Vasicine attenuates atherosclerosis via lipid regulation, inflammation inhibition, and autophagy activation in ApoE-/- mice.

Atherosclerosis is marked with the accumulation of low-density lipoproteins and chronic inflammation. The anti-inflammatory therapies exert protective effects on atherosclerosis. Vasicine is a bioactive alkaloid with anti-inflammatory activity from a medicinal plant in Ayurveda and Unani. In this study, the effects of vasicine were evaluated on atherosclerosis in vivo and in vitro. The results showed that vasicine alleviated atherosclerotic lesions and regulated the lipid synthesis by reducing the levels of TC, TG, LDL-C and inhibiting the expresses of scavenger receptors (SR-A, CD36 and LOX-1) to inhibit foam cell formations. And vasicine decreased the levels of IL-1ß, IL-6, MCP-1, and TNF-α to modulate inflammatory response. Besides, vasicine downregulated MAPK and PI3K/AKT/mTOR pathway to activated autophagy, which inhibited the procession of atherosclerosis.

Comprehensive comparative analysis and development of molecular markers for Lasianthus species based on complete chloroplast genome sequences.

BACKGROUND: Lasianthus species are widely used in traditional Chinese folk medicine with high medicinal value. However, source materials and herbarium specimens are often misidentified due to morphological characteristics and commonly used DNA barcode fragments are not sufficient for accurately identifying Lasianthus species. To improve the molecular methods for distinguishing among Lasianthus species, we report the complete chloroplast (CP) genomes of Lasianthus attenuatus, Lasianthus henryi, Lasianthus hookeri, Lasianthus sikkimensis, obtained via high-throughput Illumina sequencing. RESULTS: These showed CP genomes size of 160164-160246 bp and a typical quadripartite structure, including a large single-copy region (86675-86848 bp), a small single-copy region (17177-17326 bp), and a pair of inverted repeats (28089-28135 bp). As a whole, the gene order, GC content and IR/SC boundary structure were remarkably similar among of the four Lasianthus CP genomes, the partial gene length and IR, LSC and SSC regions length are still different. The average GC content of the CP genomes was 36.71-36.75%, and a total of 129 genes were detected, including 83 different protein-coding genes, 8 different rRNA genes and 38 different tRNA genes. Furthermore, we compared our 4 complete CP genomes data with publicly available CP genome data from six other Lasianthus species, and we initially screened eleven highly variable region fragments were initially screened. We then evaluated the identification efficiency of eleven highly variable region fragments and 5 regular barcode fragments. Ultimately, we found that the optimal combination fragment' ITS2 + psaI-ycf4' could authenticated the Lasianthus species well. Additionally, the results of genome comparison of Rubiaceae species showed that the coding region is more conservative than the non-coding region, and the ycf1 gene shows the most significant variation. Finally, 49 species of CP genome sequences belonging to 16 genera of the Rubiaceae family were used to construct phylogenetic trees. CONCLUSIONS: Our research is the first to analyze the chloroplast genomes of four species of Lasianthus in detail and we ultimately determined that the combination fragment' ITS2 + psaI-ycf4' is the optimal barcode combination for identifying the genus of Lasianthus. Meanwhile, we gathered the available CP genome sequences from the Rubiaceae and used them to construct the most comprehensive phylogenetic tree for the Rubiaceae family. These investigations provide an important reference point for further studies in the species identification, genetic diversity, and phylogenetic analyses of Rubiaceae species.

Full-Color Emissive Zirconium-Organic Frameworks Constructed via in situ "One-Pot" Single-Site Modification for Tryptophan Detection and Energy Transfer.

Organic linker-based luminescent metal-organic frameworks (LMOFs) have received extensive studies due to the unlimited species of emissive organic linkers and tunable structure of MOFs. However, the multiple-step organic synthesis is always a great challenge for the development of LMOFs. As an alternative strategy, in situ "one-pot" strategy, in which the generation of emissive organic linkers and sequential construction of LMOFs happen in one reaction condition, can avoid time-consuming pre-synthesis of organic linkers. In the present work, we demonstrate the successful utilization of in situ "one-pot" strategy to construct a series of LMOFs via the single-site modification between the reaction of aldehydes and o-phenylenediamine-based tetratopic carboxylic acid. The resultant MOFs possess csq topology with emission covering blue to near-infrared. The nanosized LMOFs exhibit excellent sensitivity and selectivity for tryptophan detection. In addition, two component-based LMOFs can also be prepared via the in situ "one-pot" strategy and used to study energy transfer. This work not only reports the construction of LMOFs with full-color emissions, which can be utilized for various applications, but also indicates that in situ "one-pot" strategy indeed is a useful and powerful method to complement the traditional MOFs construction method for preparing porous materials with tunable functionalities and properties.

The Efficacy of a Culturally-Adapted Group-based Parent Coaching Program for Autistic Children in China via Telehealth: A Randomized Controlled Trial.

The study aimed to examine the efficacy of a culturally-adapted, group-based parent coaching program for autistic children in China delivered via telehealth. A randomized controlled trial was conducted, with 18 parents allocated to the self-directed group that received the intervention through an online learning platform, and 19 parents allocated to the web + group therapy group, which included the same program along with weekly 1.5-hour group coaching sessions via videoconferencing. The primary outcomes were parents' mental health and children's adaptive functioning, while the secondary outcomes focused on the child behaviors, parenting stress and parenting style, and family quality of life. Linear Mixed Models were used to evaluate treatment effects across time and to model longitudinal trajectories of outcomes in both children and parents. Both intervention groups showed significant improvements in children's communication skills (F (1, 60.27) = 29.86, p < 0.001) and social engagement (F (1, 60.07) = 11.73, p = 0.001), as well as reductions in parenting stress (F (1, 59.07) = 8.76, p = 0.004) and anxiety levels (F (1, 57.62) = 4.84, p = 0.032). Additionally, the group-based parent coaching via videoconferencing was associated with greater improvements in children's quality of life (F (1, 59.95) = 5.90, p = 0.018) and parents' anxiety outcomes (F (1, 57.62) = 4.84, p = 0.032). This study demonstrated the efficacy of a culturally adapted telehealth intervention for both autistic children and their parents. The preliminary findings suggest positive outcomes in children's adaptive functioning and parents' mental well-being. Group-based parent coaching through videoconferencing could be a promising and practical model for in-home services, particularly for families with limited access to in-person services.

PTEN regulated by gga-miR-20a-5p is involved in chicken macrophages inflammatory response to APEC infection via autophagy.

Colibacillosis, a bacterial disease caused by avian pathogenic E. coli (APEC), is a prevalent condition in the poultry industry, resulting in substantial economic losses annually. Previously, we identified PTEN as a crucial candidate gene that may play a significant role in chicken's immune response to APEC infection. Bioinformatics analysis indicated that the PTEN protein was unstable, hydrophilic and nuclear localization, with multiple putative phosphorylation sites and a high degree of similarity to duck and goose PTEN. Moreover, PTEN exhibited high expression levels in various tissues such as the stomach, cecum, small intestine, spleen, thymus, harderian gland, muscle, cerebrum, cerebellum, lung, and liver in comparison to heart tissue. Overexpression of PTEN resulted in a significant promotion of the expression level of pro-apoptosis genes and inflammatory mediators, as well as the production of NO, with or without APEC infection, which led to cellular injury. Furthermore, overexpression of PTEN was found to regulate the expression levels of autophagy related genes, regardless of APEC infection. Additionally, PTEN was a target gene of gga-miR-20a-5p and regulated by gga-miR-20a-5p upon APEC infection. Taken together, these findings establish a foundation for investigating the biological function of chicken PTEN, providing a potential target for future treatments against APEC infection as well as the breeding of genetically resistant poultry.

Phonological Development in 3-6-Year-Old Mandarin-Speaking Children with Autism, Developmental Delays, and Typical Development.

Research on the phonological development of children with autism spectrum disorder (ASD) has not yet reached consistent conclusions, and systematic studies from different language groups are needed. This study aimed to systematically investigate the characteristics of phonological development in 3-6 year-old Mandarin-speaking children with ASD. We analyzed 10 min speech samples from 21 children with ASD, 18 development level-matched children with developmental disorders (DD), and 15 chronological age-matched typically developing (TD) children during semi-structured parent-child free play based on Mandarin phonological features. The children with ASD had a significantly smaller inventory than those with TD on the initial and final inventories. The children with ASD had only a significantly smaller initial inventory than those with DD in Phases 2 and 4. Compared with TD children, children with ASD used a higher proportion of V1 and V1V2C and a smaller proportion of V1V2V3, CV1C, and CV1V2C. No significant differences existed between ASD and DD children in the proportion of any syllable structure, but V1V2V3, CV1, and CV1V2C numbers were significantly fewer than in DD children. Children with ASD were significantly greater than children with TD in the diversity of V1V2, CV1, and overall syllables. ASD children had significantly fewer different types of syllables in both V1V2C and CV1 than did DD children and significantly greater diversity in CV1 and overall syllables than did DD children. These preliminary data suggest that the gap between TD and ASD children's language abilities increased with age, and this gap was reflected in initial, final, and syllable complexity and diversity. Children with DD and ASD showed similar language abilities, and children with DD showed detailed differences from those with ASD regarding initial, syllable complexity and diversity.

Reticular Chemistry and In Situ "One-Pot" Strategy: A Dream Combination to Construct Metal-Organic Frameworks.

The establishment of reticular chemistry has significantly facilitated the development of porous materials, especially for metal-organic frameworks (MOFs). On the other hand, as an alternative approach, in situ "one-pot" strategy has been explored as a promising approach to constructing MOFs, in which the synthesis of organic linkers and the sequential construction of MOFs are integrated into one solvothermal condition. This strategy can efficiently avoid the limitations faced in the traditional construction method, such as time-consuming organic synthesis and multiple separation and purification. Herein, inspired by the reaction of aldehydes and o-phenylenediamine and deep structural analysis of UiO-68, a series of tetra-, hexa-, and octa-topic carboxylic acids are synthesized using 2',3'-diamino-[1,1':4',1'"-terphenyl]-4,4'"-dicarboxylic acid and di-, tri-, and tetra-topic aldehydes as precursor. Then nine multicarboxylate-based zirconium MOFs (Zr-MOFs) are successfully constructed via the combination of reticular chemistry and in situ "one-pot" strategy. The resultant Zr-MOFs can be regarded as the partial face decoration of UiO-68. More importantly, the emission properties of resultant Zr-MOFs can be well controlled using aldehydes with tunable electronic structures. This work provides a new path to rational design and construction of porous materials with specific structures guided by reticular chemistry and conducted using in situ "one-pot" strategy.

Soil environmental anomalies dominate the responses of net ecosystem productivity to heatwaves in three Mongolian grasslands.

Climate change is causing more frequent and intense heatwaves. Therefore, it is important to understand how heatwaves affect the terrestrial carbon cycle, especially in grasslands, which are especially susceptible to climate extremes. This study assessed the impact of naturally occurring, simultaneous short-term heatwaves on CO2 fluxes in three ecosystems on the Mongolia Plateau: meadow steppe (MDW), typical steppe (TPL), and shrub-grassland (SHB). During three heatwaves, net ecosystem productivity (NEP) was reduced by 86 %, 178 %, and 172 % at MDW, TPL, and SHB, respectively. The changes in ecosystem respiration, gross primary production, evapotranspiration, and water use efficiency were divergent, indicating the mechanisms underlying the observed NEP decreases among the sites. The impact of the heatwave in MDW was mitigated by the high soil water content, which enhanced evapotranspiration and subsequent cooling effects. However, at TPL, insufficient soil water led to combined thermal and drought stress and low resilience. At SHB, the ecosystem's low tolerance to an August heatwave was heavily influenced by species phenology, as it coincided with the key phenological growing phase of plants. The potential key mechanism of divergent NEP response to heatwaves lies in the divergent stability and varying importance of environmental factors, combined with the specific sensitivity of NEP to each factor in ecosystems. Furthermore, our findings suggest that anomalies in soil environment, rather than atmospheric anomalies, are the primary determinants of NEP anomalies during heatwaves. This challenges the conventional understanding of heatwaves as a discrete and ephemeral periods of high air temperatures. Instead, heatwaves should be viewed as chronologically variable, compound, and time-sensitive environmental stressors. The ultimate impact of heatwaves on ecosystems is co-determined by a complex interplay of environmental, biological, and heatwave features.

Porous organic polymers assisted aptamer signal amplification for enhanced photoeletrochemical detection of MUC1.

Mucin1 (MUC1) is an extensively glycosylated transmembrane protein that is widely distributed and overexpressed on the surface of cancer cells, playing an important role in tumor occurrence and metastasis. Therefore, highly sensitive detection of MUC1 is of great significance for early diagnosis, treatment monitoring, and prognosis of cancer. Here, an ultra-sensitive photoelectrochemical (PEC) sensing platform was developed based on an aptamer amplification strategy for highly selective and sensitive detection of MUC1 overexpressed in serum and on cancer cell surfaces. The sensing platform utilized copper phthalocyanine to fabricate porous organic polymers (CuPc POPs), and was effectively integrated with g-C3N4/MXene to form a ternary heterojunction material (g-C3N4/MXene/CuPc POPs). This material effectively improved electron transfer capability, significantly enhanced light utilization, and greatly enhanced photoelectric conversion efficiency, resulting in a dramatic increase in photocurrent response. MUC1 aptamer 1 was immobilized on a chitosan-modified photoelectrode for the selective capture of MUC1 or MCF-7 cancer cells. When the target substance was present, MUC1 aptamer 2 labeled with methylene blue (MB) was specifically adsorbed on the electrode surface, leading to enhanced photocurrent. The concentration of MUC1 directly correlated with the number of MB molecules attracted to the electrode surface, establishing a linear relationship between photocurrent intensity and MUC1 concentration. The PEC biosensor exhibited excellent sensitivity for MUC1 detection with a wide detection range from 1 × 10-7 to 10 ng/mL and a detection limit of 8.1 ag/mL. The detection range for MCF-7 cells was from 2 × 101 to 2 × 106 cells/mL, with the capability for detecting single MCF-7 cells. The aptamer amplification strategy significantly enhanced PEC performance, and open up a promising platform to establish high selectivity, stability, and ultrasensitive analytical techniques.

Recyclable Au@R-Fe3O4/g-C3N4 substrates for rapid SERS detection and degradation of multiple pollutants.

Developing a Surface-enhanced Raman spectroscopy (SERS) method with excellent detecting ability, good recyclability and analyzing multiple pollutants rapidly are critical for evaluation of water quality in emergency pollution affairs. While constructing a multifunctional substrate with these characteristics to realize the application of SERS in water quality monitoring remains a challenge. In this work, a reusable Au@R-Fe3O4/g-C3N4 SERS substrate is prepared by loading Au nanoparticles (Au NPs) on Fe3O4 nanorings (R-Fe3O4) and the formed Au@R-Fe3O4 is further combined with g-C3N4 nanosheets through a simple electrostatic assembly method. The Au@R-Fe3O4/g-C3N4 nanocomposite presents multifunction of magnetic enrichment, SERS signal enhancement, multiple pollutants analyzing, and photocatalytic activity, which achieves quantitative detection of rhodamine B (RhB), tetracycline hydrochloride (TC), and 4-chlorophenol (4-CP), with detection limits of 5.30 × 10-9, 7.50 × 10-8, 7.69 × 10-8 mol/L, respectively. Furthermore, the recyclable detection capability of Au@R-Fe3O4/g-C3N4 for multi components is demonstrated by the strong SERS signal after 9 cycles of "detection-degradation" processes. Combined with good uniformity and stability, this SERS method based on Au@R-Fe3O4/g-C3N4 substrate provides a new strategy for the multi-pollutants detection and degradation in water environment.

Shizukaol C alleviates trimethylamine oxide-induced inflammation through activating Keap1-Nrf2-GSTpi pathway in vascular smooth muscle cell.

BACKGROUND: Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation. PURPOSE: The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation. METHODS: The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo, TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay. RESULTS: Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation. CONCLUSION: Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB/p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo, suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases.

Reticular chemistry guided precise construction of zirconium-pentacarboxylate frameworks with 5-connected Zr6 clusters.

Zirconium-based metal-organic frameworks (Zr-MOFs) have been extensively studied due to their very rich structural chemistry. The combination of nearly unlimited carboxylic acid-based linkers and Zr6 clusters with multiple connectivities has led to diverse structures and specific properties of resultant Zr-MOFs. Herein, we demonstrate the successful use of reticular chemistry to construct two novel Zr-MOFs, HIAM-4040 and HIAM-4040-OH, with zfu topology. Based on a thorough structural analysis of (4,4)-connected lvt-type Zr-tetracarboxylate frameworks and a judicious linker design, we have obtained the first example of a Zr-pentacarboxylate framework featuring unprecedented 5-connected organic linkers and 5-connected Zr6 clusters. Compared with HIAM-4040, a larger Stokes shift is achieved in HIAM-4040-OH via hydroxyl group induced excited-state intramolecular proton transfer (ESIPT). HIAM-4040-OH exhibits high chemical and thermal stability and is used for HClO detection in aqueous solution with excellent sensitivity and selectivity.

Unveiling biomarkers and therapeutic targets in IgA nephropathy through large-scale blood transcriptome analysis.

INTRODUCTION: IgA nephropathy (IgAN) is the most prevalent form of glomerulonephritis. Unfortunately, molecular biomarkers for IgAN derived from omics studies are still lacking. This research aims to identify critical genes associated with IgAN through large-scale blood transcriptome analysis. METHODS: We constructed novel blood transcriptome profiles from peripheral blood mononuclear cells (PBMCs) of 53 Chinese IgAN patients and 28 healthy individuals. Our analysis included GO, KEGG, and GSEA for biological pathways. We analyzed immune cell profiles with CIBERSORT and constructed PPI networks with STRING, visualized in Cytoscape. Key differentially expressed genes (DEGs) were identified using CytoHubba and MCODE. We assessed the correlation between gene expressions and clinical data to evaluate clinical significance and identified hub genes through machine learning, validated with an open-access dataset. Potential drugs were explored using the CMap database. RESULTS: We identified 333 DEGs between IgAN patients and healthy controls, mainly related to immune response and inflammation. Key pathways included NK cell mediated cytotoxicity, complement and coagulation cascades, antigen processing, and B cell receptor signaling. Cytoscape revealed 16 clinically significant genes (including KIR2DL1, KIR2DL3, VISIG4, C1QB, and C1QC, associated with sub-phenotype and prognosis). Machine learning identified two hub genes (KLRC1 and C1QB) for a diagnostic model of IgAN with 0.92 accuracy, validated at 1.00 against the GSE125818 dataset. Sirolimus, calcifediol, and efaproxiral were suggested as potential therapeutic agents. CONCLUSION: Key DEGs, particularly VISIG4, KLRC1, and C1QB, emerge as potential specific markers for IgAN, paving the way for future targeted personalized treatment options.

Cang-ai volatile oil ameliorates imiquimod-induced psoriatic skin lesions by suppressing the ILC3s.

ETHNOPHARMACOLOGICAL RELEVANCE: Cang-ai volatile oil (CAVO) is an aromatic Chinese medicine with potent antibacterial and immune regulatory properties. While CAVO has been used to treat upper respiratory tract infections, depression, otomycosis, and bacterial infections in the skin, its effect on psoriasis is unknown. AIM OF THE STUDY: This study explores the effect and mechanism of CAVO in psoriasis intervention. MATERIAL AND METHODS: The effect of CAVO on the expression of IL-6 and IL-1ß was assessed in TNF-α-induced HaCaT cells using enzyme-linked immunosorbent assay (ELISA). Mice were given imiquimod (IMQ) and administered orally with different CAVO doses (0.03 and 0.06 g/kg) for 5 days. The levels of inflammatory cytokines related to group-3 innate lymphoid cells (ILC3s) in the skin were assessed using hematoxylin and eosin (H&E) staining, ELISA, and western blotting (WB). The frequency of ILC3s in mice splenocytes and skin cells was evaluated using flow cytometry. RESULTS: The results demonstrated that CAVO decreased the expression of IL-6 and IL-1ß in TNF-α- induced HaCaT cells. CAVO significantly reduced the severity of psoriatic symptoms in IMQ-induced mice. The expression of inflammatory cytokines in the skin, such as IL-1ß, IL-6, IL-8, IL-22, IL-23, and IL-17 A were decreased, whereas IL-10 levels were increased. The mRNA expressions of TNF-α, IL-23 A, IL-23 R, IL-22, IL-17 A, and RORγt were down-regulated in skin tissues. CAVO also decreased the levels of NF-κB, STAT3, and JAK2 proteins. CONCLUSIONS: CAVO potentially inhibits ILC3s activation to relieve IMQ-induced psoriasis in mice. These effects might be attributed to inhibiting the activation of NF-κB, STAT3, and JAK2 signaling pathways.

Ultrabright Green-Emissive Nanodots for Precise Biological Visualization.

Developing general methods to fabricate water-dispersible and biocompatible fluorescent probes will promote different biological visualization applications. Herein, we report a metal-facilitated method to fabricate ultrabright green-emissive nanodots via the one-step solvothermal treatment of rose bengal, ethanol, and various metal ions. These metal-doped nanodots show good water dispersity, ultrahigh photoluminescence quantum yields (PLQYs) (e.g., the PLQY of Fe-doped nanodots (FeNDs) was ∼97%), and low phototoxicity. Owing to the coordination effect of metal ions, the FeNDs realize glutathione detection with outstanding properties. Benefiting from the high endoplasmic reticulum (ER) affinity of the chloride group, the FeNDs can act as an ER tracker with long ER imaging capacity (FeNDs: >24 h; commercial ER tracker: ∼1 h) and superb photostability and can achieve tissue visualization in living Caenorhabditis elegans. The metal-doped nanodots represent a general nanodot preparation method and may shed new light on diverse biological visualization uses.

Baiheqingjin formula reduces inflammation in mice with asthma by inhibiting the PI3K/AKT/NF-κb signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Baiheqingjin Decoction (BHQJ), which consists of 7 traditional Chinese herbs including Baibu (Stemona tuberosa Lour.), Hezi (Terminalia chebula Retz.), Mahuang (Ephedra sinica Stapf.), Ziwan (Aster tataricus L. f.), Dilong (Pheretima), Sangbaipi (Morus alba L.), and Xianhecao (Agrimonia pilosa Ledeb.). BHQJ is commonly used for treating cough asthma, and variant cough-variant asthma as it, is effective in improving asthma symptoms and reducing airway inflammation. AIM OF THE STUDY: To investigate the mechanisms of BHQJ in treating allergic asthma. MATERIALS AND METHODS: We collected information about the components and targets of 6 Chinese medicines (excluding Pheretima) from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Additionally, we obtained genes associated with asthma from six disease databases. To create a protein-protein interaction network, we conducted an intersection analysis using differentially expressed genes derived from RNA transcriptome data. Subsequently, we carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. To validate the findings from network pharmacology and transcriptomics, we established an allergic asthma mouse model induced by ovalbumin and conducted in vivo experiments. RESULTS: Using network pharmacology and transcriptomics analyses, we identified the pathways including the PI3K/AKT signaling pathway, and NF-κB signaling pathway. Among these, the involvement of the PI3K/AKT/NF-κB signaling pathway in various pathological processes of asthma, such as airway inflammation, smooth muscle contraction, and excessive mucus production, are well-documented. Histopathological examinations indicated that BHQJ had the potential to mitigate inflammatory cell infiltration and the excessive growth of goblet cells in the airways of asthmatic mice, consequently reducing mucus secretion. Results from Western blot demonstrated that BHQJ could inhibit the activation of the PI3K/AKT/NF-κB pathway at the protein levels. Enzyme-linked immunosorbent assay findings revealed that BHQJ could reduce the production of typical "type 2 asthma" cytokines and immunoglobulin (Ig) E in the blood. These discoveries imply that BHQJ has the potential to reduce the release of inflammatory cytokines and suppress the overactivation of the PI3K/AKT/NF-κB signaling pathway, thus offering a therapeutic approach for asthma. CONCLUSION: Our research offers initial insights into the fundamental mechanisms through which BHQJ treats asthma. This study reveals the potential mechanism of BHQJ in treating asthma, particularly its role in reducing inflammatory cytokines, mucus production, and cell infiltration, as well as inhibiting the expression of PI3K/AKT/P65 phosphorylated protein. These findings indicate the potential of BHQJ in treating asthma. In summary, our study provides preliminary insights into the asthma treatment mechanism of BHQJ and provides guidance for future research.

Inhibitory effects of catalpol on DNCB-induced atopic dermatitis and IgE-mediated mast cells reaction.

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation. Catalpol is an iridoids, possessing anti-inflammatory, antioxidant, and neuroprotective activities. It can be added to food as a dietary supplement. To evaluate the effects and mechanisms of catalpol on AD, both in vitro and in vivo studies were conducted. It was found that catalpol downregulated the phosphorylation of Lyn and Syk to inhibit various downstream pathways, including intracellular Ca2+ elevation, cytokines generation, and histamine release, which ultimately controlled mast cell (MCs) degranulation. The results showed that catalpol alleviated AD-like skin lesions and MC infiltration via regulation of pro-Th2 and Th2 cytokines in vivo. Furthermore, this compound reduced the levels of IgE in AD mice and improved allergic reactions in PCA mice. The results provided that catalpol was potentially developed as a dietary supplement to improve AD and other atopic diseases.

New Insights into Phylogenetic Relationship of Hydrocotyle (Araliaceae) Based on Plastid Genomes.

Hydrocotyle, belonging to the Hydrocotyloideae of Araliaceae, consists of 95 perennial and 35 annual species. Due to the lack of stable diagnostic morphological characteristics and high-resolution molecular markers, the phylogenetic relationships of Hydrocotyle need to be further investigated. In this study, we newly sequenced and assembled 13 whole plastid genomes of Hydrocotyle and performed comparative plastid genomic analyses with four previously published Hydrocotyle plastomes and phylogenomic analyses within Araliaceae. The plastid genomes of Hydrocotyle exhibited typical quadripartite structures with lengths from 152,659 bp to 153,669 bp, comprising a large single-copy (LSC) region (83,958-84,792 bp), a small single-copy (SSC) region (18,585-18,768 bp), and a pair of inverted repeats (IRs) (25,058-25,145 bp). Each plastome encoded 113 unique genes, containing 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. Comparative analyses showed that the IR boundaries of Hydrocotyle plastomes were highly similar, and the coding and IR regions exhibited more conserved than non-coding and single-copy (SC) regions. A total of 2932 simple sequence repeats and 520 long sequence repeats were identified, with specificity in the number and distribution of repeat sequences. Six hypervariable regions were screened from the SC region, including four intergenic spacers (IGS) (ycf3-trnS, trnS-rps4, petA-psbJ, and ndhF-rpl32) and two coding genes (rpl16 and ycf1). Three protein-coding genes (atpE, rpl16, and ycf2) were subjected to positive selection only in a few species, implying that most protein-coding genes were relatively conserved during the plastid evolutionary process. Plastid phylogenomic analyses supported the treatment of Hydrocotyle from Apiaceae to Araliaceae, and topologies with a high resolution indicated that plastome data can be further used in the comprehensive phylogenetic research of Hydrocotyle. The diagnostic characteristics currently used in Hydrocotyle may not accurately reflect the phylogenetic relationships of this genus, and new taxonomic characteristics may need to be evaluated and selected in combination with more comprehensive molecular phylogenetic results.

Structural insights into the human niacin receptor HCA2-Gi signalling complex.

The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. Extensive efforts have been made to identify HCA2 targeting lipid lowering agents with fewer adverse effects, despite little being known about the molecular basis of HCA2 mediated signalling. Here, we report the cryo-electron microscopy structure of the HCA2-Gi signalling complex with the potent agonist MK-6892, along with crystal structures of HCA2 in inactive state. These structures, together with comprehensive pharmacological analysis, reveal the ligand binding mode and activation and signalling mechanisms of HCA2. This study elucidates the structural determinants essential for HCA2 mediated signalling and provides insights into ligand discovery for HCA2 and related receptors.

Reticular Chemistry with Art: A Case Study of Olympic Rings-Inspired Metal-Organic Frameworks.

Herein, we demonstrate the successful utilization of reticular chemistry as an excellent designing strategy for the deliberate construction of a zirconium-tetracarboxylate metal-organic framework (MOF) inspired by the Olympic rings. HIAM-4017, with an unprecedented (4,8)-c underlying net topology termed jcs, was developed via insightful reconstruction of the rings and judicious design of a nonsymmetric organic linker. HIAM-4017 exhibits high porosity and excellent chemical and thermal stability. Furthermore, excited-state intramolecular proton transfer (ESIPT) was achieved in an isoreticular MOF, HIAM-4018, with a large Stokes shift of 155 nm as a result of introducing the hydroxyl group to the linker skeleton to induce OH···N interactions. Such interactions were analyzed thoroughly by employing the time-dependent density functional theory (TD-DFT). Because of their good thermal and chemical stability, and strong luminescence, nanosized HIAM-4017 and HIAM-4018 were fabricated and used for Cr2O72- detection. Both MOFs demonstrate excellent sensitivity and selectivity. This work represents a neat example of building structure- and property-specific MOFs guided by reticular chemistry.