A new triterpenoid saponin and a new natural saponin from the roots of Bupleurum scorzonerifolium willd.

Sixteen triterpenoid saponins were isolated from the roots of Bupleurum scorzonerifolium Willd., including a new triterpenoid saponin and new natural saponin that was characterised by NMR for the first time, along with 14 known triterpenoid saponins. The structures of the compounds were established by 1D and 2D NMR spectroscopy, HR-ESI-MS, and comparison with the literature. The cytotoxic activity of the compounds against 4T1 cells was determined using the CCK8 method. Compounds 9 and 6 showed the strongest cytotoxic activity with IC50 values of 2.75 ± 0.86 and 3.78 ± 0.50 µM, respectively. Compounds 2-5 and 8 showed potent cytotoxic activity. Compounds 14 and 16 showed moderate cytotoxicity.

A PCB image segmentation model based on rotational X-ray computed laminography imaging.

BACKGROUND: The rapid development of industrialization in printed circuit board (PCB) warrants more complexity and integrity, which entails an essential procedure of PCB inspection. X-ray computed laminography (CL) enables inspection of arbitrary regions for large-sized flat objects with high resolution. PCB inspection based on CL imaging is worthy of exploration. OBJECTIVE: This work aims to extract PCB circuit layer information based on CL imaging through image segmentation technique. METHODS: In this work, an effective and applicable segmentation model for PCB CL images is established for the first time. The model comprises two components, with one integrating edge diffusion and l0 smoothing to filter CL images with aliasing artifacts, and the other being the fuzzy energy-based active contour model driven by local pre-fitting energy to segment the filtered images. RESULT: The proposed model is able to suppress aliasing artifacts in the PCB CL images and has good performance on images of different circuit layers. CONCLUSIONS: Results of the simulation experiment reveal that the method is capable of accurate segmentation under ideal scanning condition. Testing of different PCBs and comparison of different segmentation methods authenticate the applicability and superiority of the model.

Fourteen undescribed steroidal saponins from Solanum capsicoides leaves and their neuroprotective effects.

A total of 14 previously undescribed steroidal saponins named capsicsaponins A-N were isolated from the leaves of Solanum capsicoides, encompassing various types, including cholesterol derivatives and pseudospirostanol saponins. The structures of all compounds were determined through comprehensive analysis of spectroscopic data (1D NMR and 2D NMR), along with physicochemical analysis methods (acid hydrolysis, OR, and UV). Moreover, in the H2O2-induced pheochromocytoma cell line model, compounds 1-14 were screened for their neuroprotective effects on cells. The bioassay results demonstrated compounds 8-14 were able to revive cell viability compared to the positive control edaravone. The damage neuroprotection of the most active compound was further explored.

Seven new triterpenoids from the roots of Adenophora tetraphylla (Thub.) Fisch.

Seven new triterpenoids, named Adeterpenoids A-G (1-7) and eight known compounds (8-15), were isolated from 70% ethanol extract of the roots of Adenophora tetraphylla (Thub.) Fisch. The compounds from it were separated by column chromatography techniques such as silica gel, ODS, and preparative liquid chromatography. Their structures were clarified based on extensive spectral analysis (1D, 2D-NMR, HR-ESI-MS, IR, UV, and CD) and comparison with the literature. At the same time, all compounds were evaluated for their cytotoxic activity against the LN229 (human glioma cell line). The results showed that compounds 2, 5, 6, 13, and 14 had a significant inhibitory effect on LN229 cells.

Distribution pattern and influencing factors of bacterial communities in different soil depths of Caragana jubata shurb in Luya Mountain, China.

Soil microorganisms are important components of terrestrial ecosystems, affecting soil formation and fertility, plant growth and stress tolerance, nutrient turnover and carbon storage. In this study, we collected soil samples (humus layer, 0-10 cm, 10-20 cm, 20-40 cm, and 40-80 cm) from Caragana jubata shrubland in Shanxi subalpine to explore the composition, diversity, and assembly of soil bacterial communities at different depths across the soil profile. The results showed that Actinomycota (19%-28%), Chloromycota (10%-36%) and Acidobacteria (15%-24%), and Proteobacteria (9%-25%) were the dominant bacterial phyla. α-diversity of soil bacterial community significantly decreased with the increases of soil depth. Soil bacterial ß-diversity varied across different soil depths. Soil pH, water content, and enzyme activity were the main ecological factors affecting the distribution of soil bacterial communities. Soil bacterial communities had more complex interactions in humus layer and 0-10 cm layer. On the whole, soil bacterial communities were dominated by coexistence in C. jubata shrubland, and the soil bacterial community assembly was driven by random process.

Hydrogen exerts neuroprotective effects after subarachnoid hemorrhage by attenuating neuronal ferroptosis and inhibiting neuroinflammation.

OBJECTIVE: Spontaneous subarachnoid hemorrhage (SAH), the third most common stroke subtype, is associated with high mortality and disability rates. Therefore, finding effective therapies to improve neurological function after SAH is critical. The objective of this study was to investigate the potential neuroprotective effects of hydrogen in the context of SAH, specifically, by examining its role in attenuating neuronal ferroptosis and inhibiting neuroinflammation, which are exacerbated by excess iron ions after SAH. METHODS: Mice were exposed to chambers containing 3% hydrogen, and cells were cultured in incubators containing 60% hydrogen. Neurological function in mice was assessed using behavioral scores. Protein changes were detected using western blotting. Inflammatory factors were detected using enzyme linked immunosorbent assay. Probes, electron microscopy, and related kits were employed to detect oxidative stress and ferroptosis. RESULTS: Hydrogen improved the motor function, sensory function, and cognitive ability of mice after SAH. Additionally, hydrogen facilitated Nuclear factor erythroid 2 -related factor 2 activation, upregulated Glutathione peroxidase 4, and inhibited Toll-like receptor 4, resulting in downregulation of inflammatory responses, attenuation of oxidative stress after SAH, and inhibition of neuronal ferroptosis. CONCLUSION: Hydrogen exerts neuroprotective effects by inhibiting neuronal ferroptosis and attenuating neuroinflammation after SAH.

Five new sesquiterpenoids isolated from Dictamnus dasycarpus Turcz.

Five new sesquiterpenoids, dictamtrinorguaianols E and F (1-2), and dictameudesmnosides F, G, and H (3-5), along with seven known sesquiterpenoids (6-12) were isolated from Dictamnus dasycarpus Turcz. The structures of all new compounds were characterized by spectroscopic methods, including UV, IR, HR-ESI-MS, and 1D and 2D NMR. The In-vitro anti-proliferative activities of all the compounds against two human cancer cell lines (SW982 and A549) were evaluated by CCK-8 assay. Compounds 1 and 4 showed medium anti-proliferative activity against SW982 cells, with IC50 values of 3.49 ± 0.10 and 6.42 ± 1.23 µM, respectively. Additionally, compounds 2, 7, and 8 exhibited medium anti-proliferative activity against A549 cells, with IC50 values ranging from 0.80 ± 0.05 to 6.60 ± 0.46 µM.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Failure mechanical properties of lumbar intervertebral disc under high loading rate.

BACKGROUND: Lumbar disc herniation (LDH) is the main clinical cause of low back pain. The pathogenesis of lumbar disc herniation is still uncertain, while it is often accompanied by disc rupture. In order to explore relationship between loading rate and failure mechanics that may lead to lumbar disc herniation, the failure mechanical properties of the intervertebral disc under high rates of loading were analyzed. METHOD: Bend the lumbar motion segment of a healthy sheep by 5° and compress it to the ultimate strength point at a strain rate of 0.008/s, making a damaged sample. Within the normal strain range, the sample is subjected to quasi-static loading and high loading rate at different strain rates. RESULTS: For healthy samples, the stress-strain curve appears collapsed only at high rates of compression; for damaged samples, the stress-strain curves collapse both at quasi-static and high-rate compression. For damaged samples, the strengthening stage becomes significantly shorter as the strain rate increases, indicating that its ability to prevent the destruction is significantly reduced. For damaged intervertebral disc, when subjected to quasi-static or high rates loading until failure, the phenomenon of nucleus pulposus (NP) prolapse occurs, indicating the occurrence of herniation. When subjected to quasi-static loading, the AF moves away from the NP, and inner AF has the greatest displacement; when subjected to high rates loading, the AF moves closer to the NP, and outer AF has the greatest displacement. The Zhu-Wang-Tang (ZWT) nonlinear viscoelastic constitutive model was used to describe the mechanical behavior of the intervertebral disc, and the fitting results were in good agreement with the experimental curve. CONCLUSION: Experimental results show that, both damage and strain rate have a significant effect on the mechanical behavior of the disc fracture. The research work in this article has important theoretical guiding significance for preventing LDH in daily life.

Identification of potential diagnostic biomarkers associated with periodontitis by comprehensive bioinformatics analysis.

Periodontitis is a chronic inflammatory disease that affects the tissues surrounding the teeth, including the gums and the bones supporting the teeth. Early detection and intervention are crucial for effective management of periodontitis. Our study aims to identify a diagnostic biomarker for periodontitis and explore the pathways associated with the occurrence and development of periodontitis. The expression of gingival tissue from periodontitis and healthy control were downloaded from the Gene Expression Omnibus. The weighted gene co-expression network analysis (WGCNA) were used to analyze module genes associated with periodontitis and DESeq2 were performed to identify differently expressed genes (DEGs) between periodontitis and healthy control. Then the candidate genes were obtained by intersecting the genes from interest modules and DEGs. Functional enrichment analysis was performed using gene ontology and kyoto encyclopedia of gene and genomes, followed by the protein-protein interaction (PPI) network analysis. The hub genes were identified by the cytoCNA plugin in Cytoscape. Finally, immunohistochemical staining of the hub genes was performed to validate the findings. WGCNA analysis found that the expression of the MEblack module was significantly higher in individuals with periodontitis compared to those in the healthy control group. A total of 888 DEGs, including 750 upregulated and 138 downregulated genes, were identified. Finally, 427 candidate genes were identified potentially associated with periodontitis after intersecting the DEGs and the black module genes. Several critical signaling pathways were identified associated with periodontitis by functional enrichment analysis, including cytokine-cytokine receptor interaction, neutrophil extracellular trap formation, Staphylococcus aureus infection, and Interleukin-17 signaling pathway. The PPI network analysis revealed that C-X-C motif chemokine ligand 5 (CXCL5) and C-X-C motif chemokine ligand 6 (CXCL6) could play an important role in the process of periodontitis. The gene expression level of CXCL5 and CXCL6 detected using immunohistochemical verified the findings. In conclusion, we found that CXCL5 and CXCL6 are closely associated with the occurrence of periodontitis. Our present pilot study suggests that CXCL5 and CXCL6 have the potential to be used as a diagnostic biomarker of periodontitis.

Reversible modulation of interlayer stacking in 2D copper-organic frameworks for tailoring porosity and photocatalytic activity.

The properties of two-dimensional covalent organic frameworks (2D COFs), including porosity, catalytic activity as well as electronic and optical properties, are greatly affected by their interlayer stacking structures. However, the precise control of their interlayer stacking mode, especially in a reversible fashion, is a long-standing and challenging pursuit. Herein, we prepare three 2D copper-organic frameworks, namely JNM-n (n = 7, 8, and 9). Interestingly, the reversible interlayer sliding between eclipsed AA stacking (i.e., JNM-7-AA and JNM-8-AA) and staggered ABC stacking (i.e., JNM-7-ABC and JNM-8-ABC) can be achieved through environmental stimulation, which endows reversible encapsulation and release of lipase. Importantly, JNM-7-AA and JNM-8-AA exhibit a broader light absorption range, higher charge-separation efficiency, and higher photocatalytic activity for sensitizing O2 to 1O2 and O2•- than their ABC stacking isostructures. Consequently, JNM-8-AA deliver significantly enhanced photocatalytic activities for oxidative cross-coupling reactions compared to JNM-8-ABC and other reported homogeneous and heterogeneous catalysts.

Relationships among protozoa, bacteria and fungi in polycyclic aromatic hydrocarbon-contaminated soils.

Soil bacterial and fungal communities play key roles in the degradation of organic contaminants, and their structure and function are regulated by bottom-up and top-down factors. Microbial ecological effects of polycyclic aromatic hydrocarbons (PAHs) and trophic interactions among protozoa and bacteria/fungi in PAH-polluted soils have yet to be determined. We investigated the trophic interactions and structure of the microbiome in PAH-contaminated wasteland and farmland soils. The results indicated that the total concentration of the 16 PAHs (∑PAHs) was significantly correlated with the Shannon index, NMDS1 and the relative abundances of bacteria, fungi and protozoa (e.g., Pseudofungi) in the microbiome. Structural equation modelling and linear fitting demonstrated cascading relationships among PAHs, protozoan and bacterial/fungal communities in terms of abundance and diversity. Notably, individual PAHs were significantly correlated with microbe-grazing protozoa at the genus level, and the abundances of these organisms were significantly correlated with those of PAH-degrading bacteria and fungi. Bipartite networks and linear fitting indicated that protozoa indirectly modulate PAH degradation by regulating PAH-degrading bacterial and fungal communities. Therefore, protozoa might be involved in regulating the microbial degradation of PAHs by predation in contaminated soil.

Two new alkaloids isolated from Dictamnus dasycarpus Turcz.

Two new quinoline alkaloids (1-2) together with twenty-two known alkaloids (3-24) were isolated and identified from Dictamnus dasycarpus Turcz. Compounds 6-7, 9, 11, 15-16, 19 and 24 were isolated from D. dasycarpus for the first time. The structures of all compounds were characterised by spectroscopic methods (1D, 2D NMR and HRESIMS). The anti-proliferative activity was mediated by the arrest of three human cancer cell lines (SW982, HepG2 and A549) of all the compounds that were evaluated by CCK-8 assay.

Discovery of Novel Coumarin-quinolinium Derivatives as Pan-KRAS Translation Inhibitors by Targeting 5'-UTR RNA G-Quadruplexes.

Hyperactivated KRAS mutations fuel tumorigenesis and represent attractive targets for cancer treatment. While covalent inhibitors have shown clinical benefits against the KRASG12C mutant, advancements for non-G12C mutants remain limited, highlighting the urgent demand for pan-KRAS inhibitors. RNA G-quadruplexes (rG4s) in the 5'-untranslated region of KRAS mRNA can regulate KRAS translation, making them promising targets for pan-KRAS inhibitor development. Herein, we designed and synthesized 50 novel coumarin-quinolinium derivatives, leveraging our previously developed rG4-specific ligand, QUMA-1. Notably, several compounds exhibited potent antiproliferative activity against cancer cells as pan-KRAS translation inhibitors. Among them, 15a displayed exceptional capability in stabilizing KRAS rG4s, suppressing KRAS translation, and consequently modulating MAPK and PI3K-AKT pathways. 15a induced cell cycle arrest, prompted apoptosis in KRAS-driven cancer cells, and effectively inhibited tumor growth in a KRAS mutant xenograft model. These findings underscore the potential of 15a as a pan-KRAS translation inhibitor, offering a novel and promising approach to target various KRAS-driven cancers.

Immunocompetent mouse models revealed that S100A4+ monocytes/macrophages facilitate long-term Zika virus infection in the testes.

During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4+ monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4+ monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.

Phenolic components from the fruits of Solanum xanthocarpum with anti-inflammatory activity.

Two new compounds (1 and 2), along with thirty-one known compounds (3-33) were isolated from the fruits of Solanum xanthocarpum. The structure of isolates was elucidated by analysis of spectroscopic data and the physicochemical methods. Meanwhile, the anti-inflammatory activity of isolates was determined using LPS-induced RAW 264.7 cells. The results of anti-inflammatory assays indicated that most isolated compounds (3, 4, 6, 8-14, 17-20, and 30) possessed significant nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-induced RAW 264.7 cells with IC50 values ranging from 14.33 to 48.55 µM.

Cytotoxic withanolides from the leaves of Datura stramonium L.

Six novel withanolides, along with nine known related compounds were isolated from the leaves of Datura stramonium L. The structures and absolute configurations of the new withanolides were elucidated by employing various spectral techniques and comparing them with those previously reported in the literature. In addition, four withanlides demonstrated interesting cytotoxic activity on LN229 cells with IC50 <20 µM.

Cytotoxicity sesquiterpenoids from the leaves of Datura stramonium L.

Four new sesquiterpenoids, dstramonins A-D (1-4), and one new natural product (5), together with three known compounds (6-8), were isolated from the leaves of Datura stramonium L. The structures of new compounds were elucidated by extensive spectroscopic analysis and comparison with the literature. The cytotoxicity of isolates against LN229 cells was assessed and compounds 2-4, and 7 displayed cytotoxic activity with IC50 values ranging from 8.03 to 13.83 µM.

Steroidal saponins from the roots of Paris verticillata and their anti-proliferative and anti-inflammatory activities.

Thirteen previously undescribed steroidal saponins, named parisverticilloside A-M (1-13) and twenty known steroidal saponins (14-33) were isolated from ethanol extract of the roots of Paris verticillata. Their structures were identified by a series of spectroscopic methods, including 1D and 2D NMR, HR-ESI-MS, optical rotatory dispersion and chemical processes. The anti-proliferative activities of all compounds against LN229, HepG2, MDA-MB-231 and 4T1 cell lines were evaluated using the CCK8 assay with cisplatin or capecitabine as the positive control. The anti-inflammatory activities of all compounds were measured by inhibition of LPS-induced NO release from BV2 cell lines, with dexamethasone as the positive control.

Single-cell RNA sequencing to understand host-virus interactions.

Single-cell RNA sequencing (scRNA-seq) has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell resolution. This review summarizes the existing scRNA-seq technologies together with their strengths and weaknesses. The applications of scRNA-seq in various virological studies are discussed in depth, which broaden the understanding of the immune atlas, host-virus interactions, and immune repertoire. scRNA-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.