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Robust Plasma-Assisted Growth of 2D Janus Transition Metal Dichalcogenides and Their Enhanced Photoluminescent Properties.

Janus transition metal dichalcogenides (TMDs) are a novel class of 2D materials with unique mirror asymmetry. Plasma-assisted synthesis at room temperature is favored for producing Janus TMDs due to its energy efficiency and prevention of alloying. However, current methods require stringent control over growth conditions, risking defects or unintended materials. A robust plasma-assisted (RPA) synthesis strategy is introduced, incorporating a built-in tube with a suitable inner diameter into the plasma-assisted system. This innovation creates a mild, uniform plasma atmosphere, allowing for broader variations in growth parameters without significantly affecting Janus MoSSe's morphology and characteristics. This approach simplifies the synthesis process and enhances the success rate of Janus TMD production. Additionally, methods are explored to enhance the photoluminescence (PL) of Janus MoSSe. Releasing MoSSe from the growth substrate and annealing it removes strain and unintentional doping, improving PL performance. MoSSe on hexagonal boron nitride (h-BN) flakes after annealing shows a 32-fold increase in PL intensity. Bis(trifluoromethane) sulfonimide (TFSI) treatment of MoSSe results in a remarkable 70-fold increase in PL intensity, a 2.5-fold extension in exciton lifetime, and quantum yield (QY) reaching up to ≈31.2%. These findings provide critical insights for optimizing the luminescence properties of 2D Janus materials, advancing Janus optoelectronics.

Development of an Intravenously Stable Disulfide-Rich Peptide for the Treatment of Chemotherapy-Induced Neuropathic Pain.

α-conotoxins (α-Ctxs), a class of disulfide-rich conopetides, are excellent drug leads due to their small size, high selectivity, and potency for specific membrane receptors and ion channels involved in pain transmission. However, their high susceptibility to proteolytic degradation limits their therapeutic potential. In this study, we designed and synthesized a series of conformationally stable analogues of α-Ctx Mr1.1[S4Dap] using various structural optimization strategies. The Mr1.1[S4Dap, C16Pen] analogue maintained potency at human α9α10 nicotinic acetylcholine receptors, with a half-maximal inhibitory concentration (IC50) of 4 nM. It exhibited over a 5-fold increase in serum stability compared to Mr1.1[S4Dap], without disrupting its overall conformation. Furthermore, intravenous application of Mr1.1[S4Dap, C16Pen] showed potent analgesic activity in oxaliplatin-induced cold allodynia, indicating a high potential for drug development. Overall, the results from this study provide valuable insights for optimizing the serum stability of disulfide-rich peptides in future therapeutic applications.

Ethanol crude leaf extract of weeping fig (Ficus benjamina) causes mild hepatotoxicity in Sprague dawley rats

Weeping fig (Ficus benjaminaeaf extract has diverse medicinal properties but little is reported about its hepatotoxicity. This study determined the mean lethal dose (LD50) and investigated the effects of F. benjamina ethanol crude leaf extract on biochemical parameters and liver histology of Sprague Dawley rats. Twenty-nineemale rats weighing 133-204 g were used. The LD50 was determined with nine rats based on Lorke’s method. The experimental groups consisted of twenty rats, divided into four groups of five. Each group received treatment as follows: Control (feed and water only) and low, medium, and high doses (500, 1000, 1500 mg/kg respectively) of the extract orally for 21 days. All animals were weighed and sacrificed using Ketamine intra-peritoneal injection. Blood samples were collected for biochemical parameters of total bilirubin, conjugated bilirubin, aspartate aminotransferase (AST) alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Liver tissues were removed and processed by the formalin-fixed-paraffin wax-embedding method. The tissue blocks were sectioned and subjected to Hematoxylin/Eosin and Masson trichrome staining. The extract’s LD50 was >5000 mg/kg. The rats’ body weights did not change statistically (p=0.985). Total bilirubin (p=0.003), conjugated bilirubin, AST, ALT, and ALP values (p=0.001) increased significantly. The AST high-doseroup had the highest fold increase (4.8). The liver histology showed mild sinusoidal dilation at 500 mg/kg. There was marked hemorrhage and fibrosis at medium and high doses. Although the extract had relatively low acute toxicity, 1000 and 1500 mg/kg doses were associated with mild hepatotoxicity characterized by veno-occlusion disease. The 500 mg/kg dose is safer for medicinal purposes.

Echocardiographic parameters for weaning from Extracorporeal Membrane Oxygenation - the role of longitudinal function and cardiac time intervals.

Limited data exist on echocardiographic predictors of weaning from veno-arterial extracorporeal membrane oxygenation (V-A ECMO). We aimed to test the performance of different echocardiographic indices to predict weaning from V-A ECMO. and free survival after weaning. Observational study including patients with cardiogenic shock submitted to V-AECMO. Echocardiography was performed after V-AECMO placement and daily during the weaning trial to assess cardiac recovery. Echocardiography data after V-A ECMO implantation and during the last weaning-trial before V-A ECMO removal were analyzed. Besides traditional parameters, total isovolumic time (t-IVT, a left ventricular performance index) and mitral annular plane systolic excursion (MAPSE) were also tested.76 patients were included. A greater ventricular velocity-time integral (LVOT VTI) at baseline was associated with a 5-fold increase in weaning success (p < 0.001) as MAPSE lateral >6.15 mm (p 0.001) did. TAPSE and S' at tricuspid annulus showed an analogous association. During the weaning trial t-IVT, LVEF, MAPSE, LVOT VTI and TAPSE all improved significantly (p <0.001 for all). At regression analysis t-IVT <14.4second/minute (<0.001), LVOT VTI >12.3cm (p <0.001), MAPSE >8.9mm (p < 0.001), TAPSE> 16mm (<0.001) and E/e' <15.5 (p 0.001) were associated with weaning success and free survival after weaning. LVEF did not predict the weaning success and survival at any time-point (p 0.230). Longitudinal function, t-IVT and native ejection, measured with LVOT VTI, are reliable parameters to predict weaning success in V-A ECMO whereas the LVEF, although dynamically changing during weaning trial, it is not.

Effect of Oxidative Stress on Sperm TERRA Expression and Chromatin Function in Infertile Males: A Preliminary Finding

Telomeres are vital for cellular function. Oxidative stress is detrimental to telomere function as it causes telomere attrition. Increase in oxidative stress has a negative impact on sperm telomere and chromatin integrity and therefore, on sperm function and male fertility. TERRA, a long non-coding RNA is a fundamental component required for telomere length homeostasis. Aim: The present work aimed to study the effect of H2O2 induced oxidative stress on sperm TERRA expression and chromatin function. Methodology: 5 infertile and 5 fertile males were selected for the study. Baseline semen analysis was done as per WHO manual 2021. Sperm TERRA expression was assessed by real time qPCR. To assess chromatin function nuclear chromatin decondensation test was done. Results: Study showed that 500µM H2O2 increased TERRA expression as compared to untreated groups and the difference was found to be statistically significant. As compared to controls, cases showed more fold increase in TERRA expression. When treated samples of control and cases were compared, cases had more TERRA expression than controls however, the baseline TERRA expressions in untreated samples were less in cases as compared to controls. Both comparisons yielded statistically nonsignificant results. When nuclear chromatin decondensation was compared before and after H2O2 treatment, the percentage of sperm head decondensation decreased in both cases and controls. When treated and untreated samples of cases and controls were compared, the difference was statistically nonsignificant. Conclusion: Oxidative stress led to an increase in the expression of sperm TERRA and had a negative impact on nuclear chromatin decondensation. Similar studies with greater sample size can provide much more insight into TERRA mediated regulation of telomere function and chromatin integrity and how it is affected by oxidative stress.

Impact of pasture feeding cows and seasonality on the concentration of selected fat-soluble compounds in milk and their ability to be used as biomarkers of “Grass-Fed” dairy

This study investigated the impact of proportion of pasture in the cow diet on the concentration of selected fat-soluble compounds in milk including β-carotene, lutein, retinol (vitamin A), α-tocopherol (vitamin E) and zeaxanthin. Bulk tank milk samples (n = 102) were collected weekly (n = 34) across an entire lactation from three herds operating either a high (GRS), medium (PMR) or no pasture allowance (TMR) feeding system. Concentrations of β-carotene and lutein increased significantly with increasing pasture allowance, with a > 2 fold increase of β-carotene in milk, between high and no pasture allowance treatments. GRS feeding system resulted in milks with higher concentrations of retinol, α-tocopherol, and zeaxanthin, compared to both PMR and TMR systems. A biomarker model based on the fat-soluble compounds concentration in milk, demonstrated excellent differentiation of high pasture allowance derived milks from that of medium and no pasture milks, with area under the curve scores of 0.955 and 0.971 respectively. Strong correlations were observed between the concentrations of lutein and zeaxanthin in milk and the milks corresponding yellow colour, while a significant correlation was exhibited between β-carotene and b*-value. Such correlations with milk colour may have a significant impact on the consumer preference of milk and dairy products produced therefrom.

Risk of developing a subsequent primary cancer among adult cancer survivors.

Improvements in cancer control have led to a drastic increase in cancer survivors who may be at an elevated risk of developing subsequent primary cancers (SPC). In this study, we assessed the risk and patterns of SPC development among 196,858 adult cancer survivors in Alberta, Canada. We used data from the Alberta Cancer Registry to identify all first primary cancers occurring between 2004 and 2020. A SPC was considered as the next primary cancer occurring in a different site. We estimated standardized incidence ratios (SIR) for SPC development as the observed number of SPC (O) divided by the expected number of SPC (E), where E is a weighted-sum of the population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up. The risk of developing a SPC up to fifteen years after an initial cancer was 16.2% for males and 12.2% for females. Overall, both males (SIR=1.50) and females (SIR=1.58) had an increased risk of a SPC. There were significant increases in SPC risk for nearly all age groups, with a greater than 5-fold increase for survivors diagnosed between ages 18-39. Screen-detectable cancers including colorectal, lung, cervix, and breast accounted for 46% and 27% of SPCs among females and males. Cancer survivors of nearly every initial site had substantially increased risk of a SPC, compared to the cancer risk in the general population. Screen-detectable cancers were common SPC sites and highlights the need to investigate optimal strategies for screening the growing population of cancer survivors.

Polygenic risk scores stratify breast cancer risk among women with benign breast disease.

Most breast biopsies are diagnosed as benign breast disease (BBD), with 1.5- to fourfold increased breast cancer (BC) risk. Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in BC risk assessment of these patients. We assessed whether a 313-SNP polygenic risk score (PRS) stratifies risk of BBD patients. We pooled data from five Breast Cancer Association Consortium case-control studies (mean age = 59.9 years), including 6,706 cases and 8,488 controls. Using logistic regression, we estimated BC risk associations by self-reported BBD history and strata of PRS, with median PRS category among women without BBD as the referent. We assessed interactions and mediation of BBD and PRS with BC risk. BBD history was associated with increased BC risk (OR = 1.48, 95% CI: 1.37-1.60; p < .001). PRS increased BC risk, irrespective of BBD history (p-interaction = 0.48), with minimal evidence of mediation of either factor by the other. Women with BBD and PRS in the highest tertile had over 2-fold increased odds of BC (OR = 2.73, 95% CI: 2.41-3.09) and those with BBD and PRS in the lowest tertile experienced reduced BC risk (OR = 0.79, 95% CI: 0.70-0.91), compared to the reference group. Women with BBD and PRS in the highest decile had a 3.7- fold increase (95% CI: 3.00-4.61) compared to those with median PRS without BBD. BC risks are elevated among women with BBD and increase progressively with PRS, suggesting that optimal combinations of these factors may improve risk stratification.

Enhancing preventive and therapeutic cancer vaccine efficacy through biotherapeutic ligand-associated extracellular vesicles

Extracellular vesicles (EVs), secreted by almost all living cells, have gained significant attention for their role in intercellular communication and their potential as versatile carriers for biotherapeutics. However, the clinical translation of EV-based therapies faces significant challenges, primarily due to the lack of efficient methods for loading biotherapeutic agents into EVs. This study introduces a simple, reproducible strategy for the simultaneous incorporation of various biotherapeutics within EVs. The process is gentle and preserves the essential physicochemical and biological characteristics of EVs, thereby protecting labile ligands from premature degradation and elimination. The binding and uptake efficiency of EVs by target cells reached approximately 97 % within 24 h of incubation. Administration of EVs loaded with oligodeoxynucleotides (ODN) resulted in a 4-fold increase in IFNγ+ CD4+ T cells and a 5-fold increase in IFNγ+ CD8+ T cells in the spleens and lymph nodes. Additionally, the co-administration of EVs with ODN and ovalbumin (OVA) induced elevated Th1-biased antibody responses and antigen-specific cytotoxic T-cell responses, providing long-lasting complete protection in 60 % of mice against T-cell thymoma challenge. Furthermore, EVs associated with three different ligands (OVA, CpG-ODN, and α-GalCer) effectively regressed established murine melanoma and significantly improved survival rates in mice. This study presents a powerful and promising approach to overcoming the limitations of EV-based cancer vaccines, advancing the development of effective cancer immunotherapies. SummaryImmunization with EVs that are co-associated with antigen and biotherapeutic cargo through a lyophilization-based technique elicits potent anti-cancer immunity.

Dose-Response Effect of Various Concentrations of Cl-Containing Water-Soluble Derivatives of C60 Fullerenes on a Selective Regulation of Gene Expression in Human Embryonic Lung Fibroblasts (HELF).

The new synthesized water-soluble derivatives of C60 fullerenes are of a great interest to researchers since they can potentially be promising materials for drug delivery, bioimaging, biosonding, and tissue engineering. Surface functionalization of fullerene derivatives changes their chemical and physical characteristics, increasing their solubility and suitability for different biological systems applications, however, any changes in functionalized fullerenes can modulate their cytotoxicity and antioxidant properties. The toxic or protective effect of fullerene derivatives on cells is realized through the activation or inhibition of genes and proteins of key signaling pathways in cells responsible for regulation of cellular reactive oxygen species (ROS) level, proliferation, and apoptosis. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to assess cells viability. Flow cytometry analyses was applied to measure proteins levels in human embryonic lung fibroblasts (HELF) cells. HELF is a standard, stable and well described human cell line that can be passaged many times. Quantitation of ROS was assessed using H2DCFH-DA. Fluorescence images were obtained using microscopy. Expression of BCL2, CCND1, CDKN2A, BRCA1, BAX, NFKB1, NOX4, NRF2, TBP (reference gene) was analyzed using real-time Polymerase chain reaction (PCR). We found that high and low concentrations of fullerene C60 derivatives with the five residues of potassium salt of 6-(3-phenylpropanamido)hexanoic (F1) or 6-(2-(thiophen-2-yl)acetamido)hexanoic (F2) acid and a chlorine atom attached directly to the cage cause diametrically opposite activation of genes and proteins of key signaling pathways regulating the level of oxidative stress and apoptosis in HELF. High concentrations of F1 and F2 have a genotoxic effect, causing NADPH oxidase 4 (NOX4) expression activation in 24-72 hours (2-4 fold increase), ROS synthesis induction (increase by 30-40%), DNA damage and breaks (2-2.5 fold 8-oxodG level increases), and activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (by 40-80%) against the background of reduced NF-E2-related factor 2 (NRF2) expression (by 20-45%). Low concentrations of F1 and F2 produced a cytoprotective effect: in 24-72 hours they reduce the oxidative DNA damage (by 20-40%), decrease the number of double-strand DNA breaks (by 20-30%), increase the level of anti-apoptotic proteins and enhance the antioxidant response activating the NRF2 expression (NRF2 gene expression increases 1.5-2.3 fold, phosphorylated form of the NRF2 protein increases 2-3 fold). Obtained results show that in low doses studied fullrens may serve as perspective DNA protectors against the damaging genotoxic factors.

Single-Step Extrusion Process for Formulation Development of Self-Emulsifying Granules for Oral Delivery of a BCS Class IV Drug.

This study aimed to develop and optimize formulations containinga BCS Class IV drug by improving its solubility and permeability. Herein development of self-emulsifying solid lipid matrices was investigated as carrier systems for a BCS Class IV model drug. Self-emulsifying drug delivery systems (SEDDS) have been extensively investigated for formulating drugs with poor water solubility. However, manufacturing SEDDS is challenging. These systems usually have low drug-loading capacities, and the incorporated drugs tend to recrystallize during storage, which severely impacts the storage stability in vitro and performance in vivo. Moreover, they require greater amounts (>80%) of lipid carriers, cosolvents, surfactants, and other excipients to keep them from recrystallizing. This in turn is again challenging for high-dose drugs as it affects the size of the final drug product (tablets and capsules). Also, the final liquid nature of the formulation affects the handling and processability of the formulation, which poses challenges during the manufacturing and packaging steps. In this work, we have studied the feasibility of a single-step extrusion process to formulate and optimize solid self-emulsifying granules with a relatively higher drug loading of Ritonavir (RTV), a BCS Class IV drug. Further, we have compared the performance of using these granules as the feedstock for direct powder extrusion-based 3D printing as opposed to the use of physical blends. The stability and solubility-permeability advantage of these granules was also evaluated where SEDDS showed about 27 and 20 fold increase in apparent solublity and permeability compared to bulk drug, respectively. Combining the capabilities of HME to form drug-loaded homogeneous granules as a continuous process along with application of direct printing extruiosn (DPE) 3D printing improves the drug delivery prospects for such candidates.

Investigating deep learning strategies for fast denoising of 5D cardiac photon-counting micro-CT images

&#xD;Photon-counting detectors (PCDs) for CT imaging use energy thresholds to simultaneously acquire projections at multiple energies, making them suitable for spectral imaging and material decomposition. Unfortunately, setting multiple energy thresholds results in noisy analytical reconstructions due to low photon counts in high-energy bins. Iterative reconstruction provides high quality photon-counting CT (PCCT) images but requires enormous computation time for 5D (3D + energy + time) in vivo cardiac imaging. &#xD;&#xD;Approach. &#xD;We recently introduced UnetU, a deep learning (DL) approach that accurately denoises axial slices from 4D (3D + energy) PCCT reconstructions at various acquisition settings. In this study, we explore UnetU configurations for 5D cardiac PCCT denoising, focusing on singular value decomposition (SVD) modifications along the energy and time dimensions and alternate network architectures such as 3D U-net, FastDVDNet, and Swin Transformer UNet. We compare our networks to multi-energy non-local means (ME NLM), an established PCCT denoising algorithm. &#xD;&#xD;Main results. &#xD;Our evaluation, using real mouse data and the digital MOBY phantom, revealed that all DL methods were more than 16 times faster than iterative reconstruction. DL denoising with SVD along the energy dimension was most effective, consistently providing low root mean square error and spatio-temporal reduced reference entropic difference, alongside strong qualitative agreement with iterative reconstruction. This superiority was attributed to lower effective rank along the energy dimension than the time dimension in 5D cardiac PCCT reconstructions. ME NLM sometimes outperformed DL with time SVD or time and energy SVD, but lagged behind iterative reconstruction and DL with energy SVD. Among alternate DL architectures with energy SVD, none consistently outperformed UnetU Energy (2D). &#xD;&#xD;Significance. &#xD;Our study establishes UnetU Energy as an accurate and efficient method for 5D cardiac PCCT denoising, offering a 32-fold speed increase from iterative reconstruction. This advancement sets a new benchmark for DL applications in cardiovascular imaging.

Magnetic, conductive nanoparticles as building blocks for steerable micropillar-structured anodic biofilms

In bioelectrochemical systems (BES), biofilm formation and architecture are of crucial importance, especially for flow-through applications. The interface between electroactive microorganisms and the electrode surface plays an important and often limiting role, as the available surface area influences current generation, especially for poor biofilm forming organisms. To overcome the limitation of the available electrode surface, nanoparticles (NPs) with a magnetic iron core and a conductive, hydrophobic carbon shell were used as building blocks to form conductive, magnetic micropillars on the anode surface. The formation of this dynamic three-dimensional electrode architecture was monitored and quantified in situ using optical coherence tomography (OCT) in conjunction with microfluidic BES systems. By cyclic voltammetry the assembled three-dimensional anode extensions were found to be electrically conductive and increased the available electroactive surface area. The NPs were used as controllable carriers for the electroactive model organisms Shewanella oneidensis and Geobacter sulfurreducens, resulting in a 5-fold increase in steady-state current density for S. oneidensis, which could be increased 22-fold when combined with Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) aggregates. In the case of G. sulfurreducens, the steady-state current density was not increased, but was achieved four times faster. The study presents a controllable, scalable and easy-to-use method to increase the electrode surface area in existing BES by applying a magnetic field and adding conductive magnetic NPs. These findings can most likely also be transferred to other electroactive microorganisms.

Photoconductivity and Photovoltaic Effect Strengthened via Microstructural Cotuning in Ferroelectrics: Intuitively Assessed by Macroscopic Transparency.

Photoferroelectrics that involve strong light-matter coupling are regarded as promising candidates for realizing bulk photovoltaic and photoelectric effects via light absorption. Nonetheless, understanding the photoresponse mechanism or modulation of performance from a microscopic point of view is scarcely explored through quantification of macroscopic properties. Herein, we design a model material, Gd3+-doped (K0.5Na0.5)NbO3 ferroelectric-transparent ceramics, and present an advantageous strategy to enhance the optoelectronic coupling through joint modulations of lattice distortion and oxygen vacancies, along with inner defects and ferroelectric domains. Significantly, their microcosmic manipulation can be intuitively and facilely evaluated by the optical transparency of each ceramic. An approximately 104 fold increase in conductivity under ultraviolet irradiation was produced. Under the cocoupling between external physical fields, the synergy of photoelectric stimulation increased the photoconductivity of the ceramics by 13.89 times. Additionally, a significant increase (4.5-fold) in the current output from the photovoltaic effect was achieved via ferroelectric domains of moderate size, whose size could be easily assessed by optical transmittance. In situ microscopic observations confirmed that the configuration of oxygen vacancy-dependent ferroelectric domains contributes to the enhanced optoelectronic response. This research provides a distinct way to develop inexpensive optocoupler devices and meet the requirements for multifunctional integration in single photoferroelectrics.

Metabolic engineering of hairy root cultures in Beta vulgaris for enhanced production of vanillin, 4-hydroxybenzoic acid, and vanillyl alcohol.

The flavor of vanilla is a complex blend of compounds, with vanillin as the most prominent, along with vanillyl alcohol and 4-hydroxybenzoic acid. Natural vanillin extracted from vanilla beans is expensive, so researchers use heterologous synthesis to produce nature-identical vanillin in plant hosts. Consequently, alternative traditional farming and gathering methods are required to bridge the significant disparity between supply and demand. The current research successfully developed a method to induce hairy root formation from leaves. It integrated the Vanillin synthase (VpVAN) gene into transgenic hairy root lines of Beta vulgaris, synthesizing vanillin-related compounds. The presence of the VpVAN gene in transgenic roots was confirmed using PCR analysis. Additionally, RT-qPCR analysis demonstrated the expression of the VpVAN gene in the transgenic root lines. The transgenic hairy root clones H1, H2, and H5 showed enhanced vanillin production, vanillyl alcohol, and 4-hydroxybenzoic acid. Elicitation with methyl jasmonate (MJ) and salicylic acid (SA) further improved the production of these compounds in B. vulgaris hairy roots. The maximum hairy root biomass was observed after 60 days, with the maximum synthesis of vanillin and 4-hydroxybenzoic acid obtained from hairy root clones H5 and HR2, respectively. Vanillyl alcohol HR2 was obtained on the 45th day of cultivation. Elicitation with wound-associated hormone methyl jasmonate and salicylic acid enhanced the yield of vanillin, vanillyl alcohol, and 4-hydroxybenzoic acid, with a 215-fold increase in vanillin, a 13-fold increase in vanillyl alcohol, and a 21 fold increase in 4-hydroxybenzoic acid. The study results indicate that establishing transgenic hairy root cultures with the VpVAN gene is a promising alternative method for enhancing the production of vanilla flavor compounds such as vanillin, vanillyl alcohol, and 4-hydroxybenzoic acid. A cost-effective protocol has been developed to mass-produce phenolic compounds using a hairy root culture of B. vulgaris. This approach addresses the increasing demand for these substances while reducing the cost of natural vanillin production, making it suitable for industrial-scale applications.

Engineering Tk1656, a highly active l-asparaginase from Thermococcus kodakarensis, for enhanced activity and stability

l-Asparaginases catalyze the hydrolysis of l-asparagine to l-aspartic acid and ammonia. These enzymes have potential applications in therapeutics and food industry. Tk1656, a highly active and thermostable l-asparaginase from Thermococcus kodakarensis, has been proved effective in selective killing of acute lymphocytic leukemia cells and in reducing acrylamide formation in baked and fried foods. However, it displayed <5 % activity under physiological conditions compared to the optimal activity at 85 °C and pH 9.5. We have attempted engineering of this valuable enzyme to improve the characteristics required for therapeutic and industrial applications. Based on the literature and crystal structure of Tk1656, nine specific mutant variants were designed, produced in Escherichia coli, and the purified mutant enzymes were compared with the wild-type. One of the mutants, K299L, displayed >20 % increase in activity at 85 °C. H158S substitution resulted in >5 °C increase in the optimal temperature. Similarly, a mesophilic-like mutation L56D, resulted in >5-fold increase in activity at pH 7.0 and 37 °C compared to that of the wild-type enzyme. The substrate specificity of the mutant variants remained unchanged. These results demonstrate that L56D and K299L variants of Tk1656 are the potent enzymes for therapeutics and acrylamide mitigation applications, respectively.

Prevalence and costs of eosinophilic esophagitis in the United States

Background and AimsEosinophilic esophagitis (EoE) has been continually increasing in prevalence but current estimates are lacking. We aimed to determine updated estimates of the prevalence and medical costs associated with EoE in the United States. MethodsWe used two large administrative databases, MarketScan and Medicare, and International Classification of Disease codes to calculate annual prevalence of EoE, as well as age- and sex- stratified estimates, standardized to the U.S. population. Health care utilization, including medications and endoscopic procedures was quantified, and annual EoE-associated costs were estimated. ResultsWe identified 20,435 EoE cases in MarketScan in 2022 and 1,913 EoE cases in Medicare in 2017. This translated to prevalences of 163.08 cases/100,000 and 64.83 cases/ 100,000 in MarketScan and Medicare, respectively. There was a 5-fold increase in prevalence in both databases since 2009. In MarketScan, prevalence was higher among males (204.45/100,000 vs 122.06/100,000 among females); for both sexes, peak prevalence was from 40–44years. Standardized to the U.S. population, the prevalence of EoE was 142.5/100,000, extrapolating to 472,380 cases. Total EoE-associated healthcare costs were estimated to be $1.32 billion in 2024 dollars after accounting for inflation. ConclusionsThe prevalence of EoE continues to increase, with a rate of 1 in 617 in 2022 in those <65 years of age, and 1 in 1562 in 2017 those ≥65 years. Standardized to the U.S. population, the overall prevalence was approximately 1 in 700. EoE-associated annual costs were estimated to be $1.3 billion in 2024 dollars, representing a substantial financial burden.

Colorectal tumor comorbidity is common in patients with duodenal tumors: Exploratory cross-sectional study.

Background and study aims The duodenum and colorectum are target organs for familial colorectal adenomatous polyposis, however, the association of duodenal epithelial tumors (DETs) and colorectal tumors is still controversial. The aim of our study was to elucidate the association between DET and colorectal tumor. Patients and methods This was an exploratory cross-sectional study of patients with DETs treated by endoscopic resection at our hospital, between November 2018 and October 2022. Individuals who underwent colonoscopy as part of the health screening comprised the reference control group for comparison. In both groups, lesions suspected of being tumors were resected. The main outcome was the adenoma detection rate (ADR). Other outcomes were the detection rate for advanced neoplasia (AN) and risk factors for colorectal adenoma and AN, evaluated using univariate and multivariable analyses. Results Analyses were based on data from 163 individuals in the DET group and 177 in the control group. ADR was higher in the DET (63.2%) than in the control (23.6%) group ( P < 0.001). AN and invasive cancer rates were also significantly higher in the DET than in the control group (AN: 20.9% vs 3.4%, respectively, P < 0.001; invasive cancer: 3.1% vs 0%, respectively, P < 0.001). On logistic regression analysis, DET was found to be associated with a 5-fold increase in the detection rate of adenoma and 6-fold increase in AN detection. Conclusions The study revealed significant association between DET and high ADR and a higher frequency of AN and invasive cancer. Screening colonoscopy is suggested for patients with DETs.

Efficient Li+/Mg2+ separation by two-dimensional montmorillonite membrane with stable channel structure through ion exchange and metal–organic coordination strategy

Two-dimensional (2D) nanochannel membranes stacked by nanosheets are promising membrane separation materials. However, intrinsic swelling properties of 2D membrane have emerged as a significant challenge to establish stable nanochannels and achieve high separation performance. Inspired by the natural ion exchange property of montmorillonite (MMT), we constructed a two-dimensional MMT membrane with robust nanochannels by exchanging Fe3+ into interlayer of the membrane, and further achieved efficient separation of Li+/Mg2+ through coordination manipulation of tannic acid (TA) and Fe3+. Swelling was dramatically prevented by strong interlayer interaction between exchanged Fe3+ and nanosheets resulting in a 32-fold increase in anti-swelling properties. Furthermore, experiments and simulations revealed that TA could rapidly chelate with Fe3+ to form a dense hydrophilic functional layer on the membrane interface, which endowed MMT membranes with enhanced mechanical strength, cation transport and recognition, as well as anti-fouling properties. Consequently, the resulting MMT membranes showed the Li+/Mg2+ selectivity as high as 9.98 with a fast Li+ permeation rate (0.108 mol m-2h−1), which exceeded most of the previously reported membranes. This study proposed a novel strategy to diminish the trade-off effect among stability, ion flux, and selectivity of membranes, and inspired the development of next-generation ion selective separation membranes.

The enhanced antibacterial and antibiofilm properties of titanium dioxide nanoparticles biosynthesized by multidrug-resistant Pseudomonas aeruginosa

AbstractThe emergence of Multidrug-resistant (MDR) bacteria are becoming a major worldwide health concern, encouraging the development effective alternatives to conventional antibiotics. The study identified P. aeruginosa and assessed its antimicrobial sensitivity using the Vitek-2 system. Carbapenem-resistant genes were detected through Polymerase chain reaction (PCR). MDR- P. aeruginosa isolates were used to biosynthesize titanium dioxide nanoparticles (TiO2NPs) and characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM). A study involving 78 P. aeruginosa isolates revealed that 85.8% were MDR, with meropenem and amikacin showing effectiveness against 70% of the isolates. The most prevalent carbapenemase gene was blaOXA-48, present in 83% of the isolates. Majority of the isolates formed biofilms, and biosynthesized TiO2NPs were able to reduce biofilm formation by 94%. TiO2NPs exhibited potent antibacterial action against MDR-Gram-negative bacilli pathogens and showed synergistic activity with antibiotics, particularly piperacillin, with a significant fold increase in areas (283%). A new local strain of P. aeruginosa, identified as ON678251 in the World GenBank, was found capable of producing TiO2NPs. Our findings demonstrate the potential of biosynthesized TiO2NPs to manage antibiotic resistance and regulate the formation of biofilms. This presents a promising direction for the creation of novel antimicrobial agents or substitutes for use in clinical settings, particularly in the management of isolates capable of resisting multiple drugs.