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Immunotherapy, particularly αPD-1 therapy, has been hailed as a significant breakthrough in cancer treatment. However, the limited response rates and unknown mechanisms hinder the clinical application of αPD-1 blockade boosting with hybrid nanoparticles. Herein, we introduce a strategy to enhance cancer immunotherapy by leveraging cuproptosis, initiated by the spiky copper-based metal-organic framework (S@Cu-MOF) loaded with polyphyllin I (PPI) and synergized with αPD-1 therapy. Interestingly, the unique spiky structure of S@Cu-MOF not only significantly enhances tumor cell uptake but also leads to pronounced DNA damage. The application of S@Cu-MOF/PPI with αPD-1 therapy led to obvious tumor regression and prolonged survival due to cuproptosis, which involved substantial mitochondrial damage. This process amplifies the cGAS/STING immune pathway, enhancing the immune response against cancer. Additionally, this strategy promoted immunogenic cell death (ICD), recruitment of mature dendritic cells (DCs), T cell-mediated immunity, and effective memory CD8+ T cells, resulting in significant abscopal tumor suppression and lung metastasis reduction. Our study highlights the potential of S@Cu-MOF/PPI as a sensitizer for αPD-1 with the mechanism of cuproptosis and the cGAS/STING pathway, offering a promising strategy for the next generation of immunotherapy. [Display omitted] • Engineered spiky Cu-MOF nanosystem enhanced antitumor effects, highlighting the impact of morphology on therapy. • Spiky Cu-MOF nanosystem boosted cGAS/STING-mediated antitumor immunity via cuproptosis. • Spiky Cu-MOF nanosystem and αPD-1 therapy combined to reverse immune suppression, boosting antitumor immunity. [ABSTRACT FROM AUTHOR]

[Display omitted] • The recombinant human ferritin heavy chain (rhFTH) was expressed and self-assembled in E. coli. • Non-chromatographic procedure with optimized pH, temperature and NaCl was critical to the purity of rhFTH. • rhFTH with intact nanoparticle structure was obtained with high recovery. Recombinant human ferritin heavy chain (rhFTH) was highly expressed and self-assembled in E. coli bacteria. To establish a robust purification scheme, we developed a non-chromatographic precipitation procedure as a key step for extracting rhFTH from the disrupted supernatant. Three factors including heating temperature, pH value and sodium chloride concentration were systematically investigated and optimized for this precipitation procedure. Almost all of the unrelated proteins could be efficiently removed by the optimized precipitation procedure. Combining with hydrophobic interaction chromatography of Capto Butyl, the rhFTH was efficiently purified from the post-precipitated supernatant, the purity of the finally obtained rhFTH was above 98 % and the target protein recovery was around 66 % roughly estimated by optical density. ESI-MS analysis showed a molecular weight of 21086.0 Da that was almost identical with the theoretical value. Circular dichroism analysis revealed alpha-helix structure as major structure content and fluorescence analysis demonstrated that aromatic amino acids residues were highly buried inside. HP-SEC analysis showed a geometrically symmetrical peak, indicating rhFTH exists as homogeneous structure with a relatively large size, and further being validated by DLS and TEM. DSC analysis revealed that the extreme stability against temperature contributed mainly to the feasibility of the developed precipitation treatment. [ABSTRACT FROM AUTHOR]

Abstract The properties of agricultural soils in various regions of the world are variable and can have a significant but poorly understood impact on soil nitrogen (N) transformations and nitrous oxide (N 2 O) emissions. For this reason, we undertook a study of gross N transformations and related N 2 O emissions in contrasting agricultural soils from China and the UK. Seven Chinese and three UK agricultural soils were collected for study using a 15N tracing approach. The soil pH ranged from 5.4 to 8.7, with three acidic soils collected from Jinjing, Lishu and Boghall; one neutral soil collected from Changshu, and the other six alkaline soils collected from Quzhou, Zhangye, Changwu, Jinzhong, Boxworth and Stetchworth. Our results showed that the main N transformation processes were oxidation of ammonium (NH 4 +) to nitrate (NO 3 −) (O NH4), and mineralization of organic N to NH 4 +. The gross autotrophic nitrification rates calculated in the three acidic soils were between 0.25 and 4.15 mg N kg−1 d−1, which were significantly lower (p < 0.05) than those in the remaining neutral and alkaline soils ranging from 6.94 to 14.43 mg N kg−1 d−1. Generally, soil pH was positively correlated (p < 0.001) with gross autotrophic nitrification rate and cumulative N 2 O emissions, indicating that soil pH was an important factor regulating autotrophic nitrification and N 2 O emissions. There was also a significant positive correlation between the gross autotrophic nitrification rate and cumulative N 2 O emissions, highlighting the importance of this process for producing N 2 O emissions in these agricultural soils under aerobic conditions. Gross NH 4 + immobilization rates were very low in most soils except for the Jinjing soil with the lowest pH. In conclusion, the gross autotrophic nitrification rates and related N 2 O emissions were controlled by soil pH irrespectively of the soil's origin in these agricultural soils. Graphical abstract Unlabelled Image Highlights • We examined gross N transformations in Chinese and UK agricultural soils. • Autotrophic nitrification and mineralization were the key N transformation processes. • Autotrophic nitrification was important for N 2 O emission under aerobic conditions. • pH was the primary factor controlling autotrophic nitrification and N 2 O emissions. • Gross N transformation rates were not related to the origin of soil sampling sites. [ABSTRACT FROM AUTHOR]

As the only "tropical base of agricultural production" in China, Hainan lsland is vigorously developing high-value agriculture and is becoming the province with the highest proportion of cash crops. However, this intensive farming with large nutrient inputs has caused cropland degradation, nitrogen (N) and phosphorus (P) overloads and water pollution, which have been reversed to initiate the construction of free trade ports. Here, we systematically review the status, driving factors, and environmental impacts of cropland degradation and nutrient overload with quantified evaluations and compared with other global tropics. Over the last 30 years, the soil pH in Hainan decreased by 0.3 units, and the soil organic carbon (SOC) decreased by 20%. This soil degradation has consequently aggravated nutrient losses, caused low use efficiency, and has required farmers add additional large nutrient to maintain harvests. P overuse is more serious than N overuse in Hainan due to the misuse of high P content compound fertilizers. The current N and P usage densities were 4% and 66% higher than the national average per crop season, i.e., 301 kg N ha−1 and 98 kg P ha−1, respectively, and the application rates were even higher for vegetables, i.e., 43% and 115% higher than the national average for vegetables. Consequently, water quality degradation occurred. The nutrient contents of several estuaries have exceeded the Class III standards. Potential improvement strategies are proposed: (i) Organic materials must be recycled to curb the declines in SOC and pH, and more benefits would be obtained by together use of biochar. (ii) Nutrient quotas must be implemented to balance nutrient budgets and reduce excessive surpluses and losses. (iii) The service functions of ecological protection zones for water and soil conservation must be strengthened. These strategies also apply to other global tropics that face similar challenges of soil and ecological degradation. [Display omitted] • Cropland degradation, nutrient overloads and water pollutionimpeded the construction of free trade ports of Hainan Island. • Over the last 30 years, the soil pH decreased by 0.3 units and the soil organic carbon (SOC) decreased by 20% in Hainan. • The current N and P usage densities were 4% and 66% higher than the national average per crop season. • Potential improvement strategies and insights are proposed. [ABSTRACT FROM AUTHOR]

Hot moments of nitrous oxide (N 2 O) emissions induced by interactions between weather and management make a major contribution to annual N 2 O budgets in agricultural soils. The causes of N 2 O production during hot moments are not well understood under field conditions, but emerging evidence suggests that short-term fluctuations in soil oxygen (O 2) concentration can be critically important. We conducted high time-resolution field observations of O 2 and N 2 O concentrations during hot moments in a dryland agricultural soil in Northern China. Three typical management and weather events, including irrigation (Irr.), fertilization coupled with irrigation (Fer.+Irr.) or with extreme precipitation (Fer.+Pre.), were observed. Soil O 2 and N 2 O concentrations were measured hourly for 24 h immediately following events and measured daily for at least one week before and after the events. Soil moisture, temperature, and mineral N were simultaneously measured. Soil O 2 concentrations decreased rapidly within 4 h following irrigation in both the Irr. and Fer.+Irr. events. In the Fer.+Pre. event, soil O 2 depletion did not occur immediately following fertilization but began following subsequent continuous rainfall. The soil O 2 concentration dropped to as low as 0.2% (with the highest soil N 2 O concentration of up to 180 ppmv) following the Fer.+Pre. event, but only fell to 11.7% and 13.6% after the Fer.+Irr. and Irr. events, which were associated with soil N 2 O concentrations of 27 ppmv and 3 ppmv, respectively. During the hot moments of all three events, soil N 2 O concentrations were negatively correlated with soil O 2 concentrations (r = −0.5, P < 0.01), showing a quadratic increase as soil O 2 concentrations declined. Our results provide new understanding of the rapid short response of N 2 O production to O 2 dynamics driven by changes in soil environmental factors during hot moments. Such understanding helps improve soil management to avoid transitory O 2 depletion and reduce the risk of N 2 O production. • N2O production instantly responded to rapid short O2 dynamics in in situ soils. • Soil N2O concentrations increased quadratically as soil O2 decreased at hot moments. • Anaerobic microsites existed widely in dryland soils after extreme rainfall. • O2 recovered within 24 h after short-term irrigation in in situ structured soils. • Hot moments of N2O production were promoted by intense rainfall not by irrigation. [ABSTRACT FROM AUTHOR]

Enhanced efficiency nitrogen fertilizers (EENFs), including nitrification inhibitors (NIs) and slow-release fertilizer (SRF), are considered promising approaches for mitigating nitrous oxide (N 2 O) emissions while improving crop yield. This study investigated the combined application of EENFs with improved water and fertilizer management in an intensively irrigated spring maize rotation over five years in Northwestern China. High-frequency measurements of N 2 O fluxes were made throughout each year (both during crop growth and the fallow season) in five treatments: no N fertilizer as a control (CK), conventional N fertilization and irrigation (Con), optimum N fertilization and irrigation (Opt, 33% reduction in N fertilizer and 25% reduction of irrigation water), optimum N fertilization and irrigation with nitrification inhibitor (Opt + NI), and optimum N fertilization and irrigation with slow-release fertilizer (Opt-SRF). Annual mean cumulative N 2 O emissions reached 0.31 ± 0.07, 3.66 ± 0.19, 1.87 ± 0.16, 1.23 ± 0.13, and 1.61 ± 0.16 kg N 2 O–N ha−1 for CK, Con, Opt, Opt + NI, and Opt-SRF, respectively, with annual mean nitrogen use efficiency (NUE) of 36, 54, 61 and 59% for Con, Opt, Opt + NI, and Opt-SRF, respectively. The Opt, Opt + NI and Opt-SRF treatments significantly reduced cumulative N 2 O emissions by 49%, 66%, and 56% (P < 0.05), respectively, and increased NUE by 51%, 70%, and 66% (P < 0.05), respectively, relative to Con. However, mean above-ground N uptake (288–309 kg N ha−1) and mean grain yields (12.7–12.8 Mg ha−1) did not differ significantly between the Con, Opt, Opt + NI, and Opt-SRF treatments during the five-year study. High N 2 O emissions mainly occurred within a few days of fertilization with irrigation, which could have been produced by microbially-mediated nitrifier or nitrifier denitrification processes. The fallow seasons had significantly lower cumulative N 2 O emissions, which were mainly attributed to the low temperature, low N inputs of crop residues, and low soil moisture conditions. Our study clearly indicated that the combined application of EENFs with optimum N fertilization and irrigation management can reduce environmental impacts while maintaining high crop yields in dryland regions such as Northwest China. Image 1 • Combined application of EENFs with optimum N fertilization and irrigation significantly reduced N 2 O area based emissions. • EENFs significantly increased nitrogen use efficiency, decreased yield-scaled emissions, and maintained grain yields. • High N 2 O emissions after fertilization with irrigation could be caused by microbially-mediated nitrifier or nitrifier denitrification processes. • The low temperature, low N inputs, and the low soil moisture conditions led to the low cumulative N 2 O emissions in fallow. [ABSTRACT FROM AUTHOR]

Potential mechanisms of Baoyuan Jiedu decoction to improve pre-metastatic niche. Baoyuan Jiedu decoction inhibits the accumulation of MDSC in pre-metastatic niche of lung via TGF-β/CCL9 pathway. • Baoyuan Jiedu decoction reverses the pre-metastatic niche of lung. • Baoyuan Jiedu decoction inhibits the accumulation of MDSC in pre-metastatic niche of lung. • Baoyuan Jiedu decoction downregulates TGF-β/CCL9 pathway activation. Baoyuan Jiedu (BYJD for short) decoction, a traditional Chinese medicine formula, is composed of Astragalus, Ginseng, Aconite root, Honeysuckle, Angelica, Licorice, which has the functions of nourishing qi and blood, enhancing immune function, improving quality of life and prolonging survival time of tumor patients. The present study aimed to investigate the effect and mechanism of BYJD decoction on reversing the pre-metastatic niche. We showed that BYJD decoction could prolong the survival time of 4T1 tumor-bearing mice. Moreover, we found that the BYJD decoction inhibited the formation of lung pre-metastatic niche and inhibited recruitment of myeloid derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and genes expression of TGF-β, Smad2, Smad3, p-Smad2/3, Smad4, CCL9 in the TGF-β/CCL9 signaling pathway were suppressed by BYJD decoction. In line with the above findings, our results confirm that BYJD decoction inhibits the accumulation of MDSC in pre-metastatic niche of lung via TGF-β/CCL9 pathway. [ABSTRACT FROM AUTHOR]

• Fucoidan was prepared from A. japonicus and evaluated in LPS-challenged mice. • This fucoidan reduced expression of pro-inflammatory factor: TNF-α, IL-1β and IL-6. • This fucoidan reduced the expression of iNOS, and inactivated MAPK/NF-κb pathway. • This fucoidan suppressed the AKT/mTOR pathway by inhibition of phosphorylation. Sea cucumber is a functional food in Asia countries. This study was designed to investigate whether the fucoidan from sea cucumber A. japonicus has an anti-inflammatory effect in the liver of lipopolysaccharide (LPS)-challenged mice. Our results demonstrated for the first time that the fucoidan reduced the pathologic changes and levels of pro-inflammatory cytokines, such as, TNF-α, IL-1β and IL-6. RT-PCR and western blot results demonstrated that this fucoidan significantly reduced the expression of iNOS and the phosphorylation of NF-κB P65, P38 and ERK1/2, but not JNK compared to the model group. Furthermore, this fucoidan significantly suppressed the phosphorylation of AKT, mTOR, p70S6K, RPS6 and GSK3β, but not GSK3α. These results demonstrated this fucoidan has a powerful anti-inflammatory effect in the liver of LPS-challenged mice via down-regulating MAPK/NF-κB and AKT/mTOR pathways, and the expression of iNOS. Collectively, food intake of sea cucumber may have a potential effect against inflammation. [ABSTRACT FROM AUTHOR]

Agricultural soils are a major source of anthropogenic N 2 O, but their N 2 O emission estimates are highly uncertain, mainly due to the complexity of nitrogen (N) processes. Most soil N models include only primary N processes such as nitrification and denitrification, which limits their ability to realistically simulate N transformations in soils and accurately estimate N 2 O emissions from soils. This study introduces a Microbial-Explicit Model incorporating Comprehensive Nitrogen processes (MEMCN) to evaluate and quantify the influences of various N processes on the production of N 2 O as well as NO and N 2 , including nitrification, denitrification, anaerobic ammonium oxidation (ANAMMOX), dissimilatory nitrate reduction to ammonium (DNRA), mineralization, and microbial assimilation (i.e., growth) and death. The MEMCN was evaluated in laboratory experiments using agricultural soils with different levels of N additions under anaerobic and aerobic conditions, and reproduced well the dynamics of NH 4 +, NO 3 −, NO 2 −, NO, N 2 O, and N 2. After nitrification and denitrification, ANAMMOX and assimilation were found to be most important in controlling N transformations in agricultural soils. ANAMMOX directly increased N 2 emissions by 139% at the beginning of the simulations (i.e., 48 h) under anaerobic conditions, while microbial assimilation indirectly reduced NO, N 2 O, and N 2 emissions by 88%, 54%, and 58%, respectively, at the end of the simulations (i.e., 336 h) under aerobic conditions. Correspondingly, the biomass of ANAMMOX bacteria increased significantly at the beginning of the simulations under anaerobic conditions, while the biomass of nitrite oxidizing bacteria increased substantially under aerobic conditions. In contrast, DNRA, mineralization and microbial death had minor effect on soil N transformations, and the biomass of DNRA bacteria and heterotrophs did not change significantly during the simulations. Our study shows that it is necessary to include ANAMMOX and microbial assimilation in soil N models, while explicit simulation of microbial biomass dynamics may only be necessary if microbial biomass pools change significantly. • Develope a Microbial-Explicit Model incorporating Comprehensive N processes. • Quantify contributions of individual N processes to gaseous N production. • ANAMMOX increased N 2 produciton under aerobic and anaerobic condtions. • Assimilation reduced NO, N 2 O, and N 2 emissions under aerobic condtions. • Micoribal biomass should be explicitly expressed as they change substantially. [ABSTRACT FROM AUTHOR]

• Morphological traits of bryophytes in arid and semi-arid areas of Tibet were studied. • Morphological traits of bryophytes were closely related to environmental changes. • Hair-point length and plant height showed high CV and phenotypic plasticity. • Effects of environmental factors were different on terricolous and saxicolous moss. As the main part of the Qinghai-Tibet Plateau, Tibet has a large range of elevations. Its complex topography and diverse vegetation types constitute various micro-habitat conditions, which may exert great influence on ecosystems. The bryophytes are higher plant with simple structure, and widely distributed, and extremely sensitive to environmental variation as well. As one of the important indicator plants, its response to environmental variation is important to explore. In this study, to better understand the response of bryophytes to environmental variation, we explored the relationship between the morphological traits of Bryum argenteum and its surrounding climate, topography, soil, and other environmental factors in the arid and semi-arid regions of Tibet. The Bryum argenteum specimens collected in the arid and semi-arid regions of Tibet from 2007 to 2015 were taken for 8 samples each specimen, and slides of plants and leaves were made. The slides were photo graphed and we measured the plant height, leaf length, leaf width, costa length, costa width and hair-point length, and measured the correlations between them and the environmental factors. Our results showed that the morphological characteristics of bryophytes are closely related to environmental variation, among which the hair-point length and plant height showed high coefficient of variation and phenotypic plasticity. The effects of environmental variation on bryophytes are largely different in different substrates. The morphological traits of terricolous Bryum argenteum are largely influenced by growing season precipitation, soil pH, and soil texture, while the morphological traits of saxicolous Bryum argenteum are largely influenced by elevation, growing season temperature, annual precipitation, and total nitrogen, available phosphorus and organic matter in soil. Our study showed the various functional traits of bryophytes are closely related and the combination of these traits collaboratively responds to environmental variation. [ABSTRACT FROM AUTHOR]

A series of 6-hydroxyaurones and their analogues have been synthesized and evaluated for their in vitro α-glucosidase inhibitory and glucose consumption-promoting activity. These compounds exhibited varying degrees of α-glucosidase inhibitory activity, 11 of them showing higher potency than that of the control standard acarbose (IC 50 = 50.30 μM). Surprisingly, analogues devoid of a substituent at C-2 but having an aryl group at C-5 were found to be highly active (e.g., 7f , IC 50 = 9.88 μM). Docking analysis substantiated these findings. The kinetic analysis of compound 7f , the most potent α-glucosidase inhibitor of this study, revealed that it inhibited α-glucosidase in an irreversible and mixed competitive mode. In addition, compounds 7f and 10c exhibited significant glucose consumption promoting activity at 1 μM. [ABSTRACT FROM AUTHOR]

Continuous cropping of Fenghua taro leads to poor quality. In this research, two pollution tolerant algae, Spirulina platensis and Chlorella vulgaris , were selected as conditioners for continuous cropping obstacles of taro production. The composition, abundance, and biodiversity of the bacteria and fungi communities in soil rhizosphere of continuous cropping were compared to non-continuous cropping, and studied in-depth. These results showed that the growth of taro during continuous cropping, when irrigated with Chlorella vulgaris and Spirulina platensis, was significantly better than the control group without algal cell irrigation. Accordingly, the plant height, leaf length, leaf area, moisture, carbohydrate, and protein in continuous cropping were 128 cm, 69 cm, 56 cm, 72 g/100 g, 10.8 g/100 g and 2.4 g/100 g, respectively, when watered with Chlorella vulgaris. Furthermore, compared with continuous cropping, the abundance of plant pathogens in the taro rhizosphere, fertilized with Spirulina platensis, were significantly reduced, while the corresponding abundance of soil beneficial bacteria was significantly increased. Specifically, the abundance of beneficial bacteria Ceratobasidium and Pulveroboletus increased, and the pathogens such as Curvularia , Erysiphe , and Clonostachys decreased, during continuous cropping when irrigated with Spirulina platensis. Live microalgae, after wastewater treatment, could be used as potential conditioners to avoid obstacles during continuous cropping of taro production. [Display omitted] • Chlorella vulgaris and Spirulina platensis grew well in swine wastewater. • Spirulina platensis improved the growth of taro with continuous cropping. • Soil microbial community may be the important factor affecting taro growth. • Algae alleviate taro growth obstacles by optimizing the abundance of microbes. • Live microalgae could be used as potential conditioners to taro production. [ABSTRACT FROM AUTHOR]

• Didymodon rigidulus flexibly adapts to the cold and dry environment in Tibet. • 12 morphological traits of plant height, leaves and cells were investigated. • Greater variations were observed in plant height and leaf size than in cell traits. • MAT and PET but not precipitation drive the variations of moss traits. Plant traits reflect the response and adaptation of plants to environmental changes and play important roles in the prediction of the effects of different environmental conditions on plants and plant-mediated processes. However, few studies have focused on the traits of nonvascular plants, such as bryophytes, although such plants are important participants in the primary productivity and biogeochemistry in harsh environments. In this study, the adaptive morphological traits and their interactions in the moss species that adapt to harsh and acute changeable environment were determined. Environmental factors that drive the changes in these traits were also evaluated. A total of 43 specimens of Didymodon rigidulus were collected from 38 sampling sites in arid and semi-arid regions in Tibet. Twelve morphological traits were investigated by microscope measurement, and then their interrelations and relations to environmental variables were quantified by employing Spearman's correlation analysis, hierarchical partitioning analysis, and partial least squares path modeling. Results showed that along with the environmental gradient, the plant height, leaves, and cells of D. rigidulus had changed significantly, and these parameters were largely interpretable in functional and adaptive terms. The lower the mean annual temperature (MAT) was, the thicker was the surface cell wall and the wider was the cell cavity of D. rigidulus. The higher potential evapotranspiration (PET) was, the thicker was the surface cell wall but the smaller were the leaves. MAT and PET were the main driving forces for the development of such traits of D. rigidulus. These results provide important insight into the adaptive syndrome of nonvascular plants associated with stress tolerance in the varied and harsh environment in Tibet. This study indicated the importance of considering the effects of climate change, especially the warming temperature on species adaption and community assemblage. [ABSTRACT FROM AUTHOR]

Celiac disease affects approximately 1% of the population and is a major public health problem worldwide. It is trigged by gluten-derived peptides, which have unusually high proline-glutamine motif content and are highly resistant to proteolysis by digestive enzymes of the gastrointestinal tract. The only treatment for celiac disease is strict, lifelong adherence to a gluten-free diet, which is effective but costly and difficult to maintain. Therefore, novel non-dietary therapies for celiac disease are urgently needed. Gluten-degrading enzymes are promising non-dietary treatments, and some enzymes have been investigated in preclinical or clinical studies. A combination of prolyl endopeptidase from Sphingomonas capsulata (SC PEP) and a glutamine-specific endoprotease (EP-B2 from barley) known as latiglutenase showed insufficient benefits in phase II clinical trials, likely because of its low enzyme activity in the gastric environment. Therefore, improving enzyme activity is essential for the clinical application of SC PEP. Enzyme activity can be enhanced using computer-aided rational protein design tools. In this study, we combined molecular docking and molecular dynamics simulation to rationally design SC PEP mutants and experimentally evaluated their activities. We identified mutants with up to 90–103% increases in specific activity and up to 80–202% increases in the catalytic rate. We have investigated the mechanism underlying the enhanced activity of these mutants, and found that a conformational transition of the β-propeller domain and catalytic domain of SC PEP was important for enzyme activity, and this transition was affected by residues in the catalytic domain and at the domain interface; a shorter distance between the substrate Pro and the oxyanion holes was also crucial for improving SC PEP catalytic activity. Our results provide useful information for the rational design of highly active SC PEPs to accelerate the development of enzyme therapeutics candidates for Celiac disease. Image 1 • SC PEP mutants with increases in specific activity and catalytic rate were identified using rational enzyme engineering. • The mechanism underlying the enhanced activity of SC PEP mutants was investigated based on the molecular dynamics simulation. • Computer-aided rational enzyme design parameters, such as interdomain angle, were set for designing SC PEP. • Our findings are beneficial for the development of enzyme therapeutics candidates for Celiac disease. [ABSTRACT FROM AUTHOR]

α-Glucosidase inhibitors are known to prevent the digestion of carbohydrates and reduce the impact of carbohydrates on blood glucose. Three series of tetracyclic oxindole derivatives were designed, synthesized and evaluated for α-glucosidase inhibitory activity in vitro . Compound 6t exhibited the most potent inhibitory activity with IC 50 0.7 μM and was about 170 times as active as acarbose (IC 50 = 115.8 μM). The kinetic analysis of compound 6t revealed it inhibited α-glucosidase in an irreversible and mixed manner. Fluorescence spectra indicated that 6t directly bound to α-glucosidase. Docking simulation showed the existence of potential H-bonding, van der Waals, Pi and Sigma-Pi interactions between 6t and α-glucosidase. [ABSTRACT FROM AUTHOR]

Three series of prenylated and/or geranylated flavonoids were synthesized and evaluated for their α-glucosidase inhibitory activity. The 3′,5′-digeranylated chalcone ( 16 ) was identified as a new α-glucosidase inhibitor whose activity (IC 50 = 0.90 μM) was 50-fold more than that of acarbose (IC 50 = 51.32 μM). Molecular docking studies revealed the existence of strong hydrophobic interaction and H-bonding between compound 16 and α-glucosidase’s active site. The inhibitory mode analysis showed that 16 exhibited a competitive inhibitory mode. [ABSTRACT FROM AUTHOR]