High Molecular Weight Research Articles

Trypsin Encapsulation in the Zeolitic Imidazolate Framework for Low-Molecular Weight Protein Analysis with High Selectivity and Efficiency.

Low-molecular weight proteins (LWPs) are important sources of biological information in biomarkers, signaling molecules, and pathology. However, the separation and analysis of LWPs in complex biological samples are challenging, mainly due to their low abundance and the complex sample pretreatment procedure. Herein, trypsin modified by poly(acrylic acid) (PAA) was encapsulated by a zeolitic imidazolate framework (ZIF-L). Mesopores were formed on the ZIF-L with the introduction of PAA. An alternative strategy for separation and pretreatment of LWPs was developed based on the prepared ZIF-L-encapsulated trypsin with adjustable pore size. The mesoporous structure of the prepared materials selectively excluded high-molecular weight proteins from the reaction system, allowing LWPs to enter the pores and react with the internal trypsin, resulting in an improved separation efficiency. The hydrophobicity of the ZIF-L simplified the digestion process by inducing significant structural changes in substrate proteins. In addition, the enzymatic activity was significantly enhanced by the developed encapsulation method that maintained the enzyme conformation, allowed low mass transfer resistance, and possessed a high enzyme-to-substrate ratio. As a result, the ZIF-L-encapsulated trypsin can achieve highly selective separation, valid denaturation, and efficient digestion of LWPs in a short time by simply mixing with substrate proteins, greatly simplifying the separation and pretreatment process of the traditional hydrolysis method. The prepared materials and the developed strategy demonstrated an excellent size-selective assay performance in model protein mixtures, showing great potential in the application of proteomics analysis.

Synthesis of Cycloaliphatic Polyamides via Palladium-Catalyzed Hydroaminocarbonylative Polymerization.

Polyamides represent one class of materials that is important in modern society. Because of the numerous potential applications of polyamides in various fields, there is a high demand for new polyamide structures, which necessitates the development of new polymerization methods. Herein, we report a novel and efficient palladium-catalyzed hydroaminocarbonylative polymerization of dienes and diamines for the synthesis of cycloaliphatic polyamides. The method employs readily available starting materials, proceeds in an atom-economic manner, and creates a series of new functional polyamides in high yields and high molecular weights. In contrast with the traditional polyamides based on adipic acid, the cycloaliphatic polyamides have superior thermal resistance, higher glass-transition temperature, and better solubility in common organic solvents, thus probably featuring the merits of high-performance and good processability.

Investigation of scaling inhibition and biofouling potential of different molecular weight fractions of a PAA antiscalant

This study investigates the scale inhibition performance of a commercial polyacrylic acid-based (PAA) antiscalant used for drinking water production and its molecular weight fractions (≤ 500 Da, ≥ 500 Da). The investigated antiscalant is used to prevent sulfate and carbonate scaling in treatment of drinking water sources by reverse osmosis or nanofiltration (RO/NF). Based on two complementary tests involving determination of induction time in a batch test and rate of flux decline in a lab-scale RO/NF plant, concordant results were obtained, proving that the overall performance of commercial PAA was controlled almost entirely by the higher molecular weight fraction. The low molecular weight fraction, which is potentially more permeable through the NF/RO membrane, showed poor inhibition against both sulfate and carbonate scalants. Furthermore, measurements on the assimilable organic carbon (AOC) by flow cytometry reveals that the low molecular weight PAA fraction has low biological stability, as its potential transport into the permeate of a NF270 nanofiltration membrane was inferred by elevated AOC values in the NF-permeate. These results are crucial information for water utilities, plant engineering, regulatory bodies and public authorities with respect to the possible operation of RO/NF especially in drinking water production.

PSII-9 Whole genome sequences of two nitrate-reducing strains of Selenomonas ruminantium isolated from the rumen

Abstract Selenomonas ruminantium is a functionally diverse, non-fibrolytic member of the rumen microbial community with two subspecies: lactilytica and ruminantium. Some strains of S. ruminantium can reduce nitrate and nitrite, which may be associated with ruminal fiber degradation and, thus, greater forage diets. Most work done with S. ruminantium has been culture-based, with less genomic and functional data. Here, we performed whole genome sequencing with an Oxford Nanopore GridION on two isolated, nitrate-reducing strains of S. ruminantium to provide complete genomic data and determine the nitrogen usage functional capacities of these novel strains. The two isolated strains, 223 and 231, were shipped on dry ice to the University of Wisconsin-Madison, where they were grown, pelleted, and observed under a microscope to determine purity. The samples were processed with a 3 min bead-beating step before extraction with the Zymo Quick-DNA High Molecular Weight MagBead Kit. Subsequently, the extracted samples underwent a quality assessment step before moving into library preparation for Oxford Nanopore sequencing. The two libraries were then loaded onto two R9.4.1 flow cells per library and were sequenced on an Oxford Nanopore GridION for 72 h. The data were extracted from the GridION, and the combined passed reads from each of the two flow cells per library were assembled with Canu and Flye, long-read de novo genome assemblers designed for noisy, single-molecule sequences. The assembled genomes were compared with a reference S. ruminantium genome with Quast, a quality assessment tool that evaluates assembly accuracy. Finally, the assembled genomes with the highest accuracy were analyzed with prodigal to generate protein-coding gene predictions and then with BLAST to assign functional predictions. For each strain, a different assembly was used. The Canu assembly of strain 223 had greater accuracy rates at 3205.23 mismatches per 100 kbp, while the Flye assembly of strain 231 had 2494.40 mismatches per 100 kbp. The two strains had similar genome sizes: 3,098,553 base pairs for strain 223 and 3,138,614 base pairs for strain 231. Strain 223 had less GC content than strain 231 of 51.02%, while strain 231 had a GC content of 52.80%, which were both less than the 50.68% GC content of the reference genome. These genomes provide a resource for understanding nitrate reduction in the rumen and work to build a better database for analyzing the rumen microbiome.

High-Molecular-Weight Hyaluronic Acid Can Be Used as a Food Additive to Improve the Symptoms of Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS)

Hyaluronic acid (HA) is a new functional food additive which has the potential to ameliorate persistent inflammation, immunosuppression and catabolism syndrome (PICS), but the biological effects of HA with various molecular weights differ dramatically. To systematically investigate the efficacy of HA in altering PICS symptoms, medium-molecular-weight (MMW) HA was specifically selected to test its intervention effect on a PICS mouse model induced by CLP through oral administration, with high-molecular-weight (HMW) and low-molecular-weight (LMW) HA also participating in the experimental validation process. The results of pathological observations and gut flora showed that MMW HA rapidly alleviated lung lesions and intestinal structural changes in PICS mice in the short term. However, although long-term MMW HA administration significantly reduced the proportions of harmful bacteria in gut flora, inflammatory responses in the intestines and lungs of PICS mice were significantly higher in the MMW HA group than in the HMW HA and LMW HA groups. The use of HMW HA not only rapidly reduced the mortality rate of PICS mice but also improved their grip strength and the recovery of spleen and thymus indices. Furthermore, it consistently promoted the recovery of lung and intestinal tissues in PICS mice, and it also assisted in the sustained restoration of their gut microbiota. These effects were superior to those of LMW HA and MMW HA. The experimental results indicate that HMW weight HA has the greatest potential to be an adjunct in alleviating PICS as a food additive, while the safety of other HAs requires further attention.

Effects of UV/H2O2 Degradation on the Physicochemical and Antibacterial Properties of Fucoidan

The applications of fucoidan in the food industry were limited due to its high molecular weight and low solubility. Moderate degradation was required to depolymerize fucoidan. A few studies have reported that fucoidan has potential antibacterial activity, but its antibacterial mechanism needs further investigation. In this study, the degraded fucoidans were obtained after ultraviolet/hydrogen peroxide treatment (UV/H2O2) at different times. Their physicochemical properties and antibacterial activities against Staphylococcus aureus and Escherichia coli were investigated. The results showed that the average molecular weights of degraded fucoidans were significantly decreased (up to 22.04 times). They were mainly composed of fucose, galactose, and some glucuronic acid. Fucoidan degraded for 90 min (DFuc-90) showed the strongest antibacterial activities against Staphylococcus aureus and Escherichia coli, with inhibition zones of 27.70 + 0.84 mm and 9.25 + 0.61 mm, respectively. The minimum inhibitory concentrations (MIC) were 8 mg/mL and 4 mg/mL, respectively. DFuc-90 could inhibit the bacteria by damaging the cell wall, accumulating intracellular reactive oxygen species, reducing adenosine triphosphate synthesis, and inhibiting bacterial metabolic activity. Therefore, UV/H2O2 treatment could effectively degrade fucoidan and enhance its antibacterial activity.

Folate-PEG-PROTAC Micelles for Enhancing Tumor-Specific Targeting Proteolysis In Vivo.

Proteolysis targeting chimeras (PROTACs) technology is rapidly developed as a novel and selective medicinal strategy for the degradation of cellular proteins in cancer therapy. However, the applications of PROTACs as heterobifunctional molecules are largely limited by high molecular weight, low bioavailability, poor permeability, insufficient targeting, and low efficacy in vivo. Herein, self-assembling micelles of FA-PEG-PROTAC are designed for cancer cell selective targeting and reductive-response proteolysis in tumor-bearing mice. FA-PEG-PROTAC is prepared by conjugating folic acid (FA)-PEG with EGFR-targeting PROTAC via a disulfide bond. The FA-PEG-PROTAC micelles, formed by self-assembling, are demonstrated to significantly improve tumor targeting efficacy and exhibit excellent anti-tumor efficacy in the mouse xenograft model compared to the traditional PROTACs. The strategy of applying self-assembled FA-PEG-PROTAC micelles in tumor therapy can not only improve targeted proteolysis efficiency but also broaden applications in the development of PROTAC-based drugs.

Graphite counter electrode modified Tropaeolin‐O photo‐sensitized photogalvanic cells for solar power and storage

AbstractAn optimization, photo‐stability, and hysteresis property of the Graphite counter electrode‐modified Tropaeolin‐O (TPO) photo‐sensitized photogalvanic (PG) cells has been investigated. A complex H‐shaped cell design, a costly and delicate saturated calomel electrode (counter electrode), and a heavy sensitizer molecule (dye having high molecular weight, low diffusivity, and low photo‐stability) have been exploited for fabricating most of the PG cells so far. All these factors are not suitable for the fabrication of durable and cheap PG cells. Therefore, in the present study, the highly conductive/catalytically active robust graphite electrode with TPO dye photosensitizer (having a low molecular weight, higher diffusivity, and higher photo‐stability) has been exploited with diffusion‐friendly low cost and a simple transparent cylindrical glass tube. The cheap and robust graphite counter electrode has been exploited for optimization and long‐term study of the TPO photo‐sensitized PG cells. The observed electrical output is potential 676 mV, current 2000 µA, and power 340.0 μW. The power, current, and efficiency, have been found quite independent of the illumination window size. The potential and current have been observed to be quite stable over a long time during illumination, and the same has been supported by the hysteresis study.

Template Assisted Synthesis of Linear [5]Catenane by Post-Functionalization of Templated [2]Catenane and Using Click Reaction.

Polymers with all mechanically interlocked rings, such as linear [n]catenanes, have great potential as functional materials due to possible higher degrees of freedom that may contribute to their flexibility but remain elusive. All the synthetic methods used to prepare such a polymer yield mixtures of products.In the absence of higher molecular weight linear [n]catenanes, emphasis on synthesizing low molecular weight oligomers is being pursued. Here, we have described the synthesis of a linear [5]catenane by post-functionalizing a Co(III) templated [2]catenane having a pyridine-diamide unit free for further metal ion coordination. Two molecules were synthesized with suitable threading groups: one, two terminal azide groups, and two, with two terminal alkyne groups to form two [3]pseudorotaxane utilizing Co(III) coordination. These units were then joined, forming a macrocycle, using click reaction, giving the desired metallated linear [5]catenane in 40% yield. Removal of metal ions leads to linear [5]catenane. In addition, the formation of linear [3] and [2]catenane are also observed. All synthesized structures have been isolated by column chromatographic technique and characterized by1H-NMR,13C-NMR, and mass spectroscopy.

Survey of pharmaceutical industry's best practices around in vitro transporter assessment and Implications for Drug Development: Considerations from the IQ Transporter Working Group.

The IQ Transporter Working Group had a rare opportunity to analyse a cross-pharma collation of in vitro data and assay methods for the evaluation of drug transporter substrate and inhibitor potential. Experiments were generally performed in accordance with regulatory guidelines. Discrepancies, such as not considering the impact of pre-incubation for inhibition and free or measured in vitro drug concentrations, may be due to the retrospective nature of the dataset and analysis. Lipophilicity was a frequent indicator of cross-transport inhibition (P-gp, BCRP, OATP1B and OCT1) with high molecular weight ({greater than or equal to}500 Da) also common for OATP1B and BCRP inhibitors. A high level of overlap in in vitro inhibition across transporters was identified for BCRP, OATP1B1 and MATE1 suggesting that prediction of DDIs for these transporters will be common. In contrast inhibition of OAT1 did not coincide with inhibition of any other transporter. Neutrals, bases, and compounds with intermediate-high lipophilicity tended to be P-gp and/or BCRP substrates whilst compounds with MW <500 Da tended to be OAT3 substrates. Interestingly the majority of in vitro inhibitors were not reported to be followed up with a clinical study by the submitting company, whilst those compounds identified as substrates generally were. Approaches to metabolite testing were generally found to be similar to parent testing with metabolites generally being equally or less potent than parent compounds. However, examples where metabolites inhibited transporters in vitro were identified supporting the regulatory requirement for in vitro testing of metabolites to enable integrated clinical DDI risk assessment. Significance Statement A diverse dataset showed transporter inhibition often correlated with lipophilicity and molecular weight (>500 Da). Overlapping transporter inhibition was identified, particularly that inhibition of BCRP, OATP1B1 and MATE1 was frequent if the compound inhibited other transporters. In contrast inhibition of OAT1 did not correlate with the other drug transporters tested.

Macrocrowding of Polyethylene Glycol Facilitates the Formation of Polydopamine Nanoparticles and Derivatives via Depletion Stabilization

Mussel‐inspired polydopamine nanoparticles (PDA NPs) show promise in biosensing, drug delivery, and energy storage. However, it is still difficult to obtain monodispersed PDA NPs and metal‐containing PDA NPs in mild aqueous conditions. Herein, we report a facile strategy to modulate the growth and formation of PDA NPs in a macrocrowding condition using inert polymers as crowders. Our results show that both high concentrations and molecular weights are important for polymer‐enabled particle stabilization. Importantly, we demonstrate that only polymers with a weak interaction with PDA could facilitate PDA NPs formation. Lastly, we show that this strategy could be extended to metal‐containing PDA derivatives, and enzyme‐encapsulated PDA NPs. Overall, our findings offer a simple and effective approach for producing uniform biocompatible nanomaterials, while also shedding light on the role of depletion forces in nanoparticle stabilization in solution.

A facile and scalable method to synthesize PEGylated PDMAEMA for gene delivery.

In recent years, cationic polymer vectors have been viewed as a promising method for delivering nucleic acids. With the advancement of synthetic polymer chemistry, we can control chemical structures and properties to enhance the efficacy of gene delivery. Herein, a facile, cost-effective, and scalable method was developed to synthesize PEGylated PDMAEMA polymers (PEO-PDMAEMA-PEO), where PEGylation could enable prolonged polyplexes circulation time in the blood stream. Two polymers of different molecular weights were synthesized, and polymer/eGFP polyplexes were prepared and characterized. The correlation between polymers' molecular weight and physicochemical properties (size and zeta potential) of polyplexes was investigated. Lipofectamine 2000, a commercial non-viral transfection reagent, was used as a standard control. PEO-PDMAEMA-PEO with higher molecular weight exhibited slightly better transfection efficiency than Lipofectamine 2000, and the cytotoxicity study proved that it could function as a safe gene vector. We believe that PEO-PDMAEMA-PEO could serve as a model to investigate more potential in the gene delivery area.

Integrated neuromuscular training intervention applied in schools induces a higher increase in salivary high molecular weight adiponectin and a more favorable body mass index, cardiorespiratory fitness and muscle strength in children as compared to the traditional physical education classes

BackgroundHigh-molecular-weight adiponectin (HMW-adiponectin) is a cardio-metabolic health protector. Objectives: (1) to compare body mass index (BMI), cardiorespiratory fitness (CRF) and muscle strength (MS) in healthy school-children depending on their baseline salivary-HMW-adiponectin concentration; and (2) to apply a 3-month integrated neuromuscular training (INT) and evaluate its effects on salivary-HMW-adiponectin concentration, BMI, CRF and MS in the same children. Additional goal: to identify if any potential changes during the 3-month period may be related to a potential change in salivary-HMW-adiponectin concentration.MethodsNinety children (7.4 ± 0.3 years) were recruited in primary schools and randomly allocated into control or intervention group. The intervention consisted of a 3-month INT applied during physical education (PE) classes, twice-weekly, while the control group had traditional PE classes. Body mass and height were measured, BMI was calculated and HMW-adiponectin was quantified in saliva. To assess CRF and MS, 800 m-run and hand-dynamometry were applied, respectively. All measurements were performed twice, at baseline and after 3 months.ResultsChildren with higher baseline salivary-HMW-adiponectin have more favorable BMI (p = 0.006) and slightly higher CRF (p = 0.017) in comparison to the children with lower baseline salivary-HMW-adiponectin. There were no big changes after the 3-month-period neither in the control, nor the INT group. However, it is worthy to note that the INT induced slightly higher increase in salivary-HMW-adiponectin (p = 0.007), and a slightly higher improvement in BMI (p = 0.028), CRF (p = 0.043) and MS (p = 0.003), as compared to the traditional PE classes. Finally, the INT-induced improvement in CRF was associated with the increased post-salivary-HMW-adiponectin concentration (p = 0.022).ConclusionMain findings may suggest the potential utility of an INT as a cost-effective strategy that can be applied in schools to induce cardio-protective effects in school-children.

Abstract PO4-25-08: Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population

Abstract Secretory breast carcinoma (SBC) is a rare and distinct disease, comprising approximately 0.01% of all breast carcinomas. This is a case of an 8-year-old boy who presented with a 1.5-year history of a non-tender, slowly enlarging left subareolar mass, not associated with nipple discharge. Serologic workup revealed minimally elevated prolactin with normal-range FSH, LH, estradiol and testosterone, as well as normal-range beta-hCG, LDH and AFP. Ultrasound showed a circumscribed solid hypoechoic lesion with internal arterial vascularity, favoured to represent a sebaceous cyst. Excisional biopsy was performed, and histologic examination revealed the classic intra- and extracellular secretory material typically seen in SBC. Immunohistochemical (IHC) stains for mammaglobin, S-100 and high molecular weight keratin (CK5) were positive. ER was positive, though not strong staining, and PR and HER2 were negative. A screen for NTRK fusions with pan-TRK IHC was positive. No skin, perineural or lymphovascular invasion was identified. RNA-based NGS demonstrated ETV6-NTRK3 fusion and confirmed the diagnosis of SBC. The patient underwent mastectomy and SLNB, which showed no residual tumor and no positive lymph nodes. A full metastatic work-up was not performed and the patient did not receive neoadjuvant therapy. First described as “juvenile breast carcinoma,” SBC has since been recognized to occur across a wide age range, with most cases occurring in adults. SBC in male pediatric patients is exceptionally rare, with fewer than 20 cases reported in the literature. In this demographic, SBC is usually detected clinically as a subareolar mass not associated with nipple discharge, and appears as a well-circumscribed mass on imaging, mimicking benign entities. SBC is usually detected at a low stage, treated surgically, and follows a clinically indolent course with excellent outcomes. Positive axillary nodes have been identified in a few male children, who subsequently underwent chemo- and/or radiotherapy, with no recorded recurrences in these cases. Distant metastases are an extremely uncommon feature of SBC and have not been reported in the pediatric male population; however, due to the rarity of this diagnosis, particularly in this demographic, robust long-term follow-up data are still lacking. The name “secretory” derives from the histologic appearance of the dense eosinophilic secretory material seen in tumor lumina and bubbly material in the cytoplasm of tumor cells. Similar to the cytologic characteristics of other translocation-driven neoplasms, SBC shows minimal pleomorphism. Mitoses are absent or rare. IHC stains are typically positive for S-100 and high molecular weight keratins and negative for ER, PR, and HER2. Despite the immunophenotypic similarities to triple negative/basal-like carcinomas (TNBC/BLC) the molecular relationship between SBC and TNBC/BLC is unclear. Though initially defined by its distinctive secretions on histology, SBC is now chiefly characterized by a balanced translocation, t(12;15)(p13;q25), resulting in oncogenic ETV6-NTRK3 fusion. Recent cases have demonstrated this using a variety of molecular techniques, including FISH, RT-PCR, and in our case, RNA-based NGS. This translocation also characterizes non-breast secretory carcinomas and has been identified in several other neoplasms, including pediatric mesenchymal tumours and adult acute myeloid leukemia. The rarity of SBC, particularly in the male pediatric population, underlines the necessity of this case report. Additionally, this case highlights the importance of considering SBC as a potential diagnosis in male children presenting with a breast mass, even in the presence of benign imaging characteristics. Table 1: Clinicoradiologic and pathomolecular characteristics of SBC in pediatric males AND, axillary node dissection; CT, chemotherapy; ER, estrogen receptor; FISH, fluorescence in situ hybridization; LE, local excision; MRM, modified radical mastectomy; nd, no data; NED, no evidence of disease; NGS, next-generation sequencing; NS, nodal sampling; PA, periareolar; PR, progesterone receptor; RA, retroareolar; RM, radical mastectomy; PCR, polymerase chain reaction; RT, radiotherapy; SA, subareolar; SLNB, sentinel lymph node biopsy; SM, simple mastectomy; WLE, wide local excision *Not reported as strong staining Table 2: Immunohistochemical phenotype of secretory breast carcinoma EMA, epithelial membrane antigen; ER, estrogen receptor; PR, progesterone receptor *Not reported as strong staining Table 3: Laboratory investigations AFP, alpha fetoprotein; FSH, follicle stimulating hormone; hCG, human chorionic gonadotropin; LDH, lactate dehydrogenase; LH, luteinizing hormone Citation Format: Rebecca Brassington, Svetlana Silverman, Ioana Bratu. Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-08.

Mitral regurgitation is associated with similar loss of von Willebrand factor large multimers, but less anemia as compared to aortic stenosis

BackgroundVarious cardiovascular diseases cause acquired von Willebrand syndrome (AVWS), which is characterized by a decrease in high molecular weight (large) von Willebrand factor (VWF) multimers. Mitral regurgitation (MR) has been reported as a cause of AVWS. However, much remains unclear about AVWS associated with MR. ObjectivesTo evaluate VWF multimers in MR patients and examine their impact on clinical characteristics. MethodsModerate or severe MR patients (n=84) were enrolled. VWF parameters such as the VWF large multimer index (VWF-LMI), a quantitative value that represents the amount of VWF large multimers, and clinical data were prospectively analyzed. ResultsAt baseline, the mean hemoglobin level was 12.9 ± 1.9 g/dL and 58 patients (69.0%) showed loss of VWF large multimers defined as VWF-LMI < 80%. VWF-LMI in patients with degenerative MR exhibited lower than those with functional MR. VWF-LMI appeared to be restored the day after mitral valve intervention and the improvement was maintained 1 month after the intervention. Seven patients (8.3%) had a history of bleeding, 6 (7.1%) of whom had gastrointestinal bleeding. Gastrointestinal endoscopy was performed in 23 patients (27.4%) to investigate overt gastrointestinal bleeding, anemia, etc. Angiodysplasia was detected in 2 of the 23 patients (8.7%). ConclusionModerate or severe MR is frequently associated with loss of VWF large multimers and degenerative MR may cause more severe loss compared to functional MR. Mitral valve intervention corrects the loss of VWF large multimers. Gastrointestinal bleeding may be relatively less frequent and hemoglobin level remains stable in MR patients.

Linking Dissolved Organic Matter Composition to Landscape Properties in Wetlands Across the United States of America

AbstractWetlands are integral to the global carbon cycle, serving as both a source and a sink for organic carbon. Their potential for carbon storage will likely change in the coming decades in response to higher temperatures and variable precipitation patterns. We characterized the dissolved organic carbon (DOC) and dissolved organic matter (DOM) composition from 12 different wetland sites across the USA spanning gradients in climate, landcover, sampling depth, and hydroperiod for comparison to DOM in other inland waters. Using absorption spectroscopy, parallel factor analysis modeling, and ultra‐high resolution mass spectroscopy, we identified differences in DOM sourcing and processing by geographic site. Wetland DOM composition was driven primarily by differences in landcover where forested sites contained greater aromatic and oxygenated DOM content compared to grassland/herbaceous sites which were more aliphatic and enriched in N and S molecular formulae. Furthermore, surface and porewater DOM was also influenced by properties such as soil type, organic matter content, and precipitation. Surface water DOM was relatively enriched in oxygenated higher molecular weight formulae representing HUPHigh O/C compounds than porewaters, whose DOM composition suggests abiotic sulfurization from dissolved inorganic sulfide. Finally, we identified a group of persistent molecular formulae (3,489) present across all sites and sampling depths (i.e., the signature of wetland DOM) that are likely important for riverine‐to‐coastal DOM transport. As anthropogenic disturbances continue to impact temperate wetlands, this study highlights drivers of DOM composition fundamental for understanding how wetland organic carbon will change, and thus its role in biogeochemical cycling.

Optimization and Techno-Economic analysis of catalytic gasification of wheat straw biomass using ASPEN PLUS model

Biomass gasification efficiently produces heat, electricity, and power. However, removing harmful contaminants from raw syngas is crucial. Tar production is a challenge due to blockage, plugging, and corrosion. Tar steam reforming (TSR) is the most promising technique, converting high molecular weight hydrocarbons into CO, CO2, H2, and CH4. In this study, a model of biomass gasification using wheat straw as biomass feedstock has been developed using Aspen Plus. The gasification flow sheet encompasses gasification, catalytic filter candle, gas cleaning, impurity removal reactor, separator, and subsequent sorbent reactors. Ni-based catalysts with Ni ratios (5%, 10%, and 15%) are used to simulate TSR reactions. Results show that the 15% Ni-Co-Al2O3 catalyst outperforms the 10% and 5% Ni-Co-Al2O3 catalysts. This study explores the impact of temperature, catalyst loadings, and steam-to-carbon (S/C) ratios on toluene conversion and hydrogen yield in catalytic steam reforming, along with temperature, steam-to-biomass ratios, and equivalence ratio on syngas fraction in gasification. It includes a techno-economic analysis of wheat straw gasification to improve syngas energy through efficient tar conversion.

Biodistribution of Native and Nanoformulated Innate Defense Regulator Peptide 1002.

Innate defense regulator-1002 (IDR-1002) is a synthetic peptide with promising immunomodulatory and antibiofilm properties. An appreciable body of work exists around its mechanism of action at the cellular and molecular level, along with its efficacy across several infection and inflammation models. However, little is known about its absorption, distribution, and excretion in live organisms. Here, we performed a comprehensive biodistribution assessment with a gallium-67 radiolabeled derivative of IDR-1002 using nuclear tracing techniques. Various dose levels of the radiotracer (2-40 mg/kg) were administered into the blood, peritoneal cavity, and subcutaneous tissue, or instilled into the lungs. The peptide was well tolerated at all subcutaneous and intraperitoneal doses, although higher levels were associated with delayed absorption kinetics and precipitation of the peptide within the tissues. Low intratracheal doses were rapidly absorbed systemically, and small increases in the dose level were lethal. Intravenous doses were rapidly cleared from the blood at lower levels, and upon escalation, were toxic with a high proportion of the dose accumulating within the lung tissue. To improve biocompatibility and prolong its circulation within the blood, IDR-1002 was further formulated onto high molecular weight hyperbranched polyglycerol (HPG) polymers. Constructs prepared at 5:1 and 10:1 peptide-to-polymer ratios were colloidally stable, maintained the biological profile of the peptide payload and helped reduce red blood cell lysis. The 5:1 construct circulated well in the blood, but higher peptide loading was associated with rapid clearance by the reticuloendothelial system. Many peptides face pharmacokinetic and biocompatibility challenges, but formulations such as those with HPG have the potential to overcome these limitations.

Analytical data of Acacia nilotica var. Nilotica gum

This study aimed to characterize the exudate gum from Acacia nilotica var. nilotica in Sudan and compare its physicochemical properties to Acacia seyal var. seyal and Acacia senegal var. senegal (gum Arabic). Samples were collected from six different states in Sudan over three seasons. The gum had a moisture content of 10.50%, ash content of 1.86%, pH value of 5.19, specific optical rotation of +94.70, intrinsic viscosity of 10.44 cm3 g-1, nitrogen content of 0.024%, protein content of 0.16%, acid equivalent weight of 1907.82, and total uronic acid content of 10.18%. Sugar content analysis revealed arabinose (41.20%), galactose (17.43%), and rhamnose (10.68%). Potassium was the predominant cation, followed by calcium, magnesium, sodium, lead, and iron. Acacia nilotica was classified as part of the Gummeferae series and exhibited a positive specific optical rotation. The Number average molecular weight (Mn) was estimated using osmometric measurements and gel permeation chromatography. The gum had a higher molecular weight and lower intrinsic viscosity compared to gum Arabic, suggesting a spheroidal shape of molecule. Amino acid analysis showed similarities with gum Arabic, with hydroxyproline and serine as principal amino acids. Variations in cationic composition were attributed to differences in soil type among collection locations. KEY WORDS: Physicochemical characterization, Acacia senegal var. senegal gum, Acacia seyal var. seyal gum, Acacia nilotica var. nilotica gum, gammiferae Bull. Chem. Soc. Ethiop. 2024, 38(4), 839-852.                                                          DOI: https://dx.doi.org/10.4314/bcse.v38i4.2

Discovery of a New Anti-Inflammatory Agent from Anemoside B4 Derivatives and Its Therapeutic Effect on Colitis by Targeting Pyruvate Carboxylase.

Anemoside B4 (AB4), a triterpenoidal saponin from Pulsatilla chinensis, shows significant anti-inflammatory activity, and may be used for treating inflammatory bowel disease (IBD). Nevertheless, its application is limited due to its high molecular weight and pronounced water solubility. To discover new effective agents for treating IBD, we synthesized 28 AB4 derivatives and evaluated their cytotoxic and anti-inflammatory activities in vitro. Among them, A3-6 exhibited significantly superior anti-inflammatory activity compared to AB4. It showed a significant improvement in the symptoms of DSS-induced colitis in mice, with a notably lower oral effective dose compared to AB4. Furthermore, we discovered that A3-6 bound with pyruvate carboxylase (PC), then inhibited PC activity, reprogramming macrophage function, and alleviated colitis. These findings indicate that A3-6 is a promising therapeutic candidate for colitis, and PC may be a potential new target for treating colitis.