Bioactive prenylated c6-c3 derivatives from the roots of Illicium brevistylum.

Three new prenylated C6-C3 compounds (1-3), together with two known prenylated C6-C3 compounds (4-5) and one known C6-C3 derivative (6), were isolated from the roots of Illicium brevistylum A. C. Smith. The structures of 1-3 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, CD experiments and ECD calculations. The structure of illibrefunone A (1) was confirmed by single-crystal X-ray diffraction analysis. All compounds were evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated murine RAW264.7 macrophages and murine BV2 microglial cells, antiviral activity against Coxsackievirus B3 (CVB3) and influenza virus A/Hanfang/359/95 (H3N2). Compounds 3 and 4 exhibited potent inhibitory effects on the production of NO in RAW 264.7 cells with IC50 values of 20.57 and 12.87 µM respectively, which were greater than those of dexamethasone (positive control). Compounds 1 and 4-6 exhibited weak activity against Coxsackievirus B3, with IC50 values ranging from 25.87 to 33.33 µM.

Microfluidic Mechanoporation: Current Progress and Applications in Stem Cells.

Intracellular delivery, the process of transporting substances into cells, is crucial for various applications, such as drug delivery, gene therapy, cell imaging, and regenerative medicine. Among the different approaches of intracellular delivery, mechanoporation stands out by utilizing mechanical forces to create temporary pores on cell membranes, enabling the entry of substances into cells. This method is promising due to its minimal contamination and is especially vital for stem cells intended for clinical therapy. In this review, we explore various mechanoporation technologies, including microinjection, micro-nano needle arrays, cell squeezing through physical confinement, and cell squeezing using hydrodynamic forces. Additionally, we highlight recent research efforts utilizing mechanoporation for stem cell studies. Furthermore, we discuss the integration of mechanoporation techniques into microfluidic platforms for high-throughput intracellular delivery with enhanced transfection efficiency. This advancement holds potential in addressing the challenge of low transfection efficiency, benefiting both basic research and clinical applications of stem cells. Ultimately, the combination of microfluidics and mechanoporation presents new opportunities for creating comprehensive systems for stem cell processing.

Enhanced precision and efficiency in metabolic regulation: Compartmentalized metabolic engineering.

Metabolic engineering has witnessed remarkable advancements, enabling successful large-scale, cost-effective and efficient production of numerous compounds. However, the predominant expression of heterologous genes in the cytoplasm poses limitations, such as low substrate concentration, metabolic competition and product toxicity. To overcome these challenges, compartmentalized metabolic engineering allows the spatial separation of metabolic pathways for the efficient and precise production of target compounds. Compartmentalized metabolic engineering and its common strategies are comprehensively described in this study, where various membranous compartments and membraneless compartments have been used for compartmentalization and constructive progress has been made. Additionally, the challenges and future directions are discussed in depth. This review is dedicated to providing compartmentalized, precise and efficient methods for metabolic production, and provides valuable guidance for further development in the field of metabolic engineering.

A New Potent Inhibitor against α-Glucosidase Based on an In Vitro Enzymatic Synthesis Approach.

Inhibiting the activity of intestinal α-glucosidase is considered an effective approach for treating type II diabetes mellitus (T2DM). In this study, we employed an in vitro enzymatic synthesis approach to synthesize four derivatives of natural products (NPs) for the discovery of therapeutic drugs for T2DM. Network pharmacology analysis revealed that the betulinic acid derivative P3 exerted its effects in the treatment of T2DM through multiple targets. Neuroactive ligand-receptor interaction and the calcium signaling pathway were identified as key signaling pathways involved in the therapeutic action of compound P3 in T2DM. The results of molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations indicate that compound P3 exhibits a more stable binding interaction and lower binding energy (-41.237 kcal/mol) with α-glucosidase compared to acarbose. In addition, compound P3 demonstrates excellent characteristics in various pharmacokinetic prediction models. Therefore, P3 holds promise as a lead compound for the development of drugs for T2DM and warrants further exploration. Finally, we performed site-directed mutagenesis to achieve targeted synthesis of betulinic acid derivative. This work demonstrates a practical strategy of discovering novel anti-hyperglycemic drugs from derivatives of NPs synthesized through in vitro enzymatic synthesis technology, providing potential insights into compound P3 as a lead compound for anti-hyperglycemic drug development.

Cadinane sesquiterpenes from the stems and branches of Illicium ternstroemioides.

Three new cadinane sesquiterpenes (1-3) and three known sesquiterpenes were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith. The structures of the new compounds were elucidated by extensive analysis of spectroscopic and HRESIMS data. The structures of illiternins A-C (1-3) were confirmed by single crystal X-ray diffraction, allowing for the determination of their absolute configurations. Compounds 3 and 6 exhibited antiviral activity against Coxsackievirus B3 with IC50 values of 33.3 and 57.7 µM, respectively.

Microbial production and applications of ß-glucosidase-A review.

ß-Glucosidase exists in all areas of living organisms, and microbial ß-glucosidase has become the main source of its production because of its unique physicochemical properties and the advantages of high-yield production by fermentation. With the rise of the green circular economy, the production of enzymes through the fermentation of waste as the substrate has become a popular trend. Lignocellulosic biomass is an easily accessible and sustainable feedstock that exists in nature, and the production of biofuels from lignocellulosic biomass requires the involvement of ß-glucosidase. This review proposes ways to improve ß-glucosidase yield and catalytic efficiency. Optimization of growth conditions and purification strategies of enzymes can increase enzyme yield, and enzyme immobilization, genetic engineering, protein engineering, and whole-cell catalysis provide solutions to enhance the catalytic efficiency and activity of ß-glucosidase. Besides, the diversified industrial applications, challenges and prospects of ß-glucosidase are also described.

SVFR: A novel slice-to-volume feature representation framework using deep neural networks and a clustering model for the diagnosis of Alzheimer's disease.

Deep neural networks (DNNs) have been effective in classifying structural magnetic resonance imaging (sMRI) images for Alzheimer's disease (AD) diagnosis. In this study, we propose a novel two-phase slice-to-volume feature representation (SVFR) framework for AD diagnosis. Specifically, we design a slice-level feature extractor to automatically select informative slice images and extract their slice-level features, by combining DNN and clustering models. Furthermore, we propose a joint volume-level feature generator and classifier to hierarchically aggregate the slice-level features into volume-level features and to classify images, by devising a spatial pyramid set pooling module and a fusion module. Experimental results demonstrate the superior performance of the proposed SVFR, surpassing the majority of the state-of-the-art methods and achieving comparable results to the best-performing approach. Experimental results also showcase the efficacy of the slice-level feature extractor in the selection of informative slice images, as well as the effectiveness of the volume-level feature generator and classifier in the integration of slice-level features for image classification. The source code for this study is publicly available at https://github.com/gll89/SVFR.

Hosts engineering and in vitro enzymatic synthesis for the discovery of novel natural products and their derivatives.

Novel natural products (NPs) and their derivatives are important sources for drug discovery, which have been broadly applied in the fields of agriculture, livestock, and medicine, making the synthesis of NPs and their derivatives necessarily important. In recent years, biosynthesis technology has received increasing attention due to its high efficiency in the synthesis of high value-added novel products and its advantages of green, environmental protection, and controllability. In this review, the technological advances of biosynthesis strategies in the discovery of novel NPs and their derivatives are outlined, with an emphasis on two areas of host engineering and in vitro enzymatic synthesis. In terms of hosts engineering, multiple microorganisms, including Streptomyces, Aspergillus, and Penicillium, have been used as the biosynthetic gene clusters (BGCs) provider and host strain for the expression of BGCs to discover new compounds over the past years. In addition, the use of in vitro enzymatic synthesis strategy to generate novel compounds such as triterpenoid saponins and flavonoids is also hereby described.

Dynamic metabolites: A bridge between plants and microbes.

Plant metabolites have a great influence on soil microbiomes. Although few studies provided insights into plant-microbe interactions, we still know very little about how plants recruit their microbiome. Here, we discuss the dynamic progress that typical metabolites shape microbes by a variety of factors, such as physiographic factors, cultivar factors, phylogeny factors, and environmental stress. Several kinds of metabolites have been reviewed, including plant primary metabolites (PPMs), phytohormones, and plant secondary metabolites (PSMs). The microbes assembled by plant metabolites in return exert beneficial effects on plants, which have been widely applied in agriculture. What's more, we point out existing problems and future research directions, such as unclear mechanisms, few species, simple parts, and ignorance of absolute abundance. This review may inspire readers to study plant-metabolite-microbe interactions in the future.

Understanding evolutionary process of public participation leveraging agent-based simulation: The case of waste incineration power projects.

Public participation, as a vital way for conflict management, has attracted increasing attention. Although previous studies have examined the determinants of public participation, the evolutionary process of the participatory behavior has seldom been investigated. Based on the motivation-opportunity-ability theory, a concept model was constructed to illustrate individual behavior of participation in waste incineration power (WIP) projects. Data collected from a questionnaire survey was used to examine the important factors involved in the concept model that significantly influence public's willingness to participate in WIP projects. Thereafter, an agent-based simulation within a social network based on the opinion propagation dynamics was developed to simulate the change of the agents and several simulation experiments were implemented. It was found that with the dissemination of information and the interaction of opinions, the whole network tends to converge to a few central nodes, and the difference of degree of each node also increases gradually. The increase of interaction threshold and moral incentive significantly enhance average participation intention and the proportion of participants. The findings advocate for promoting information disclosure, strengthening opinion interaction between individuals, and emphasizing the internalization of moral sense into the individual's own sense of obligation. This study could enhance the understanding of evolutionary process of public participation in WIP projects and provide valuable suggestions for the promotion of sustainable development of environmental projects.

Diverse prenylated C6-C3 derivatives from the stems and branches of Illicium ternstroemioides A. C. Smith with anti-inflammatory and antiviral activities.

Fifteen unreported prenylated C6-C3 derivatives (1-15) were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith, including one bis-prenylated C6-C3 derivative (1), three prenylated C6-C3 derivative-shikimic acid ester hybrids (2-4) and 11 prenylated C6-C3 monomers (5-15). The structures of compounds 1-15 were elucidated by spectroscopic analysis (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of the compounds were determined using electronic circular dichroism (ECD), induced circular dichroism (ICD), and the modified Mosher's method. Among the isolates, compounds 11, 12, and 15 exhibited significant anti-inflammatory activities by inhibiting the nitric oxide with IC50 values ranging from 1.89 to 24.83 µM in lipopolysaccharide-stimulated murine RAW 264.7 macrophages and murine BV2 microglial cells; compounds 2, 3, and 7 exhibited antiviral activitives against Coxsackievirus B3 with an IC50 value of 33.3, 25.9, and 27.8 µM, respectively.

Bergamotane-type sesquiterpenes from the leaves and twigs of Illicium oligandrum and their anti-inflammatory activities.

Eight undescribed ß-bergamotene-type sesquiterpene oliganins A-H (1-8) and one known α-bergamotene-type sesquiterpene (9) were isolated from the leaves and twigs of Illicium oligandrum Merr. & Chun. The structures of compounds 1-8 were elucidated by extensive spectroscopic data, and the absolute configurations were determined by using a modified Mosher's method and electronic circular dichroism calculations. The isolates were further evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated RAW264.7 and BV2 cells. Compounds 2 and 8 exhibited potent inhibitory effects on the production of NO with IC50 values ranging from 21.65 to 49.28 µM, which were greater than or comparable to those of dexamethasone (positive control).

Development of structural equation models to unveil source-sink switches of mid-latitude soils for semi-volatile banned pesticides.

A variety of semi-volatile banned pesticides (SVBPs) are ubiquitous in soils of mid-latitude regions. SVBPs undertake complicated soil-gas exchange processes in mid-latitude regions, challenging the understanding of source or sink roles of soils for the semi-volatile contaminants. Herein, we develop structural equation models (SEMs) to unveil source or sink roles of mid-latitude soils (Liaoning, China) in winter and summer for 12 SVBPs (7 organochlorine and 5 organophosphorus pesticides). The 12 SVBPs exhibit different distribution patterns in soils, dependent of sampling seasons, soil characteristics, topographic/climate conditions of soil sites and chemical properties of compounds. SEM Model I (winter) and Model II (summer) reveal the distribution patterns of SVBPs in soils over season changes, indicating sink-source switches of soils for SVBPS from winter to summer. In winter, soil is a sink of 12 SVBPs in the study area, associated with the inputs of SVBPs in soils by air-particulate partition and dry depositions. However, in summer, soil is mainly a source of the same contaminants, mainly through the volatilization and leaching of SVBPs in soils. The sink-source switches of soils for SVBPs are usually dependent of chemical properties of compounds to higher extents than soil characteristics and topographic/climate conditions of soil sites, though these parameters pose different influences in winter and summer. It has been revealed that soil acts as a sink of SVBPs in winter, associated with the inputs of SVBPs in soils by air-particulate partition and dry depositions, whereas soil acts as a source of SVBPs in summer, mainly through the volatilization and leaching of SVBPs in soils. This finding may provide new insights into the unique distribution patterns of SVBPs in soils in mid-latitude regions.

seco-Sesquiterpenes and acorane-type sesquiterpenes with antiviral activity from the twigs and leaves of Illicium henryi Diels.

Chemical investigation of an alcohol extract from the twigs and leaves of Illicium henryi Diels resulted in the isolation of two new acorane-related seco-sesquiterpenes (1 and 3), two new acorane-related seco-norsesquiterpenes (2 and 4), one new 2-epi-cedrane sesquiterpene (5), eight new acorane-type sesquiterpenes (6-13), and a known major constituent of acorenone B (14). Their structures were established by interpreting extensive spectroscopic data, including HRESIMS, NMR (1H and 13C NMR, 1H-1H COSY, HSQC, and HMBC), and NOE difference spectra analysis. The absolute configurations of 1, 2, 4-7, 9, 10, and 14 were determined by X-ray crystallography, while chemical transformation methods were performed with compound 14 as the starting material to elegantly solve the absolute configuration issue of compounds 8 and 11-13. Notably, 1 and 2 are seco-sesquiterpenes that are related to acorane and possess an unusual ketal-linked hemiacetal in a 6,8-dioxabicyclo[3.2.1]octan-7-ol scaffold ring system. Plausible biosynthetic pathways for compounds 1-14, which were derived from the acorane skeleton, were proposed. All the isolated compounds (1-14) were evaluated for their antiviral and cytotoxic activities.

Current approaches and strategies to identify Hedgehog signaling pathway inhibitors for cancer therapy.

The Hedgehog signaling pathway plays a vital role in embryonic development and tissue patterning. Aberrant regulation of this pathway is commonly associated with the occurrence, development and progression of various types of malignancies. The development of inhibitors targeting Hedgehog pathway has attracted significant interests in cancer therapy and led to the discovery of three drugs Vismodegib, Sonidegib and Glasdegib. However, their clinical application has been hampered due to adverse effects and resistance issues, highlighting the urgent need for new inhibitors. Herein we give a systematic overview of the current status and characteristics of various approaches to developing the Hedgehog pathway inhibitors, including library screening, natural product-oriented approach, analogue approach, drug repositioning, in silico tools and others. The future prospects are also discussed for the discovery and development of next-generation inhibitors.

Chemical constituents from the fruits of Illicium simonsii and their antiviral activity and neuroprotective effect.

One undescribed diterpenoid illisimonone A, four undescribed sesquiterpenes named (±)-simonones A, simonterpenoids A and B, and two undescribed lignans, illisimonins A and B, along with five known compounds were isolated from the fruits of Illicium simonsii. Their structures were elucidated by extensive spectroscopic data. The absolute configuration of illisimonone A was determined by single-crystal X-ray diffraction analysis. Illisimonone A showed potential antiviral activity against the Coxsackie B3 virus, with an IC50 value of 3.70 µM. Illisimonin B and henrylactone A showed potential neuroprotective effects against oxygen-glucose deprivation induced cell injury in SK-N-SH cells, with survival rates of 57.6%, 58.0%, respectively.

Copper-Catalyzed Cascade Annulation of o-Hydroxyphenyl Propargylamines with Pyrazolin-5-ones to Access Pyrano[2,3-c]pyrazoles.

An efficient copper-catalyzed cascade annulation of o-hydroxyphenyl propargylamines and pyrazolin-5-ones is described. This methodology leads to the rapid assembly of a series of valuable pyrano[2,3-c]pyrazoles with good yields across a wide range of substrates in a simple fashion. This novel reaction involves the formation of alkynyl ortho-quinone methides, a 1,4-conjugate addition, and a subsequent 6-endo cyclization process. The mechanistic elucidation is well supported by control experiment and literature precedents.

Prenylated C6-C3 derivatives from the stems and branches of Illicium ternstroemioides A. C. Smith with antiviral activity.

Thirteen compounds were isolated from the lipid-soluble extracts of Illicium ternstroemioides A. C. Smith, including eleven previously undescribed prenylated C6-C3 compounds, a previously undescribed prenylated C6-C3 derivative-abscisic acid ester hybrid, and a known compound (4S)-illicinone I. Their structures and configurations were mainly elucidated by spectroscopic analyses, CD experiments and X-ray crystallography. (2S,4R,11S)-4-O-methyl-12-chloroillifunone C, (2S,4R,11R)-2,3-dihydro-4-O-methyl illioliganfunone D, and illiternfunol A were found to exhibit weak activity against Coxsackievirus B3, with IC50 values ranging from 27.8 to 33.3 µM. Illiternone B exhibited more potent activities against Coxsackievirus B3 and influenza virus A than did its geometric isomer illiternone A, with IC50 values of 7.7 µM and 2.5 µM, respectively. None of these compounds displayed cytotoxic activities.

Bioavailability for organic chemical bioaccumulation follows the power law.

Despite the importance of bioavailability for organic chemical bioaccumulation by terrestrial and benthic invertebrates, the principles of bioavailability for organic chemical bioaccumulation remain poorly understood. Here we use large-scale databases with contrasting geographic, compound and organism coverage (from 925 sites, 446 compounds and 184 invertebrate species), and report that bioavailability for organic chemical bioaccumulation follows the power law. It represents that the internal concentration of organic chemicals is the composite power function of the lipid fraction of invertebrates, bulk site concentration of compounds, and organic carbon content of soils/sediments. This law directly links environmental exposures and body burdens of organic chemicals in contaminated sites, and provides a method for enabling case-specific risk assessments of a vast number of organic chemicals and contaminated sites. Our findings may pave the way for translating bioavailability knowledge into risk-oriented regulation of organic chemicals and contaminated sites.

Rh(III)-Catalyzed Regioselective Annulations of 3-Arylisoxazolones and 3-Aryl-1,4,2-dioxazol-5-ones with Propargyl Alcohols: Access to 4-Arylisoquinolines and 4-Arylisoquinolones.

The Rh(III)-catalyzed dual directing group assisted C-H activation/annulation of 3-arylisoxazolones with propargyl alcohols has been developed, which expands the application scope of isoxazolones in organic synthesis. This protocol also worked well with 3-aryl-1,4,2-dioxazol-5-ones to produce synthetically and biologically important 4-arylisoquinolones.