-type Escherichia coli Nissle 1917 (EcN) has been used for over a century to treat various gastrointestinal disorders. However, little is known about the impacts of EcN on hyperuricemic mice. In this study, we identified an anaerobic uric acid metabolism pathway in EcN. It degraded 65.6 % uric acid in 24 h under anaerobic condition in vitro. In addition, oral administration of EcN and allopurinol reduced serum uric acid in hyperuricemic mice by 46 % and 37 %, respectively, compared to the control group. Further analysis showed that allopurinol changed the gut microbiota of mice. However, the microbiota of the EcN and control groups was similar. Histological observations suggested that EcN also ameliorated the intestinal and renal tissue damage in hyperuricemic mice. These results suggested that wild-type EcN may be an alternative method for hyperuricemic treatment.

Based on the previous work conducted by Fujii et al., NdBaInO4 compounds present modest oxide-ion conductivities. Therefore, it has been an attractive system of significant interest. In this study, we attempted to partially substitute Ca for Nd and the total electrical conductivity was successfully improved due to the generation of oxygen vacancies. The synthesis, crystal structure, density, surface topography, and electrical properties of NdBaInO4 and Ca-doped NdBaInO4 have been studied, respectively. NdBaInO4 and 10% and 20% molar fractions of Ca-doped NdBaInO4 were synthesized through solid-state reactions. The crystal structure of them was obtained from Le Bail refinement of the XRD pattern, giving the result of the monoclinic structure, which belongs to P21/c space group. The highest total electrical conductivity of 4.91 × 10−3 S cm−1 was obtained in the Nd0.9Ca0.1BaInO3.95 sample at a temperature of 760 °C in the dry atmosphere and the activation energy was reduced from 0.68 eV to 0.58 eV when the temperature was above 464 °C (737 K) after doping the NdBaInO4 with a 0.1 molar fraction of Ca2+. Moreover, the total conductivity of Nd0.9Ca0.1BaInO3.95 in the wet atmosphere at moderate temperature was relatively higher than that in the dry atmosphere, which suggests that potential proton conduction may exist in wet atmospheres. In addition, the oxygen diffusion coefficients of Nd0.9Ca0.1BaInO3.95 (D* = 1.82 × 10−8 cm2/s, 850 °C) was about two times higher than that of Nd0.8Ca0.2BaInO3.90 (D* = 7.95 × 10−9 cm2/s, 850 °C) and was increased significantly by two orders of magnitude when compared with the oxygen diffusion coefficient of the undoped NdBaInO4 (D* = 8.25 × 10−11 cm2/s, 850 °C).

Avec le vieillissement des installations industrielles, la recherche d’endommagements par corrosion au droit de zones inaccessibles (notamment sous supportages de tuyauterie) par les méthodes conventionnelles de CND attire de plus en plus l'attention. L'objectif principal étant d'évaluer la conformité de l'épaisseur résiduelle en regard de l'épaisseur de calcul des composants contrôlés. Les solutions actuelles sont apportées principalement par des techniques d’examen ultrasonores conventionnelles, multiéléments ou EMAT, à moyenne et longue portée, telles que la technique Multibonds, la technique CHIME et les techniques d’ondes guidées, avec une incertitude significative sur la précision d'évaluation de l’extension en profondeur des zones de corrosion détectées. ONET Technologies a réalisé nombreuses prestations de contrôle de zones sous supportage de tuyauteries à géométries complexes en milieux hostiles. Plus de 10 années d’expériences sur le terrain nous ont permis de développer une solution de contrôle novatrice, intégrant notamment, le développement d’un scanner motorisé dédié, l’amélioration des performances de détection et de quantification par l’utilisation combinée de différentes techniques ultrasonores, l’étude de nouveaux algorithmes d'analyse et le développement d’un outil informatique permettant d’accroitre la précision de mesure et de réduire l’impact du facteur humain. Ce nouveau produit développé par ONET dans le cadre d’un projet de R&D subventionné par France Relance permet une quantification et un suivi en service beaucoup plus précis de l'épaisseur résiduelle minimale des zones de corrosion détectées sous la forme d’une profilométrie de la perte d’épaisseur en zone affectée avec ses incertitudes associées. Dans cet article nous allons présenter les résultats de nos développements.

Du fait de ses nombreux avantages en termes de facilité de mise en oeuvre, de vitesse d’examen, de performances de détection et de caractérisation des indications, la technique de contrôle TOFD (Time of Flight Diffraction) est de plus en plus utilisée dans le cadre des examens non destructifs de fabrication et de suivi en service d’assemblages soudés. Cependant, certaines limitations inhérentes au principe de mise en oeuvre de l’examen TOFD (notamment en termes d’imprécision de localisation des indications en profondeur et par rapport à l’axe de la soudure) font que cette technique est généralement associée à un examen UT conventionnel ou multiéléments complémentaire impactant de manière significative la durée et le coût des contrôles. ONET Technologies a fait face au défi en développant un principe de mise en oeuvre et d’analyse de la technique TOFD permettant de s’affranchir de ces limitations de localisation des indications sans impacter les durées d’examen. La solution présentée intègre une électronique d’acquisition dédiée, un principe de mise en oeuvre novateur et un logiciel d’analyse et de localisation des indications basé sur des algorithmes développés par notre service R&D. Dans cet article, nous présenterons la solution d'inspection novatrice TOFD+® développée par ONET Technologies et un exemple d'inspection permettant de juger de l’apport de ce principe en termes d’amélioration des performances de localisation et de caractérisation des indications.

Abstract Aim This study mainly evaluates the clinical characteristics and chest chest computed tomography (CT) findings of AFB-positive and AFB-negative pulmonary tuberculosis (PTB) patients to explore the relationship between AFB-positive and clinico-radiological findings. Methods A retrospective analysis of 224 hospitalized tuberculosis patients from 2018 to 2020 was undertaken. According to the AFB smear results, they were divided into AFB-positive pulmonary tuberculosis (positive by Ziehl–Neelsen staining) and AFB-negative pulmonary tuberculosis and patients’ CT results and laboratory test results were analyzed. Results A total of 224 PTB patients were enrolled. AFB-positive (n = 94, 42%) and AFB-negative (n = 130, 58%). AFB-positive patients had more consolidation (77.7% vs. 53.8%, p

Abstract Background The tumor microenvironment (TME) has received an increasing amount of attention. CXC chemokines can regulate immune cell transport and tumor cell activity to exert anti-tumor immunity. However, studies on the expression and prognosis of CXC chemokines in cervical cancer (CC) are more limited. Methods The study investigated the role of CXC chemokines in TME of CC by using public databases. Moreover, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) of CXC chemokines were performed to further verify. Results The transcriptional levels of CXCL1/3/5/6/8/9/10/11/13/16/17 in CC tissues were significantly elevated while the transcriptional levels of CXCL12/14 were significantly reduced. We reached a consistent conclusion that the expression of CXCL9/10/11/13 was verified by quantitative real-time PCR and immunohistochemistry. Moreover, CC patients with low transcriptional levels of CXCL1/2/3/4/5/8 were significantly associated with longer overall survival (OS). The CCL family was related to CXC chemokines neighboring alteration. RELA, NFKB1, LCK and PAK2 were the key transcription factors and kinase targets of CXC chemokines, respectively. We also found there were significant correlations between the expression of CXCL9/10/11 and the infiltration of immune cells (CD8+ T cell, CD4+ T cell, neutrophils and dendritic cells). Conclusions In brief, we conducted a comprehensive analysis of CXC chemokines via clinical data and some online public databases. Our results may provide a new idea for the selection of immunotherapeutic targets and prognostic biomarkers for cervical cancer.

Grapholita molesta (Busck) (Lepidoptera: Tortricidae), Oriental fruit moth (OFM), attacks fruits and shoots of the economically important trees in Rosaceae. Amygdalin is a cyanogenic glucoside of rosaceous plants that may be related to the seasonal patterns of infestation in many pests. The amygdalin concentration of fruits and shoots of peach, pear, and apple varies over the growing season. However, the relationship between the amygdalin concentration and G. molesta performance has not been reported. Here, we measured the performance (feeding, growth, development, and fecundity) of G. molesta larvae (as subsequent adults) reared on artificial diets with six amygdalin concentrations (0, 3, 6, 12, 24, and 48 mg/g), and we then calculated the population parameters. We found that these different concentrations of amygdalin affected the developmental time and fecundity, except for the proportion of larvae feeding on the diet and the survival rates of larvae and pupae. When compared with the control diet without amygdalin, diets with 3 or 6 mg/g (low and moderate concentrations) of amygdalin shortened developmental times and increased the number of eggs laid by females; however, a diet with 12 mg/g (moderate concentration) of amygdalin only increased the number of eggs laid by females and did not affect the larval and pupal developmental rate. A diet with 48 mg/g (high concentration) of amygdalin prolonged developmental times and reduced the number of eggs laid by females when compared with the control diet without amygdalin. Furthermore, the intrinsic rate of increase (rm) for insects reared on diets with 3 or 6 mg/g (low and moderate concentrations) of amygdalin versus the control diet without amygdalin showed a slightly improved population growth. However, this increase in the rm value did not persist over ten successive generations of rearing on the same diet. We concluded that the diet with 6 mg of amygdalin per g of diet can enhance the performance and population growth of G. molesta, but the effects of amygdalin are concentration-dependent.

Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, is commonly found in clinical settings and immuno-compromised patients. It is difficult to be eradicated due to its strong antibiotic resistance, and novel inactivation strategies have yet to be developed. Selenium is an essential microelement for humans and has been widely used in dietary supplement and chemoprevention therapy. In this study, the physiological and biochemical effects of sodium selenite on P. aeruginosa PAO1 were investigated. The results showed that 0~5 mM sodium selenite did not impact the growth of PAO1, but increased the lethality rate of PAO1 with antibiotics or H2O2 treatment and the antibiotics susceptibility both in planktonic and biofilm states. In addition, sodium selenite significantly reduced the expression of quorum sensing genes and inhibited various virulence factors of this bacterium, including pyocyanin production, bacterial motilities, and the type III secretion system. Further investigation found that the content of ROS in cells was significantly increased and the expression levels of most genes involved in oxidative stress were up-regulated, which indicated that sodium selenite induced oxidative stress. The RNA-seq result confirmed the phenotypes of virulence attenuation and the expression of quorum sensing and antioxidant-related genes. The assays of Chinese cabbage and Drosophila melanogaster infection models showed that the combination of sodium selenite and antibiotics significantly alleviated the infection of PAO1. In summary, the results revealed that sodium selenite induced oxidative stress and inhibited the quorum sensing system of P. aeruginosa, which in turn enhanced the antibiotic susceptibility and decreased the pathogenicity of this bacterium. These findings suggest that sodium selenite may be used as an effective strategy for adjunct treatment of the infections caused by P. aeruginosa.

Glutathione (GSH) is the most abundant antioxidant in all living organisms. Previously, we have shown that a deletion mutant in the glutathione synthetase gene (ΔgshB) decreases the expression of type III secretion system (T3SS) genes of Pseudomonas aeruginosa. However, the mechanism remains elusive. In this study, a comprehensive transcriptomic analysis of the GSH-deficient mutant ΔgshAΔgshB was used to elucidate the role of GSH in the pathogenesis of P. aeruginosa. The data show that the expression of genes in T3SS, type VI secretion system (T6SS) and some regulatory genes were impaired. ΔgshAΔgshB was attenuated in a mouse model of acute pneumonia, swimming and swarming motilities, and biofilm formation. Under T3SS inducing conditions, GSH enhanced the expression of T3SS in both wild-type PAO1 and ΔgshAΔgshB, but not in Δvfr. Genetic complementation of Δvfr restored the ability of GSH to induce the expression of T3SS genes. Site-directed mutagenesis based substitution of cysteine residues with alanine in Vfr protein abolished the induction of T3SS genes by GSH, confirming that GSH regulates T3SS genes through Vfr. Exposure to H2O2 decreased free thiol content on Vfr, indicating that the protein was sensitive to redox modification. Importantly, GSH restored the oxidized Vfr to reduced state. Collectively, these results suggest that GSH serves as an intracellular redox signal sensed by Vfr to upregulate T3SS expression in P. aeruginosa. Our work provides new insights into the role of GSH in P. aeruginosa pathogenesis.

Pseudomonas aeruginosa is an important human pathogen which uses the type III secretion system (T3SS) as a primary virulence factor to establish infections in humans. The results presented in this report revealed that the ATP-binding protein PA4595 (named ArtR, a Regulator that is an ATP-activated Repressor of T3SS) represses T3SS expression in P. aeruginosa. The expression of T3SS genes, including exoS, exoY, exoT, exsCEBA, and exsD-pscB-L, increased significantly when artR was knockout. The effect of ArtR on ExsA is at the transcriptional level, not at the translational level. The regulatory role and cytoplasm localization of ArtR suggest it belongs to the REG sub-family of ATP-binding cassette (ABC) family. Purified GST-tagged ArtR showed ATPase activity in vitro. The conserved aspartate residues in the dual Walker B motifs prove to be essential for the regulatory function of ArtR. The regulation of T3SS by ArtR is unique, which does not involve the known GacS/A-RsmY/Z-RsmA-ExsA pathway or Vfr. This is the first REG subfamily of ATP-binding cassette that is reported to regulate T3SS genes in bacteria. The results specify a novel player in the regulatory networks of T3SS in P. aeruginosa.

Pseudomonas aeruginosa is becoming an increasingly prevalent pathogen, capable of causing numerous life threatening infections in immunocompromised patients. The three hierarchically arranged quorum sensing (QS) systems, namely las, rhl, and pqs play key roles in coordinating virulence expression in P. aeruginosa. However, the regulatory mechanisms of the pqs system have not been fully elucidated. To identify new genes involved in synthesis of the Pseudomonas quinolone signal (PQS), a transposon mutagenesis library was constructed. PA1429 was found to inhibit PQS biosynthesis. The PA1429 deletion mutant also exhibited increased bacterial motility, biofilm formation, and virulence in a mouse model of acute lung infection. Interestingly, it also displayed reduced tolerance to oxidative stress. Mutated pqsH in the PA1429 deletion background restored bacterial susceptibility to H2O2. In addition, our data showed that PA1429 repressed the expression of las and rhl systems. Overall, these results provide new insights into the complex regulatory networks of quorum-sensing and virulence expression in P. aeruginosa.

This paper concerns the health monitoring of pipelines and tubes. It proposes the k-means clustering algorithm as a simple tool to monitor the integrity of a structure (i.e., detecting defects and assessing their growth). The k-means algorithm is applied on data collected experimentally, by means of an ultrasonic guided waves technique, from healthy and damaged tubes. Damage was created by attaching magnets to a tube. The number of magnets was increased progressively to simulate an increase in the size of the defect and also, a change in its shape. To test the performance of the proposed method for damage detection, a statistical population was created for the healthy state and for each damage step. This was done by adding white Gaussian noise to each acquired signal. To optimize the number of clusters, many algorithms were run, and their results were compared. Then, a semi-supervised based method was proposed to determine an alarm threshold, triggered when a defect becomes critical.

RNA aptamers selected to bind fluorophores and activate their fluorescence offer a simple and modular way to visualize native RNAs in cells. Split aptamers which are inactive until the halves are brought within close proximity can become useful for visualizing the dynamic actions of RNA assemblies and their interactions in real time with low background noise and eliminated necessity for covalently attached dyes. Here, we design and test several sets of F30 Broccoli aptamer splits, that we call fluorets, to compare their relative fluorescence and physicochemical stabilities. We show that the splits can be simply assembled either through one-pot thermal annealing or co-transcriptionally, thus allowing for direct tracking of transcription reactions via the fluorescent response. We suggest a set of rules that enable for the construction of responsive biomaterials that readily change their fluorescent behavior when various stimuli such as the presence of divalent ions, exposure to various nucleases, or changes in temperature are applied. We also show that the strand displacement approach can be used to program the controllable fluorescent responses in isothermal conditions. Overall, this work lays a foundation for the future development of dynamic systems for molecular computing which can be used to monitor real-time processes in cells and construct biocompatible logic gates.

This paper presents an overview and description of the approach to be used to investigate the behavior and the defect sensitivity of various ultrasonic guided wave (UGW) modes propagating specifically in composite cylindrical vessels in the framework of the safety of hydrogen energy transportation such as hydrogen-powered aircrafts. These structures which consist of thick and multi-layer composites are envisioned for housing hydrogen gas at high pressures. Due to safety concerns associated with a weakened structure, structural health monitoring techniques are needed. A procedure for optimizing damage detection in these structural types is presented. It is shown that a finite element method can help identify useful experimental parameters including frequency range, excitation type, and receiver placement.

This study deployed ultrasonic-assisted extraction (UAE), combined with natural deep eutectic solvents (NADES), to extract phenolics and flavonoids from the black mulberry fruit, and the antioxidant activity was examined. The extraction yields of NADES-based UAE were assessed based on the yields of phenolics and flavonoids extracted from the black mulberry fruit. This study selected the molar ratios of hydrogen bond acceptors (HBA) and hydrogen bond donors HBD at 1:2 from previous studies. Choline chloride-lactic acid showed the highest solubility with phenolics and flavonoids among NADES systems. One-factor experiments evaluated the effect of UAE conditions (liquid-to-solid ratio (LSR), water content in NADES, temperature, and time) on TPC, TFC, and antioxidant activity. The suitable NADES-based UAE conditions for extracting phenolics and flavonoids from the black mulberry fruit were 60 ml/g of LSR, 40% water content, 70 °C, and 15 min. Response surface methodology with the Box-Behnken design model optimized the NADES-based UAE process based on response (TPC, TFC, ABTS, OH, and DPPH). The optimal conditions for the NADES-based UAE process were 70 ml/g of LSR, 38.9% water content in NADES, 67.9 °C, and 24.2 min of extraction time. The predicted values of the Box-Behnken design were compatible with the experimental results. Moreover, scanning electron microscopy (SEM) was used to survey the surface of black mulberry fruit with and without sonication. SEM can assist in demonstrating the destructive effect of NADES and ultrasonic waves on material surfaces. SEM findings indicated the high surface destruction capacity of NADES, which partially contributed to a superior extraction yield of NADES than conventional organic solvents. The study proposes an efficient and green method for extracting bioactive compounds from black mulberry fruits. The black mulberry fruit extracts can be applied to meat preservation and beverages with high antioxidants., (© 2023. Springer Nature Switzerland AG.)

Background: Artificial skin substitute templates have been shown to be a reliable solution for the reconstruction of large scalp defects with exposed skull bone, but there is a lack of long-term data., Objective: The aim of this retrospective study was to investigate the long-term outcome of the procedure in a large cohort of 68 cases., Materials and Methods: In total, 58 patients with 68 full thickness scalp defects with exposed skull bone, were included. Mean follow-up time was 24 (±19) months., Results: The mean size of the defects was 63 (±54) cm2. During the follow-up period, no local recurrences occurred. Complications were observed in 13% of the cases including template necrosis (4%), infections (4%), ulcerations (3%), and autograft necrosis (2%). During the final follow-up, 26 patients had died due to internal diseases not associated with the surgery. Cosmetic results were rated good by the patients and an independent observer., Conclusion: The use of a dermal regeneration template for the reconstruction of large, full thickness defects of the scalp with exposed skull bone is a reliable method regarding the complication rate, safety of the procedure, and cosmetic outcome. Limitations of this study are the retrospective and single center design., (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

A point mutation in the BRAF gene, leading to a constitutively active form of the protein, is present in 45%-60% of patients and acts as a key driver in melanoma. Shortly after therapy induction, resistance to MAPK pathway-specific inhibitors develops, indicating that pathway inhibition is circumvented by epigenetic mechanisms. Here, we mimicked epigenetic modifications in melanoma cells by reprogramming them into metastable induced pluripotent cancer cells (iPCCs) with the ability to terminally differentiate into non-tumorigenic lineages. iPCCs and their differentiated progeny were characterized by an increased resistance against targeted therapies, although the cells harbor the same oncogenic mutations and signaling activity as the parental melanoma cells. Furthermore, induction of a pluripotent state allowed the melanoma-derived cells to acquire a non-tumorigenic cell fate, further suggesting that tumorigenicity is influenced by the cell state., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

The sry-related high-mobility box (SOX)-2 protein has recently been proven to play a significant role in progression, metastasis, and clinical prognosis spanning several cancer types. Research on the role of SOX2 in melanoma is limited and currently little is known about the mechanistic function of this gene in this context. Here, we observed high expression of SOX2 in both human melanoma cell lines and primary melanomas in contrast to melanocytic nevi. This overexpression in melanoma can, in part, be explained by extra gene copy numbers of SOX2 in primary samples. Interestingly, we were able to induce SOX2 expression, mediated by SOX4, via TGF-β1 stimulation in a time-dependent manner. Moreover, the knockdown of SOX2 impaired TGF-β-induced invasiveness. This phenotype switch can be explained by SOX2-mediated cross talk between TGF-β and non-canonical Wnt signaling. Thus, we propose that SOX2 is involved in the critical TGF-β signaling pathway, which has been shown to correlate with melanoma aggressiveness and metastasis. In conclusion, we have identified a novel downstream factor of TGF-β signaling in melanoma, which may have further implications in the clinic., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The combination of cancer-focused studies and research related to nuclear reprogramming has gained increasing importance since both processes-reprogramming towards pluripotency and malignant transformation-share essential features. Studies have revealed that incomplete reprogramming of somatic cells leads to malignant transformation indicating that epigenetic regulation associated with iPSC generation can drive cancer development [J Mol Cell Biol 2011;341-350; Cell 2012;151:1617-1632; Cell 2014;156:663-677]. However, so far it is unclear whether incomplete reprogramming also affects cancer cells and their function. In the context of melanoma, dedifferentiation correlates to therapy resistance in mouse studies and has been documented in melanoma patients [Nature 2012;490:412-416; Clin Cancer Res 2014;20:2498-2499]. Therefore, we sought to investigate directed dedifferentiation using incomplete reprogramming of melanoma cells. Using a murine model we investigated the effects of partial reprogramming on the cellular plasticity of melanoma cells. We demonstrate for the first time that induced partial reprogramming results in a reversible phenotype switch in melanoma cells. Partially reprogrammed cells at day 12 after transgene induction display elevated invasive potential in vitro and increased lung colonization in vivo. Additionally, using global gene expression analysis of partially reprogrammed cells, we identified SNAI3 as a novel invasion-related marker in human melanoma. SNAI3 expression correlates with tumor thickness in primary melanomas and thus, may be of prognostic value. In summary, we show that investigating intermediate states during the process of reprogramming melanoma cells can reveal novel insights into the pathogenesis of melanoma progression. We propose that deeper analysis of partially reprogrammed melanoma cells may contribute to identification of yet unknown signaling pathways that can drive melanoma progression., (© 2016 AlphaMed Press.)

Neurofibromatosis type 1 (NF1) is a frequent genetic disease leading to the development of Schwann cell-derived neurofibromas or melanocytic lesions called café-au-lait macules (CALMs). The molecular mechanisms involved in CALMs formation remain largely unknown. In this report, we show for the first time pathophysiological mechanisms of abnormal melanocyte differentiation in a human NF1(+/-) -induced pluripotent stem cell (iPSC)-based model. We demonstrate that NF1 patient-derived fibroblasts can be successfully reprogrammed in NF1(+/-) iPSCs with active RAS signaling and that NF1 loss induces senescence during melanocyte differentiation as well as in patient's-derived CALMs, revealing a new role for NF1 in the melanocyte lineage., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Melanoma is a malignant tumor which is inclined to metastasize promptly into the lymphatic system and other organs such as lung, liver, brain or bone. Therefore early diagnosis remains crucial for improving clinical outcome for melanoma patients. Current chemotherapy and chemo-immunotherapy regimes have shown little clinical benefit with no improvement in overall survival. However, new advances in melanoma biology such as the discovery of predisposed gene signatures and key somatic events have changed clinical practice. New therapeutic approaches are being tested or have been approved by the FDA/EMA recently including targeted therapies, such as BRAF- and MEK-inhibitors, and novel immunotherapies, such as anti-CTLA4 or anti-PD1 therapies. For these therapies an improvement of progression-free and overall survival has been seen in patients with advanced non-resectable melanoma. The following review summarizes recent therapeutic options after the ASCO and ESMO annual meetings 2014 for the treatment of malignant melanoma., (Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Regenerative medicine allows for the customization of tissues and organs which may bring hope to patients with incurable diseases and severe injuries. Therefore, reliable and safe methods for the generation of specific cell types must be established. Recently, different strategies have emerged to convert somatic cells into differentiated cells of interest. One of these strategies is cellular reprogramming, which converts somatic cells into induced pluripotent stem cells (iPSCs). These iPSCs are embryonic stem cell-like cells with almost unlimited developmental potential and can be differentiated into specific lineages. Alternatively, the method of transdifferentiation can be used to directly convert one terminally differentiated cell into another cell type. Both of these methods have proven to have the potential to push the field of cell replacement therapy forward. In this context, the skin is of particular interest because it represents an ideal source of somatic cells for reprogramming to pluripotency as well as transdifferentiation. In this review, we briefly compare both above-mentioned strategies and summarize the latest advances in this highly dynamic field of research.

SOX2 is a gene that encodes for a transcription factor belonging to the SOX gene family and contains a high-mobility group (HMG) domain, which permits highly specific DNA binding. Consequently, SOX2 functions as an activator or suppressor of gene transcription. SOX2 has been described as an essential embryonic stem cell gene and moreover, a necessary factor for induced cellular reprogramming. SOX2 research has only recently switched focus from embryogenesis and development to SOX2's function in disease. Particularly, the role of SOX2 in cancer pathogenesis has become of interest in the field. To date, studies have shown SOX2 to be amplified in various cancer types and affect cancer cell physiology via involvement in complicated cell signaling and protein-protein interactions. Recent reviews in this field have highlighted SOX2 in mammalian physiology, development and pathology. In this review, we comprehensively compile what is known to date about SOX2's involvement in cancer biology, focusing on the most recent findings in the fields of cellular signaling and cancer stem cells. Lastly, we underscore the role of SOX2 in the clinic and highlight new findings, which may provide novel clinical applications for SOX2 as a prognostic marker, indicator of metastasis, biomarker or potential therapeutic target in some cancer types.

Background: Direct wound closure, flaps or grafts are considered to be gold standards for the reconstruction of defects. However, these techniques may not be applicable in all cases, especially for the challenging closure of large defects., Objective: We developed a technique to close large defects, of varying size and shape, using serial tightening loop sutures. In 64 consecutive patients, loop sutures were applied to defects from 3 cm(2) up to 173 cm(2) for a maximum of 42 days with tightening every 2-7 days., Results: The median size of the defects was 20 cm(2). In 58 patients (91%) the defects were closed by direct approximation of the wound edges within a median time of 11 days (range: 4-42 days). Two patients received a skin transplant after a significant reduction of the defect size and four remaining defects healed by secondary intention. The skin stretching of defects located on the trunk was faster compared with defects on the extremities. Defects located on the scalp were closed hair bearing with little scarring. Overall, aesthetic results were satisfying., Conclusion: The use of loop sutures allows the delayed closure of large defects avoiding the need for skin flaps or grafts in most cases., (© 2013 The Authors Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology.)