Programmable Chemical Evolution with Natural/non-natural Building Blocks.

Non-natural building blocks (BBs) present a vast reservoir of chemical diversity for molecular recognition and drug discovery. However, leveraging evolutionary principles to efficiently generate bioactive molecules with a larger number of diverse BBs poses challenges within current laboratory evolution systems. Here, we introduce programmable chemical evolution (PCEvo) by integrating chemoinformatic classification and high-throughput array synthesis/screening. PCEvo initiates evolution by constructing a diversely combinatorial library to create ancestral molecules, streamlines the molecular evolution process and identifies high-affinity binders within 2-4 cycles. By employing PCEvo with 108 BBs and exploring >10^17 chemical space, we identify bicyclic peptidomimetic binders against targets SAR-CoV-2 RBD and Claudin18.2, achieving nanomolar affinity. Remarkably, Claudin18.2 binders selectively stain gastric adenocarcinoma cell lines and patient samples. PCEvo achieves expedited evolution in a few rounds, marking a significant advance in utilizing non-natural building blocks for rapid chemical evolution applicable to targets with or without prior structural information and ligand preference.

An ontological framework for the formalization, organization and usage of TCM-Knowledge.

BACKGROUND: The traditional Chinese Medicine Language System (TCMLS) is a large-scale terminology system, developed from 2002 on by the Institute of Information of Traditional Chinese Medicine (IITCM). Until now, more than 120,000 concepts, 300,000 terms and 1.27 million semantic relational links are included. Its top-level framework, called TCMLS-semantic network (SN), provides an important basis for the standardization and mapping of traditional Chinese Medicine (TCM) terminology systems. Though, many data produced and stored in TCMLS have poor quality for historical reasons or because of human factors. There is a large number of classification errors or inconsistent expressions of terms remained in the current TCMLS- SN, which hamper an efficient utilization of the data stored in TCMLS in practical applications. METHODS: We start with analyzing the technical specification based on TCMLS, considering some obvious classification errors and problems of ambiguity of semantic expressions in TCMLS-SN, followed with using a top-down approach for building a middle level ontology which is based on the framework General Formal Ontology (GFO), take into account the compatibility with TCM related concepts, turn out the results of a modification of the current TCMLS-SN, called GFO-TCM. RESULTS: Through comparison with TCMLS-SN, according to viewpoints of GFO, some semantic types and relations were reconstructed within GFO-TCM. We propose a middle level ontology for TCMLS which may support entailment and ensure coherence, we also draw out a mapping which possess a more reasonable framework with a unified semantic criterion, it is application scenarios oriented and can be further updated and extended. CONCLUSIONS: The goal is to construct a formal middle-level ontology that is compatible with both the traditional medical terminology system and modern medical terminology standards. it is intended to satisfy functional requirements which are relevant for natural language processing, information extraction, semantic retrieval, clinical decision support in the field of traditional Chinese medicine. It also provides a foundation and methodology for building a large-scale, unified semantic and extensible knowledge graph platform.

Penthorum chinense Pursh leaf tea debittering mechanisms via green tea manufacturing process and its influence on NAFLD-alleviation activities.

The green-tea manufacturing process showed good effect of flavor improving, debittering and shaping in making Penthorum chinensePursh leaf (PL) tea (PLT), which serves as a polyphenol dietary supplement and beverage raw material. GC-MS results showed that its unpleasant grassy odor decreased by 42.8% due to dodecanal, geranylacetone, and (E)-2-nonenal reduction, coupled with 1-hexadecanol increasing. UPLC-ESI-TOF-MS identified 95 compounds and showed that the debittering effect of green-tea manufacturing process was attributed to decreasing of flavonols and lignans, especially quercetins, kaempferols and luteolins, and increasing of dihydrochalcones which act as sweeteners bitterness-masking agents, while astringency was weakened by reducing delphinidin-3,5-O-diglucoside chloride, kaempferol-7-O-ß-d-glucopyranoside, and tannins. The increase of pinocembrins and catechins in aqueous extracts of PLT, maintained its hepatoprotective, NAFLD-alleviation, and hepatofibrosis-prevention activities similar to PL in high fat-diet C57BL/6 mice, with flavonoids, tannins, tannic acids, and some newfound chemicals, including norbergenin, gomisin K2, pseudolaric acid B, tanshinol B, as functional ingredients.

[Research on ontology construction of acupuncture effect based on ISO/TS 16843-6: 2022].

In order to specify the information expression of acupuncture effect and realize the knowledge reuse and sharing, in view of animal experiments and clinical trials, the relevant knowledge of acupuncture effect is allocated. Using seven-step method and Protégé5.5.0 tool, the ontology of acupuncture effect is constructed on the base of ISO/TS 16843-6: 2022. A total of 199 classes are constructed, including 7 categories (acupuncture point, acupuncture therapy, needling method, biological process, genes and gene products, disorder, and anatomic structure), 12 object properties, 1 108 instances and 5 123 axioms. A semantic network with the characteristics of acupuncture and moxibustion is established and the structured expression for the knowledge of acupuncture effects is obtained, which lays the foundation for the innovation and development in the field of acupuncture and moxibustion.

Anti-hyperglycemic effect of chebulagic acid from the fruits of Terminalia chebula Retz.

In the present study, we firstly compared rat intestinal α-glucosidase inhibitory activity by different ethanol-aqueous extractions from the dried fruits of Terminalia chebula Retz. The enzymatic assay showed that the 80% ethanol extract was more potent against maltase activity than both 50% and 100% ethanol extracts. By HPLC analysis, it was determined that the 80% ethanol extract had a higher content of chebulagic acid than each of 50% or 100% ethanol extract. Next, we investigated how efficiently chebulagic acid could inhibit sugar digestion by determining the glucose level on the apical side of the Caco-2 cell monolayer. The result showed that the maltose-hydrolysis activity was down-regulated by chebulagic acid, which proved to be a reversible inhibitor of maltase in Caco-2 cells. On the other hand, chebulagic acid showed a weak inhibition of sucrose-hydrolysis activity. Meanwhile, chebulagic acid did not have an obvious influence on intestinal glucose uptake and was not effective on glucose transporters. Further animal studies revealed that the oral administration of chebulagic acid (100 mg/kg body weight) significantly reduced postprandial blood glucose levels by 11.1% in maltose-loaded Sprague-Dawley (SD) rats compared with the control group, whereas the oral administration of chebulagic acid did not show a suppressive effect on postprandial hyperglycemia in sucrose- or glucose-loaded SD-rats. The results presented here suggest that chebulagic acid from T. chebula can be used to control blood glucose and manage type 2 diabetes, although clinical trials are needed.

(+)-Terpinen-4-ol Inhibits Bacillus cereus Biofilm Formation by Upregulating the Interspecies Quorum Sensing Signals Diketopiperazines and Diffusing Signaling Factors.

Bacillus cereus is a Gram-positive endospore-forming foodborne pathogen that causes lethal food poisoning and significant economic losses, usually through biofilm- and endospore-induced recurrent cross- and postprocessing contamination. Due to the lack of critical inhibitory targets and control strategies, B. cereus biofilm contamination is a problem that urgently needs a solution. In this study, the antibacterial and antibiofilm activities of several natural potential bacterial quorum sensing (QS) interferers, a group of spice-originated monoterpenoids, were screened, and terpinen-4-ol effectively inhibited B. cereus growth and biofilm and spore germination with minimum growth inhibition and 50% biofilm inhibitory concentrations of 8 and 2 µmol/mL, respectively. FESEM/CLSM and phenotypic research illustrated that in addition to a decrease in the number of attached B. cereus cells, (+)-terpinen-4-ol also obviously reduced extracellular matrix synthesis, especially exopolysaccharides, and inhibited the swarming motility and protease activity of B. cereus. (+)-Terpinen-4-ol did not exert a significant effect on AI-2 signals in B. cereus. Accordingly, the B. cereus-produced interspecies QS signals diffusing signal factors (DSFs, C8-C15) and diketopiperazines (DKPs) were detected and identified here, which suppressed B. cereus biofilm formation in a concentration-dependent manner. (+)-Terpinen-4-ol significantly increased the levels of specific DSF and DKP signals in B. cereus and down-regulated the gene expression of some rpfB homologues in transcription level. Moreover, both DKPs and DSFs inhibited swarming motility and protease activity in B. cereus, while just the DSF signals 2-dodecenoic acid and 11-methyl-2-dodecenoic acid inhibited exopolysaccharide synthesis like (+)-terpinen-4-ol. In summary, B. cereus strains were found to produce nine DSF- and six DKP-type QS signaling molecules, which repressed B. cereus biofilm formation. (+)-Terpinen-4-ol was confirmed to be a promising antibacterial and antibiofilm agent against B. cereus upregulating DSFs and DKPs levels, and it could target the critical genes rpfB for DSFs turnover.

Premna microphylla Turcz leaf pectin exhibited antioxidant and anti-inflammatory activities in LPS-stimulated RAW 264.7 macrophages.

Premna microphylla turcz leaf juice with polysaccharides (PMPs) as its main component, are raw material of jelly-like Chinese traditional food "Guanyin tofu", which were also experiencedly used to relieve inflammation-related symptoms. Here three kinds of PMPs were extracted in alkaline (APMP), water (WPMP) and acidic (HPMP) conditions, being characteristic of RG I, high- and low-methoxyl HG pectin, respectively, in amorphous form with diverse surface microstructures, among which APMP predominantly composed of Glucose instead of galacturonic acid, showing wider molecular weight distribution and more branched chains. PMPs showed remarkable radical scavenging capability, and especially APMP at concentrations above 50 µg/mL effectively inhibited the reactive oxygen species and malondialdehyde production in LPS-stimulated RAW 264.7 macrophages, by enhancing enzymatic activities of endogenous superoxide dismutase, glutathione peroxidase and catalase, and accordingly alleviated inflammatory cytokines. Thus, PMPs could be promising non-toxic natural dietary supplement to improve chronic inflammation-induced diseases.

Biomechanical behaviour of temporomandibular joints during opening and closing of the mouth: A 3D finite element analysis.

Temporomandibular joints (TMJs) constitute a pair of joints that connect the jawbone to the skull. TMJs are bilateral joints which work as one unit in conducting daily functions such as speaking, mastication, and other activities associated with the movement of the jaw. Issues associated with the TMJs may arise due to various factors-one such factor being the internal load on the TMJ. These issues may contribute to temporomandibular disorders (TMD). This study aims to evaluate the mandibular trajectories and the associated stress changes during the process of opening the mouth on the TMJs of an asymptomatic subject. The mouth opening motion was recorded by a motion capturing system using models of the mandible and maxilla constructed based on the computed tomography (CT). Two discs constructed based on magnetic resonance imaging (MRI). Finite element analysis was performed on the relative motion of the mandible to the maxilla and validated. The process modelled by these displacements provided less than 10% error in terms of deformation. The simulation results indicate that the lateral intermediate zone-the head and neck of the mandible-and the articular eminence sustained the most significant stresses during the mouth opening motion. The results also suggested that the stresses increase as the range of opening increases with the greatest von Mises stress, tensile, and compressive stress found at the position of maximal opening.

Defining Acupuncture-Moxibustion: A Delphi Study Protocol.

BACKGROUND: With the worldwide use and modern development of acupuncture-moxibustion, there is disagreement on its basic definition. There has been an obstacle for clinical practice, research, and legislation. Considering this challenge, the World Federation of Acupuncture-Moxibustion Societies proposes to develop the definition and basic scope of acupuncture-moxibustion with a Delphi study. METHODS: A reactive Delphi method will be used to ask a group of experts to rate the relevance and clarity of a predesigned initial item list. This list was generated by the steering committee through a literature review and group discussion. Forty experts will be selected from many disciplines and continents to ensure appropriate representation. Predefined rules will be applied to modify the items until a consensus is achieved. After achieving the consensus on all items through the survey round, the steering committee will form the definition and basic scope of acupuncture-moxibustion by organizing a literal statement with a detailed explanation.

Numerical calculation of boundary layers and wake characteristics of high-speed trains with different lengths.

Trains with different numbers of cars running in the open air were simulated using the delayed detached-eddy simulation (DDES). The numbers of cars included in the simulation are 3, 4, 5 and 8. The aim of this study was to investigate how train length influences the boundary layer, the wake flow, the surface pressure, the aerodynamic drag and the friction drag. To certify the accuracy of the mesh and methods, the drag coefficients from numerical simulation of trains with 3 cars were compared with those from the wind tunnel test, and agreement was obtained. The results show that the boundary layer is thicker and the wake vortices are less symmetric as the train length increases. As a result, train length greatly affects pressure. The upper surface pressure of the tail car reduced by 2.9%, the side surface pressure of the tail car reduced by 8.3% and the underneath surface pressure of the tail car reduced by 19.7% in trains that included 3 cars to those including 8 cars. In addition, train length also has a significant effect on the friction drag coefficient and the drag coefficient. The friction drag coefficient of each car in a configuration decreases along the length of the train. In a comparison between trains consisting of 3 cars to those consisting of 8 cars, the friction drag coefficient of the tail car reduced by 8.6% and the drag coefficient of the tail car reduced by 3.7%.

Analysis of N-nitrosodiethylamine by ion chromatography coupled with UV photolysis pretreatment.

Nitrosamines such as N-nitrosodiethylamine (NDEA) are commonly detected by spectrophotometry after photolysis and Griess reaction (PG) in food industries for lower cost. Results of this research indicate that NDEA decays rapidly under UV irradiation, and concentrations of the generated NO2- and NO3- ions vary with photolysis conditions. Thus, the measurement of the PG method may be inconsistent because it is based on the amount of photoproduced NO2-. In addition, more errors may be present in the PG method since NO3- cannot be measured colorimetrically using Griess reagent. In this work, the sum of the concentrations of photoproduced NO2- and NO3- was found to be equivalent to the initial NDEA before photolysis, and a photolysis-ion chromatography method was validated, which may serve as a feasible and accurate method to determine nitrosamines.

The rheological properties of tara gum (Caesalpinia spinosa).

The rheological properties of tara gum, as affected by concentration, temperature, pH and the presence of salts and sucrose, were investigated by using steady and dynamic shear measurements and atomic force microscope observation. Tara gum exhibited non-Newtonian, pseudoplastic behaviour without thixotropy at tested concentrations (0.2-1.0%, w/v). Salts (CaCl2 and NaCl) led to a viscosity reduction, which was more sensitive to Ca(2+) than to Na(+). The gum had stable viscosity over a wide pH range (pH 3-11), and the influence of sucrose was concentration dependent. Increasing temperature from 20°C to 80°C decreased the gum viscosity. Frequency sweeps indicated that tara gum (1.0% w/v) behaved as a liquid at low frequency, and acted more like a gel at high frequency. With the decrease of concentration, tara gum may show a viscous property rather than an elastic one. These results are potentially useful for the application of tara gum in food processing.

Antioxidant activity and characterization of antioxidant polysaccharides from pine needle (Cedrus deodara).

A novel antioxidant polysaccharide (APC) was isolated and characterized from pine needles of Cedrus deodara with the evaluation of its in vitro antioxidant activity. According to gel filtration chromatography, high performance size exclusion chromatography, gas chromatography-mass spectrometry, partial acid hydrolysis, periodic acid oxidation, Smith degradation and methylation analysis, APC was observed to be an acidic heteropolysaccharide (composed of glucose, arabinose, mannose and xylose in a molar ratio of 45.84:1:2.35:1.73) with the molecular weight of 1.53×10(4)Da, and the backbone was mainly composed by glucose, mannose and xylose in the form of (1→4) linked. Meanwhile, APC exhibited the remarkable antioxidant activity to scavenge free radicals and inhibit the oxidative injury of DNA and cells. The present results suggested that APC could be a potential antioxidant agent for preparing functional foods and nutraceuticals applied in food and pharmaceutical industries.

Characterization of antioxidant polysaccharides from Auricularia auricular using microwave-assisted extraction.

Influence of microwave-assisted extraction (MAE) to the characterization and corresponding antioxidant activity of polysaccharides from Auricularia auricula (AAP) was determined. According to gas chromatography-mass spectrometry, high performance size exclusion chromatography, Fourier transform infrared spectroscopy, partial acid hydrolysis, periodic acid oxidation, Smith degradation, methylation analysis and atomic force microscopy, AAP was a heteropolysaccharide (composed of glucose, galactose, mannose, arabinose and rhamnose at the molar ratio of 37.53:1:4.32:0.93:0.91) with the molecular weight of 2.77×10(4) Da, observed as a spherical lump, and the backbone of AAP was mainly composed by glucose with (1→3) linked. Moreover, AAP exhibited significant in vitro antioxidant activity in scavenging free radicals (ABTS, DPPH, superoxide and hydroxyl radicals), in lipid peroxidation and reducing power assays. The present result suggested that AAP by MAE had low molecular weight and remarkable antioxidant capability.

Chemical composition, antioxidant, and antimicrobial activities of essential oil from pine needle (Cedrus deodara).

UNLABELLED: The chemical composition of essential oil from pine needles (Cedrus deodara) was determined, and its antioxidant and antimicrobial activities were evaluated. Twenty-three components, representing 95.79% of the oil, were identified by gas chromatography mass spectrometry. The main components include α-terpineol (30.2%), linalool (24.47%), limonene (17.01%), anethole (14.57%), caryophyllene (3.14%), and eugenol (2.14%). Pine needle essential oil showed remarkable antioxidant activity in scavenging free radicals, in lipid peroxidation, and in reducing power assays. Moreover, the essential oil revealed strong antimicrobial activity against typical food-borne microorganisms, with minimum inhibitory concentration and minimum bactericidal concentration values of 0.2 to 1.56 and 0.39 to 6.25 µg/mL, respectively. Transmission electron microscope observation ascertained that the bactericidal mechanism of pine needle essential oil may be the induction of cytoplasmic outflow and plasmolysis. These results suggest that the essential oil from pine needles has potential to be used as a natural antioxidant and antimicrobial agent in food processing. PRACTICAL APPLICATION: The present study provides a theoretical basis for the potential application of essential oil from pine needles (C. deodara) to be used as a natural resource of antioxidant and antimicrobial agents in food industry.

Chemical composition, antimicrobial and antioxidant activities of essential oil from Gnaphlium affine.

The chemical composition of the essential oil from Gnaphlium affine was determined, and its antimicrobial and antioxidant activities were evaluated. Twenty-four compounds, representing 94.95% of the amount of total oil, were identified by gas chromatography-mass spectrometry (GC-MS) analysis. Main constituents of the essential oil were found to be eugenol (18.24%), linalool (10.62%), trans-caryophyllene (8.86%), α-terpineol (5.97%), p-cymene (5.75%), hexadecanoic acid (5.63%), γ-cadinene (4.98%), δ-cadinene (4.22%), α-humulene (3.22%), and (-)-ß-elemene (3.15%). The essential oil revealed a remarkable antimicrobial effect against the tested food-borne microorganisms with the MIC and MBC values in the ranges of 0.2-1.56 µg/ml and 0.39-3.13 µg/ml, respectively. The essential oil showed a potent antioxidant activity in ABTS radical scavenging, lipid peroxidation and reducing power assay. It was suggested that the essential oil from G. affine may be a new potential source as natural antimicrobial and antioxidant agents applied in food systems.

Antibrowning and antimicrobial activities of the water-soluble extract from pine needles of Cedrus deodara.

UNLABELLED: The antibrowning and antimicrobial activities of the water-soluble extract from pine needles of Cedrus deodara (CDE), a traditional Chinese medicine and raw materials of pine needle tea, was investigated. Total phenols of CDE were 31.4 ± 0.53 mg gallic acid equivalent/g, and total flavonoids were 23.1 ± 0.79 mg rutin equivalent/g. CDE showed a strong antioxidant activity against ABTS free radicals with IC(50) (the half-inhibitory concentration) of 25.5 ± 0.64 µg/mL. In mushroom tyrosinase inhibitory assay, IC(50) values were 2.1 ± 0.98 and 2.27 ± 0.93 mg/mL for monophenolase and diphenolase, respectively. Evaluated by detecting changes of L* (indicated the darkness of sample), a* (indicated the redness of sample), and b* (indicated the yellowness of sample) values in fresh-cut apple slices model, CDE showed a significant antibrowning effect when compared with ascorbic acid. In addition, it was discovered that CDE in combination with 0.5% ascorbic acid exhibited a synergistic antibrowning effect. Meanwhile, CDE was observed to show a potent antimicrobial effect on all of the tested Gram-positive and Gram-negative bacteria. In conclusion, the results of the present research suggested that pine needles of C. deodara could be used as a natural resource of antibrowning and antimicrobial agents in food preservation. PRACTICAL APPLICATION: The present study provides a theoretical basis for the potential application of pine needles of C. deodara to be used as a natural resource of antibrowning and antimicrobial agents in food industry.