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. 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, dual GLP-1/GIP receptor agonists, and triple GLP-1/GIP/glucagon receptor agonists. The GLP-1/GIP receptor co-agonist, tirzepatide, was approved by the US 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.

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.

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.

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.

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.

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.

An updated patent review of GLP-1 receptor agonists (2020-present).

INTRODUCTION: Type 2 diabetes (T2DM) and obesity present significant global health issues, requiring the development of long-lasting and highly effective pharmacotherapies. Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) are commonly used for diabetes treatment, their potential for addressing obesity is still being explored. AREAS COVERED: This review offers a comprehensive overview of recently published patents from January 2020 to July 2023, focusing on modified GLP-1RAs, small molecule GLP-1RAs, GLP-1 R-based multi-agonists, GLP-1RA-based fusion proteins, and combination therapies. The patents discussed pertain to the treatment and prevention of diabetes and obesity. Patent searches were conducted using the PATENTSCOPE database of the World Intellectual Property Organization, using the keywords GLP-1, GLP-1/GIP, GLP-1/GCG, and GLP-1/GCG/GIP. EXPERT OPINION: In recent years, patents have emphasized two main goals for developing GLP-1RAs drugs: oral delivery and improved weight reduction effects. To address the growing demand for improved treatments, researchers have focused their efforts on developing GLP-1 R-based multi-agonists, orally administered GLP-1RAs, and combination therapies utilizing GLP-1RAs. These new approaches offer promising benefits, such as improved effectiveness by targeting multiple pathways and reduced side effects. Additionally, the development of new uses, oral forms, and long-lasting preparations will be crucial in shaping the future market potential of GLP-1 drugs.

Filamentous cyanobacteria and hydrophobic protein in extracellular polymeric substances facilitate algae-bacteria aggregation during partial nitrification.

In algae-bacteria symbiotic wastewater treatment, the excellent settling performance of algae-bacteria aggregates is critical for biomass separation and recovery. Here, the composition of extracellular polymeric substances (EPS), microbial profiles, and functional genes of algae-bacteria aggregates were investigated at different solid retention times (SRTs) (10, 20, and 40 d) during partial nitrification in photo sequencing bioreactors (PSBRs). Results showed that SRTs greatly influenced the nitrogen transformation and the formation and morphological structure of algae-bacteria aggregates. The highest nitrite accumulation, the largest particle size (~1.54 mm) and the best settling performance were observed for the algae-bacteria aggregates in the PSBR with an SRT of 10 d, where the abundant occurrence of filamentous cyanobacteria with the highest ratio of chlorophyll a/b and the lowest EPS amount with the highest protein-to-polysaccharide ratio were observed. In particular, the EPS at 10 d of SRT contained a higher amount of protein-related hydrophobic groups and a lower ratio of α-helix/(ß-sheet + random coil), indicating a looser protein structure, which might facilitate the formation and stabilization of algae-bacteria aggregates. Moreover, algal-bacterial aggregation greatly depended on the composition and evolution of filamentous cyanobacteria (unclassified _o__Oscillatoriales and Phormidium accounted for 56.29 % of the identified algae at SRT 10 d). The metagenomic analysis further revealed that functional genes related to amino acid metabolism (e.g., genes of phenylalanine, tyrosine, and tryptophan biosynthesis) were expressed at high levels within 10 d of SRT. Overall, this study demonstrates the influence of EPS structures and filamentous cyanobacteria on algae-bacteria aggregation and reveals the biological mechanisms driving photogranule structure and function.

Evaluating the impacts of biochemical processes on nitrogen dynamics in a tide gate-controlled river flowing into the South China Sea.

This study aimed to evaluate the nitrogen (N) dynamics in Lijiang River, a tide gate-controlled river flowing into South China Sea, and to quantify the biochemical processes affecting nitrate fate and transport during the closed-tide gate period. The continuous on-line water monitoring indicates a chemostatic NH4+-N pattern with respect to variable discharges in the upstream section. The survey via daily grab water sampling from July to December 2020 at four equidistant locations in the lower stretch showed that a gradual increase in NO3--N and decrease in NH4+-N concentrations occurred along the river from upstream to downstream sections and with the time from September to December (the closed-tide gate period). The mean difference between nitrification and denitrification rate peaked at 0.43 mg L-1 d-1 in October in the upper section and gradually reduced to -0.26 mg L-1 d-1 in December in the middle section, indicating the increased advantage of denitrification over nitrification with time. A gradual increase in the mean NO3--N assimilatory uptake rate with time and a decrease from upstream to downstream were also observed. These results show that the closed-tide gate promoted N biotransformation in Laingian River and significant N removal was achieved through coupled nitrification-denitrification.

Phytochemistry and pharmacology of natural prenylated flavonoids.

Prenylated flavonoids are a special kind of flavonoid derivative possessing one or more prenyl groups in the parent nucleus of the flavonoid. The presence of the prenyl side chain enriched the structural diversity of flavonoids and increased their bioactivity and bioavailability. Prenylated flavonoids show a wide range of biological activities, such as anti-cancer, anti-inflammatory, neuroprotective, anti-diabetic, anti-obesity, cardioprotective effects, and anti-osteoclastogenic activities. In recent years, many compounds with significant activity have been discovered with the continuous excavation of the medicinal value of prenylated flavonoids, and have attracted the extensive attention of pharmacologists. This review summarizes recent progress on research into natural active prenylated flavonoids to promote new discoveries of their medicinal value.

New insights into multi-strategies of sludge granulation in up-flow anaerobic sludge blanket reactors from community succession and interaction.

This study aimed to elucidate the multiple strategies employed by anaerobes during granulation in a laboratory upflow anaerobic sludge blanket reactor, based on microbial succession and interactions. The anaerobic granulation process featured staged dominance of microbial genera, corresponding well with the environmental traits. Across the stages (selection, seeding, expansion, and maturation), chemotaxis attraction of nitrogen and/or carbon sources and flagellar motion were the primary strategy of microbial assembly. The second messengers - cyclic adenosine and guanosine monophosphates - partially regulated the agglomeration of filamentous Euryachaeota and Chloroflexi as the inner cores, while quorum sensing mediated the expansion of granules prior to maturation. Antagonism or competition governed the interactions within the phylogenetic molecular ecological network during sludge granulation, which were largely driven by the low-abundance (<1%) taxa. These new insights suggest that better engineering solutions to enhance chemotaxis attraction and species selection could achieve more efficient anaerobic granular sludge processes.

Metagenomics and network analysis decipher profiles and co-occurrence patterns of bacterial taxa in soils amended with biogas slurry.

Microbial community and interaction play crucial roles in ecological functions of soil including nutrient cycling carbon storage, and water maintenance etc. Numerous studies have shown that the application of fertilizers alters bacterial diversity; However, it remains unknown whether and how the continuous application of biogas slurry from anaerobic digestion affects the spatiotemporal heterogeneity of soil layers, complexity and stability of microbial networks, and functions related to C and N cycling. Here, we investigated the bacterial taxa of purple soils treated with swine biogas slurry for four different periods (0, 1, 3 and 8 years) and five different soil depths (20, 40, 60, 80 and 100 cm). The results showed that the application period of biogas slurry and soil depth were two powerful drivers of bacterial diversity and communities. Biogas slurry input resulted in marked changes in the bacterial diversity and composition at the soil depths of 0-60 cm. The relative abundances of Acidobacteriota, Myxococcot, and Nitrospirota decreased, while Actinobacteria, Chloroflexi, and Gemmatimonadota increased with repeated biogas slurry input. The decreasing complexity and stability of the bacterial network with decreasing nodes, links, robustness, and cohesions were found with increasing years of biogas slurry application, suggesting that the bacterial network of soils treated by the biogas slurry became more vulnerability compared with the control. Also, the linkages between the keystone taxa and soil properties were weakened after biogas slurry input, leading to the cooccurrence patterns being less affected by the keystones in the high level of nutrients. Metagenomic analysis confirmed that biogas slurry input increased the relative abundance of liable-C degradation and denitrification genes, which could highly impact the network properties. Overall, our study could give comprehensive understandings on the impacts of biogas slurry amendment on soils, which could be useful for maintaining sustainable agriculture and soil health with liquid fertilization.

Discovery of novel OXM-based glucagon-like peptide 1 (GLP-1)/glucagon receptor dual agonists.

Novel glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP-1R) dual agonists are reported to have improved efficacy over GLP-1R mono-agonists in treating type 2 diabetes (T2DM) and obesity. Here, we describe the discovery of a novel oxyntomodulin (OXM) based GLP-1R/GCGR dual agonist with potent and balanced potency toward GLP-1R and GCGR. The lead peptide OXM-7 was obtained via stepwise rational design and long-acting modification. In ICR and db/db mice, OXM-7 exhibited prominent acute and long-acting hypoglycemic effects. In diet-induced obesity (DIO) mice, twice-daily administration of OXM-7 produced significant weight loss, normalized lipid metabolism, and improved glucose control. In DIO-nonalcoholic steatohepatitis (NASH) mice, OXM-7 treatment significantly reversed hepatic steatosis, and reduced serum and hepatic lipid levels. These preclinical data suggest the therapeutic potential of OXM-7 as a novel anti-diabetic, anti-steatotic and/or anti-obesity agent.

Cytotoxic phenyl polyketides from Hypericum curvisepalum N. Robson.

(±)-Hypecurvone A (1) and B (2), two new undescribed phenyl polyketides, along with seven known analogues (3-9) were isolated from the whole plant of Hypericum curvisepalum. Chiral separation of 1 and 2 yielded two pairs of enantiomers 1a/1b and 2a/2b, respectively. The structures of these compounds were elucidated by extensive spectroscopic analyses and ECD spectra simulations. All isolates exhibited moderate cytotoxicity against human hepatocellular carcinoma SMMC-7721 cells, and compound 3 also showed weak cytotoxicity toward MGC-803 cells. The cytotoxicity of these compounds was found to be related to enhanced mitochondria-mediated apoptosis and inhibition of the G2/M phase of the cell cycle.

Cucurbitane-type triterpenoids from the fruits of Citrullus colocynthis.

A phytochemical investigation of the fruits of Citrullus colocynthis resulted in the isolation of 21 structurally diverse cucurbitane triterpenoids, including 9 previously undescribed ones, colocynins A-I (1-9). Their absolute configurations were elucidated by means of quantum chemical electronic circular dichroism (ECD) calculations, CD exciton chirality method, and single-crystal X-ray crystallography. Colocynins A-C (1-3) represent the first examples of nonanorcucurbitane-type triterpenoids. An anti-acetylcholinesterase activity assay showed that 6, 10, 13, 18, and 20 exhibited inhibitory activities, with IC50 values ranging from 5.0 to 21.7 µM. In addition, 18 and 21 showed significant cytotoxicity against PACA, A431, and HepG2 cells, with IC50 values ranging from 0.042 to 0.60 and 3.6-14.4 µM, respectively.

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.

Purifying water with silver nanoparticles (AgNPs)-incorporated membranes: Recent advancements and critical challenges.

In the face of the growing global water crisis, membrane technology is a promising means of purifying water and wastewater. Silver nanoparticles (AgNPs) have been widely used to improve membrane performance, for antibiofouling, and to aid in photocatalytic degradation, thermal response, and electro-conductivity. However, several critical issues such as short antimicrobial periods, trade-off effects and silver inactivation seriously restrict the engineering application of AgNPs-incorporated membranes. In addition, there is controversy around the use of AgNPs given the toxic preparation process and environmental/biological risks. Hence, it is of great significance to summarize and analyze the recent developments and critical challenges in the use of AgNPs-incorporated membranes in water and wastewater treatment, and to propose potential solutions. We reviewed the different properties and functions of AgNPs and their corresponding applications in AgNPs-incorporated membranes. Recently, multifunctional, novel AgNP-incorporated membranes combined with other functional materials have been developed with high-performance. We further clarified the synergistic mechanisms between AgNPs and these novel nanomaterials and/or polymers, and elucidated their functions and roles in membrane separation. Finally, the critical challenges of AgNPs-incorporated membranes and the proposed solutions were outlined: i) Prolonging the antimicrobial cycle through long-term and controlled AgNPs release; ii) Overcoming the trade-off effect and organic fouling of the AgNPs-incorporated membranes; iii) Preparation of sustainable AgNPs-incorporated membranes; iv) Addressing biotoxicity induced by AgNPs; and v) Deactivation of AgNPs-incorporated membrane. Overall, this review provides a comprehensive discussion of the advancements and challenges of AgNPs-incorporated membranes and guides the development of more robust, multi-functional and sustainable AgNPs-incorporated membranes.

A Novel Anaerobic Gravity-Driven Dynamic Membrane Bioreactor (AnGDMBR): Performance and Fouling Characterization.

Despite numerous studies undertaken to define the development and significance of the dynamic membrane (DM) formed on some coarse materials, the optimization of reactor configuration and the control of the membrane fouling of anaerobic dynamic membrane bioreactor (AnDMBR) need to be further investigated. The aim of this study was to design a novel anaerobic gravity-driven dynamic membrane bioreactor (AnGDMBR) for the effective and low-cost treatment of municipal wastewater. An 800 mesh nylon net was determined as the optimal support material based on its less irreversible fouling and higher effluent quality by the dead-end filtration experiments. During the continuous operation period of 44 days, the reactor performance, DM filtration behavior and microbial characteristics were studied and compared with the results of recent studies. AnGDMBR had a higher removal rate of chemical oxygen demand (COD) of 85.45 ± 7.06%. Photometric analysis integrating with three-dimensional excitation-emission matrix fluorescence spectra showed that the DM effectively intercepted organics (46.34 ± 16.50%, 75.24 ± 17.35%, and 66.39 ± 17.66% for COD, polysaccharides, and proteins). The addition of suspended carriers effectively removed the DM layer by mechanical scouring, and the growth rate of transmembrane pressure (TMP) and the decreasing rate of flux were reduced from 18.7 to 4.7 Pa/h and 0.07 to 0.01 L/(m2·h2), respectively. However, a dense and thin morphological structure of the DM layer was still observed in the end of reactor operation and plenty of filamentous microorganisms (i.e., SJA-15 and Anaerolineaceae) and the acidogens (i.e., Aeromonadaceae) predominated in the DM layer, which was also embedded in the membrane pore and led to severe irreversible fouling. In summary, the novel AnGDMBR has a superior performance (higher organic removal and lower fouling rates), which provides useful information on the configuration and operation of AnDMBRs for municipal wastewater treatment.

Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum scabrum.

Eighteen polycyclic polyprenylated acylphloroglucinols were isolated from the whole plant of Hypericum scabrum Linn., including six new compounds (1-6). Their structures were elucidated by comprehensive spectroscopic analyses. The evaluation of their cytotoxic activities was carried out against SMMC-7721 and MGC-803 cell lines. We found that most tested compounds exhibited moderate cytotoxic activities against SMMC-7721 cell line except for 11 and 12, while compounds 1, 5-7, 13 and 16 also showed cytotoxic activities on MGC-803 cells. Besides, Bacillus subtilis, MRSA and MDPRA were also used to test inhibitory activity of these compounds. Our results showed that only compounds 12 and 13 presented weak inhibitory activity against Bacillus subtilis, while compounds 7, 13 and 14 also inhibited MRSA weakly.

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.