Serum Albumin Research Articles

Hypoalbuminemia in children with acute lymphoblastic leukemia: relation to asparaginase therapy and impact on high dose methotrexate elimination

Abstract Purpose High-dose methotrexate (HDMTX) therapy is an important component in treatment regimens for acute lymphoblastic leukemia (ALL). Courses are associated with a risk of renal injury, delayed elimination, and increased systemic toxicity. Recently hypoalbuminemia has been recognized as yet another risk factor. Methods To examine the impact of serum albumin we reviewed 325 HDMTX 5 g/m2 courses in a cohort of 51 children treated on the NOPHO ALL 2008 protocol, dividing the courses into four groups with different levels of baseline albumin (A < 25 g/L, B 25–29 g/L, C 30–34 g/L and D ≥ 35 g/L). Results Hypoalbuminemia was present in 51% of the courses, mostly in the early phases of chemotherapy while asparaginase therapy is ongoing, and especially if given less than 2 weeks after a dose (78%). Hypoalbuminemia had a significant impact on the end-of-infusion serum MTX, depending on the degree of hypoalbuminemia: MTX > 150 µM was seen in 37%, 32%, 20% and 8% in groups A to D. Serum albumin < 30 g/L was significantly associated with low MTX clearance < 10 L/h/1.73m2 (78% vs. 36%) and high AUC ≥ 1000 µM*h (44% vs. 31%). The frequency of rising creatinine or prolonged elimination was not increased, but the risk of stomatitis was significantly higher (42% vs. 19%). Conclusion Low serum albumin is caused by concurrent asparaginase therapy and has a clinically significant impact on MTX disposition. Guidelines for administering HDMTX may need adjustment if serum albumin < 30 g/L, and, if possible, HDMTX courses should not be scheduled soon after asparaginase doses.

Interaction between modified magnetic nanoparticles and human albumin: Kinetics and isotherm studies and application in protein depletion

Magnetic nanoparticles modified with tetraethyl orthosilicate (Fe3O4@TEOS) and bovine serum albumin (Fe3O4@TEOS@BSA) were evaluated as sorbent in albumin depletion from human serum samples by magnetic dispersive solid phase extraction. Characterization studies were carried out by X-ray diffraction, thermogravimetry, Fourier transform infrared spectroscopy, zeta potential, and scanning electron microscopy. Both nanoparticles also showed high thermal stability and pH-dependent surface charges. The human serum albumin adsorption protocol was optimized using a central composite rotatable design. Nanoparticle mass, pH, and albumin concentration were the most influential variables. Avrami's fractional order and Freundlich isotherm models best fitted the data for human albumin adsorption kinetic and isotherm studies for Fe3O4@TEOS and Fe3O4@TEOS@BSA, and the maximum adsorption capacities were 11.93 and 14.89 mg g−1, respectively. The protein desorption was influenced by the pH of samples and eluent volume. Electrophoresis in a polyacrylamide gel containing sodium dodecyl sulfate showed different patterns of serum protein bands when consecutive depletions were performed. The Fe3O4@TEOS showed greater affinity for HSA and efficiency in depletion. The process was versatile, and the depleted albumin proportion could be controlled by the nanoparticle masses. The proposed method is a powerful sample preparation technique for rapid, reliable, and specific depletion of albumin.

Abstract B154: Effect modification of United States residency and length of time in US on the relationship between allostatic load and cancer mortality risk in Hispanic/Latinx Americans: Insights from NHANES (1999-2019)

Abstract Allostatic load (AL) a measure of the cumulative physiological stress occurs when external stressors exceed an individual's ability to adapt, increasing the risk of chronic diseases, including cancer. In the United States (US), Hispanic/Latinx people face acculturation-related stressors like family separation, low socioeconomic status, language barriers, racism, and discrimination, which can elevate AL and cancer risk. This study aims to examine the moderating role of US citizenship status and length of time living in US on the relationship between high allostatic load and risk of cancer mortality among Hispanic/Latinx people. We performed a retrospective analysis using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010 among 7,299 Hispanic/Latinx people linked with National Death Index with follow-up through December 31, 2019. We defined high AL as having more than three abnormal measures among the following nine biomarkers: body mass index, C-reactive protein, diastolic blood pressure, glycated hemoglobin, systolic blood pressure, total cholesterol, serum triglycerides, and serum creatinine (above the 75th percentile), or serum albumin (below the 25th percentile). We compared differences in participant characteristics using Rao-Scott Chi-Square tests for weighted survey data. We fit weighted Cox proportional hazards models to estimate hazard ratios and associated 95% confidence intervals of cancer death, stratified by US residence and length of time in US Among 7,299 Hispanic/Latinx people, 2,835 (33.4% weighted) had high AL, and 4,464 (66.6% weighted) had low AL. Hispanic/Latinx people with high AL were more likely to be male, aged 40-59, have a lower level of formal education (52.0% vs. 43.6%, p- value <0.001), and were more often surveyed during the 2007-2010 NHANES period (43.2% vs. 37.2%, p-value <0.001) compared to those with low AL. When considering US residency, participants with high AL were more likely to live in the US longer than 15 years (38.2% vs. 24.8%, p-value <0.001) and be US citizens (65.0% vs. 54.7%, p-value <0.001). Regarding health behaviors, participants with high AL were less likely to have been diagnosed with heart attack and less likely to have any history of smoking. We observed that among Hispanic/Latinx people, those with high AL have a 97% increased risk of dying from any cancer (HR = 1.97, 95% CI = 1.24 - 1.34) when compared to those with low AL. When stratifying by US citizenship status, among Hispanic/Latinx US citizen population those with high AL have a 2.3-times higher risk of cancer death when compared to those with low AL (HR = 2.30, 95% CI = 1.22 - 4.32). Among those who are Hispanic/Latinx non-US citizens, those with high AL have 48% increased risk of cancer death compared to those with low AL, though non-significant (HR = 1.48, 95% CI = 0.64 - 3.43). Our preliminary findings highlight that Hispanic/Latinx people with US citizenship who experience high levels of chronic stress, as measured by AL, have an increased risk of cancer mortality. Citation Format: Jessica Amezcua, Mellisa Lopez-Pentecost, Jessica Y. Islam, Marlo Vernon, Kathleen L. O'Connor, Justin X. Moore. Effect modification of United States residency and length of time in US on the relationship between allostatic load and cancer mortality risk in Hispanic/Latinx Americans: Insights from NHANES (1999-2019) [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B154.

A 3D Epithelial-Mesenchymal Co-Culture Model of the Airway Wall Using Native Lung Extracellular Matrix.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by ongoing inflammation, impaired tissue repair, and aberrant interplay between airway epithelium and fibroblasts, resulting in an altered extracellular matrix (ECM) composition. The ECM is the three-dimensional (3D) scaffold that provides mechanical support and biochemical signals to cells, now recognized not only as a consequence but as a potential driver of disease progression. To elucidate how the ECM influences pathophysiological changes occurring in COPD, in vitro models are needed that incorporate the ECM. ECM hydrogels are a novel experimental tool for incorporating the ECM in experimental setups. We developed an airway wall model by combining lung-derived ECM hydrogels with a co-culture of primary human fibroblasts and epithelial cells at an air-liquid interface. Collagen IV and a mixture of collagen I, fibronectin, and bovine serum albumin were used as basement membrane-mimicking coatings. The model was initially assembled using porcine lung-derived ECM hydrogels and subsequently with COPD and non-COPD human lung-derived ECM hydrogels. The resulting 3D construct exhibited considerable contraction and supported co-culture, resulting in a differentiated epithelial layer. This multi-component 3D model allows the investigation of remodelling mechanisms, exploring ECM involvement in cellular crosstalk, and holds promise as a model for drug discovery studies exploring ECM involvement in cellular interactions.

Comparative Analysis of the Potential Adaptability of Tibetan Dzo and Yellow Cattle Based on Blood Indices, Metabolites, and Fecal Microbiota.

This study aimed to investigate the differences in environmental adaptability between dzo and Tibetan yellow cattle by using corresponding assay kits to analyze blood indices, utilizing mass spectrometry for blood metabolite profiling, and performing 16S rDNA sequencing of fecal microbiota. Forty female cattle were randomly divided into a dzomo (female dzo) group (MG, n = 20) and a Tibetan-yellow-cattle group (HG, n = 20). After 150 days of uniform feeding, six cattle from each group were randomly picked for jugular blood sampling and collection of fecal microorganisms. The results showed that the serum albumin, creatinine, total protein, superoxide dismutase, IgG, and IgM concentrations in the MG group were higher (p < 0.05), whereas the serum triglyceride concentration was lower, compared to the HG group (p < 0.05). The higher level of phospholipids containing long-chain polyunsaturated fatty acids (PUFAs) (PC (18:5e/2:0), PC (20:5e/2:0), LPC 18:2, LPC 20:5) observed in the serum of the dzo suggests that they have an advantage in adapting to the challenging conditions of the plateau environment. The fecal microbiota analysis showed that Akkermansia was significantly enriched in the MG group; this might be the key bacterial genus leading to the strong adaptability of dzo. Our findings indicated the dzo's superior adaptation to the Tibetan Plateau's harsh environment.

An evaluation of serum blood parameters and amyloid-A levels in women with hyperemesis gravidarum; A prospective observational study.

This study aimed to investigate whether serum amyloid A (AA) level can be used as a biomarker in women with hyperemesis gravidarum (HEG). This prospective observational study was conducted at the Antalya Training and Research Hospital Gynecology and Obstetrics Clinic, Türkiye, between July and December 2023. Forty women diagnosed with HEG and 40 healthy women were included. No statistically significant differences were observed between the groups in terms of sociodemographic data such as age, body mass index, family history, educational status, economic level, place of residence, occupation, smoking and alcohol use, or drug habits. However, obstetric characteristics such as number of miscarriages, number of dilatation curettages, and gestational age and laboratory values including complete blood count, hematocrit, leukocyte, neutrophil, lymphocyte, platelet, free T4, albumin, alanine aminotransferase, aspartate aminotransferase, urea, creatinine, hs-C-reactive protein, and sodium (P > .05) all differed significantly. In addition, significant differences were observed between the HEG and healthy groups in terms of numbers of gravidities (2 [1-3] vs 1 [0-1], respectively, P < .001), numbers of parities (1 [0-1] vs 1 [0-1], P < .001), numbers of living children (1 [0-2] vs 1 [0-1], P < .001), presenting complaints (nausea 0 [0%], nausea + vomiting 0 [0%], none 40 [100.0%] vs nausea 27 [67.5%], nausea + vomiting 13 [32.5%], none 0 [0%], P < .001), serum thyroid-stimulating hormone (1.16 ± 0.56 vs 1.81 ± 0.624, P = .004), potassium (4.1 ± 0.7 vs 3.8 ± 0.2, P = .001), and AA values (7.29 ± 2.61 vs 10.74 ± 3.04, P < .001). At receiver operating characteristic analysis, the area under the curve (AUC: 0.881) was statistically significant for serum AA (P: <.001), with a cutoff value of ≥ 8.79 ([95% confidence interval] 0.743-0.919, sensitivity 87.4%, specificity 80.2%). The positive predictive value of serum AA was 81.1% and the negative predictive value was 80.4%. The study results showed that serum AA can be used as a diagnostic biomarker in HEG. Prospective studies involving more participants are now required to confirm our results.

Turbocharging protein binding site prediction with geometric attention, inter-resolution transfer learning, and homology-based augmentation

BackgroundLocating small molecule binding sites in target proteins, in the resolution of either pocket or residue, is critical in many drug-discovery scenarios. Since it is not always easy to find such binding sites using conventional methods, different deep learning methods to predict binding sites out of protein structures have been developed in recent years. The existing deep learning based methods have several limitations, including (1) the inefficiency of the CNN-only architecture, (2) loss of information due to excessive post-processing, and (3) the under-utilization of available data sources.MethodsWe present a new model architecture and training method that resolves the aforementioned problems. First, by layering geometric self-attention units on top of residue-level 3D CNN outputs, our model overcomes the problems of CNN-only architectures. Second, by configuring the fundamental units of computation as residues and pockets instead of voxels, our method reduced the information loss from post-processing. Lastly, by employing inter-resolution transfer learning and homology-based augmentation, our method maximizes the utilization of available data sources to a significant extent.ResultsThe proposed method significantly outperformed all state-of-the-art baselines regarding both resolutions—pocket and residue. An ablation study demonstrated the indispensability of our proposed architecture, as well as transfer learning and homology-based augmentation, for achieving optimal performance. We further scrutinized our model’s performance through a case study involving human serum albumin, which demonstrated our model’s superior capability in identifying multiple binding sites of the protein, outperforming the existing methods.ConclusionsWe believe that our contribution to the literature is twofold. Firstly, we introduce a novel computational method for binding site prediction with practical applications, substantiated by its strong performance across diverse benchmarks and case studies. Secondly, the innovative aspects in our method— specifically, the design of the model architecture, inter-resolution transfer learning, and homology-based augmentation—would serve as useful components for future work.

A Multi-Spectroscopic and Molecular Docking Analysis of the Biophysical Interaction between Food Polyphenols, Urolithins, and Human Serum Albumin

A Multi-Spectroscopic and Molecular Docking Analysis of the Biophysical Interaction between Food Polyphenols, Urolithins, and Human Serum Albumin

Novel thiazole-based cyanoacrylamide derivatives: DNA cleavage, DNA/BSA binding properties and their anticancer behaviour against colon and breast cancer cells

A novel series of 2-cyano-3-(pyrazol-4-yl)-N-(thiazol-2-yl)acrylamide derivatives (3a–f) were synthesized using Knoevenagel condensation and characterized using various spectral tools. The weak nuclease activity of compounds (3a–f) against pBR322 plasmid DNA was greatly enhanced by irradiation at 365 nm. Compounds 3b and 3c, incorporating thienyl and pyridyl moieties, respectively, exhibited the utmost nuclease activity in degrading pBR322 plasmid DNA through singlet oxygen and superoxide free radicals’ species. Furthermore, compounds 3b and 3c affinities towards calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were investigated using UV–Vis and fluorescence spectroscopic analysis. They revealed good binding characteristics towards CT-DNA with Kb values of 6.68 × 104 M−1 and 1.19 × 104 M−1 for 3b and 3c, respectively. In addition, compounds 3b and 3c ability to release free radicals on radiation were targeted to be used as cytotoxic compounds in vitro for colon (HCT116) and breast cancer (MDA-MB-231) cells. A significant reduction in the cell viability on illumination at 365 nm was observed, with IC50 values of 23 and 25 µM against HCT116 cells, and 30 and 9 µM against MDA-MB-231 cells for compounds 3b and 3c, respectively. In conclusion, compounds 3b and 3c exhibited remarkable DNA cleavage and cytotoxic activity on illumination at 365 nm which might be associated with free radicals’ production in addition to having a good affinity for interacting with CT-DNA and BSA.Graphical

Amylase intrapancreatic infusion delays insulin release during an intravenous glucose tolerance test, proof of acini-islet-acinar interactions.

The possible existence of an acini-islet-acinar (AIA) reflex, involving mutual amylase and insulin interactions, was investigated in the current acute experiment on pigs. To confirm the existence of an AIA reflex and justify the placement of the exocrine and endocrine pancreatic components within the same organ. The study was performed on six pigs under general anesthesia. An intravenous glucose tolerance test was performed, with a bolus infusion of 50% glucose to the jugular vein, while amylase (5000 U/kg) or vehicle intrapancreatic infusions were administered via the pancreaticoduodenalis cranialis artery during 30 min with a 1 mL/min flow rate. The amylase infusion to pancreatic arterial circulation inhibited and delayed the insulin release peak which is usually associated with the highest value of blood glucose and is typically observed at 15 min after glucose infusion, for > 1 h. The intrapancreatic infusion of the vehicle (saline) did not have any effect on the time frame of insulin release. Infusion of 1% bovine serum albumin changed the insulin release curve dramatically and prolonged the high range of insulin secretion, far beyond the glucose peak. Intrapancreatic arterial infusion of amylase interrupted the integrated glucose-insulin interactions. This confirms an AIA reflex and justifies placement of the exocrine and endocrine pancreatic components within the same organ.

An in vitro and machine learning framework for quantifying serum albumin binding of per- and polyfluoroalkyl substances

Abstract Per- and polyfluoroalkyl substances (PFAS) are a diverse class of anthropogenic chemicals; many are persistent, bioaccumulative, and mobile in the environment. Worldwide, PFAS bioaccumulation causes serious adverse health impacts, yet the physiochemical determinants of bioaccumulation and toxicity for most PFAS are not well understood, largely due to experimental data deficiencies. As most PFAS are proteinophilic, protein binding is a critical parameter for predicting PFAS bioaccumulation and toxicity. Among these proteins, human serum albumin (HSA) is the predominant blood transport protein for many PFAS. We previously demonstrated the utility of an in vitro differential scanning fluorimetry assay for determining relative HSA binding affinities for 24 PFAS. Here, we report HSA affinities for 65 structurally diverse PFAS from 20 chemical classes. We leverage these experimental data, and chemical/molecular descriptors of PFAS, to build 7 machine learning classifier algorithms and 9 regression algorithms, and evaluate their performance to identify the best predictive binding models. Evaluation of model accuracy revealed that the top performing classifier model, logistic regression, had an AUROC statistic of 0.936. The top performing regression model, support vector regression, had an R2 of 0.854. These top performing models were then used to predict HSA-PFAS binding for chemicals in the EPAPFASINV list of 430 PFAS. These developed in vitro and in silico methodologies represent a high-throughput framework for predicting protein-PFAS binding based on empirical data, and generate directly comparable binding data of potential use in predictive modeling of PFAS bioaccumulation and other toxicokinetic endpoints.

Alleviation of bovine serum albumin on the neurotoxicity of silver nanoparticles in zebrafish (Danio rerio) larvae

Silver nanoparticles (AgNPs) are ubiquitous in the aquatic environment and have attracted extensive attention to their toxic effects on aquatic species. However, responses of the nervous system to AgNPs are little known, especially co-existing with the ubiquitous natural organic matter (NOM), which is critical for the ability to act in aquatic species. Here, this study investigated the neurotoxicology of environmentally relevant AgNPs with or without bovine serum albumin (BSA; a classical NOM) to zebrafish (Danio rerio) using visualized transgenic zebrafish. Exposure to AgNPs reduced the locomotor behavior of zebrafish by 28%–45%, including swimming distance and velocity, exhibiting obvious behavioral inhibition. The visualized transgenic zebrafish treated with AgNPs showed developmental retardation in the early development of the heart, central nervous, and motor nerve, as well as the related neurodevelopment genes, which may be responsible for the lowered locomotor behavior. In addition, AgNPs can specifically interfere with the cholinergic system and affect neuronal signaling, ultimately leading to behavioral abnormalities. However, the co-existing BSA alleviated the neurotoxicity of AgNPs in zebrafish, which may partially be attributed to the increased size and electronegativity of AgNPs caused by BSA, thus reducing the direct interaction of AgNPs with cells. The interaction between BSA and the released Ag+ from AgNPs may also be responsible for the alleviation of the neurodevelopment dysfunction in zebrafish. These findings provide valuable insights into the toxicity and risks of AgNPs in natural aquatic environments.

Novel extracorporeal treatment for severe neonatal jaundice: a mathematical modelling study of allo-hemodialysis

Severe Neonatal Jaundice (SNJ) causes long-term neurocognitive impairment, cerebral palsy, auditory neuropathy, deafness, or death. We developed a mathematical model for allo-hemodialysis as a potential blood purification method for the treatment of SNJ in term or near-term infants. With allo-hemodialysis (allo-HD), the neonate’s blood flows through hollow fibers of a miniature 0.075 m2 hemodialyzer, while the blood of a healthy adult (“buddy”) flows counter-currently through the dialysate compartment. We simulated the kinetics of unconjugated bilirubin in allo-hemodialysis with neonate blood flow rates of 12.5 and 15 mL/min (for a 2.5 kg and 3.5 kg neonate, respectively), and 30 mL/min for the buddy. Bilirubin production rates in neonate and buddy were set to 6 and 3 mg/kg/day, respectively. Buddy bilirubin conjugation rate was calculated to obtain normal steady-state bilirubin levels. Albumin levels were set to 1.1, 2.1, 3.1 g/dL for the neonate and 3.3 g/dL for the buddy. Model simulations suggest that a 6-h allo-hemodialysis session could reduce neonatal bilirubin levels by > 35% and that this modality would be particularly effective with low neonatal serum albumin levels. Due to the high bilirubin conjugation capacity of an adult’s healthy liver and the larger distribution volume, the buddy’s bilirubin level increases only transiently during allo-hemodialysis. Our modelling suggests that a single allo-hemodialysis session may lower neonatal unconjugated bilirubin levels effectively. If corroborated in ex-vivo, animal, and clinical studies, this bilirubin reduction could lower the risks associated with SNJ, especially kernicterus, and possibly avoiding the morbidity associated with exchange transfusions.

Antifouling ultrafiltration membranes based on acrylic fibers waste/nanochitosan for Congo red and crystal violet removal

AbstractIn this study, acrylic fibers waste blended with different ratios of nanochitosan (0.5%, 1%, 2% and 4%, in weight) were converted into antifouling ultrafiltration nanocomposite membranes using a phase separation technique for the remediation of Congo red (CR) and crystal violet (CV) dyes from water. The fabricated nanocomposite membranes were investigated using Fourier Transform Infrared (FTIR), thermal gravimetric analysis (TGA), X-ray diffraction (XRD) and scanning electron microscope (SEM). The membrane hydrophilicity was estimated using contact angle measurements, which revealed that the 4% loaded nanochitosan had the highest hydrophilicity. Additionally, the water uptake, porosity, water contact angle and water flux of the nanocomposite membranes were assessed. The membrane filtration performances were explored for the removal of CR and CV as anionic and cationic dyes, respectively, at different concentrations and various applied pressures (1 bar to 4 bar). The experimental data revealed a high rejection (R) performance for CR (R≃100%) with a high water flux of about 150 L/(m2·h) to 183 L/(m2·h) for the optimized membrane with 2% nanochitosan at an applied pressure of 4 bar. The rejection for CV showed a variant rejection (70%–99%) at different dye concentrations with fluxes ranging from 93.6 L/(m2·h) to 149.5 L/(m2·h) for the same composite membrane. The composite membrane showed enhanced flux recovery after fouling by bovine serum albumin and was resistant to widespread gram-positive (Staphylococcus aureus) bacteria. Graphical abstract

Exploration of newly synthesized transition metal(II) complexes for infectious diseases.

Aim: In the annals of human history, infectious diseases significantly influencing the collective well-being of people worldwide. Consequently, to identify effective agents for infectious ailments, the octahedral Co(II), Ni(II), Cu(II), Zn(II) complexes of 4-(3-methoxyphenyl)pyrimidin-2-amine and 2-methoxy-1-napthaldehyde based ligand were synthesized and well characterized in the current investigation.Results & methodology: The synthesized compounds were evaluated for anti-TB, anti-inflammatory, antibacterial, antifungal activities by microplate Alamar blue, bovine serum albumin, serial dilution assays. The [Zn(L1)2(H2O)2] complex (5) demonstrates robust potency with 0.0040±0.0007 and 0.0038μmol/ml MIC value in anti-tuberculosis and antimicrobial activities, correspondingly while 06.57±0.03μM IC50 value in anti-inflammatory investigation.Conclusion: Complex (5) show promising potential as targets for pathogen deformities, supported by rigorous biological and computational investigations including pharmacophore modelling, molecular docking (binding score -121.018 and -59.8662kcal/mol for 6H53 and 1CX2 proteins, respectively), DFT (Density functional theory), MESP (MolecularElectrostaticPotential) and ADMET (absorption, distribution, metabolism, excretion and toxicity).

Comparative Feasibility Analysis of Retrograde Double J Stenting, Antegrade Double J Stenting, and Percutaneous Nephrostomy Tube Placement for Ureteric Obstruction Secondary to Pelvic Malignancies

Background: The management of ureteric obstruction secondary to pelvic malignancies (UOPM) presents a significant challenge. Objectives: Our study aimed to assess the factors affecting the feasibility of interventions for patients with UOPM - including retrograde and antegrade double J (DJ) stenting, and percutaneous nephrostomy (PCN) insertion. Methods: We conducted a retrospective analysis of patients who underwent intervention for UOPM over two years, from January 2022 to December 2023. Patients were categorized into groups based on intervention type: Group 1: Retrograde DJ stenting, group 2: Antegrade DJ stenting, and group 3: PCN insertion. Demographic, clinical, radiological, cystoscopic, and laboratory data were compared between the three groups. Analysis of Variance (ANOVA), logistic regression, and marginal mean plots were utilized for statistical analysis. Results: Fifty–nine patients were included in the study, consisting of 14 males and 45 females, and the mean age of the study population was 60.1 ± 10.8 years. Retrograde DJ stenting was successfully achieved in 59.3% of patients, with 10.2% undergoing antegrade DJ stenting and 30.5% needing PCN insertion. Serum albumin (P = 0.04), serum creatinine (P = 0.02), albumin creatinine ratio (P &lt; 0.001), and severity of hydroureteronephrosis (HDUN) (P = 0.02) were significantly associated with intervention outcomes. There was an increased likelihood of PCN insertion in higher serum creatinine and lower serum albumin levels. Multinomial logistic regression with univariate and multivariate analysis revealed significance among the above-mentioned variables. Conclusions: Even though DJ stenting remains common, a significant proportion of patients require PCN insertion. Serum albumin, serum creatinine, albumin creatinine ratio, and HDUN severity are significant predictors of intervention success. Further research is warranted to validate these findings and enhance management strategies for UOPM.

Population Pharmacokinetics of Casirivimab and Imdevimab in Pediatric and Adult Non-Infected Individuals, Pediatric and Adult Ambulatory or Hospitalized Patients or Household Contacts of Patients Infected with SARS-COV-2.

Casirivimab (CAS) and imdevimab (IMD) are two fully human monoclonal antibodies that bind different epitopes on the receptor binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and block host receptor interactions. CAS + IMD and was developed for the treatment and prevention of SARS-CoV-2 infections. A population pharmacokinetic (PopPK) analysis was conducted using pooled data from 7598 individuals from seven clinical studies to simultaneously fit concentration-time data of CAS and IMD and investigate selected covariates as sources of variability in PK parameters. The dataset comprised CAS + IMD-treated pediatric and adult non-infected individuals, ambulatory or hospitalized patients infected with SARS-CoV-2, or household contacts of patients infected with SARS-CoV-2. CAS and IMD concentration-time data were both appropriately described simultaneously by a two-compartment model with first-order absorption following subcutaneous dose administration and first-order elimination. Clearance estimates of CAS and IMD were 0.193 and 0.236 L/day, respectively. Central volume of distribution estimates were 3.92 and 3.82 L, respectively. Among the covariates identified as significant, body weight and serum albumin had the largest impact (20-34%, and ~ 7-31% change in exposures at extremes, respectively), while all other covariates resulted in small differences in exposures. Application of the PopPK model included simulations to support dose recommendations in pediatrics based on comparable exposures of CAS and IMD between different weight groups in pediatrics and adults following weight-based dosing regimens. This analysis provided important insights to characterize CAS and IMD PK simultaneously in a diverse patient population and informed pediatric dose selection.

Site-Selective Biofunctionalization of 3D Microstructures Via Direct Ink Writing.

Two-photon lithography has revolutionized multi-photon 3D laser printing, enabling precise fabrication of micro- and nanoscale structures. Despite many advancements, challenges still persist, particularly in biofunctionalization of 3D microstructures. This study introduces a novel approach combining two-photon lithography with scanning probe lithography for post-functionalization of 3D microstructures overcoming limitations in achieving spatially controlled biomolecule distribution. The method utilizes a diverse range of biomolecule inks, including phospholipids, and two different proteins, introducing high spatial resolution and distinct functionalization on separate areas of the same microstructure. The surfaces of 3D microstructures are treated using bovine serum albumin and/or 3-(Glycidyloxypropyl)trimethoxysilane (GPTMS) to enhance ink retention. The study further demonstrates different strategies to create binding sites for cells by integrating different biomolecules, showcasing the potential for customized 3D cell microenvironments. Specific cell adhesion onto functionalized 3D microscaffolds is demonstrated, which paves the way for diverse applications in tissue engineering, biointerfacing with electronic devices and biomimetic modeling.

Biocompatible WSe2@BSA Dots with Merged Catalyst and Coreactant for Efficient Electrochemiluminescence.

Electrochemiluminescence (ECL) is a powerful tool for clinical diagnosis due to its exceptional sensitivity. However, the standard tripropylamine (TPrA) coreactant for Ru(bpy)3Cl2, the most widely studied and used ECL system, is highly toxic. Despite extensive research on alternative coreactants, they often fall short in poor efficiency. From a reaction kinetics perspective, accelerating electrooxidation rate of Ru(bpy)3Cl2 is an essential way to compensate the efficiency limitation of coreactants, but is rarely reported. Here, a hybrid electrocatalyst@coreactant dots for the ECL of Ru(bpy)3Cl2 is reported. The as-prepared WSe2@bovine serum albumin (WSe2@BSA) dots is biocompatible, and demonstrate dual functions, i.e., the BSA shell works as a coreactant, meanwhile, the WSe2 core effectively catalyzes Ru(bpy)3Cl2 oxidation. As a result, WSe2@BSA dots exhibit an exceptionally high efficiency comparable to TPrA for the ECL of Ru(bpy)3Cl2. In addition, the procedure for synthesizing WSe2@BSA dots is facile (room temperature, atmospheric conditions), rapid (5min), and scalable (for millions of bioassays). A biosensor utilizing WSe2@BSA dots shows promise for highly sensitive detecting glypican-3 in clinical liver cancer serum samples, especially for alpha-fetoprotein-negative patients. This work opens a new avenue for developing a highly efficient ECL system for biosensing and clinical diagnosis.

Theoretical Study of the Effects of Different Coordination Atoms (O/S/N) on Crystal Structure, Stability, and Protein/DNA Binding of Ni(II) Complexes with Pyridoxal-Semi, Thiosemi, and Isothiosemicarbazone Ligand Systems

Nickel transition metal complexes have shown various biological activities that depend on the ligands and geometry. In this contribution, six Ni(II) nitrate complexes with pyridoxal-semi, thiosemi, and isothiosemicarbazone ligands were examined using theoretical chemistry methods. The structures of three previously reported complexes ([Ni(PLSC)(H2O)3]∙2NO3−, [Ni(PLTSC)2] ∙2NO3−∙H2O, and [Ni(PLITSC)(H2O)3]∙2NO3−) were investigated based on Hirshfeld surface analysis, and the most important stabilization interactions in the crystal structures were outlined. These structures were optimized at the B3LYP/6-311++G(d,p)(H,C,N,O,(S))/LanL2DZ(Ni) level of theory, and the applicability was checked by comparing theoretical and experimental bond lengths and angles. The same level of theory was applied for the optimization of three additional structures, ([Ni(PLSC)2]2+, [Ni(PLTSC)(H2O)3]2+, and [Ni(PLITSC)2]2+). The interactions between selected ligands and Ni(II) were examined using the Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) approaches. Particular emphasis was placed on interactions between oxygen, sulfur, and nitrogen donor atoms and Ni(II). Human Serum Albumin (HSA) and the DNA-binding properties of these complex cations were assessed using molecular docking simulations. The presence of water molecules and various substituents in the thermodynamics of the processes was demonstrated. The results showed significant effects of structural parameters on the stability and reactivity towards important biomolecules.