Appearance of Recalcitrant Dissolved Black Carbon and Dissolved Organic Sulfur in River Waters Following Wildfire Events.

Increasing wildfire frequency, a consequence of global climate change, releases incomplete combustion byproducts such as aquatic pyrogenic dissolved organic matter (DOM) and black carbon (DBC) into waters, posing a threat to water security. In August 2022, a series of severe wildfires occurred in Chongqing, China. Samples from seven locations along the Yangtze and Jialing Rivers revealed DBC, quantified by the benzene poly(carboxylic acid) (BPCA) method, comprising 9.5-19.2% of dissolved organic carbon (DOC). High concentrations of BPCA-DBC with significant polycondensation were detected near wildfire areas, likely due to atmospheric deposition driven by wind. Furthermore, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) revealed that wildfires were associated with an increase in condensed aromatics, proteins, and unsaturated hydrocarbons, along with a decrease in lignins. The condensed aromatics primarily consisted of dissolved black nitrogen (DBN), contributing to abundant high-nitrogen-containing compounds in locations highly affected by wildfires. Meanwhile, wildfires potentially induced the input of recalcitrant sulfur-containing protein-like compounds, characterized by high oxidation, aliphatic nature, saturation, and low aromaticity. Overall, this study revealed the appearance of recalcitrant DBC and dissolved organic sulfur in river waters following wildfire events, offering novel insights into the potential impacts of wildfires on water quality and environmental biogeochemistry.

Development of prognostic models for predicting 90-day neurological function and mortality after cardiac arrest.

BACKGROUND: The survivors of cardiac arrest experienced vary extent of hypoxic ischemic brain injury causing mortality and long-term neurologic disability. However, there is still a need to develop robust and reliable prognostic models that can accurately predict these outcomes. OBJECTIVES: To establish reliable models for predicting 90-day neurological function and mortality in adult ICU patients recovering from cardiac arrest. METHODS: We enrolled patients who had recovered from cardiac arrest at Binhaiwan Central Hospital of Dongguan, from January 2018 to July 2021. The study's primary outcome was 90-day neurological function, assessed and divided into two categories using the Cerebral Performance Category (CPC) scale: either good (CPC 1-2) or poor (CPC 3-5). The secondary outcome was 90-day mortality. We analyzed the relationships between risk factors and outcomes individually. A total of four models were developed: two multivariable logistic regression models (models 1 and 2) for predicting neurological function, and two Cox regression models (models 3 and 4) for predicting mortality. Models 2 and 4 included new neurological biomarkers as predictor variables, while models 1 and 3 excluded. We evaluated calibration, discrimination, clinical utility, and relative performance to establish superiority between the models. RESULTS: Model 1 incorporates variables such as gender, site of cardiopulmonary resuscitation (CPR), total CPR time, and acute physiology and chronic health evaluation II (APACHE II) score, while model 2 includes gender, site of CPR, APACHE II score, and serum level of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1). Model 2 outperforms model 1, showcasing a superior area under the receiver operating characteristic curve (AUC) of 0.97 compared to 0.83. Additionally, model 2 exhibits improved accuracy, sensitivity, and specificity. The decision curve analysis confirms the net benefit of model 2. Similarly, models 3 and 4 are designed to predict 90-day mortality. Model 3 incorporates the variables such as site of CPR, total CPR time, and APACHE II score, while model 4 includes APACHE II score, total CPR time, and serum level of UCH-L1. Model 4 outperforms model 3, showcasing an AUC of 0.926 and a C-index of 0.830. The clinical decision curve analysis also confirms the net benefit of model 4. CONCLUSIONS: By integrating new neurological biomarkers, we have successfully developed enhanced models that can predict 90-day neurological function and mortality outcomes more accurately.

Three New Xanthones from Hypericum scabrum and Their Quorum Sensing Inhibitory Activities against Chromobacterium violaceum.

Quorum sensing (QS) plays an important role in the production of virulence factors and pathogenicity in pathogenic bacteria and is, therefore, a hopeful target to fight against bacterial infections. During our search for natural QS inhibitors, two new xanthonolignoids (1 and 2), each existing as a racemic mixture, one new simple oxygenated xanthone (7), and eight known analogs (3-6, 8-11) were isolated from Hypericum scabrum Linn. Chiral separation of 1 yielded a pair of enantiomers 1a and 1b. The structures of these compounds were elucidated by spectroscopic analysis and ECD (electrostatic circular dichroism) calculations. All isolates were evaluated for their QS inhibitory activity against Chromobacterium violaceum. Both 9 and 10 exhibited the most potent QS inhibitory effects with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 31.25 and 62.5 µM, respectively. Crystal violet staining was used to further evaluate the biofilm inhibition potential of compounds 7, 9 and 10, and the formation of biofilms increased with decreasing drug concentration in a classic dose-dependent manner. The results of a cytotoxicity assay revealed that compounds 7, 9 and 10 exhibited no cytotoxic activity on PC-12 cells at the tested concentration.

Monoterpenoid Glycosides from the Leaves of Ligustrum robustum and Their Bioactivities.

The leaves of Ligustrum robustum have been applied as Ku-Ding-Cha, a functional tea to clear heat, remove toxins, and treat obesity and diabetes, in Southwest China. The phytochemical research on the leaves of L. robustum led to the isolation and identification of eight new monoterpenoid glycosides (1-8) and three known monoterpenoid glycosides (9-11). Compounds 1-11 were tested for the inhibitory activities on fatty acid synthase (FAS), α-glucosidase, α-amylase, and the antioxidant effects. Compound 2 showed stronger FAS inhibitory activity (IC50: 2.36 ± 0.10 µM) than the positive control orlistat (IC50: 4.46 ± 0.13 µM), while compounds 1, 2, 5 and 11 displayed more potent ABTS radical scavenging activity (IC50: 6.91 ± 0.10~9.41 ± 0.22 µM) than the positive control L-(+)-ascorbic acid (IC50: 10.06 ± 0.19 µM). This study provided a theoretical basis for the leaves of L. robustum as a functional tea to treat obesity.

Non-classical cardenolides from Calotropis gigantea exhibit anticancer effect as HIF-1 inhibitors.

Six new non-classical cardenolides (1-6), and seventeen known ones (7-23) were isolated from Calotropis gigantea. All cardenolides showed inhibitory effect on hypoxia inducible factor-1 (HIF-1) transcriptional activity with IC50 of 8.85 nM-16.69 µM except 5 and 7. The novel 19-dihydrocalotoxin (1) exhibited a comparable HIF-1 inhibitory activity (IC50 of 139.57 nM) to digoxin (IC50 of 145.77 nM), a well-studied HIF-1 inhibitor, and 11, 12, 14, 16 and 19 presented 1.4-15.4 folds stronger HIF-1 inhibition than digoxin. 1 and 11 showed a dose-dependent inhibition on HIF-1α protein, which led to their HIF-1 suppressing effects. Compared with LO2 and H9c2 normal cell lines, both 1 and 11 showed selective cytotoxicity against various cancer cell lines including HCT116, HeLa, HepG2, A549, MCF-7, A2780 and MDA-MB-231. Moreover, a comprehensive structure-activity relationship was concluded for these non-classical cardenolides as HIF-1 inhibitors, which may shed some light on the rational design and development of cardenolide-based anticancer drugs.

Lycosquarrines A-R, Lycopodium Alkaloids from Phlegmariurus squarrosus.

Eighteen new Lycopodium alkaloids, lycosquarrines A-R (1-18), and eight known alkaloids were isolated from the aerial parts of Phlegmariurus squarrosus. Compounds 1-5 and 19, identified from natural sources for the first time, are uncommon lycopodine-type alkaloids with ß-oriented H-4. Pentacyclic 4 and 5 represent the first examples of 5,12- and 5,11-epoxy Lycopodium alkaloids, respectively, and an epoxide-opening cyclization reaction is suggested to be a key step in their biosynthesis. Compound 18 possesses the same carbon skeleton as carinatine A (22), which was previously reported as a unique Lycopodium alkaloid with a 5/6/6/6 ring system. X-ray crystallographic data analysis was used to determine the absolute configuration of 18, leading to the establishment of the absolute configuration of 22 by comparison of the ECD spectra. An anti-acetylcholinesterase activity assay showed that 11 and 20 exhibited inhibitory activities with IC50 values of 4.2 and 2.1 µM, respectively.

Linking Exoproteome Function and Structure to Anammox Biofilm Development.

Extracellular proteins are of paramount importance in the cell-cell interactions of anammox biofilms. However, the inherent aggregation mechanisms of anammox have largely remained elusive. Herein, using a quartz sand extraction protocol and follow-up iTRAQ-based quantitative proteomics, we identified 367 extracellular proteins from initial colonizers, mature biofilm, and detached biofilm. The extracellular proteins were mainly membrane-associated. Most of the recovered proteins (226, 72.5%) originated from the phylum Planctomycetes. In summary, 215 and 190 of the 367 proteins recovered were up- and/or downregulated at least 1.2-fold during the biofilm formation and detachment periods, respectively. These differentially expressed proteins were dominantly involved in metal ion binding, which was regarded as strong evidence for their abilities to enhance ionic bridges in extracellular polymeric substances (EPS). Scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX) analysis of the biofilms further showed substantial levels of calcium and iron minerals. Critically, representative Sec-dependent secretory proteins affiliated with coccoid Planctomycetes, rod-shaped Proteobacteria, and filamentous Chloroflexi (11, 4, and 2 with differential expression, respectively) were found to have typical and abundant inner ß-sheet structures, wherein hydrophobic moieties can promote anammox aggregation. Overall, these findings highlight links between differentially expressed protein functions and morphologic traits of anammox consortia during biofilm development.

Functional Determinants of Extracellular Polymeric Substances in Membrane Biofouling: Experimental Evidence from Pure-Cultured Sludge Bacteria.

The aim of this work was to better understand the roles of extracellular polymeric substances (EPS) in membrane biofouling at the single-strain level. In the present study, a total of 23 bacterial strains were isolated from a sludge sample. The EPS extracted from pure-cultured bacteria were assessed for their fouling potentials and were simultaneously analyzed using Fourier transform infrared spectroscopy (FTIR). Further, the impact of calcium on the chemical composition of EPS and membrane fouling behavior was investigated in a strain-dependent manner. The EPS of the 23 bacterial strains exhibited different IR features for protein and polysaccharide regions. In addition, an α-1,4-glycosidic linkage (920 cm-1) and amide II (1,550 cm-1) correlated very well with the fouling potentials of all pure-cultured bacteria. In contrast to low-fouling strains, medium- and high-fouling strains exhibited two distinct peaks at 1,020 cm-1 (uronic acids) and 1,250 cm-1 (O-acetyl), which accelerate membrane fouling given their gelling capacities. In the presence of calcium, the fouling potential of a high-fouling strain (Bacillus sp. strain JSB10) was profoundly reduced (P < 0.0005) due to the binding activity of an α-1,4-glycosidic linkage and amide II with calcium. However, the impact of calcium on a low-fouling strain (Vagococcus sp. strain JSB21) was insignificant. Two-dimensional FTIR correlation spectroscopic (2D-FTIR-COS) analysis further revealed that the susceptibilities of functional groups to calcium largely relied on the composition and abundance of the above-described functional groups in EPS. These findings suggest that bacterial strains with different fouling potentials exhibit varied responses to calcium.IMPORTANCE Membrane biofouling is one of the main challenges for the operation of membrane-based processes used for water and wastewater treatment. This study revealed the functional determinants of EPS in membrane biofouling of 23 bacterial strains isolated from a full-scale membrane bioreactor (MBR) plant. We found that an α-1,4-glycosidic bond, amide II, and uronic acids of EPS significantly correlated with the fouling potentials of bacteria. The roles of these EPS groups in membrane fouling were impacted by calcium resulting from EPS-calcium interactions. In addition, our results also demonstrated that any perturbations in the sludge bacterial community in MBRs can lead to varied filtration potentials of the bulk liquor.

Unveiling the Susceptibility of Functional Groups of Poly(ether sulfone)/Polyvinylpyrrolidone Membranes to NaOCl: A Two-Dimensional Correlation Spectroscopic Study.

A clear understanding of membrane aging process is essential for the optimization of chemical cleaning in membrane-based facilities. In this study, two-dimensional (2D) Fourier transformation infrared (FTIR) correlation spectroscopy (CoS) analysis was first used to decipher the sequential order of functional group changes of NaOCl-aged poly(ether sulfone)/polyvinylpyrrolidone (PES/PVP) membranes. The synchronous maps showed 12 major autopeaks in total. Based on the asynchronous maps, a similar aging sequence of membrane groups was clearly identified at three pHs (i.e., 6, 8, and 10): 1463, 1440, and 1410 (cyclic C-H structures) > 1662 (amide groups) > 1700 (succinimide groups) > 1320, 1292 (S═O asymmetric) > 1486, 1580 (aromatic structures) > 1241 (aromatic ether bands) > 1105, 1150 cm-1 (O═S═O symmetric). Among them, membrane chlorination occurred at 1241, 1410, and 1440 cm-1. Moreover, the initial degradation of PVP and the subsequent transformation of PES could be highly responsible for the increased water permeability and the enlargement of membrane pores, respectively, both leading to serious fouling with humic acid filtration. In summary, the 2D-FTIR-CoS analysis is a powerful approach to reveal the interaction mechanisms of NaOCl-membrane and could be also useful to probe the process of membrane fouling and chemical cleaning.

Selective elimination of chromophoric and fluorescent dissolved organic matter in a full-scale municipal wastewater treatment plant.

Effluent organic matter (EfOM) from municipal wastewater treatment plants potentially has a detrimental effect on both aquatic organisms and humans. This study evaluated the removal and transformation of chromophoric dissolved organic matter (CDOM) and fluorescent dissolved organic matter (FDOM) in a full-scale wastewater treatment plant under different seasons. The results showed that bio-treatment was found to be more efficient in removing bulk DOM (in term of dissolved organic carbon, DOC) than CDOM and FDOM, which was contrary to the disinfection process. CDOM and FDOM were selectively removed at various stages during the treatment. Typically, the low molecular weight fractions of CDOM and protein-like FDOM were more efficiently removed during bio-treatment process, whereas the humic-like FDOM exhibited comparable decreases in both bio-treatment and disinfection processes. Overall, the performance of the WWTP was weak in terms of CDOM and FDOM removal, resulting in enrichment of CDOM and FDOM in effluent. Moreover, the total removal of the bulk DOM (P<0.05) and the protein-like FDOM (P<0.05) displayed a significant seasonal variation, with higher removal efficiencies in summer, whereas removal of CDOM and the humic-like FDOM showed little differences between summer and winter. In all, the results provide useful information for understanding the fate and transformation of DOM, illustrating that sub-fractions of DOM could be selectively removed depending on treatment processes and seasonality.

Characterization and Significance of Sub-Visible Particles and Colloids in a Submerged Anaerobic Membrane Bioreactor (SAnMBR).

The distribution, composition and morphological structure of subvisible particles and colloids (0.01-10 µm) in the supernatant of a lab-scale submerged anaerobic membrane bioreactor (SAnMBR), and their role in membrane fouling, was investigated. Photometric analysis showed that the supernatant and membrane foulants were dominated by particles and colloids (0.45-10 µm), which accounted for over 90% of the total organics (proteins and polysaccharides). Excitation-emission matrix (EEM) fluorescence spectra and monosaccharide analysis showed that these particles and colloids were rich in fluorescent proteins, rhamnose, ribose and arabinose, all of which could be related to cellular and extracellular substances. Fluorescence and scanning electron microscopy confirmed the presence of bacterial cells in/on the subvisible particles and colloids. The microparticles (5-10 µm) were primarily composed of Streptobacilli and/or filamentous bacteria in the form of microcolonies, while the submicrometer particles and colloids (1-5 µm and 100 kDa-1 µm) had more free/single cocci and bacilli. The ratio of live/dead cells varied in different size-fractions, and the particles (1-10 µm) contained more live cells compared with the colloids (100 kDa-1 µm). Our findings suggest that bacterial cells in/on the particles and colloids could have an important effect on fouling in SAnMBRs as they represent pioneering species attaching to membranes to form fouling layers/biofilm. Such insights reveal that previous foulant-characterization studies in MBRs tended to overestimate organic fouling, while the biofouling induced by these bacteria in/on the particles and colloids was overlooked.

Polycyclic Polyprenylated Derivatives from Hypericum uralum: Neuroprotective Effects and Antidepressant-like Activity of Uralodin A.

The isolation of the new polycyclic polyprenylated acylphloroglucinols uraliones A-K (1-11) together with five known analogues (12-16) from a whole Hypericum uralum plant was reported. The structures of these compounds were established through spectroscopic methods, and a single-crystal X-ray diffraction analysis was used to confirm the absolute configuration of 1. The protective effects of the isolates against corticosterone-induced PC12 cell injury were assessed. Except for compound 9, all tested compounds exhibited significant protective effects against induced injury in PC12 cells. Uralodin A (14), orally administered in doses of 13 and 26 mg/kg, exhibited antidepressant-like activity in the tail suspension and forced-swimming tests in mice.

[Study on Flavonoids of Ophioglossum thermal].

Objective: To investigate the chemical components of Ophioglossum thermale,one of the original species of Chinese medicine "Yizhijian". Methods: The air-dried whole plant material of Ophioglossum thermale was extracted by thermal reflux with 95%Et OH,then separated and purified by joint utilization of various chromatography techniques including macroporous resin,silica gel,Sephadex LH-20 column chromatography and HPLC. Their structures were elucidated on the basis of spectroscopic methods. Results: Six flavonoids were isolated and identified as 3-O-methylquercetin( 1),ophioglonol( 2),3-O-methylquercetin 7-O-ß-D-glucopyranoside( 3),3-O-methylquercetin 7-O-ß-D-glucopyraosyl-4'-O-ß-D-glucopyranoside( 4),kaempferol 3-O-( 6-O-caffeoyl)-ß-D-glucopyranosyl-( 1 →2)-α-L-rhamnopyranosyl-7-O-α-L-rhamnopyranoside( 5) and quercetin 3-O-( 6-O-caffeoyl)-ß-D-glucopyranosyl( 1→2)-α-L-rhamnopyranosyl-7-O-α-L-rhamnopyranoside( 6). Conclusion: Compounds 2 ~ 6 are isolated from this plant for the first time,compounds 5 and 6are firstly isolated from Ophioglossaceae family.

Metaproteomic analysis of biocake proteins to understand membrane fouling in a submerged membrane bioreactor.

Metaproteomic analyses, including two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) separation and matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)/TOF mass spectrometer (MS) detection, were used to trace and identify biocake proteins on membranes in a bench-scale submerged membrane bioreactor (MBR). 2D-PAGE images showed that proteins in the biocake (S3) at a low transmembrane pressure (TMP) level (i.e., before the TMP jump) had larger gray intensities in the pH 5.5­7.0 region regardless of the membrane flux, similar to soluble microbial product (SMP) proteins. However, the biocake (S2 and S4) at a high TMP level (i.e., after the TMP jump) had many more proteins in the pH range of 4.0­5.5, similar to extracellular polymeric substance (EPS) proteins. Such similarities between biocake proteins and SMP or EPS proteins can be useful for tracing the sources of proteins resulting in membrane fouling. In total, 183 differentially abundant protein spots were marked in the three biocakes (S2, S3, and S4). However, only 32 protein spots co-occurred in the 2D gels of the three biocakes, indicating that membrane fluxes and TMP evolution levels had significant effects on the abundance of biocake proteins. On the basis of the MS and MS/MS data, 23 of 71 protein spots were successfully identified. Of the 23 proteins, outer membrane proteins (Omp) were a major contributor (60.87%). These Omps were mainly from potential surface colonizers such as Aeromonas, Enterobacter, Pseudomonas, and Thauera. Generally, the metaproteomic analysis is a useful alternative to trace the sources and compositions of biocake proteins on the levels of molecules and bacteria species that can provide new insight into membrane fouling.

Four New Flavonoids with α-Glucosidase Inhibitory Activities from Morus alba var. tatarica.

Four new flavonoids, mortatarins A-D (1-4, resp.), along with eight known flavonoids (5-12) were isolated from the root bark of Morus alba var. tatarica. Their structures were established on the basis of spectroscopic data analysis, and the absolute configuration of 4 was determined by analysis of its CD spectrum. All isolates were tested for inhibitory activities against α-glucosidase. Compounds 4, 7, and 8 exhibited a significant degree of inhibition with IC50 values of 5.0 ± 0.3, 7.5 ± 0.5, and 5.9 ± 0.2 µM, respectively.

Gut hormone multi-agonists for the treatment of type 2 diabetes and obesity: advances and challenges.

The rapidly rising incidence of obesity, coupled with type 2 diabetes mellitus (T2DM), is a growing concern. Glucagon-like peptide 1 (GLP-1), an endogenous peptide secreted by enteroendocrine L-cells, demonstrates exceptional pharmacological potential for the treatment of T2DM and obesity, primarily through its pivotal roles in regulating glucose homeostasis, stimulating glucose-dependent insulin secretion, and promoting satiety. Considering its proven efficacy in glucoregulation and weight loss, GLP-1 receptor agonists (GLP-1RAs) have emerged as a revolutionary breakthrough in the arena of diabetes management and weight control. Additional gastrointestinal hormones, such as glucose-dependent insulinotropic peptide (GIP) and glucagon, exhibit structural similarities to GLP-1 and work synergistically to lower blood glucose levels or aid in weight loss. Today, various classes of gut hormone receptor multiple agonists are steadily progressing through development and clinical trials, including dual GLP-1/glucagon receptor agonists (first discovered in 2009), dual GLP-1/GIP receptor agonists (first described in 2013), and triple GLP-1/GIP/glucagon receptor agonists (initially designed in 2015). The GLP-1/GIP receptor co-agonist, tirzepatide, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of T2DM, outperforming basal insulin or selective GLP-1RAs by providing superior HbA1c reductions. Remarkably, tirzepatide also facilitated unprecedented weight loss of up to 22.5% in non-diabetic individuals living with obesity. This result is comparable to those achieved with certain types of bariatric surgery. Therefore, the advent of gut hormone multi-agonists signifies the dawn of an exciting new era in peptide-based therapy for obesity and T2DM. This review offers a comprehensive summary of the various types of gut hormone multiple agonists, including their discovery, development, action of mechanisms, and clinical effectiveness. We further delve into potential hurdles, limitations, and prospective advancements in the field.

Discovery of a Novel Glucagon-like Peptide-1 (GLP-1) Analogue from Bullfrog and Investigation of Its Potential for Designing GLP-1-Based Multiagonists.

In this study, we aimed to discover novel GLP-1 analogues from natural sources. We investigated GLP-1 analogues from fish and amphibians, and bullfrog GLP-1 (bGLP-1) showed the highest potency. Starting with bGLP-1, we explored the structure-activity relationship and performed optimization and long-acting modifications, resulting in a potent analogue called 2f. Notably, 2f exhibited superior effects on food intake, glycemic control, and body weight compared to semaglutide. Furthermore, we explored the usefulness of bGLP-1 in designing GLP-1-based multiagonists. Using the bGLP-1 sequence, we designed novel dual GLP-1/glucagon receptor agonists and triple GLP-1/GIP/glucagon receptor agonists. The selected dual GLP-1/glucagon receptor agonist 3o and triple GLP-1/GIP/glucagon receptor agonist 4b exhibited significant therapeutic effects on lipid regulation, glycemic control, and body weight. Overall, our study highlights the potential of discovering potent GLP-1 receptor agonists from natural sources. Additionally, utilizing natural GLP-1 analogues for designing multiagonists presents a practical approach for developing antiobesity and antidiabetic agents.

Extracellular polymeric substances as paper coating biomaterials derived from anaerobic granular sludge.

Recovering extracellular polymeric substances (EPS) from waste granular sludge offers a cost-effective and sustainable approach for transforming wastewater resources into industrially valuable products. Yet, the application potential of these EPS in real-world scenarios, particularly in paper manufacturing, remains underexplored. Here we show the feasibility of EPS-based biomaterials, derived from anaerobic granular sludges, as novel coating agents in paper production. We systematically characterised the rheological properties of various EPS-based suspensions. When applied as surface sizing agents, these EPS-based biomaterials formed a distinct, ultra-thin layer on paper, as evidenced by scanning electron microscopy. A comprehensive evaluation of water and oil penetration, along with barrier properties, revealed that EPS-enhanced coatings markedly diminished water absorption while significantly bolstering oil and grease resistance. Optimal performance was observed in EPS variants with elevated protein and hydrophobic contents, correlating with their superior rheological characteristics. The enhanced water-barrier and grease resistance of EPS-coated paper can be attributed to its non-porous, fine surface structure and the functional groups in EPS, particularly the high protein content and hydrophobic humic-like substances. This research marks the first demonstration of utilizing EPS from anaerobic granular sludge as paper-coating biomaterials, bridging a critical knowledge gap in the sustainable use of biopolymers in industrial applications.

In vitro and in vivo Biological Evaluation of Newly Tacrine-Selegiline Hybrids as Multi-Target Inhibitors of Cholinesterases and Monoamine Oxidases for Alzheimer's Disease.

Purpose: Alzheimer's disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs. Methods: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo. Results: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs (hAChE: IC50 = 1.57 µM, hBuChE: IC50 = 0.43 µM) and MAOs (hMAO-A: IC50 = 2.30 µM, hMAO-B: IC50 = 4.75 µM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics. Conclusion: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD.

Bioactive benzofuran neolignans from Aristolochia fordiana.

Six new benzofuran neolignans (1-6) were isolated from the EtOAc-soluble fraction of the aerial part of Aristolochia fordiana, together with twelve known analogues (7-18). The structures of the isolated compounds were elucidated by spectroscopic methods. All isolates were evaluated for their inhibitory effects on nitric oxide production in lipopolysaccaride-activated RAW264.7 macrophages and for their cytotoxic activities on three human cancer cell lines. Compound 2 showed significant nitric oxide production inhibitory activity with an IC50 value of 10.00 µM, while compound 16 exhibited cytotoxic activity with an IC50 value of 11.9 µM against MG-63 and compound 18 of 9.15 µM against HepG2 cell lines, respectively.