Exploring the chemical diversity of sesquiterpenes from the rarely studied south China sea soft coral Sinularia tumulosa assisted by molecular networking strategy.

Molecular networking strategy-based prioritization of the isolation of the rarely studied soft coral Sinularia tumulosa yielded 14 sesquiterpenes. These isolated constituents consisted of nine different types of carbon frameworks, namely asteriscane, humulane, capillosane, seco-asteriscane, guaiane, dumortane, cadinane, farnesane, and benzofarnesane. Among them, situmulosaols A-C (1, 3 and 4) were previously undescribed ones, whose structures with absolute configurations were established by the combination of extensive spectral data analyses, quantum mechanical-nuclear magnetic resonance and time-dependent density functional theory electronic circular dichroism calculations, the Snatzke's method, and the modified Mosher's method. Notably, situmulosaol C (4) was the second member of capillosane-type sesquiterpenes. The plausible biogenetic relationships of these skeletally different sesquiterpenes were proposed. All sesquiterpenoids were evaluated for their antibacterial, cytotoxic and anti-inflammatory effects. The bioassay results showed compound 14 exhibited significant antibacterial activities against a variety of fish and human pathogenic bacteria with MIC90 values ranging from 3.6 to 33.8 µg/mL. Moreover, moderate cytotoxic effects against HEL cells for components 13 and 14 and moderate inhibitory effect on lipopolysaccharide-induced inflammatory responses in RAW264.7 cells for substance 13 were also observed.

Prediction of mortality and overt hepatic encephalopathy undergoing transjugular intrahepatic portosystemic shunt: a retrospective cohort study.

PURPOSE: Data on medium- and long-term efficacy and safety of Transjugular intrahepatic portosystemic shunt (TIPS) using Viatorr stents in Chinese patients are limited. This study aimed to evaluate the 5-year mortality and the incidence of overt hepatic encephalopathy (OHE) after Viatorr stent insertion, and construct a model to predict post-TIPS OHE preoperatively. METHODS: One hundred thirty-two patients undergoing Viatorr stent insertion in our institution between August 2016 and December 2019 were included, and randomly divided into training and validation cohort at a 70/30 ratio. Patients were followed up until death or the end date of follow-up (December 31st, 2021). The primary end point was all-cause mortality, and the secondary end points were OHE, variceal rebleeding, recurrent ascites and shunt dysfunction. RESULTS: The 1-, 2-, 3-, 4- and 5-year cumulative survival rates were 92.4%, 87.9%, 85.3%, 80.2% and 80.2%, respectively. Post-TIPS OHE and Child-Pugh grade were independent prognostic factors. The rates of variceal rebleeding, recurrent ascites, shunt dysfunction and post-TIPS OHE were 9.1%, 14.3%, 5.3% and 28.0%, respectively. The variables of nomogram predicting post-TIPS OHE included age, diabetes and ascites grade. The area under time-dependent receiver operation characteristic (ROC) curve (AUC) in training and validation cohort were 0.806 and 0.751, respectively. The decision curve analysis (DCA) showed good net benefit both in training and validation cohort. CONCLUSION: Post-TIPS OHE and Child-Pugh grade are independent prognostic factors for early mortality in cirrhosis patients, thus we construct a simple and convenient prediction model for post-TIPS OHE to identify high-risk patients preoperatively.

Four New Diterpenoids from the South China Sea Soft Coral Sinularia nanolobata and DFT-Based Structure Elucidation.

Three new cembranoids (1-3) and a new casbanoid (4), along with three known analogues (5-7), have been isolated from the soft coral Sinularia nanolobata collected off Ximao Island. The structures, including the absolute configurations of new compounds, were established using extensive spectroscopic data analysis, time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations, and the comparison with spectroscopic data of known compounds. In the in vitro bioassay, compounds 1 and 5 exhibited moderate cytotoxic activities against human erythroleukemia (HEL) cell lines, with IC50 values of 37.1 and 42.4 µM, respectively.

Ocellatuspyrones A‒G, new antibacterial polypropionates from the Chinese mollusk Placobranchus ocellatus.

Marine invertebrates serve as rich sources of secondary metabolites with intriguing chemical diversities and a wide spectrum of biological activities. Particularly, marine shell-less sacoglossan mollusks have attracted much attentions due to the fact that mollusks apply complex metabolites as chemical defense agents against to their predators. With the purpose of discovering bioactive secondary metabolites to develop marine-derived medicines from the South China Sea, we have conducted a chemical study on the photosynthetic mollusk Placobranchus ocellatus. As a result, seven new γ-pyrone polypropionates, namely ( ±)-ocellatuspyrone A (1), ( ±)-ocellatuspyrone B (2), and ocellatuspyrones C-G (5, 9-12), along with five known polypropionates, have been isolated and characterized from the South China Sea photosynthetic mollusk Placobranchus ocellatus. Extensive spectroscopic analysis, single crystal X-ray diffraction analysis, modified Mosher's method, ECD comparison, CD exciton chirality method, TDDFT-ECD calculation, and chemical conversion were used to determine the structures and absolute configurations of the new compounds and the stereochemistry of undefined known compounds 4, 6 and 7. All these isolated polypropionates were evaluated in bioassays for their biological activities, including antibacterial, neuroprotective effect, anti-inflammatory, PTP1B inhibitory, and antiviral activities. Compounds 7, 8 and 11 were found for the first time to show antibacterial activity against fish pathogenic bacteria Streptococcus parauberis (the main pathogen causing fish streptococcal infections and acute death) with MIC values of 35.8, 34.2, and 37.4 µg/mL, respectively, which might be potential novel antibacterial agents for the treatment of fish infectious diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00179-w.

Two new compounds from the Hainan Soft Corals Sinularia tumulosa and Sinularia depressa with their anti-inflammatory or cytotoxic activities.

The detailed chemical investigations of the South China Sea soft corals Sinularia tumulosa and Sinularia depressa, yielded two new compounds, namely tumulosterol A (1) and 11'-hydroxy-α-tocopherylquinone (3), along with four related known ones (2, 5-7). Their structures were determined by extensive spectroscopic analysis and comparison with the spectral data previously reported in the literature. In bioassays, compound 1 displayed significant cytotoxic effects against H1975 and MDA-MB-231 cells with IC50 values of 6.0 and 6.3 µM, respectively. In addition, compound 3 exhibited interesting inhibitory effect on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells with IC50 value of 9.5 µM.

Boosting membrane carbon capture via multifaceted polyphenol-mediated soldering.

Advances in membrane technologies are significant for mitigating global climate change because of their low cost and easy operation. Although mixed-matrix membranes (MMMs) obtained via the combination of metal-organic frameworks (MOFs) and a polymer matrix are promising for energy-efficient gas separation, the achievement of a desirable match between polymers and MOFs for the development of advanced MMMs is challenging, especially when emerging highly permeable materials such as polymers of intrinsic microporosity (PIMs) are deployed. Here, we report a molecular soldering strategy featuring multifunctional polyphenols in tailored polymer chains, well-designed hollow MOF structures, and defect-free interfaces. The exceptional adhesion nature of polyphenols results in dense packing and visible stiffness of PIM-1 chains with strengthened selectivity. The architecture of the hollow MOFs leads to free mass transfer and substantially improves permeability. These structural advantages act synergistically to break the permeability-selectivity trade-off limit in MMMs and surpass the conventional upper bound. This polyphenol molecular soldering method has been validated for various polymers, providing a universal pathway to prepare advanced MMMs with desirable performance for diverse applications beyond carbon capture.

Cembrane Diterpenes Possessing Nonaromatic Oxacycles from the Hainan Soft Coral Sarcophyton mililatensis.

Documents on the chemical composition of the soft coral Sarcophyton mililatensis are sparse. The present investigation of the Hainan soft coral S. mililatensis resulted in the discovery of six new cembrane diterpenes, sarcoxacyclols A-F (1-6) and four known analogs (7-10). Their structures were elucidated by extensive spectroscopic analysis along with a comparison with the data in current literature. The nonaromatic oxacycles in their structures were the rarely found tetrahydrofuran ether across C-1 and C-12 and tetrahydropyran ether across C-1 and C-11, respectively. Moreover, the absolute configuration of compound 4 was established unambiguously by X-ray diffraction analysis using Ga Kα radiation (λ = 1.34139 Å). Based on the biogenetical consideration, the absolute configurations of other five new compounds were tentatively assumed. Assessment of the bioactivity for these secondary metabolites revealed that compound 1 exhibited significant tumor necrosis factor (TNF)-α inhibitory activity (IC50 = 9.5 µmol/L), similar to the positive control dexamethasone (IC50 = 8.7 µmol/L), but no obvious cytotoxicity towards RAW264.7 cells (CC50 > 50 µmol/L). The preliminary molecular docking suggested the crucial roles of the hydroxyl and acetoxyl groups in the computational prediction of the binding mode between the diterpene and the protein.

Ocellatuperoxides A-F, Uncommon Anti-Tumoral γ-Pyrone Peroxides from a Photosynthetic Mollusk Placobranchus ocellatus.

Six new pairs of γ-pyrone polypropionate enantiomers with an unusual peroxyl bridge at the side chain, namely (±)-ocellatuperoxides A-F (1-6), were isolated and characterized from the South China Sea photosynthetic mollusk Placobranchus ocellatus. Extensive spectroscopic analysis, single crystal X-ray diffraction analysis, ECD- (electronic circular dichroism) comparison, and TDDFT (time-dependent density functional theory) ECD computation were used to determine the structures and absolute configurations of new compounds. In a cell viability assay, several compounds showed considerable anti-tumoral effects on human non-small cell lung cancer cells A549 with Gefitinib (7.4 µM) and Erlotinib (2.1 µM) as positive controls. Further RNA-sequencing analysis and gene expression evaluation indicated that the anti-tumoral activity of the most effective compound 3 was associated with the regulation of several important genes, such as FGFR1 and HDAC5.

Nomogram Models Based on the Gene Expression in Prediction of Breast Cancer Bone Metastasis.

Objective: The aim of this study is to design a weighted co-expression network and build gene expression signature-based nomogram (GESBN) models for predicting the likelihood of bone metastasis in breast cancer (BC) patients. Methods: Dataset GSE124647 was used as a training set, while GSE16446, GSE45255, and GSE14020 were taken as validation sets. In the training cohort, the limma package in R was adopted to obtain differentially expressed genes (DEGs) between BC nonbone metastasis and bone metastasis patients, which were used for functional enrichment analysis. After weighted co-expression network analysis (WGCNA), univariate Cox regression and Kaplan-Meier plotter analyses were performed to screen potential prognosis-related genes. Then, GESBN models were constructed and evaluated. The prognostic value of the GESBN models was investigated in the GSE124647 dataset, which was validated in GSE16446 and GSE45255 datasets. Further, the expression levels of genes in the models were explored in the training set, which was validated in GSE14020. Finally, the expression and prognostic value of hub genes in BC were explored. Results: A total of 1858 DEGs were obtained. The WGCNA result showed that the blue module was most significantly related to bone metastasis and prognosis. After survival analyses, GAJ1, SLC24A3, ITGBL1, and SLC44A1 were subjected to construct a GESBN model for overall survival (OS). While GJA1, IGFBP6, MDFI, TGFBI, ANXA2, and SLC24A3 were subjected to build a GESBN model for progression-free survival (PFS). Kaplan-Meier plotter and receiver operating characteristic analyses presented the reliable prediction ability of the models. Cox regression analysis further revealed that GESBN models were independent prognostic predictors for OS and PFS in BC patients. Besides, GJA1, IGFBP6, ITGBL1, SLC44A1, and TGFBI expressions were significantly different between the two groups in GSE124647 and GSE14020. The hub genes had a significant impact on patient prognosis. Conclusion: Both the four-gene signature and six-gene signature could accurately predict patient prognosis, which may provide novel treatment insights for BC bone metastasis.

Mililatensols A-C, New Records of Sarsolenane and Capnosane Diterpenes from Soft Coral Sarcophyton mililatensis.

Three unusual diterpenes with rare sarsolenane and capnosane skeletons, namely mililatensols A-C (1-3), were isolated from the South China Sea soft coral Sarcophyton mililatensis, leading to the first record of sarsolenane and capnosane diterpenes from the title animal. The structures of compounds 1-3 were established by extensive spectroscopic analysis and comparison with the literature data. Moreover, the absolute configuration of 2 was determined by TDDFT ECD calculations. In an in vitro bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages. In the preliminary virtual screening of inhibitory potential against SARS-CoV-2 by molecular docking, the results showed these three diterpenes were potential SARS-CoV-2 Mpro inhibitors.

Two New Austocystin Analogs from the Marine-Derived Fungus Aspergillus sp. WHUF05236.

Two new austocystin analogs, austocystin P (1) and austocystin Q (2), along with fourteen known compounds (3-16) were isolated from the fermentation extract of Aspergillus sp. WHUF05236. The planar structures of 1 and 2 were elucidated through 1D, 2D NMR and MS analyses. Their absolute configurations were determined by the time-dependent density functional (TDDFT)-ECD calculation. Compounds 3, 11, and 12 exhibited antimicrobial activities against Helicobacter pylori with MIC values ranging from 20.00 to 43.47 µM. Compounds 3, 6, and 7 showed cytotoxicities against the human colon cancer cell lines Hct-116 with IC50 values of 101.79, 65.46, and 36.72 µM, respectively.

Investigation of the Physical Properties and Clinical Application of Embosphere Microspheres.

BACKGROUND: The aim of this study was to understand physical characteristics of Embosphere microspheres for the clinical use of microsphere chemotherapy embolization of liver cancer. METHODS: The morphology of Embosphere microspheres in different states, including static, oscillating, and in a magnetic field was observed with the naked eye. Ninety-five patients diagnosed with primary hepatocellular carcinoma (HCC) were separated into 3 groups based on the types of embolic material as follows: 32 cases of sole microspheres, 34 cases of iodinated oil (17 cases with additional application of gelatin sponge particle), and 29 cases of iodinated oil + Embosphere microspheres. RESULTS: The diameter of the microspheres ranged from 100 to 300 µm, with a sedimentation rate υ = 0.0375 cm/s in physiological saline. The diameter of microspheres ranged from 300 to 500 µm, with a sedimentation rate υ = 0.1875 cm/s. The swelling rate of microspheres was 90%. Microspheres showed nondirectional movement in a 1.5- or 3.0-T magnetic field during magnetic resonance imaging. A volumetric ratio of 1:1.4-1:1.5 between microspheres and contrast agent resulted in optimal suspension properties. Microspheres appeared circular with a smooth surface upon water adsorption. Microsphere embolism was observable in blood vessels of pathological sections. The surface of microspheres can adsorb 5-fluorouracil and arsenic trioxide. There are statistically significant differences in local-regional tumor control conditions among patients treated with sole microspheres, iodinated oil, and iodinated oil + microspheres during transarterial chemoembolization. CONCLUSIONS: Embosphere microspheres can be used to embolize patients with rupture and hemorrhage of HCC. Embosphere microsphere embolization is superior to iodinated oil and iodinated oil + microsphere for HCC.

Enhancement of Nicotiana tabacum Resistance Against Dehydration-Induced Leaf Senescence via Metabolite/Phytohormone-Gene Regulatory Networks Modulated by Melatonin.

Melatonin (MEL) is a pleiotropic agent with crucial functions reported in a variety of stress responses and developmental processes. Although MEL involvement in plant defense against natural leaf senescence has been widely reported, the precise regulatory mechanisms by which it delays stress-induced senescence remain unclear. In this study, we found that foliar spraying of melatonin markedly ameliorated dehydration-induced leaf senescence in Nicotiana tabacum, accompanied by attenuated oxidative damage, expression of senescence-related genes, and reduced endogenous ABA production. Metabolite profiling indicated that melatonin-treated plants accumulated higher concentrations of sugars, sugar alcohol, and organic acids, but fewer concentrations of amino acids in the leaves, than untreated plants after exposure to dehydration. Gene expression analysis revealed that the delayed senescence of stressed plants achieved by melatonin treatment might be partially ascribed to the upregulated expression of genes involved in ROS scavenging, chlorophyll biosynthesis, photosynthesis, and carbon/nitrogen balances, and downregulated expression of senescence-associated genes. Furthermore, hormone responses showed an extensively modulated expression, complemented by carotenoid biosynthesis regulation to achieve growth acceleration in melatonin-treated plants upon exposure to dehydration stress. These findings may provide more comprehensive insights into the role of melatonin in alleviating leaf senescence and enhancing dehydration resistance.

High expression of PARD3 predicts poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most commonly cancers with poor prognosis and drug response. Identifying accurate therapeutic targets would facilitate precision treatment and prolong survival for HCC. In this study, we analyzed liver hepatocellular carcinoma (LIHC) RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), and identified PARD3 as one of the most significantly differentially expressed genes (DEGs). Then, we investigated the relationship between PARD3 and outcomes of HCC, and assessed predictive capacity. Moreover, we performed functional enrichment and immune infiltration analysis to evaluate functional networks related to PARD3 in HCC and explore its role in tumor immunity. PARD3 expression levels in 371 HCC tissues were dramatically higher than those in 50 paired adjacent liver tissues (p < 0.001). High PARD3 expression was associated with poor clinicopathologic feathers, such as advanced pathologic stage (p = 0.002), vascular invasion (p = 0.012) and TP53 mutation (p = 0.009). Elevated PARD3 expression also correlated with lower overall survival (OS, HR = 2.08, 95% CI = 1.45-2.98, p < 0.001) and disease-specific survival (DSS, HR = 2.00, 95% CI = 1.27-3.16, p = 0.003). 242 up-regulated and 71 down-regulated genes showed significant association with PARD3 expression, which were involved in genomic instability, response to metal ions, and metabolisms. PARD3 is involved in diverse immune infiltration levels in HCC, especially negatively related to dendritic cells (DCs), cytotoxic cells, and plasmacytoid dendritic cells (pDCs). Altogether, PARD3 could be a potential prognostic biomarker and therapeutic target of HCC.

Lagerindicine, a New Pyrrole Alkaloid Isolated from the Flowers of Lagerstroemia indica Linnaeus.

A phytochemical investigation of the EtOH extract of the flowers of Lagerstroemia indica L. led to the isolation and characterization of a new pyrrole alkaloid, named lagerindicine (1), along with four known compounds (2-5). Their structures were elucidated by the detailed spectroscopic analysis and comparison with literature data, whereas the structure, in particularly, the absolute configuration (AC) of 1, was firmly determined by total synthesis. All the isolates were evaluated for their cytotoxic effects against human colon cancer cell (HCT-116), and compound 3 exhibited weak cytotoxicity with IC50 value of 28.4 µM.

Rare new bicyclic cembranoid ethers and a novel trihydroxy prenylated guaiane from the Xisha soft coral Lobophytum sp.

Seven new cembrane-type diterpenes, lobophytolins C-I (3-9), and one new prenylated-guiane-type diterpene, lobophytolin J (10), along with six known related ones (1, 2, 11-14), have been isolated from the soft coral Lobophytum sp. collected off the Xisha Island in the South China Sea. Their structures were elucidated by extensive spectroscopic analysis and quantum mechanical (QM)-NMR methods. The absolute configuration of lobophytolin H (8) was determined by the application of the modified Mosher's method and chemical transformation. Lobophytolin D (4) exhibited promising cytotoxicities in in vitro bioassays against HT-29, Capan-1, A549, and SNU-398 human cancer cell lines with IC50 values of 4.52, 6.62, 5.17, and 6.15 µM, respectively.

Complex Polypropionates from a South China Sea Photosynthetic Mollusk: Isolation and Biomimetic Synthesis Highlighting Novel Rearrangements.

Placobranchus ocellatus is well known to produce diverse and complex γ-pyrone polypropionates. In this study, the chemical investigation of P. ocellatus from the South China Sea led to the discovery and identification of ocellatusones A-D, a series of racemic non-γ-pyrone polyketides with novel skeletons, characterized by a bicyclo[3.2.1]octane (1, 2), a bicyclo[3.3.1]nonane (3) or a mesitylene-substituted dimethylfuran-3(2H)-one core (4). Extensive spectroscopic analysis, quantum chemical computation, chemical synthesis, and/or X-ray diffraction analysis were used to determine the structure and absolute configuration of the new compounds, including each enantiomer of racemic compounds 1-4 after chiral HPLC resolution. An array of new and diversity-generating rearrangements is proposed to explain the biosynthesis of these unusual compounds based on careful structural analysis and comparison with six known co-occurring γ-pyrones (5-10). Furthermore, the successful biomimetic semisynthesis of ocellatusone A (1) confirmed the proposed rearrangement through an unprecedented acid induced cascade reaction.

Uncommon nornardosinane, seconeolemnane and related sesquiterpenoids from Xisha soft coral Litophyton nigrum.

Three new nardosinane-type sesquiterpenoids linardosinenes A-C (1-3) and four new neolemnane-type sesquiterpenoids lineolemnenes A-D (4-7), together with the related known compound 4-acetoxy-2,8-neolemnadien-5-one (8), were isolated from the Xisha soft coral Litophyton nigrum. The structures of these new compounds were elucidated by comprehensive analyses of spectroscopic data, in association withmodified Mosher's method and ECD calculations for configurational assignments and the absolute configuration of8was determined by X-ray diffraction analysis for the first time. Structurally uncommon nornardosinane and seconeolemnane skeletons for compounds 1 and 7, respectively, are rare carbon frameworks in naturally occurring sesquiterpenoids. The absolute configurations of 1, 7, and 8 were determined by modified Mosher's method, TDDFT ECD approach, and X-ray diffraction analysis, respectively. This is the first chemical study of L. nigrum and the first report of nornardosinane, seconeolemnane and related sesquiterpenoids from the genus Litophyton. The isolates 1-7 were evaluated for their cytotoxicity against THP-1, SNU-398, HT-29, Capan-1 and A549 cell lines and inhibitory activities against PTP1B, BRD4, HDAC1 and HDAC6 protein kinases. The results indicated that compounds 2-5 inhibited proliferation of human cancer cells. However, none of them were potent inhibitors of protein kinases.

A new bis-γ-pyrone polypropionate of onchidiol family from marine pulmonate mollusk Onchidium sp.

A new bis-γ-pyrone polypropionate, 4,16-di-epi-onchidiol (1), along with three known related compounds (2-4) were isolated from the marine pulmonate mollusk Onchidium sp. The structure of compound 1 was elucidated by extensive spectroscopic analysis and by comparison the NMR data with its stereoisomers 2-4, whereas its absolute configuration was determined by the combination of X-ray diffraction analysis and TDDFT-ECD calculation. In bioassay, the isolated compounds exhibited broad cytotoxicity against several cancer cell lines with IC50 values ranging from 24.6 to 88.5µM.

Two new hydroperoxy steroids from the South China Sea gorgonian Rumphella sp.

Two new hydroperoxy steroids, namely, xidaosteroids A and B (1 and 2), along with five known related compounds 3-7, were isolated from the South China Sea gorgonian Rumphella sp.. Their structures were established by extensive spectroscopic analyses and comparison of the spectral data with those reported in the literature. In bioassay, compound 3 showed weak cytotoxicities against SNU-398 and Capan-1 cells.