Overexpression of the adhesion signaling pathway is linked to short-term survival in pancreatic ductal adenocarcinoma.

BACKGROUND AND OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is known for its unfavorable prognosis. Gaining insights into the molecular mechanisms that contribute to its progression is crucial for developing effective therapies. In this study, our objective was to investigate the molecular pathways associated with short-term survival in patients with PDAC. METHODS: Immune profiles were analyzed from both long-term survivors (n = 10) and short-term survivors (n = 10) after surgical resection. Pathway scores were calculated to compare the two groups. RESULTS: The "Adhesion" pathway emerged as the most significant pathway, exhibiting a notably higher score in the samples of short-term survivors (P < 0.009). Within this pathway, significant findings were observed in genes related to integrins and CEACAM. CONCLUSION: The role of integrins in the tumor microenvironment of pancreatic cancer is of utmost importance, as they are found to be overexpressed in short-term survivors. These findings provide valuable insights into the underlying biology of PDAC and have potential implications for the development of therapeutic strategies.

Changes in morphological traits, anatomical and molecular alterations caused by gamma-rays and zinc oxide nanoparticles in spinach (Spinacia oleracea L.) plant.

Spinach seeds were irradiated with gamma-rays after that soaked in zinc oxide nanoparticles (ZnO-NPs) at 0.0, 50, 100 and 200 ppm for twenty-four hours at room temperature. Vegetative plant growth, photosynthetic pigments, and proline contents were investigated. Also, anatomical studies and the polymorphism by the SCoT technique were conducted. The present results revealed that the germination percentage was at the maximum values for the treatment of 100 ppm ZnO-NPs (92%), followed by 100 ppm ZnO-NPs + 60 Gy (90%). The application of ZnO-NPs resulted in an enhancement in the plant length. The maximum of chlorophylls and carotenoids content was recorded in the treatment, 100 ppm ZnO-NPs + 60 Gy. Meanwhile, the irradiation dose level (60 Gy) with all ZnO-NPs treatments increased proline content and reached its maximum increase to 1.069 mg/g FW for the treatment 60 Gy combined with 200 ppm ZnO-NPs. Also, the anatomical studies declared that there were variations between the treatments; un-irradiated and irradiated combined with ZnO-NPs plants which reveal that the leave epidermal tissue increased with 200 ppm ZnO-NPs in both the upper and lower epidermis. While irradiated plants with 60 Gy combined with 100 ppm ZnO-NPs gave more thickness of upper epidermis. As well as SCoT molecular marker technique effectively induced molecular alterations between the treatments. Where, SCoT primers targeted many new and missing amplicons that are expected to be associated with the lowly and highly expressed genes with 18.2 and 81.8%, respectively. Also, showed that the soaking in ZnO-NPs was helped for reducing molecular alteration rate, both spontaneous and induced by gamma irradiation. This nominates ZnO-NPs as potential nano-protective agents that can reduce irradiation-induced genetic damage.

Action mechanisms and biocontrol of Purpureocillium lilacinum against green mould caused by Penicillium digitatum in orange fruit.

AIMS: The present study evaluated, for the first time, the inhibitory effects of the filtrate of Purpureocillium lilacinum against Penicillium digitatum. METHODS AND RESULTS: No direct contact between P. lilacinum and P. digitatum was observed during the dual culture test and the inhibition zone was 6·1 mm. The filtrate of P. lilacinum completely inhibited P. digitatum growth and spore germination at the concentration of 64%. The filtrate increased the permeability of the cell membrane and the content of MDA in P. digitatum. The ergosterol content in P. digitatum was strongly inhibited at 32% by 81·1%. The green mould incidence and severity in filtrate-treated fruit at 64% were 71·7 and 80·7% lower than in the control, respectively. The filtrate enhanced the activity of PAL, PPO and POD enzymes in orange fruit. The POD and PAL gene expression levels were significantly upregulated in the fruit treated with the filtrate. CONCLUSIONS: This study indicated that the antifungal mechanism of P. lilacinum filtrate against P. digitatum is mainly by the damage of the fungal cell membrane and its components. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides the pioneer evidence on the application of P. lilacinum filtrate as a novel biocontrol agent for orange green mould.

Fabrication and Characterization of Microcellular Polyurethane Sisal Biocomposites.

In this study, microcellular polyurethane (PU)-natural fiber (NF) biocomposites were fabricated. Polyurethanes based on castor oil and PMDI were synthesized with varying volume ratios of sisal fiber. The effect of natural fiber treatment using water and alkaline solution (1.5% NaOH) and load effect were investigated. Biocomposites were mechanically and physically investigated using tensile, viscoelasticity, and water absorption tests. The interfacial adhesion between PU and sisal fiber was studied using SEM. Short NF loads (3%) showed a significant improvement in the mechanical properties of the PU-sisal composite such as modulus of elasticity, yield and tensile strength up to 133%, 14.35 % and 36.7% respectively. Viscoelastic measurements showed that the composites exhibit an elastic trend as the real compliance (J') values were higher than those of the imaginary compliance (J''). Increasing NF loads resulted in a decrease of J'. Applying variable temperatures (120-80 °C) caused an increase in the stiffness at different frequencies.

Polymeric Solar Cell with 19.69% Efficiency Based on Poly(o-phenylene diamine)/TiO2 Composites.

Conducting poly orthophenylene diamine polymer (PoPDA) was synthesized via the oxidative polymerization route. A poly(o-phenylene diamine) (PoPDA)/titanium dioxide nanoparticle mono nanocomposite [PoPDA/TiO2]MNC was synthesized using the sol-gel method. The physical vapor deposition (PVD) technique was successfully used to deposit the mono nanocomposite thin film with good adhesion and film thickness ≅ 100 ± 3 nm. The structural and morphological properties of the [PoPDA/TiO2]MNC thin films were studied by X-ray diffraction (XRD) and scanning electron microscope (SEM). The measured optical properties of the [PoPDA/TiO2]MNC thin films such as reflectance (R) in the UV-Vis-NIR spectrum, absorbance (Abs), and transmittance (T) were employed to probe the optical characteristics at room temperatures. As well as the calculations of TD-DFT (time-dependent density functional theory), optimization through the TD-DFTD/Mol3 and Cambridge Serial Total Energy Bundle (TD-DFT/CASTEP) was employed to study the geometrical characteristics. The dispersion of the refractive index was examined by the single oscillator Wemple-DiDomenico (WD) model. Moreover, the single oscillator energy (Eo), and the dispersion energy (Ed) were estimated. The obtained results show that thin films based on [PoPDA/TiO2]MNC can be utilized as a decent candidate material for solar cells and optoelectronic devices. The efficiency of the considered composites reached 19.69%.

Development of an in vitro regeneration system from immature inflorescences and CRISPR/Cas9-mediated gene editing in sudangrass.

BACKGROUND: Sudangrass (Sorghum sudanense) is a major biomass producer for livestock feed and biofuel in many countries. It has a wide range of adaptations for growing on marginal lands under biotic and abiotic stresses. The immature inflorescence is an explant with high embryogenic competence and is frequently used to regenerate different sorghum cultivars. Caffeic acid O-methyl transferase (COMT) is a key enzyme in the lignin biosynthesis pathway, which limits ruminant digestion of forage cell walls and is a crucial barrier in the conversion of plant biomass to bioethanol. Genome editing by CRISPR/Cas9-mediated mutagenesis without a transgenic footprint will accelerate the improvement and facilitate regulatory approval and commercialization of biotech crops. METHODS AND RESULTS: We report the overcome of the recalcitrance in sudangrass transformation and regeneration in order to use genome editing technique. Hence, an efficient regeneration system has been established to induce somatic embryogenesis from the immature inflorescence of two sudangrass cultivars on four MS-based media supplemented with different components. Our results indicate an interaction between genotype and medium composition. The combination of Giza-1 cultivar and M4 medium produces the maximum frequency of embryogenic calli of 80% and subsequent regeneration efficiency of 22.6%. Precise mutagenesis of the COMT gene is executed using the CRISPR/Cas9 system with the potential to reduce lignin content and enhance forage and biomass quality in sudangrass. CONCLUSION: A reliable regeneration and transformation system has been established for sudangrass using immature inflorescence, and the CRISPR/Cas9 system has demonstrated a promising technology for genome editing. The outcomes of this research will pave the road for further improvement of various sorghum genotypes to meet the global demand for food, feed, and biofuels, achieving sustainable development goals (SDGs).

Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men.

Higher plasma leucine, isoleucine and valine (BCAA) concentrations are associated with diabetes, obesity and insulin resistance (IR). Here, we evaluated the effects of 6-weeks very-low calorie diet (VLCD) upon fasting BCAA in overweight (OW) non-diabetic men, to explore associations between circulating BCAA and IR, before and after a weight loss intervention. Fasting plasma BCAAs were quantified in an OW (n = 26; BMI 32.4 ± 3 kg/m2; mean age 44 ± 9 y) and a normal-weight (NW) group (n = 26; BMI 24 ± 3.1 kg/m2; mean age 32 ± 12.3 y). Ten of the OW group (BMI 32.2 ± 4 kg/m2; 46 ± 8 y) then underwent 6-weeks of VLCD (600-800 kcal/day). Fasting plasma BCAA (gas chromatography-mass spectrometry), insulin sensitivity (HOMA-IR) and body-composition (DXA) were assessed before and after VLCD. Total BCAA were higher in OW individuals (sum leucine/isoleucine/valine: 457 ± 85 µM) compared to NW control individuals (365 ± 78 µM, p < 0.001). Despite significant weight loss (baseline 103.9 ± 12.3 to 93 ± 9.6 kg and BMI 32.2 ± 4 to 28.9 ± 3.6 kg/m2), no changes were observed in BCAAs after 6-weeks of VLCD. Moreover, although VLCD resulted in a significant reduction in HOMA-IR (baseline 1.19 ± 0.62 to 0.51 ± 0.21 post-VLCD; p < 0.001), Pearson's r revealed no relationships between BCAA and HOMA-IR, either before (leucine R2: 2.49e-005, p = 0.98; isoleucine R2: 1.211-e006, p = 0.9; valine R2: 0.004, p = 0.85) or after VLCD (leucine R2: 0.003, p = 0.86; isoleucine R2: 0.006, p = 0.82; valine R2: 0.002, p = 0.65). Plasma BCAA are higher in OW compared to NW individuals. However, while 6-weeks VLCD reduced body weight and IR in OW individuals, this was not associated with reductions in BCAA. This suggests that studies demonstrating links between BCAA and insulin resistance in OW individuals, are complex and are not normalised by simply losing weight.

Electrochemical regeneration of hexavalent chromium from aqueous solutions in a gas sparged parallel plate reactor.

In this study anodic oxidation of Cr2(SO4)3 was carried out in an air-sparged divided parallel plate cell. Variables studied were current density, Cr2(SO4)3 concentration, and superficial air velocity. The rate constant of Cr2(SO4)3 oxidation was found to increase with increasing current density and Cr2(SO4)3 concentration. The effect of air sparging was found to depend on Cr2(SO4)3 concentrations, at high Cr2(SO4)3 concentration (> 0.1 M) air sparging does not affect the rate constant of the reaction denoting that the reaction is charge transfer controlled. As Cr2(SO4)3 concentration decreases below 0.1 M the reaction becomes under mixed diffusion and chemical control and the rate constant increases with increasing air superficial velocity, the lower Cr2(SO4)3 concentration the higher the contribution of diffusion to the reaction rate. The current efficiency of the process ranged from 20 to 85% depending on current density and Cr2(SO4)3 concentration. Electrical energy consumption which ranged from 1.8 to 14.4 kW h/kg of Cr6+ was found to increase with increasing current density and decreases with increasing Cr2(SO4)3 concentration. Air sparging was found to decrease electrical energy consumption in the case of dilute solutions << 0.1 M Cr2(SO4)3.

High Thermoelectric Power Generation by SWCNT/PPy Core Shell Nanocomposites.

Polypyrrole (PPy) is a conducting polymer with attractive thermoelectric (TE) properties. It is simple to fabricate and modify its morphology for enhanced electrical conductivity. However, such improvement is still limited to considerably enhancing TE performance. In this case, a single-wall carbon nanotube (SWCNT), which has ultrathin diameters and exhibits semi-metallic electrical conductivity, might be a proper candidate to be combined with PPy as a core shell one-dimensional (1D) nanocomposite for higher TE power generation. In this work, core shell nanocomposites based on SWCNT/PPy were fabricated. Various amounts of pyrrole (Py), which are monomer sources for PPy, were coated on SWCNT, along with methyl orange (MO) as a surfactant and ferric chloride as an initiator. The optimum value of Py for maximum TE performance was determined. The results showed that the SWCNT acted as a core template to direct the self-assembly of PPy and also to further enhance TE performance. The TE power factor, PF, and figure of merit, zT, values of the pure PPy were initially recorded as ~1 µW/mK2 and 0.0011, respectively. These values were greatly increased to 360 µW/mK2 and 0.09 for the optimized core shell nanocomposite sample. The TE power generation characteristics of the fabricated single-leg module of the optimized sample were also investigated and confirmed these findings. This enhancement was attributed to the uniform coating and good interaction between PPy polymer chains and walls of the SWCNT through π-π stacking. The significant enhancement in the TE performance of SWCNT/PPy nanocomposite is found to be superior compared to those reported in similar composites, which indicates that this nanocomposite is a suitable and scalable TE material for TE power generation.

One-Dimensional Nanocomposites Based on Polypyrrole-Carbon Nanotubes and Their Thermoelectric Performance.

Conducting polymers have attracted significant attention due to their easy fabrication, morphology modification, and their electrical properties. Amongst them, polypyrrole (PPy) has attractive thermoelectric (TE) properties. Engineering of this polymer in one-dimensional (1D) nanostructured form is found to enhance its TE performance. This was achieved in the present work by using multi-walled carbon nanotubes (MWCNTs) as a core template to direct the self-assembly of PPy and also to further enhance its TE performance. The growth of PPy on the sidewalls of MWCNTs was performed in an acidic medium based oxidative in situ polymerization. Various concentrations of MWCNTs within the range 1.1-14.6 wt.% were used to form the MWCNTs/PPy nanocomposites in 1D core-shell structures. The morphology and microstructure results of the produced nanocomposite samples showed that this MWCNTs were successfully coated by thick and thin layers of PPy. At low concentrations of MWCNTs, thick layers of PPy are formed. While at high concentrations thin layers are coated. The formed 1D nanocomposites have enhanced TE performance, particularly those containing higher contents of MWCNTs. The power factor and figure of merit values for the formed 1D nanocomposites recorded around 0.77 µV/mK2 and 1 × 10-3 at room temperature (RT), respectively. This enhancement was attributed to the perfect coating and good interaction between PPy and MWCNT through π-π stacking between the polymer chains and these nanotubes. These results might be useful for developing future TE materials and devices.

Assessment of Blend PVDF Membranes, and the Effect of Polymer Concentration and Blend Composition.

In this work, PVDF homopolymer was blended with PVDF-co-HFP copolymer and studied in terms of morphology, porosity, pore size, hydrophobicity, permeability, and mechanical properties. Different solvents, namely N-Methyl-2 pyrrolidone (NMP), Tetrahydrofuran (THF), and Dimethylformamide (DMF) solvents, were used to fabricate blended PVDF flat sheet membranes without the introduction of any pore forming agent, through a non-solvent induced phase separation (NIPS) technique. Furthermore, the performance of the fabricated membranes was investigated for pressure and thermal driven applications. The porosity of the membranes was slightly increased with the increase in the overall content of PVDF and by the inclusion of PVDF copolymer. Total PVDF content, copolymer content, and mixed-solvent have a positive effect on mechanical properties. The addition of copolymer increased the hydrophobicity when the total PVDF content was 20%. At 25% and with the inclusion of mixed-solvent, the hydrophobicity was adversely affected. The permeability of the membranes increased with the increase in the overall content of PVDF. Mixed-solvents significantly improved permeability.

Neurodevelopmental consequences of gestational exposure (GD14-GD20) to low dose deltamethrin in rats.

Effect of low level in utero exposure to deltamethrin (DT) (1mg /kg wt.) during gestation day 14-20 was studied on selected neurobehavioral, neurochemical, immunohistochemical parameters in rats at 6 and 12 weeks postnatal period. The significant increase in acetylcholinesterase activity and decrease in (3)H-quinuclidinyl benzilate binding in the hippocampal region of DT exposed animals, suggesting impairment in cholinergic (muscarinic) receptors. A significant decrease in the learning and memory performances was also observed both at 6 and 12 weeks, which is directly correlated with decrease in muscarinic receptor binding. Immunohistochemistry and image analysis of growth associated protein-43, a neuron specific protein present in axonal growth cone and a marker for neuronal differentiation and synaptogenesis, exhibit aberrant increase in its expression in the hippocampus in DT exposed rats at both time periods. The data suggests that low level exposure to DT in utero during brain growth spurt period adversely affects the developing brain and the changes persist even up to 12 weeks postnatal period in rats. Although there is no significant recovery at 12 weeks assessment but still significant impairment persist on biochemical and behavioural parameters.

Induced expression of early response genes/oxidative injury in rat pheochromocytoma (PC12) cell line by 6-hydroxydopamine: implication for Parkinson's disease.

The expression of early response gene proteins c-Fos, c-Jun, and GAP-43 and their association with 6-hydroxydopamine (6-OHDA)-mediated oxidative injury were investigated using catecholaminergic PC12 cell line. Significant induction in the expression of c-Fos (P < 0.01), c-Jun (P < 0.001) and GAP-43 (P < 0.05) was observed following 2 h exposure to 6-OHDA (10(-6) M), which persisted during 24 h of observation. The exposed cells exhibited an increase in lipid peroxidation (48, 59 and 33%) along with decreased catalase activity (49, 30 and 13%) and glutathione levels (39, 28 and 16%) following 24, 48 and 72 h exposure, respectively. A concentration-dependent functional impairment of mitochondria as studied by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and decreased cell survival were also observed following 6-OHDA (10(-4), 10(-5) M) exposure for 24, 48 and 72 h. The results indicate a role of the early response gene in oxidative stress-mediated dopaminergic cell death by 6-OHDA. Similar mechanisms may also be operative in the development of Parkinson's disease, as an increased presence/formation of endogenous 6-OHDA has been reported in Parkinson's patients.

Acquisition of p53 mutations in response to the non-genotoxic p53 activator Nutlin-3.

Wild-type p53 is a stress-responsive tumor suppressor and potent growth inhibitor. Genotoxic stresses (for example, ionizing and ultraviolet radiation or chemotherapeutic drug treatment) can activate p53, but also induce mutations in the P53 gene, and thus select for p53-mutated cells. Nutlin-3a (Nutlin) is pre-clinical drug that activates p53 in a non-genotoxic manner. Nutlin occupies the p53-binding pocket of murine double minute 2 (MDM2), activating p53 by blocking the p53-MDM2 interaction. Because Nutlin neither binds p53 directly nor introduces DNA damage, we hypothesized Nutlin would not induce P53 mutations, and, therefore, not select for p53-mutated cells. To test this, populations of SJSA-1 (p53 wild-type) cancer cells were expanded that survived repeated Nutlin exposures, and individual clones were isolated. Group 1 clones were resistant to Nutlin-induced apoptosis, but still underwent growth arrest. Surprisingly, while some Group 1 clones retained wild-type p53, others acquired a heterozygous p53 mutation. Apoptosis resistance in Group 1 clones was associated with decreased PUMA induction and decreased caspase 3/7 activation. Group 2 clones were resistant to both apoptosis and growth arrest induced by Nutlin. Group 2 clones had acquired mutations in the p53-DNA-binding domain and expressed only mutant p53s that were induced by Nutlin treatment, but were unable to bind the P21 and PUMA gene promoters, and unable to activate transcription. These results demonstrate that non-genotoxic p53 activation (for example, by Nutlin treatment) can lead to the acquisition of somatic mutations in p53 and select for p53-mutated cells. These findings have implications for the potential clinical use of Nutlin and other small molecule MDM2 antagonists.

Protein kinase Cvarepsilon mediates Stat3Ser727 phosphorylation, Stat3-regulated gene expression, and cell invasion in various human cancer cell lines through integration with MAPK cascade (RAF-1, MEK1/2, and ERK1/2).

Protein kinase C epsilon (PKCvarepsilon), a novel calcium-independent PKC isoform, has been shown to be a transforming oncogene. PKCvarepsilon-mediated oncogenic activity is linked to its ability to promote cell survival. However, the mechanisms by which PKCvarepsilon signals cell survival remain elusive. We found that signal transducers and activators of transcription 3 (Stat3), which is constitutively activated in a wide variety of human cancers, is a protein partner of PKCvarepsilon. Stat3 has two conserved amino-acid (Tyr705 and Ser727) residues, which are phosphorylated during Stat3 activation. PKCvarepsilon interacts with Stat3alpha isoform, which has Ser727, and not with Stat3beta isoform, which lacks Ser727. PKCvarepsilon-Stat3 interaction and Stat3Ser727 phosphorylation was initially observed during induction of squamous cell carcinomas and in prostate cancer. Now we present that (1) PKCvarepsilon physically interacts with Stat3alpha isoform in various human cancer cells: skin melanomas (MeWo and WM266-4), gliomas (T98G and MO59K), bladder (RT-4 and UM-UC-3), colon (Caco-2), lung (H1650), pancreatic (PANC-1), and breast (MCF-7 and MDA:MB-231); (2) inhibition of PKCvarepsilon expression using specific siRNA inhibits Stat3Ser727 phosphorylation, Stat3-DNA binding, Stat3-regulated gene expression as well as cell invasion; and (3) PKCvarepsilon mediates Stat3Ser727 phosphorylation through integration with the MAPK cascade (RAF-1, MEK1/2, and ERK1/2). The results indicate that PKCvarepsilon-mediated Stat3Ser727 phosphorylation is essential for constitutive activation of Stat3 and cell invasion in various human cancers.

Unilateral aural atresia in childhood: case selection and rehabilitation.

The classic management of children and adolescents with unilateral aural atresia, with or without microtia, is to assess audition, to exclude cholesteatoma formation both clinically and radiologically, to offer amplification in unilateral cases, and to consider surgical repair in bilateral cases. However, evidence indicates that children with unilateral hearing loss from any cause are at risk for delayed language development, attention deficit, and poor school performance. Favourable factors for reconstruction of hearing include a normal bone line with good word discrimination, a normal or recognizable auricle (microtia grade I or II), radiographic evidence of an air-containing middle ear cleft with an estimated volume close to the normal side, the presence of ossicles, the facial nerve running in its expected (though abnormal) course, and the absence of any syndrome affecting mid-face development or of any associated mandibular malformation. In unilateral pediatric cases, only minor auricular malformations (grades I and II) were considered for otologic repair. If microtia was more severe (grade III and IV), or if the child had any other mid-face or mandibular problem, otologic repair was delayed until these were corrected. In many cases, otologic repair was deferred throughout childhood. A summary of selection criteria, case examples, and outcomes of surgery will be presented. Carefully selected unilateral cases may be reconstructed during childhood. Unfavourable cases should be amplified or observed.

Effect of presence of 18-crown-6 on the response of 1-pyrrolidine dicarbodithioate-based lead selective electrode.

The lipophilic ammonium salt of 1-pyrrolidine dicarbodithioic acid (PCDT)[I] was introduced as a selective ionophore for a sensitive Pb-ion selective electrode. Also, the effect of immobilization of 18-crown-6 (CW), into the above membrane, on the electrode performance was discussed. The slope of the PCDT-based [I] electrode was (26-30 mV decade(-1)), while it was (29-30 mV decade(-1)) for (PCDT+CW)-based [II] electrode according to the doping time. The linear concentration ranges were (1x10(-6)-1x10(-1) M) and (5x10(-5)-1x10(-1) M) for electrode types [I] and [II] after one-day doping. The working pH ranges were (5.0-10.0) and (7.0-10.0) for electrode types [I] and [II], respectively. Most of the common cations were tested for the evaluation of the electrode selectivity with correlation to the ionic radii of the tested cations. Among them only Na(+), Ag(+) and Fe(3+) were the real interference. Application of using the electrode for the determination of lead in lubrication oil samples was performed with RSD (0.86-1.03%). The obtained results were compared to those of an atomic absorption spectrophotometric method.