Active Components Research Articles

Abstract C036: Pharmacological modulation of glutamine metabolism alters macrophage activity and tumor immune responses

Abstract As a critical component of innate and adaptive immunity, macrophages play an important role in shaping the tumor microenvironment (TME), which affects tumor initiation, progression, and response to treatment. Tumor-associated macrophages can display anti-tumor or pro-tumor activity, a cell fate attributed to macrophage polarization that depends on metabolomic regulation. Targeting macrophage metabolism could be a promising approach for cancer treatment by converting a pro-tumor TME into an anti-tumor TME. To examine in vivo mechanisms behind glutamine metabolism on macrophages, we treated immunocompetent murine ovarian cancer models with a clinical-grade glutamine prodrug, JHU083, and performed single-cell RNA sequencing (scRNAseq). In addition to the significant anti-tumor efficacy of JHU083, we found that JHU083 specifically suppressed the M2-like tumor macrophages while sparing M1-like macrophages. To better understand the molecular mechanism of how JHU083 causes macrophage polarization shift, we cultured an M1-like macrophage cell line with DON (6-Diazo-5-oxo-L-norleucine), the active component of JHU083, and performed bulk RNA sequencing. Using bulk RNAseq and scRNAseq transcriptome analyses on M1-like macrophages, glutamine inhibitor treatment significantly enhanced MHC class II genes, including CD74, H2-Aa, H2-Eb1, H2-Ea, H2-Ab1, and TNF family genes including Tnfsf12, and Tnfrsf14 which may promote T cell trafficking and cytotoxicity through reversing immunosuppressive tumor microenvironment. Moreover, DON-treated bone marrow-derived M1 macrophages promoted CD4+ T cell expansion. On the other hand, DON treatment significantly suppressed bone marrow-derived M2 macrophages. In conclusion, our findings suggest that glutamine metabolism reprogramming can promote anti-tumor functions in tumor macrophages. Therefore, targeting glutamine metabolism to regulate macrophage function and polarization can be a promising direction for future cancer therapy. Citation Format: Jiawei Fan, Sumeng Qi, Ie-Ming Shih, Tian-Li Wang. Pharmacological modulation of glutamine metabolism alters macrophage activity and tumor immune responses [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C036.

Sennoside A represses the malignant phenotype and tumor immune microenvironment of non-small cell lung cancer cells by inhibiting the TRAF6/NF-κB pathway.

Non-small cell lung cancer (NSCLC) is a prominent cause of cancer death worldwide. Sennoside A (SA) is the primary anthraquinone active component from Rheum officinale Baill and exerts antitumor functions in multiple human tumors. This research aimed to elucidate the function and mechanism of SA in NSCLC. SA functions in NSCLC were determined using Cell Counting Kit-8 (CCK-8) assay, Terminal deoxynucleotidyl transferase dUTP nick-end labeling analysis, Transwell assay, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blot. Meanwhile, the SA mechanism in NSCLC was examined with Western blot, immunofluorescence assay, CCK-8 assay, Transwell analysis, and ELISA. Furthermore, SA functions in NSCLC growth in vivo were assessed by the establishment of a tumor xenograft model, hematoxylin-eosin staining, analysis of NSCLC tissue apoptosis, and immunohistochemistry assays. Functionally, less than 200µM SA had no significant effect on normal human bronchial epithelial cell BEAS-2B cell viability. Furthermore, H460 cell viability was decreased when the SA dose was greater than or equal to 25µM (IC50 = 53.34µM). A549 cell viability was reduced when the SA dose was greater than or equal to 12.5µM (IC50 = 48.21µM). Also, SA repressed NSCLC cell proliferation and boosted cell apoptosis. SA restrained NSCLC cell invasion and tumor microenvironment. Mechanically, SA weakened NSCLC cell proliferation, invasion, and tumor microenvironment, yet this impact was abolished after transfecting pcDNA3.1-TRAF6, which indicated that SA repressed NSCLC cell proliferation, invasion, and tumor microenvironment through inactivating TRAF6/NF-κB. Moreover, SA reduced subcutaneous tumor volume and promoted NSCLC tissue apoptosis in vivo. SA repressed NSCLC cell proliferation, invasion, and tumor microenvironment through inactivating TRAF6/NF-κB.

Histopathological Evaluation of the Anti-Obesity Effects of the Plant Kenger (Gundelia tournefortii L.) in an Experimental Model of Obesity Induced in Rats

In this study, the anti-obesity effects of Gundelia tournefortii extract were histopathologically investigated in experimental obesity induced by a high-calorie diet in rats. For this purpose, Wistar-Albino male rats were divided into four groups, each consisting of 10 rats: Control (C), High-Calorie Diet (HCD), High-Calorie Diet + Gundelia tournefortii 200 mg/kg (HCDG1), and High-Calorie Diet + Gundelia tournefortii 400 mg/kg (HCDG2). The study was conducted over a period of three months. Histopathological analyses of liver tissue samples revealed that the HCD group exhibited fatty degeneration, with coagulation necrosis observed in hepatocytes. In the HCDG1 group, the liver showed macro-microvesicular fat vacuoles in hepatocytes of the pericentral regions, although this accumulation was significantly milder compared to the HCD group. Conversely, the HCDG2 group displayed a histological appearance close to that of the control group, with only rare microvesicular fat vacuoles present in hepatocytes. In conclusion, it is suggested that the Gundelia tournefortii extract administered alongside a high-calorie diet has hepatoprotective effects, potentially attributed to the antioxidant properties of its active components.

Application of metabolomics in quality control of traditional Chinese medicines: a review

Plant metabolites are the components endowing traditional Chinese medicine (TCM) with therapeutic effects, and, simultaneously, they are the primary targets for quality control. From germplasm selection and origin determination to field management, growth duration, harvesting and processing, and, finally, storage and transportation, each step profoundly influences TCM quality. The complexity of these plant or herb metabolites poses numerous quality control challenges. Metabolomics, as a comprehensive and systematic approach, has demonstrated value in this field. This technique not only meets the requirements for studying the complex mechanisms of TCM but also has significant advantages in identifying the TCM components, including active components. Therefore, in this article, several key factors affecting the chemical characteristics and quality traits of TCM, including their origin, harvesting period, medicinal parts, and processing methods, are researched. Additionally, the current challenges of integrating metabolomics with other omics technologies (transcriptomics, spatial metabolomics, etc.) are discussed. Furthermore, a future development trends and prospects are highlighted. With the continuous deepening of research and ongoing updates in technological capabilities, metabolomics will play an increasingly important role in the quality control of TCM, providing more scientific and robust support for quality assurance and safety evaluation.

HC-HA/PTX3 from Human Amniotic Membrane Induced Differential Gene Expressions in DRG Neurons: Insights into the Modulation of Pain

Background: The biologics derived from human amniotic membranes (AMs) demonstrate potential pain-inhibitory effects in clinical settings. However, the molecular basis underlying this therapeutic effect remains elusive. HC-HA/PTX3 is a unique water-soluble regenerative matrix that is purified from human AMs. We examined whether HC-HA/PTX3 can modulate the gene networks and transcriptional signatures in the dorsal root ganglia (DRG) neurons transmitting peripheral sensory inputs to the spinal cord. Methods: We conducted bulk RNA-sequencing (RNA-seq) of mouse DRG neurons after treating them with HC-HA/PTX3 (15 µg/mL) for 10 min and 24 h in culture. Differential gene expression analysis was performed using the limma package, and Gene Ontology (GO) and protein–protein interaction (PPI) analyses were conducted to identify the networks of pain-related genes. Western blotting and in vitro calcium imaging were used to examine the protein levels and signaling of pro-opiomelanocortin (POMC) in DRG neurons. Results: Compared to the vehicle-treated group, 24 h treatment with HC-HA/PTX3 induced 2047 differentially expressed genes (DEGs), which were centered on the ATPase activity, receptor–ligand activity, and extracellular matrix pathways. Importantly, PPI analysis revealed that over 50 of these DEGs are closely related to pain and analgesia. Notably, HC-HA/PTX3 increased the expression and signaling pathway of POMC, which may affect opioid analgesia. Conclusions: HC-HA/PTX3 induced profound changes in the gene expression in DRG neurons, centered around various neurochemical mechanisms associated with pain modulation. Our findings suggest that HC-HA/PTX3 may be an important biological active component in human AMs that partly underlies its pain inhibitory effect, presenting a new strategy for pain treatment.

Network pharmacology and in vitro experiments to investigate the anti-gastric cancer effects of paeoniflorin through the RAS/MAPK signaling pathway.

The aim of this study was to investigate the key targets and signaling pathways of paeoniflorin (PF) for the treatment of gastric cancer (GC). First, the differentially expressed genes (DEGs) of gastric cancer were obtained by analyzing GSE118916 Gene Chip, and then the active components of paeoniflorin and their targets of action were found. And the intersection genes of the two were analyzed for target and pathway analysis. In addition, cell viability after PF intervention was detected by CCK-8. Clone formation assay, wound scratch assay, transwell assay were used to detect cell migration and invasion. The qRT-PCR and Western blot methods were used to verify the mechanism of action. The results showed that a total of 286 paeoniflorin targets and 1799 DEGs were obtained. Secondly, we found that PF could treat gastric cancer through RAS/MAPK signaling pathway. In addition, through in vitro cellular experiments, we also found that PF had a significant therapeutic effect on gastric cancer. Therefore, we believe that PF inhibits the proliferation and metastasis of gastric cancer, and its effect may be exerted by regulating the RAS/MAPK signaling pathway. PF is a promising drug for the treatment of gastric cancer. Combined with the in vitro experiments, we found that the therapeutic effect of PF is related to the regulation of the RAS/MAPK signaling pathway, and the results of the present study preliminarily revealed its complex mechanism, which will lay the foundation for future clinical treatment.

Interface Engineering for Efficient Photocarrier Generation and Transfer in Strongly Coupled Metallic/Semiconducting 1T'/2H MoS2 Heterobilayers.

Developing alternative two-dimensional (2D) metallic/semiconducting (M/S) van der Waals heterostructures (vdWHs) along with an understanding of interfacial photocarrier behavior is crucial for designing high-performance optoelectronic devices. Here, we comprehensively explored the photophysical model of photocarrier generation and interfacial transfer in as-grown 2D 1T'/2H MoS2 vdWHs using various spectroscopic characterizations. We demonstrated the transitions of activated photocarrier transfer trajectories by tuning the pump photon energies across the 2H MoS2 bandgap. The importance of confined bilayer transfer systems and strong interlayer coupling at vdW interfaces for transfer efficiency was elucidated. Additionally, the fluorophlogopite substrate was found to be an external method for regulating photocarrier generation in individual 2H layers through the p-doping effect at the substrate-2H layer interfaces, and this influence was alleviated after introducing the 2H-1T' vdW interface. Particularly, 1T' MoS2 as a broadband hot carrier absorber enabled the ultrafast (∼133 fs) injection and extraction of energetic hot carriers into the 2H layer via a photothermionic emission mechanism, achieving a high efficiency of ∼41% under 900 nm photoexcitation at room temperature. Our work offers fundamental insights into the complex interfacial carrier photophysics in 2D M/S vdWHs, providing a way of constructing advanced multifunctional devices by using these emerging materials as active components and interface engineering.

Design of a Feedforward Decoupled Current Controller and an Optimized Voltage‐Oriented Control for Bi‐Directional Power Flow for V2G Application

ABSTRACTBi‐directional power exchange between the lithium‐ion battery and the grid can be achieved using vehicle‐to‐grid (V2G) technology. Bi‐directional battery chargers for V2G applications present opportunities and challenges, as the rapid growth of active components can compromise system reliability. This paper proposes an adaptive control mechanism for a three‐phase bi‐directional battery charging system to address this. The system integrates a bi‐directional active front‐end (AFE) converter (BAC) with an interleaved buck‐boost converter to enable adaptive constant current/constant voltage (CC/CV) mode operation and bi‐directional power flow. A feedforward decoupled current controller and pulse width modulation scheme optimize battery charging, while an optimized voltage‐oriented control (OVOC) model‐based controller ensures stable bi‐directional power exchange between the electric vehicle (EV) and the utility. Experimental results validate the effectiveness of the proposed approach, with findings demonstrating low total harmonic distortion (THD), unity power factor (UPF), and minimal DC voltage ripple. A 12.5 kW prototype further confirms the practical viability of the design, offering a promising solution for enhanced reliability and performance in V2G battery chargers.

Metabolomic and transcriptomic analyses reveals candidate genes and pathways involved in secondary metabolism in Bergenia purpurascens.

Bergenia purpurascens is an important medicinal, edible and ornamental plant. The lack of omics information hinders the study of its metabolic pathways and related genes. In order to investigate candidate genes and pathways involved in secondary metabolism in B. purpurascens, roots, stems and leaves of B. purpurascens were subjected to metabolomic and transcriptomic analyses in this study. A total of 351 differentially accumulated secondary metabolites were identified. We identified 120 candidate genes involved in phenylpropanoid and flavonoid biosynthesis pathway, from which 29 key candidate genes were obtained by WGCNA. Five UDP-Glycosyltransferases and four O-methyltransferases were suggested to be the candidate enzymes involved in synthetic pathway from gallic acid to bergenin by correlation analysis between transcriptional and metabolic levels and phylogenetic analysis. This study provides data resources and new insights for further studies on the biosynthesis of major active components in B. purpurascens.

Abstract A029: Novel high-purity CTC isolation technology for downstream analysis: A “Cell- Circuit” magnetophoretic-microfluidic hybrid device

Abstract Circulating Tumor Cells are the only blood analytes that contain comprehensive multi-omic information regarding living tumor cells. As such, CTCs are an essential tool for the precise diagnosis of cancer. This has led to increased interest in both enumeration, and more significantly, the downstream analysis of bulk and single CTCs. One primary technical limitation that limits adoption of CTCs into routine clinical practice is the ability to effectively isolate CTCs from non-target cells. While several technologies have been developed and commercialized including initial clinical adoption, most technologies have fundamental limitations in sample purity which limits the quality of downstream analysis. Another limitation is the number of steps needed to complete enrichment, especially in high purity isolation where 2 techniques are usually required to be performed in sequence. The authors propose a novel, single-cell isolation technology called L:Cell™. This technology utilizes precise micro-magnetic patterns to allow immuno-magnetically labeled cells to be isolated individually and directed to user-defined locations. Such “Cell-Circuits” enable parallel, computer-circuit-like manipulation of a large array of single cells – combining both precision and throughput. Passive and active single-cell control is made possible by circuit components such as gates, single-cell capacitors, and transistors. The technology also enables the classification of cells based on size in addition to the presence of magnetic beads. A "passive component" performs its function under an external rotating magnetic field, manipulating cells without the need for an electrical current. The majority of circuitry on-chip are such passive components, which enable the device's key advantage of parallelized control. In contrast, an "active component" is designed in conjunction with passive components to create a local magnetic field at specific locations. This allows cells to be rerouted or manipulated on-demand. Using active components, users can selectively isolate individual cells (e.g., based on size, morphology, or fluorescence). While micro-magnetophoretic technology has been explored by various research teams, the authors have advanced this technology further by micro-magnetic simulation and integrating microfluidic technology. This integration improves the inlet and outlet structures for cell samples and the alignment of particles’ flow, thereby maximizing the commercialization potential of this sophisticated technology. In lab-scale modeling, the authors demonstrated a high separation purity level of 92%. By allowing manipulation at single-cell level using magnetic fields only, the technology minimizes any stress on the cells during isolation processes. The authors developed a user- friendly interface utilizing microfluidic channels for the extraction of CTCs from whole blood using this hybrid device. Additionally, the authors are conducting further adaptation studies to apply this technology to various downstream techniques, such as genomic analysis and protein profiling. Citation Format: Chanhee Lee, Hun Heo, Youngwoo Park, Donghee Ko. Novel high-purity CTC isolation technology for downstream analysis: A “Cell- Circuit” magnetophoretic-microfluidic hybrid device [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A029.

Compact grounded memristor model with resistorless and tunability features

This research article provides a circuit illustration of a grounded memristor emulator. An operational transconductance amplifier (OTA) is one of its active components, along with two transistors and one capacitor. With a simple flip of the input ports, the incremental and decremental settings for the proposed memristor may be preserved. With the capacity to function in the megahertz band, the circuit offers a resistorless and controllable feature. Using the Cadence Virtuoso EDA tool in an analog design environment (ADE), PSPICE simulation with 0.18 µm TSMC technology parameter has been used to illustrate the viability of the suggested memristor. It has been confirmed in the simulation section that the operating frequency and tunability responses in the current-voltage (I-V) plane are in reasonable agreement with the theory. The suggested memristor model’s resilience has also been tested using process corner, Monte Carlo analysis, and temperature analyses, as well as single and parallel connected structures. The suggested memristor model is simple and does not need additional sub-circuit components, making it appropriate for implementation in integrated circuits. The experimental demonstration has been carried out by making a prototype on a breadboard using ICs, which exhibits good agreement with theoretical and simulation results. Single/parallel combinations of memristor, chaotic oscillator, and high pass filter have been presented to demonstrate its application.

Effects of Straw Addition on Soil Priming Effects Under Different Tillage and Straw Return Modes

This study aims to investigate the impact of straw addition on soil activation effects under different tillage practices, providing a scientific basis for establishing reasonable straw return measures in the southern Northeast Plain, thus enhancing soil fertility, and mitigating greenhouse effects. Soil samples were collected from various straw return practices that were conducted continuously for two years as follows: rotary tillage without straw return (RTO), deep tillage combined with straw incorporation (PT), rotary tillage with straw incorporation (RT), and no-till with straw cover (NT). The samples were incubated in the dark at 25 °C for 70 days. We measured the CO2 release rate and cumulative release, apparent activation effect, soil organic carbon, active microbial biomass organic carbon, soluble organic carbon, and easily oxidizable organic carbon to clarify the effects of straw addition on soil activation under different tillage practices. The results indicate that a straw addition promotes the mineralization of soil organic carbon while also increasing the content of active organic carbon components. The CO2 release rates and cumulative release under different tillage practices were as follows: PT > NT > RT. The contents of the active microbial biomass organic carbon, soluble organic carbon, and easily oxidizable organic carbon increased by 16.62% to 131.88%, 4.36% to 57.59%, and 12.10% to 57.97%, respectively, compared to the control without the straw addition. Except for the RT practice, the addition of straw significantly enhanced the instability of soil organic carbon in the PT, NT, and RTO practices, with increases of 51.75%, 48.29%, and 27.90%, respectively. Different straw return practices altered the physical and chemical properties of the soil, resulting in significant differences in the strength of the apparent activation effect. Notably, the apparent activation effect of RT was reduced by 86.42% compared to RTO, while that of NT was reduced by 36.99% compared to PT. A highly significant positive correlation was observed between the apparent activation effect and the unstable carbon components in the soil, indicating that higher levels of easily decomposable organic carbon corresponded to stronger apparent activation effects. In conclusion, it is recommended that in this region, rotary tillage should be adopted for straw return in the first 2 to 3 years, as this practice is beneficial for the formation and stabilization of organic carbon in the short term. As the duration of straw return increases, adjustments can be made based on the degree of soil organic carbon retention and soil fertility status.

Improvement of construction and technological properties of cement hardening systems for building composites

The article provides information on the formation of hardening systems of building composites (STSC) as a result of directional structure formation and the involvement of the active component of metallurgical slags. It is shown that the structures of the STSC can be represented as a consequence of formation (design and synthesis) of the structures of the particle addition system of the raw material mixture, and for more complex technologies – as a growth system. The main physico-chemical properties and characteristics of modifying additives for STSC are considered. The influence of slag additives on the main construction and technological properties of hardening systems based on man-made raw materials has been established. Special attention is paid to the kinetics of the grinding capacity of the designed hardening systems of building composites.

Comparative analysis of oral saliva microbiomes and metabolites in Han population at different altitudes

ObjectiveThis study investigated the differences in oral saliva microbiota composition and metabolic products among Han Chinese populations living at different altitudes, as well as their correlations.MethodThe analysis was conducted using the 16S rRNA gene sequencing method and untargeted metabolomics.Results16S gene sequencing results showed significant differences in bacterial diversity and composition between HH (High altitude Han) group and LH (Low altitude Han) group. LEfSe analysis showed that Selenomonas, Leptotrichia, Veillonella, Prevotella relatively abundant are higher in HH group, Haemophilus, Neisseria, Actinobacillus, Aggregatibacter are higher in LH group (p<0.05). Furthermore, as depicted in the phylogenetic tree, there are differences observed between the two groups at all taxonomic levels: 4 phyla, 6 classes, 6 orders, 9 families, 9 genera and 8 species (p<0.05). After conducting PICRUSt functional prediction analysis, we identified 11 significantly different KEGG categories (level 2) between the two groups. These categories primarily encompass energy metabolism, amino acid metabolism, and carbohydrate metabolism. Furthermore, non-targeted metabolomics analysis revealed a total of 997 distinct metabolites in the two groups. These differentiated metabolites can be classified into 13 Class I categories including amino acids and their metabolites, benzene and its derivatives, organic acids and their derivatives, heterocyclic compounds, aldehydes, ketones and esters, nucleotides and their metabolites among others. Additionally, fatty acyl compounds, alcohols and amines as well as glycerophospholipids are present along with carbohydrates and other physiologically active components such as hormones. Finally, Pearson correlation analysis of the top 20 differential metabolites with microorganisms demonstrated an interaction between them; however further experimental verification is required to elucidate the specific mechanism of action.ConclusionTherefore, this study revealed the effect of altitude on oral saliva microbes and metabolites, as well as their correlations.

Recent Advances in NO Reduction with NH3 and CO Over Cu-Ce Bimetallic and Derived Catalysts

Sintering flue gas contains significant amounts of harmful gases, such as carbon monoxide and nitrogen oxides (NOx), which pose severe threats to the ecological environment and human health. Selective catalytic reduction (SCR) technology is widely employed for the removal of nitrogen oxides, with copper-cerium-based bimetallic catalysts and their derivatives demonstrating excellent catalytic efficiency in SCR reactions, primarily due to the significant synergistic effect between copper and cerium. This paper summarizes the main factors affecting the catalytic performance of Cu-Ce-based bimetallic catalysts and their derivatives in the selective catalytic reduction of ammonia and carbon monoxide. Key considerations include various preparation methods, doping of active components, and the effects of loading catalysts on different supports. This paper also analyzes the influence of surface oxygen vacancies, redox capacity, acidity, and specific surface area on catalytic performance. Additionally, the anti-poisoning performance and reaction mechanisms of the catalysts are discussed. Finally, the paper proposes strategies for designing high-activity and high-stability catalysts, considering the development prospects and challenges of Cu-Ce-based bimetallic catalysts and their derivatives, with the aim of providing theoretical guidance for optimizing Cu-Ce-based catalysts and promoting their industrial applications.

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives

The study of organic small molecule semiconductor materials as active components of organic electronic devices continues to attract considerable attention due to the range of advantages these molecules can offer. Here, we report the synthesis of three dicyanomethylene-functionalised violanthrone derivatives (3a, 3b and 3c) featuring different alkyl substituents. It is found that the introduction of the electron-deficient dicyanomethylene groups significantly improves the optical absorption compared to their previously reported precursors 2a–c. All compounds are p-type semiconductors with low HOMO–LUMO gaps (≈1.25 eV). The hole mobilities, measured from fabricated organic field-effect transistors, range from 3.6 × 10−6 to 1.0 × 10−2 cm2 V−1 s−1. We found that the compounds featuring linear alkyl chains (3b and 3c) displayed a higher mobility compared to the one with branched alkyl chains, 3a. This could be the result of the more highly disordered packing arrangement of this molecule in the solid state, induced by the branched side chains that hinder the formation of π–π stacking interactions. The influence of dicyanomethylene groups on the charge transport properties was most clearly observed in compound 3b which has a 60-fold improvement in mobility compared to 2b. This study demonstrates that the choice of the solubilising group has a profound effect on the hole mobility on these organic semiconductors.

Elucidating the gastroprotective mechanisms of Imperata cylindrica Beauv.var. major (Nees) C.E.Hubb through UHPLC-MS/MS and systems network pharmacology.

Imperata cylindrica Beauv.var. major (Nees) C.E.Hubb., commonly known as BaiMaoGen (BMG), a medicinal and edible traditional Chinese medicinal (TCM) herb commonly used in health supplements, has been observed to offer protective effects against gastrointestinal disorders. However, the specific bioactive compounds and their molecular mechanisms have not been fully elucidated. This study employed ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and systematic network pharmacology to analyze and identify the key active components and their interactions with biological targets. Thirty-six main active compounds, including 3,4-dihydroxybenzoic acid and p-hydroxybenzoic acid, were identified and analyzed for their interaction with key protein targets using molecular docking and dynamic simulations. This combined approach highlighted the therapeutic pathways involved, particularly the PI3K/AKT signaling pathways, providing new insights into the molecular basis of BMG's gastroprotective effects. Our findings suggested that BMG's complex multi-target action can potentially be harnessed to develop effective treatments for gastrointestinal toxicity.

Anti-breast cancer effects of dairy protein active peptides, dairy products, and dairy protein-based nanoparticles

Breast cancer is the most frequently diagnosed and fatal cancer among women worldwide. Dairy protein-derived peptides and dairy products are important parts of the daily human diet and have shown promising activities in suppressing the proliferation, migration, and invasion of breast cancer cells, both in vitro and in vivo. Most of the review literature employs meta-analysis methods to explore the association between dairy intake and breast cancer risk. However, there is a lack of comprehensive summary regarding the anti-breast cancer properties of dairy protein-derived peptides, dairy products, and dairy protein-based nanoparticles as well as their underlying mechanisms of action. Therefore, the present study discussed the breast cancer inhibitory effects and mechanisms of active peptides derived from various dairy protein sources. Additionally, the characteristics, anti-breast cancer activities and active components of several types of dairy products, including fermented milk, yogurt and cheeses, were summarized. Furthermore, the preparation methods and therapeutic effects of various dairy protein-containing nanoparticle delivery systems for breast cancer therapy were briefly described. Lastly, this work also provided an overview of what is currently known about the anti-breast cancer effects of dairy products in clinical studies. Our review will be of interest to the development of natural anticancer drugs.

Lingguizhugan decoction alleviates obesity in rats on a high-fat diet through the regulation of lipid metabolism and intestinal microbiota

BackgroundIndividuals with obesity often experience elevated blood lipid levels, leading to a chronic low-grade inflammatory state, exacerbating liver oxidative stress, and increasing the risk of various metabolic diseases. Recent evidence suggests that intestinal microbiota and short-chain fatty acids (SCFAs) play crucial roles in the development and progression of obesity. While the mechanisms by which Lingguizhugan decoction (LGZGD) intervenes in obesity by improving lipid metabolism, enhancing insulin sensitivity, and reducing inflammatory responses are well-documented, its potential in intestinal microbiota and SCFAs remains unclear. This study aims to explore the impact of LGZGD on high-fat diet (HFD) induced obesity in rats and its regulatory effects on intestinal microbiota and SCFAs, providing new insights for obesity prevention and treatment.MethodsFifty-one male SD rats were randomly divided into groups, with six in the normal control group (NC) receiving a ddH2O treatment and a standard diet. The remaining 45 rats were fed a high-fat diet (HFD) using D12451 feed. After 10 weeks, the rats on the HFD gained 20% more weight than the NC group, confirming the successful modeling of obesity. These rats were then randomly divided into the following groups: ddH2O high-fat diet model group (MC), 20 mg/kg/day Orlistat positive control group (Orlistat), 1.62 g/kg/day low-dose LGZGD group (LGZGL), and 3.24 g/kg/day high-dose LGZGD group (LGZGH) for 8 weeks. We evaluated changes in body weight, serum total cholesterol (TC), total triacylglycerol (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) levels. Fat and liver tissues were collected for pathological analysis. Intestinal contents were aseptically collected for 16S rRNA gene sequencing and gas chromatography–mass spectrometry (GC–MS) to assess gut microbiota and SCFA levels.ResultsLGZGD reduces body weight, TC, TG, LDL, and HDL levels, significantly reducing hepatic steatosis. Besides, it restored the richness and diversity of gut microbiota, which was reduced by HFD, altering the overall structure. Specifically, LGZGD significantly promoted the growth of Muribaculaceae and Dubosiella while inhibiting the growth of Christensenellaceae_R_7_group and UCG_005. It also restricts the production of caproic acid. Correlation analysis indicated positive correlations: Muribaculaceae with Butyric acid and Isovaleric acid; UCG_005 with TC, LDL, and HDL; and Christensenellaceae_R_7_group with TC and LDL.ConclusionLGZGD increased the abundance of beneficial gut microbiota in HFD-induced obese rats, improved gut microbiota dysbiosis, and inhibited the increase in caproic acid content. These results suggest that LGZGD can mitigate HFD-induced obesity, and its active components warrant further investigation.

Mid-infrared arrayed waveguide gratings using a quantum cascade laser gain medium as core material

Mid-infrared photonics is a widely researched field with several applications, such as chemical sensing and spectroscopy. The development of photonic integrated circuits for the mid-infrared can enable the reduction in device size, weight, and power (SWaP) consumption. This paper demonstrates arrayed waveguide gratings working in the mid-infrared regime (5–5.4 µm). Our devices are fabricated on an InP-based quantum cascade laser platform with the gain medium as the waveguide core. To minimize the propagation losses caused by free carrier absorption and intersubband absorption in the unbiased QCL structure, we exposed the photonic chips to proton implantation. The performance of three sets of AWGs with different etch depths was characterized. The lowest waveguide losses were measured to be 2 dB/cm. The best performing 7×1 AWG and 13×1 AWG designs featured insertion losses of −2dB and −2.5dB, respectively. This study showcases the feasibility of applying such a platform for easy integration with active components like lasers and photodetectors, paving the path for on-chip mid-infrared applications.