10-fold Decrease Research Articles

Eco-friendly property modulation of biobased gels of carboxymethyl cellulose-integrated poly(tertiary amine)s for the removal of azo-food dyes

Anionic polysaccharide-based gels enable the design of biobased materials with biochemical properties, non-toxic and natural origin. A new set of cationic gels was prepared from carboxymethylcellulose (CMC)-doped tertiary amino functional cationic monomers 2-(dimethylamino)ethyl methacrylate and N-(3-(dimethylamino)propyl) methacrylamide via the formation of semi-interpenetrated network (semi-IPN) at different polymerization temperatures, Tprep. A detailed understanding of the temperature-dependent synthesis and physicochemical response is required for the design of interpenetrating networks with CMC as an adsorbent that provides effective sources for the removal of azo-food dyes such as tartrazine and carmoisine from aqueous solutions. The variation of elasticity and swelling properties with respect to polymerization temperature was investigated. CMC-integration and polymerization temperature played a decisive role in the compressive elasticity. Incorporation of CMC into copolymer matrix led to a significant increase in elasticity of semi-IPNs, while mechanically weaker gels were obtained with increasing Tprep. Addition of CMC increased the swelling modulus of semi-IPNs formed at −18 °C by 2.6-fold. While the transparency changed depending on Tprep and microstructure, addition of CMC decreased the swelling rate of gels at all polymerization temperatures. The compressive modulus decreased with the swelling process in accordance with the Rubber elasticity theory. Semi-IPN gels showed stable swelling against pH-change in aqueous solutions and exhibited excellent pH-sensitivity significantly in low pH. A 4 to 12 fold decrease in maximum volume was observed by varying the pH between 2.1 and 9.8. The correlation between polymerization temperature and removal of azo-food dyes; tartrazine and carmoisine from contaminated wastewater with CMC-based gels was studied. Dynamic adsorption equilibrium was reached in 30 min, and tartrazine and carmoisine removal performances varied between 92.8 % and 98.4 %. respectively. The adsorption data for azo-dyes were evaluated by Langmuir, Freundlich, Temkin, Dubinin-Radushkevich, Redlich-Patterson, Sips, and Tooth isotherm models, but were best described by Langmuir and Redlich-Patterson models as they gave the highest correlation. Pseudo-first order, pseudo-second order, Elovich, Avrami kinetic and intra-particle diffusion models were investigated and dye adsorption was represented by pseudo-second-order model. After the adsorption process, semi-IPNs can easily be regenerated and effectively reused over five cycles. The study provided new insights towards the facile and sustainable synthesis of eco-friendly multifunctional CMC-based gels carrying tertiary amino groups for effective removal of azo-based food colorants.

A critical Review on Advanced Membrane Bioreactors for Wastewater Treatment: Fouling Reduction and Energy Demand

Objectives:Rapid industrialization has highlighted the importance of addressing environmental issues and the increasing demand for water supply. As a result, innovative solutions to improve water circulation management in both public and industrial sectors have been proposed, one of which is the introduction of Membrane Bioreactor (MBR) technology. This study aims to understand the mechanisms and characteristics of membrane fouling in MBR processes and compare the associated energy consumption, with the goal of improving process efficiency and energy performance.Methods:In this study, various factors influencing the MBR process were considered to analyze the mechanisms and characteristics of membrane fouling. The impact of fouling on the process was assessed, and energy consumption was compared. Specifically, the power consumption of flat-sheet and hollow-fiber MBRs was analyzed, focusing on the proportion of energy used for microbial treatment and membrane cleaning. The Specific Energy Demand (SED) was calculated to evaluate the energy consumption efficiency of different fouling control methods in MBRs.Results and Discussion:In typical MBR processes, 68.0% (flat-sheet) and 53.0% (hollow-fiber) of the power consumption is attributed to air scouring for microbial treatment and membrane cleaning. Notably, 57.0% (flat-sheet) and 36.0% (hollow-fiber) of the power is consumed to supply air for detaching adhered foulants to maintain filtration performance. These results indicate that aeration is a major energy consumer in MBR processes. SED is a critical indicator for assessing the energy consumption of specific fouling control methods, with typical MBR processes having an SED of 0.2-0.3kWh/m3. In contrast, using a non-aerated membrane module with reciprocating inertial force for fouling control reduces SED to 0.005-0.01 kWh/m3, representing a 20-60 fold decrease in energy consumption, highlighting the need for energy reduction.Conclusion:This study provides insights into fouling reduction characteristics in MBR processes, suggesting a new paradigm for enhancing the economic feasibility of MBR technology. Applying non-aerated membrane modules to reduce energy consumption can significantly improve MBR efficiency, contributing to energy reduction and environmentally friendly technology development. Therefore, strategies to maximize energy efficiency and minimize environmental impact in MBR processes are essential.

Cold snaps lead to a 5-fold increase or a 3-fold decrease in disease proliferation depending on the baseline temperature

BackgroundClimate change is driving increased extreme weather events that can impact ecology by moderating host–pathogen interactions. To date, few studies have explored how cold snaps affect disease prevalence and proliferation. Using the Daphnia magna–Ordospora colligata host-parasite system, a popular model system for environmentally transmitted diseases, the amplitude and duration of cold snaps were manipulated at four baseline temperatures, 10 days post-exposure, with O. colligata fitness recorded at the individual level.ResultsCold snaps induced a fivefold increase or a threefold decrease in parasite burden relative to baseline temperature, with complex nuances and varied outcomes resulting from different treatment combinations. Both amplitude and duration can interact with the baseline temperature highlighting the complexity and baseline dependence of cold snaps. Furthermore, parasite fitness, i.e., infection prevalence and burden, were simultaneously altered in opposite directions in the same cold snap treatment.ConclusionsWe found that cold snaps can yield complicated outcomes that are unique from other types of temperature variation (for example, heatwaves). These results underpin the challenges and complexity in understanding and predicting how climate and extreme weather may alter disease under global change.

Blocking S100A9-signaling is detrimental to the initiation of anti-tumor immunity.

S100A9, a multifunctional protein mainly expressed by neutrophils and monocytes, poses an immunological paradox. In virus infections or sterile inflammation, it functions as an alarmin attracting innate immune cells, as well as mediating proinflammatory effects through TLR4 signaling. However, in cancer, S100A9 levels have been shown to associate with poor prognosis and lack of response to immunotherapy. Its expression by myeloid cells has been related to an immune suppressive phenotype, the so-called myeloid derived suppressor cells (MDSCs). Targeting S100A9 in cancer has therefore been proposed as a potential way to relieve myeloid-mediated immune suppression. Surprisingly, we found that blocking the extracellular TLR4 signaling from S100A9 using the inhibitor Paquinimod, resulted in increased tumor growth and a detrimental effect on anti-PD-L1 efficacy in the CT26 tumor model. This effect was caused by a reduction in the tumor immune infiltration to about half of untreated controls, and the reduction was made up of a 5-fold decrease in Ly6Chigh monocytic cells. The suppressive Ly6G+ myeloid cells compartment was not reduced by Paquinimod treatment, suggesting alternative mechanisms by which S100A9 contributes to myeloid-mediated suppression. Intratumoral injection of recombinant S100A9 early after mice inoculation with CT26 cells had an anti-tumor effect. These findings indicate an important yet understudied role of S100A9 as an alarmin and immune stimulatory signal in cancer settings, and highlight the potential to exploit such signals to promote beneficial anti-tumor responses.

Physiological characteristics of microbial transformation during chronic exposure to triclosan as a hydrophobic antibacterial agent and post-antibacterial cessation

ABSTRACT The use of triclosan (TCS) in hygiene products and other materials raises concerns about increased antimicrobial resistance. Research has shown that bacteria can develop resistance to TCS, but there is limited understanding of how bacterial behavior changes after TCS is removed. This study focuses on how bacteria adapt to prolonged TCS exposure and recover after its removal. It aims to improve practices for using antimicrobial agents in sanitation products and emphasize the importance of understanding exposure and recovery times to prevent resistance development. The study evaluated the bacterial behavior, determining the minimum inhibition concentration of TCS that 90% of Escherichia coli was inhibited (MIC90), predicting bacterial growth kinetics using the Modified Gompertz model and membrane permeability recovery. Bacteria showed a significant increase in resistance levels during exposure, with the MIC90 steadily increasing over 30 days and peaking at 16 mg/L. Upon removal, there was a notable 2-fold decrease in resistance after 10 days of reculturing in a non-chemical medium, likely due to restructuring changes in cell membranes. Therefore, in addition to reducing the occurrence of antibacterial agents in the environment, advanced treatments for eliminating antibacterial resistance should be performed on wastewater before being discharged into the environment.

Estimation of Gestational Age-Specific Reference Intervals for Coagulation Assays in a Neonatal Intensive Care Unit Using Real-World Clinical Data

Abstract Interpretation of coagulation testing in neonates currently relies on reference intervals defined from adult cohorts. These likely do not reflect the normative values for neonates, in whom immature synthesis of vitamin K-dependent factors may contribute to this divergence. Direct reference interval estimation studies are difficult, particularly in neonatal populations; however, advances in indirect estimation may allow us to infer normative distributions from routinely collected clinical data. To accomplish this, initial coagulation testing results from all patients admitted to a level IV neonatal intensive care unit between 1/1/2018 - 1/1/2023 were extracted from the electronic health record and analyzed. Results prior to June 2021 were performed on the viscosity-based STA Compact Max (Diagnostica Stago. Parsippany, NJ, USA). Afterward, results were performed on a nephelometry-based ACL Top (Instrumentation Laboratory. Bedford, MA, USA). Specimens collected after transfusion of blood products were excluded. Prothrombin times (PT) and international normalized ratios (INR) were available for 1,117 neonates, while activated partial thromboplastin times (aPTT) were available for 790 neonates. The 95% confidence intervals (CI) of the median PT for extremely preterm, very preterm, preterm and term neonates were [19 - 21s], [18 - 22s], [17 - 19s] and [17 - 18s]. For INR, the CI were [1.6 - 1.8], [1.5 - 1.8], [1.4 - 1.6], and [1.4 - 1.5]. For aPTT, the CI were [51 - 61s], [47 - 58s], [45 - 50s], and [42 - 46s]. Indirect reference intervals (IRIs) were then estimated across gestational age groups (binning all patients delivered at less than 37 weeks into one preterm category) using refineR. The IRI for PT was 10 - 24s for preterm,10 - 22s for term, and 10 - 24s for all neonates. The IRI for INR was 0.7 - 2.1 for preterm, 0.8 - 1.8 for term, and 0.8 - 1.9 for all neonates. The IRI for aPTT was 24.5 - 68.4s for preterm, 24.7 - 58.2s for term, and 25 - 62.3s for all neonates. When compared to currently reported reference intervals, the lower limits of the IRI were similar to currently reported reference intervals; however, the upper limits of the IRIs were 1.3 - 1.8 times higher than current reference intervals. Theoretically, implementation of these IRIs would lead to a 3-fold decrease in the number of results flagged as abnormal. In conclusion, IRIs for coagulation assays estimated from neonates using routine clinical data show substantial divergence from current reference intervals in their upper limits, possibly due to the decreased factor concentrations seen prior to liver maturation. If implemented, these IRIs would substantially reduce the proportion of abnormal results. Future work will explore whether switching to these reference intervals could lead to a reduction in unnecessary transfusions or improved clinical outcomes.

The lasso peptide produced by Bacillus licheniformis MCC 2514 demonstrates efficacy in treating in-vivoSalmonella Typhimurium infection

Salmonella, a significant pathogen transmitted through food, presents a substantial threat to public health. The issue of antibiotic misuse is causing a quest for alternative replacements. An antimicrobial peptide, predicted as lasso peptide 2514 (LP-2514), derived from the probiotic bacteria Bacillus licheniformis MCC 2514, has demonstrated effectiveness against various foodborne pathogens including Salmonella. This study aims to assess the efficacy of this peptide in vivo. Mice infected with Salmonella Typhimurium received daily oral administration of LP-2514 (30 mg/kg/day) for 2 weeks until the symptoms subsided. After the treatment, biochemical and histopathological parameters were examined. LP-2514 treated mice demonstrated reduced infection, as evidenced by a 5-fold decrease in aspartate aminotransferase concentration and a 10-fold decrease in alanine aminotransferase concentration in plasma. Nitric oxide generation was decreased by 61.23 %, C-reactive protein by 75.9 %, and numerous antioxidant enzymes were elevated to suppress the infection. Increased expression of the anti-inflammatory marker Interleukin-10 (IL-10) by 43-fold was observed in treated mice, while untreated mice displayed elevated expression of pro-inflammatory cytokines indicating the severity of infection. Hence, LP-2514 successfully alleviated the disease symptoms caused by S. Typhimurium, thus exhibiting as a potential replacement for antibiotics or food-grade preservatives.

Investigation of steady-state gas diffusion through angled metallised polymer films for applications in fibre reinforced pressure vessels as barrier membranes

Pressure vessels used for the storage of hydrogen gas, particularly carbon-fibre reinforced pressure vessels (CPVs), must demonstrate sufficient leak tightness. Currently, this is achieved by costly metallic liners which come at a weight disadvantage compared to CPVs. Therefore, novel concepts for designing CPVs with low permeation characteristics are of high interest for various industrial applications. In this paper, a new concept is proposed based on overlapping intersections of metallised polymer films. Manufacturing trials are carried out on a laboratory scale to demonstrate the feasibility of a new barrier membrane design that can also be integrated into the winding process of CPVs. An efficient analytical model, as well as finite element simulations, are compared against experimental findings for the permeation of Helium. The findings indicate significant promise for implementing the barrier concept in CPVs, with tests and models demonstrating an over 1000 - fold decrease in the permeability of the barrier membrane compared to pure polymer, even when utilizing unoptimized tape materials. Reductions by a factor of over 10 000 are possible with material optimisation.

Мегабентос западного прибрежья архипелага Новая Земля в приловах донного трала

As a part of a marine expedition on the R/V «Dalnye Zelentsy» along the western coast of the Novaya Zemlya archipelago, an assessment of megabenthic species diversity and biomass in bycatch of trawl was carried out in August 2023 specimens of 29 taxa belonging to 6 phyla were identified during the survey. The highest species diversity (20 species) was recorded in the northern coastal area of the Novaya Zemlya archipelago, where the dominant forms in terms of biomass were sea urchins Strongylocentrotus pallidus – 237.1 kg/km2. A tendency for a 5-fold decrease in megabenthos species diversity and a decrease in the average biomass of organisms – from 17.2 to 0.47 kg/km2 was detected with transition from north to south. The association of sea urchins S. pallidus and brittle stars Gorgonocephalus sp. (84 % biomass share of representatives in bycatch) is identified in the north of the study area, which is replaced by the association of sea urchins S. pallidus and crustaceans Chionoecetes opilio (74.6 %) when moving to the south. According to the results of the RDA analysis, the effects of trawl fishing and type of water mass have the greatest impact on species diversity and biomass of megabenthic organisms. Trawling intensity, type of water mass, and sediment characteristics explain 75 % of the observed variability in these biological parameters.

12489 Senolytics Dasatinib And Quercetin Alleviate Type 1 Diabetes-Related Cardiac Fibrosis In Male Akita Ins-/+Mice

Abstract Disclosure: N. Kadoumi: None. G. Zatarah: None. J. Stokar: None. P. Shivam: None. I. Gurt: None. R. Dresner-Pollak: None. People living with type 1 diabetes (T1D) have a markedly shorter life expectancy compared to non-diabetic age- and sex-matched controls primarily due to cardiovascular disease. Diabetic cardiomyopathy is characterized by structural and functional alterations that occur independently of hypertension or coronary artery leading to congestive heart failure. The pathogenesis of diabetic cardiomyopathy involves endothelial cell dysfunction, microangiopathy, mitochondrial dysfunction, and oxidative stress, resulting in inflammation, extensive remodeling, cardiomyocyte hypertrophy, interstitial fibrosis, and apoptosis. T1D is associated with accelerated aging. Cellular senescence is a hallmark of aging, it is characterized by cell cycle arrest, distinct morphological alterations and the release of molecules referred to as the senescence-associated secretory phenotype (SASP). Senescent cardiomyocytes secrete SASPs that promote activation of fibroblasts, hypertrophy of cardiac muscle cells, and dysfunction of cardiac endothelial cells. An increase in cardiac cellular senescence was demonstrated in mouse models of T1D. Senolytics are compounds that clear senescent cells. Senolytics were shown to improve multiple outcomes in age-associated conditions in mice and humans.We investigated the effects of senolytics Dasatinib (D) and Quercetin (Q) on cardiac fibrosis in the AKITA Ins-/+ mouse model of T1D.We first assessed if there is increased collagen type1 expression in the heart ventricles and perivascular in 3-month-old in AKITA Ins-/+ vs. WT male mice using Immunofluorescence. Increased perivascular and interstitial expression of collagen 1 was found in AKITA Ins-/+ compared to WT age-and sex-matched mice (0.0811±0.008177 µm2 vs. 0.0533± 0.007960 µm2 ,P=0.0476), (105.7±10.29 µm2 vs. 54.85±14.61 µm2, P=0.0476), respectively. Next, 3-month-old AKITA Ins-/+wmale mice were randomly assigned to treatment with Dasatinib (5 mg/kg) and Quercetin (50 mg/kg) or vehicle administered once monthly by oral gavage for a total of four months (n=20, 10 in each group). Heart samples were analyzed for gene expression, collagen 1 protein by western blotting and Immunofluorescence and analyzed using QuPath 0.5.0 Software. Interstitial and perivascular fibrosis was separately assessed in the right and left ventricles. Treatment with D+Q resulted in a 2-fold decrease in COL1A1 gene and Collagen 1 protein expression by RT-PCR and western blot analysis (P= 0.011 and 0.042, respectively) in AKITA Ins-/+ mice. Immunostaining analysis revealed reduced Collagen 1 deposition in both the left and right ventricles (105.7±10.29 µm2 vs. 43.53±16.31 µm2, P=0.0571), as well as in the perivascular area (0.0811±0.008177 µm2 vs. 0.052±0.006163 µm2, P=0.1143). Treatment with senolytics D+Q reduces the expression of Collagen I, a key factor in myocardial fibrosis, in adult male AKITA Ins-/+ mice. Presentation: 6/3/2024

Early menstrual cycle impacts of oestrogen and progesterone on the timing of the fertile window.

What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window? Both oestrogen and progesterone contribute to a delay in the onset of the fertile window. Oestrogen enhances cervical mucus secretion while progesterone inhibits it. Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder. Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva. Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle. This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings. This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction. The authors declare no conflicts of interest. No funding was provided for this secondary data analysis. N/A.

B-105 Farr Radioimmunoprecipitation Method Enhances Serial Monitoring of Quantitative Anti-dsDNA (double-stranded) Antibody Measurements in Lupus

Abstract Background Anti-double stranded DNA (anti-dsDNA) antibodies are an important criterion in the diagnosis, classification, and management of systemic lupus erythematous (SLE). High avidity anti-dsDNA IgG may be more clinically relevant and specific for SLE. As such, radioimmunoassay according to the Farr technique (Farr-RIPA) is often considered more sensitive and quantitative than enzyme-linked immunosorbent assay (ELISA) and Crithidia luciliae immunofluorescence assay (CLIFT) methods. Methods Measurements of anti-dsDNA antibodies in 147,016 serum patient samples were obtained by lab-developed Farr-RIPA. Serum with endogenous antibodies binds to 125I-radiolabelled dsDNA and undergoes subsequent immunoprecipitation under high salt conditions which selects for highly avidity anti-dsDNA antibodies. The analytic measurement range (AMR) of the assay is 5.7 to 85 IU/mL, and dilutional linearity is validated to 68,000 IU/mL for results >85 (ULOQ). Inter-assay precision is <10% CV. Results Of 147,016 measured samples, 5.4% (7800) were positive for anti-ds DNA antibodies (mean 251.7) with numeric values, ranging from 8.0 to 55,399 IU/mL. The numeric distribution of all positive results was such that 76% (5859/7800) were between 8.0 - 60 IU/mL, and the median was 19.4 with an interquartile range (IQR) of 36.1. A small percentage (3.9%) had very high anti-dsDNA levels greater than 1000 IU/mL and 0.4% (35/7800) were greater than 10,000 IU/mL. Serial measurements comprised almost half (45.5%) of all positives, occurring in 1016 unique patients an average of 3.5 levels within a 2-year time frame. A fifth of those patients, 200, were more frequently monitored with at least 4 levels. Of patients with the very highest dsDNA (>10,000), we analyzed the results of 17 unique patients who were frequently monitored an average of 6.1 times. Peak and nadir values yielded a mean delta of 20,751 with a mean of 264 days elapsing between peak and nadir. All except one showed a marked decrease in Anti-dsDNA over time with an average decrease of 15,685 IU/mL. Conclusions Here, we performed 147,016 Anti-dsDNA antibody measurements by Farr-RIPA, a precise method with a broad analytic range as compared to other methods which have a limited upper limit of quantitation or are semi-quantitative. Our 7800 positive Farr-RIPA results exhibited quantitative results from 8.0 to 55,399 IU/mL. The median of 19.4 and IQR of 36.1 showed most results to be <55.5 IU/mL. Very high levels >300 and >1000 IU/mL were seen in 10% and 4% of patient samples, respectively. Serial monitoring was frequent. In patients with the very highest levels >10,000, an-eight fold decrease in peak Anti-dsDNA levels was achieved over a mean of 264 days with more than half (9/17) achieving levels <250. The ability to detect and meaningfully monitor these patients is enhanced by the Farr-RIPA method. In conclusion, in 7800 positive samples, we demonstrated a wide range of inter- and intra-patient numeric Anti-dsDNA concentrations that denote the clinical usefulness of serial monitoring by Farr-RIPA.

N-803, an IL-15 Superagonist Complex as Maintenance Therapy After Allogeneic Donor Stem Cell Transplant for Acute Myeloid Leukemia or Myelodysplastic Syndrome; A Phase 2 Trial

Maintenance therapy may improve natural killer (NK) cell surveillance after allogeneic donor hematopoietic cell transplant (HCT) for myeloid malignancies and represents a potential approach to improve cure rates. Interleukin-15 (IL-15) enhances lymphocyte proliferation and antitumor activity. In a prior Phase 1 study of an IL-15 superagonist (N-803) in patients with AML who relapsed after HCT, we observed in vivo expansion of NK cells and antitumor responses. The primary objective of this Phase 2 trial was to determine if post-transplant N-803 could reduce relapse. We administered N-803 (n = 20) (dosed 6 mcg/kg subcutaneously [SQ] at day 60 after HCT to patients with myelodysplastic syndrome [MDS] or acute myeloid leukemia [AML] who were in complete remission [CR]). N-803 treatment was planned weekly, biweekly or every 4 weeks in 2 sequential cohorts. The most common adverse events after administration were self-limited injection sites skin rashes (n = 20). One week after an N-803 dose, we observed enhanced NK cell proliferation and improved antitumor cytotoxicity without inducing immune exhaustion. Five patients who developed acute graft versus host disease (aGVHD) after N-803 responded promptly to steroids and 4 patients developed chronic GVHD. Patients receiving >4 doses of N-803 had a 3-fold decrease in relapse at two years (P = .06). These findings support the safety, immune activation, and potential efficacy of N-803 to prevent relapse of AML/MDS after HSCT.

Effect of mixing-ratio and current on Mo-Cu-WC-Si coating via EDC

The present study investigates the influence of the mixing ratio of copper (Cu) and molybdenum (Mo) powders in Mo-Cu-WC-Si composite powder metallurgy (P/M) briquettes on the performance of coatings produced on Al-2014 alloy using electrical discharge coating. Three mixing ratios of Cu and Mo are selected during briquette preparation, by varying Cu in 5 wt.% decrements and Mo in 5 wt.% increments: 50Cu:30Mo, 45Cu:35Mo, and 40Cu:40Mo, with fixed 15WC:5Si. The results indicate that even a 5 wt.% variation of copper significantly affects the coating output responses. At 3 A current the 50Cu:30Mo combination shows lowest roughness of 2.4 μm, followed by 3.2 μm, and 5.4 μm roughness with 45Cu:35Mo and 40Cu:40Mo. Coating with 50Cu:30Mo ratio shows the highest wear reduction, achieving a 3-fold decrease compared to the uncoated Al-2014. Furthermore, coated samples depict a 42% reduction in corrosion rate compared to uncoated sample. Experimental results suggest that the briquette with a higher copper percentage (50 wt.%) provides a more suitable coating.

Intraband cascade electroluminescence with weakly n-doped HgTe colloidal quantum dots.

Room temperature 6μm intraband cascade electroluminescence (EL) is demonstrated with lightly n-doped HgTe colloidal quantum dots of ∼8nm diameter deposited on interdigitated electrodes in a metal-insulator-metal device. With quantum dot films of ∼150nm thickness made by solid-state-ligand-exchange, the devices emit at 1600cm-1 (6.25μm), with a spectral width of 200cm-1, determined by the overlap of the 1Se-1Pe intraband transition of the quantum dots and the substrate photonic resonance. At the maximum current used of 20 mA, the bias was 30V, the external quantum efficiency was 2.7%, and the power conversion efficiency was 0.025%. Adding gold nano-antennas between the electrodes broadened the emission and increased the quantum efficiency to 4.4% and the power efficiency to 0.036%. For these films, the doping was about 0.1 electron/dot, the electron mobility was 0.02cm2V-1s-1, and the maximum current density was 0.04kAcm-2. Higher mobility films made by solution ligand exchange show a 20-fold increase in current density and a 10-fold decrease in EL efficiencies. Electroluminescence with weak doping is interesting for eventually achieving electrically driven stimulated emission, and the requirements for population inversion and lasing are discussed.

A New Drying Method of Thermolabile Flexible Endoscope Channels by Laminar and Turbulent Airflow: A Prospective, Randomized-Controlled, Single-Center, Proof-of-Concept Trial.

International guidelines suggest different possibilities for drying of endoscopes during reprocessing. Clinical results of these available drying methods are not satisfactory. The aim of this study was to compare the drying cycle of a standard endoscope washer-disinfector (EWD) (standard drying method [SD]) with a shortened mandatory drying by the EWD followed by a special drying device using laminar and turbulent air flow (novel drying method [ND]). Sixty endoscopes (duodenoscopes, colonoscocopes, and gastroscopes) from 3 different manufacturers underwent high-level disinfection and drying depending on the randomization group. Operational time of drying was measured for both groups. Residual fluid in the channels was measured using a laboratory scale. After a 14-day storage period, a sample of the endoscope channels was obtained to determine bacterial contamination. ND had significantly fewer residual water in endoscope channels (SD: 90% vs ND: 0%; P < 0.001) after high-level disinfection and drying and less bacterial contamination after storage for 14 days (SD: 47% vs ND: 20%; P = 0.028). Time consumed for drying in ND was also significantly shorter (SD: 16 minutes 4 seconds vs ND: 5 minutes 59 seconds; P < 0.001). Drying with a special automatic drying device was superior compared with an EWD's drying program as evidenced by no measurable residual water, reduced microbiological contamination, and a more than 2-fold decrease in operational time. Thus, drying by laminar and turbulent airflow may represent an attractive alternative to the currently used standard approach in the reprocessing process of flexible endoscopes.

Abstract A059: Understanding the events that promote pancreatic cancer metastasis

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy due to overwhelming metastatic burden. PDAC cells migrate and invade by two distinct epithelial-to-mesenchymal transition phenotypes: collective (partial-EMT) or single-cell (complete-EMT). The mechanism(s) by which these invasive phenotypes intravasate is unknown. The Tumor Microenvironment of Metastasis (TMEM) doorway, which is formed by a tumor cell, macrophage and an endothelial cell in direct contact, causes opening of the vasculature in which tumor cells intravasate. Intravasation via TMEM doorway is inhibited by Tie2 blockade. Whether this occurs in PDAC and whether the EMT phenotype affects intravasation is unknown. We hypothesize that PDAC cells intravasate through TMEM-dependent mechanisms regardless of EMT phenotype. Tumor samples from murine models were stained for TMEM doorways using a triple immunohistochemistry (IHC) stain (tumor cells expressing the actin regulatory protein Mena, macrophages expressing CD68, and endothelial cells expressing CD31). TMEM doorway opening was assessed in murine models of PDAC treated with or without Tie-2 inhibitor by analyzing TMEM-mediated extravasation of high-molecular weight dextran (155kD-TMR dextran) by Intravital Imaging, IHC and immunofluorescence (IF) of serial slides and circulating tumor cells. An intravasation trans-endothelial migration assay was also performed to assess the intravasation event by TMEM doorway in vitro. A student t-test was used for the analyses. TMEM doorways were observed in all PDAC murine models. For the first time in PDAC, focal extravasation of dextran events followed by a tumor cell intravasation was visualized by intravital imaging. PDAC tumor bearing mice treated with Tie2 inhibitor had a 2-fold decrease in the number of circulating tumor cells compared to control (958 ± 499.8 vs 534 ± 479.9 cells/mL blood, p=0.0257). The intravasation trans-endothelial migration assay showed that C-EMT cells have a higher migration rate than P-EMT cells (17.8 ± 5.53 vs 10.94 ± 3.84 migrating cells p=0.01), and this ratio increases with the presence of macrophages (23.75 ± 5 vs 15.54 ± 3.09 migrating cells p=0.005). The Tie-2 inhibition decreases the number of C-EMT and P-EMT migrating cells (7.69 ± 1.3 vs 3.67 ± 1.2 migrating cells p=0.01). Orthotopic tumors from C-EMT phenotype grow at a faster rate than the P-EMT (0.49mg ± 0.09 vs 0.12mg ± 0.05 p&amp;lt;0.05). Tumors from C-EMT and P-EMT cells will be analyzed for TMEM doorway score, TMEM activity and stemness signatures around TMEM doorway to determine if TMEM doorway is a niche for stemness in PDAC. TMEM doorways are present in PDAC mouse model. Inhibition of Tie2 leads to decreased TMEM doorway function and circulating tumor cells in PDAC. In addition, regarding the EMT phenotype, TMEM doorways are functional mechanisms of intravasation in vitro. This is a novel mechanism in PDAC and suggests a promising therapeutic target for decreasing intravasation and potential metastasis in PDAC. Citation Format: Erika Pereira Zambalde, Lina Ariyan, Francisco Puerta-Martinez, Yuqin Zhu, John Condeelis, Ben Stanger, John McAuliffe. Understanding the events that promote pancreatic cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A059.

Fabrication of an IgG-imprinted monolith micro-solid phase extraction chip for IgG extraction from human plasma

Molecular imprinted polymers (MIPs), also known as synthetic antibodies, offer a novel and promising approach for protein separation at analytical scale. In proteomics research, this approach could capture target high abundant proteins from biological fluids to reduce sample complexity. In this study, we have explored the potential to imprint human immunoglobulin G (IgG) to develop a micro-solid phase extraction chip for selective removal of IgG from human plasma. Imprinting of IgG within the polyhydroxy ethyl methacrylate monolith containing dimethyl amino ethyl methacrylate (DMAEMA) as a functional monomer was successfully achieved and characterized using FT-IR spectroscopy and protein assay kit. 0.1 M tris buffer (pH 7) and UV-polymerization were identified as the ideal buffer and polymerization strategy to imprint IgG within 30 min. Template (IgG) elution using 10 % acetic acid containing 10 % (v/v) SDS as elution buffer was moderately successful (25 % IgG-template free monolith was obtained). Protein shape has influenced its imprinting and elution from the monolith. The protocol developed to imprint one protein cannot be translated to another protein without further modifications. A 10-fold decrease of DMAEMA concentration within the monolith and a sequential elution step has resulted in >90 % IgG-template free monolith. The IgG-template free monolith has displayed an adsorption capacity of ∼ 3.7 mg per g monolith and showed good IgG selectivity as compared to other tested human proteins (human serum albumin, transferrin and fibrinogen). Translation of imprinted monolith protocol to develop a micro-solid phase extraction chip was successful. The chip can be re-used for 5 cycles with >95 % reusability and has selectively captured IgG from human plasma.

Regulation of an RNA toxin-antitoxin system, SdsR-RyeA, by a small RNA GcvB

The toxin-antitoxin (TA) system regulates many physiological processes in free-living bacteria. One such TA system in Escherichia coli comprises an RNA toxin SdsR and an antitoxin RyeA. An overabundance of SdsR is toxic to the cells. RyeA normalizes SdsR abundance and helps the cells to adapt to altered conditions. The current study showed that a novel small RNA (sRNA) regulator GcvB directly interacts with RyeA to maintain its abundance in the cells under normal or low pH conditions. The deletion of the gcvB allele in the E. coli chromosome resulted in a ∼3-fold decrease in intrabacterial RyeA accumulation. An ectopic expression of GcvB in ΔgcvB strain reinstated RyeA abundance to its normal level. Induction of GcvB in the cells upon exposure to low pH resulted in a simultaneous increase in intracellular RyeA. While GcvB increases RyeA abundance in the cells, SdsR accumulation is divergently regulated by GcvB. The absence of the gcvB gene in E. coli leads to upregulation of SdsR and vice versa. The GcvB-mediated decrease of SdsR accumulation stems from the increased RyeA-driven normalization of SdsR. This study delineates a novel mechanism for the regulation of the expression of an RNA toxin SdsR by another sRNA regulator GcvB through a feed-forward control.

Dual Chemotherapeutic Loading in Oxalate Transferrin-Conjugated Polymersomes Incorporated into Chitosan Hydrogels for Site-Specific Targeting of Melanoma Cells.

In this work, we developed a smart drug delivery system composed of poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) loaded with doxorubicin (DOX) and vemurafenib (VEM). To enhance targeted delivery to malignant melanoma cells, these drug-loaded nanovesicles were conjugated to the oxalate transferrin variant (oxalate Tf) and incorporated into three-dimensional chitosan hydrogels. This innovative approach represents the first application of oxalate Tf for the precision delivery of drug-loaded polymersomes within a semi-solid dosage form based on chitosan hydrogels. These resulting semi-solids exhibited a sustained release profile for both encapsulated drugs. To evaluate their potency, we compared the cytotoxicity of native Tf-Ps with oxalate Tf-Ps. Notably, the oxalate Tf-Ps demonstrated a 3-fold decrease in cell viability against melanoma cells compared to normal cells and were 1.6-fold more potent than native Tf-Ps, indicating the greater potency of this nanoformulation. These findings suggest that dual-drug delivery using an oxalate-Tf-targeting ligand significantly enhances the drug delivery efficiency of Tf-conjugated nanovesicles and offers a promising strategy to overcome the challenge of multidrug resistance in melanoma therapy.